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Biomedical subjects

R Midha

Publications and source records attributed to R Midha.

8 recordsLinked to original sources
PubMed1992

Subcutaneous injection of oral cyclosporin A solution.

Cyclosporin A (CyA) is the agent of choice for immunosuppression in the majority of rodent organ and tissue allotransplantation experiments. Subcutaneous injection of suitably dissolved pure CyA powder preparation is the acceptable standard of drug administration. We investigated the possibility of using oral CyA solution in an injectable form and compared its availability with that of the standard solution in a rat model. Oral CyA solution diluted in placebo (olive oil) and standard solution prepared from pure compound were injected subcutaneously at a dose of 5 mg/kg/day to two groups of rats. Trough whole blood CyA concentrations were measured on day 10 following initiation of treatment. Blood CyA levels of the standard solution group (1,167 +/- 246 micrograms/liter, mean +/- SD) were virtually identical to those of the oral solution group (1,105 +/- 179 micrograms/liter; P greater than 0.05). In addition, the oral solution was easier to prepare and caused less injection site morbidity than the standard solution. We conclude that placebo-diluted oral CyA solution may be safely injected subcutaneously to rats and results in consistent blood levels, comparable to those achieved with standard solution prepared from pure compound.

Administration, Oral↗
PubMed1992

Chronic cyclosporin A therapy in rats.

We investigated the pharmacokinetics of cyclosporin A (CsA) blood levels and drug toxicity in a chronic rat study in which long-term (30 weeks) CsA was administered. Ninety Lewis rats received subcutaneous CsA at 5 mg/kg/day for 12 weeks, at which time CsA injections were stopped in 50 animals. The remaining 40 rats were maintained on 5 mg/kg CsA daily until week 18 and then switched to an alternate day dosing until week 30. All rats were observed daily and weighed weekly. Whole blood CsA levels were determined by a commercially available radioimmunoassay kit. The daily dosing regimen resulted in greatly elevated trough CsA levels (greater than 1,600 micrograms/liter) and substantial chronic systemic toxicity, with weight loss and death in eight animals. Alternate day dosing reduced trough levels (mean 1,311 micrograms/liter) and decreased toxicity. Chronic administration by the subcutaneous route resulted in a considerable depot effect, with constancy of drug levels over a 48 hr dosing interval and a slow decline of drug levels (15 days) upon cessation of treatment. These results underscore the importance of monitoring both body weight and blood CsA levels in rodent studies when CsA is employed. Investigators should be aware of drug accumulation with chronic therapy and the consequent need to modify dosing to prevent toxicity.

Animals↗
PubMed1992

An assessment of regeneration across peripheral nerve allografts in rats receiving short courses of cyclosporin A immunosuppression.

While peripheral nerve reconstruction could benefit from the use of nerve allografts, long term immunosuppression for non-vital organ transplantation is controversial. This study investigated the effectiveness of short course Cyclosporin A immunosuppression. Fourteen Lewis (RT1l) rats were the recipients of 3 cm sciatic nerve grafts from ACI (RT1a) donors, repaired to the transected sciatic nerve of the recipient animal. Animals were treated with Cyclosporin A (5 mg/kg/day) for eight weeks. Neuromuscular function was assessed every two weeks by sciatic function index determinations until 20 weeks. Electrophysiological, histological and morphological evaluations were performed at 14 (n = 6) and 20 weeks (n = 8) postengraftment. Rats had significantly improving functional studies from four to eight weeks (P = 0.01). Function decreased following cessation of Cyclosporin A treatment. Rats evaluated at 14 weeks had histological evidence of graft rejection with inflammatory cell infiltration, extensive demyelination and remyelination, and some Wallerian degeneration. Rats demonstrated improvement in morphological parameters and motor function from 14 to 20 weeks after engraftment. In this sciatic nerve allograft model, short course Cyclosporin A immunosuppression, although resulting in an initial episode of graft rejection, was successful in permitting good long term functional regeneration of neuromuscular function.

Animals↗
PubMed1991

Transsphenoidal management of Rathke's cleft cysts. A clinicopathological review of 10 cases.

We report detailed data on 10 patients who underwent transsphenoidal microsurgical management of histopathologically confirmed Rathke's cleft cysts. Preoperatively, pituitary dysfunction was present in 90%, headaches in 80%, hyperprolactinemia in 70%, and visual interference in 40%. Computed tomography and magnetic resonance imaging had 90% and 100% sensitivity, respectively, in disclosing the lesion. The mean follow-up duration was 22 months. There was no mortality. The only morbidity was sustained diabetes insipidus in one case. Resolution or improvement in preoperative dysfunction occurred in the majority of patients: headaches in 100%, visual deficits in 75%, normalization of hyperprolactinemia in 83%, and reversal of panhypopituitarism in 33%. We conclude that Rathke's cleft cysts can be managed safely and effectively with transsphenoidal drainage and partial excision of the wall.

Adult↗
PubMed1991

Vernix caseo granulomatous meningitis (vernicomyelia).

An apneic and tetraplegic infant with an open lumbosacral myelomeningocele and an Arnold-Chiari malformation is reviewed. An exuberant chronic aseptic meningitis with foreign body giant cells and immunoreactive keratin was present around the spinal cord and brainstem. This paper discusses the recognition and role of granulomatous meningitis in the clinical course and in the pathogenesis of the unusual cerebellar abnormalities found in this infant.

Abnormalities, Multiple↗
PubMed1975

Exercise-induced bronchospasm: evaluation of albuterol aerosol.

Albuterol aerosol was compared with isoproterenol and placebo in a double-blind, cross-over study in 12 asthmatic children. A significant increase in mean peak expiratory flow rate 15 minutes after albuterol inhalation persisted for at least five hours after treatment. Inhalation of albuterol one hour before treadmill exercise inhibited exercise-induced bronchospasm.

Adolescent↗