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Free radical-derived quinone methide mediates skin tumor promotion by butylated hydroxytoluene hydroperoxide: expanded role for electrophiles in multistage carcinogenesis. Free radical derivatives of peroxides, hydroperoxides, and anthrones are thought to mediate tumor promotion by these compounds. Further, the promoting activity of phorbol esters is attributed, in part, to their ability to stimulate the cellular generation of oxygen radicals. A hydroperoxide metabolite of butylated hydroxytoluene, 2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone (BHTOOH), has previously been shown to be a tumor promoter in mouse skin. BHTOOH is extensively metabolized by murine keratinocytes to several radical species. The primary radical generated from BHTOOH is a phenoxyl radical that can disproportionate to form butylated hydroxytoluene quinone methide, a reactive electrophile. Since electrophilic species have not been previously postulated to mediate tumor promotion, the present study was undertaken to examine the role of this electrophile in the promoting activity of BHTOOH. The biological activities of two chemical analogs of BHTOOH, 4-trideuteromethyl-BHTOOH and 4-tert-butyl-BHTOOH, were compared with that of the parent compound. 4-Trideuteromethyl-BHTOOH and 4-tert-butyl-BHTOOH have a reduced ability or inability, respectively, to form a quinone methide; however, like the parent compound, they both generate a phenoxyl radical when incubated with keratinocyte cytosol. The potency of BHTOOH, 4-trideuteromethyl-BHTOOH, and 4-tert-butyl-BHTOOH as inducers of ornithine decarboxylase, a marker of tumor promotion, was commensurate with their capacity for generating butylated hydroxytoluene quinone methide. These initial results were confirmed in a two-stage tumor promotion protocol in female SENCAR mice. Together, these data indicate that a quinone methide is mediating tumor promotion by BHTOOH, providing direct evidence that an electrophilic intermediate can elicit this stage of carcinogenesis. | neoplasms |
Health care screening for people with mental handicap living in the community OBJECTIVE--To determine what contact people with mental handicap had had with their general practitioner in the previous year; what prescribed drugs they were taking and whether these had been reviewed; when hearing and vision had last been screened; and what medical problems were found on examination. DESIGN--Case series. SETTING-Day centre for adults with mental handicap. SUBJECTS--A balanced sample of 75 of the 150 people attending the day centre. 10 Were excluded because consent was not given. RESULTS--The subjects did not consult their general practitioners more frequently than the general population but were more likely to be taking prescribed drugs, and 57% of these prescriptions had not been reviewed by a doctor. Thirty three people failed vision screening, including 13 who wore glasses. Twenty seven of the 62 who were testable had a hearing impairment. CONCLUSIONS--As only eight out of 65 people examined in the study did not have an appreciable problem brought to light, screening seems to be worth while. Whether such screening needs to be done by a medically qualified person needs further research. | nervous system diseases |
Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. The human T-lymphotropic virus type I (HTLV-I), the first human retrovirus to be characterized, is associated with adult T-cell leukaemia and a chronic progressive disease of the central nervous system termed tropical spastic paraparesis, or HTLV-I-associated myelopathy. Only 1% of individuals infected with HTLV-I develop clinical disease however. The various manifestations of an HTLV-I infection may be related to differences in the genetic backgrounds of individuals, infection with variant strains of HTLV-I, differences in viral tropism or host immune response to the virus. Whereas the humoral response to HTLV-I is well characterized, little is known about the human cellular immune response, such as the production of cytotoxic T lymphocytes. Here we report the presence of high levels of circulating HTLV-I-specific cytotoxic T lymphocytes in patients with HTLV-I associated neurological disease but not in HTLV-I seropositive individuals without neurological involvement. These cytotoxic T lymphocytes are CD8+, HLA class I- restricted and predominantly recognize the HTLV-I gene products encoded in the regulatory region pX. These findings suggest that HTLV-I-specific cytotoxic T lymphocytes may contribute to the pathogenesis of associated neurological disorders associated with HTLV-I. | neoplasms |
Role of phenytoin in healing of large abscess cavities. The promotion of healing of large abscess cavities attained with topical phenytoin was evaluated in controlled studies of clinical and experimental wounds. In the clinical abscess cavities, phenytoin application in 20 patients compared with conventional treatment in 20 patients resulted in earlier separation of slough, decrease in oedema, control of pain and overall enhanced healing. The mean(s.d.) rate of reduction of wound area was 2.02(0.48) cm2/day in the phenytoin group versus 1.58(0.51) cm2/day in controls (P less than 0.05) on day 10, and 1.8(0.32) cm2/day versus 1.19(0.21) cm2/day (P less than 0.01) on day 20. The mean volume reduction rates at both the 10th and 20th day were 0.48(0.01) cm3/day for phenytoin versus 0.32(0.04) cm3/day for controls; (P less than 0.005). By day 20, 17 of the patients treated with phenytoin were rated as having healed completely, compared with only one of the controls. In a standardized guinea-pig model of the clinical abscess cavity, which included inoculation of the wound with Bacillus proteus and Klebsiella pneumoniae, an enhanced healing rate was also observed (at 7 days 0.40(0.05) cm2/day with phenytoin versus 0.21(0.08) cm2/day in controls; P less than 0.005). All eight of the animals treated with phenytoin healed by day 21, compared with one of the eight controls. Biopsies of wounds treated with phenytoin showed less inflammation, no necrosis, and enhanced neovascularization, collagen deposition and fibroblast proliferation compared to controls. Bacterial colonies also decreased more rapidly with the use of phenytoin. | general pathological conditions |
Spinal anaesthesia in day-care surgery with a 26-gauge needle. We studied 106 day-care surgical patients (52 male) aged 18-70 yr (mean 49.6 yr) who received spinal anaesthesia with a 26-gauge spinal needle. The incidence of headache, back pain and patient acceptability were investigated after operation using a questionnaire. The incidence of postspinal headache was 7.5%, and 11.3% of patients developed back pain. One patient remained in hospital because of hypotension and dizziness. There were no major complications and patient acceptability was almost 100%. We conclude that spinal anaesthesia for day-care surgery is easy to perform and cost effective. | nervous system diseases |
Delayed endolymphatic hydrops and its relationship to Meniere's disease. Delayed endolymphatic hydrops (EH) can be characterized as having ipsilateral and contralateral types. They are similar in that both have early and late phases of otologic symptoms and that the early phase is a profound hearing loss in one ear. The late phases differ, however, in that the ipsilateral type develops the symptoms of EH (episodic vertigo) in the deaf ear and the contralateral type develops the symptoms of EH (fluctuating hearing loss and/or episodic vertigo) in the hearing ear. In more than half the cases of both types of delayed EH, the profound hearing losses in the early phase are simply discovered to be present in early childhood without a known time of onset. The temporal bones of two patients with contralateral delayed EH show pathologic changes in the deaf ears that are similar to those known to occur in mumps and measles labyrinthitis, whereas the pathologic changes in the hearing ears are similar to those known to occur in Meniere's disease. These observations support the proposition that Meniere's disease may occur as a delayed sequela of inner ear damage sustained during an attack of subclinical viral labyrinthitis occurring in childhood. | general pathological conditions |
Optimal escort for interhospital transport of pediatric emergencies. The charts of 130 seriously ill or injured children transported to tertiary level intensive care were examined to determine the incidence of secondary insults incurred, as a function of escort training. Of all insults incurred, approximately 8% occurred with specialized pediatric transport escorts who were accompanied by a tertiary care physician (Group III, n = 52); 20% with specialized pediatric transport escorts alone (Group II, n = 44); and 72% with escorts who had not received specialized pediatric transport training (Group I, n = 34). Based on our results, we recommend that all transport coordinators review the qualifications and experience of their transport team members and all potential escorts to assess their ability to provide optimal care for the children they transport, particularly during long journeys, transfer by air, and when serious illness or injury is involved. | nervous system diseases |
A clinically applicable method for long-term salvage of postischemic skeletal muscle. The clinical significance and applicability of interventions aimed at reducing reperfusion injury in postischemic skeletal muscle remain unproven, since long-term muscle salvage has not been demonstrated by most treatment protocols that attenuate early reperfusion injury. We have shown that reperfusion of ischemic skeletal muscle results in an early and prolonged sequestration of white blood cells and activation of the alternative complement cascade. The purpose of this study was to determine if 40 minutes of reperfusion with blood depleted of white blood cells and complement proteins, followed by 2 days of normal perfusion, would reduce muscle necrosis after 5 hours of ischemia. The isolated paired canine gracilis muscle model was used. The treatment muscle was initially reperfused with arterial blood that had been spun, washed, passed through a leukocyte removal filter, and resuspended in hydroxyethyl starch (greater than 99.9% removal of white blood cells and the complement proteins factor B and C4). The contralateral control muscle was subjected to unaltered reperfusion. Blood flow (ml/min/100 gm) was measured by timed collection of gracilis venous blood. Myeloperoxidase activity (absorbance at 655 nm/min/mg tissue protein) in muscle biopsies was used to monitor white blood cell sequestration. After 48 hours of reperfusion in vivo, necrosis was quantified by nitroblue tetrazolium staining. Initial reperfusion with white blood cell and complement depleted blood significantly reduced muscle necrosis (53% +/- 3% vs 29% +/- 8%, p less than 0.0025, paired t test). Early blood flow was improved, (p = 0.0025, repeated measure-ANOVA), but subsequent white blood cell sequestration was not altered (p = 0.33, repeated measure-ANOVA). This suggests that a significant amount of white blood cell mediated injury occurs during the first 40 minutes of reperfusion. Preventing early complement activation and white blood cell mediated reperfusion injury is an intervention that is feasible during surgery and may result in clinically significant salvage of postischemic skeletal muscle. | general pathological conditions |
Diarrhea in ciguatera fish poisoning: preliminary evaluation of pathophysiological mechanisms. Ciguatera fish poisoning is a clinical syndrome consisting of a combination of gastrointestinal and neurological symptoms occurring after eating toxin-containing tropical reef fish; it is a major cause of morbidity in Hawaii, the South Pacific, Australia, and the Caribbean. In an effort to define pathophysiological mechanisms responsible for the diarrheal component of the illness, we examined the effect of crude and fractionated toxin preparations on isolated rabbit ileal tissue in a Ussing chamber model. Both the crude toxin preparation (prepared from toxic Ctenochaetus strigosus) and 10% and 50% methanol-chloroform toxin fraction (prepared from a pool of toxic fish samples) gave a striking increase in transepithelial electrical potential difference and short-circuit current. Enterotoxic activity seemed to be mediated by calcium. When examined by light microscopy, the intestinal mucosa was not damaged by the toxin preparations used. Our data demonstrate that toxins involved in ciguatera fish poisoning directly stimulate intestinal fluid secretion without accompanying tissue damage and suggest that calcium is the "second messenger" mediating the process. | digestive system diseases |
Spontaneous rupture of the spleen in initial presentation of Hodgkin's disease. A 46-year-old man presented with a four-week history of fevers, occasional chills, and a two-week history of sweats and poor appetite. He also complained of progressive weakness and lethargy. After initial evaluation, while awaiting further consultation, the patient developed rapidly progressing abdominal pain and light-headedness. He was moved immediately into the emergency treatment area. He was noted to have an acute abdomen and was taken to surgery. An enlarged Hodgkin's-infiltrated spleen with an actively bleeding hematoma was removed. The patient denied any history of trauma. | digestive system diseases |
Effect of acute hypercapnia on limb muscle contractility in humans. The effect of acute hypercapnia on skeletal muscle contractility and relaxation rate was investigated. The contractile force of fresh and fatigued quadriceps femoris (QF) and adductor pollicis (AP) was studied in normal humans by use of electrical stimulation. Maximum relaxation rate from stimulated contractions was measured for both muscles. Acute hypercapnia led to a rapid substantial reduction of contraction force. The respiratory acidosis after 9% CO2 was breathed for 20 min [mean venous blood pH 7.26 and end-tidal PCO2 (PETCO2) 65.1 Torr] reduced 20- and 100-Hz stimulated contractions of QF to 72.8 +/- 4.4 and 80.0 +/- 5.1% of control values, respectively. After 8 and 9% CO2 were breathed for 12 min, AP forces at 20- and 50-Hz stimulation were also reduced. Twitch tension of AP was reduced by a mean of 25.5% when subjects breathed 9% CO2 for 12 min [mean arterialized venous blood pH (pHav) 7.25 and PETCO2 66 Torr]. Over the range of 5% (pHav 7.38 and PETCO2 47 Torr) to 9% CO2, there was a linear relationship between twitch tension loss and pHav, arterialized venous blood PCO2, and PETCO2. Acute respiratory acidosis (mean PETCO2 61 Torr) increased the severity of low-frequency fatigue after intermittent voluntary contractions of AP. At 20 min of recovery, twitch tension was 63.2 +/- 13.4 and 46.8 +/- 16.4% of control value after exercise breathing air and 8% CO2, respectively. Acute hypercapnia (mean PETCO2 65.1 and 60.5 Torr) did not alter the maximum relaxation rate from tetanic contractions of fresh QF and from twitch tensions of AP. | general pathological conditions |
Interleukin-6 and its receptor are expressed by human megakaryocytes: in vitro effects on proliferation and endoreplication. Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in the megakaryocytic differentiation. Recently, we have observed that IL-6 is synthesized by several human cell lines with megakaryocytic features. In this study, we have investigated whether a similar phenomenon occurs during normal megakaryocytic differentiation. Human megakaryocytes (MK) were obtained by culturing normal marrow in liquid culture with aplastic plasma (AP). First, an IL-6 secretion in bone marrow culture enriched in MK as well as in purified MK populations was demonstrated by a biologic assay. Second, IL-6 mRNA was detected in a purified population of MK by the polymerase chain reaction and dot blot analysis. IL-6 mRNA and protein were undetectable in platelets. Third, in situ hybridization procedure demonstrated the presence of IL-6 mRNA in individual immature MK. Fourth, IL-6 protein was detected in MK at the unicellular level by an immunoalkaline phosphatase technique using a monoclonal antibody against IL-6. Furthermore, the presence of IL-6 receptor (IL-6-R) on MK was demonstrated by in situ hybridization using an IL-6-R probe and in situ autoradiography after binding with [125I]-labeled recombinant IL-6. The IL-6 endogenously produced in liquid cultures containing normal human plasma or AP was subsequently neutralized. This resulted in a 50% decrease of the MK growth with a minor shift in the ploidy distribution toward lower values. In semisolid cultures the addition of anti-IL-6 antibodies led to a 42% decrease in colony number in cultures stimulated by IL-3 but not in other conditions of culture. These results suggest that normal human megakaryocytopoiesis might be regulated in part by an IL-6 autocrine loop. | general pathological conditions |
Developmental dysmnesia in a poor reader. A 22-yr-old subject with moderate developmental dyslexia experienced poor memory from an early age. In spite of normal intelligence he had great difficulty in learning historical and geographical names, mathematical formulae, poems and songs, and verbal series such as the letters of the alphabet and the months of the year. His recognition of familiar faces was also faulty at times. A battery of memory tests confirmed a moderate deficit of verbal as well as visual memory, whereas spatial memory was preserved. Other cognitive functions were intact, except for a mild reading disability. No evidence of brain pathology was provided by his history, neurological examination and CT scanning. | nervous system diseases |
Diagnosis of noninfective cardiac mass lesions by two-dimensional echocardiography. Comparison of the transthoracic and transesophageal approaches. This study was conducted in 46 patients with cardiac thrombi, 15 patients with atrial myxomas, and 32 patients with other cardiac or paracardiac tumors. Diagnoses were subsequently proven by surgery, autopsy, computed tomography, magnetic resonance imaging, or angiography in all patients. All patients underwent precordial and transesophageal two-dimensional echocardiography to assess the various mass detection rates. Atrial myxomas and predominantly left-sided cardiac tumors were identified by both echocardiographic techniques with comparable detection rates. Left ventricular apical thrombi were detected more frequently by precordial echocardiography. In contrast, transesophageal echocardiography was superior in visualizing left atrial appendage thrombi, small and flat thrombi in the left atrial cavity, thrombi and tumors in the superior vena cava, and masses attached to the right heart and the descending thoracic aorta. These data indicate that transesophageal echocardiography leads to a clinically relevant improvement of the diagnostic potential in patients in whom cardiac masses are suspected or have to be excluded in order to ensure the safety of clinical procedures. | neoplasms |
Electron-microscopic identification of pseudoexfoliation material in extrabulbar tissue. The structure and distribution of pseudoexfoliation material in extrabulbar tissues from five eyes with typical unilateral intraocular pseudoexfoliation syndrome and two intraocularly unaffected fellow eyes were examined by transmission electron microscopy. In all seven eyes, unevenly distributed pseudoexfoliation aggregates were found in limbal conjunctivae, extraocular rectus and oblique muscles, orbital connective-tissue septa, and the walls of the posterior ciliary arteries, vortex veins, and central retinal vessels passing through the optic nerve sheaths. Typical pseudoexfoliation fibers occurred in close association with connective-tissue components, especially elastic fibers; a moderate predisposition of pseudoexfoliation clumps to accumulate around blood vessels was observed. The findings of pseudoexfoliation material in similar extrabulbar locations in intraocularly uninvolved fellow eyes indicates that pseudoexfoliation fiber formation outside the globe precedes its intraocular manifestation. The intermingling of pseudoexfoliation fibers, microfibrils, and elastic and collagen fibers suggests that pseudoexfoliation fiber formation might result from a disordered synthesis and/or assembly of connective-tissue microfibrils. | general pathological conditions |
Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. Two independent blinded observers reported the preoperative MRIs in a series of 81 consecutive patients with intractable temporal lobe epilepsy who were undergoing temporal lobectomy. We then compared the nature and lateralization of the MRI abnormalities with the pathologic diagnosis and the side of lobectomy. The MRI criteria of hippocampal sclerosis were an increased T2-weighted signal and the signal's confinement to a unilaterally small hippocampus. Imaging was performed in coronal and axial planes, specially orientated along and perpendicular to the long axis of the hippocampal body. We found diagnostic MRI abnormalities in 25 of the 27 cases with pathologically proven hippocampal sclerosis (sensitivity 93%, specificity 86%). In addition, we detected all 13 foreign tissue lesions on MRI. Overall, we detected lateralized lesions on MRI that correctly predicted the side of the epileptogenic temporal lobe in 72 cases (89%), with 2 possible errors. A learning effect in appreciating the relatively subtle MRI changes of hippocampal sclerosis was apparent in our later cases, as shown by an improved correlation between the 2 observers. This study demonstrates that hippocampal sclerosis can be identified on MRI with a high degree of sensitivity and specificity. | general pathological conditions |
Spinal cord stimulation: a contemporary series Forty-three patients with chronic pain disorders of different causes were selected for spinal cord stimulation. All underwent implantation of a ribbon electrode through a small laminotomy, under general anesthesia. Thirteen patients (30%) failed to obtain significant pain relief during a period of trial stimulation, and their electrodes were removed. The remainder underwent a definitive implant and were followed for a mean of 13 months (range, 3-33 months). Nineteen of them (63%) continued to experience pain relief. A detailed analysis of this series, as well as a literature review, is presented. | general pathological conditions |
Molteno implants and operating microscope-induced retinal phototoxicity. A clinicopathologic report. The right eye of a 75-year-old man with a history of cataract extraction, three penetrating keratoplasties, laser trabeculoplasty, two Molteno implants, and an operating microscope-induced retinal phototoxic lesion was studied post mortem. Histopathologic examination of the anterior segment showed evidence of penetrating keratoplasty, cataract surgery, and two Molteno implants with minimal associated tissue response. Ultrastructural examination showed a loose collagenous matrix surrounding the Molteno reservoirs, suggesting aqueous percolation from the reservoirs into the conjunctiva. Posteriorly, in the area of the phototoxic operating microscope-induced lesion, a nodule of retinal pigment epithelial hyperplasia with overlying atrophy of the photoreceptor cell layer of the neurosensory retina was noted. The retina also contained cystoid macular edema and an extensive preretinal membrane that was clinically unexpected. | general pathological conditions |
Pregnancy associated with Gorlin's syndrome. A pregnant woman with Gorlin's syndrome presented for the removal of malignant ovarian tumours. The main problem encountered by the anaesthetists was an unexpected increase in arterial blood pressure. This was most probably associated with surgical manipulation of the ovaries with an increase in prorenin/renin production. | cardiovascular diseases |
Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component. A clinical, histopathologic, and immunohistochemical study of six cases. We studied six cases of heavily pigmented melanocytic lesions with features of blue nevi within the dermis, but with an additional junctional dendritic component. This compound variant of blue nevus is an uncommon lesion that has not been previously identified as a distinct histologic entity. Immunoperoxidase staining for S100 protein and counterstaining with azure B distinguished the presence of melanocytes among numerous melanophages within the dermis. The compound variant of blue nevus can be distinguished histologically from combined blue nevus, pigmented spindle cell nevus, malignant melanoma, and melanosis due to a regressed malignant melanoma. The six lesions were from three men and three women whose ages ranged from 11 to 51 years (mean, 31 years). Three lesions were located on the trunk, two on the extremities, and one on the head. After a mean follow-up period of 47 months (range, 38 to 58 months), there was no evidence of recurrence. | neoplasms |
Anaesthetic management of the brain dead for organ donation. An increasing number of anaesthetists is being called upon to manage organ donors during organ retrieval procedures. We briefly describe the technical aspects of the surgical procedure together with a guide to the anaesthetic management. The aims of the latter may be summarized as the "Rule of 100": systolic blood pressure greater than 100 mmHg, urine output greater than 100 ml.hr-1, PaO2 greater than 100 mmHg, haemoglobin concentration greater than 100 g.L-1. Common management problems (hypotension, arrhythmias, diabetes insipidus, oliguria, and coagulopathy) are discussed in detail. The intraoperative management of the brain-dead organ donor provides the anaesthetist with the challenge of a major surgical procedure in a subject with important physiological derangements. | nervous system diseases |
Laparoscopic cholecystectomy: an initial report. Sixty consecutive patients underwent an elective attempt at laparoscopic cholecystectomy between March 15 and July 31, 1990 at the Mount Sinai Hospital in New York. Fifty-two patients had successful completion of the laparoscopic cholecystectomy (87%). The reasons for conversion to open cholecystectomy were acute cholecystitis (four patients), inability to define the cystic duct-common duct junction (three patients), and one patient with an unexpected choledochal cyst variant. Forty patients (77%) were discharged on the first post-operative day, and the remaining 12 patients on the second post-operative day. Thirty-three patients (63%) required only oral pain medication, and 11 patients (21%) needed no pain medication post-operatively. Fifty-one patients (98%) had resumed normal activities by the seventh post-operative day. Cholecystectomy remains the treatment of choice for biliary colic. Laparoscopic cholecystectomy minimizes length of stay in the hospital, lessens post-operative pain, allows quicker return to normal activities, and has a superior cosmetic result. | digestive system diseases |
Unilateral diffuse pulmonary artery involvement in Takayasu's arteritis associated with coronary-pulmonary artery fistula and bronchial-pulmonary artery fistula: a case report. Diffuse involvement of the right pulmonary artery associated with fistulas between the pulmonary artery and systemic artery is reported in a woman with Takayasu's arteritis. The most proximal portion of the abdominal aorta was pronouncedly narrowed and the aortic wall was markedly calcified. Both the celiac artery and the superior mesenteric artery were totally occluded and drained by the meandering artery arising from the inferior mesenteric artery. The proximal right pulmonary artery was focally narrowed and the middle lobe artery was occluded. All other branches of the right pulmonary artery were diffusely narrowed with sparse distributions of their distal branches. Fistulas were identified between the right coronary artery and the right pulmonary artery and between the right bronchial artery and the right pulmonary artery. This is the first English report of Takayasu's arteritis presenting with a coronary-pulmonary artery fistula that is secondary to a diffuse unilateral involvement of the pulmonary artery. | cardiovascular diseases |
Catheter modification of the atrioventricular junction with radiofrequency energy for control of atrioventricular nodal reentry tachycardia. BACKGROUND. The utility of transcatheter application of radiofrequency energy to eliminate atrioventricular nodal reentrant tachycardia (AVNRT) was investigated. METHODS AND RESULTS. Thirty-nine patients (mean age, 53 +/- 20 years; range 14-86 years) with medically refractory AVNRT underwent perinodal ablation with radiofrequency energy. A custom-designed 6F catheter with a large (3-mm-long) distal electrode and interelectrode pacing of 2 mm was used in the majority of cases. The catheter used for ablation was initially positioned across the tricuspid anulus to obtain the largest His bundle electrogram, then withdrawn to obtain the largest atrial:ventricular electrogram ratio, with a small His bundle electrogram (less than or equal to 100 microV). Each application of radiofrequency energy (350-550 kHz, 16.2 +/- 5.2 W) was stopped after 60 seconds or if PR prolongation or an impedance rise was noted. The endpoints of the procedure were persistent modification of atrioventricular nodal conduction (either first-degree atrioventricular block or impairment of ventriculoatrial conduction) and noninducibility of AVNRT before and during isoproterenol administration. Radiofrequency energy was applied a mean of 6.8 +/- 3.5 times per session. After a mean follow-up of 8 +/- 3.0 months, 32 of the 39 patients (82%) have been free of AVNRT, and did not have high grade AV block. Three patients (8%) developed complete atrioventricular block and had pacemakers implanted. Two patients had unsuccessful initial procedures, and two patients had initially successful ablations but had recurrences of tachycardia 4-6 weeks later. Elimination of AVNRT appeared to be due to effects on the retrograde fast pathway in most patients. CONCLUSIONS. Radiofrequency ablation of the perinodal right atrium appears to be safe and effective for treatment of typical AVNRT. | cardiovascular diseases |
Patterns of chromosomal breakpoint locations in Burkitt's lymphoma: relevance to geography and Epstein-Barr virus association. We have examined, by Southern blotting, the patterns of chromosomal breakpoint locations in 55 cases of Burkitt's lymphoma (BL) with respect to geography and Epstein-Barr virus (EBV) association. We have confirmed the association between chromosome 8 breakpoint and geography: 74% of endemic (eBL) but only 9% of sporadic BL (sBL) had breakpoints outside the HindIII fragment encompassing the c-myc gene (P2 less than .00001). Conversely, not only did 91% of sBL manifest a rearranged HindIII fragment, but at least 56% of these cases, in contrast to 17% of eBL cases, had a breakpoint within the first exon or intron of c-myc (P2 less than .004). Breakpoints outside the switch mu (S mu) region (ie, the HindIII fragment encompassing S mu) on chromosome 14 were twice as common overall (73%) as those within S mu (27%), but in the 15 tumors with S mu breakpoints, 13 (87%) had a rearranged c-myc gene. Breakpoints outside the HindIII fragment encompassing c-myc on chromosome 8 were predominantly associated with non-S mu breakpoints on chromosome 14 (85%) and this was the combination most frequently associated with eBL (65%; 6% of sBL, P2 less than .00001). In sBL, the most frequent breakpoint combination was a rearranged c-myc gene with a non-S mu breakpoint (63%; 13% of eBL). Twenty-eight percent of sBL and 13% of eBL had breakpoints both within c-myc and within S mu. EBV DNA was present in 19 of 20 tumors with breakpoints outside c-myc, in none of 7 with a breakpoint in the immediate 5' region of c-myc, in 4 of 5 tumors with breakpoints in the first exon, and in 7 of 12 tumors with breakpoints in the first intron. These data suggest that the pathogeneses of eBL and sBL differ with regard to the mechanism of c-myc deregulation, and probably also with regard to the state of differentiation of the target cell for malignant transformation. We have formulated a testable hypothesis regarding the potential role of EBV in pathogenesis: that it is required to contribute to the deregulation of c-myc in the presence of some, but not all, types of c-myc damage arising from the chromosomal translocations. | general pathological conditions |
Valproate metabolism during hepatotoxicity associated with the drug. Plasma concentrations of valproate and certain of its metabolites and their patterns of excretion in urine are described in three adults who developed hepatotoxicity during treatment of epilepsy with sodium valproate. One patient also developed a degree of reversible renal insufficiency, whilst another may have had associated infectious mononucleosis. All three cases showed evidence of impaired mitochondrial beta-oxidation of valproate. In one the impairment was at the stage catalysed by fatty acyl-CoA dehydrogenase, in another at the stage catalysed by 3-hydroxyacyl-CoA dehydrogenase and in the third at the stage catalysed by enoyl-CoA hydratase and possibly also at the next stage catalysed by 3-hydroxyacyl-CoA dehydrogenase. The impaired beta-oxidation meant that valproate metabolism was diverted into various alternative pathways. Plasma concentrations of the suspected hepatotoxic metabolite 4-en-valproate were normal for the valproate-treated population in all cases. By analogy with certain spontaneous and acquired human disorders of branched chain amino acid metabolism, it is suggested that valproate-associated hepatotoxicity may represent the consequences of a valproate overload on a limited mitochondrial beta-oxidation capacity, causing accumulation of a toxic product of endogenous branched chain amino acid metabolism. | digestive system diseases |
Experimental reduction of portal hypertension by mechanical increase of liver portal flow Studies on the isolated perfused rat liver demonstrated that an increase in portal pressure is associated with an increase in the portal blood flow in normal and in cirrhotic livers. In two pigs with portal hypertension mesenteric portal pressure was lowered by mechanically increasing the liver portal blood flow by means of a balloon pump around the portal vein. | digestive system diseases |
Red cell autoantibodies, multiple immunoglobulin classes, and autoimmune hemolysis. The effects and interrelationships of multiple immunoglobulin coating (i.e., increased red cell [RBC]-bound IgM and/or IgA in addition to IgG) were investigated in 404 patients with warm-reactive RBC autoantibodies on 590 occasions. Multiple immunoglobulins were detected by enzyme-linked direct antiglobulin tests in 218 samples (37%), but in only 87 (15%) by agglutination methods. Differences in populations were examined by chi-square, with p less than 0.005 being required for significance because of the multiple tests. Compared with IgG coating alone, multiple immunoglobulins were significantly associated with larger quantities (greater than 800 molecules/RBC) of IgG, multiple IgG subclasses, IgG3 and C3d bound to the cells, and with serum haptoglobin levels of less than 0.1 g per L. The latter association was still significant when higher levels of RBC-bound IgG and subclass pattern were taken into account. In samples with multiple immunoglobulin coating, there was no significant relationship (p greater than 0.05) between haptoglobins of less than 0.1 g per L and either C3d or multiple IgG subclasses. It was concluded that multiple immunoglobulin coating, even when undetected by agglutination methods, is a major cause of hemolysis: it is part of a more generalized autoimmune response and acts with other factors such as the quantity of bound IgG, the IgG subclass pattern, and complement; it also has an important hemolytic effect in its own right. | general pathological conditions |
Occupational sunlight exposure and melanoma in the U.S. Navy. Melanoma is the second most common cancer, after testicular cancer, in males in the U.S. Navy. A wide range of occupations with varying exposures to sunlight and other possible etiologic agents are present in the Navy. Person-years at risk and cases of malignant melanoma were ascertained using computerized service history and inpatient hospitalization files maintained at the Naval Health Research Center. A total of 176 confirmed cases of melanoma were identified in active-duty white male enlisted Navy personnel during 1974-1984. Risk of melanoma was determined for individual occupations and for occupations grouped by review of job descriptions into three categories of sunlight exposure: (1) indoor, (2) outdoor, or (3) indoor and outdoor. Compared with the U.S. civilian population, personnel in indoor occupations had a higher age-adjusted incidence rate of melanoma, i.e., 10.6 per 100,000 (p = .06). Persons who worked in occupations that required spending time both indoors and outdoors had the lowest rate, i.e., 7.0 per 100,000 (p = .06). Incidence rates of melanoma were higher on the trunk than on the more commonly sunlight-exposed head and arms. Two single occupations were found to have elevated rates of melanoma: (1) aircrew survival equipmentman, SIR = 6.8 (p less than .05); and (2) engineman, SIR = 2.8 (p less than .05). However, there were no cases of melanoma or no excess risk in occupations with similar job descriptions. Findings on the anatomical site of melanoma from this study suggest a protective role for brief, regular exposure to sunlight and fit with recent laboratory studies that have shown vitamin D to suppress growth of malignant melanoma cells in tissue culture. A mechanism is proposed in which vitamin D inhibits previously initiated melanomas from becoming clinically apparent. | neoplasms |
Management of perineal wounds following abdominoperineal resection with inferior gluteal flaps. Our experience treating perineal wounds secondary to abdominoperineal resection, either for inflammatory bowel disease or cancer, is presented. A total of 16 patients were treated either on a delayed basis or at the same time as the abdominoperineal resection. All wounds were closed using the inferior gluteal myocutaneous flap. Fifteen of 16 patients have achieved healing, eight of whom had no complications. Only minor revisions or local wound care were required in the remaining patients, with only one patient failing to heal. Our results compare favorably with previous reports of treatment of this difficult problem. | neoplasms |
Myeloma manifesting as a large jugular tumor: case report. The authors report a case of cranial plasmacytoma with multiple myelomas and palsy of the lower cranial nerves. The osteolytic lesion adjacent to the jugular foramen was demonstrated by an angiogram to be exceedingly hypervascular, with arteriovenous shunting resembling that seen in paragangliomas. Forty-five cases of cranial and intracranial plasmacytoma from the literature were reviewed. The findings indicate that a cranial plasmacytoma commonly appears to be a hypervascular tumor, whereas most dural tumors or intraparenchymal tumors have poor vascularity. | neoplasms |
Cardiorespiratory effects of antagonism of diazepam sedation with flumazenil in patients with cardiac disease. The specific benzodiazepine antagonist flumazenil is currently under intense study. Despite much clinical experience, no detailed invasive hemodynamic studies of its use in cardiac patients have been published. In the present study, hemodynamic and respiratory variables were measured in 10 cardiac patients undergoing catheterization of the right and left sides of the heart, before and after sedation with intravenous diazepam, and after reversal of sedation with flumazenil. A sleep dose of diazepam (12.2 +/- 5.1 mg, mean +/- SD) caused only slight decreases in mean arterial pressure (103 +/- 12 to 98 +/- 14 mm Hg; P less than 0.05), pulmonary capillary wedge pressure (13.2 +/- 6.3 to 11.7 +/- 6.6 mm Hg; P less than 0.05), and left ventricular end-diastolic pressure (20.8 +/- 7.5 to 17.3 +/- 10.0 mm Hg; P less than 0.05), with no significant changes in respiratory gas homeostasis. Intravenous flumazenil (0.22 +/- 0.07 mg) resulted in spontaneous awakening and return to full orientation, yet caused no significant alteration in either hemodynamic or respiratory variables measured. Reversal of diazepam-induced sedation by flumazenil in cardiac patients appears safe and effective. | cardiovascular diseases |
Hyperplastic gastric polyps associated with persistent Helicobacter pylori infection and active gastritis. We report two cases of patients with 3-yr histories of upper gastrointestinal symptoms, hyperplastic gastric polyps, and active chronic gastritis. Biopsies retrospectively stained with Giemsa revealed the persistent presence of Helicobacter pylori (HP) in gastric biopsies of both patients throughout the 3 yr. After treatment with amoxicillin and bismuth subsalicylate, both became asymptomatic, one demonstrating disappearance and recurrence of the gastric polyps in conjunction with the HP. These cases demonstrate 3 yr of hyperplastic gastric polyps associated with HP and active gastritis. | general pathological conditions |
Restoration by insulin of impaired prostaglandin E1/I2 receptor activity of platelets in acute ischemic heart disease. Treatment of normal platelet-rich plasma with a physiological amount of insulin (100 microunits/ml, optimum concentration) for 3 hours at 23 degrees C stimulated the binding of prostaglandin E1 by more than twofold (3,940 +/- 250 sites/10(8) platelets) compared with the nontreated, control platelet-rich plasma (1,590 +/- 265 sites/10(8) platelets). After platelet-rich plasma from patients with acute ischemic heart disease (n = 43), whose platelets showed impaired prostaglandin E1/I2 receptor activity (850 +/- 100 sites/10(8) platelets), was incubated with insulin (optimum amounts varied from 100 to 200 microunits/ml), the binding of the prostanoid was restored to normal levels (1,790 +/- 140 sites/10(8) platelets) in 75% of the cases. Twenty-five percent of the patients did not respond to the stimulatory effect of insulin. The increased binding of the prostanoid to the insulin-treated platelets also resulted in increased cyclic AMP levels both in normal subjects (44.14 +/- 3.1 pmol/10(8) [insulin-treated] platelets versus 16.35 +/- 2.91 pmol/10(8) [control] platelets) and in patients with acute ischemic heart disease (23.87 +/- 4.1 pmol/10(8) [insulin-treated] platelets versus 7.70 +/- 2.0 pmol/10(8) [control] platelets) by the prostanoid (1.0 microM). The treatment of platelet-rich plasma with the hormone decreased the minimum inhibitory concentration of the prostanoid from 34 +/- 14 to 15 +/- 9 nM (p less than 0.001) in the case of normal volunteers and from 49 +/- 15 to 32 +/- 11 nM (p = 0.002) in the case of "responder" patients. Insulin did not produce any effect on the inhibition of platelet aggregation by the prostaglandin in "nonresponder" patients. In the follow-up study, although the stimulatory effects of insulin on platelets from responder patients were improved to normal levels, the platelets from the nonresponder patients remained persistently unresponsive to the effect of the hormone. | general pathological conditions |
Impairment of sequences of memory-guided saccades after supplementary motor area lesions. Different paradigms of saccades were recorded electro-oculographically in 2 patients with infarction affecting the left supplementary motor area. Saccades made toward visual targets (visually-guided saccades) or away from them (antisaccades) were normal in both patients. Memory-guided saccades, made to the remembered position of a flash occurring 2 seconds before, were preserved in 1 patient and only slightly impaired in the other. However, sequences of two or three memory-guided saccades were severely impaired in both patients. It has previously been reported that the supplementary motor area plays an important role in programming sequential limb movements. Our data suggest that this area plays a similar role in the control of sequential eye movements. | nervous system diseases |
Ventricular arrhythmias after correction of ventricular septal defects: importance of surgical approach. To compare the prevalence of conduction disturbances and ventricular arrhythmias in cases of postoperative ventricular septal defect, 100 patients (50 with repair by right atriotomy, group 1; and 50 with repair by right ventriculotomy, group 2) underwent complete evaluation including an electrocardiogram (ECG) and 24 h ambulatory ECG monitoring. The two groups were comparable except for a shorter follow-up duration (7 +/- 3 versus 12.4 +/- 7 years) and a younger age at evaluation (12.4 +/- 5 versus 16.9 +/- 7 years) in group 1. Complete right bundle branch block was less frequent in group 1 than in group 2 (20% versus 50%, p less than 0.05) but three of the four patients with complete atrioventricular (AV) block detected on ambulatory monitoring were in group 1. Six patients had significant supraventricular arrhythmias, all well tolerated. Ambulatory monitoring revealed significant ventricular arrhythmias (modified Lown grade 2 or higher) in 39 patients, with a lower prevalence in group 1 (30% versus 48%, p = 0.05). No correlation was found between prevalence of ventricular arrhythmias and right ventricular systolic pressure, cardiopulmonary bypass duration, presence of a synthetic patch, previous pulmonary artery banding, presence of complete right bundle branch block and cardiomegaly on chest X-ray film. Prevalence of ventricular arrhythmias increased with follow-up duration, age at evaluation and age at surgery. These were always well tolerated and did not warrant treatment. Thus, right atriotomy reduces the prevalence of right bundle branch block but does not prevent late AV block. Ventricular arrhythmias are frequent after surgical closure of ventricular septal defect whatever the surgical approach and their prevalence is not statistically different from that in postoperative tetralogy of Fallot. | cardiovascular diseases |
Lovastatin decreases coenzyme Q levels in humans. Lovastatin is clinically used to treat patients with hypercholesterolemia and successfully lowers cholesterol levels. The mechanism of action of lovastatin is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA. Inhibition of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol. The clinical use of lovastatin is to reduce a risk of cardiac disease, and if lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function. We have conducted three related protocols to determine whether lovastatin does indeed inhibit the biosynthesis of CoQ10. One protocol was done on rats, and is reported in the preceding paper [Willis, R. A., Folkers, K., Tucker, J. L., Ye, C.-Q., Xia, L.-J. & Tamagawa, H. (1990) Proc. Natl. Acad. Sci. USA 87, 8928-8930]. The other two protocols are reported here. One involved patients in a hospital, and the other involved a volunteer who permitted extraordinary monitoring of CoQ10 and cholesterol levels and cardiac function. All data from the three protocols revealed that lovastatin does indeed lower levels of CoQ10. The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy before lovastatin or after taking lovastatin. Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10. | cardiovascular diseases |
Aggravation of human and experimental myasthenia gravis by contrast media. After observing a 72-year-old myasthenic patient develop an acute myasthenic exacerbation following the administration of routine diagnostic IV contrast material, an observation rarely described in the literature, we used the experimental autoimmune myasthenia gravis model in rabbits injected with a contrast agent to simulate the situation. There was significant worsening of the decremental response to 3 Hz repetitive nerve stimulation from 40 +/- 29% to 55 +/- 27% following the IV administration of contrast agent at doses similar to those used in humans. IV calcium partially reversed this aggravation. Caution is merited when myasthenic patients are administered contrast media. | general pathological conditions |
Effect of recombinant hirudin, a specific inhibitor of thrombin, on endotoxin-induced intravascular coagulation and acute lung injury in pigs. We hypothesized that thrombin activation may play a prominent role in endotoxin-induced secondary organ failure, such as acute lung injury. To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs. The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters. A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin. Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin. All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment. Data are expressed as the mean (95% confidence interval). Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002). These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin. Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm-5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299). | general pathological conditions |
The development of neutralizing antibodies in a patient receiving subcutaneous recombinant and natural interleukin-2. Systemic administration of interleukin-2 (IL-2) in humans may induce antibodies specific to IL-2. The case is reported of a patient with metastatic rectal carcinoma who was treated with long-term subcutaneous IL-2 and a combination of subcutaneous IL-2 and interferon-alpha 2b (IFN-alpha 2b). This patient developed nonneutralizing and neutralizing anti-IL-2 antibodies recognizing both the recombinant and natural cytokine. Detectable serum levels of neutralizing antibodies were accompanied by the inhibition of immune responsiveness to systemic IL-2 in vivo. | neoplasms |
Nerve growth factor corrects developmental impairments of basal forebrain cholinergic neurons in the trisomy 16 mouse. The trisomy 16 (Ts16) mouse, which shares genetic and phenotypic homologies with Down syndrome, exhibits impaired development of the basal forebrain cholinergic system. Basal forebrains obtained from Ts16 and euploid littermate fetuses at 15 days of gestation were dissociated and cultured in completely defined medium, with cholinergic neurons identified by choline acetyltransferase (ChAT) immunoreactivity. The Ts16 cultures exhibited fewer ChAT-immunoreactive neurons, which were smaller and emitted shorter, smoother, and more simplified neurites than those from euploid littermates. Whereas the addition of beta-nerve growth factor (100 ng/ml) augmented the specific activity of ChAT and neuritic extension for both Ts16 and euploid cholinergic neurons, only Ts16 cultures exhibited an increase in the number and size of ChAT-immunoreactive neurons. Furthermore, Ts16 ChAT-immunoreactive neurites formed varicosities only in the presence of beta-nerve growth factor. | general pathological conditions |
Longitudinal study of women with negative cervical smears according to endocervical status A longitudinal study of 20,222 women who received negative cervical smear reports in 1987 showed that the incidence of definite or equivocal cervical intraepithelial neoplasia (CIN) was not significantly different between those whose first smear lacked an endocervical component and those whose smear included an endocervical component. The incidence of definite cytological evidence of CIN was significantly lower in women whose first smear did not include an endocervical component. It is concluded that women whose smears are reported as negative but lack an endocervical component should not be rescreened any earlier than women with negative smears that include an endocervical component. | neoplasms |
An evaluation of the distinction of ectopic and pituitary ACTH dependent Cushing's syndrome by clinical features, biochemical tests and radiological findings. The efficiency of various laboratory and radiological investigations in the differentiation of ectopic from pituitary dependent Cushing's syndrome was studied, based on findings in 23 patients with verified Cushing's disease and seven patients with the ectopic ACTH syndrome. Clinical features strongly favouring the ectopic type were male sex and history for less than 18 months. Basal biochemical features strongly indicating the ectopic syndrome included plasma K+ less than 3.0 mmol/l and HCO3 greater than 30 mmol/l; serum cortisol at 9 a.m. or midnight of greater than 800 nmol/l; urine free cortisol greater than 1300 nmol/24 hours; plasma ACTH greater than 100 ng/l. In the high-dose dexamethasone suppression test, suppression by less than 50 per cent of 9 a.m. serum cortisol, urine free cortisol or 17-oxogenic steroids was usually indicative of an ectopic source of ACTH. A mean suppressed value of greater than 450 nmol/l for the 9 a.m. and midnight cortisol combined occurred in all of those with the ectopic syndrome, but in none of the 23 patients with Cushing's disease. For urine free cortisol, a mean suppressed value of less than 1000 nmol/24 hours was found in all patients with Cushing's disease, but in none of those in the ectopic group. In the metyrapone test, there was an increase of less than or equal to 3-fold in 11-deoxycortisol at 24 hours in patients with ectopic ACTH; the increase was greater than 3-fold in all but one of the patients with Cushing's disease. Failure to respond to either dexamethasone or metyrapone was found in only one of the patients with Cushing's disease (Patient 16); in the ectopic group, all patients except Patient D failed to respond to either test. It is concluded that patients presenting with clinically obvious Cushing's syndrome along with measurable plasma ACTH can be reliably divided by conventional tests into those that are driven from the pituitary and those driven by ectopic ACTH. | neoplasms |
Comparative ophthalmologic studies on children and adults with craniopharyngiomas. The subjects of the study are 74 patients with craniopharyngiomas treated at the Clinic of Neurosurgery, Bulgarian Medical Academy, within the period 1960-1989. Fifty of the patients are children and 24 adults. The diagnosis of all patients is made on the base of clinical, X-ray and histological studies. The ophthalmologic state was studied in all patients, prior to operation, via routine methods. Reduced visual acuity was established in 69.6% of the children and 81.8% of the adults. The presence of congestive optic papilla was diagnosed in 22% of the children and 12.5% of the adults. Optic atrophy was established in 62.5% of the adults and 52% of the children. Various defects in the visual field were established in 67.7% of the children and 81.8% of the adults with the predomination of bitemporal defects. The use of highly informative conventional and modern X-ray methods is recommended in all patients suspected of compression of the visual pathways. | neoplasms |
Assessment of right ventricular oxidative metabolism by positron emission tomography with C-11 acetate in aortic valve disease. Evaluation of right ventricular (RV) oxidative metabolism is limited by the inability to easily determine oxygen extraction by the RV myocardium and the complex morphology of this ventricle. Because left ventricular C-11 clearance rate constants closely correlate with myocardial oxygen consumption, it was postulated that C-11 clearance rate constants for the RV free wall should also reflect its oxygen consumption. Therefore, RV C-11 clearance rate constants were compared with RV loading in 21 patients with aortic valve disease to assess the possible use of this technique for noninvasive evaluation of RV oxidative metabolism. RV free wall C-11 clearance rate constants correlated with the product of systolic pulmonary artery pressure and heart rate for all patients (r = 0.65, p = 0.002), but the relation was stronger if 2 patients with overt RV dysfunction were excluded (r = 0.83, p = 0.001). On the basis of mean pulmonary artery pressures, patients were stratified into subgroups with normal (group I, n = 8) and elevated (group II, n = 13) pulmonary pressures and were compared with 10 normal control subjects. RV C-11 clearance rate constants were significantly higher in group II than in group I and in normal control subjects (p less than 0.05). These data suggest that RV C-11 acetate clearance rate constants can provide noninvasive evaluation of RV oxidative metabolism. This technique may allow serial assessment of RV performance in various cardiac and pulmonary diseases, and particularly of changes associated with therapeutic interventions. | cardiovascular diseases |
Effects of neuroleptic agents on rat skeletal muscle contracture in vitro. The purpose of this investigation was to examine and compare the effects of both in vivo pretreatment and in vitro treatment with the neuroleptic agents droperidol, haloperidol, and trifluoperazine on skeletal muscle contracture using an in vitro model. Strips of normal rat diaphragm were challenged with succinylcholine and halothane (halothane: 1% and 3%) subsequent to either in vitro administration (10-100 microM) or in vivo pretreatment (0.35-2.80 mg/kg) with droperidol, haloperidol, or trifluoperazine. After equilibration, maximum increases in tension were recorded and mean data analyzed by analysis of variance (P less than 0.05). When either droperidol or trifluoperazine was administered in vivo, contracture values after exposure to succinylcholine and halothane were significantly decreased. After in vivo pretreatment with haloperidol or in vitro administration of droperidol, succinylcholine-induced contractures were significantly reduced; contractures subsequently induced by halothane did not significantly differ from that of controls. In vitro treatment with haloperidol and trifluoperazine, however, produced significant increases in tension in muscles exposed to succinylcholine and halothane. This study provides evidence that droperidol may be considered a safe anesthetic adjunct in malignant hyperthermia-susceptible patients, and, additionally, that caution should be exercised when interpreting results from studies in which contracture testing is performed on muscle from patients treated with neuroleptic agents. | general pathological conditions |
Volume conduction of the parietal N20 potential to the prerolandic frontal area. Somatosensory evoked potentials were recorded from the frontal and parietal areas in patients with various lesions in the central nervous system on stimulation of the median nerve. Five representative cases who showed a selective loss of the positive potential from the frontal area are reported. In each case, the parietal N20 potential was relatively well preserved, and the midposition between the frontal and central areas (FC area) showed a negative potential following P14. The peak of this negative potential was synchronous with that of the parietal N20 potential. This negativity on the FC area is considered to be a volume conducted potential from the parietal N20 to the prerolandic frontal area. Such an anterior volume conduction of the parietal N20 would not be explained by the concept of a tangentially oriented dipole generated in the posterior bank of the central sulcus. Instead, for the generator of the parietal N20 potential, a radically oriented dipole generated mainly in the parietal area is postulated. | nervous system diseases |
Dynamic changes in left ventricular outflow tract flow velocities after amyl nitrite inhalation in hypertrophic cardiomyopathy. Doppler echocardiography was performed in 21 patients with hypertrophic cardiomyopathy (HC), in nine patients with no evidence of left ventricular (LV) hypertrophy by two-dimensional echocardiography, and in five patients with systemic hypertension and concentric LV hypertrophy. The LV outflow tract (LVOT) peak velocity was recorded by continuous wave Doppler technique at rest and after amyl nitrite inhalation. The LVOT pressure gradient was calculated by the modified Bernoulli equation. A significant increase in heart rate and a drop in systolic blood pressure were observed in all patients after amyl nitrite inhalation; no adverse effects were encountered. The peak LVOT velocity and pressure gradient increased significantly after provocation in all patients, but the increase was much more pronounced in patients with HC (peak LVOT velocity increased from 2.2 +/- 0.8 to 4.3 +/- 1.0 m/sec and peak gradient increased from 22 +/- 17 to 78 +/- 36 mm Hg). The Doppler spectral signal in patients with HC demonstrated a characteristic contour, with peak velocity occurring in late systole. However, the observed increase in LVOT peak velocity was not statistically different between treated (with beta-blockers and calcium blockers) and untreated patients with HC. We conclude that LVOT peak velocity and pressure gradients in patients with HC can be readily assessed by Doppler echocardiography both at rest and after amyl nitrite inhalation. The dynamic changes in LVOT velocity induced by this provocation have certain characteristic features in obstructive HC but appear to be independent of the medical regimen used, at least in the dosages tested in our study. | cardiovascular diseases |
Reduced frequency of hypertensive disorders in placenta previa The isthmic segment of the uterine artery's ascending branch has a freer course and wider diameter than distal parts of the vessel. Therefore, we assumed that this arterial segment would provide better blood flow and prevent hypoxia of the trophoblast. As a result, placenta previa pregnancies would be complicated by hypertensive disorders less often than are pregnancies with normally implanted placentas. To test this hypothesis, 491 placenta previa pregnancies, among a population of 106,866 pregnant women, were compared with pregnancies with normally implanted placentas. Clinically meaningful and statistically significant reductions in the rates and risks of hypertensive disorders were found in placenta previa pregnancies (P = .002, relative risk = 0.44, 95% confidence interval 0.25-0.78). The differences persisted when primiparous and multiparous women were examined separately and when preterm and term deliveries were separated. In a multivariate logistic regression analysis, patients with placenta previa had a third of the risk for hypertensive disorders compared with pregnant women with normally implanted placentas (relative risk = 0.36, 95% confidence interval 0.20-0.64), even after controlling for parity and preterm or term delivery. In the same model, primiparity and preterm delivery were each associated with a doubling of risk for hypertensive disorders, regardless of the placental implantation site. Thus, regardless of parity and preterm or term delivery, placenta previa and hypertensive disorders are inversely related. | cardiovascular diseases |
Does primary fibromyalgia exist? Twenty-one of 25 consecutive primary fibromyalgia or fibrositis patients, identified during a 5-year period in a tertiary care day-ward for pain syndromes, were re-examined. Fifteen fulfilled criteria for fibromyalgia but unexpectedly, all cases had either psychiatric disturbance or thyroid dysfunction. Of the four patients not seen at follow-up, two had developed neurological diseases, another rheumatoid arthritis and one other hypothyroidism. Thus, after 5 years no patient fulfilled the criteria for primary fibromyalgia. Women occupied as manual workers were over-represented. Most patients reported beneficial effects of physiotherapy. None of the patients has been able to return to full time work. | nervous system diseases |
Prognostic significance of nondiploid DNA determined by flow cytometry in sporadic and familial medullary thyroid carcinoma. To clarify the role of DNA measurements in predicting outcome after surgical treatment of medullary thyroid carcinoma (MTC), we performed flow cytometric analysis in nuclear suspensions of 119 MTC tumors. Of the 119 patients, 63 (53%) patients had sporadic tumors and 56 (47%) patients had familial tumors; survivors were followed for a mean of 13 years. DNA content was normal in 92 (77%) patients and abnormal (nondiploid) in 27 (23%) patients. Ten-year cause-specific mortality rates were 12%, 42%, and 49% with diploid, tetraploid/polyploid, or aneuploid tumors (p = 0.0009) and were greater with nondiploid tumors both in the sporadic (p = 0.012) and multiple endocrine neoplasia (familial) cases (p = 0.114). None of 27 patients with TNM stage I disease died of MTC. In patients with TNM stages II, III, and IV disease, DNA nondiploid tumors were associated with increased deaths from MTC. In a Cox proportional hazards model involving all 119 patients and adjusted for disease stage and inheritance pattern, nondiploid DNA was independently associated with increased deaths from MTC (p = 0.008). In an identical Cox model restricted to the 92 DNA diploid tumors, an S-phase fraction of 15.0% or more remained a significant variable (p = 0.034) after adjustment for stage and inheritance pattern. We therefore conclude that DNA measurements do have a role to play in predicting outcome after surgical treatment of MTC. | neoplasms |
Differential reading recovery in patients with severe to moderate closed head injury. A differential recovery was seen when alternate forms of a nationally standardized test of Reading Vocabulary, Literal Reading Comprehension and Inferential Reading Comprehension was administered serially to 10 consecutive closed head injury admissions to a university rehabilitation hospital. Inferential Reading Comprehension was the most impaired and had the fastest recovery rate. Subtle cognitive deficits in Inferential Reading Comprehension were detected when Reading Vocabulary was at or better than a twelfth grade level. Maximal recovery of all three reading functions occurred within 4 months after trauma, with most occurring in the first 3 months. The reading recovery pattern parallels the recovery of intelligence scores in the literature. | general pathological conditions |
Warm heart surgery. Hypothermia is widely acknowledged to be the fundamental component of myocardial protection during cardiac operations. Although it prolongs the period of ischemic arrest by reducing oxygen demands, hypothermia is associated with a number of major disadvantages, including its detrimental effects on enzymatic function, energy generation, and cellular integrity. We hypothesized that the ideal protected state of the heart would be electromechanically arrested and perfused with blood, that is, aerobic arrest. Under these conditions the fundamental need for hypothermia becomes questionable. We have developed a novel approach to myocardial protection during cardiac operations based on these concepts, in which the chemically arrested heart is perfused continuously with blood and maintained at 37 degrees C. In 121 consecutive coronary bypass procedures we have compared this approach with a historical cohort of 133 consecutive patients treated with hypothermic cardioplegia. Perioperative myocardial infarction was significantly less prevalent (1.7% versus 6.8%; p less than 0.05) in the warm cardioplegic group, as was the use of the intraaortic balloon pump (0.9% versus 9.0%; p less than 0.005) and the prevalence of low output syndrome (13.5% versus 3.3%; p less than 0.005). Cardiac output immediately after bypass was significantly higher than before bypass (3.1 +/- 0.9 versus 4.9 +/- 1.0 L/min; p less than 0.001) only in the warm cardioplegia group. Furthermore, the heartbeat in 99.2% of patients treated with continuous warm cardioplegia converted to normal sinus rhythm spontaneously after removal of the aortic crossclamp compared with only 10.5% of the hypothermic group. The time from removal of the aortic crossclamp to discontinuation of cardiopulmonary bypass (i.e., reperfusion time) was significantly shorter in the warm cardioplegia group (11 +/- 4.3 versus 27 +/- 5.6 minutes; p less than 0.001). Our results suggest that continuous normothermic blood cardioplegia is safe and effective. Conceptually, this represents a new approach to the problem of maintaining excellent myocardial preservation during cardiac operations. | general pathological conditions |
Presymptomatic and prenatal diagnosis of myotonic muscular dystrophy with linked DNA probes. Advances in neurogenetics are facilitating clinical care. Localization of the mutant gene that causes myotonic muscular dystrophy (DM) to chromosome 19 enabled our predictive testing using linked DNA probes in 74 members of 12 families at risk. Individuals sought either diagnostic confirmation or exclusion with childbearing in mind, or requested prenatal diagnosis. Valuable information was provided for 11 of 12 families. Of 14 individuals at 50% risk, 12 learned they did not have DM, two learned they did (although presymptomatic), and prenatal diagnoses of affected fetuses were made in three families--all with high degrees of certainty. The future opportunity for prenatal diagnosis was provided for 3 other families. The potential health risks to an affected female and her affected or nonaffected fetus provide cogent reasons for physicians to inform DM families in their care about these important advances and opportunities to avert grave complications. | nervous system diseases |
Identification of viruses in a study of acute respiratory tract infection in children from Uruguay. For the purpose of identifying viral agents associated with acute respiratory tract infections (ARI) in children less than 5 years old, a longitudinal community study was undertaken in Montevideo, Uruguay, from May 1985 to December 1987. This report includes results obtained by cell culture and immunofluorescence techniques for detection of respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza 1 and 3 viruses, and adenovirus. Two populations were studied: children visited at home by pediatricians (group 1) and children with an ARI episode who attended an outpatient clinic (group 2). Nasopharyngeal aspirates were obtained at the time of an ARI episode: 858 from group 1 and 488 from group 2. Viruses were identified in 15.3% of group 1 specimens and in 17.6% of group 2 specimens. RSV was the most frequently recovered agent, accounting for 67.9% and 58.1%, respectively, of all viruses detected. The sensitivity and specificity of RSV isolation by cell culture are compared with detection by indirect immunofluorescence. | general pathological conditions |
Intraoperative radioimmunodetection of ovarian cancer using monoclonal antibody B72.3 and a portable gamma-detecting probe. To assess the value of radioimmunoguided surgery in the intraoperative detection of ovarian cancer, we used monoclonal antibody B72.3, radiolabeled with 125I, and a hand-held gamma-detecting probe in 13 women with ovarian cancer undergoing exploratory laparotomy. B72.3, which recognizes a tumor-associated glycoprotein, TAG 72, was injected 12-29 days preoperatively (intraperitoneally in four cases, intravenously in nine, and by both routes in one). Intraoperatively, the abdomen was surveyed with the probe and probe counts were correlated with biopsies and excised specimens studied by routine histologic stains. Probe counts were positive in four of seven evaluable patients with histologically confirmed disease. In three of these four patients, the probe detected cancer in specimens interpreted as normal on frozen histologic sections. The probe also identified microscopic cancer in the one patient who had no gross disease. The specificity of the probe was 70%. Preoperative computed tomography was normal in all patients, including those with tumors as large as 3 cm. This pilot study shows the ability of radioimmunoguided surgery to detect occult ovarian cancer. | neoplasms |
A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy. A multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis (MG) in Italy. Data from 1152 patients, fairly representative of the myasthenic population seeking medical advice, were analysed for diagnostic criteria, clinical aspects and therapeutic approaches. Mean follow-up was 4.9 years. The disease was correctly diagnosed within 2 years of the onset in 80% of cases. Onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males. At first observation 87% of the patients had generalized MG. Maximal worsening was observed within 3 years in 77% of patients. At the last follow-up, 35% of cases were symptom-free (pharmacological remission 24%, remission without treatment 11%). The more severe the disease at the first observation and at the maximal worsening of symptoms, the lower was the proportion of remissions. Steroids were given in 54% and immunosuppressants in 18%. Thymectomy was performed in 72%, mostly in women, younger than age 40, and with generalized MG. Thymectomy seemed to improve the course of the disease, mostly in patients operated on shortly after diagnosis and those with generalized mild-to-moderate disease and with a normally involuted thymus. MG was lethal in 4% of patients, principally men, older than 40, in grade 3 or worse at first observation, with a short history of disease, and with thymona. | neoplasms |
Emergency cardiopulmonary bypass support in patients with cardiac arrest. Emergency percutaneous cardiopulmonary bypass support was instituted in 11 patients in cardiac arrest refractory to conventional resuscitation measures. Emergency percutaneous cardiopulmonary bypass support was used in five patients in whom cardiac arrest occurred as a result of a complication in the cardiac catheterization laboratory (group 1) and in six other patients in cardiac arrest (group II). A 21F cannula and a 17F cannula were percutaneously inserted into the femoral vein and artery. Flow rates of 3 to 5 L/min were achieved with restoration of mean arterial pressure to 70 mm Hg (range 50 to 75). The status of all 11 patients was improved initially both clinically and hemodynamically with percutaneous cardiopulmonary bypass. Of the group II patients, three had anatomy unsuitable for percutaneous transluminal coronary angioplasty or coronary bypass grafting, could not be weaned from cardiopulmonary support, and died; three of these patients had coronary artery bypass grafting and two survived. All five group I patients underwent successful coronary bypass grafting and survived. Of the seven patients with anatomically correctable disease, all seven were discharged from the hospital. With conventional management nearly all seven of these patients would have died. Nine of 11 patients underwent a cardiac operation and seven of the nine survived. The operative mortality rate was 22% and the overall survival rate was 64%. At follow-up (mean 7 months), all seven patients are alive and six have resumed a normal and active life-style. In conclusion, emergency percutaneous cardiopulmonary bypass support is a powerful resuscitative tool that may stabilize the condition of patients in cardiogenic shock and cardiac arrest to allow for definitive intervention. | general pathological conditions |
Rapid intravenous rehydration in the pediatric emergency department Children suffering from mild to moderate (3 to 6%) dehydration likely caused by viral gastroenteritis are often hospitalized because they are unable to tolerate oral fluids. We studied 17 such children, aged one to six years, who were otherwise healthy. All had isonatremic dehydration and were treated with 30 ml/kg of 3.3% dextrose and 0.3% saline over a period of three hours in the emergency department before being discharged. No patient required admission to the hospital. Only one patient required another course of rapid intravenous rehydration and subsequently improved without hospitalization. Although all our patients experienced vomiting before treatment, 65% had no vomiting after treatment. Rapid intravenous rehydration is an effective treatment, for children with mild to moderate dehydration secondary to presumed viral gastroenteritis, that obviates the need for hospitalization. | digestive system diseases |
Biopsy of the breast for mammographically detected lesions. We prospectively studied 718 women who underwent biopsy of the breast for suspicious, mammographically detected mammary lesions in an attempt to identify key clinical risk factors, as well as roentgenographic characteristics associated with the appearance of early carcinoma of the breast. Patients with a benign outcome had an average age of 55 years versus 63 years for patients with carcinoma of the breast. Seventy-six per cent of these patients had no previous history of mammary problems, 20 per cent had a positive family history for carcinoma of the breast, 58 per cent were premenopausal and 21 per cent had used birth control pills. Except for age (p less than 0.001), the distribution of clinical risk factors was equal among patients with benign or malignant outcomes. Suspicious mammographic findings included mass lesions (53 per cent), calcifications (36 per cent) and the association of both (11 per cent). The predominant Wolfe pattern on mammography was P1 (36 per cent). No relationship was observed between Wolfe pattern and malignant conditions. In this group of patients, mammography was poorly specific; however, the positive predictive value increased with age and is related to the age-specific prevalence of carcinoma of the breast. Eight hundred and twenty-five lesions were removed. Twenty-five per cent (n = 203) of the specimens taken at biopsy contained carcinoma. Stellate mass lesions were highly suggestive of a malignant growth (p less than 0.0001). No relationship between the size of the suspicious mammographic mass and the malignant lesion was observed. A marked correlation (chi-square test with Yate's correction) was observed between malignant tumor and lesions with a linear or branching pattern, more than 15 calcifications, or small sized calcifications. The presence of a mass with calcifications was associated with carcinoma in 34 per cent. The incidence of invasive carcinoma was much higher for mass lesions (81 per cent) than for suspicious calcifications (56 per cent) (p less than 0.0001). | neoplasms |
Progressive hemolytic anemia due to delayed recognition of a Beall mitral valve prosthesis. In addition to a working knowledge of general complications such as thromboembolism and infective endocarditis, optimal care of the patient with a prosthetic valve requires specific knowledge concerning the characteristics of a given patient's prosthesis. This may need to include the ability to identify the valve roentgenographically when history and records are unavailable. A 53-year-old woman with mitral stenosis secondary to rheumatic heart disease and status post a reported Bjork-Shiley mitral valve (MV) replacement 17 years prior to hospital admission was referred for evaluation of severe hemolytic anemia. Previous cinefluoroscopy in 1986 at the time of a cerebrovascular accident revealed a normally functioning caged disc prosthesis and not the tilting disc of a Bjork-Shiley prosthetic valve. The valve was not further characterized and she continued receiving warfarin therapy until May 1989 when she presented with laboratory findings showing a marked hemolytic anemia with a hemoglobin of 6.5 mg/dl and lactate dehydrogenase (LDH) value of 2100 IU. Echocardiography revealed normal valvular function without evidence of perivalvular leak. The patient was referred for further evaluation with chest roentgenogram at the time of hospital admission revealing a valve configuration characteristic of the Beall model 103/104 series that has been found to manifest progressive disc variance with a high degree of hemolytic anemia (despite normal noninvasive evaluation of MV function), disc tilting with intermittent regurgitation, and catastrophic disc embolization in extreme cases. The precise identification of valvular prosthesis in patients after valve replacement is crucial for optimal management. As in our case, the mere identification of a particular valve may necessitate certain management and therapy based on the natural history of that valve. In the absence of reliable history and/or records, the roentgenographic examination should lead to the precise identification. | general pathological conditions |
A small animal model of human Helicobacter pylori active chronic gastritis. Isolation of a spiral-shaped bacterium closely related to Helicobacter pylori from the cat stomach made it possible to investigate new small animal models of gastric infection. Pure cultures of this bacterium, provisionally named "Helicobacter felis," were fed to germ-free mice. The organism colonized the stomach in large numbers in mucus and deep in the gastric pits and showed the same gastric trophism found with H. pylori. Significant histopathology was seen in all H. felis-infected mice. At 2 weeks postinfection, an acute inflammatory response was seen composed primarily of eosinophils and neutrophils. At 3 weeks, the polymorphonuclear response was more pronounced with large numbers of neutrophils in some areas forming small microabscesses. Lymphocytes also increased in number. By 8 weeks, several relatively large lymphoid nodules were present in the submucosa. Multiple small microabscesses were still present in the pyloric mucosa. This is the first animal model of bacterial gastritis to be described that shows progression from acute inflammation to persistent acute on chronic inflammation (active chronic) as is seen in human infection with H. pylori. | general pathological conditions |
Care of diabetic patients by optometrists in New York State. OBJECTIVE: This study was undertaken to learn about the involvement of optometrists in the eye care of diabetic patients in New York and to collect baseline data for planning intervention programs in diabetic eye disease. RESEARCH DESIGN AND METHODS: This study was conducted by a mail survey being sent to all optometrists in New York whom we could identify through state sources (n = 2270). Three follow-up mailings were conducted. RESULTS: Eighty-six percent who received our mailing responded, 87% of whom reported that they see diabetic patients. Analysis was confined to this 87%. Routine retinal examinations were provided by 68% of the respondents who see diabetic patients, 62% of whom dilate the pupils. Sixty-eight percent who see diabetic patients diagnose retinopathy solely by their own examination, and 60% of these dilate. Follow-up of retinopathy was provided by 15% of optometrists who see diabetic patients, 90% of whom dilate the pupils of their diabetic patients. Twenty-five percent of respondents who see diabetic patients refer them to an ophthalmologist for diagnosis of retinopathy, and 67% refer all retinopathy patients to an ophthalmologist for follow-up. Although 91% of respondents recommended eye examinations at least annually for diabetic patients, only 68% specifically recommended annual examinations through dilated pupils. Those who dilate were significantly more likely to recommend annual dilated examinations than those who do not dilate, regardless of practice setting. CONCLUSIONS: These findings indicate that optometrists as a group see many diabetic patients. Intervention strategies should include increased emphasis on the use of dilation when examining diabetic patients and annual dilated retinal examinations. | general pathological conditions |
The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome. Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins. | neoplasms |
Augmentation mammaplasty by means of the transrectus route. A new operative technique has been developed for augmentation mammaplasty. Through an inframammary incision, the anterior rectus sheath is entered, and the pocket is dissected in an entirely submuscular plane. We have performed this procedure in 112 patients to date. Complications have been few. The capsular contracture rate in 90 patients followed for greater than 1 year is 7 percent. The inframammary crease can be lowered using this technique, making mastopexy unnecessary in most patients with moderate ptosis. | general pathological conditions |
National allocation of cadaveric kidneys by HLA matching. Projected effect on outcome and costs. BACKGROUND. Although receiving a cadaveric kidney matched at the HLA-A, B, and DR loci enhances graft survival in cyclosporine-treated patients, the value of a national system of kidney allocation based on HLA matching, with the attendant increased likelihood of better matching, is still questioned. Some fear that the costs of a national system are unjustified when only a small fraction of donors would exactly match any of the 16,000 potential recipients anyway. We estimated the effect on graft survival of the use of HLA matching for all allocations of cadaveric kidneys in the United States. METHODS. The graft-survival rates in five mutually exclusive groups of transplants with increasing numbers of HLA mismatches were estimated by partitioning the data for 22,190 first-time recipients of cadaveric kidneys. Overall graft survival was projected as a weighted average with use of the percentages of transplants in the hierarchical groups in recipient waiting pools of various sizes. We compared the benefits and costs of HLA matching in a national system with those of introducing cyclosporine, which was projected to enhance graft survival by 7 percentage points at 10 years. RESULTS. Sharing kidneys nationally on the basis of hierarchical HLA matching was estimated to enhance graft survival by an additional 5 percentage points at 10 years. The anticipated five-year cost of national allocation of kidneys by HLA matching for 7000 recipients, including consideration of the costs of graft removal and dialysis after transplant rejection, would be +4F6.5 million less than the cost of using cyclosporine alone. CONCLUSIONS. The use of an HLA allocation system will not add to the cost of renal transplantation, but it will improve the long-term results to the same extent as cyclosporine. We propose the initiation of a national kidney-sharing system based on hierarchical levels of HLA matches. | general pathological conditions |
Life table analysis of fecundity in intravenously gonadotropin-releasing hormone-treated patients with normogonadotropic and hypogonadotropic amenorrhea. The success of pulsatile intravenous (IV) gonadotropin-releasing hormone (GnRH) treatment in patients with normogonadotropic and hypogonadotropic amenorrhea was studied retrospectively using life table analysis. Two hundred forty-four ovulatory cycles in 48 normogonadotropic and hypogonadotropic patients were evaluated. The cumulative conception rate after 12 cycles was 93%, with a mean conception rate of 22.5% per cycle. Comparing cycles 1 to 6 with cycles 7 to 12, no significant difference in conception rate was observed. Subdivisions were made relative to the presence of additional infertility factors, history of weight loss, actual weight, estrogenic status, and primary versus secondary amenorrhea. The life table curves of patients either with or without other infertility factors were significantly different. No statistically significant differences were found in the other subdivisions. It is concluded that IV GnRH therapy is highly successful in patients with normogonadotropic and hypogonadotropic amenorrhea, especially if no other infertility factors are present. | general pathological conditions |
Resections and reconstructions for tumors of the distal radius. The primary objective in surgical management of the patient with a distal radius tumor is control of the disease. Accurate staging and diagnostic methods applied preoperatively will predict not only the amount of resection necessary to obtain adequate tumor margins, but also the amount of remaining bone and soft tissues to assist reconstruction. With this information, a method of reconstruction can be chosen that provides the patient optimal long-term function and stability with predictable results and the fewest potential complications. | neoplasms |
Computed tomography and the TNM classification of lung cancer. Computed tomography (CT) of the thorax and upper abdomen was prospectively evaluated in 84 patients with potentially operable lung cancer. Invasion into the thoracic wall and the mediastinal structures was not accurately demonstrated by CT. For metastatic mediastinal lymph nodes, the sensitivity and specificity of CT were, respectively, 86% and 61% and the positive and negative predictive indices 49% and 91%. For T1, T2 and T3 tumours the negative indices were 100%, 96% and 71%. Positive predictive index did not differ between squamous cell carcinoma and adenocarcinoma. Adrenal metastases were CT-suspected in 17 cases and liver metastases in eight, but were verified by ultrasonography in only one and four cases. CT should be used in preoperative investigation of lung cancer, irrespective of stage. Demonstration of thoracic-wall or mediastinal invasion need not exclude tumour resection. Preoperative mediastinoscopy is indicated if CT shows nodal metastases or if there are signs of tumour invasion, but not in CT-negative T1 or T2 tumour. Abdominal metastases indicated by CT should be investigated with CT-guided needle biopsy. | neoplasms |
Adenotonsillectomy in children with sickle cell disease. The pediatric patient with sickle cell disease risks having a vasoocclusive episode during adenotonsillectomy under general anesthesia. With proper patient selection and appropriate perioperative management, adenotonsillectomy can be accomplished safely in children with sickle cell disease. We review the management of 10 children with sickle hemoglobinopathies who had adenotonsillectomy. Indications for surgery were recurrent streptococcal infections in four and obstructive sleep apnea in six of these children. No complications resulted from any of these procedures, and the mean length of postoperative hospitalization was 2.4 days. The principal feature of preoperative management was the transfusion of red blood cells to suppress the patient's endogenous erythropoiesis and to reduce the concentration of sickle cell hemoglobin to less than 30%. Though a prospective, multi-institutional clinical trial will ultimately be required to settle the issue of the safest preoperative management of children with sickle cell disease, balancing the risks of transfusion-related complications against anesthesia-related complications, our experience supports the operative safety of hypertransfusion therapy in children with sickle cell disease. | general pathological conditions |
Thoracic epidural anesthesia improves global and regional left ventricular function during stress-induced myocardial ischemia in patients with coronary artery disease. The aim of the present investigation was to study the effects of high thoracic epidural anesthesia (TEA), including the cardiac sympathetic segments, on ischemic ST-segment changes and left ventricular global and regional wall motion abnormalities. Ten patients with a two- or three-vessel coronary artery disease, all treated with the beta-adrenergic blocker metoprolol because of severe stable angina pectoris, performed two identical exercise stress tests, the first without TEA (control exercise) and the second with TEA (TEA exercise). Before each stress test, intravenous metoprolol was given to achieve maximal or near maximal beta-adrenoceptor blockade. Systolic and diastolic arterial pressures (radial artery cannula), heart rate, and rate-pressure product, as well as global and regional ejection fractions, using equilibrium radionuclide angiography in the left anterior oblique projection, were measured at rest and during maximal exercise. ST-segment analysis (V3 or V5) was performed, and the regional wall motion score was calculated at control exercise and TEA exercise. Intravenous metoprolol or intravenous metoprolol plus TEA at rest did not cause any significant changes of any of the variables. During TEA exercise, systolic arterial pressure, diastolic arterial pressure, and rate-pressure product, but not heart rate, were significantly lower compared to control exercise. The global and anterolateral ejection fractions were significantly higher (52.8% versus 46.5% and 53.2% versus 46.0%, respectively, P less than 0.05), and the regional wall motion score was significantly lower (8.8 versus 11.8, P less than 0.01) during TEA exercise than during control exercise. ST-segment depression was significantly lower during TEA exercise (-1.03 versus -1.84 mV, P less than 0.01). | cardiovascular diseases |
Chronic pulmonary thromboembolism in dogs treated with tranexamic acid. BACKGROUND. Many questions remain regarding the pathogenesis, natural history, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension in patients. To answer such questions, we developed an animal model of this disorder. The brisk thrombolytic response of canines to acute embolism has, previously, prevented the establishment of such a model. METHODS AND RESULTS. The fibrinolytic inhibitor tranexamic acid was given orally to canines before, and for intervals after, pulmonary emboli were released from venous thrombi formed in vivo in femoral veins or the inferior vena cava. Preliminary studies disclosed that embolic residuals from femoral vein thrombi were not sufficient to cause significant, persistent pulmonary hypertension. With repetitive, larger thrombi embolized from the inferior vena cava, however, persistent pulmonary hypertension was achieved in most animals. CONCLUSIONS. Resolution of emboli in the canine can be inhibited by tranexamic acid. As in humans, a spectrum of embolic residuals is encountered, and the perfusion lung scan consistently underestimates the extent of embolic residuals. Studies of this animal model continue. | cardiovascular diseases |
Acute febrile neutrophilic dermatosis in childhood (Sweet's syndrome). We report a case of Sweet's syndrome in childhood. Our patients suffered from repeated fevers, chest infections and had characteristic erythematous plaques. The severity of his illness increased with age and warranted oral steroid treatment. We review 16 cases reported to date in the literature and comment on the management and prognosis of the disease in childhood. | general pathological conditions |
Renormalization of high cardiac output and of left ventricular size following long-term recombinant human erythropoietin treatment of anemic dialyzed uremic patients. To obtain information on the effects of the correction of uremic anemia on cardiac function and size, nine normotensive dialyzed patients were studied before, during and six months after the start of i.v. treatment with recombinant human erythropoietin (rHuEPO). Pulsed-doppler echocardiographic determinations of the cardiac index (CI) and M-Mode echocardiographic estimations of the indexed left ventricular end diastolic diameter (LVEDDi), interventricular septum (IVSi), left ventricular posterior wall (LVPWi), with calculations of the left ventricular mass index (LVMi), were made on every occasion. Mean (+/- SD) hemoglobin (Hb) concentration before rHuEPO was 5.9 +/- 1.3 g/dl and rose significantly (p less than 0.0001) up to the third month, then remained constant. Baseline CI (3.4 +/- 0.6 l/min/m2bsa) was significantly higher (p less than 0.0001) than in healthy subjects (2.5 +/- 0.5 l), and decreased after the third month to a value (2.8 +/- 0.5 l) no longer different from that of controls. From pooled baseline and third month data, an inverse relationship between Hb and CI was found (p less than 0.0001). Baseline LVEDDi (32.7 +/- 4.3 mm/m2bsa), IVSi (6 +/- 1.1 mm/m2bsa) and LVPWi (5 +/- 0.8 mm/m2bsa) were all significantly higher than in controls. After three months of therapy, the only change was a decrease in LVPWi while after six months all indices, including the LVMi, decreased to values no longer higher than in controls. From pooled baseline and six months data, an inverse relationship between Hb and LVMi was found (p less than 0.0001). We conclude that treatment of uremic patients by rHuEPO is able to renormalize their already increased cardiac output soon after correction of the anemia. | general pathological conditions |
Combined tensor fasciae latae musculocutaneous flap and sartorius musculocutaneous flap for the repair of wide defects of the lower leg. The tensor fasciae latae musculocutaneous flap has great advantages for reconstruction of the abdominal wall, but the medial border of its territory is limited to the thigh. In order to expand the territory, a combined tensor fasciae latae musculocutaneous flap and sartorius musculocutaneous flap was devised. This flap was successfully used to resurface a large defect in the lower leg as a distally based musculocutaneous flap. The advantages of this flap are its extremely large territory, the fact that total necrosis of the flap cannot occur, and that as a proximally or distally pedicled flap it is suitable for large defects in the abdominal wall, lower leg, and gluteal region. | neoplasms |
Perianal streptococcal cellulitis with penile involvement. Perianal streptococcal cellulitis is described occurring in a 5-year-old boy. The condition also involved the penis and presented as a possible case of sexual abuse. The correct diagnosis was established by culturing beta-haemolytic streptococci group A from the penile and perianal skin. | digestive system diseases |
The empiric use of naloxone in patients with altered mental status: a reappraisal. STUDY OBJECTIVE: To determine whether clinical criteria (respirations of 12 or less, mitotic pupils, and circumstantial evidence of opiate abuse) could predict response to naloxone in patients with acute alteration of mental status (AMS) and to evaluate whether such criteria predict a final diagnosis of presence or absence of opiate overdose as accurately as response to naloxone. CASES AND SETTING: Seven hundred thirty patients with AMS who received naloxone for diagnostic or therapeutic purposes at the discretion of two large, urban, paramedic base teaching hospitals. METHODS: We reviewed paramedic run sheets and audiotapes on all 730 patients as well as available hospital records of all patients who demonstrated any response to naloxone to determine whether overdose was responsible for their clinical presentations. We also reviewed hospital records for a selected sample of naloxone nonresponders. MAIN RESULTS AND CONCLUSION: Only 25 patients (3.4%) demonstrated a complete response to naloxone, whereas 32 (4.4%) manifested a partial or equivocal response. Nineteen of 25 complete responders (76%), two of 26 partial responders (8%) (with known final diagnosis), and four of 195 non-responders (2%) (with known final diagnosis) were ultimately diagnosed as having overdosed. Respirations of 12 or less or the presence of any one of the three clinical findings as a group were each highly sensitive in predicting response to naloxone, and at least as sensitive as response to naloxone in predicting a diagnosis of opiate overdose. Selective administration of naloxone for AMS would have decreased the use of this drug by 75% to 90% while still administering it to virtually all naloxone responders who had a final diagnosis of opiate overdose. | general pathological conditions |
Admission and mid-stay MedisGroups scores as predictors of death within 30 days of hospital admission. We examined the ability of MedisGroups, a severity measure based on clinical data abstracted from the medical record, to predict mortality 30 days following admission. MedisGroups measures severity both on admission and approximately one week into the hospital stay. The data base was a random sample of 20,985 admissions of Medicare beneficiaries with one of six conditions from 833 hospitals in seven states between January 1985 and May 1986. In all six conditions, higher admission and mid-stay severity scores were generally associated with higher risk of death. Across the six conditions, the R-squared values for predicting death using admission scores ranged from 0.01 to 0.16; R-squared values using mid-stay scores ranged from 0.03 to 0.34; and R-squared values from combining admission and mid-stay scores ranged from 0.05 to 0.41. Admission MedisGroups score was thus only modestly predictive of 30-day mortality. While the mid-stay score was more powerful, it may not be an appropriate severity adjuster to screen for quality using hospital mortality rates because it could be influenced by substandard care. | cardiovascular diseases |
Cardiovascular sequelae of therapeutic thoracic radiation. Mediastinal radiation damages endothelial cells, with resulting loss of capillaries and ischemia at the level of the microcirculation. These changes lead to increases in collagen and proliferation of fibrous tissue throughout the heart. Cardiac dysfunction following radiotherapy is surprisingly common and may be due to pericardial, myocardial, valvular, conduction system, or coronary artery disease. Greater awareness of cardiotoxicity has prompted changes in radiation techniques that appear to reduce clinical cardiovascular complications. | cardiovascular diseases |
Clinical significance of intratesticular arterial anatomy. Testicular atrophy has been reported in 2 to 18% of the patients following orchiopexy for cryptorchidism. A possible cause of this atrophy is interference with the testicular blood supply by placement of a testicular traction suture through the tunica albuginea. Arterial casts of 32 adult human testes were created following placement of a 3-zero silk traction suture through the lower pole of the testis to determine the effects of this suture upon intragonadal arterial circulation. Significant arterial blockage, manifested as failure of the parenchymal branches to fill, was observed in 14% of the casts produced via injection through the internal spermatic artery and in 100% of the casts produced via injection through the deferential artery. The results of this study support discontinuing the routine use of parenchymal testicular traction sutures during orchiopexy. | general pathological conditions |
Axillary lymphadenectomy for intraductal carcinoma of the breast. During a ten year period, 175 axillary lymph node dissections were done as part of the treatment for intraductal carcinoma of the breast; 98 patients were treated with modified radical mastectomy and 77 were treated by mammary preservation, consisting of excision of the lesion, axillary dissection and radiation therapy. One of 175 axillary node dissections yielded positive nodes. Axillary dissection for intraductal carcinoma of the breast is unlikely to yield involved nodes and is not indicated for use in most instances. It should be reserved for lesions demonstrating microinvasion. | neoplasms |
Comparison of gall bladder bile and endoscopically obtained duodenal bile. In 10 patients with gall stone disease (eight women, two men; mean (SD) age 47.4 (13) years), bile was obtained by endoscopic aspiration after stimulation of the gall bladder with ceruletid and also by fine needle puncture of the gall bladder under local anaesthetic. The total lipid concentration of the puncture bile samples was mean (SD) 11.9 (4.7) g/dl, significantly higher than the endoscopic bile samples (3.9 (3.3) g/dl, p less than 0.001). Total bile acids, phospholipids, and biliary cholesterol (expressed in mol%) and cholesterol saturation index showed no significant differences between the two types of samples. The glycocholic acid concentration in the endoscopically obtained bile (27.7 (6.6) mol% v 23.3 (5.4) mol%; p less than 0.01) was significantly higher than the puncture bile samples. Puncture bile exhibited a significantly shorter nucleation time (3.5 (3.3) days v 19.6 (11.9) days; p less than 0.001). For determination of the nucleation time, endoscopic bile aspiration after gall bladder stimulation with ceruletid led to adequately concentrated samples in 50% of the study subjects. Cholesterol monohydrate crystal formation in native bile was observed in six samples of puncture bile and in three samples of the endoscopically obtained bile. The presence of cholesterol crystals and the determination of nucleation time in the puncture bile were the best discriminants between cholesterol and pigment gall stones and correlated well with computed tomogram analysis. | digestive system diseases |
Familial autosomal recessive rigid spine syndrome with neurogenic facio-scapulo-peroneal muscle atrophy. Two sisters and a first cousin presented with rigid spine and facio-scapulo-peroneal muscle atrophy. The patients belonged to a family with two first-cousin marriages. Electromyography, muscle and nerve biopsy showed neurogenic muscle atrophy without peripheral nerve involvement. Follow up did not show progression of the disease. This is the first observation of an association of neurogenic facio-scapulo-peroneal and rigid spine syndrome. The double first-cousin marriage suggests autosomal recessive inheritance. | general pathological conditions |
Development of a traumatic intracranial hematoma after a "minor" head injury. We have analyzed features of patients who had what appeared initially to be a minor head injury but who developed an acute traumatic intracranial hematoma. Over a 10-year period, 183 patients who were able to open their eyes spontaneously, were oriented to person, place, and time, and who obeyed commands when they were first seen at a hospital subsequently underwent operation for an acute intracranial hematoma. The hematoma was extradural in 54% of these patients. A history of altered consciousness or symptoms of headache and vomiting were present in 61% of the patients; 33% had a focal neurological deficit, and 43% had either focal deficit or signs of a basal skull fracture. A skull fracture was shown radiologically in 60% of patients, including 52% of those not clinically suspected of having an intracranial lesion. Six months after injury, 77% of the patients had made a moderate or good recovery. The possibility that a patient who has recently sustained a head injury might develop an acute intracranial hematoma can never be completely discounted, even when there are no abnormal clinical signs, and a skull x-ray retains a useful place in the investigation of selected patients with a minor head injury. | nervous system diseases |
Intra-abdominal abscess in regional enteritis. Intra-abdominal abscess (IAA) developed in 129 of 610 patients (21.2%) with Crohn's disease confined to the small bowel. The location of the abscess was intraperitoneal (IPA) in 109 (17.9%) and retroperitoneal (RPA) in 20 (3.3%). There was a marked preponderance of male patients in the retroperitoneal group (ratio, 18:2) (p less than 0.0001). All 129 patients were operated on. Thirteen of one hundred nine patients (12%) with IPA were reoperated on for recurrent abscess, and nine (8.2%) for other reasons. External fistula developed in 24 patients (22%) after simple incision and drainage. Four (3.7%) died; one from hepatitis, and three from sepsis 5, 14, and 90 days after surgery. Of the 20 patients with RPA, two (10%) were reoperated on for recurrent abscess and four (20%) for other reasons. External fistula developed in two patients (10%). There were no deaths in this group. A small number of patients with IAA complicating regional enteritis had persistent sepsis causing postoperative death, which is, however, six times lower than in our comparable series of Crohn's (ileo)colitis. | general pathological conditions |
Acute hemodynamic effects of intravenous diperdipine, a new dihydropyridine derivative, in coronary heart disease. The acute hemodynamic effects of a new dihydropyridine calcium channel blocker, diperdipine, which is suitable for intravenous administration, were studied by right and left cardiac catheterization in 16 patients with coronary heart disease. Diperdipine markedly reduced systemic vascular resistance and improved stroke index and left ventricular ejection fraction. Mean pulmonary artery and wedge pressures were slightly increased as a possible consequence of enhanced venous return, whereas right atrial and left ventricular end-diastolic pressures were not significantly changed. Nevertheless, an increase in preload was clearly indicated by an augmented left ventricular end-diastolic volume index after administration of diperdipine. Left ventricular contractility, which was estimated by the end-systolic pressure-volume ratio and by dP/dt max was not significantly changed, though analysis of individual data suggests a minimally negative inotropic effect. However, such a minor effect on left ventricular contractility was largely counterbalanced by the marked reduction of afterload, which produced a sharp improvement of stroke index. Enhancement of left ventricular ejection fraction and reduction in systemic vascular resistance were inversely and directly correlated to control values. Overall, diperdipine was well tolerated, but one patient had a major untoward reaction that consisted of an ischemic episode that was possibly related to drug administration. In conclusion, intravenous diperdipine appears to be a potent arteriolar dilating agent that does not affect left ventricular contractility. | cardiovascular diseases |
Mechanical sutures in perforation of the thoracic esophagus as a safe procedure in patients seen late. Between 1976 and 1988, we treated 13 perforations of the thoracic esophagus, excluding ruptured carcinoma and intraoperative wounds, by mechanical sutures without exclusion. The delay between perforation and treatment ranged from eight to 168 hours, more than 24 hours in 11. The length of perforation was 0.5 to 15.0 centimeters. Suture was covered with a flap in ten instances; an antireflux procedure was associated with five instances. No digestive ostomies were performed. There was one death; a patient who was comatose upon arrival. The results of this small series suggest that myotomy exposing the mucosa and a flap are two essential elements of the technique; perforations of less than 6 centimeters, even when seen late, may be treated by primary surgical closure. | digestive system diseases |
A rational attitude toward serum alanine aminotransferase measurement by blood banks, based on a longitudinal study of a cohort of repeat blood donors. A cohort of 879 blood donors was followed over a 3-year period. Of the 3858 units of blood collected, 112 (2.9%), obtained from 64 donors, had an alanine aminotransferase (ALT) activity over 45 IU per L; of these, 39 had a single ALT elevation. The incidence of ALT increase was 2.01 per 100 units, or 5.1 per 100 donors, per year. The pattern of elevated ALT was followed in 72 donors, 54 of whom were from the 64 cited above. At the second blood donation (BD2), about 5 months later, 62.5 percent had a normal ALT value, and most (91%) retained those values at blood donation 3 (BD3). However, 19 (70.3%) of the 27 whose ALT levels had not returned to normal at BD2 had an increased value at BD3. These results led to the formulation of the following algorithm to improve the management of blood donors; at the first donation, the ALT assay is done after the blood collection, but, at the next donation, the ALT level is measured before donation if the preceding ALT activity had been abnormal. If ALT is elevated, blood is not collected. Three consecutive ALT elevations are a criterion for permanent exclusion of the donor. | digestive system diseases |
Drug-induced supraventricular tachycardia: a case report of fluoxetine. We report the occurrence of supraventricular tachycardia and hypotension in a 54-year-old woman after maintenance therapy with fluoxetine. Although cases of tachycardia and palpitations have been reported, supraventricular tachycardia and hypotension have not been directly attributed to fluoxetine. | cardiovascular diseases |
One-year outcome after cerebral infarction in whites, blacks, and Hispanics. Little is known about outcome after cerebral infarction for different ethnic groups. Of 590 stroke patients hospitalized from 1983 to 1986 at the Neurological Institute, cerebral infarction over age 39 years occurred in 135 whites, 177 blacks, and 82 Hispanics. Outcome after cerebral infarction differed by ethnicity. The 1-month mortality rate was similar in whites and blacks and least in Hispanics. Whites had a slightly greater risk of recurrent stroke or death than blacks or Hispanics until 6 months after infarction, when their risk stabilized, while the risk in blacks and Hispanics continued to rise for the entire year of follow-up. By 1 year, the rate of recurrent stroke or death was 34.8 +/- 4.2% in whites, 31.1 +/- 3.6% in blacks, and 21.4 +/- 4.8% in Hispanics (p = 0.04). Differences were found in the distribution of various stroke risk factors in the three ethnic groups. A Cox proportional hazards model demonstrated that the ethnic differences in stroke risk factors and infarct subtype were responsible for the ethnic differences in outcome. An abnormal first electrocardiogram was a risk factor for stroke recurrence or death in all three ethnic groups, while a nonlacunar infarct subtype and a history of diabetes were significant only in Hispanics. Understanding the associations of stroke determinants with ethnicity may lead to more focused secondary prevention of recurrent stroke. | nervous system diseases |
Adult T-cell leukemia/lymphoma of the tongue. A case of posterior tongue lymphoma associated with adult T-cell leukemia (ATL) that occurred as a lesion in the lingual dorsal portion is reported in a 64-year-old woman. Initially, a diagnosis of Hodgkin's lymphoma was considered as no findings associated with ATL except lymphadenopathy and serum anti-ATLA antibodies were present. Combined radiotherapy and chemotherapy were administered with favorable results; however, 4 months later, Pneumocystis carinii pneumonia developed, and 2 months later, generalized lymphadenopathy and hypercalcemia evolved. At this time, a diagnosis of ATL was made. The patient died of renal dysfunction 6 months after the initial presentation. In suspected cases of ATL and malignant diseases of T-cell lineage, namely, malignant lymphoma and mycosis fungoides, the presence of HTLV-1 infection should be confirmed by testing for anti-ATLA antibodies. | neoplasms |
Preservation of oscillations in postocclusive reactive hyperemia. Oscillations in skin blood flow (SkBF) during postocclusive reactive hyperemia are believed to be due to locally mediated events in the microcirculation. We characterized the activity of these oscillations in nine healthy young men who underwent 0, 10, and 40 Torr of lower body negative pressure (LBNP). Postocclusive SkBF was estimated in both forearms simultaneously in a stable thermal environment with laser-Doppler velocimetry. Periodic behavior of SkBF was characterized by frequency-domain power spectral analysis. LBNP at 40 Torr increased heart rate, decreased forearm blood flow, and decreased postocclusive SkBF amplitude but did not change the periodicity of SkBF in the frequency response range that is characteristic of postischemic SkBF oscillations (0.11 +/- 0.04 Hz). We observed that LBNP did not alter the frequency response of the postocclusive SkBF as quantified in the periodogram, even though the amplitude of the SkBF was markedly diminished as a part of the general decrease in arm blood flow. We found inferential evidence for a disseminated common pacemaker mechanism that performs similarly at distant sites. We conclude that the LBNP baroreflex-mediated modulation of SkBF reduces the amplitude but does not change the frequency behavior of postocclusive SkBF. We propose on the basis of our findings that the preservation of vasomotion suggests that this phenomenon is an adaptation to the ischemic changes induced by disruption of blood flow. | cardiovascular diseases |
Angioplasty of occluded coronary arteries: use of thin shaft balloon over-the-wire system without pre-dilatation. A retrospective review was done on 13 consecutive patients who underwent PTCA of totally occluded coronary arteries using a recently released thin shaft balloon over-the-wire angioplasty system. Balloon size was determined by the closest fit to the arterial size and used without predilatation techniques. This technique was initially successful in 12 patients with only 2 clinically insignificant episodes of distal embolization and one probable early reclosure. Using thin shaft angioplasty systems, balloon dilatation of totally occluded coronary arteries can be done safely with a single balloon in many cases resulting in simplified procedures and economic benefits. | cardiovascular diseases |
Subclavian artery to innominate vein fistula after insertion of a hemodialysis catheter. Insertion of hemodialysis catheters for temporary use is now preferentially performed by percutaneous infraclavicular subclavian vein catheterization. This method involves passage of a stiff dilator and a peel-away sheath over a guide wire, and is usually carried out without fluoroscopy. For the most part this has proved to be a valuable and safe approach. However, a small incidence of major complications occurs, which needs to be emphasized. Sixteen cases of arteriovenous fistulas between the subclavian artery or its branches and the subclavian vein have been reported so far in the literature. To date only one case of subclavian artery to innominate vein fistula has been reported. We report the second case with this complication and suggest possible preventive measures. | general pathological conditions |
Platelet thromboxane release and delayed cerebral ischemia in patients with subarachnoid hemorrhage. Adenosine diphosphate-induced platelet aggregation and associated thromboxane B2 release were studied in 52 patients with subarachnoid hemorrhage (SAH) in order to detect a possible association between altered platelet function and development of cerebral ischemic complications after SAH. Compared to the values on admission, the patients showed significantly increased platelet aggregability (p less than 0.05) and thromboxane release (p less than 0.001) 1 to 2 weeks after SAH. The highest values of thromboxane release were seen in patients who deteriorated due to delayed cerebral ischemia with a permanent neurological deficit. Thromboxane release was significantly higher (p less than 0.05) before the onset of severe delayed ischemia in six patients with preoperative ischemia compared to the patients without delayed ischemia. In five others, both ischemic deterioration and elevated thromboxane release occurred after operation. These patients had preoperative values similar to the values in those without ischemic symptoms. The observations suggest that increased platelet aggregability and thromboxane release are associated with delayed cerebral ischemia both before and after surgery. | cardiovascular diseases |
A prospective, double-blind study of metoclopramide hydrochloride for the control of migraine in the emergency department STUDY OBJECTIVE: To determine the effectiveness of IV metoclopramide as sole therapy for relieving the pain of acute migraine in the emergency department. DESIGN: Prospective study. Fifty patients were divided randomly into subjects and placebo controls with blinding of the treating physician and the patient. PARTICIPANTS: Patients presenting to the ED with migraine requiring parenteral treatment. INTERVENTIONS: Subjects received 10 mg IV metoclopramide and controls received IV normal saline; patient assessment of relief was followed by means of a numerical scale. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of subjects compared with 19% of controls had effective pain relief within one hour (P less than .001). Subjects achieved mean relief scores of 2.46 compared with 1.69 for controls (P less than .02). No significant side effects were observed. CONCLUSION: IV metoclopramide as a single agent is effective and safe therapy for migraine in the ED. | nervous system diseases |
Doxazosin in the treatment of essential hypertension in general medical practice in Latin America. This Latin American study assessed in the general practice setting the efficacy and tolerance of once-daily doxazosin in the treatment of mild or moderate essential hypertension (sitting diastolic blood pressure, 95 to 115 mm Hg). Patients (n = 220) were treated with doxazosin for 12 weeks as monotherapy or in combination with other antihypertensive agents. At the final visit, doxazosin produced a mean change in sitting systolic/diastolic blood pressure of -18.4/-14.4 mm Hg, at a mean daily dose of 4.3 mg. One hundred sixty-three (77.6%) of the 210 evaluable patients were considered a therapeutic success. Lipid analyses identified a statistically significant (p = 0.02) reduction in total serum cholesterol (4.85%) and an overall decrease in triglyceride levels (5.12%). According to the Framingham Heart Study equation, doxazosin produced a highly significant (p less than 0.001) 20% reduction in the calculated probability of developing coronary heart disease in 10 years. Of the 220 patients evaluated, 54 (24.5%) reported side effects that were considered related to treatment. Ten (4.5%) patients reported side effects unrelated to treatment and 37 (16.8%) reported events of unknown relationship. Most side effects were mild or moderate and were tolerated or disappeared with continued treatment. Nine patients (4.1%) were discontinued from therapy and in 13 (5.9%) the dose was reduced. The most prevalent side effects were headache and dizziness. The investigator's overall assessment of antihypertensive efficacy was excellent or good for 176 patients (80.4%); tolerance was considered excellent or good in 193 patients (88.5%). | cardiovascular diseases |
Community lifestyle characteristics and risk of acute lymphoblastic leukaemia in children. High rates of leukaemia in children and young people have been associated with features of community isolation and population growth. Incidence data collected by two specialist registries were used to compare incidence rates at ward level with relevant ward characteristics derived from routine census and Ordnance Survey data for England and Wales. An excess risk of childhood acute lymphoblastic leukaemia (ALL) was found for wards which are farthest from large urban centres. The excess was greatest for wards of higher socioeconomic status and for children aged 1-7 years (the childhood peak), for which a two-fold excess was seen. These findings in general support the hypothesis that childhood leukaemia has an infectious aetiology. | neoplasms |
Cardiac fluoroscopy for the diagnosis of coronary artery disease: a meta analytic review. To evaluate variability in the reported accuracy of fluoroscopically detected coronary calcific deposits for predicting angiographic coronary disease, we applied meta analysis to 13 consecutively published reports comparing the results of cardiac fluoroscopy with coronary angiography. Population characteristics and technical and methodologic factors were analyzed. Sensitivity and specificity for predicting serious coronary disease compare quite well with those from the literature on the exercise ECG and the exercise thallium scintigram. Sensitivity increases and specificity decreases more significantly with patient age, and sensitivity is paradoxically lower in laboratories testing patients with more severe disease, as well as when 70% rather than 50% diameter narrowing is used to define angiographic disease. Work-up and test review bias were also significantly related to reported accuracy. | cardiovascular diseases |
Physician response to notification of acute problems in nursing homes. A frequently cited example of physicians' alleged disinterest in nursing home patients is their failure to respond rapidly or appropriately to telephone calls about acute events or important changes in patient status. This study of 45 SNFs and their 15 attached ICFs evaluated the length of time required to reach physicians by phone about significant clinical changes in patients' conditions and the appropriateness and timeliness of action taken by the physicians once contact was made. Calls on administrative matters, updating of orders, and similar routine calls were excluded. Seven hundred and fifty calls were identified from 24-hour nursing reports; the nature of the problem and the time and details of physicians' responses were recorded from patient charts. Judgment on the quality of physicians' responses was made by consensus of the regional UR committee except in the case of infections where decisions were based on detailed criteria developed in a previous study. The most frequent clinical problems were acute infections (32%), trauma (12%), GI tract disorders (11%), cardiorespiratory problems (10%), neurological disorders (7%), and diabetic control (7%). Results were very encouraging: 96% of physicians' call-backs and actions were judged to be timely, and 87% of physicians' actions taken were judged to be appropriate. However, actions taken were judged inappropriate for certain specific clinical problems, ie, in 22% (54/243) of infections, 24% (4/17) of CVA's, and 12% (6/49) of diabetic control problems. Implications for nursing home care and recommendations for improving the response to acute problems are discussed. | general pathological conditions |