Expression of the Human Immunoglobulin Heavy Chain VH6 Gene Element by Fetal B Lymphocytes

Fetal B lymphocytes in mice and humans use a limited number of the available V_H gene segments. Mouse fetal B cells primarily utilize 3' V_H elements, suggesting that the localization of these elements determines their rearrangement frequency. The previously reported non-random usage of human V_H genes has been more difficult to explain. In this study the authors analysed the expression of the most proximal 3' human V_H element (V_H6) using a monoclonal antibody (JE-6). V_H6 expression was assessed in various B cell differentiation stages from fetal liver, bone marrow and spleen at 12–20 weeks of gestation. The authors demonstrate that the level of V_H6 expression does not exceed a stochastic usage frequency. This suggests that the localization of V_H6 does not significantly promote its expression during human fetal life, and that other factors must affect the usage of V_H genes during human fetal development.     

Vomiting after ophthalmic surgery

The usefulness of intra-operative antiemetics and postoperative oral fluid restriction in the prevention of vomiting following anaesthesia for ophthalmic surgery, was studied in 200 patients. They were allocated into four groups of 50 and given either saline (as control), droperidol, metoclopramide or prochlorperazine. Oral intake was restricted postoperatively in half of the patients of each group. Anaesthesia comprised morphine and atropine premedication and a halothane, nitrous oxide and oxygen spontaneous breathing technique. No significant beneficial effects resulted from intra-operative antiemetics; vomiting incidences of 26% after saline and droperidol, 28% after metoclopramide and 14% after prochlorperazine were observed. Younger patients and females vomited most frequently. Restriction of oral fluids did not decrease the incidence of vomiting but demonstrated that approximately half of those patients who vomit do so with their first postoperative oral intake. Vomiting was observed more frequently after non intra-ocular surgery than after intra-ocular surgery (37% cf. 16%, p less than 0.01) and postoperative analgesics were required by more non intra-ocular patients than by intra-ocular patients (25% cf. 5%, p less than 0.001). Squint patients vomited most frequently (48%) and most frequently required postoperative analgesia (35%).     

Frusemide and Its Acyl Glucuronide Show a Short and Long Phase in Elimination Kinetics and Pharmacodynamic Effect in Man

The pharmacokinetics of 80 mg frusemide given orally were investigated in normal subjects using a direct HPLC method for parent drug and its acyl glucuronide conjugate. Two half-lives could be distinguished in the plasma elimination of both frusemide and its conjugate, with values of 1.25 ± 0.75 and 30.4 ± 11.5 h for frusemide and 1.31 ± 0.60 and 33.2 ± 28.0 h for the conjugate. The renal excretion rate-time profile showed two phases; the rapid elimination phase lasted from 0–15 h and the second and slow phase, from 15–96 h. During the first 15 h, 33.3 ± 4.8% of the dosed frusemide was excreted; in the remaining period 15–96 h, 4.6 ± 1.5% was excreted. In the same two periods the excretion of the glucuronide was 13.4 ± 4.7 and 1.9 ± 1.1%, respectively. The mean renal clearance of frusemide was 90.2 ± 16.9 mL min^?1 during the first period and 91.5 ± 29.3 mL min^?1 in the remaining period, during which the stimulation of urine production was absent. The renal clearance of the acyl glucuronide was 702 ± 221 mL min^?1 in the first period, but only 109 ± 51.0 mL min^?1 in the second period. The stimulated urine production in the first 6 h after administration amounted to 2260 ± 755 mL (measured urine production minus baseline value of 1 mL min^?1 (360 mL). During the second or rebound period (6–96 h after drug administration), the quantity of urine was 990 ± 294 mL lower than what would have been expected from the baseline production of 5400 mL. This reduced production (0.82 mL min^?1) is equivalent to an 18% reduction in the average urine flow rate of 1 mL min^?1.     

Sweet's syndrome—therapy with cyclosporin

We report the case of a 39-year-old female patient suffering from Sweet's syndrome after an upper respiratory tract infection. Cyclosporin A at a dose of 10 mg/kg per day was given as initial treatment. Skin lesions and general malaise resolved within 9 days. The cyclosporin dose was decreased within 21 days, without recurrence of the eruption. Cyclosporin is a potent inhibitor of T lymphocytes, but affects granulocyte and monocyte functions as well. Success of treatment in our case shows that cyclosporin represents an alternative to steroid treatment in patients with Sweet's syndrome.     

HETEROZYGOTES FOR 17α-HYDROXYLASE DEFICIENCY CAN BE DETECTED WITH A SHORT ACTH TEST

A short ACTH test was performed in the six parents, and four siblings, of three cases with 17 alpha-hydroxylase deficiency. Baseline steroid levels were all normal in female heterozygotes but in males 17 alpha-hydroxyprogesterone levels were elevated. After ACTH-stimulation, plasma levels of corticosterone were elevated in five obligate heterozygotes and 18-hydroxydeoxycorticosterone levels were increased in four of them. Two of the four siblings had biochemical signs of heterozygosity. The short ACTH test appears to be an efficient method for detecting heterozygosity, but the abnormalities found are more heterogeneous than previously suggested.     

Disproportional impact of the revised AIDS surveillance definition on the AIDS incidence among drug users compared to homosexual men

The impact of changes in 1993 of the old 1987 WHO/CDC AIDS casedefinition was studied in a cohort of 153 HIV-infected injectiondrug users (IDUs) and 502 HIV-infected homosexual men in Amsterdam.It appeared that the extension in Europe of the old AIDS definitionto also include recurrent pneumonia, pulmonary tuberculosisand invasive cervical neoplasia, strongly increases the numberof persons diagnosed with AIDS among IDUs, but will hardly influencethe AIDS incidence among homosexual men. As recurrent pneumoniaand pulmonary tuberculosis are present among drug users withhigh CD4 cell counts, the incidence of these diseases may partlybe determined by environmental factors. The extension of theold 1987 AIDS definition in the USA with CD4 count <200 cells/mm³In addition to the 3 above-mentioned diseases, will also havea larger impact on drug users than on homosexual men.     

Demonstration of the Feasibility of Implantation of a Skeletal Muscle Pulse Generator for Fecal Incontinence in a Patient with an Implanted Unipolar DDD Pacemaker

Electromagnetic fields and myopotentials from skeletal muscle may interfere with the function of a cardiac pacemaker. A 65-year-old woman with a unipolar DDD cardiac pacemaker underwent dynamic graciloplasty (transposition of the gracilis muscle around the anal canal and subsequent implantation of a bipolar pulse generator to stimulate the gracilis muscle), for the treatment of fecal incontinence. This gracilis pulse generator is turned "off" with an external magnet to allow defecation. Appropriate functioning of these two pulse generators (the cardiac pacemaker and the gracilis pulse generator) was tested during implantation of the gracilis pulse generator and afterwards. It was demonstrated that the combination could be used safely in this patient.     

Disposition and Elimination of Three Polychlorinated Dibenzofurans in the Liver of the Rat

Disposition and Elimination of Three Polychlorinated Dibenzofuransin the Liver of the Rat. VAN DEN BERG, M., DE JONGH, J., ECKHART,P., AND VAN DER WIELEN, F. W. M. (1989). Fundam. Appl. Toxicol.12, 738–747. The disposition and elimination of 1,2,3,6,7,8-HxCDF(HxCDF), 1,2,3,7,8-PnCDF (1-PnCDF), and 2,3,4,7,8-PnCDF (4-PnCDF)were studied in liver of female Sprague-Dawley rats after administrationof a single oral dose of 3.5–6.3 µg/kg. The dispositionof these PCDF congeners was structure and vehicle dependent.Administration in peanut oil caused the highest liver retention,compared with administration through the standard diet. Half-livesin liver for 1-PnCDF, 4-PnCDF, and HxCDF were 3.3, 108, and73 days, respectively. 4-PnCDF showed very high liver retention:70% of the dose in the first days after administration. To studykinetic interaction in the liver, mixtures of 1-PnCDF and 4-PnCDF(Experiment I) and of 4-PnCDF and HxCDF (Experiment II) wereadministered. The presence of 4-PnCDF in Experiment I did notsignificantly influence the half-life of I-PnCDF. In ExperimentII the estimated half-life of 4-PnCDF was again 108 days, butfor HxCDF an increased half-life was found, 156 days. It isconcluded that PCDFs with a chlorine substituent(s) adjacentto the oxygen bridge (4- and 6-positions) are eliminated vcryslowly with 14 much greater than that of TCDD.