[Left atrial booster pump function in patients with hypertrophic cardiomyopathy and essential hypertension: evaluations based on left atrial pressure-volume relationship]. In patients with hypertrophic cardiomyopathy (HCM) and essential hypertension (HT), left ventricular dysfunction in early diastole which is associated with left atrial contraction plays an important role in left ventricular filling. To evaluate left atrial booster pump function, we analyzed left atrial preload (left atrial pressure at the end of diastasis; LAPd, left atrial volume index at the end of diastasis; LAVd), left atrial afterload (left ventricular end-diastolic pressure; LVEDP, left ventricular chamber stiffness constant; K), and left atrial ejection indices (left atrial ejection fraction during atrial contraction; LAEF, left atrial ejection volume index during atrial contraction; ACVI). The study subjects consisted of control subjects (n = 5), HT patients (n = 6), and HCM patients (n = 11). The left ventricular wall was significantly thicker in the HT and HCM groups. The left ventricular rapid filling volume index was less in the HT group, and significantly less in the HCM than in the control group. LAPd and LAVd were greater in the HT group than in the control group, and greater in the HCM group than in the HT group. LVEDP and K were greater in the HT group than in the control group, and significantly greater in the HCM group than in the other 2 groups. ACVI was greater in the HT group than in the control group, but in the HCM group, ACVI was significantly less than in the HT group and did not differ significantly from that in the control group. LAEF was significantly less in the HCM group than in the other 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)


A comparative study of flurbiprofen and piroxicam in osteoarthritis. In this single-blind, multiple-dose study the efficacy and tolerability of flurbiprofen was compared with that of piroxicam in 60 adult patients suffering from osteoarthritis of the knee. The patients were randomly allocated to receive either flurbiprofen 100 mg twice daily or piroxicam 20 mg once daily for a period of four weeks. Clinical assessments w.r.t. pain, tenderness, stiffness, swelling and general activity of patient were carried out prior to initiation of trial therapy and thereafter at weekly intervals for four weeks. The findings were graded. Though significant improvements as compared to baseline data occurred in both the treatment groups, flurbiprofen was found to be superior to piroxicam in improving pain on movement and at rest (p < 0.05). The incidence of side effects was less in the group receiving flurbiprofen (6% compared to 47% observed with piroxicam).


What should be called a brisk 'Y' descent? Patients with pericardial constriction show a prominent 'y' descent in right atrial and vena caval pressure traces. In all earlier hemodynamic descriptions of constrictive pericarditis, the 'y' descent has been described as 'brisk', 'sharp' or 'rapid' but no effort has been made to quantify the same. In this study, we have tried to objectively evaluate and describe this 'y' descent by measuring its negative slope (-dy/dt) at its steepest portion. Forty one patients were studied hemodynamically, 9 with constrictive pericarditis (Group I) and 32 normals (Group II). The negative slope of the 'y' descent in patients with constrictive pericarditis (69.95 +/- 23.04 mm Hg) was found to be significantly greater than normals (35.13 +/- 7.84 mm Hg, p < 10(-6). Discriminant analysis was used to determine its sensitivity, specificity, predictive value and overall accuracy, in the diagnosis of pericardial constriction. Value of > or = 45 mm Hg/sec was found to have the highest overall accuracy (0.88). The correlation between the right ventricular end diastolic pressure and the slope of 'y' descent in patients with pericardial constriction (r = 0.66) and in normals (r = 0.60) was fair. It is concluded that -dy/dt is significantly different in patients with constrictive pericarditis as compared to normals. The diagnostic utility of this parameter needs to be evaluated in patients with equivocal clinical and hemodynamic data, in those with occult pericardial constriction and in post-pericardiectomy cases where the pressures do not normalise immediately after adequate pericardial resection.


Wildervanck syndrome (cervico-oculo-acoustic syndrome). Wildervanck syndrome i.e. cervico (Klippel-Feil anomalad) -oculo (Duane-Stilling-Turk phenomenon with bilateral abducens palsy)-acoustic (deafness) is a rare syndrome. We report here 4 cases diagnosed as Wildervanck syndrome and analyse their findings. One patient had an an atrial septal defect. Such association of congenital heart disease with Wildervanck syndrome has not been reported previously.


Relevance of plasma fibrinogen estimation in obstetric complications. We present a study of fibrinogen levels in 133 patients who were prone to develop disseminated intravascular coagulation as a result of an underlying complication of pregnancy such as abruptio placentae, pregnancy-induced hypertension, missed abortion, septic abortion, intrauterine fetal death, vesicular mole and amniotic fluid embolism. A high incidence of hypofibrinogenemia was found in cases of abruptio placentae (43.9%) and pregnancy-induced hypertension (25%). Hypofibrinogenemia occurred in 10% cases of intrauterine fetal death within 4 weeks of fetal demise. The use of this simple investigation makes possible the diagnosis of hemostatic failure and also helps to guide replacement therapy during the fibrinopenic state. There were 4 maternal deaths and 12 perinatal losses in this study.


Study of intrarenal vasculature in cases of primary and secondary hypertension (by metallic impregnation technique on whole kidney section). Study of intrarenal vasculature was carried out by using the metallic impregnation technique on whole kidney sections in 31 [corrected] cases of (primary and secondary) hypertension and 10 normal controls. Distinct patterns of intrarenal vasculature were noted in controls and in cases of hypertension. Gradual tapering of vessels, absence of tortuosity and good peripheral vascularisation were noted in controls. Abrupt tapering, tortuosity of vessels and poor peripheral vascularisation were noted in hypertensive cases. In essential hypertension moderate to severe changes of dilatation of the segmental and/or arcuate arteries was noted. The degree of dilatation was related to the level of systolic BP rather than diastolic in cases of essential hypertension. Secondary hypertension even if severe, rarely showed significant dilatation lesions. Avascular zones and conglomeration of vessels at poles was seen only in cases of pyelonephritis. This helped in distinguishing these, from cases of glomerulonephritis.


Hydatid cyst of the tibia.

Hydatid cyst of the tibia. A case of hydatid cyst of the tibia, which manifested as a pathologic fracture is being reported. Pain and swelling of left lower limb with inability to bear the weight were the main features. Tender swelling was also noted at the upper and middle third of tibia. Open biopsy revealed the hydatid cyst wall and scolices of Echinococcus granulosus. Albendazole treatment was followed by curettage and bone grafting.


Craniopharyngioma: treatment by conservative surgery and radiation therapy. Benign neoplasms are curable only when excised. This applies even to craniopharyngiomas. The proximity of craniopharyngiomas to the hypothalamus and neurovascular structures makes total excision difficult to achieve. Over the last 3-4 decades, it has become increasingly obvious that craniopharyngiomas respond to radiation therapy. Early, unhappy results with major excisions have prompted us to adopt a policy of conservative surgery and radiation therapy to the residual tumour. Preliminary results suggest a good outcome in 35 of the 63 patients so treated from 1981. Details of the study are presented.


Use of aminocaproic acid (ACA) in extra-amniotic MTP in patients on anti-coagulant therapy. A case of rheumatic heart disease (RHD) with prosthetic mitral valve endocarditis receiving anticoagulation with heparin, underwent medical termination of pregnancy in a second trimester. The following report entails the use of aminocaproic acid (ACA) in preventing excessive bleeding during and after the procedure, while the patient continued to receive anticoagulant therapy.


Orbital cysticercosis.

Orbital cysticercosis. Orbital cysticercosis is a rare condition. We report here 3 cases with orbital cysticercosis who presented with proptosis and ptosis (Case no. 1 and 2) and focal seizures (Case no. 3). All of them had a vision of 6/6. Diagnosis of cysticercosis was made on CT Scan. The lesions isolated in Cases 1 and 2 and were excised. Drug therapy was given to treat any persisting infestation. Case no 3 had multiple brain cysticerci in addition to the orbital one. However, the patient was lost to follow-up.


[Lupus anticoagulant].

[Lupus anticoagulant]. Lupus anticoagulant (LAC) is an acquired inhibitor of prothrombin activator complex, which probably interferes with the phospholipid portion. Characteristically, LAC prolongs the partial prothrombin time, but only slightly prolongs the prothrombin time. It is a paradoxical fact that LAC is characterized by thrombosis. It was initially described in patients with SLE, but recently, it has been described as occurring with other autoimmune disorders. Patients with LAC have been treated with steroid and aspirin, anti platelet agents or warfarin. Steroid and aspirin therapy has been reported useful for habitual abortion associated with LAC. In our study, 11 patients, whose prior pregnancies resulted in habitual abortion (41 abortions), received intentional prednisolone (40 mg/day) and aspirin (81 mg/day) therapy before further pregnancies. The doses of both agents were decreased gradually, and the therapy with prednisolone (10-15 mg/day) and aspirin (40.5 mg/day) was maintained during the pregnancy period. The outcome of pregnancy was successful in 7 out of 10 pregnancies. To evaluate the relationship between LAC and glomerulopathy, we examined the renal biopsy from 5 LAC cases without SLE. In pathological findings, there were 3 of with mild proliferative GN and 2 cases of minor glomerular abnormality. There were no characteristic findings in LAC nephropathy.


Epithelioid sarcoma of the upper extremity with cerebral metastases. A forty year old male patient presented with swollen, deformed right hand with multiple irregular ulcers. The axillary lymph nodes were enlarged, firm and tender. The biopsy of nodules present on the hand revealed areas of haemorrhage and necrosis. The histopathological examination confirmed the clinical diagnosis of epithelioid sarcoma. Following below-elbow amputation, patient failed to regain consciousness and expired. On autopsy, distant metastases were found in the regional lymph nodes, pleura, kidney and cerebrum.


[Nephritis and complement].

[Nephritis and complement]. There are many cases in which renal biopsies show glomerular complement accumulation. Some of these cases have low serum complement levels, but the extent to which the complement system participates in the pathogenesis of glomerulonephritis is unknown. We examined the activation system in acute poststreptococcal glomerulonephritis (PSGN). Ordinarily in PSGN an alternative pathway is activated. In the early stage of the disease, both C3 and C4 serum complement levels were depressed in one fourth. This suggested that the classical pathway is also activated in PSGN. Serum complement levels are very important in the diagnosis of the type and severity of lupus nephritis. Serum complement levels and activity index of lupus nephritis were very well correlated in our cases. The improvement of serum complement levels may corresponds to the improvement of the pathological activity of the disease.


Cytodiagnosis for pelvic tuberculosis.

Cytodiagnosis for pelvic tuberculosis. A 25 yr old married woman with complaints of lower abdominal pain for 2 months, was found to have a irregular nontender mass in pelvis, adherent to uterus. Her Papanicolaou smear was inflammatory. To confirm the diagnosis of either ovarian malignancy or pelvic tuberculosis made on the basis of observations during exploratory laparotomy, ovarian biopsy was taken. The imprint cytodiagnosis was tuberculosis. The patient was then managed surgically and the previous diagnosis was reconfirmed by histopathology. Imprint cytodiagnosis appears to be a valuable technique whenever facilities for frozen section are not available.


Multiple chylous cysts of abdomen causing intestinal obstruction. A case of multiple chylous cysts of the abdomen in a 35 years old female is presented here. The patient presented with signs and symptoms of acute intestinal obstruction. Exploratory laparotomy revealed few intestinal adhesions along with multiple small cysts containing blood stained gelatinous material in the abdominal cavity, some of which were excised alongwith lymph nodes. The abdomen was closed after a saline peritoneal lavage. Chylous nature of the cysts was confirmed on histopathology. The post-operative course was asymptomatic.


[Glomerulonephritis and superoxide dismutase]. To study the role of reactive oxygen species (ROS) in chronic renal disease, we studied the localization of Cu, Zn-superoxide dismutase (SOD) in glomeruli of patients with IgA nephropathy by immunohistochemistry on 37 kidney specimens consisting of 32 IgA nephropathy and normal parts of the 5 resected kidneys with renal tumors serving as controls. To evaluate the change in renal function, creatinine clearance (Ccr) was assessed at the time of biopsy and 1 year after the biopsy. In the normal kidney, Cu, Zn-SOD was localized in the tubular cells, and not in the glomeruli. In the kidney with IgA nephropathy, Cu, Zn-SOD was detected on the epithelial side of the glomerular capillary wall in addition to the tubular cells. The extent of localization of this enzyme was compared with the clinical findings at the time of biopsy. When Cu, Zn-SOD was stained strongly in the glomeruli, the histological change of the glomeruli was milder, and the renal function appeared to be more preserved; the decrease in Ccr one year after the renal biopsy was inhibited. These findings suggest that Cu, Zn-SOD has beneficial actions for renal function as anti-oxidative factors.


[Clinical and laboratory evaluation of pediatric kidney disease]. In infancy, the kidney by itself is immature and the body fluid composition is extremely different from that in adults. Further more, there are various renal diseases in children with characteristics different from those in adults. Thus in childhood, consideration for aging is critical for evaluation of renal function, and diagnosis of the disease. Recently, mass screening for infants or children in kindergarten or school has enabled us to find many children with renal disease, in whom symptoms are not overt. Thus the disease can be treated in an early phase. This may give a better prognosis for such children. To make an early diagnosis of renal disease it is essential to consider what laboratory tests are chosen and how the data accumulated are interpreted. In the present study, individual laboratory tests for the diagnosis of renal diseases and an indication of such tests as well as interpretation of the data are reviewed.


[Laboratory data in chronic dialysis patients]. The principle of prescribing dialysis therapy is treatment of uremic symptoms and morbidity, and adequate therapy to prevent complication of long term dialysis. For this purpose careful measurement and monitoring of various parameters should be done in chronic dialysis patients. We analyzed the laboratory data of 82 patients treated at our dialysis center. We started correction of renal anemia with erythropoietin from 1987, and the mean hematocrit was improved from 24% to 28%. The blood transfusion volume was decreased markedly. There was a significant correlation between plasma alpha-human atrial natriuretic peptide (HANP) levels and the size of the heart. Plasma HANP seems to be a reliable parameter of the so-called dry weight in patients on maintenance dialysis. We analyzed the parameters of bone for the recent four years. Alkaline phosphatase (ALP) and C-PTH increased throughout the duration of dialysis, while bone mineral density (BMD) decreased. Annual changes of sigma GS/D were negatively correlated with ALP and C-PTH. In relation to duration of dialysis, changes of sigma GS/D were less in the group treated for less than 3 years. Nine patients (60% of patients on dialysis more than 10 years) had carpal tunnel syndrome (CTS) with symptoms and signs. Median nerve distal motor latency was positively correlated with the duration of dialysis. The beta 2-microglobulin (beta 2-MG) level of dialysis patients was very high and even though the beta 2-MG level was lowered by hemodiafiltration CTS was not improved.


Primary extrapancreatic gastrinoma.

Primary extrapancreatic gastrinoma. Extrapancreatic gastrinoma is a rare clinical entity encountered in surgical practice. A patient was referred to us who had a history of recurring symptoms of peptic ulcer disease and ulcer perforation located at an unusual site. Serum gastrin levels were abnormally high. Scopy revealed multiple ulcers in the antrum and duodenum. A mass superior to the head of the pancreas was detected on USG, which later on found to be a separate mass on CT scan. The tumour was excised and confirmed on histopathology. Results of conservative surgery were found to be satisfactory.


Pulmonary metastases on bone scan in a patient with osteogenic sarcoma. This paper describes a young man who was treated with amputation for osteogenic sarcoma of the lower end of the right tibia. Pre-operative whole body bone scan with 99 mTc did not reveal abnormal tracer concentration in the lungs. A similar follow-up bone scan six months post-operatively demonstrated an area of abnormal tracer concentration in the lower lobe of each lung.


[Laboratory tests in acute renal failure]. This review is focused on the roles of laboratory test in acute renal failure (ARF). The roles of the laboratory test changes along with the alterations in clinical features and with the advances of treatment. Recent acute renal failure is characterized by the following three features: most of the ARF develops in hospitals, the frequency of nonoliguric ARF is increasing, and the association of other organ failure such as heart failure, liver failure or respiratory failure, increases the mortality rate. Hemodialysis is instituted in the early phase of ARF to enable the supply of enough nutriments and drugs. These features of recent ARF increases the importance of the frequent analysis of plasma creatinine in patients, who are at risk for ARF, to diagnose ARF at the onset. After the development of ARF, laboratory tests for the evaluation of other organ function is repeated. The development of new drugs increases the incidence of interstitial nephritis, and the advances in the therapeutic approach on systemic diseases (such as SLE or PN), which frequently develop ARF, alter the prognosis of these diseases. Since the early diagnosis of these diseases is important, it is necessary to develop noninvasive and reliable tests for the diagnosis of these diseases.


Insulinoma.

Insulinoma. A case of insulinoma who had episoic bizarre behaviour is presented here. Pre-operative fasting and two hour post-prandial blood sugar values indicated hypoglycemia with inappropriately high insulin levels. USG and CT scan of the abdomen revealed a tumor of head of the pancreas. The tumour was enucleated surgically. Histopathological examination confirmed the origin as islet cells. The post-operative blood sugar and insulin levels were found to be in normal range. Since insulinoma is a rare pancreatic tumor, differential diagnoses along with a brief review of the literature is also presented.


[Diagnosis on Mycoplasma pneumoniae infections by DNA-probe assay in comparison with serological tests]. To evaluate the usefulness of DNA diagnosis as a diagnostic approach to Mycoplasma pneumoniae infections, we compared the DNA-probe assay with serological tests in 32 patients who were clinically suspected of having Mycoplasma pneumonia. The DNA-probe assay was carried out using the Gen-probe kit. Serological tests included complement fixation and passive hemagglutination tests. At first visit 10 patients were positive for the DNA-probe assay, while only 2 of them were positive for serological tests. The other 3 patients became positive for serological tests during the clinical course. In accordance with clinical improvement, these patients became negative for the DNA-probe assay. Three patients were negative for DNA-probe assay while they were positive for the serological tests. However, these patients had already received antibiotics; therefore, their conditions were considered to have been improved at the time of the study. The other 19 patients were negative for both the DNA-probe assay and serological tests. These patients might have suffered from respiratory tract infections of pathogenic organisms other than M. pneumoniae or the number of M. pneumoniae might have been too small to be detected by the DNA-probe assay. The results of the present work demonstrate that the DNA-probe assay was valuable in the diagnosis of mycoplasmal infections at the early stage, which indicates that DNA diagnosis provides useful information to determine the most appropriate therapeutic regimen.


[Genetic diagnosis of phenylketonuria: identification of the mutations of phenylalanine hydroxylase gene by PCR direct sequencing]. To investigate the mutations of the phenylalanine hydroxylase (PAH) gene in Orientals, direct sequencing was conducted on DNA fragments amplified by the polymerase chain reaction, using solid phase technology involving the biotin-streptavidin system. Four mutations possibly associated with phenylketonuria (PKU) were identified in a Chinese and four Japanese patients. A novel Arg158 (CGG)-to-Trp158 (TGG) mutation was identified in exon 5 of the PAH gene in a Chinese PKU patient. The second change was due to a G-to-A transversion at the last base of intron 4. The third change was a compound heterozygote; one mutation was a G-to-A transversion at the last base of intron 4. The other was a G-to-C transversion at the second base of codon 413, which resulted in a substitution of Arg(CGC) by Pro(CCC) in exon 12. The last change was due to a Tyr204(TAT) -to-cys204(TGT) mutation in exon 6 of the PAH gene in two Japanese. This preliminary study revealed a novel PKU mutation and considerable genetic heterogeneity in the PAH gene among Orientals.


[Detection of the mutation responsible for adenine phosphoribosyltransferase deficiency among Japanese patients]. Adenine phosphoribosyltransferase (APRT) deficiency causes 2,8-dihydroxyadenine(DHA) urolithiasis and renal failure. Recently, two different common mutations were identified; one was APRT* J with a substitution of ACG for ATG at codon 136, called "Japanese-type", another was APRT* Q0 with TGA for TGG at codon 98. Approximately 98% of all Japanese patients with this disorder have been estimated to have these mutations APRT* J (approximately 80%) and/or APRT*Q0 (approximately 20%). We developed a diagnostic method to detect these genotypes. After gene amplification by PCR, target DNA was hybridized with a biotinylated specific probe in the presence of the non-labelled competitive probe on a dot-blotted membrane. To detect the APRT* J (or APRT* Q0) mutation, the biotinylated APRT* J (or APRT* Q0) probe and non-labelled normal probe for the same region were used as specific and competitive probes, respectively. After incubation at 60 degrees C for 30 min, the temperature was gradually decreased from 60 degrees C to 40 degrees C during 120 min, and then incubation was continued at 40 degrees C for 30 min. By using method, we were able to omit the posthybridization process, and the detecting signal was clear and highly specific. This method is useful for detecting point mutations in other genes.


[Clinical application of anti double-stranded and single-stranded DNA antibodies measurements by enzyme-linked immunosorbent assay (ELISA) using E. coli plasmid DNA]. Anti double-stranded (ds) and single-stranded (ss) DNA IgG antibodies were detected in patients with various connective tissue diseases by RECOMBIGEN ELISA Anti ds-DNA Kit and ELISA Anti ss-DNA Kit (Nippon DPC Co) using E. coli plasmid DNA. High levels of anti ds-DNA and anti ss-DNA antibodies were mostly found and distributed in patients with systemic lupus erythematosus(SLE) and allied disorders. The sensitivity of Anti ds-DNA Kit was higher than that of current ELISA kit using calf thymus DNA antigen. In SLE patients with anti DNA antibodies sixty per cent of sera were reacted with both ds- and ss-DNA antigens, and forty per cent of sera were reacted only with ss-DNA antigen; there was no sample reacted positively with ds-DNA antigen alone. RECOMBIGEN ELISA Anti ds-DNA Kit and ELISA Anti ss-DNA Kit are highly sensitive and useful methods to detect anti ds- and/or ss-DNA IgG antibodies in patients with SLE.


[Flow cytometric determination of active oxygen produced by neutrophils in patients with inflammatory diseases]. We investigated active oxygen (H2O2) production by neutrophils in patients with inflammatory diseases such as connective tissue disease and respiratory tract infection. The analysis was done by flow cytometry using as small volume of whole-blood as 100 microliters. H2O2 production as well as C-reactive protein (CRP) were increased in connective tissue diseases, and was decreased after steroid therapy. In a case of neuro-Behçet's disease, changes in H2O2 production was observed in agreement with those in clinical symptoms such as gait disturbance. H2O2 production as well as CRP and neutrophil count were increased in acute respiratory tract infection, but in chronic patients H2O2 production alone was rather reduced. In stages of enhanced H2O2 production, tissue damage or inflammation may exist, the degree of which seems to be well reflected by H2O2 production. During stages of impaired H2O2 production, care should be taken to prevent infections. Using flow cytometry, H2O2 production can be easily determined as one of functions of neutrophils.


[OK-432-induced cytokines production by peripheral blood mononuclear cells]. Cytokines production by OK-432-stimulated peripheral blood mononuclear cells (PBMC) were measured to investigate the in vitro function of macrophages (M phi) and lymphocytes. PBMC (1 x 10(6) cells/ml) were cultured with OK-432 (0.05 KE/ml) for 72 hr at 37 degrees C under 5% CO2, then interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2) and soluble IL-2 receptor (sIL-2R) levels in the culture supernatants were measured by ELISA. While there was no significant differences of IL-1 beta production between patients with chronic active hepatitis type B (CAH-B) and controls, sIL-2R production (335 +/- 219 U/ml, mean +/- SD) was significantly decreased (p < 0.001) in patients with CAH-B. On the other hand, in pregnant women, production of both IL-1 beta (6.3 +/- 3.9 ng/ml, p < 0.01) and sIL-2R (300 +/- 169 U/ml, p < 0.001) were significantly lower than those in controls (13.5 +/- 3.8 ng/ml, 969 +/- 154 U/ml). These results suggest that the expression of IL-2R alpha on lymphocytes membrane is suppressed in patients with CAH-B, and that decreased M phi function is present in pregnant women.


[Studies on the fragments of FDP in 4 patients with DIC]. We previously studied fibrinolysis and fibrinogenolysis by analyzing fragments of fibrin/fibrinogen degradation products (FDP) employing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In this report, we characterized the fragments of FDP in four patients with disseminated intravascular coagulation (DIC), that were caused by various diseases. In the patients suffering from acute lymphoblastic leukemia (case 1) and acute suppurative cholangitis (case 3), DD and DY/X fragments resulting from fibrinolysis accounted for the most part of the FDP fragments. In case 3, D fragments resulting from fibrinogenolysis were also observed to much less extent. In a DIC associated with acute myeloblastic leukemia (case 2), both fibrinolysis and fibrinogenolysis were increased and resulted in high levels of D, Y and DY/X fragments, concomitant with moderate levels of DD and high molecular weight (HMW) fragments in the patient's sera. The increased fibrinogenolysis in this case was attributed to accelerated activation of plasmin. In a DIC patient of case 4, who underwent an operation due to hepatocellular carcinoma, marked increase in DY/X and HMW fragments and slight increase in DD fragment were observed on the day of operation. Hyperfibrinolysis documented in case 4 was explained by both increased production of thrombin and moderately accelerated activation of plasmin. Both qualitative and quantitative changes in the fragments of FDP during the courses of treatment in two cases of DIC were also noted. In summary, each underlying disease expresses characteristic pattern of FDP fragments in DIC.


[A new method for the determination of xanthine oxidase activity by high-performance liquid chromatography with electrochemical detection]. A non-radiochemically sensitive method for the determination of xanthine oxidase (XO, EC 1.1. 3.22) activity is devised. We have enabled to detect the low activity of XO in human serum or peripheral lymphocyte lysates by the pretreatment of samples with activated charcoal, and by the employment of a sensitive high-performance liquid chromatography with electrochemical detection. This method was shown to be reliable and reproducible, and allowed us to evaluate XO activity in various clinical samples. XO activity in serum, but not in peripheral lymphocytes reflected the degree of liver damage. No relationship was found between serum XO activity and serum uric acid. No XO activity was detected in sera from patients with hereditary xanthinuria. These results suggested this method to be quite useful for rapid diagnosis of the patients with abnormal purine metabolism, especially in that with hereditary xanthinuria.


[Study of prognostic factors and estimation of prognosis in patients with fungemia]. The estimation of prognosis is necessary in the treatment of fungemia because of its high mortality rate. We studied prognostic factors and estimated prognosis by scoring clinical and laboratory findings in 41 patients with fungemia treated at Tenri Hospital between 1976 and 1990. Although the mortality rate was low (33%) in 18 patients in whom the route of infection had been an intravenous catheter or the urinary tract, it was high (91%) in 23 patients with other or unknown route of infection. The risk of death was high in patients with disseminated intravascular coagulopathy (DIC), shock (systolic blood pressure > or = 90 mmHg), malnutrition (cholinesterase < 0.05 delta pH and albumin < or = 3.0 g/dl), renal failure (urea-N > or = 30 mg/dl and creatinine > or = 3.0 mg/dl), neutropenia (neutrophils < or = 500/microliters) or advanced age (age > or = 60 years old). Application scoring system taking into account of the presence or absence of DIC or shock, the degree of malnutrition, renal failure and neutropenia, and age (20 possible points) in 36 patients revealed that the scores of the 23 patients who died significantly different from those of the 13 survivors; score was less than 6 in every survivor (100%), while it was more than 6 in twenty-two (96%) of the patients who died. Seven of 10 patients with persistent fungal infection had greater than 15. The prognosis of patients with fungemia is adversely influenced by the presence of DIC, shock, malnutrition, renal failure, neutropenia and advanced age, and the scoring of these clinical and laboratory findings is useful in the estimation of prognosis and detection of persistent fungal infection in these patients.


[Historical aspects of clinical enzymology]. The field of clinical enzymology has markedly progressed in recent years. Diagnostic enzymology, therapeutic enzymology and enzymes as analytical reagents continue to contribute to the progress of health care. However, there are many aspects of the historical changes that have taken place in this field that are surprisingly unknown. The presentation I am about to give attempts to provide an overview of the history of the development of clinical enzymology and clinical chemistry. I hope it will be of reference to you.


[Symposium: the role of laboratory medicine in modern medical care--chairman's remarks]. Recent developments in laboratory techniques have brought dramatic changes in medical diagnosis, that is, a change from physical diagnosis to laboratory diagnosis. It is imperative that laboratory medicine develop further to meet the continuously growing needs of medical care. Major progress in medical care is classified into two categories, (A) treatment of severe disorders by modern technology and (B) health maintenance to prevent disease and achieve a higher quality of life. In this symposium, category (A) is subdivided in to (A-1) development of new drugs and (A-2) organ transplantation. In (A-1) the field of new drugs, "Recent Trends in Granulocyte Colony Stimulating Factor Therapy and its Relation to Clinical Laboratory Tests" is reviewed as an example of applying recombinant peptides to treatment. In (A-2) transplantation, two papers (A-2a) "Effect of HLA Matching in Renal Transplantation" and (A-2b) "Liver Transplantation and Function of the Graft Liver" are reported. In category (B), health maintenance, (B-1) exercise and (B-2) nutrition are important subjects. (B-1a) "The Role of Clinical Laboratory Examinations During Physical Exercise Therapy for Diabetes Mellitus" and (B-1b) "Exercise Loading Test for Evaluating Cardio-Pulmonary Functions" are given attention. In (B-2) nutrition, artificial feeding, such as intravenous hyperalimentation (IVH) is a current issue. The role of laboratory medicine in modern medical care will be discussed under each of these subjects.


[Physical exercise therapy in diabetes mellitus--the role of clinical laboratory examinations]. Physical training has been generally recommended for patients with diabetes mellitus as a basic therapeutic tool. In the present study the metabolic and endocrinological effects during the training program were examined in patients with non insulin dependent diabetes mellitus (NIDDM). Moreover the significance of continuous blood lactate monitoring and that of the determination of plasma atrial natriuretic polypeptide (ANP) during exercise loading in diabetics was also studied. (1) The glucose metabolic clearance rate (MCR) during euglycemic insulin clamp was higher in athletes than in patients with NIDDM and control subjects. (2) MCR increased significantly in the training group after the eight weeks program and a significant relationship between the changes of MCR and those of HbAIc observed. Moreover a decrease in the triglyceride level and increase in the HDL cholesterol level in plasma were significantly related with the improvement of MCR. (3) A continuous blood lactate monitoring system was newly developed. This system was simple and showed good reproducibility. The anaerobic threshold (AT) determined using this system corresponded to that obtained by respiratory gas analysis. It was useful for the determination of the exercise intensity without overloading in patients with diabetes mellitus. (4) The increase of plasma ANP during exercise loading was higher in diabetics than healthy controls, and a significant relationship was found between the increment of ANP during exercise and the diastolic function judged from the echocardiogram in diabetics. In conclusion clinical laboratory examinations and medical checkups are important in the practice of physical exercise therapy in patients with diabetes mellitus.


[Liver transplantation and functions of the graft liver]. Partial liver transplantation from living donors is a new surgical operation on patients in the final stage of liver dysfunction. Among about 90 operations so far done in the world, 34 were performed at the Second Department of Surgery in Kyoto University Hospital (as of June, 1992). Good but limited cooperation between surgeons and clinical laboratories has contributed to saving the lives of as many as 28 patients. Analysis of laboratory data and clinical course of patients indicated that pre-, mid-, and postoperational examinations of blood flow through the graft liver by the use of Doppler echography and the monitoring of the liver capacity to generate ATP by the aid of the arterial ketone body ratio are most important for early detection of dysfunctioning liver grafts. An unusually high incidence of the transient hyperphosphatasemia-like elevation of alkaline phosphatase and a frequent appearance of liver-type arginase in serum during the postoperative stage seemed to indicate some pathological changes of the liver.


[Effect of HLA matching in renal transplantation]. Evaluation of HLA-matching is useful in determining graft function and survival in a recipient in cadaveric renal transplantation. The effects of HLA on graft function, which serum creatinine indicative of, and graft survival were examined in both living and cadaveric transplantation in 280 Japanese renal transplants performed at Osaka University and Osaka Prefectural Hospital between October, 1982 and December, 1991 (cadaver 68, living 212). HLA-DR mismatch had a strong effect in living transplants, whereas no disparity was found in cadaver transplants with HLA-DR mismatch. HLA-B, DR mismatch had more effect than HLA-DR in cadaver transplants, and the same effect as HLA-DR in living transplants. HLA-AB affected graft function. It can be used to predict the effect of long-term graft survival. The HLA-haplotype match had the strongest association with graft survival and function in both cases of living and cadaver transplants. HLA-haplotypes of a cadaveric donor and a recipient were presumed by means of the linkage disequilibrium. These findings showed that HLA-matching, especially of haplotype, is an essential factor in relatively low risk renal transplant survival and function. 1-haplotype-matched transplantation, determined by the family study or presumed by the linkage disequilibrium is recommended if not 2-haplotype matched.


[Reevaluation of optimum extraction condition for urinary organic acids using a stable isotope dilution technique]. We reevaluated the optimum conditions for analysis of 13 urinary organic acids using solvent extraction and GC/MS by the stable isotope dilution technique. The acids analyzed were uracil, and lactic, oxalic, 3-hydroxybutyric, succinic, fumaric, glutaric, adipic, pyroglutamic, 2-ketoglutaric, orotic, sebacic, and citric acids. Analytical recovery and accuracy for 13 organic acids ranged from 90 to 107% and from 1.6 to 13.7%, respectively. The optimal pH for most organic acids was 1-2, while that for oxalic and citric acids was 0.25, and that for 2-ketoglutaric and orotic acids was 0.5. The presence of urinary albumin decreased the extraction rates of organic acids, especially of orotic and citric acids; in slight albuminuria (0.5 g/l) the extraction recovery (the extraction rate with albumin/that without albumin) of orotic and citric acid was 38% and 67%, respectively, and in more marked albuminuria (5 g/l), 6% and 26%. Membrane pretreatment with Centricon-3 improved these extraction rates under the condition of albuminuria. Dehydration with the desiccant agent decreased urinary acid extraction rates, especially of uracil and orotic and citric acids. The extraction rates of these three organic acids was decreased in albuminuria and by the desiccant agent. Accurate quantitative analysis of urinary organic acids by the stable isotope dilution technique is necessary for routine examination conducted in clinical laboratories.


[Determination and clinical significance of human hepatocyte growth factor in serum]. Hepatocyte growth factor (HGF) is the most potent mitogen for mature parenchymal hepatocytes in primary culture, and seems to be a hepatotrophic factor that acts as a trigger for liver regeneration after partial hepatectomy and liver injury. In the present study, we evaluated an enzyme-linked immunosorbent assay, using monoclonal antihuman HGF (h-HGF) antibody, for measuring serum h-HGF levels. Intra- and inter-assay coefficients of variation were 2.2-3.3% and 3.4-4.0%, respectively. Detection limit of this method was 0.1 ng/ml, determining by the dilution test. The substances tested did not interfere with this assay, except for high concentrations of hemoglobin. Furthermore, no interference was observed with plasminogen and lipoprotein (a), which show the structural homology to h-HGF, and with various kinds of cytokines. Reference ranges of serum h-HGF determined with 187 healthy subjects were 0.1-0.23 ng/ml. Serum h-HGF concentrations were increased in various kinds of liver diseases, in particular those were significantly higher in fulminant hepatic failure. Furthermore, prognosis of the patients with higher h-HGF values were strikingly worse than those with lower levels. We concluded that the determination of serum h-HGF plays important roles in the early diagnosis and prognosis of fulminant hepatic failure.


[Cytofluorometric analysis of DNA content in proliferating cells of coronary arteriosclerotic lesions]. Cytofluorometric determination of DNA content was done on paraffin-embedded tissues of 19 cases of coronary arteriosclerotic lesions including fibrocellular intimal thickening lesions (FT) or atherosclerosis (AS). DNA distribution pattern of medial smooth muscle cells of coronary arteries with FT and AS was all diploid. The average proliferative index (PI) of both medial smooth muscle cells of coronary arteries with FT and AS was 4.8 +/- 0.6. DNA distribution patterns of intimal cells of coronary arteries with FT and AS were also diploid. The average PI of intimal cells of coronary arteries with FT and AS was 8.4 +/- 1.0 and 9.1 +/- 0.7, respectively. These results suggest that intimal cellular proliferation plays an important role in the development of atherosclerosis.


[Immunohistochemical study of the lymph-follicles and lymphocytes in the gastric mucosa]. Immunohistochemical stainings according to ABC method (UCHL-1,L-26,MT-1,MB-1,IgG,IgA,IgD,IgM, kappa, lambda, LN-1 and LN-2) for the lymphocytes in the germinal center, mantle zone and infiltrative lymphocytes in the gastric mucosa of 30 cases of chronic gastritis and 10 cases of reactive lymphoreticular hyperplasia (RLH) were performed. Lymphocytes in the germinal center and mantle zone consisted usually of B-cells positively stained by L-26 and MB-1. However, in the interstitially infiltrative cells,T-cells positively stained by UCHL-1 and MT-1 were not infrequently contained. Immunoglobulin stainings revealed marked positivity for IgG,IgA,IgD,IgM, kappa and lambda in the interstitial lymphocytes and plasma cells. As to the RLH, small number of T-cells scattered in the germinal center and surrounding area of lymph follicles, and large number of T-cells were found among the follicles, where B-cells were more infrequently found than in the interstitial area of propria mucosae. Confusion of enlarged germinal centers and monotonous proliferation of lymphocytes among the lymph follicles showing monotonous positivity for the stains of heavy and light chains in the cases of RLH were suggestive of malignant change.


[Detection of Campylobacter species by using polymerase chain reaction and nonradioactive DNA probes. II. PCR direct sequencing of the Campylobacter DNA]. We have developed a sensitive DNA hybridization assay for the detection and identification of Campylobacter species which are recognized as important pathogens of acute diarrheal disease in humans. This technique utilizes DNA probes complementary to nucleotide sequences present in 16S ribosomal RNA (rRNA) of C. jejuni, C. coli, C. laridis, C. fetus, C. fetus subsp. fetus, C. fetus subsp. venerealis and C. hyointestinalis, and polymerase chain reaction. The partial sequence of DNAs encoding the Campylobacter rRNA was first analyzed by direct solid phase sequencing in order to select suitable DNA probes. Amplified target DNA of 240 base pairs could be resolved on ethidium bromide-stained gels, and hybridized with DNA probes conjugated to alkaline phosphatase. In identification experiments, one of the 10 probes tested here gave a positive hybridization reaction with C. jejuni, C. coli and C. hyointestinalis but not with other Campylobacter species. The other was specifically reactive with C. fetus, C. fetus subsp. fetus and C. fetus subsp. venerealis. When applied to stool specimens, a good correlation was found between the results obtained by the present assay and by biochemical tests. These findings suggest that the nonradioactive probe assay can be used as the practical criterion for differentiating Campylobacter species.


[Identification and differentiation of the human herpes virus group using the PCR method]. Six kinds of human herpes viruses have been identified and classified on the basis of structure and characteristics. We studied the identification and classification of these types using PCR to amplify the virus-specific DNA sequences. This method showed higher sensitivity than the conventional method of virus isolation and culture for HSV and CMV detection. For each positive control, the viral DNA was amplified only when the complementary primers themselves were used. PCR apparently detects only the activated virus, because normal controls were negative when this method was used. Therefore, the present method is thought to closely reflect viral activation and infectious diseases in patients with latent infections.


[Comparable evaluation of serological diagnostic tests (ELISA, IFA and PA methods) for the detection of anti-Borrelia burgdorferi antibody]. We have evaluated the usefulness of the enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody assay (IFA) and particle agglutination (PA) method as serological screening tests for Lyme-borreliosis. Serum samples obtained from two patients with Lyme-borreliosis showed marked high antibody titers for Borrelia burgdorferi when measured by these methods. Of the serum of 368 healthy members of the Self-Defense Force in north-eastern Japan screened for the antibody to B. burgdorferi, 8.4%, 3.7%, 4.6% were found positive by the ELISA, IFA, and PA method, respectively. However, Western blot analysis of these "positive" sera demonstrated no identical bands to those seen in the serum from the patients with Lyme-borreliosis. While 85% and 15% of Treponema pallidum hemagglutination test (TPHA)-positive sera (20 samples) showed a false-positive reaction by the ELISA and IFA method, respectively, no cross-reaction to the anti-B. burgdorferi antibody was observed in these sera by the PA method. The analysis of the serum of the patients with autoimmune diseases (rheumatoid arthritis; 11 cases, systemic lupus erythematosus; 46 cases) by the ELISA and PA methods resulted in a cross-reaction to some extent, which suggested that the antibodies produced by autoimmune mechanisms such as the anticardiolipin antibody can cause a cross-reaction to the anti-B. burgdorferi antibody. These findings indicate that the PA and ELISA rather than the IFA method should be recommended for rapid and conventional screening of Lyme-borreliosis and that serum "positive" for the anti-B. burgdorferi antibody determined by these tests should be confirmed by Western blot analysis to negate the cross-reactions.


[False positive reaction in measurement of allergen-specific IgE--comparison of 3M IgE FAST-Plus Test using polystyrene well as adsorbent with Phadezym RAST]. Irrelevant IgE binding to cellulose discs is known to give false positive results in Phadezym RAST (Pharmacia) for the estimation of allergen-specific IgE in serum. We investigated FAST-Plus Test (3M Diagnostic Systems), an enzyme-linked sandwich type Fluoro-Allergo-Sorbent Test in which a particular allergen was coated to polystyrene well. Phadezym RAST and CAP RAST (Pharmacia) using cellulose-derivative discs as adsorbent were used as reference methods. Patients' sera which gave negative blank reactions to uncoated filter paper disc in the Phadezym RAST system were assayed for specific IgE to 6 allergens using FAST-Plus Test, CAP RAST and Phadezym RAST, and the results of the former two were compared with those of Phadezym RAST using a comparable class system. FAST-Plus Test showed variable correlations with Phadezym RAST, the correlation coefficients ranged from 0.41 to 0.97 (r = 0.462 in house dust 1, r = 0.713 in house dust 2, r = 0.412 in Candida albicans, r = 0.952 in Dermatophagoides peteronyssinus, r = 0.969 in Dermatophagoides farinae and r = 0.682 in Japanese cedar), although most of the results were within one class difference. Similar correlations were obtained between CAP RAST and Phadezym RAST. Of 3004 patients' sera tested in the past two years using Phadezym RAST, 132 (96 cases) displayed positive blank reactions to the uncoated filter paper disc. Of the 96 cases, 80 sera were assayed for binding of IgE to the uncoated cellulose-derivative disc in the CAP RAST system. 18 showed positive results up to 7 IU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)


[Recent advances in laboratory tests for liver diseases]. Many tests for hepatitis C virus (HCV) infection have been developed and have proved useful for prevention of post-blood transfusion hepatitis C. However, there are at least 4 genotypes of HCV and the predominant type is different among countries. None of the tests using antigens from one genotype are sensitive in detecting the antibodies against another genotype. More sensitive tests using a more stable part of the HCV RNA sequences such as 5'-noncoding region must be developed for clinical use. Automated PCR methods and DNA sandwich hybridization methods using branched DNA amplification multimers may be candidates. Recently a hepatocyte growth factor test has been developed in Japan. Multicenter trials of this test reveal that it is useful for assessment of acute severe hepatitis. Tests for collagen type IV, fibronectin receptor, and prolyl hydroxylase have been reported useful for assessment of liver fibrosis. However, serum prolyl hydroxylase is prone to increase in response to hepatocellular damage as well as fibrotic processes. Enzymatic methods for determination of branched amino acids and tyrosine have been developed. The molar ratio of branched amino acids to tyrosine seems to have same pathophysiological meaning as the ratio of branched amino acids to aromatic amino acids (Fischer ratio) in assessment of liver cirrhosis. Lidocaine test is reported to be useful for predicting survival of transplanted liver and also assessing the function of the cirrhotic liver. Profiles of alpha-fetoprotein subfractions based on lectin-reactivity and galactosyl transferase II isoenzyme have been reported to be useful for detecting hepatocellular carcinoma but this remains to be proved.


[Blood coagulation factors in hepatic disorders]. The major factors related to the coagulo-fibrinolytic reactions are synthesized in the hepatic cells. As a reticuloendothelial organ, the liver also removes the activated factors and metabolic products in the coagulo-fibrinolytic process from the plasma. Therefore, many investigators have been trying to use measurements of the coagulo-fibrinolytic factors for the evaluation of the type and degree of a hepatic disorder and for the determination of therapeutic effects or prognosis. On the other hand, the recent advances in the blood coagulation study show that the hemostatic mechanism is a kind of maintenance mechanism of homeostasis for blood-flow. The functions of many factors in and from the platelets and vascular endothelial cells as well as those produced by the liver have been identified. Recently, some hemostatic molecular markers and complexes of activated factors with their inhibitors can also be measured. In this article, the recent concept of hemostatic mechanism and the relation between various hemostatic factors and hepatic disorders are presented.


[Effects of antibiotics on the dissociation of platelet adherence in pseudothrombocytopenia]. To elucidate the effects of antibiotics on platelet adherence phenomena, we examined dissociation of platelet adherence in EDTA-dependent pseudothrombocytopenia by adding Kanamycin or Colimycin. We found the rapid dissociation of platelet adherence caused by addition of Kanamycin (20 mg) or Colimycin (20 mg) in 1 ml of EDTA-anticoagulated blood from patients with EDTA-dependent pseudothrombocytopenia. This dissociation was most remarkable in the sample treated within 30 minutes after venipuncture. When the dissociation occurred, no adherent platelet was found on microscopical examinations. Complete blood cell counts and their histogram patterns after dissociation were almost same as those just after venipuncture. The dissociation occurred as soon as the antibiotics were added and remained fairly long time. The dissociation decreased in proportion to the periods of time between venipuncture and addition of antibiotics. The dissociation was caused by many other antibiotics. However, severer damage were found morphologically by adding most of them in both histogram patterns and microscopical examinations than those of aminoglycoside or peptide antibiotics.


[Evaluation of novel assays for the detection of crosslinked fibrin degradation products in whole blood by the agglutination of the red blood cells]. We evaluated the clinical significance of two novel assays for the detection of crosslinked fibrin degradation products (XDP) in whole blood using the agglutination of the red blood cells (SimpliRED D dimer and SimpliRED D dimer-500, AGEN, Australia). XDP made serially by plasmin in vitro, were detected by the SimpliRED D dimer assay, but fibrinogen degradation products showed weak reactivity. Ten of the fifty four clinical samples collected with EDTA-2K, changed to positive on these assays after overnight incubation at 4 degrees C. Anemia and hemolytic samples had no effect on the assay results. The results obtained by the SimpliRED D dimer were negative for the normal subjects (n = 50) without exception. In our study, 81% and 95% of the patients, who showed abnormal levels of XDP in plasma and E fragments in serum respectively, were positive on the SimpliRED D dimer assay. The assay was as sensitive as the Rapidia-D dimer assay. In conclusion, the SimpliRED D dimer assay was clinically useful as a screening assay for the diagnosis of hypercoagulable and fibrinolytic states, since it could be performed simply and quickly.


[Changes of differential leukocyte counts during pregnancy and in the postpartum period]. We examined differential leukocyte counts in peripheral blood from 177 pregnant and postpartum women with an automated leukocyte differential system, and compared them with those of 52 nonpregnant and non-postpartum women. The proportions and numbers of neutrophils and monocytes increased throughout pregnancy, returned to the non-pregnant levels within one month after delivery, and decreased transiently at 4 or 7 to 10 months postpartum. The proportions and numbers of lymphocytes and eosinophils decreased throughout pregnancy, and increased transiently at 4 to 10 months postpartum and one month postpartum, respectively. The proportion and number of basophils decreased during pregnancy and one month postpartum, and those of large unstained cells (LUC) decreased in the third trimester of pregnancy, and both returned to the non-pregnant levels at 4 months postpartum and within one month postpartum, respectively. These data indicate that differential leukocyte counts change dynamically during pregnancy and after delivery until 1 year postpartum.


[Clinical usefulness of benzoate tolerance test in patients with liver cirrhosis]. The capacity of the liver to metabolize intravenously loaded benzoic acid to hippuric acid was examined in 7 healthy adults and 18 patients with liver cirrhosis. Blood samples were withdrawn at 5 to 120 min after infusion of benzoic acid (15 mg/Kg), and then serum was obtained to determine the contents of the fatty acids by HPLC as well as to examine several pharmacokinetic parameters under a two-compartment model program. The urinary samples were collected at 60 min after the infusion. In the serum of the patient group, the maximum concentration (Cmax) and area under the concentration curve from zero time to the infinity (AUC) for benzoic acid remained in the normal range, but the mean transit time(MRT) and half-life time(T1/2) were significantly delayed. In serum of the patient group, the AUC for hippuric acid was hardly reduced but the Cmax was significantly reduced. Moreover, MRT, T1/2 and time to reach Cmax(Tmax) were significantly delayed. In urine at 60 min after the loading, benzoic acid was below the limit of detection and was recovered as hippuric acid with a recovery rate of 70% in the healthy adult group and 40% in the patient group.


[Clinical and laboratory correspondence to outpatients with the extreme value of C-reactive protein]. It is the policy of Tenri Hospital to notify the patient promptly whenever an extreme laboratory data value is detected. We investigated the utility of forwarding clinical and laboratory correspondence to outpatients with extreme value of C-reactive protein (CRP). Sixty-eight outpatients with CRP levels more than 20 mg/dl detected during 1986 were studied. CRP was measured by turbidometric method, and a sample with CRP level more than 15 mg/dl was diluted with CRP negative serum (CRP level less than 0.2 mg/dl) and was reanalyzed. Fifty-two of 68 patients (76%) had infectious diseases as the causal disease of high CRP, and eight (12%) had other diseases. In the remaining (12%) the causes were unknown. In most patients the causal diseases were diagnosed within one or two days, but diagnosis required more than 4 days in those with acute pyelonephritis, meningitis, liver abscess or renal abscess, as these diseases were diagnosed after the examination of urine or cerebrospinal fluid, or after ultrasonography. Thirty-seven of 58 patients (64%) who had appointments with their physician on the day of the laboratory examination were admitted the same day, and two of 10 patients (20%) who had appointments on the following day were admitted on that day. Seventeen of 25 patients (68%) with urea-N levels more than 30 mg/dl, cholinesterase levels less than 0.7 delta pH and albumin levels less than 3.5 g/dl required more than 15 days to recover, while 29 of 32 patients (91%) with only 2 or fewer of these laboratory values required less than 14 days. The prompt notification of extreme CRP value is an important aspect of medical care. The examination of urine and cerebrospinal fluid and ultrasonography are necessary screening techniques accompanying examination of blood and plain chest X-ray. Urea-N, cholinesterase and albumin values should be determined at the same time as CRP value to assess prognosis.


[O-serotypes, biotypes, and antimicrobial susceptibility of Serratia marcescens isolates from clinical specimens: 3rd report]. O-serotypes, biotypes, and drug resistance of Serratia marcescens strains isolated from various clinical specimens in Showa University Fujigaoka Hospital were investigated: period I (1979. 1-1982.3), 122 strains; period II (1983. 1-1985. 3), 198; period III (1985. 4-198. 3), 129; period IV (1989. 1-1991. 3), 99. The frequency of serotype O 3 was higher than those of the other serotypes after the period II and ranged 17 to 37%. The isolation frequency (27%) of serotype O 4 was higher than those of other serotypes in the period I. However, this frequency decreased in the period II to III and, in the period IV (10%), was higher than in the period III. The isolation frequency of serotype O 17 suddenly increased in the period II (27%) alone, and 42% of the biotypes, obtained with API 20E, showed 5305701. The isolation frequency of non-typable strains ranged 9 to 14% through all periods. The group including 5317721 and 5307721 clustered by the furthest neighbor method, more frequently appeared through all periods. The former code of urease positive more frequently appeared in the period II to IV. The isolation frequency of the latter code of urease negative reduced to a minimum (18%) in period II, though it increased in the period II to IV. The isolation frequency (22%) of the pigmented strains in the period IV increased much higher than in the period I to III (ranged 2 to 4%). The frequency of the pigmented strains of serotype O 3, not belonged to the Grimont's biotype, was 27% of all pigmented strains isolated in the period IV.(ABSTRACT TRUNCATED AT 250 WORDS)


[A study of intraoperative rapid frozen section diagnosis focusing on accuracy and quality assessment]. Accuracy of frozen section (FS) diagnoses was investigated in a consecutive series of 1129 intraoperative consultations. In our series, the correct diagnosis including clinically not serious minor errors was made in 96.9% of the cases. Whereas the accuracy ratio of FS diagnosis for unknown pathologic process decreased to 92.2%. Among all the types of tissues, central nervous system was shown to be the most frequently handled for FS, followed by lung/bronchus, breast, liver/biliary tract, lymph node and so forth. The requesting ratio of FS, on the other hand, tended to be high in the following specialties; neurosurgery (46.5%), thoracic surgery (19.0%), general surgery, (10.0%). Deferred diagnosis with a provisional diagnosis and misinterpretations in histology typing without serious clinical problem accounted for 2.7% and 3.1% respectively. Causes of erroneous diagnoses seemed to be multifactorial, such as inappropriate sampling, diagnosis on poor quality histology sections, lack of clinical information, lack of enough experience in FS practice of pathologists, or a combination of more than two of them, though inevitable cases showing minimal cytological and structural atypia were included. Intraoperative consultation by FS diagnosis is now essential to serve a good quality medication to patients. It is thus necessary that to establish a tight peer review system and also to provide an education program with regard to practice in FS diagnosis particularly for young pathologists.


The effect of coffee deprived of irritant substances upon some indices of lipid metabolism in healthy volunteers and patients with hyperlipoproteinemia. Effect of 14 days coffee drinking upon some blood serum indices of lipid metabolism was studied on 20 healthy volunteers and 20 patients with hyperlipoproteinemia (type IIb). The study was done in two subgroups: healthy volunteers or patients with hyperlipoproteinemia which had belonged to the first subgroup drank ordinary coffee and the ones which belonged to the second subgroup drank coffee deprived of irritant substances. (4 glasses per day). It was found that in healthy volunteers ordinary coffee had given rise to a significant increase of serum total cholesterol and to a decrease of serum HDL-cholesterol. These changes were not observed in subgroup drinking coffee deprived of irritant substances. More significant rise of serum total cholesterol and decrease of serum HDL-cholesterol were found in patients with hyperlipoproteinemia. Drinking of modified coffee does not cause any significant changes in serum indices of lipid metabolism. The authors concluded that drinking of ordinary coffee should be restricted in patients with hyperlipoproteinemia and coffee deprived of irritant substances might be recommended to patients with this disease.


Esophageal motility in the personnel operating heavy self-propelled mining machines. We examined 47 men exposed to whole-body vibration for a long time (average 9.8 years) and tested esophageal motility. The following parameters were measured: mean pressure in the body of esophagus during the passing of peristaltic wave, maximum value of pressure during the passing of peristaltic wave, mean and maximum duration of spasm and peristaltic wave transmission velocity was calculated. In over 1/4 exposed to whole-body vibration disorders of esophagus motility were observed. These disorders are probably a consequence of vocational exposure to whole-body vibration.


Assessment of clinical value of Bernstein test and attempts of its modification. Bernstein test has been applied for over 30 years in the diagnosis of the causes of pyrosis. Its drawback is a considerable percentage of false positive results in healthy persons, caused by a too large amount of 0.1 M HCl given. Presented in the paper are studied results in 34 patients with symptoms of gastroesophageal reflux disease (GERD), and in 23 healthy persons in which into the body of the esophagus and into the cardia was given alternately 0.1 M HCl and 0.15 M NaCl at a speed of 0.8 cm3.min-1. During the testing the complaints reported by the patients were recorded, and by means of polyphysiograph the spasms of the body of the esophagus were recorded and morphologically assessed. In addition, in 12 volunteers of 23 healthy persons Bernstein classic test was carried out by giving them alternately 0.1 M HCl and 0.15 M NaCl at a speed of 0.8 cm3 x min-1. The testing carried out shows that a reduction in the amount of acid given in Bernstein test causes a decrease in the percentage of false positive results in healthy persons. HCl infusion into the body of the esophagus and into the cardia in patients with symptoms of GERD caused pathological motility in the body of the esophagus. The most frequent anomaly were multipeaked spasms, which can be an additional diagnostic criterion of this disease.


Disturbances of the pulmonary perfusion after endoscopic sclerotherapy of oesophageal varices. Haemorrhage from oesophageal varices is one of the most common reason of death of patients with liver cirrhosis. The possibility of treatment and prevention of the haemorrhage by endoscopic sclerotherapy (ES) has become one of the achievements of contemporary medicine. Nevertheless there are some complications described after this procedure, the most severe being the pulmonary embolia. In our study we analyzed the pulmonary circulation by perfusion scintigraphy after ES. Among twelve patients treated by ES we found two cases of disturbed pulmonary perfusion. We did not find clinical or gasometric changes in these patients. We suggest there should be done pulmonary perfusion monitoring after ES.


Non-ulcer dyspepsia.

Non-ulcer dyspepsia. During the last decade a new disease entity numbered among functional disorders of the digestive tract and defined as "non-ulcer dyspepsia", has been isolated. This disease is diagnosed most frequently at the age of 20 to 40 years. In West-European countries it is diagnosed in about 30% of out patients. Symptomatology of the disease is very ample and is, after exclusion of organic diseases of the digestive tract, the basis of diagnosis and classification. Present knowledge on the pathophysiology of "non-ulcer dyspepsia" is incomplete and based mainly on study results of the motility of the stomach and small intestine under manometric examination. In spite of that one attains satisfactory therapeutical effects during a prolonged administration of prokinetic drugs (dopamine receptor antagonists and peripheral parasympathomimetics).


Role of oxygen radicals in hepatocellular impairment in cerulein-induced acute pancreatitis. Acute pancreatitis was induced in male Wistar rats by i.v. infusion of cerulein in the dose of 5 x 10(-6) g x kg-1 x h-1 for periods of 3 and 12h. The most important finding in our study was the increase of malondialdehyde concentration in hepatic tissue, observed after 12 h of cerulein infusion, accompanied by ultrastructural changes predominantly in the sinusoids. Obtained date suggest that products originating from lipid peroxidation in pancreatic tissue, in concert with activated Kupffer cells, may be responsible for such impairment of hepatic tissue.


Helicobacter pylori, chronic gastritis and peptic ulcer. H. pylori infection is strongly associated with chronic gastritis and is probably the main course of chronic inflammation in the gastric mucosa. Acquisition of the infection will lead to gastritis and the eradication of the bacterium results in healing and final cure of the gastritis. Chronic gastritis and H. pylori infection may occur in antrum and/or corpus, and will gradually result in atrophy of the underlying mucosa in a great number of affected persons. Correspondingly, impairments in several important functions of the gastric mucosa are consequences of the atrophy and inflammation. Hp infection and gastritis associate with important gastroduodenal diseases, such as peptic ulcer diseases and gastric cancer. There are reasons to suggest that the infection and subsequent gastritis precede these diseases, and that they are important risk factors for both disorders. In fact, peptic ulcer can be seen a late frequent complication of an H. pylori infection. In addition, the type and grade of gastritis can be used in prediction of the ulcer risk if adequate biopsy specimens are available for microscopy from both antrum and corpus mucosa (Table II). An association between chronic gastritis and Helicobacter pylori (Hp) infection is strong. Clearly more than 80% of cases with chronic gastritis are related to coexistent Hp infection. Furthermore, both Hp and gastritis are extremely common in patients with peptic ulcer supporting the view that they are causally related to the ulcer disease. Correspondingly, similar suggestions may also be presented about the links between Hp and gastritis in the pathogenesis of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)


Is the low anterior resection justified in midrectal cancer? The main reasons for using a resection in midrectal cancer are presented. The knowledge about the direction of the lymph-drainage and the cell infiltration in the rectal wall and the progress in the dissection technique of the ampulla now allow the preservation of the sphincterorgan without severe oncological doubts. The results are well comparable with those after the exstripation but the comfort of the patient is better.


Surgical reconstruction of the oesophagus. Reconstructive oesophageal surgery underwent 322 patients in our clinic. The surgery was indicated because of cicatrical obstructions or cancer of the thoracic part of the oesophagus. The continuity of the alimentary tract was re-established by pedunculated intestinal segment from the jejunum, ileum or left side of the colon in the anisoperistaltic position. The right side of colon was used either in iso- or anisoperistaltic position. The follow-up after completion of the reconstructive operation ranges from 1-40 years.


The technique of the low anterior resection made by hand or with stapler. After a short historical review of the surgical intervention for rectal cancer the precondition for the resection are presented. The technique of the resection is described in the following. We use routinely the double row suture for the anastomosis. Also the stapler technique for deeper localized growth is presented.


Is steroid dependent Crohn's disease a separate entity? Crohn's disease has been sometimes considered as a syndrome including different entities. In this prospect we tried to assess whether steroid dependent Crohn's disease could be a separate sub-group. Eighty five patients (mean follow-up: 6 years) with documented Crohn's disease were classified into 3 groups: 1--patients never treated with steroids (NS) (N = 37); 2--patients in whom steroids had been given but had been withdrawn (NSD) (N = 37); 3--patients dependent on continuous steroid therapy (SD) (N = 11). Ten variables were considered: age at onset, sex, CDAI, cumulative topography of lesions, extra-intestinal symptoms, albuminemia, ESR, surgical operations, annual frequency of relapses. Monofactorial analysis (analysis of variance and CHI2 test) showed group SD to be significantly different from group NS and in term of age at onset, CDAI, ESR, annual frequency of relapses, extra-intestinal symptoms, surgical operations. In contrast, a multivariate analysis of correspondences applied to the 3 groups and to 9 dichotomous variables showed that group SD is not a separate entity, but the limit of a continuum extending from group NS to group NSD. This was ascertained by a CHI2 test applied to the dichotomous variables. Thus, within the limits of this study Crohn's disease appears to be a homogeneous entity rather than a heterogeneous syndrome.


Anal incontinence: evaluation and biofeedback therapy. Incontinence is a very stigmatizing symptom in our society. About 1% of the adult population is affected by fecal incontinence. In the evaluation anorectal manometry and defecography play a major role. Therapy often is still disappointing. In recent years simple retaining or biofeedback therapy have been reported to improve about 70% of incontinent patients. Within one year we treated 19 patients. Success was achieved in 69%. Biofeedback training, therefore, should be attempted prior to considering surgery.


Diagnostic and surgical procedures in acute necrotizing pancreatitis (ANP). The main subject of considerations is acute necrotizing pancreatitis, based on the authors opinion and literature. Frequency of the necrosis in acute pancreatitis is established in between 7-15%. Because of very severe and often lethal complications these patients need special surgical attention. Enhanced CT is the most valuable diagnostic procedure to visualize the extend of pancreatic necrosis. There is no common agreement upon the mode of treatment except from that infected necrotizing pancreatitis should be operated. Indications for surgical treatment with particular analysis to necrosectomy and laparostomy is discussed.


Comparison of qualitative and quantitative blood determinations in stools of healthy persons and patients with colorectal tumours. The possibility of using fecal blood determination for early diagnosis of colorectal cancer is based on the fact that in most cases bleeding from the tumour occurs early in the asymptomatic phase of the disease. The qualitative Haemoccult test is now regarded as most suitable for screening. The test is cheap and simple, but its drawback is a high per cent of false negative and false positive results. Therefore there is a need to look for other methods of greater sensitivity and specificity. One of these methods may be quantitative determination of blood in stools. The purpose of the present study is: 1) to assess the specificity of quantitative fecal blood determinations, 2) to compare the sensitivity of the qualitative and quantitative tests for the detection of colorectal neoplasms. Quantitative blood determination included the heating of stool samples with citric and oxalic acids. The citric acid reagent caused passing into the solution of the so called intestinal porphyrin fraction which is produced from haem spontaneously in the upper gastrointestinal tract. The oxalic acid reagent converts in vitro haem remaining in the stools to porphyrins, without changing the structure of the intestinal-fraction porphyrins. The obtained solutions were subjected to three-phase extraction for removal of non-porphyrin substances. The concentration of porphyrins was read in a spectrofluorimeter at 402 nm excitation wavelength and 600 m emission wavelength. Haemoccult II test was used for qualitative blood determination in three consecutive stools. The result was considered as positive if the colour of the test slide was changed to blue within 30 seconds, at least in one of the six test "windows".(ABSTRACT TRUNCATED AT 250 WORDS)


The evaluation of clinical results of hepatic artery embolization. The clinical symptoms and liver function following hepatic artery embolization (h.a.e.) in patients with inoperable liver neoplasms were evaluated. The study was performed on 28 patients 11 of whom were male in the age of 53-72 years and 17 female aged 16-76. Before embolization liver function was evaluated on the basis of clinical data and laboratory tests. Transcatheter hepatic artery embolization was performed using Spongostan. Following h.a.e. clinical status and biochemical analysis of blood and urine were checked repeatedly. Twenty-two patients developed post embolization syndrome dominated by: epigastric pain, nausea, and vomiting. Fourteen patients and disturbed intestinal motoric. All those symptoms were transient and lasted 1-3 days. Elevated body temperature was observed in 14 patients. There was a statistically significant increase of ALAT & AspAT after embolization lasting for a few days. There were however no statistically significant changes in the results of tymol test and total bilirubin level in blood.


Low-dose antacids versus ranitidine in the short-term treatment of patients with duodenal ulcer. Endoscopic and histologic placebo-controlled study. In this double-blind randomized placebo-controlled trial we compared the efficiency of two Polish antacids (Alugastrin, dihydroxyaluminium sodium carbonate and Alumag, aluminium hydroxide with magnesium hydroxide; buffering capacity 189 and 224 mmol) with ranitidine in the healing of duodenal ulcer. We also examined the effect of drugs on the frequency and severity of gastritis and selected morphometric parameters of the fundic mucosa. The study showed that low-dose antacids effectively promote the healing of duodenal ulcer during four week therapy, similarly to ranitidine (72%, 76% and 80%, respectively) and significantly better than placebo (46%). Both antacids and ranitidine were without effects on the chronic gastritis and did not cause any trophic changes of the gastric mucosa.


Effect of cisapride and cimetidine on 24-hour intraesophageal pH monitoring in patients with gastroesophageal reflux disease. In 16 patients with symptomatic gastroesophageal reflux disease (GERD) 24-h intraesophageal pH monitoring (Medilog 1010, Oxford) was carried out after placebo, cisapride (4 x 5 mg) and cimetidine (3 x 200 mg plus 400 mg at bedtime). The per cent time at which intraesophageal pH < 4.0 (refluxive time) was analysed. Cisapride shortened daytime and postprandial refluxive time from 16.1 +/- 14.5% and 12.6 +/- 9.2% to 5.1 +/- 4.4% and 7.5 +/- 6.5%, respectively (p < 0.01, p < 0.05). Whereas, cimetidine shortened particularly night refluxive time from 24.7 +/- 14.1% to 8.8 +/- 6.9% (p < 0.01) and total time from 20.4 +/- 12.8% to 12.0 +/- 6.4% (p < 0.05).


[Pharmacological Society in Paris and its awards]. The Société de Pharmacie de Paris started in 1804 to award prizes firstly intended for students in pharmacy after competitive examinations, then, from 1807, for anyone devoted to the advancement of pharmaceutical sciences. Since 1861, the Société de Pharmacie, which became Académie de Pharmacie in 1946 and Académie Nationale de Pharmacie in 1979, has payed particular attention to awarding a prize to the best thesis defended each year at the Ecole de Pharmacie de Paris (now Faculté de Pharmacie).


[Method for angiographic identification of the labyrinth artery]. Digital subtraction angiography in Stenvers standard setting performed atraimatically has been tried in 106 emergency cases admitted to N. V. Sklifosovsky Research Institute of Critical Care. This new method of identification (in 75% of the cases) and verification of the labyrinthine artery intravitally proved safe and reliable. The patients were exposed to cerebral angiography by various methods for diagnosis of the underlying disease. Standard methods of vertebral angiography were found unsatisfactory.


[Radiologic anatomy of the labyrinth artery]. Carotid and vertebral angiographic investigations were performed to study x-ray anatomy of the artery of the labyrinth (AL) in 96 inpatients admitted to the N. F. Sklifosovsky emergency care clinic. According to the angiograms, AL originated from the distal parts of the inferior anterior cerebellar artery in 66.3% of the patients. In this case it has a straight form. When initiating from the proximal parts of the basilar artery (33.7% of the patients), AL was shorter (0.8 +/- 0.3 against 2.5 +/- 0.8 cm) and curved. In any case AL was situated along the upper edge of the pyramid before it entered the internal acoustic meatus. By the meatus or inside it AL forms a characteristic loop or semiloop. A complete AL left-right symmetry was observed in 61.8% of the cases.


[Current research on oxygen carriers for transfusion: hemoglobin solutions and fluorocarbon emulsions]. Although products currently under study are usually called "artificial blood" or "blood substitutes", it concerns only, for the moment, to achieve preparations able to carry and release oxygen to tissues while allowing also a temporary restoration of "blood" volume. The most advanced scopes are related to hemoglobin solutions and fluorocarbons emulsions. The limitations of free hemoglobin impose to modify it. The reestablishment of a normal, even reduced, affinity for oxygen is obtained by the fixation on hemoglobin of a 2,3-DPG substitute whose most known example is pyridoxal phosphate. The enhancement of vascular retention may be achieved by intramolecular cross-linking, intermolecular polymerization or covalent binding of hemoglobin on macromolecules. The two modifications of hemoglobin must be performed successively et numerous possibilities have been proposed. Bovine and recombinant hemoglobins are also promising. Originally and logically, fluorocarbons are synthetic compounds derived from hydrocarbons by an important or maximal substitution of hydrogen by fluorine. The physical properties of these molecules, impose, for transfusion, their emulsification in an aqueous physiological solution. They need an oxygen enriched atmosphere and their storage in tissues is often extended. At present, the most known emulsion is Fluosol DA, a mixture of perfluorodecalin and perfluorotripropylamine. It allowed to realize numerous researches and the proposal of the multiple possible employment for this category of oxygen carriers. The limitations of Fluosol DA led to fluorocarbons under investigation such as F dimethyl bicyclononanes, F methyladamantane, bis (F-butyl) ethene or F-octylbromide. The new hemoglobin solutions and fluorocarbons emulsions start to meet the requirements of potential users.


[Characteristics of protein metabolism in labyrinthine tissue]. The synthesis of total protein in organic culture of the internal ear was studied in 16-day embryo of CBA mice exposed to altering factors. The experiments showed feasibility of partial recovery for impaired metabolic processes in the labyrinth following phonophoretic introduction of mitochondrial coenzymes and inhibitors of lysosomal activity. Formation of systemic structural trace by modelling of acoustic stress and verification of protein stress agents was tested making it possible to identify an important component in dysadaption mechanism in mature CBA mice labyrinth.


[Affinity chromatography for extracorporeal purification or for separation of molecules for biological use: technical and legal restraints]. Affinity and/or immunoaffinity chromatography is one of the less commonly method used for large scale separation purposes. As this technic is greatly selective and gives high yields, it allows in vivo removal, in an extracorporeal circulation, of harmful substances in patient plasma as well as purification of molecules for biological and therapeutic uses. Large development with increased safety of such a method is dependent on some economic, technical and legal requirements. Particular attention must be drawn to the following points. Possibility of multiple uses of affinity supports contributes to lowering the cost of the method. Desorption agents should be chosen according to the best compromise between total desorption and preservation of adsorption capacity over runs. It is likewise essential to store affinity supports in conditions allowing prevention from contamination without loss of adsorption capacity. In developing and optimizing an affinity chromatography procedure, it is important to minimize the amount of ligand released from the affinity support. Besides economic and technical aspects, it is necessary to take into account legal requirements, particularly those related to the preparation of the ligand especially if it is monoclonal or polyclonal antibodies. An important consideration for the therapeutic use of antibodies (either in the preparation of biological products or in an extracorporeal circulation procedure) is the possible presence of viruses and/or potentially oncogenic macromolecules. Source material should be shown to be free of viruses, the cell banks (for monoclonal antibodies) and the production of antibodies must be closely controlled, viral inactivation of antibodies should be performed and the inactivation process should be shown to be effective.


[Cerebral ischemia: massive increase of the dopamine release or stagnation?]. Massive increase of the dopamine (DA) in the dialysates, obtained by cerebral microdialysis in the striatum or in the hippocampus, during cerebral ischemia in animals, was interpreted as a large increase of the DA release in these two cerebral areas. The experimental data analysis displayed in this paper suggests that it could rather be a stagnation of the DA and of the NA (in the hippocampus) as a result of the blood circulation arrest in these brain areas. Oxidation (chemical and enzymatic) of the accumulated DA and NA (in the hippocampus) could potentiate the action of the glumatergic receptors, responding to the N-methyl-D-aspartic acid (NMDA), via their redox site and could originate, probably in association with other potentiating components (glycinergic or polyaminergic), the excessive neurotoxicity observed in the striatum or the hippocampus after cerebral ischemia.


[Stabilization and function of liposomes]. Liposomes stability can be improved by covering them with polysaccharide derivatives. The anchoring mechanism of these derivatives into the lipid membrane has been studied and explained. In order to improve liposome specificity, protein transfer from erythrocytes and platelets into liposome membrane has been carried out. The effect of a newly developed phospholipid, DDPC, on the efficiency and the selectivity of protein transfer is reported.


[The effectiveness of stabilographic vertebrogenic test in diagnosing secondary cochleovestibular disorders]. The study included 211 healthy subjects, 65 and 95 patients with affected vestibular analyzer without hemodynamic disorders in the vertebrobasilar branches and with them, respectively. It was found possible to use the stabilographic vertebrogenic test (SVT) both for diagnosis of vestibular dysfunction in vertebrogenic insufficiency and prediction of its appearance. The range of SVT changes (12-17%) reflects subclinical level of vertebrogenic impact on equilibrium system induced by unfavorable effects on the peripheral or central structures of the vestibular analyzer.


[Structural typology assay of principal anticancer agents on the basis of molecular fragmentation]. The developed formula of 58 anticancer agents used in therapeutic or still in clinical essays were treated by molecular connectivity matrix method. This technic allows the search and the automatically count of structural fragments of the different studied molecules. Then it has been possible to build a spanning tree (Prim's arborescent skeleton) which gathers the different molecules and permits to put a priori new structures.


[Spasmolytic and antinoradrenergic activities of para-hydroxybenzonitrile on the isolated duodenum and vas deferens in rats]. The para-hydroxy-benzonitrile (PHB) show spasmolytic activity of the muscular of duodenum provoked by acetylcholine or barium chloride. The results obtained on the vas deferent of the rat versus the contracture effects of norepinephrine show that PHB is an antagonist of the neuromediator on the post-synaptic alpha adrenoceptors.


[Determination of silicon dioxide in colloidal silica]. This is made without using hydrofluoric acid. The dissolution of silicas is carried out by ammonium fluoride in aqueous solution with potassium chloride. The potassium fluosilicate obtained is then isolated; its mass corresponds to 3,666 x SiO2. The values obtained corroborate the validity of this method.


Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model. Little is known about delivery of aerosolised steroids to neonatal patients undergoing assisted positive pressure ventilation and after extubation. A rabbit model has been established to investigate factors influencing drug delivery. Beclomethasone dipropionate, in a metered dose inhaler, was radiolabelled with technetium 99m. The mass median aerodynamic diameter of the aerosol was 3.3 (2.0) microns and the impactor measurements confirmed that the technetium distribution corresponded with that of the drug particles. The metered dose inhaler was actuated into a collapsible spacer that was used to ventilate and deliver aerosol to anaesthetised rabbits by a tracheostomy. From each actuation of the drug 2.9 (0.4)% of the aerosol deposited in the trachea and main bronchi and 1.2 (0.4)% in the lung. When the drug was delivered by a spacer device, with face-mask attachment, to rabbits breathing freely through a tracheostomy, aerosol deposition increased to 4.4 (2.1)% in the trachea and main bronchi and 1.9 (0.9)% in the lung lobes. The maximum change in systolic blood pressure after administration of aerosol by the collapsible spacer was a decrease of 13%. The methods described may prove useful for the delivery of inhaled steroids to neonatal patients likely to develop bronchopulmonary dysplasia.


Left hemiparalexia.

Left hemiparalexia. Three patients with left splenial lesions made paralexic errors restricted to the left end of words. Errors appeared more frequently when a correct response was highly dependent on the initial letter of the stimulus. One patient had full visual fields with hemialexia affecting the left visual field. The other two patients had complete right hemianopia. We attribute left-sided reading errors in the hemianopic patients to a retinotopically restricted disconnection pattern that selectively disrupts transfer of information originating from the peripheral left visual field. Functional resistance of the more numerous transcallosal projections representing visual field adjacent to the vertical meridian may account for such a pattern. The emergence of positional reading errors from retinotopically restricted left hemifield disconnection suggests that callosal information transfer during normal reading may primarily involve elemental sensory rather than lexical/semantic information.


Chronic cutaneous lupus erythematosus presenting as periorbital edema and erythema. We report two unusual cases of cutaneous lupus erythematosus presenting as dramatic eyelid edema and erythema. Neither patient had evidence of systemic or other significant cutaneous involvement. The eyelid edema and erythema were unilateral in one case and bilateral in the other. Both cases responded to therapy with antimalarial drugs.


Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire. A retrospective epidemiological study of ulcerative colitis (UC) and proctitis was performed in Leicestershire from 1972-89. Potential cases were identified from hospital departments of pathology, endoscopy, and medical records and from general practitioners. The county population includes more than 93,000 South Asians. There were 573 cases of UC and 286 of proctitis in Europeans and 115 cases of UC and 29 of proctitis in South Asians. The standardised incidence of UC in Europeans and South Asians was stable, except in Sikhs in whom it had increased rapidly. The relative risk of UC to South Asians was 2.45. The standardised incidences of UC in South Asians during the 1980s were: 10.8/10(5)/year in Hindus (95% confidence interval (CI) 7.4-14.1 cases/10(5)/year) 16.5/10(5)/year in Sikhs (95% CI 7.9-25.2 cases/10(5)/year), and 6.2/10(5)/year in Muslims (95% CI 1.6-10.9 cases/10(5)/year). There was no difference in incidence between Asians from East Africa and India. The standardised incidence of UC in Europeans was 5.3/10(5)/year (95% CI 4.3-6.3 cases/10(5)/year). The standardised incidences of proctitis were 3.1/10(5)/year (95% CI 1.9-2.5 cases/10(5)/year) in South Asians and 2.3/10(5)/year (95% CI 1.8-2.4 cases/10(5)/year) in Europeans. Ethnic groups had a similar disease distribution, except Sikhs in whom it was less extensive. Despite the similar disease distribution, South Asians had fewer operations and complications from UC than Europeans. There was a bimodal age specific incidence in Europeans, but not in other ethnic groups. First and second generation South Asians were at similar risk. Hindus and Sikhs have a significantly higher incidence of UC than Europeans in Leicestershire.


Myocardial lesions induced after trauma and treatment. In order to clarify the effect of trauma and treatment as stresses on myocardia, we examined histological changes of myocardia in victims who received various kinds of traumata and treatments. We also undertook a histochemical study for calmodulin, which we found useful in the diagnosis of early ischemia. Those who died shortly after stab wounds, traffic accident or head injuries, showed mild cardiac lesions such as contraction bands or fragmentation and mild diffusion of calmodulin, a marker for necrosis. A case with hemorrhagic shock after a traffic accident, involving intense resuscitation for 2 h, showed severe cardiac lesions such as contraction bands, hydropic change and subendocardial hemorrhage along with severe diffusion of calmodulin. In most of the instant death cases after falls, severe contraction band necrosis and severe calmodulin diffusion were observed. Myocardia of victims, who died several days after head injuries or traffic accidents, generally demonstrated distinct diffusion of calmodulin as compared to the mild and non-specific lesions detected by hematoxylin-eosin (H&E) staining. In cases of long-term survival in a state of brain death, calmodulin staining was very low, which was not always associated with the severity of the lesions on H&E staining. In cases with intensive or extended treatment, it appeared to be difficult to determine the cause-effect relationship between trauma and cardiac lesions or to distinguish the lesions due to extrinsic factors from those of disease. In some cases, calmodulin intensely stained the areas with hydropic appearance or hypereosinophilia, which may be related to calcium overload.


Cleft lip with or without cleft palate in Shanghai, China: evidence for an autosomal major locus. Orientals are at higher risk for cleft lip with or without cleft palate (CL +/- P) than Caucasians or blacks. We collected demographic and family data to study factors contributing to the etiology of CL +/- P in Shanghai. The birth incidence of nonsyndromic CL +/- P (Shanghai 1980-87) was 1.11/1,000, with a male/female ratio of 1.42. Almost 2,000 nonsyndromic CL +/- P probands were ascertained from individuals operated on during the years 1956-83 at surgical hospitals in Shanghai. Detailed family histories and medical examinations were obtained for the probands and all available family members. Genetic analyses of the probands' families were performed under the mixed model with major locus (ML) and multifactorial (MFT) components. The hypotheses of no familial transmission and of MFT alone could be rejected. Of the ML models, the autosomal recessive was significantly most likely and was assumed for testing three complex hypotheses: (1) ML and sporadics; (2) ML and MFT; (3) ML, MFT, and sporadics. None of the complex models were more likely than the ML alone model. In conclusion, the best-fitting, most parsimonious model for CL +/- P in Shanghai was that of an autosomal recessive major locus.


Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease. We studied the topographic distribution of Alzheimer's disease (AD)-type pathologic changes in the brains of 25 presumed nondemented elderly individuals. Neurofibrillary tangles (NFT) and senile plaques (SP) were evaluated quantitatively in nine to 20 cytoarchitectural fields using thioflavine S, Alz-50, and anti-beta/A4 amyloid immunohistochemistry. Our observations suggest that (1) most individuals over the age of 55 have at least a few NFT and SP; (2) the topographic distribution of NFT and SP in nondemented elderly individuals follows a consistent pattern of vulnerability in different cytoarchitectural areas; (3) NFT occur most frequently in the entorhinal and perirhinal cortices and the CA1/subiculum field of the hippocampus, while neocortical areas are less frequently affected; (4) immunohistochemically defined subtypes of SP have distinct patterns of distribution. beta/A4 immunoreactive SP are present in neocortical areas much greater than limbic areas. Alz-50 immunoreactive SP are infrequent and limited to those areas that contain Alz-50-positive neurons and NFT. These patterns closely match the hierarchical topographic distribution of NFT and SP observed in AD, suggesting a commonality in the pathologic processes that lead to NFT and SP in both aging and AD.