Influence of haemodialysis on the pharmacokinetics of ciprofloxacin

The elimination of ciprofloxacin from serum was studied in 16 patients (10 F, 6M, age 44–70 years) with end stage renal disease, treated with haemodialysis. The dosage of ciprofloxacin was 200 mg i.v. given by bolus injection (10 patients) or 250 mg orally (6 patients) on a day without and a day with dialysis (8 hours before dialysis was started). Samples were taken at regular intervals from the arteriovenous shunt and from venous peripheral blood. Concentrations of ciprofloxacin were measured by a biological assay. The mean peak serum levels after 200 mg i.v. were 3.5 mg/l measured 0.5 hour after the gift. After an oral dose of 250 mg the mean peak serum level measured one hour after the gift amounted to 1.5 mg/l. The serum half life was 8.5 h without dialysis and 5.5 h with dialysis. It was calculated from AUC values during dialysis that about 15% of the drug was eliminated by the artificial kidney.     

Irritable bowel syndrome: pathophysiology and (future) treatment options]

Abnormalities of intestinal motility, altered visceral perception and psychological influences are the most important factors in the pathogenesis of irritable bowel syndrome. Current pharmacological treatment options are limited and lack specificity. In the future, it is likely that a number of therapeutic agents with stronger spasmolytic effects (selective muscarinic receptor antagonists), more specific colokinetic properties (5-hydroxytryptamine (5HT)4 agonists) and a positive influence on visceral perception (serotonin (5HT3) receptor antagonists, kappa-agonists) will become available.     

Effect of octreotide on fasting gall bladder emptying, antroduodenal motility, and motilin release in acromegaly.

Subcutaneous octreotide (Sandostatin) injections lead to gall stone formation in 13-50% of acromegaly patients during one year of therapy. This study explored the effects of octreotide on interdigestive gall bladder emptying, antroduodenal motility, and motilin release. Ambulatory antroduodenal manometry was performed in six acromegaly patients before and after two months of octreotide therapy (100 micrograms thrice daily, subcutaneously). Ultrasonographic gall bladder volume measurements and plasma motilin concentrations were obtained during two migrating motor complex (MMC) cycles. Before octreotide treatment, nine of 26 phase III activities started in the antrum and 17 of 26 in the duodenum whereas during treatment 47 of 48 of phase III activity started in the duodenum (p < 0.05). Before treatment, interdigestive gall bladder emptying (mean (SEM) 39.9 (4.0)% of maximal fasting volume) and plasma motilin peaks preceded antral phase III but not duodenal phase III. During octreotide therapy no significant motilin fluctuation or gall bladder emptying was seen. Fasting gall bladder volume increased from 40.9 (9.1) ml before to 68.0 (14.8) ml (p < 0.05) during octreotide treatment. In conclusion, two months' treatment with octreotide increases the number of duodenal phase III like activity and virtually abolishes antral phase III, plasma motilin peaks, and interdigestive gall bladder emptying. These effects might contribute to the high risk of gall stone formation during longterm octreotide treatment.     

Proximal Gastric Motor Activity in Response to a Liquid Meal in Type I Diabetes Mellitus with Autonomic Neuropathy

Disordered gastric emptying occurs in 30-50% ofpatients with diabetes mellitus. Although the rate ofgastric emptying is dependent on the integration ofmotor activity in different regions of the stomach, there is limited information about the functionof the proximal stomach in diabetes mellitus. In thepresent study the response of the proximal stomach to aliquid meal was examined in eight diabetic patients with autonomic neuropathy and gastrointestinalsymptoms and in 10 healthy volunteers, using anintragastric bag connected to an electronic barostat.Postprandial relaxation of the proximal stomach wasmeasured as an increase of intragastric bag volume at aconstant pressure level of 1 mm Hg above theintraabdominal pressure. During the experiment the bloodglucose levels were maintained within the euglycemic range. Before ingestion of the meal theintragastric bag volume was larger in the diabeticpatients than in the healthy volunteers, 234.4 ±29.1 ml vs 155.3 ± 15.3 ml (P = 0.06). Themaximum volume was not different in diabetics compared to the healthy controls(386.3 ± 45.2 ml versus 399.0 ± 35.2 ml).However, the maximum volume increase was significantlyless in diabetics (143.7 ± 38.6 ml) compared tothe controls (231.4 ± 30.5 ml, P < 0.04). Bloatingwas inversely correlated with the volume changes, whichsuggests that impaired relaxation of the proximalstomach may play a role in the genesis of thissensation. In conclusion, this study shows a lower fastingfundal tone and a decrease in volume change of thegastric fundus after a nutrient drink in patients withautonomic neuropathy due to type I diabetes mellitus. These abnormalities may play a role in theabnormal distribution of food, disordered liquid gastricemptying, and in the genesis of the sensation ofbloating observed in these patients.     

Karyotyping urine sediment cells confirms trisomy 12 mosaicism detected at amniocentesis

A newborn is described in whom trisomy 12 mosaicism was detected prenatally at third trimester amniocentesis during the fourth pregnancy of a 34-year-old woman. After birth, trisomy 12 cells were found in placental tissue and in cultured urine sediment cells. A sample of cord blood and a skin biopsy revealed only normal (46,XX) cells. Both parents had a normal karyotype. After a difficult start with unexplained hypoglycaemias and convulsion equivalents, the girl is doing well at the age of 9 months: there are no signs of central motor disturbance. The importance of the use of cultured urine sediment cells in confirming chromosomal mosaicism is stressed.     

Immunological Responsiveness in Idiopathic and Drug-induced Panmyelopathy: Discrepancy between Sensitization with DNCB and Haemocyanin

S ummary . Immunological responsiveness to two primary antigens, haemocyanin and dinitrochlorobenzene, was tested in seven patients with idiopathic or drug-induced panmyelopathy. Humoral immunity was quite normal, but cell-mediated immunity was partially deficient. Six patients showed in vitro lymphocyte reactivity to haemocyanin and positive intracutaneous tests with haemocyanin after immunization. The one patient in whom sensitization to haemocyanin did not develop had received prednisone during immunization because of overt bleeding tendency. In contrast to the successful immunization with haemocyanin, sensitization with DNCB did not succeed in any of the seven patients. PHA reactivity of the lymphocytes was not significantly lowered.