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Geriatric constipation: brief update on a common problem. Constipation occurs frequently in the elderly and is often multifactorial in origin. A search for an underlying cause is necessary, and can often be found by taking an adequate history and performing a thorough physical examination. A minority of patients require further investigation, guided by the clinical setting. Management should be directed at correcting the underlying cause and providing dietary advice and, less commonly, medication to allow restoration of a normal bowel habit.
general pathological conditions
Efficacy and safety of doxazosin in the treatment of patients with mild or moderate essential hypertension and elevated levels of cholesterol. In hypertensive patients, elevated serum cholesterol is a frequent and sinister additional coronary risk factor. Selective alpha 1-adrenoreceptor inhibitors appear to have the unique ability to control both risk factors. Forty-two patients, ages 42 to 65 years, including 21 men with sustained hypertension and elevated serum cholesterol levels, were included in a trial of monotherapy with doxazosin administered once daily (range, 1 to 16 mg). The influence of the drug on high blood pressure and elevated serum cholesterol was evaluated over a 28-week period, which consisted of a 4-week, single-blind placebo lead-in period, an open 10-week dose-adjustment period, and finally a 14-week maintenance period. Of the 39 efficacy-evaluable patients, 25 (64%) achieved adequate blood pressure control (diastolic blood pressure less than 90 mm Hg or a decrease in diastolic blood pressure greater than 10 mm Hg) at a mean daily dose of 2 mg of doxazosin. No persistent changes occurred in heart rate. In the 32 patients with evaluable lipid data, there were nonsignificant trends to an increase in high-density lipoprotein cholesterol and a reduction in total cholesterol, together with a significant reduction in serum triglyceride concentration. The combined changes in blood pressure and blood lipid levels resulted in a reduction of 36% in the calculated risk of coronary heart disease. Eleven patients reported side effects and four were withdrawn from therapy. These results confirm the antihypertensive and anticholesterolemic efficacy of once-daily treatment with doxazosin.
cardiovascular diseases
Vasospasm contributes to monosodium glutamate-induced headache. Consumption of monosodium glutamate has long been considered to precipitate headaches in susceptible patients. In this study the direct effects of glutamate and its metabolite, glutamine, on arterial contractility were examined using rings of rabbit aorta. In a high concentration glutamate caused significant concentration-dependent contractions (EC50, 10(-1)M; maximum tension, 188.4 +/- 33.3 mg wt tension/mg tissue). Agonists and antagonists for alpha-adrenergic, histaminergic, serotonergic, cholinergic, and GABA-nergic receptors as well as inhibition of prostaglandin synthesis failed to influence glutamate contractions. At high concentrations (10(-5)M) the calcium channel blocker, verapamil, inhibited the glutamate response. Glutamate and glutamine both exhibited concentration dependent relaxation of norepinephrine (NE), phenylephrine (PE), histamine, serotonin (5-HT), and prostaglandin F2 alpha (PGF2 alpha)-induced contractions. Kainic acid (10(-4)M), an agonist of one subpopulation of central glutamate receptor, potentiated glutamate-induced vasoconstriction; a higher concentration (10(-3)M) produced an irreversible inhibition of glutamate contractility. Only the central glutamate receptor antagonist, ketamine (10(-4)-10(-2)M), induced a reversible, concentration dependent inhibition of glutamate-induced contractions. Glutamate contractility was not dependent on extracellular calcium, an intact endothelium or neuronal function. These results demonstrate a direct effect of glutamate on peripheral arterial tone. Dietary consumption of large quantities of MSG may represent a serious health hazard to certain individuals with pre-existing vascular disease.
nervous system diseases
Surgical epicardial ablation of left ventricular pathway using sling exposure We report our experience with 43 consecutive patients with left free wall pathways operated on since December 1988 using a modified direct epicardial approach through a medial sternotomy, without the adjunct of normothermic cardiopulmonary bypass. The left atrioventricular sulcus is exposed by dislocating the heart cephalad and to the right using a sling made of a large sponge passed around the ventricle through the transverse sinus. While the arterial pressure is monitored, the heart is positioned to obtain adequate exposure without compromising the ventricular function. The left atrioventricular junction is exposed using a direct approach. The epicardium is incised along the ventricular edge and a plane of dissection is identified and opened using blunt dissection over the ventricular wall. The entire left atrioventricular junction can be exposed. After dissection, electrophysiological testing is repeated to assess accessory pathway conduction. Epicardial cryoablation was used when accessory pathway conduction was not present (42 patients). Transmural cryoablation was used under normothermic cardiopulmonary bypass when accessory pathway conduction persisted after dissection (subendocardial pathway). In all, cardiopulmonary bypass was not used in 41 patients. There was one early relapse that required transmural cryoablation. There were no complications.
cardiovascular diseases
Rationalisation of follow-up in patients with non-invasive bladder tumours. A preliminary report. The risk of recurrence and progression in 170 patients presenting with pTa urothelial tumours of the bladder has been estimated so that follow-up can be rationalised. Patients were followed up for between 1 and 15 years, the original pathology reviewed and those with carcinoma in situ (CIS) or dysplasia of the background urothelium excluded. Only 5 patients progressed over the whole follow-up period, giving an overall progression rate of 3%. Solitary tumours had an annual initial recurrence risk (AIR) of 0.23 in the first year; after the first year the AIR fell to approximately 0.1 but did not fall significantly in subsequent years up to 8 years. Of the 45 patients with multiple tumours, 32 suffered recurrences within the first year (AIR 0.71). Tumour grade did not influence either recurrence or progression. The results indicate that for solitary pTa tumours, less frequent endoscopic follow-up is justified but some continued surveillance after 5 disease-free years is necessary. The estimated risk of recurrence is a useful factor to consider when planning follow-up.
neoplasms
Coronary and left ventricular hemodynamic responses following reversal of flunitrazepam-induced sedation with flumazenil in patients with coronary artery disease. The effects of reversal of flunitrazepam-induced sedation with flumazenil on coronary hemodynamics, myocardial oxygen consumption (MVO2), and left ventricular (LV) performance were investigated, in a double-blind trial, in 12 patients with stable coronary artery disease undergoing cardiac catheterization. Coronary sinus blood flow was measured by continuous thermodilution. Arterial and coronary sinus blood were analyzed for oxygen and lactate contents. The determinants of LV performance were obtained from the cardiac output measured by thermodilution and from left heart catheterization data. To reverse flunitrazepam-induced sedation, patients were randomly allocated to receive placebo or flumazenil (by increment, up to 1 mg) at the end of procedure. In the placebo group, no significant hemodynamic changes were observed. In the flumazenil group, heart rate, cardiac index, maximum velocity of shortening, and relaxation time constant were not significantly altered. By contrast, mean aortic pressure and LV end-diastolic pressure (baselines: 90 +/- 5 and 7.3 +/- 4.1 mmHg, respectively) increased (9%, P less than 0.05 and 67%, P less than 0.05, respectively) after flumazenil administration, but these changes represented mainly a return toward presedation values. MVO2 and coronary resistance were not significantly altered, whereas CSBF increased slightly (baseline: 119 +/- 20 ml/min; increase 10%, P less than 0.05). No electrocardiographic evidence of myocardial ischemia was observed during the study. These data show that reversal of benzodiazepine effects with flumazenil is not associated with a major alteration of LV systolic function, relaxation, or coronary hemodynamics in patients with coronary artery disease. Nevertheless, it should be cautiously used when LV end-diastolic pressure is increased at the time of its administration.
cardiovascular diseases
Etoposide in acute leukemia. Past experience and future perspectives. Etoposide as a single agent is active in relapsed and refractory acute myelogenous leukemia (AML), with complete responses (CR) rates of 10% to 25%. The drug has been safely combined with cytarabine, azacytidine, vinca alkaloids, and anthracyclines, inducing remission rates of 20% to 60% in patients with previously treated AML. The experience with etoposide in acute lymphoblastic leukemia is less extensive, but the drug seems to be active in combination with cytarabine or aclacinomycin. In addition, etoposide is combined with cytarabine and anthracyclines for the primary treatment of AML. The response rates thus achieved are comparable with those obtained with standard regimens. A Phase I/II trial was initiated to study the efficacy of the NOVE combination (mitoxantrone [10 mg/m2/d, days 1 to 5] plus etoposide [100 mg/m2/d for 3, 4, or 5 days] in patients with refractory AML. The results showed that extended duration of etoposide administration is associated with higher CR rates. Overall, a CR rate of 43% was achieved in 61 patients. A sequential regimen with IDAC (idarubicin/cytarabine) and NOVE was designed for primary treatment of adult patients with AML. Cycles of IDAC or NOVE are applied depending on response. The results of the pilot study with this strategy were encouraging with 18 of 20 patients achieving CR. Further studies are under way to verify the efficacy of this strategy.
neoplasms
Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. The experimental metastatic potential of 13762NF mammary adenocarcinoma clone MTLn3 was tested after pretreatment in serum-free medium containing transforming growth factor (TGF) beta 1 at 0-5000 pg/ml. Lung colonies were measured 2 weeks after inoculation in syngeneic F344 rats, and a bell-shaped dose-response curve with 2- to 3-fold increase in number of surface lung metastases was seen. Maximal enhancement occurred at the 50 pg/ml dose level. The effect was specific because addition of neutralizing anti-TGF-beta antibody blocked the stimulatory activity at all levels of TGF-beta 1 pretreatment, but when antibody was given alone, neutralizing anti-TGF-beta antibody had no effect on untreated cells. Increased metastatic potential appears to be from an increased propensity of cells to extravasate as tested in the membrane invasion culture system. MTLn3 cells penetrated reconstituted basement-membrane barriers 2- to 3.5-fold more than did untreated control cells, depending upon length of TGF-beta 1 exposure. Increased invasive potential is apparently due, in part, to a 2- to 6-fold increase in type IV collagenolytic (gelatinolytic) and a 2.4-fold increase in heparanase activity. TGF-beta 1 treatment of MTLn3 cells did not alter their growth rate or morphology in the presence of serum; however, growth was inhibited in serum-free medium. Likewise, adhesion to human umbilical vein endothelial cell monolayers or to immobilized reconstituted basement membrane or fibronectin matrices was unchanged. These results suggest that TGF-beta 1 may modulate metastatic potential of mammary tumor cells by controlling their ability to break down and penetrate basement-membrane barriers.
neoplasms
Venous infarction following the interhemispheric approach in patients with acute subarachnoid hemorrhage. Postoperative venous infarction following aneurysm surgery was studied in 48 patients with anterior communicating artery aneurysms operated on through the interhemispheric approach at the acute stage of subarachnoid hemorrhage (SAH). Of 23 patients whose bridging veins were sacrificed during surgery, 11 (47.8%) showed venous infarction in the frontal lobes. In contrast, only one (5.9%) of 17 patients whose bridging veins were preserved developed cerebral edema. None of eight patients who were operated on after Day 11 (the day of SAH was defined as Day 0) showed this complication, although bridging veins were sacrificed in six of them. Venous infarction following acute aneurysm surgery tended to occur more frequently in patients of higher SAH grade and/or more advanced age, but these correlations were not significant. However, the correlation between the sacrifice of veins and venous infarction was significant (p less than 0.025). Because this potential complication may compromise the benefit of acute aneurysm surgery and cause damage, it is important to preserve the venous system and in some instances to select another surgical approach based on the pattern of venous drainage in the frontal lobe.
cardiovascular diseases
Osteoblastoma of the spine. A review of 75 cases. Clinical and radiologic features of 75 cases of osteoblastoma of the spine were reviewed. In addition to pain, which was the most frequent complaint, 18 patients demonstrated objective neurologic deficit, while scoliosis was observed in 17 patients. Aspirin yielded pain relief in 13 patients. Pathologic fracture was not encountered. The radiologic and histologic characteristics of osteoblastoma of the spine are indistinguishable from those arising in other sites. The typical lesion exhibited a well-defined, geographic margin with a sclerotic, frequently lobulated border. Approximately one half of the cases were predominantly lucent, the remainder displaying varying degrees of matrix mineralization. Distribution of the osteoblastomas through the spinal axis was as follows: cervical-29, thoracic-16, lumbar-17, sacral-13. Other significant findings included posterior element involvement in 73 of 75 cases, and a striking male to female ratio of 2.5 to 1.
nervous system diseases
Holter monitoring of ventricular arrhythmias in a randomised, controlled study of intravenous streptokinase in acute myocardial infarction. The occurrence of ventricular arrhythmias attributed to streptokinase treatment in acute myocardial infarction is not well defined. Holter monitoring was performed for 24 hours in 81 patients with suspected acute myocardial infarction randomised in a ratio of 2:1 to intravenous streptokinase 1.5 x 10(6) IU (n = 55) or placebo infusion (n = 26) 6.7 hours (mean) after the onset of symptoms. No episodes of ventricular fibrillation were recorded. For the whole 24 hour period and during the first three hours after the start of treatment the incidence and frequency of ventricular arrhythmias were similar in the patients randomised to streptokinase and to placebo. But when the results in patients randomised "early" after the onset of symptoms of suspected acute myocardial infarction were analysed separately the frequency of abnormal complexes, pairs, runs, and repetitive arrhythmias seemed to be higher in patients allocated to streptokinase. This may reflect arrhythmias associated with reperfusion.
general pathological conditions
Bilateral intrapulmonary hematomas. A 67-yr-old man, known to have chronic obstructive lung disease, developed bilateral localized pulmonary densities on chest radiographs after cardiopulmonary resuscitation. An autopsy disclosed bilateral intrapulmonary hematomas without communication with bronchi, pulmonary arteries, or pleural cavities. We suggest blunt pulmonary injury is the most probable cause of the hematomas and discuss its pathogenic mechanism. Intrapulmonary hematomas should be considered in the differential diagnosis of pulmonary densities developing after a vigorous resuscitation.
general pathological conditions
Testicular carcinoma in patients positive and at risk for human immunodeficiency virus. Patients with the acquired immunodeficiency syndrome are at increased risk for certain malignancies. Because acquired immunodeficiency syndrome and testicular cancer affect primarily young men, the potential complications that acquired immunodeficiency syndrome might impose raise significant concern. To address this question we performed a retrospective review of all cases of testicular cancer during an 11-year period. Of 140 patients 6 had human immunodeficiency virus infection and 7 were from human immunodeficiency virus risk groups. All cases were either stage I or II disease with seminoma in 8, teratocarcinoma in 3, embryonal cell carcinoma in 1 and teratoma in 1. The clinical presentations of these patients were comparable to those of patients without human immunodeficiency virus risk factors. The majority of the patients received standard therapy, including orchiectomy followed by lymphadenectomy, radiation therapy or chemotherapy depending on stage and pathological subtype. Patients tolerated therapy well with only 1 course of radiation therapy complicated by Pneumocystis carinii pneumonia. All patients achieved complete remission and none died of testicular cancer. Since treatment of these patients may worsen the immunosuppression, surveillance is recommended after orchiectomy for acquired immunodeficiency syndrome patients with stage I disease. However, the majority of patients with human immunodeficiency virus infection should receive standard therapy.
neoplasms
Pancreatic involvement in human immunodeficiency virus infection. Involvement of the pancreas by human immunodeficiency virus (HIV) infection has not been adequately addressed and is the object of this review. I analyzed the English language literature, including single case reports of pancreatic involvement and larger series reporting detailed pathological findings of patients with HIV infection. Nonspecific pathological changes in the pancreas are frequently seen at autopsy of HIV-infected patients, but are not more common than in controls. Several types of infections (mainly cytomegalovirus, Cryptococcus neoformans, and Mycobacteria) and neoplasms (lymphoma and Kaposi's sarcoma) can involve the pancreas because they are usually disseminated. Although the serum amylase may be elevated, the patient remains asymptomatic. Occasional instances of severe and even fatal pancreatitis have been reported with HIV infections and attendant drug toxicity. Pentamidine has a predictable incidence of hypoglycemic episodes and 2',3'-dideoxyinosine provokes pancreatitis in a minority of treated patients. Such drug toxicity seems to deserve greater clinical concern than opportunistic infections or neoplasms.
neoplasms
Immunochemical characterization and quantitative distribution of pancreatic stone protein in sera and pancreatic secretions in pancreatic disorders. A fluorometric immunoassay has been established to quantitate pancreatic stone protein providing a sensitivity for concentrations from 0.015 to 0.5 micrograms/mL. When concentrations of pancreatic stone protein were determined from pancreatic secretions obtained either from patients suffering from chronic pancreatitis (n = 31) [including the calcifying forms (n = 10)], pancreatic cancer (n = 22), or nonpancreatic diseases (n = 17), no significant differences were found. In contrast, increased concentrations were found in serum samples from patients with chronic (39/66) and acute pancreatitis (16/20) compared with control patients. The differences between these diagnostic groups and controls were highly significant (P less than 0.0001) and independent of pancreatic enzyme activity. Immunochemical analyses of serum pancreatic stone protein showed an isoelectric point (pH 9) similar to that reported for the pancreatic thread protein. With respect to recent communications, these data do not support the etiopathogenic role postulated for pancreatic stone protein in chronic pancreatitis and chronic calcifying pancreatitis by other investigators.
digestive system diseases
Right ventricular infarction: a clinical case study. In this article we review the specific case of Mrs. F., a 63-year-old white woman who recently had classical right ventricular infarction associated with left ventricular inferior wall myocardial infarction. The presentation covers her medical history, clinical course pathophysiology of the right ventricular infarction, and goals of the medical modalities used in treatment. Nursing problems are identified specifically related to right ventricular infarcts, and treatment considerations are discussed. A brief conclusion recaps Mrs. F.'s discharge course and reviews some specific problems associated with right ventricular infarcts, of which critical care nurses need to be aware.
cardiovascular diseases
Enhanced in vitro uptake and retention of 3H-tetraphenylphosphonium by nervous system tumor cells. Photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells. Certain lipophilic cationic compounds, such as tetraphenylphosphonium (TPP), are selectively taken up by a variety of carcinomas. Although preferential retention of TPP has been demonstrated for the breast carcinoma cell line MCF-7, this compound had not been tested previously on cells derived from nervous system tumors. In the present study, tritiated-TPP (3H-TPP) uptake and retention for eight different cell cultures of three histologically different types of nervous system tumors was measured and the data were compared to a positive control (MCF-7) and negative controls (normal African Green monkey kidney epithelium (CV-1) and the normal human fibroblast (WI-38) cell lines). Uptake and retention characteristics could be grouped by specific pathological tumor types, but individual tumor variability was notable. Malignant astrocytoma (grade III/III glioblastoma) and malignant neurofibrosarcoma cells showed preferential uptake and retention of 3H-TPP relative to meningioma cells and normal controls. A clonogenic assay utilizing the cytotoxic lipophilic cationic compound dequalinium showed strong retainers of 3H-TPP to be more susceptible to the effects of dequalinium than weak retainers. These data demonstrate that certain human and experimental animal nervous system tumor cell lines retain lipophilic compounds possessing a delocalized positive charge. Lipophilic cationic compounds may be useful in the intraoperative delineation of tumor margins and in the photodynamic therapy of certain nervous system tumors.
nervous system diseases
Local hypothermia to prolong safe tourniquet time. Local hypothermia was studied as a method to safely prolong tourniquet time for reconstructive procedures of the upper extremity. An ice blanket constructed of flannel cloth and cold gel packs was applied to the limb for 45 minutes preoperatively. Seventy-eight patients were evaluated for complications resulting from hypothermia and prolonged tourniquet application. The duration of continuous tourniquet ischemia averaged two hours and 25 minutes. Intraoperative muscle temperature recordings indicated that the iced limbs were an average of 12.9 degrees cooler than noniced limbs before tourniquet inflation. Electron microscopic studies of biopsied muscle showed no evidence of ischemic changes. There were no postoperative complications associated with prolonged tourniquet inflation or the hypothermia blanket technique. Local hypothermia appears to be a safe and effective method of decreasing the adverse effects of tourniquet ischemia and allowing continuous tourniquet inflation time to extend safely beyond the customary two-hour limit.
general pathological conditions
Mucocelelike tumor of the breast associated with atypical ductal hyperplasia or mucinous carcinoma. A clinicopathologic study of seven cases. We studied seven patients with mucocelelike tumors of the breast, known to be benign lesions that may be confused with mucinous carcinomas of the breast. All patients had a palpable mass. Microscopically, the most striking feature was the cystic character of the lesion. The epithelial lining of the cysts was usually flat or cuboidal to low columnar, and mucin pools frequently appeared near the ruptured cysts. Three mucocelelike tumors contained a microscopic focus of mucinous carcinoma. The other tumors had areas of atypical ductal hyperplasia containing abundant intraluminal mucinous materials. The mucin was composed predominantly of neutral and nonsulfated acid mucins whose character was identical to that of those in mucinous carcinoma. Because all mucocelelike tumors in our series were associated with either atypical ductal hyperplasia or carcinoma and because some mucocelelike tumors may indeed be early mucinous carcinomas of the breast, we recommend examination of the entire specimen and careful clinical follow-up.
general pathological conditions
Cytokine release syndrome induced by the 145-2C11 anti-CD3 monoclonal antibody in mice: prevention by high doses of methylprednisolone. The hamster mAb 145-2C11 specific for the CD3 complex of murine T lymphocytes shares many properties with OKT3, including the induction of T cell activation. In vivo, the injection of 145-2C11 entails a variety of pathologic changes in relation to the systemic release of cytokines. We tested the effects on this cytokine release syndrome of different doses of methylprednisolone (m-PDS) given at various intervals of time before the 145-2C11 mAb. The administration of high doses of m-PDS (50 mg/kg) 2 to 3 h before the mAb resulted in an almost complete inhibition of the systemic release of TNF-alpha, IL-2, and IL-6. As far as the pathologic changes are concerned, the hypothermia, the acute renal tubular necrosis, and the fatty infiltration of the liver were completely prevented whereas the hypoglycemia was only partially attenuated. The protective effect of m-PDS on the toxicity of 145-2C11 was confirmed by the reduction of the mortality rate among galactosamine-sensitized mice. The inhibition of the release of cytokines by m-PDS did not affect the immunosuppression triggered by 145-2C11 as assessed by the CTL activity against alloantigens measured 48 h after the injection of the mAb. We conclude that the administration of very high doses of glucocorticoids 2 to 3 h before 145-2C11 prevents the release of cytokines and attenuates the acute toxicity of the mAb. Similar protocols could allow mitigation of the cytokine-release syndrome induced by the OKT3 mAb in man.
general pathological conditions
Expression of enzymatically active sucrase-isomaltase is a ubiquitous property of colon adenocarcinomas. Adenocarcinoma of the colon is one of the most prevalent and lethal of all human malignancies. The early diagnosis and management of this disease could be improved if biological markers, whose expression was restricted to malignant colon cells, were identified. Sucrase-isomaltase is a glycoprotein hydrolase expressed throughout the small intestine and fetal colon but not in the normal adult colon. This study shows that the expression of enzymatically active sucrase-isomaltase is a ubiquitous property of primary and metastatic colon adenocarcinoma. Significant sucrase enzyme activity (i.e., greater than 5 mU/mg protein) was observed in 16 colon carcinomas but not in adjacent normal colon mucosa. Sucrase-isomaltase messenger RNA was identified in all tumors using reverse transcriptase polymerase chain reaction. Using a quantitative polymerase chain reaction analysis, this study shows that the amount of sucrase-isomaltase messenger RNA in tumors examined (3.4 x 10(-8) to 3.19 x 10(-7) micrograms/micrograms total RNA) was greater than in adjacent mucosa (0 to 3.4 x 10(-8) micrograms/micrograms total RNA). This induction of sucrase-isomaltase messenger RNA and enzyme activity was corroborated by immunostaining. Of 30 colon adenocarcinomas examined, 80% were positive for sucrase-isomaltase. In addition, all colon carcinoma metastases examined were positive for sucrase-isomaltase. The staining pattern was distinct and demarcated tumor cells from the surrounding histologically normal tissue. No sucrase-isomaltase staining was seen in normal mucosa from the same patients. With the exception of lung, no sucrase-isomaltase immunostaining was observed in a variety of examined noncolonic adenocarcinomas. Thus, the specificity and ubiquity of sucrase-isomaltase expression in adenocarcinomas of the colon can be exploited to improve the clinical management of this disease. In addition, studies on the structure of the sucrase-isomaltase gene and its regulatory elements should contribute toward understanding the alteration of gene expression by oncogenic transformation of the colonic mucosa.
neoplasms
Surgeons, surgery, and immunomodulation. With the definition over the past 15 years of the altered immune state of surgical patients as a result of disease itself and surgical therapy, there have been multiple approaches to the modulation of immune status in experimental or clinical situations, but with conflicting or unhelpful results. The variable that has never been assessed is the significance of the surgeon as an immunomodulator. The expediency and the quality of the surgical act in a variety of surgical diseases have a positive effect on the immune system. Indeed, the data indicate that correction of shock, drainage of infection, excision or drainage of necrotic material, restoration of body composition, and solid basic care all have a positive influence on patients' immune responses. An immunomodulator might get credit if the role of surgical care is not properly assessed. A framework for the study of immunomodulators with the integration of clinical behavior is outlined.
general pathological conditions
Prognostic indicators of the resolution of nonimmune hydrops fetalis and survival of the fetus. To delineate any possible prognostic indicators, we reviewed the ultrasonographic and nonmorphometric findings in 19 antenatally diagnosed cases of nonimmune hydrops fetalis in which it was chosen to continue the pregnancy. Thirteen fetuses died and six survived. Of all parameters examined, including associated anomalies, abnormal karyotype, location of serous fluid, anemia, and possible cause of nonimmune hydrops fetalis, the most sensitive prognostic indicator was the real-time-directed M-mode echocardiographic measurement of the biventricular outer dimension in diastole. All fetuses with biventricular outer dimensions greater than 95% died, whereas all but one with normal biventricular outer dimensions had resolution of nonimmune hydrops fetalis and survived. This was highly significant (p less than 0.001) with the predictive value of a normal biventricular outer dimension being 86% and the predictive value of an enlarged biventricular outer dimension being 100%.
general pathological conditions
Electrocardiographic J waves after resuscitation from cardiac arrest. A patient was monitored prior to, during, and after cardiac arrest with a Holter monitor and an electrocardiograph. The arrest occurred without any premonitory signs on the ECG. At the onset of the arrest, torsades de pointes ventricular tachycardia occurred, which quickly degenerated into ventricular fibrillation. After a successful second defibrillation, the patient developed Osborn waves, which subsided within a few minutes.
cardiovascular diseases
Improved access to lesions of the central skull base by mobilization of the zygoma: experience with 54 cases. Improved access to lesions at the medial end of the sphenoid wing or in the interpeduncular cistern after mobilization of the zygoma has been a subject of growing interest in recent years. This study describes the operative technique we have adopted and records our experience with 55 operations in 54 patients who underwent the procedure in the past 3 years. Seven patients had vascular lesions, 44 had tumors, and 3 had miscellaneous lesions. The majority of the tumors were medial meningiomas, and particular note is made of those arising from the cavernous sinus with respect to their resectability. Sixteen of these tumors were encountered, and total excision was possible in 11 cases. Access to the infratemporal fossa is facilitated, and in 2 cases we were able to excise completely trigeminal neuromas that had extended there. The extra maneuver adds little to the overall operating time, and complications relating to it are uncommon, mild in degree, and usually self-limiting. We conclude that the operation is extremely valuable in appropriate circumstances.
nervous system diseases
Artificial urinary sphincters around intestinal segments--are they safe? Artificial urinary sphincters (AUS) were implanted around intestinal segments to achieve urinary continence in 8 patients and faecal continence in 1. In 6 patients the cuff was placed around the lower end of the cystoplasty following bladder neck (5) or urethral (1) erosion. Four are completely dry, 1 on self-intermittent catheterisation (SIC). One has mild stress incontinence. In 1 patient the cuff eroded at 8 months. Two patients had cuffs implanted parastomally to create continent diversion. One is satisfactory on SIC and the other had her AUS explanted because of life-threatening metabolic acidosis. The rectal cuff was explanted because of faecal impaction above the cuff. As an absolute last resort, placing an AUS round a cystoplasty appears little more hazardous than round bladder neck. The use of the AUS for continent diversion has not been pursued because of reliable techniques of non-prosthetic continent diversion. The current model of the AUS is unsuitable for the treatment of faecal incontinence.
general pathological conditions
Endosonography of peri-anal and peri-colorectal fistula and/or abscess in Crohn's disease. Transcolorectal endosonography (ES) was performed in 36 patients with Crohn's disease suspected clinically to have a fistula or abscess. A hypoechoic or anechoic duct-like lesion immediately adjacent to the anorectal lumen compatible with a fistula was found in 32 patients. A communication between the fistulous tract and adjacent structures such as the skin, anal canal, or vagina was detected in all 32 patients. An anechoic cavity adjacent to or communicating with the fistula was visualized in 29 of the 36 patients. A fistula was visualized in the remaining seven patients with no evidence of an abscess. This anechoic cavity compatible with an abscess was surgically confirmed in 14 of 17 patients. We judged the extent and configuration of the abnormalities to be more clearly visualized by ES when results were compared with fistulography in five patients. There were no ES complications, and we conclude that ES is the preferred diagnostic procedure in patients with peri-rectal pathology because of the low risk of bacterial dissemination and low incidence of patient discomfort. Utilizing ES after non-surgical treatment was successful in 19 patients for documentation of the response to therapy.
digestive system diseases
Systolic Hypertension of the Elderly Program (SHEP). Part 10: Analysis. The SHEP is a randomized, placebo-controlled trial that will follow standard clinical trial principles in analyzing data relating to its proposed hypotheses. The protocol has stated a priori the main objective as well as the secondary subgroup hypotheses. Sample size calculations for SHEP have accounted for dropins to and drop-outs from active therapy as well as for the risk of nonstroke death. The sample size achieved (4,736 participants) should be adequate to address the proposed questions. Monitoring procedures have been described and established. A data and safety monitoring board that uses these procedures is closely following the data from the trial. The board will periodically examine the data to determine whether termination of the study is warranted.
cardiovascular diseases
Haemorrhagic shock encephalopathy and sudden infant death In 2 pairs of non-identical twins, haemorrhagic-shock encephalopathy syndrome developed in 1 co-twin while the other died of sudden infant death syndrome. The twin pairs were aged 3 and 4 months, respectively, and no cause was identified. We suggest that stress protein deficiency may underlie both syndromes.
nervous system diseases
Myocardial imaging with Tc-99m teboroxime: technique and initial results. This study examined the results of Tc-99m teboroxime imaging in 22 patients aged 59 +/- 9 years and compared the results with those of thallium-201. The exercise and rest teboroxime studies were obtained within 3 hours of each other using a dose of 15 mCi/study. Because of the very short wash-out half-life of teboroxime, imaging was begun within 1 to 2 minutes after injection. Both SPECT and planar images were obtained; the SPECT protocol was modified by changing the number of frames, the time per frame, or the filters used for reconstruction of images. The planar images were obtained in the supine or upright position. Shorter acquisition time for SPECT (10 sec/frame) and the use of a Butterworth filter with a frequency cutoff of 0.3 cycle/cm and a power of 10 yielded best image quality. There was a close agreement with thallium results in identifying an abnormal or normal perfusion pattern in 89% of vascular territories. The scans were abnormal by both techniques in 12 patients, normal in nine patients, and discordant in only one patient. Thus Tc-99m teboroxime myocardial imaging is feasible at rest and during exercise using either SPECT or planar imaging. Shorter acquisition time and appropriate filtering for SPECT imaging and the upright position in planar imaging improve image quality and are convenient for the patient.
cardiovascular diseases
A pilot study of intermediate-dose methotrexate and cytosine arabinoside, "spread-out" or "up-front," in continuation therapy for childhood non-T, non-B acute lymphoblastic leukemia. A Pediatric Oncology Group study. One hundred six children with newly diagnosed non-T-, non-B-cell acute lymphoblastic leukemia (ALL) were treated in a Pediatric Oncology Group (POG) pilot study in which six courses of intermediate-dose methotrexate (MTX) and cytosine arabinoside (Ara-C) (1 g/m2 each) were added to a "backbone" of standard continuation therapy. The dose and sequence of MTX/Ara-C administration were based on a preclinical model that demonstrated synergism between MTX and Ara-C. Poor-risk patients (n = 49) were assigned to "up-front" therapy, in which the MTX/Ara-C courses were administered during the initial 15 weeks of remission. Standard-risk patients (n = 57) were assigned to "spread-out" therapy, in which the MTX/Ara-C courses were interspersed at 12-week intervals within continuation treatment. Toxicity after intermediate-dose MTX/Ara-C, principally neutropenia and fever, was judged significant but manageable. Unexpectedly, the incidence of fever and neutropenia less than 500/mm3 was greater after "spread-out" therapy (38%) than after "up-front" therapy (6%). At 4 years, the Kaplan-Meier estimate of event-free survival (EFS) is 71% (+/- 7%) for standard-risk patients and 53% (+/- 8%) for poor-risk patients. The results of this pilot study support the use of intermediate-dose MTX/Ara-C in additional studies.
digestive system diseases
Prospective study of a prosthetic H-graft portacaval shunt. This study was undertaken to prospectively evaluate the 8-mm Gore-Tex interposition H-graft portacaval shunt. Thirty-six high-risk patients at the University of South Florida-affiliated hospitals received small-diameter shunts because of bleeding esophagogastric varices over a recent 2-year period. Portal vein and portal vein-inferior vena cava gradients were significantly reduced after shunting. These pressure changes were manifested clinically by the absence of variceal rebleeding and improvement of ascites; in addition, the incidence of encephalopathy was low. The 8-mm graft maintained hepatopedal flow in 67% of the patients, but reversal of flow did not result in complications commonly associated with poor portal perfusion. Graft thrombosis occurred in four (11%) patients. All grafts were successfully revised, three by operative revision and one by an interventional radiologist. Operative mortality was low (11%), and morbidity was unusual. The small-diameter H-graft portacaval shunt is a safe and effective method of treatment for bleeding esophagogastric varices.
cardiovascular diseases
Calcium regulating hormones in essential hypertension. Importance of gender. Alterations of calcium metabolism have been described in human essential hypertension and experimental hypertension. We investigated the interrelationship of parathyroid hormone (PTH) and 1,25(OH)2-vitamin D (1,25(OH)2D) in patients with untreated essential hypertension as compared to normotensive controls. The hypertensive subjects (n = 75; 43 men, 32 women) had a mean blood pressure of 138 +/- 8/95 +/- 5 mm Hg as compared with 120 +/- 11/80 +/- 8 in the normotensive group (n = 40; 22 men, 18 women). Serum PTH was measured with an intact molecule immunochemiluminometric assay and 1,25(OH)2D was measured with radioimmunoassay after HPLC separation. Hypertensive men had PTH levels that were 36% higher than normotensive men (5.3 +/- 2.9 v 3.9 +/- 0.8 pmol/L, P = .005). When blood pressure was analyzed as a continuous variable, there was a direct correlation between it and serum PTH in men (r = .31, P = .004). In women, by contrast, there was no difference in serum PTH between hypertensive and normotensive subjects and no relationship between blood pressure and the serum PTH concentration. Blood pressure was inversely correlated with serum phosphorus levels in both sexes (r = -0.20, P = .04). In men, the elevated serum PTH levels and depressed serum phosphorus levels would have predicted that serum 1,25(OH)2D would be higher in the hypertensive subjects. However, that was not observed, as serum 1,25(OH)2D was slightly lower in hypertensive (38.3 +/- 15.2 pg/mL) than normotensive men (42.7 +/- 11.3, P = .21).
cardiovascular diseases
Surgical correction of hydrothorax from diaphragmatic eventration in children on peritoneal dialysis. Continuous ambulatory peritoneal dialysis (CAPD) is frequently used in the pediatric age group for reversible and end-stage renal failure. Most pediatric patients tolerate this therapy with few complications. Approximately 2% of children, however, develop massive unilateral hydrothorax. This major complication usually results in the discontinuation of peritoneal dialysis in all forms and the institution of hemodialysis. Occult diaphragmatic defects account for most adult and pediatric patients who develop this complication. Three pediatric patients receiving CAPD complicated by massive hydrothorax are described. All patients were successfully treated by thoracotomy and repair of the diaphragmatic eventration with an immediate return to CAPD. This is the first report of successful therapy of this kind in children. A review of the cause, diagnosis, and treatment of massive hydrothorax developing during CAPD therapy is presented.
digestive system diseases
Isometric features of orthostatic tremor: an electromyographic analysis. A patient is described with "orthostatic" tremor. Electromyography revealed tremor bursts of 15 Hz in the lower extremities while standing and with isometric activation of the muscles, but the bursts disappeared with isotonic activation of muscles. Similar tremor was recorded in the arms with isometric, but not isotonic activation. Review of previously reported cases confirms these findings. The clinical and electrophysiologic features of this tremor distinguish it from other recognized forms of tremor.
general pathological conditions
Rectourethral fistula caused by Kaposi's sarcoma. A 35-year-old man with the acquired immunodeficiency syndrome-related complex was evaluated for a persistent urethral discharge, pneumaturia and watery diarrhea. Radiographic and endoscopic procedures established the diagnosis of a rectourethral fistula. Perineal exploration and excision of the fistula revealed the pathological diagnosis of Kaposi's sarcoma. The differential diagnosis of an acquired rectourethral fistula and the significance of Kaposi's sarcoma are discussed.
general pathological conditions
Transient mitral regurgitation due to mitral valve prolapse accompanied by systolic anterior motion of the mitral valve. A grade 4/6 systolic murmur, systolic anterior motion of the mitral valve (SAM), and severe mitral regurgitation (MR) documented by two-dimensional Doppler echocardiography developed suddenly on the structurally normal heart of a patient with idiopathic portal hypertension. The patient did not have signs of congestive heart failure and the aforementioned phenomenon disappeared completely when the patient was in hepatic failure. This could be explained by a change in circulating blood volume either by gastrointestinal hemorrhage or hepatic failure.
general pathological conditions
Polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction: POLIP syndrome. We describe 5 individuals (from three separate families) with a progressive neurological disorder characterized by sensorimotor peripheral polyneuropathy, cranial neuropathies (external ophthalmoplegia, deafness), and the syndrome of chronic intestinal pseudo-obstruction. Magnetic resonance imaging showed widespread abnormality of the cerebral and cerebellar white matter in the 2 patients studied. Autopsy examination in 3 revealed widespread endoneurial fibrosis and demyelination in the peripheral nervous system, possibly secondary to axonal atrophy, and poorly defined changes in cerebral white matter (leukoencephalopathy). The cranial nerves and spinal roots were less severely involved and the neurons in the brainstem and spinal cord were intact. The fatal gastrointestinal dysmotility was due to a severe visceral neuropathy. We suggest that these patients manifested a hereditary disorder with distinctive clinical, radiological, and neuropathological features, and propose the acronym POLIP to emphasize the distinctive tetrad of polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction.
nervous system diseases
Reevaluation of the periodic acid-Schiff stain in acute leukemia with immunophenotypic analyses. To determine the sensitivity and specificity of the periodic acid-Schiff (PAS) stain in the diagnosis of acute leukemia in light of the finer characterization of this disorder now available through immunophenotyping, we examined the blasts from 51 patients with newly diagnosed acute leukemia by morphological, cytochemical, and immunophenotypic analyses. The 51 patients represented every new case of acute leukemia subjected to cytochemical stains and flow cytometry between July 1987 and February 1989. By cell-surface marker analysis, 29 exhibited lymphocytic lineage, while 21 were myelocytic. One was mixed lineage. The PAS positivity, defined by the presence of blocks or coarse granules in 5% or more of the blasts, was found in 15 of 29 lymphoblastic leukemias and in four of the myeloblastic leukemias. However, PAS-positive lymphoblastic leukemias were negative with the other cytochemical stains: myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase. The PAS-positive myeloblastic leukemias were positive with at least one other stain. Three cases of myeloblastic leukemia exhibited greater than 10% PAS-positive blasts, with all three being acute monoblastic leukemia. Thus, the sensitivity and specificity of the PAS stain alone for lymphoblastic leukemia was 52% (15 true positives of 29) and 81% (four false positives), respectively. The sensitivity of a cytochemical-staining combination of PAS positivity and myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase negativity in defining cases of lymphoblastic leukemia remained at 52%; however, the specificity of this combination for lymphoblastic leukemia was 100% (no false positives). Thus, a positive PAS stain, in combination with negative myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase stains, continues to have a diagnostic role in the distinction between lymphoblastic and myeloblastic leukemia, and greater immunologic sophistication serves to support this position.
neoplasms
Enhanced utilization of exogenous glucose improves cardiac function in hypoxic rabbit ventricle without increasing total glycolytic flux. The effects of elevated glucose on cardiac function during hypoxia were investigated in isolated arterially perfused rabbit interventricular septa. Rest tension, developed tension, intracellular potential, 42K+ efflux, lactate production, exogenous glucose utilization, and tissue high-energy phosphate levels were measured during a 50-min period of hypoxia with 4, 5, or 50 mM glucose present (isosmotically balanced with sucrose) and during reoxygenation for 60 min with perfusate containing 5 mM glucose/45 mM sucrose. At physiologic (4 or 5 mM) and supraphysiologic glucose (50 mM), lactate production and high-energy phosphate levels during hypoxia were equally well maintained, yet cardiac dysfunction was markedly attenuated by 50 mM glucose. Despite identical rates of total glycolytic flux, exogenous glucose utilization was enhanced by 50 mM glucose so that tissue glycogen levels remained normal during hypoxia, whereas glycogen became depleted with 4 or 5 mM glucose present during hypoxia. Most of the beneficial effects of 50 mM glucose occurred during the first 25 min of hypoxia. Prior glycogen depletion had no deleterious effects during hypoxia with 50 mM glucose present, but exacerbated cardiac dysfunction during hypoxia with 5 mM glucose present. These findings indicate that enhanced utilization of exogenous glucose improved cardiac function during hypoxia without increasing total glycolytic flux or tissue high-energy phosphate levels, suggesting a novel cardioprotective mechanism.
general pathological conditions
Embryo reduction in multifetal pregnancies after infertility therapy: obstetrical risks and perinatal benefits are related to operative strategy. To assess the benefits that can be expected from embryo reduction of multiple pregnancies after infertility therapy, we report 58 consecutive cases of selective termination using either a transcervical or a transabdominal approach. The initial number of embryos was five or more in 13 patients, four in 29 patients, and three in 15 patients. The miscarriage rate after transabdominal procedures (23%) was one half of that after transcervical aspiration. Forty pregnancies resulted in the live birth of one child or more. The rate of prematurity was strongly related to the number of embryos left. Mean gestational age at birth was 35.5 weeks but reached 37.7 weeks when only one embryo was left. A reduction in premature birth after selective termination appeared clear for pregnancies with four or more embryos but was less significant for triplets.
general pathological conditions
Complications of general anesthesia for Nd:YAG laser resection of endobronchial tumors. We studied the incidence and mechanisms of cardiovascular complications and postoperative respiratory insufficiency associated with GA and Nd:YAG laser endobronchial tumor resection. The records of 73 patients undergoing 87 procedures were reviewed. Preoperative status, anesthetic methods and perioperative complications were analyzed by multiple regression to determine predictors of outcome. Twenty-three percent of patients had greater than 90 percent mainstem bronchus obstruction. Longer serum elimination half-life of relaxant drug was significantly correlated with longer duration of mechanical ventilation after neuromuscular blockade reversal. Cardiovascular complications were noted in 24 procedures and often required therapeutic intervention. Variables predicting cardiovascular complications included longer duration of GA and increasing age. Perioperative respiratory and cardiovascular complications are common after GA for Nd: YAG laser resection. Short-acting neuromuscular relaxants, careful assessment prior to postoperative extubation, limiting duration of GA and cardiovascular monitoring are recommended when implementing GA for Nd: YAG laser resection of endobronchial tumors.
general pathological conditions
Evidence for role of prostacyclin as a systemic hormone in portal hypertension. The possibility that prostacyclin could be a systemic hormone and could mediate the splanchnic hyperemia of chronic portal hypertension was evaluated in rabbits in a normotensive state and in rabbits with chronic partial ligation of the portal vein. In rabbits with portal hypertension (PHT), 6-keto-prostaglandin F1 alpha (PGF1 alpha, a prostacyclin degradation product) was elevated twofold in all vascular beds (systemic arterial, systemic venous, and portal venous) when compared with levels in control animals. In PHT rabbits, exogenous prostacyclin infusion after cyclooxygenase blockade through the systemic arterial, systemic venous, or portal venous route resulted in an equal elevation of 6-keto-PGF1 alpha in the reciprocal vascular beds and restored the original precyclooxygenase blockade hemodynamics. These hemodynamic changes were of equal magnitude irrespective of site of infusion in PHT. In controls there was no significant change in 6-keto-PGF1 alpha or hemodynamics with intraportal infusion. We conclude that prostacyclin achieves systemic levels by escaping hepatic degradation resulting from portosystemic shunting in the animal with chronic portal hypertension.
digestive system diseases
Acoustic schwannoma and epidermoid cyst occurring as a single cerebellopontine angle mass. The case of a 66-year-old man with a 3-year progressive hearing loss and a homogeneous left cerebellopontine angle mass on magnetic resonance imaging scan is described. At surgery, the major portion of the mass was a typical encapsulated, solid, acoustic schwannoma, but the most rostral portion was a distinct, flaky, cystic mass without a well-defined capsule, typical of an epidermoid cyst. The radiographic and operative findings of this unique coexistence of two different benign cerebellopontine angle masses are presented.
nervous system diseases
Recurrent intracaval renal cell carcinoma: the role of intravascular ultrasonography. The presence of extension into the vena cava does not preclude curative resection for extensive renal cell carcinomas. However, preoperative assessment of (1) the proximal extent of the tumor and (2) the degree of adherence within the vena cava is necessary to plan operative strategies. The following report describes the successful use of intravascular ultrasonography in the preoperative evaluation of a patient with recurrent renal cell carcinoma with vena caval extension.
cardiovascular diseases
Experience with 50 free TRAM flap breast reconstructions. The data from the first 50 patients undergoing free TRAM flap breast reconstruction in two units were examined. Average patient age was 42 years, and average weight was 62 kg. Forty percent of patients were chronic smokers, and 26 percent had low abdominal scars. Twelve percent exercised their abdominal muscles regularly. Eighteen percent had undergone radical mastectomy, whereas 76 percent had undergone modified radical mastectomy and 6 percent had undergone subcutaneous mastectomy. Postoperative radiotherapy had been given in 16 percent of patients, and 54 percent had received postoperative chemotherapy. The average time from mastectomy was 32 months, whereas six breasts were reconstructed immediately. Average operating time was 5.6 hours, and average blood loss was 2.4 units. Average hospital stay was 11.2 days. Complications included three total flap losses (6 percent) and two partial flap losses (4 percent). Abdominal hernia occurred in two patients (4 percent).
general pathological conditions
Sexual changes in hemiparetic patients. Eighty-six patients, each with hemiparesis caused by a single stroke, were studied to assess the changes in sexual life experienced after the onset of the illness. Clinical data were collected, and a questionnaire concerning both sexual behavior and feelings about sexuality was administered to the patients and their spouses. Twenty-four couples were eliminated from further analysis because of a discrepancy between husband and wife in the answers concerning sexual behavior after stroke. A marked decline in sexual activity after stroke was found in both genders; other aspects of sexual behavior underwent fewer changes. The feeling of an overall change in sexual life was reported more frequently by male patients. Most patients' spouses reported the feeling of an overall psychological change in their partners and the feeling of an overall change in sexual life after the onset of the illness. No significant associations were found between clinical features and changes in sexual life. This study confirms that cerebrovascular accidents are generally followed by some important alterations in sexual life. Clinical factors do not seem to play a crucial role in determining these changes, which may be better explained in terms of maladjustment attributable to psychologic and interpersonal factors.
general pathological conditions
Clinical safety and efficacy of celiprolol. The management of essential hypertension requires therapeutic selections that are not only effective in reducing diastolic blood pressure but are also tailored to the individual patient, with minimal effect on patient demographics, concurrent illnesses, and cardiovascular risk factors. Celiprolol hydrochloride is a new highly cardioselective vasodilating beta-adrenoceptor antagonist that has been proven effective and safe for the treatment of essential hypertension. It is comparable to other therapies in blood pressure control while demonstrating an excellent safety profile, favorable hemodynamic activity, and minimal effects on other cardiovascular risk factors. Celiprolol may offer the physician a unique therapeutic alternative.
cardiovascular diseases
Paraileostomy hernia: a clinical and radiological study. Forty-six patients who underwent colectomy with end ileostomy for ulcerative colitis (n = 33) or Crohn's disease (n = 13) have been reviewed for paraileostomy hernia (PIH) formation 1-16 years after surgery. PIH developed in 13 of these patients (28 per cent) and was not related to the original disease or excessive weight gain. Twenty-eight patients underwent limited computed tomography (CT) scanning of the stomal region. Eight of these had a clinically detectable PIH, which was demonstrated on CT. A further two patients had PIH demonstrated on CT which was not detected by clinical examination. The rate of PIH was similar where the stoma emerged lateral to the rectus abdominis muscle (six out of 16 patients, 37 per cent) to where the stoma emerged through the rectus (four out of 12 patients, 33 per cent). Recurrence following operative repair of PIH was common. PIH occurs more frequently than previously supposed. CT can detect PIH and may be useful in evaluating a patient with stoma-related symptoms for occult PIH formation.
general pathological conditions
Chilaiditi's syndrome. A diagnostic challenge. Chilaiditi's syndrome should be considered in the differential diagnosis of abdominal and chest pain. Although interposition of the right colon is a relatively common radiologic finding, there is a distinct paucity of information in the medical literature. Chilaiditi's syndrome is usually asymptomatic, but when symptoms occur, conservative treatment is usually effective. Recognition is important because this syndrome can be mistaken for more serious abnormalities, which may lead to unnecessary surgical intervention.
general pathological conditions
Cardiac arrest after hypertonic citrate anticoagulation for chronic hemodialysis. The use of regional citrate anticoagulation as an alternative to standard therapy in hemodialysis patients at risk for bleeding complications has been well described. Recently, a method using hypertonic citrate has been reported as being safe and efficacious, and having several advantages over the usual techniques. Two patients who suffered cardiac arrests after dialysis using hypertonic citrate are discussed. Both received anticoagulation as described in the literature, although the citrate infusion rate was lower than recommended. Electrocardiograms obtained during the first such session showed no change in the Q-Tc interval with initiation of the infusion in either patient. Both were noted to have cardiac arrest within 5 minutes of discontinuation of dialysis, without warning symptoms, following the second and fifteenth treatments, respectively. The initial rhythm of ventricular fibrillation did not respond to standard advanced cardiac life support therapy, and the patients were not successfully resuscitated until they received intravenous calcium. The authors postulate that the loss of positive calcium flux from the dialysate, in conjunction with circulating unmetabolized citrate, caused an electrolyte imbalance leading to the potentially fatal arrhythmia. Caution is recommended in using this method of regional anticoagulation.
general pathological conditions
Adjuvant antibiotic therapy in duodenal ulcers treated with colloidal bismuth subcitrate. Persistence of Helicobacter pylori after duodenal ulcer healing is associated with high rates of ulcer relapse. We compared colloidal bismuth subcitrate alone with CBS combined with one of four antibiotic regimens in the treatment of duodenal ulcers. Endoscopy and antral biopsies were performed before treatment and four weeks afterwards. Biopsy specimens were examined for histological evidence of gastritis and by Gram stain and culture for H pylori infection. Altogether 141 patients were allocated to one of five treatment groups. Giving CBS and metronidazole (400 mg tid for 7 days) with and without amoxycillin (500 mg tid) achieved higher clearance rates of H pylori than treatment with CBS alone (p less than 0.01). These two combinations also achieved higher rates of antral gastritis healing than CBS alone (p less than 0.01 and p less than 0.05 respectively). Susceptibility to metronidazole was tested in 29 isolates before and in seven isolates after treatment with metronidazole by disc diffusion test and minimum inhibitory concentration assay. Twenty seven (93%) of the isolates were sensitive before treatment while six of seven (86%) were resistant afterwards. Four of the six resistant strains had acquired resistance during treatment and one of these had acquired metronidazole resistance despite concomitant treatment with amoxycillin, to which it remained sensitive. CBS with adjuvant metronidazole at a dose of 400 mg tid for seven days significantly improves the eradication of H pylori compared with CBS alone. Acquired metronidazole resistance, however, seems to be an important cause of failure to eradicate H pylori.
digestive system diseases
Acellular matrix allograft small caliber vascular prostheses. We have developed an acellular matrix vascular prosthesis (AMVP) made by detergent and enzymatic extraction of natural arteries, yielding a tissue framework of collagen and elastin from the original vessel, with preservation of the natural basement membrane at the blood flow surface. These biografts have excellent handling characteristics and suturability, as well as low thromboreactivity. Whole vessel static testing of circumferential compliance (8.9 +/- 1 [SEM] X 10(-2)% mmHg at 100 mmHg) revealed behavior virtually identical to the paired natural vessel from which each AMVP was derived in nine canine carotid arteries. We implanted 16 canine-origin AMVPs into nine dogs (12 femoral and three carotid arteries, and one infrarenal aorta) with no antithrombotic drugs. Angiographic patency was maintained in 15 of 16 (one occlusion within 3 days) for follow-up from 3 days to 6 years, with no aneurysm formation in three AMVP at over 4 1/2 years. Explant analysis revealed preservation of AMVP elastica and collagen with no inflammation or dystropic calcification of the AMVP, and almost total thrombus free flow surfaces. These results suggest that allograft AMVPs could achieve long-term patency equivalent to saphenous veins.
general pathological conditions
Subacute poisoning with phosalone, an organophosphate insecticide. An illness characterized by weakness, dizziness, and gastrointestinal symtoms was identified among a crew of 30 migrant field-workers employed by a grape grower in Madera County, California, during August 1987. The onset of symptoms occurred between August 24 and August 30 and a median of 9 days from the date of first employment. The first crew member sought medical treatment on August 26, and 10 crew members were admitted to hospital between August 27 and August 30. For most workers, gastrointestinal and constitutional symptoms resolved shortly after admission, but 4 patients had episodes of severe sinus bradycardia persisting for several days. On the day of admission, transient atrioventricular dissociation developed in 2 persons. Interviews with 16 crew members not admitted to the hospital identified only 1 additional worker ill with gastrointestinal symptoms, but all 16 had moderate to severe inhibition of both plasma and red blood cell cholinesterase. Four other workers who were tested but not interviewed also had cholinesterase depression. The crew had had exposure since August 19 to the organophosphate insecticide phosalone, which was last applied to the vineyard on July 21, or 29 days earlier. Although this is the first report unequivocally linking phosalone to field-worker poisoning, the delayed onset and nonspecific nature of the symptoms associated with subacute poisoning may have hindered the recognition of previous similar episodes.
cardiovascular diseases
Valve and great vessel stenosis: assessment with MR jet velocity mapping. For measurement of poststenotic jet velocities with magnetic resonance (MR) imaging, the authors reduced the echo time (TE) of the field even-echo rephasing (FEER) velocity mapping sequence from 14.0 to 3.6 msec, so minimizing the problem of MR signal loss from turbulent fluid. In vitro use of rotating disk and stenotic flow phantoms confirmed that the 3.6-msec TE sequence enables accurate measurement of jet velocities of up to 6.0 m/sec (r = .996). Peak jet velocity measurements were made with MR imaging in 36 patients with stenosis of native heart valves (n = 9), conduits (n = 19), or Fontan connections (n = 2) or with aortic coarctation (n = 6). Peak velocity measurements made with MR imaging agreed well with measurements made with Doppler ultrasound (US), which were available in 18 cases (standard deviation = 0.2 m/sec). Velocity mapping with fast-echo MR imaging is likely to have considerable importance as a noninvasive means of locating and evaluating stenoses, particularly at sites inaccessible to US, but care must be taken to prevent errors caused by malalignment, signal loss, phase wrap, or partial-volume effects.
general pathological conditions
Hepatocellular carcinoma: comparison of clinical features among ethnic groups in an area of low prevalence. We retrospectively surveyed the clinical features of 73 cases of hepatocellular carcinoma at two hospitals over a 12-yr period. The population was heterogeneous, with 39% representing immigrants from regions of high hepatitis B and hepatocellular carcinoma prevalence. The yearly incidence of cases was constant over the 12 yr. Patient data were analyzed by grouping into three broad categories based on origin from known high, medium, or low prevalence hepatocellular carcinoma zones. In this fashion, differences in clinical presentation were observed. Asians (N = 12) were younger, invariably presented with pain; 82% had markers of hepatitis B and did not have features of chronic liver disease. In contrast, Westerners (N = 45) were older by more than a decade. One-quarter were HBV positive and almost two-thirds were alcoholic. The clinical presentation of this group was more varied, over one-third presenting with features of decompensated liver disease or variceal bleeds. Mediterranean patients (N = 16) had features intermediary between the two other groups. A logistic regression model clinically separated patients with hepatitis B-related hepatocellular carcinoma from those with alcohol-related hepatocellular carcinoma, suggesting different ongoing pathogenetic influences.
neoplasms
Mutations of the ras proto-oncogenes in childhood monosomy 7. ras gene mutations are the most frequent molecular changes found in the preleukemic syndromes of adults and may play a role in initiating these diseases and in their progression to acute leukemia. However, little is known about the incidence or importance of these genetic mutations in childhood myeloproliferative states (MPS). The bone marrow (BM) monosomy 7 syndrome accounts for a large percentage of childhood MPS. Although the duration of the MPS is quite variable, children with monosomy 7 eventually develop acute myeloid leukemia (AML). We investigated 20 children (13 with MPS, 7 with AML) with BM monosomy 7 or 7q- for the presence of ras gene mutations using the polymerase chain reaction and hybridization with mutation-specific oligonucleotides. Mutations of N-ras and K-ras were detected in three children. Two patients carrying a ras mutation were in the myeloproliferative phase, and one had acute leukemia. All three patients with ras mutations either died of their disease or relapsed after BM transplantation as compared with 8 of 17 without ras mutations. However, this difference is not statistically significant (P = .14, not significant). We conclude that ras mutations are observed in childhood monosomy 7, though less frequently than in adult MDS, and may play a limited role in the progression of this disease to acute leukemia. More patients are needed to address the prognostic role of ras mutations in this rare disease.
general pathological conditions
In situ hybridization for the detection of Epstein-Barr virus in central nervous system lymphomas. Epstein-Barr virus (EBV) has been implicated in the development of lymphomas in immunocompromised patients. To test this hypothesis, 26 lymphomas involving the central nervous system (CNS) (11 primary, 15 systemic) were studied for the presence of EBV. In situ hybridization (ISH) was performed on formalin-fixed, paraffin-embedded tissue using a sulfur 35 (35S)-labeled EBV probe (EBV BAMH1-W). The results were interpreted without knowledge of the patients' immunologic status. The EBV sequences were detected in 11 lymphomas, nine of which were mixed or large cell subtypes. Review of the clinical information revealed that nine of the 26 lymphomas occurred in immunocompromised patients secondary to renal transplantation, human immunodeficiency virus infection, leukemia, and Wiskott-Aldrich syndrome. The EBV sequences were detected in all nine lymphomas occurring in immunocompromised patients, whereas two of the 17 lymphomas occurring in immunocompetent patients expressed EBV sequences. The authors conclude that the presence of EBV sequences in CNS lymphomas is highly correlated with a history of compromised immune status supporting a pathogenetic role of EBV in the development of CNS lymphomas in immunocompromised patients.
neoplasms
Percutaneous cholangioscopic or transpapillary insertion of self-expanding biliary metal stents. Fifty-two self-expanding metal stents were implanted in 39 patients with malignant (35 patients) or benign (4 patients) biliary stenoses. The stents were inserted and properly released by means of a 7 or 9 French gauge delivery catheter via the percutaneous (20 patients) or transpapillary (19 patients) route. In all cases the endoprostheses expanded to a diameter of 7 to 10 mm and achieved complete biliary tract drainage. Jaundice disappeared in 36 of the 39 patients. No early complication was observed. After a median follow-up of 121 days (range, 30 to 422 days), 19 of 36 patients are still alive and 17 died of non-procedure-related causes. Biliary re-obstruction occurred in five patients due to tumor overgrowth above or below the prosthesis (four patients) or bile encrustation (one patient). In patients with malignant stenoses, the probability of stent patency is 78% after 200 days. We conclude that large-bore metal stents are safe, effective, and provide better long-term patency than conventional endoprostheses.
general pathological conditions
Antigen-presenting activity of draining lymph node cells from mice painted with a contact allergen during ultraviolet carcinogenesis. The induction of skin cancers in mice by chronic UV irradiation is accompanied by a decrease in the numbers of Ia+ and Thy-1+ dendritic cells in the epidermis early in the course of UV irradiation. Subsequently, the number of Ia+ cells, but not Thy-1+ cells, increases until the time of tumor development. To assess the functional significance of these changes in cutaneous immune cells, and to help define the role these cells may play in immune surveillance against skin cancers, we tested the afferent immunologic capability of the skin during the development of UV-B radiation-induced skin cancers. Afferent immune function was measured by testing the Ag-presenting capacity of draining lymph node (DLN) cells from mice sensitized epicutaneously with dinitrofluorobenzene. A reduced contact hypersensitivity response was induced in mice immunized with DLN cells from UV-irradiated mice that had been sensitized with hapten on UV-irradiated skin. This decreased reactivity was present during the entire latent period of tumor development. However, in tumor-bearing mice, the DLN cells from UV-irradiated, sensitized animals exhibited normal Ag-presenting activity. DLN cells from UV-irradiated mice sensitized on ventral, unirradiated skin exhibited normal Ag-presenting activity. The lowest amount of Ag-presenting activity in the draining lymph nodes of UV-irradiated mice correlated temporally with the lowest number of Ia+, adenosine triphosphatase+ dendritic epidermal cells in the UV-irradiated skin. At least during the early part of the tumor latent period, an increase in the number of these cells was paralleled by an increase in the Ag-presenting activity of the DLN cells. In contrast, the number of Thy-1+ dendritic epidermal cells in UV-irradiated skin did not correlate with the Ag-presenting activity. Thus, the decrease in the number of identifiable epidermal Langerhans cells early in the course of chronic UV irradiation correlated with a decrease in Ag-presenting activity after sensitization through the UV-irradiated skin. These studies demonstrate that the afferent arm of the cutaneous immune response is impaired in the site of tumor development throughout the latent period of UV carcinogenesis.
neoplasms
Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. Forty-seven patients with metastatic malignant melanoma were treated with two 5-day cycles of 100,000 U/kg recombinant interleukin-2 (IL-2) intravenously (IV) every 4 hours separated by 1 week. This dose and schedule of IL-2 were identical to those used in a previous combined IL-2 and lymphokine-activated killer (LAK) cell phase II clinical trial of the IL-2/LAK Working Group. Patient eligibility criteria, and clinical management guidelines were similar to those used in the previous trial. Forty-six patients were assessable for response. Objective responses were observed in 10 of 46 patients (two complete responses [CRs], eight partial responses [PRs]) or 22% with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites. The median response duration was 8 months. Toxicity was significant; three patients developed myocardial infarction, and one patient died during therapy. Overall the toxicity and response rate for single-agent IL-2 are similar to that observed with IL-2 administered in combination with LAK cells in the previous trial. These results suggest that single-agent therapy with IL-2 when administered in this schedule has significant antimelanoma activity in humans, and that LAK cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of IL-2.
cardiovascular diseases
Total gastrectomy for gastric cancer in the elderly. Of 1070 patients with gastric cancers, 292 patients underwent total gastrectomy during 13 years. Sixty patients were more than 70 years of age and 232 were under 69 years. The incidence of well-differentiated carcinomas and poorly differentiated carcinomas was the same in the elderly patients, whereas the latter was dominant in the young patients. However, there was no significant difference between the two groups regarding location, size, macroscopic patterns, extent of lymph metastases, or stage classification. The rates of preoperative surgical risk factors were significantly different between the two groups (p less than 0.01): 90.0% for the elderly and 34.9% for the young patients. However, the rates of postoperative morbidity and mortality were 31.7% and 3.3% for the elderly and 24.1% and 1.3% for the young patients, respectively, with no significant difference. The 5- and 10-year survival rates after curative total gastrectomy were 48.6% and 23.2% for the elderly compared with 49.4% and 33.6% for the young patients, respectively, with no significant difference. A 5-year survival rate after noncurative operation was 0% for the elderly and 6.4% for the young patients. These results indicate that, when performed for cure, total gastrectomy with systematic lymphadenectomy can provide good long-term results for elderly, as well as young, patients.
general pathological conditions
Vimentin expression appears to be associated with poor prognosis in node-negative ductal NOS breast carcinomas. Vimentin expression in tumors from 83 node-negative and 112 node-positive patients with infiltrative ductal not otherwise specified (NOS) breast carcinomas has been compared with 5-year survival. For node-negative, but not for node-positive patients, there was a significant inverse relation between vimentin expression and survival. Five-year survival of node-negative patients with vimentin-positive tumors was significantly worse compared with vimentin-negative tumors (P less than 0.0001). In the node-negative group, only 36% of patients with vimentin-positive tumors but 82% of patients with vimentin-negative tumors survived 5 years. Tumors of all eight node-negative patients with ductal NOS cancer who died in the first 27 months expressed vimentin. Multivariate analysis of the node-negative group showed a strong correlation of vimentin expression and overall survival, but weak and not significant correlation between histologic grade or size and overall survival at 5 years. Thus vimentin expression seems to be a strong indicator of poor prognosis in node-negative ductal NOS breast carcinomas.
neoplasms
Intravenous administration of phosphorylated acid alpha-glucosidase leads to uptake of enzyme in heart and skeletal muscle of mice. The lysosomal storage disorder glycogenosis type II is caused by acid alpha-glucosidase deficiency. In this study we have investigated the possible applicability of mannose 6-phosphate receptor-mediated enzyme replacement therapy to correct the enzyme deficiency in the most affected tissues. Bovine testes acid alpha-glucosidase containing phosphorylated mannose residues was intravenously administered to mice and found to be taken up by heart (70% increase of activity) and skeletal muscle (43% increase); the major target organs. The uptake of nonphosphorylated human placenta acid alpha-glucosidase by heart and skeletal muscle appeared to be significantly less efficient, whereas uptake of dephosphorylated bovine testes enzyme was not detectable. The phosphorylated bovine testes acid alpha-glucosidase remained present in mouse skeletal muscle up to 9-15 d after administration, with a half-life of 2-4 d. Besides being measured in skeletal muscle and heart, uptake of phosphorylated bovine testes and nonphosphorylated human placenta acid alpha-glucosidase was measured in several other organs, but not in brain. The increase of acid alpha-glucosidase activity was highest in liver and spleen. We concluded that application of mannose 6-phosphate receptor-mediated enzyme replacement therapy may offer new perspectives for treatment of glycogenesis type II.
nervous system diseases
A case of multiple pilar tumors and pilar cysts involving the scalp and back. The case of a patient with multiple proliferating trichilemmal tumors and trichilemmal cysts of the scalp and back is discussed. The multicentric presentation of this tumor is unusual and, to our knowledge, has not been described previously. The appearance of trichilemmal cysts in association with multiple proliferating trichilemmal tumors suggests a common histogenesis of these two neoplasms. The typical presenting features, histologic description, and recommended treatment for these tumors are reviewed.
neoplasms
Calcium entry blockade and adrenergic vascular reactivity in hypertensives: differences between nicardipine and diltiazem. The interference of nicardipine and diltiazem infused into the brachial artery at systemically ineffective rates, with the forearm vascular response to graded exogenous norepinephrine, was evaluated in hypertensive patients. Nicardipine (1 and 3 micrograms/dl forearm tissue/min in both absence and presence of propranolol) increased forearm blood flow (venous plethysmography) and antagonized dose dependently the vasoconstrictor effect of norepinephrine, suggesting that functional alpha-antagonism may participate in the vasodilating and possibly the antihypertensive effect of the drug. On the contrary, no antagonism but rather potentiation of the responses to norepinephrine occurred after diltiazem (0.5 and 1 microgram/dl forearm tissue/min). Because intra-arterial propranolol abolished that potentiating action of the drug, whereas the local vasodilation to isoproterenol was clearly reduced, diltiazem probably interfered with beta-adrenergic receptor-mediated vasorelaxing mechanisms in human forearm arterioles. The data further stress the heterogeneity of calcium entry blockers in humans.
cardiovascular diseases
Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding. Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis, screening for oesophageal varices might be appropriate. We prospectively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months. At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1. The subsequent percentages of patients without large oesophageal varices were 74% at one year and 52% at two years. Univariate analysis showed that a longer duration of cirrhosis (p less than 0.05) and grade 1 oesophageal varices at entry (p less than 0.001) were predictive factors for the occurrence of large oesophageal varices, whereas, multivariate analysis showed that the initial size of the oesophageal varices (p less than 0.001), a high initial Child-Pugh score, and a smaller improvement in Child-Pugh score during the study were independent risk factors. Among patients with grades 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31% and 70% respectively. We have calculated that, accepting a maximum risk of first bleeding of 10% without prophylactic treatment, a patient without oesophageal varices should be screened endoscopically every other year, while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy.
general pathological conditions
Temporal bone findings in two cases of head injury. Temporal bone findings in two cases of head injury are reported. In one patient, longitudinal fractures occurred in both temporal bones, and extended to the middle ear bilaterally. Bleeding was seen in the tympanic cavity, mastoid air cells, internal auditory meatus and facial nerve canal. Bleeding was observed in the scala tympani, cochlear aqueduct and endolymphatic sac, but there were no fractures. In the other patient, bleeding was seen in the internal auditory meatus and facial nerve canal. In the right ear, endolymphatic hydrops was observed in all turns of the cochlea.
nervous system diseases
DNA aneuploidy in follicular thyroid neoplasia. The potential value of DNA aneuploidy, in distinguishing benign from malignant follicular thyroid neoplasms, was studied. The nuclear DNA content of 65 follicular thyroid neoplasms (52 adenomas and 13 carcinomas) was determined by flow cytometric analysis of paraffin embedded material; in 58 cases preparations were technically satisfactory. In 22 follicular neoplasms DNA analysis was also performed on fresh material obtained by fine needle aspiration of surgical specimens. Cell cycle analysis was performed on both fresh and fixed specimens. An aneuploid DNA profile was found on analysis of fixed tissue in eight of 45 (18 per cent) follicular adenomas and four of 13 (31 per cent) follicular carcinomas. DNA aneuploidy was also found in six of the 22 (27 per cent) fresh preparations from follicular adenomas. The frequency of DNA aneuploidy in apparently benign and malignant follicular neoplasms was similar. Follicular thyroid neoplasia are best regarded as a single entity with a low incidence of local and distant spread. All follicular neoplasia are therefore best excised.
neoplasms
Micromotion of cemented and uncemented femoral components. We evaluated the initial stability of cemented and uncemented femoral components within the femoral canals of cadaver femurs during simulated single limb stance and stair climbing. Both types were very stable in simulated single limb stance (maximum micromotion of 42 microns for cemented and 30 microns for uncemented components). However, in simulated stair climbing, the cemented components were much more stable than the uncemented components (76 microns as against 280 microns). There was also greater variation in the stability of uncemented components in simulated stair climbing, with two of the seven components moving 200 microns or more. Future implant designs should aim to improve the initial stability of cementless femoral components under torsional loads; this should improve the chances of bony ingrowth.
general pathological conditions
Report of the Canadian Cardiovascular Society's consensus conference on the Management of the Postmyocardial Infarction Patient. In October 1989, the Canadian Cardiovascular Society announced a program to achieve consensus on important issues in the care of patients with cardiovascular disease. This report on the management of the postmyocardial infarction patient represents the first in a series of these consensus conferences. The process for establishing consensus recommendations involved several steps. A primary panel of 11 experts from various fields was selected to review the available clinical evidence and to make a list of recommendations about management decisions in the postmyocardial infarction period. The initial report was distributed to a secondary panel of 16 reviewers* representing allied health care constituencies from across Canada. On the basis of the critical reviews and feedback from these reviewers, a revised report was distributed to all members (over 800) of the Canadian Cardiovascular Society for further review and feedback. This iterative approach resulted in a penultimate report that was presented at a plenary session of the annual scientific meeting of the Canadian Cardiovascular Society on Oct. 18, 1990, in Halifax, NS. On the basis of discussion and feedback from this symposium, the consensus review was completed.
cardiovascular diseases
Amniotic and thromboembolism. Embolic phenomena in pregnancy demand rapid investigation and treatment. Regardless, some patients will not survive due to the enormity of the insult. Optimally, such patients should be treated in tertiary care centers, but this is not always possible.
cardiovascular diseases
Acute naming deficits following dominant temporal lobectomy: prediction by age at 1st risk for seizures. Age at 1st risk for seizures may predict anomia following dominant anterior temporal lobectomy. We assessed confrontation naming before and 2 to 3 weeks after surgery in 45 right-handed patients grouped by side of focus and presence or absence of early (less than or equal to 5 years) risk factors. After left lobectomy, 6 of 10 (60%) patients with no early risks demonstrated significant decline (greater than or equal to 25%) in naming, but none of the patients with early risks showed this decline. After right lobectomy, there was no change. Cerebral representation of naming may be atypical in patients with early risks.
nervous system diseases
Chloroprocaine antagonism of epidural opioid analgesia: a receptor-specific phenomenon? Sixty healthy patients scheduled for elective cesarean delivery under epidural anesthesia were randomized to receive either lidocaine or 2-chloroprocaine as the primary local anesthetic agent. When patients first complained of postoperative pain in the recovery room, they were given either fentanyl 50 micrograms or butorphanol 2 mg, epidurally, in a randomized, blinded fashion. Postoperative analgesia, quantitated on a visual analogue scale, as well as time elapsed until first request for supplemental opioid, did not differ for patients receiving butorphanol after either 2-chloroprocaine or lidocaine anesthesia. In contrast, epidural fentanyl produced a shorter and lesser degree of sensory analgesia after 2-chloroprocaine use, whereas epidural fentanyl after lidocaine anesthesia provided pain relief similar to that seen in the butorphanol groups. Side effects were limited to somnolence with butorphanol and pruritus with fentanyl. No evidence of respiratory depression was seen in any patient. We conclude that 2 mg of butorphanol epidurally provides approximately 2 to 3 h of effective analgesia after cesarean delivery with either lidocaine or 2-chloroprocaine anesthesia. Epidural fentanyl seems to be antagonized when 2-chloroprocaine, but not lidocaine, is used as the primary local anesthetic agent. We suggest a possible mu-receptor-specific etiology for this effect.
general pathological conditions
Effect of maintenance digoxin therapy on aerobic performance and exercise left ventricular function in mild to moderate heart failure due to coronary artery disease: a randomized, placebo-controlled, crossover trial. Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).
cardiovascular diseases
Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A. A case-control study of breast cancer was conducted in Buffalo. Participants completed a food frequency questionnaire and donated a fasting blood sample before definitive workup for breast masses. Dietary and plasma concentrations of carotenoids and retinol for 83 women found to have breast cancer were compared with those of 113 women found to be free of breast cancer (control subjects). There were no case-control differences in dietary estimates of vitamin A intake or in plasma alpha-carotene and lycopene. However, subjects with breast cancer had lower concentrations of plasma beta-carotene than did control subjects (P = 0.02). There was no overall association between plasma retinol and breast cancer but a positive relationship was observed between retinol and breast cancer in the subgroup with low beta-carotene values. These results suggest that low plasma beta-carotene is associated with increased risk of breast cancer. Other studies will need to determine whether low carotene concentrations are a subtle effect of the disease or might be causally related to breast cancer.
neoplasms
Pathogenesis of antigen-induced arthritis in mice deficient in neutrophil elastase and cathepsin G. The contribution of neutrophil-derived elastase and cathepsin G to joint pathology has been examined in immune arthritis in the mouse. Neutrophils from beige mice are genetically deficient in lysosomal elastase and cathepsin G, but have normal levels of the acid hydrolases, beta-glucuronidase, and N-acetyl-beta-glucosaminidase. The development of antigen-induced arthritis in normal mice has been compared with that in beige mice. The pattern of synovitis (both leukocyte accumulation and plasma leakage) were indistinguishable in normal and beige mice. Cartilage proteoglycan depletion was quantified by measuring the decrease in safranin O staining intensity, and this, too, was unaltered in mice lacking elastase and cathepsin G. These results suggest that neutrophil elastase and cathepsin G do not contribute to these aspects of joint pathology in antigen-induced arthritis in the mouse.
general pathological conditions
Endotoxemia in human septic shock. To evaluate the incidence, pattern and clinical importance of endotoxemia in septic shock, frequent, serial endotoxin determinations were made prospectively in patients with shock. Detectable endotoxin occurred in 43 of 100 patients with septic shock, but in only one of ten patients with shock due to nonseptic causes. During septic shock, endotoxemia frequently occurred in the absence of Gram-negative bacteremia. Using a logistic regression model, multiple organ failure occurred 10.3 times more frequently and depression of left ventricular ejection fraction (less than or equal to 45 percent) 4.8 times more frequently in endotoxemic patients. In patients with positive blood cultures, endotoxemia was associated with a high mortality. We conclude that endotoxemia occurs frequently in septic shock and is associated with severe manifestations of this syndrome, including cardiac depression and multiple organ failure. This study suggests that endotoxin is an important mediator of septic shock and supports efforts to develop anti-endotoxin therapies for treating patients with this disease.
general pathological conditions
Clinical presentation of suspected malignant hyperthermia during anaesthesia in 402 probands. As anaesthetists have become more aware of malignant hyperthermia the mortality rate has fallen, but concommitantly the number of dubious and aborted cases has increased. All probands who developed a suspected malignant hyperthermia reaction during anaesthesia and subsequently underwent muscle biopsy were classified according to the clinical presentation. A probability for malignant hyperthermia can be calculated, using the classification, for each type of clinical presentation; this varied from 0.96 to 0.07. Certain clinical features were found to be of more value as predictors than others; these included a high creative kinase and myoglobinuria. The accuracy of prediction depends on a clear contemporaneous description of the clinical events.
general pathological conditions
Acute oculogyric crisis after administration of prochlorperazine. We report a case of acute oculogyric crisis due to prochlorperazine administration in a young black woman with a concomitant viral infection. Neuroleptic medications are the most common cause of drug-induced acute dystonic reactions such as oculogyric crisis. Prochlorperazine is an antiemetic agent with a phenothiazine-type chemical structure and is known to cause dystonic reactions. Drug-induced acute dystonic reactions are most common in young adults and in men. Viral infections may also predispose patients to these adverse reactions. Caution is warranted when this drug is used in patients who have other risk factors for an acute dystonic reaction.
nervous system diseases
Clinical and manometric aspects of diffuse esophageal spasm in a cohort of subjects evaluated for dysphagia and/or chest pain. Manometric criteria for diffuse esophageal spasm have recently been restated. In this study, a cohort of 358 subjects was evaluated in a gastrointestinal motility laboratory for dysphagia and/or chest pain. Applying the recently proposed criteria of Richter and Castell, 18 subjects (5%) were diagnosed as having DES. Dysphagia was the major complaint (89%), while 44% of patients complained of chest pain and 33% of both symptoms. All patients shared more than 30% simultaneous contractions after wet swallows interspersed with normal peristaltic sequences. Associated manometric findings were repetitive (greater than 3 peaks) contractions (67%), high-amplitude contractions (33%), spontaneous activity (22%), prolonged duration (11%), and lower esophageal sphincter abnormalities (5%). Radiology disclosed significant abnormalities in only 27% of DES patients.
digestive system diseases
Comparative in vitro activities of newer quinolones against Pseudomonas species and Xanthomonas maltophilia isolated from patients with cancer. The in vitro susceptibilities of three Pseudomonas species (Pseudomonas aeruginosa, Pseudomonas putida, and Pseudomonas fluorescens) and Xanthomonas maltophilia to quinolone antimicrobial agents were determined. Several newer agents, particularly PD117558, PD117596, PD127391, sparfloxacin (AT-4140), A-56620, and temafloxacin, were active against Pseudomonas species. X. maltophilia isolates were generally less susceptible than were Pseudomonas isolates but were inhibited by some of the newer quinolones.
neoplasms
Continuous removal of middle molecules by hemofiltration in patients with acute liver failure. In patients with acute liver failure and hepatic coma, an increase in the abnormal "middle molecules" seen on the chromatograms of the sera is suspected of playing an etiologic role in the coma. A pilot study of continuous hemofiltration using a high-performance membrane was conducted in 16 such patients in an attempt to decrease the serum levels of the middle molecules. The procedure was used alternately with plasma exchange. High-performance liquid chromatography showed a notable removal of the substances in the filtrates and a sequential removal from the serum by hemofiltration. Eight (50%) of the 16 patients had amelioration in level of consciousness and were weaned successfully from hemofiltration. Although only three of the 16 patients survived the acute illness, 13 others lived an average of 15 days and five patients survived greater than 3 wk. While the continuous removal of middle molecules from the serum may not reverse liver failure, this procedure used in conjunction with plasma exchange may provide a means of life support, e.g., for patients awaiting a liver transplant.
nervous system diseases
Magnetic resonance imaging in the evaluation of spinal tumors. Magnetic resonance imaging (MRI), which has recently begun to replace myelography, postmyelography computed tomography (CT), and to some extent, bone scans, has become the procedure of choice in the evaluation of spinal tumors; the applications of MRI in this role are reviewed. In the extradural space, MRI is the most sensitive technique for the detection of tumors in the vertebral bodies. At the same time, it provides superb delineation of suspected thecal sac impingement. In the intradural extramedullary space, MRI is generally as accurate as myelography and postmyelography CT while being noninvasive. Finally, in the intramedullary space, MRI is unquestionably the procedure of choice in the evaluation of suspected cord tumors. In general, MRI has become the best initial procedure in the evaluation of suspected tumors of the spine, regardless of the space in which they may lie; frequently, it is the only required examination.
neoplasms
Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.
general pathological conditions
Load dependence of left ventricular diastolic pressure-volume relations during short-term coronary artery occlusion. We evaluated the effect of altered loading conditions on left ventricular (LV) diastolic pressure-volume relations during acute coronary artery occlusion that was produced by inflation of an intracoronary balloon. Open-chest anesthetized dogs (n = 18) were instrumented so that LV pressure (micromanometer) and LV volume (conductance) could be measured without disturbing the pericardium. The effects of brief periods of occlusion (1-2 minutes) were assessed under steady-state conditions before and after dextran infusion with the pericardium present and absent and during vena caval occlusion. Under steady-state conditions before dextran infusion with the pericardium removed, at an LV end-diastolic pressure (EDP) of 8.4 +/- 1.4 mm Hg, occlusion resulted in a rightward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 2.7 +/- 2.3 mm Hg; delta LVEDV, 6.3 +/- 4.7 ml, both p less than 0.05 versus control). After dextran infusion (LVEDP, 20.9 +/- 6.0 mm Hg), occlusion resulted in a rightward and upward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 5.8 +/- 4.4 mm Hg; delta LVEDV, 4.2 +/- 3.0 ml, both p less than 0.05 versus control). At low cardiac volumes before dextran infusion, the intact pericardium did not affect the response to occlusion. By contrast, after dextran infusion in the presence of an intact pericardium, LVEDP significantly increased (delta, 6.4 +/- 3.6 mm Hg, p less than 0.05) but LVDEV did not (delta, 0.7 +/- 1.5 ml, p = NS). There was a parallel upward shift in the diastolic portion of the LV pressure-volume loop that was eliminated by removal of the pericardium. Thus, the change in LV diastolic pressure and volume during occlusion varied and depended on the baseline cardiac volume and presence of the pericardium. Before dextran infusion with the pericardium present and absent, coronary artery occlusion did not alter the LV diastolic chamber stiffness parameter, which was calculated from the diastolic interval of an averaged steady-state beat (0.040 +/- 0.019 versus 0.036 +/- 0.015 mm Hg/ml, p = NS). After dextran infusion with the pericardium present and absent, coronary artery occlusion increased the LV diastolic chamber stiffness parameter (0.057 +/- 0.034 and 0.074 +/- 0.034 mm Hg/ml, both p less than 0.05 versus controls, respectively). Vena caval occlusion eliminated the shifts in the diastolic portion of the LV pressure-volume loop with the pericardium present and absent.(ABSTRACT TRUNCATED AT 400 WORDS).
cardiovascular diseases
Coronary artery fistula formation secondary to permanent pacemaker placement. We present the findings in two patients who apparently developed a coronary artery fistula as a complication of an endocardial pacing electrode. This complication may actually be occurring more frequently than recognized because the patient may be asymptomatic or minimally symptomatic and therefore not undergo a coronary angiogram. Awareness of this potentially serious complication is important and stresses the need for proper electrode placement without excess pressure on the tip.
general pathological conditions
Use of magnetic resonance imaging in the diagnosis of cortical blindness in pregnancy. Magnetic resonance imaging (MRI) may be helpful in the assessment of eclampsia and preeclampsia with central nervous system symptomatology such as cortical blindness. We describe a rare case of complete binocular blindness postpartum with no other neurologic deficits, in which MRI abnormalities were undetected on computed tomography. The better soft-tissue discrimination of MRI may visualize important but subtle lesions which ultimately may help to explain the underlying pathophysiologic mechanism in such cases.
cardiovascular diseases
Auras and subclinical seizures: characteristics and prognostic significance. The characteristics and prognostic significance of subclinical seizures and independent auras were studied in 40 patients with partial epilepsy who had long-term electroencephalographic (EEG) monitoring with intracranial electrodes. Focal, restricted subclinical seizures were noted in 23 patients, and 11 patients experienced auras that were accompanied by ictal EEG discharges. Auras and subclinical seizures usually were identical in EEG appearance, but were distributed differently among patients. The subclinical seizures and auras usually had the same origin as complex partial seizures, but did not always reliably indicate complex partial seizure origin. Subclinical seizures and auras were of favorable prognostic significance for patients undergoing temporal lobectomy. A majority (greater than 80%) of individuals with subclinical seizures and auras were free of complex partial seizures after surgery, whereas a minority (29%) of patients without subclinical seizures and auras became free of complex partial seizures.
nervous system diseases
Factors associated with binocular single vision in microtropia/monofixation syndrome. We reviewed the charts of 398 patients with microtropia/monofixation syndrome to determine what factors influence the level of binocularity attained. Most patients (82%) exhibited some degree of stereoacuity. Patients with a later age at presentation of the initial deviation were more likely to exhibit stereoacuity (p less than 0.001). Patients with smaller initial deviations were also more likely to exhibit stereoacuity (p = 0.016), as were those with smaller manifest deviations on final testing (p less than 0.001). Patients with amblyopia on final testing were less likely to demonstrate stereoacuity (p = 0.0001). Generally, the more intervention required in the form of optical or surgical correction, the poorer the level of binocularity.
general pathological conditions
Role of oxygen free radicals in ischemic and reperfused myocardium. In recent years there has been considerable interest concerning the role of oxygen radicals in myocardial ischemia and reperfusion injury. The sequential univalent reduction of oxygen gives rise to very reactive intermediate products. Normally, the tissue concentration of these intermediate products of oxygen is limited and the aerobic myocardium survives because of the existence of a delicate balance between the generation of the various oxidants and the maintenance of the antioxidant defense mechanism. Several possible sources have been identified for the production of active oxygen species after ischemia and reperfusion and these sources may be mutually interactive. The ability of scavengers of oxygen free radicals, including vitamin E, to improve mechanical, mitochondrial, and sarcoplasmic reticulum function in animal models of ischemic-reperfusion injury also suggests that oxygen free radicals are partly responsible for myocardial damage in these models, although caution in the interpretation of these data is necessary.
cardiovascular diseases
The molecular biology of occlusive stroke in childhood. It is very likely that many of the same factors involved in occlusive disease in the adult are operative in the child. The major difference may be in the factors that damage endothelium in these two age groups and thereby initiate this catastrophe (atherosclerosis versus "other" causes of endothelial changes). Our task in this next decade is the rational exploration of the effects of endothelium-mediated kinins, endothelial secretory products, angiospasm, platelet aggregration, prostaglandins, and lipoproteins on pediatric stroke.
nervous system diseases
A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 month of coronary arteriography to participate in double-blind therapy with a placebo or nicardipine 30 mg three times daily. Coronary events (5 deaths, 22 myocardial infarctions, and 28 unstable anginas) occurred in 28 of 192 nicardipine patients and 23 of 191 placebo patients (p = NS). At 24 months coronary arteriography was repeated in 335 patients. Progression, defined as a 10% or more worsening in diameter stenosis, measured quantitatively, was found in 147 of 1,153 lesions (12.7%) in 168 nicardipine patients and in 170 of 1,170 lesions (14.5%) in 167 placebo patients (p = NS). Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p = NS). Regression, that is, an improvement by 10% or more in diameter stenosis, was seen in 140 of 2,323 lesions (6.0%) overall, with no significant intergroup difference. Among the 217 patients with 411 stenoses of 20% or less in the first study, such minimal lesions progressed in only 15 of 99 nicardipine patients compared with 32 of 118 placebo patients (15% versus 27%, p = 0.046). In this subgroup, 16 of 178 minimal lesions in nicardipine patients and 38 of 233 minimal lesions in placebo patients progressed (p = 0.038). By stepwise logistic-regression analysis, baseline systolic blood pressure (p = 0.04) and the change in systolic blood pressure between baseline and 6 months (p = 0.002) correlated with progression of minimal lesions. This suggested blood pressure reduction may account for the beneficial action of nicardipine. These results suggested nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of minimal lesions.
cardiovascular diseases
Results of contemporary radical cystectomy for invasive bladder cancer: a clinicopathological study with an emphasis on the inadequacy of the tumor, nodes and metastases classification. We reviewed 261 patients who underwent a radical operation at a single institution as definitive treatment of invasive bladder cancer to evaluate the survival and accuracy of the tumor, nodes and metastasis system in characterizing the prognosis. Between January 1979 and June 1987 the 261 evaluable patients underwent 1-stage radical cystectomy with pelvic node dissection and urinary diversion. No chemotherapy and/or radiation therapy was given before or after the operation. The postoperative mortality rate was 1.8%. The over-all staging error between clinical and pathological stages was as high as 44%. The over-all actuarial 5-year survival rate was 54.5%. The 5-year survival rates were 75% for stage pT1, 63% for stage pT2, 31% for stage pT3 and 21% for stage pT4 disease. A significant difference in the survival (p less than 0.002) was observed in stage pT3 by dividing tumors confined within the bladder wall (pT3a, 50%) from those extending throughout the bladder wall (pT3b, 15%). A careful evaluation of transitional cell involvement of the prostate in stage pT4a cancer led to the identification of 2 different patterns: 1) contiguous when a bladder tumor extended directly into the prostate through the bladder wall and 2) noncontiguous when a bladder tumor and a transitional cell carcinoma of the prostate were found simultaneously. These patterns had completely different (p less than 0.05) survival rates (6 versus 37%). The patients with high grade tumors had a worse prognosis in comparison with those with grades 1 and 2 tumors (41 versus 56%, p less than 0.005). The over-all 5-year survival of patients with positive nodes was 4% in comparison with 60% of those without nodal involvement (p less than 0.001). Despite current optimal surgical treatment, nearly 50% of all patients with invasive bladder cancer continue to die. The need for a modification of the current tumor, nodes and metastasis tumor classification to provide the clinician a more reliable staging system for planning treatment modalities is indeed mandatory.
general pathological conditions
Surgery or radiation for early cervical cancer. In summary, neither radiation nor surgery is clearly superior. The benefits of surgery include: 1) emotional satisfaction that the tumor has been removed, 2) accuracy of surgical staging, 3) preservation of the ovaries, 4) no secondary uterine cancer (a very uncommon problem), and 5) complications that are more readily correctable. Radiation offers the major advantages of being useful in most patients regardless of age or medical condition and is the choice for large cancers. Because stage IB cervical cancer is a very diverse pathological entity with a number of potential prognostic factors (including cell type, depth of invasion, tumor volume, lymphatic space involvement, and occult lymph node metastases), and because patients present with a number of other conditions (including excess weight, advanced age, prior pelvic surgery or infection, and severe medical illness), we are fortunate to have two good methods for treating cervical cancer. Prospective randomized studies will be necessary in the future to better define specific advantages in the various clinical settings. But, in general, the following have proven most expedient: 1) class I hysterectomy, for microinvasive cancer of 3 mm invasion or less without lymphatic space involvement, 2) modified, extended hysterectomy (class II) and pelvic lymphadenectomy for lesions of 3 mm and lymph vascular space involvement or when the lesion seems to just exceed 3 mm and for very early adenocarcinoma, 3) an extended hysterectomy (class III) and pelvic lymphadenectomy for larger IA2, IB, and IIA lesions that are less than 4 cm, particularly for the pregnant or younger patient, and when ovarian conservation is desired, 4) radiation therapy is used for lesions over 4 cm and for women with severe medical illness making extended hysterectomy too hazardous, 5) combination therapy and chemotherapy are now reserved for study in poor prognosis patients with very large lesions (greater than 6 cm), occult metastases, and unfavorable histologic criteria (Table 2).
general pathological conditions
Femoral saphenous vein bypass in a newborn. This is believed to be the youngest patient to undergo a saphenous vein bypass for iatrogenic trauma of the right superficial femoral artery. The infant had emergency right heart catheterisation and Rashkind septostomy for severe desaturation due to transposition of the great arteries. During the exposure of the saphenous vein, the superficial femoral artery was accidentally severed at it's origin. An attempt to restore the circulation by end-to-end anastomosis failed and resulted in persistent limb ischemia for over 4 hours. The baby was reoperated upon, the damaged part of the superficial femoral artery was resected and a saphenous vein graft interposed between the common and the distal superficial femoral artery.
general pathological conditions
Rett syndrome: cerebellar pathology. The cerebellar pathology at autopsy of 5 patients with Rett syndrome is described. The patients ranged in age from 7-30 years. All had markedly reduced brain weights with proportionately small cerebella. Microscopic examination revealed loss of Purkinje cells, atrophy, astrocytic gliosis of the molecular and granular cell layers, and gliosis and loss of myelin in the white matter. Cortical atrophy occurred focally along the folia and was often more marked in the tips of the folia. The 2 oldest patients had been treated with phenytoin which may have contributed to the morphologic changes. Atrophy and gliosis increased with age or in patients without phenytoin treatment; the youngest patient demonstrated only minor microscopic changes. In addition to the generalized alterations, 1 patient had several adjacent folia with severe atrophy. The results indicate that cerebellar changes in Rett syndrome consist of general hypoplasia with the addition of atrophy beginning in childhood and progressing over many years.
general pathological conditions
Stereotactic radiosurgery of meningiomas. Stereotactic radiosurgery has an expanding role in the management of selected intracranial tumors. In an initial 30-month experience using the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 50 patients with meningiomas were treated. The most frequent site of origin was the skull base. Previously, 36 patients (72%) had undergone at least one craniotomy and four patients (8%) had received fractionated external beam radiation therapy. Stereotactic radiosurgery was the primary treatment modality in 16 patients (32%) with symptomatic tumors demonstrated by neuroimaging. Computer imaging-generated isodose plans (with one to five irradiation isocenters) for single-treatment irradiation gave optimal (greater than or equal to 50% isodose line) coverage in 44 patients (88%). The proximity of cranial nerves or vascular, pituitary, and brain-stem structures to the often convoluted tumor mass was crucial to dose selection. Serial imaging studies were evaluated in all 50 patients. Twenty-four patients were examined between 12 and 36 months after treatment; 13 (54%) showed a reduction in tumor volume while nine (38%) showed no change. Of 26 patients evaluated between 6 and 12 months after treatment, four showed a decrease in tumor size while 22 showed no change. Two patients (both with large tumors that received suboptimal irradiation) had delayed tumor growth outside the radiosurgical treatment volume. The actuarial 2-year tumor growth control rate was 96%. Between 3 and 12 months after radiosurgery, three patients developed delayed neurological deficits that gradually improved, compatible with delayed radiation injury. Although extended follow-up monitoring over many years will be necessary to fully evaluate treatment, to date stereotactic radiosurgery has proved to be a relatively safe and effective therapy for selected patients with symptomatic meningiomas, including those who failed surgical resection. Radiosurgery was an effective primary treatment alternative for those patients whose advanced age, medical condition, or high-risk tumor location mitigated against surgical resection.
neoplasms
Methodologic issues in assessing the quality of life of cancer patients. Although quality of life assessments have been employed successfully in descriptive and evaluative studies in oncology, their use in cancer clinical trials has, to date, been limited. A range of issues have impeded the conduct of clinical trial-based quality of life investigations. These include: the absence of theoretical models to guide the development of quality of life measures; over-reliance on ad hoc approaches to quality of life assessment; and insufficient attention to the practical constraints operating in clinical research settings. Of primary importance is the need to develop multidimensional quality of life instruments that are brief and psychometrically robust. It is suggested that future work on instrument development focus on refining currently available generic or cancer-specific measures, and on developing new diagnostic-specific questionnaire modules. This psychometric work should be guided by appropriate theoretical models of the relationship among health-related quality of life domains. Although it is widely accepted that the patient represents the most appropriate source of quality of life data, it is suggested that efforts also be directed toward improving the validity and reliability of physician-generated assessments of patients' performance status and of treatment toxicities, and toward determining the feasibility of employing family members as proxy raters of the psychologic and social health status of patients who are unwilling or unable to provide such information. Additional attention should be paid to the many logistical problems that arise in clinical trial-based quality of life investigations. In particular, research designs and data collection procedures should be selected that minimize patient, medical staff, and institutional burden.
neoplasms
Unusual aspects of aortovenous fistulas associated with ruptured abdominal aortic aneurysms. Three unusual cases of an abdominal aortic aneurysm spontaneously rupturing into the retroperitoneum and an adherent posterior vein are reported. No patient demonstrated signs or symptoms of an aortovenous fistula before surgery. Emergent surgery prevented extensive preoperative diagnostic testing. The three abdominal aortic aneurysms were very large and averaged 13 cm in diameter. One fistula involved an inflammatory aneurysm, which is the fifth such case reported. The aortic fistulas were to the inferior vena cava (158 other cases reported in the English-language literature), a left renal vein (16 other cases reported), and an iliac vein (7 other cases reported). Routine use of the cell-saver, oversewing of the fistula from within the aneurysm, and a heightened awareness that this unusual complication is more common in the presence of a very large, ruptured abdominal aortic aneurysm should improve survival.
general pathological conditions