Improved method for production of attenuated Venezuelan equine encephalomyelitis (TC-83 strain) vaccine.

Primary chicken embryo cell cultures were evaluated a s an alternate cell system for the production of attenuated Venezuelan equine encephalomyelitis (TC-83 strain) vaccine. The TC-83 strain virus was shown to remain stable during 10 serial passages in chicken embryo cell culture with regard to plaque size and morphology, virus yield, potency, and virulence for mice and hamsters.     

Pharmacokinetics of tolfenamic acid in patients with cirrhosis of the liver

Summary Six patients with alcoholic cirrhosis of the liver received 100 mg tolfenamic acid p.o. and i.v. The disposition of tolfenamic acid could be described by a two-compartment open body model, with a mean central compartment volume of 8.71, and a -phase volume of 251. The elimination rate constant k_e averaged 1.13 h^–1 and the half-life of the -phase was 1.73 h; the mean total plasma clearance was 159 ml/min. These pharmacokinetic parameters differed only slightly from those in two groups of healthy volunteers studied previously; k_e was significantly reduced by about 30% in the patients but none of the other parameters differed significantly. There was good correlation between individual elimination rate constants or plasma clearances with the liver function tests, serum albumin and P-coagulation factors. Oral absorption was good and bioavailability of about 100% was shown by comparison of the areas under the plasma concentration — time curves after i.v. and p.o. administration. Metabolism was qualitatively and quantitatively very similar to previous observations in healthy volunteers. There seems no reason to reduce the dose of tolfenamic acid in patients with compensated alcoholic cirrhosis.     

Fine-needle biopsy of the pancreas: Results of 204 routinely performed biopsies in 190 patients

Two-hundred and four fine-needle aspiration biopsies of the pancreas have been performed in 190 patients during a 12-year period. Sixty-one of these were performed percutaneously guided by endoscopic retrograde cholangio-pancreatography, percutaneous transhepatic cholangiography, angiography, or ultrasonography; and 143 were taken intraoperatively. In 77 (67%) out of 115 patients with pancreatic cancer, a correct cytological diagnosis was obtained. Two biopsies were reported as malignant in 1 patient who ultimately was found to have chronic pancreatitis (false positives). The frequency of not representative biopsies varied from 20.8% in patients with suspected cancer biopsied intraoperatively to 48.4% in patients biopsied preoperatively. A correct cytological diagnosis of malignancy was obtained preoperatively in 54.6% of patients with cancer, in 60.0% of patients evaluated without later operation, and in 71.1% of patients biopsied during laparotomy for suspected pancreatic cancer. The overall false-negative rate was 9.8%. The predictive value of a positive test was almost 100%, whereas the predictive value of a negative test was only 69.6% (total material). Analyses may indicate that a more aggressive approach with multiple punctures may lower the not representative biopsy rate and increase the diagnostic accuracy in patients with pancreatic cancer.

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Resumen Doscientas y cuatro biopsias pancreáticas por aspiración con aguja fina han sido realizadas en 190 pacientes en un período de 12 años. Sesenta y una de éstas fueron realizadas por vía percutánea guiada por colangiopancreatografía endoscópica retrógrada, colangiografía percutánea transhepática, angiografía, o ultrasonografía, y 143 fueron intraoperatorias. En 77 (67%) de 115 pacientes con cáncer del páncreas se obtuvo un diagnóstico citológico correcto. Dos biopsias fueron informadas como malignas en un paciente en quien finalmente se demostró pancreatitis crónica (falsas positivas). La frecuencia de biopsias no representativas varió entre 20.8% en pacientes con sospecha de cáncer y biopsia realizada intraoperatoriamente, a 48.4% en pacientes con biopsias realizadas en la fase preoperatoria. El diagnóstico citológico correcto de malignidad fue logrado preoperatoriamente en 54.6% de los pacientes con cáncer, en el 60.0% de los pacientes evaluados y sin operación posterior y en el 71.1% de los pacientes en quienes se realizó biopsia durante la laparotomía por sospecha de cáncer pancreático. La tasa global de resultados falsos negativos fue de 9.8%. El valor de predicción de una prueba positiva fue de casi 100%, mientras el valor de predicción de una prueba negativa fue de sólo 69.6% (material total). La implicación práctica de esto es que cuando se obtenga un resultado negativo se debe proceder con la toma de nuevas biopsias. En conclusión, creemos que la biopsia del páncreas con aguja fina es un procedimiento seguro que puede ser recomendado en todas las fases del proceso diagnóstico o terapéutico de lesiones pancreáticas, y que es valioso en la planeación de la terapia en pacientes con cáncer. Sinembargo, las biopsias negativas en casos de sospecha clínica de cáncer no siempre excluyen su presencia. Mayor análisis puede indicar que una actitud más agresiva, con punciones mÚltiples, puede disminuir la tasa de biopsias no representativas y aumentar la precisión diagnóstica en pacientes con cáncer pancreático.

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Résumé Deux cent quatre biopsies-aspirations à l'aiguille fine du pancréas ont été pratiquées chez 190 sujets au cours d'une période de 12 ans. Soixante et une d'entre elles ont été pratiquées par voie souscutanée en étant guidées par cathétérisme rétrograde, cholangiographie transpariétale, angiographie ou ultrasonographie et 143 ont été effectuées au cours de l'intervention. Chez 77 (67%) sujets appartenant à une série de 115 malades atteints de cancer du pancréas le diagnostic cytologique exact a été porté. Deux biopsies en faveur du diagnostic de cancer répondaient en réalité à des lésions de pancréatite chronique (faux positifs). La fréquence des biopsies ininterprétables chez les sujets suspects de cancer a varié de 20.8% lorsque l'examen a été pratiqué au cours de l'intervention à 48.4% lorsque ce mÊme examen a été effectué avant l'opération. Le taux de diagnostic cytologique exact de cancer a été respectivement de 54.6%, de 60.0% et 71.1% selon que la biopsie cytologique a l'aiguille a été pratiquée avant l'intervention, après un certain délai et au cours de l'opération. Au total, le taux des faux positifs s'est élevé à 9.8%. La fiabilité de la biopsie à l'aiguille a été proche de 100% en cas de biopsie positive mais seulement de 69.6% en cas de biopsie négative. L'analyse de l'ensemble de ces faits incite à adopter une attitude plus agressive c'est-à-dire à pratiquer des biopsies multiples au lieu d'une ponction unique pour réduire le taux des prélèvements ininterprétables et accroÎtre celui des résultats exacts.

     

ECT and Anticoagulation

Electroconvulsive therapy (ECT) is an effective and safe treatment for depression. Anticoagulation therapy is used to reduce morbidity or mortality from stroke or recurrent pulmonary embolus in various cardiac and vascular conditions. We report in detail the successful ECT treatment of a patient suffering from major depression with psychotic features who continued warfarin (Coumadin) anticoagulant therapy.     

Breast cancer among Danish women occupationally exposed to diesel exhaust and polycyclic aromatic hydrocarbons, 1964–2016

Objective:The aim of this study was to explore the association between occupational exposure to diesel exhaust and polycyclic aromatic hydrocarbons (PAH), respectively, and breast cancer subtypes.Methods:The study included 38 375 women <70 years with incident breast cancer, identified in the Danish Cancer Registry, and 5 breast cancer-free controls per case who were randomly selected from the Danish Civil Registration System and matched on year of birth. Full employment history was obtained for all study subjects from a nationwide pension fund, and exposure to diesel exhaust and PAH was assessed using a job exposure matrix. Conditional logistic regression was used for estimation of odds ratios (OR) with adjustment for reproductive factors and socioeconomic status.Results:No noteworthy associations were observed for overall breast cancer in women exposed to diesel exhaust. However, diesel exhaust modestly elevated the risk of estrogen receptor negative breast tumors before age 50 [OR 1.26, 95% confidence interval (CI) 1.09–1.46]. Duration– and dose–response relationships were further observed for this subtype in this age group. No notable risk patterns were generally observed for PAH exposure.Conclusion:Occupational exposure to diesel exhaust may increase the risk of early-onset estrogen receptor negative breast tumors in women. Future studies exploring this association are warranted.     

Increased frequency of HLA-DPw2 in pauciarticular onset juvenile chronic arthritis

Thirty-six unrelated Danish patients with pauciarticular Juvenile Chronic Arthritis (PJCA) and 120 controls were typed for HLA-DPw1-w6 and the local specificity CDPHEI with bulk-expanded Primed Lymphocyte Typing (PLT) cells. The frequency of HLA-DPw2 was 52.8% in PJCA patients and 16.7% in controls (relative risk, RR = 4.5; P less than 0.001). The antigens HLA-Dw5 and/or Dw8 were present in 50% of the patients and in 21.3% of the controls (RR = 4.2; p less than 10(-3)). DPw2 was not associated (in linkage disequilibrium) with Dw5/w8 in patients or in controls, and the DP and D associations with PJCA were independent of each other. However, the combined presence of DPw2 and Dw5 and/or Dw8 gave a significantly higher risk of PJCA than each antigen alone indicating interaction of DP and DR gene products. PJCA is the first disease definitely found to be associated with a DP antigen.     

Persistent Subcutaneous Nodules in Children Hyposensitized with Aluminium-Containing Allergen Extracts

A follow-up study of 202 children who had received hyposensitization with aluminium-containing allergens showed that 1-3 years after cessation of hyposensitization 13 children still had severely pruiginous treatment-resistant subcutaneous nodules in their forearms. Because of their long persistence the nodules of six children were studied in detail. Histologically, the nodules showed infiltration with lymphocytes (forming germinal centres), macrophages, plasma cells, mast cells and a few eosinophils. In five patients aluminium crystals were found scattered between the cells and, in addition, the phagosomes of the macrophages contained aluminium. Patch tests for aluminium were positive in four of the six patients. It is concluded that persisting nodules during hyposensitization with aluminium-containing allergens may indicate development of aluminium hypersensitivity, and if this is confirmed hyposensitization should be discontinued.     

Histamine release from basophil leukocytes induced by microbial antigen preparations in patients with AIDS

Type I allergy against some common microorganisms was investigated in 14 patients with AIDS and 11 human immunodeficiency virus (HIV) antibody-positive homosexual men, and in a control group consisting of 13 heterosexual men without HIV antibodies. Basophil histamine release technique was used as a sensitive method to detect type I allergy against Candida albicans (CA), Herpes simplex virus type I (HSV-I) and cytomegalovirus (CMV). Of the 14 AIDS patients 11 (78%) showed significant histamine release when stimulated with CA, and HSV-I caused release in 10 (71%), whereas no response was obtained by CMV. In the group of HIV antibody-positive men only one released histamine when stimulated with CA and HSV-I and this patient also had lymphadenopathia. In contrast to these results, no release of histamine was obtained in the control group consisting of 13 heterosexual men. The histamine release caused by CA and HSV-I is mediated by an immunological reaction, since the release was abolished and regained by removal from and refixation to the cell surface of the cell-bound immunoglobulins. These results suggest an involvement of type I allergy as a pathogenetic co-factor in some infections in AIDS, and allergic type I reactions to CA and HSV-I might be an indicator for the presence of manifest AIDS.