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.     

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.     

Impaired effortful cognition in depression

Depressed patients have been reported to have deficits in "effortful," but not effortless, cognitive functions compared to healthy volunteers. To test the hypothesis that the effortful cognitive deficits in major depression are not simply a function of psychiatric illness or hospitalization, we administered both effort-demanding and effortless cognitive tasks to 17 inpatients with major affective disorder and 17 hospitalized psychiatric controls. The depressed patients performed significantly more poorly than the controls on the effort-demanding task. The groups did not differ on the effortless task. These findings suggest that depressed patients are impaired in performing effort-demanding cognitive tasks compared to nondepressed psychiatric patients.     

Adolescents initiating cannabis use: cultural opposition or poor mental health?

In Norway, the use of cannabis was introduced by a resourceful group of oppositional middle-class adolescents in the late 1960s. At the beginning of the 1970s there were, however, signs of a change in the recruitment of the users: youths in trouble from lower social levels gradually started to use the drug. In a prospective longitudinal study of 1311 Norwegian pupils aged 13-19, the possible links between normative and political opposition, mental health and the use of cannabis were investigated. The findings indicate that the group that experiments with cannabis, and use the drugs a few times, is still mainly characterized by a political and normative "oppositional" engagement. Heavy users of cannabis, however, also have family problems and suffer from poor mental health. Thus, the study draws attention to the importance of distinguishing between two different clusters of longitudinal predictors for adolescent cannabis use: the first consists of subcultural opposition and certain personality traits, and seems to predict the earlier stages of use. The second consists of psychosocial problems and poor mental health. From this study one may not conclude that this second cluster predicts heavy cannabis involvement. We have, however, shown that it correlates with heavy involvement, cross-sectionally.     

Primary care. Burden of proof

Evidence that the shift of services from secondary to primary care is creating extra work for GPs is limited. A study showed that it is possible to quantify additional workload for GPs, but that certain aspects, such as measuring the time input, remain problematic. Future research needs to agree workload definitions, employ sensitive measures other than consultation rates, and distinguish between workload in practices and that of individual practitioners.     

Detection of antibodies to caprine arthritis-encephalitis virus using recombinant gag proteins

Summary The coding sequences of the core proteins p17 and p28 of caprine arthritis-encephalitis virus (CAEV) were amplified using the polymerase chain reaction and cloned into the plasmid expression vector p-GEX-2T. Both p17 and p28 were expressed as fusion proteins with glutathione S-transferase. The recombinant proteins were affinity purified from induced bacterial lysates using glutathione-agarose beads. The purified proteins were used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies against CAEV in goat sera and milk samples. Three different ELISA tests were developed based on p17, p28 or the combination of these two recombinant proteins (p17+p28). A comparison was made to an ELISA based on purified whole virus particles and to agar immunodiffusion test (AGID). Sera with conflicting results in the different ELISA tests were examined by Western blotting. There was a high correlation between the ELISA tests based on p17+p28 recombinant proteins and whole virus ELISA, with an estimated value of 0.92. Only 72–75% of the sera that tested positive in these two ELISA tests were positive in AGID. Antibodies to CAEV were detected in significantly more animals when serum samples were tested compared to milk samples. Based on the time and materials required to prepare the reagents, the recombinant based ELISA test was less expensive than the whole virus ELISA.