Aging: changes in distribution of diazepam and metabolites in the rat

The brain levels of diazepam and its metabolites after a single iv injection of diazepam were measured over a 2-hr time period in young (3-4-month-old), mature (12-15-month-old), and senescent (29-31-month-old) male Fischer 344 rats. The areas under the brain level time curves were used as an index of exposure. Senescent rats were exposed to significantly more diazepam, N-desmethyldiazepam, and oxydiazepam between 0 and 120 min after an injection of 180 micrograms/kg of diazepam than the young or mature animals. The unbound plasma level failed to adequately account for the age-related increase in brain exposure to diazepam. Mechanisms other than the unbound diazepam in plasma are probably involved in eliciting the age-associated increase in brain levels of diazepam and its metabolites.     

CongenitaI Polycystic Disease of the Brain: Report of an Unusual Case

Multiple congenital supratentorial intracerebral cysts occurred in a newborn infant. The cysts, of varying size, content and lining, occupied the cerebral hemispheres. They formed a mosaic pattern on CT scan and left no trace of a recognisable ventricular system. Multiple surgical procedures were performed during the first year of life, and at one year the child was very well and asymptomatic, with two functioning shunts.     

Pharmacokinetics of two alternative dosage forms for cyclosporine: liposomes and intralipid

Cyclosporine (CsA), commercially available as iv or oral Sandimmune, is a potent immunosuppressant which can induce dose-related nephrotoxocity. In addition, the iv product contains a solubilizing agent, Cremophore EL, which in itself is reported to be nephrotoxic and can induce, in sensitized patients, anaphylactic reactions. Solubilization of CsA with liposomes or lipid emulsions could provide a suitable alternative dosage form for iv administration. With this in mind, male New Zealand white rabbits were given iv CsA (10 mg/kg) in three different dosage forms: (1) CsA:liposomes; (2) CsA:Intralipid (soybean oil and phospholipids); and (3) the commercially available Sandimmune (cyclosporine). The CsA concentration in whole blood samples was analyzed by HPLC. The terminal disposition half-life of CsA (t1/2 beta) ranged from 400 to 475 min and was not statistically different among the three groups. However, the distribution characteristics of CsA changed dramatically depending on the dosage form. The volume of distribution of CsA at steady state (Vdss) in Sandimmune was 2.7 +/- 0.2 L/kg and was significantly lower than that of either Intralipid (10.6 +/- 2.7 L/kg) or liposomes (7.4 +/- 2.3 L/kg). A significantly lower total body clearance (TBC) of CsA also was seen for Sandimmune (12.7 +/- 0.3 mL/min/kg) as compared with that of either Intralipid (24.4 +/- 8.2 mL/min/kg) or liposomes (18.9 +/- 3.9 mL/min/kg). Since CsA is extensively bound to lipoproteins, it is surprising that both test vehicles showed a different distribution pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recombinant activated factor VII for intractable bleeding post splenectomy in a patient with myeloproliferative disorder.

Recombinant activated factor VII has been Food and Drug Administration approved to treat hemorrhages in hemophiliac patients with inhibitors and in acquired hemophilia patients. Recombinant activated factor VII use has also been considered for the management of uncontrolled bleeding in a number of congenital and acquired hemostatic abnormalities. The myeloproliferative disorders are a group of clonal hematologic diseases where, frequently, abnormal platelet function is considered a hallmark. This is the first case report addressing the clinical benefit of off-label use of recombinant activated factor VII in an attempt to control intractable bleeding in a patient with a myeloproliferative disorder after splenectomy.     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.