Dorsal root ganglia cocultured with macrophages: an in vitro model to study experimental demyelination

The present investigation introduces an in vitro model to study macrophage properties during demyelination. Rat dorsal root ganglia (DRG) were cultured for obtaining myelinated peripheral nerve fibers. These cultures were exposed to non-resident macrophages. In untreated control cultures, there was no indication of myelin removal by the added macrophages. DRG were exposed to enzymatically generated oxygen radicals using the xanthin/xanthin oxidase or the glucose/glucose oxidase system. Assessment of Schwann cell viability and ultrastructural morphology revealed different patterns of cell cytotoxicity and morphological changes in different experiments. High concentrations caused complete tissue necrosis of the DRG, while low concentrations did not affect either cell viability or ultrastructural morphology. Under intermediate experimental conditions, oxygen radicals caused non-lethal Schwann cell damage leading to Schwann cell retraction and myelin sheath rejection. Myelin lamellae were disrupted and decompacted. These changes were followed by a selective macrophage attack on myelin sheats, resulting in demyelination. Axons, Schwann cells and sensory ganglion cells survived this attack. The specificity of the oxygen radical effects was tested in experiments using the oxygen radical scavengers catalase and superoxide dismutase. Catalase prevented the described effects on cell morphology and subsequently blocked demyelination by non-resident macrophages.Supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) (Br 1274/1-1)     

Severe tubulopathy and kidney graft rupture after coadministration of mannitol and ciclosporin.

Spontaneous allograft rupture after kidney transplantation is a rare complication usually due to an acute rejection of the interstitial type. In a 32-year-old man kidney transplantation was performed under immunosuppression with prednisolone and ciclosporin (CS). The dose of CS was 5 mg/kg body weight intravenously for the first 24 h, on the 2nd day 10 mg/kg/day orally, with gradually decreasing doses thereafter. The patient remained oliguric in the postoperative period and received additionally 600 ml mannitol solution intravenously for osmodiuresis within a period of 6 days. On the 8th postoperative day, 48 h after the last intravenous infusion of mannitol, spontaneous renal rupture occurred. The CS concentrations in the blood during the days before the rupture were within the upper normal range for effective immunosuppression (300-600 ng/ml). Intraoperatively the kidney appeared enlarged due to edematous swelling of the graft, but it showed no signs of rejection. The histological finding was a toxic tubulopathy with extensive isometric vacuolization and peritubular congestion, a known side effect of both of CS and of mannitol. The rupture was successfully repaired. Thirty-four days after the transplantation diuresis increased and hemodialysis therapy could be discontinued. In a second biopsy of the kidney the signs of toxic tubulopathy with isometric vacuolization were reduced. On the following days the serum creatinine dropped below 160 mumol/l. It can be assumed that the combination of CS therapy and administration of massive and continued doses of mannitol in an oliguric patient with allograft kidney may potentiate severe tubulopathy with concomitant edematous swelling of the graft. This can result in an increasing danger of spontaneous renal rupture.     

Extraocular changes in congenital aniridia]

The authors draw attention to possible extraocular changes in children with congenital aniridia. Of 31 investigated patients they were found in 5 children. Among these changes, because of its serious character, Wilms tumour holds the first place; it was found by the authors in two children. To ensure its early detection, the authors emphasize the necessity to dispensarize all children with congenital aniridia. Collaboration with an experienced X-ray specialist and child oncologist is essential. In addition to Wilms' tumour congenital aniridia can be associated with serious somatic developmental changes. The authors observed in one child and AGR triad and in two patients deformities of the skeleton of the head and lower extremities.     

The effect of quinidine on the analgesic effect of codeine

Summary We have studied the hypoalgesic effect of codeine (100 mg) after blocking the hepatic O-demethylation of codeine to morphine via the sparteine oxygenase (CYP2D6) by quinidine (200 mg). The study was performed in 16 extensive metabolizers of sparteine, using a double-blind, randomized, four-way, cross-over design. The treatments given at 3 h intervals during the four sessions were placebo/placebo, quinidine/placebo, placebo/codeine, and quinidine/codeine. We measured pin-prick pain and pain tolerance thresholds to high energy argon laser stimuli before and 1, 2, and 3 h after codeine or placebo.After codeine and placebo, the peak plasma concentration of morphine was 6–62 (median 18) nmol·.l^–1. When quinidine pre-treatment was given, no morphine could be detected (<4 nmol·l^–1) after codeine. The pin-prick pain thresholds were significantly increased after placebo/codeine, but not after quinidine/codeine compared with placebo/placebo. Both placebo/codeine and quinidine/codeine increased pain tolerance thresholds significantly. Quinidine/codeine and quinidine/placebo did not differ significantly for either pin-prick or tolerance pain thresholds.These results are compatible with local CYP2D6 mediated formation of morphine in the brain, not being blocked by quinidine. Alternatively, a hypoalgesic effect of quinidine might have confounded the results.     

Cerebral involvement in adult onset Still's disease

Still's disease was diagnosed in a 40-year-old patient as a cause of psycho-organic syndrome with complete disorientation and stupor, sensory and motor aphasia. There were no signs of a tumour, cerebrovascular accident, bacterial or viral infection. The patient recovered quickly from the cerebral disturbances under treatment with corticosteroids. Similar symptoms in adult patients with Still's disease are seldom found in the literature.     

Venous surgery in veno-occlusive dysfunction: long-time results after deep dorsal vein resection.

Follow-up of patients 1 year after deep dorsal vein resection gives evidence of an approximate 50-60% success rate. A careful selection of only this small percentage of patients, in whom abnormal drainage through the penile dorsum is obvious, is mandatory. Men with an arterial cofactor have to be excluded or to be subsequently treated by intracavernosal autoinjection of vasoactive substances. Late results from our study demonstrate a further loss of sufficient erection, also in men considered as persistent success by us, in the subjective view of the patient and/or his sexual partner.     

Über die Beziehungen des chronischen Lupus erythematodes zur Tuberkulose

Ohne ZusammenfassungHiezu Taf. XXXVII.     

Die secundären Erregbarkeitsänderungen an der Cathode eines andauernd polarisirten Froschnerven

Ohne Zusammenfassung     

National survey on the management of primary hyperparathyroidism by Swiss endocrinologists

Background From the endocrine surgeon’s perspective, it is important to know how endocrinologists manage patients with primary hyperparathyroidism (pHPT). The aim of this survey was to evaluate the preoperative diagnostic workup and referral pattern for parathyroidectomy by Swiss endocrinologists. Materials and methods The survey was conducted by mailing a questionnaire to all members of the Swiss Society for Endocrinology and Diabetes in spring 2005. Results The questionnaire was sent back by 68 of 124 endocrinologists (55%). The median annual case volume of patients with pHPT was 6 (range 1–50). The mean fraction of these patients referred for surgery was 59 ± 24%. This fraction was significantly higher in the German-speaking part of Switzerland than in the French-speaking part (67 ± 21% vs 51 ± 27%). When considering surgery for asymptomatic pHPT, 62% of the endocrinologists rely routinely on the recommendations of the NIH consensus conference and 86% on the subsequent guidelines of the workshop in 2002. Sixty-seven percent of the endocrinologists routinely perform localization studies before possible referral for surgical exploration. Typically, they consisted of an ultrasonography of the neck (93%) and a ^99mTc-MIBI scintigraphy (80%). The impact of the availability of a minimally invasive surgical procedure on the number of patients referred for surgery seems to be considerable. Sixty-one percent of the participants would expand the indication for surgery if the operation could be done by a limited surgical approach. Conclusions In a relevant fraction of patients with pHPT, endocrinologists still do not regard curative therapy as mandatory. Surprisingly, there are significant cultural differences concerning referral patterns to surgery between the German-speaking and the French-speaking parts of Switzerland. Minimally invasive procedures seem to lower the threshold for referral for surgical therapy. This work was presented at the 2nd Biennial Congress of the ESES, May 2006, Krakow, Poland.