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Biomedical subjects

R Midha

Publications and source records attributed to R Midha.

49 records · Page 3Linked to original sources
PubMed1993

Comparison of regeneration across nerve allografts with temporary or continuous cyclosporin A immunosuppression.

The efficacy of short-term immunosuppression in a nerve allograft model was examined by comparing regeneration across peripheral nerve allografts with either temporary (12 weeks) or continuous (30 weeks) cyclosporin A treatment. One-hundred fifty Lewis rats received 2-cm nerve grafts from allogeneic ACI or syngeneic Lewis rat donors and were allocated to the following groups: allogeneic grafts and continuous cyclosporin A, with 18 weeks (20 rats) or 30 weeks (20 rats) of survival after graft placement; allogeneic grafts and temporary cyclosporin A, with 12 weeks (10 rats), 18 weeks (20 rats), or 30 weeks (20 rats) of survival; and control rats with allogeneic and syngeneic grafts, no cyclosporin A, with 12, 18, or 30 weeks (10 rats each) of survival. Functional regeneration across the nerve grafts was serially assessed with walking-track analysis. Endpoint evaluations included electrophysiological, histological, and morphometric studies. Both walking-track and electrophysiological function reached a plateau at a significantly worse level in nonimmunosuppressed allograft recipients than in syngeneic or treated allograft recipients. The group with temporary therapy experienced significant worsening in both motor and electrophysiological function at Week 18, 6 weeks after cyclosporin A withdrawal, compared to the group with continuous treatment. At Week 30, motor and electrophysiological function in the temporary-treatment group recovered to levels similar to those of the syngeneic and continuous cyclosporin A groups. Histological assessment of the graft segments from the temporary cyclosporin A group at 18 weeks showed evidence of rejection, with mononuclear cell infiltration and demyelination; morphometric evaluation demonstrated significantly decreased numbers of nerve fibers in the distal host segment. These histological and morphometric changes were no longer present in the nerves from the temporarily immunosuppressed rats at Week 30. Withdrawal of immunosuppression after successful regeneration through nerve allografts results in short-term graft rejection. Eventual restoration of graft histological and function parameters is comparable to continuously immunosuppressed rats. Temporary immunosuppression of nerve allograft recipients is feasible.

Analysis of Variance↗
PubMed1993

A double-blind, long-term, comparative study on quality of life, safety, and efficacy during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicenter study.

Amlodipine (5-10 mg, once daily) and enalapril (10-40 mg, once daily) were compared in terms of quality of life, efficacy, and tolerability, in a multicenter, double-blind trial lasting for 50 weeks in 461 mild or moderate hypertensive patients. Both drugs were similarly effective in lowering blood pressure while maintaining quality of life. Apart from class-typical effects, such as edema for calcium antagonists, and cough for angiotensin-converting enzyme inhibitors, both drugs were equally well tolerated, with few adverse effects of clinical significance. Only a few patients [eight amlodipine (4%); nine enalapril (4%)] were withdrawn from the trial due to drug-related adverse events, demonstrating that tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. Both drugs reduced the calculated risk of coronary heart disease over the next 10 years. It was concluded that amlodipine compared favorably with enalapril as an effective and well-tolerated antihypertensive drug.

Adult↗
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↗
PubMed1987

Assessment of spinal cord injury by counting corticospinal and rubrospinal neurons.

This paper describes an objective, quantifiable technique for assaying the degree of severity of spinal cord injury. Twenty-one rats underwent a C7-T1 laminectomy: 12 received a C8 spinal cord clip compression injury with forces of either 2.3, 16.9 or 53.0 g; 4 had cord transection at C8, and 5 had no cord lesion. Postoperative clinical neurological assessment was performed by the inclined plane method. At 4 weeks, the spinal cord-injured rats underwent a T10 transection and insertion of a Gelfoam pledget impregnated with horseradish peroxidase (HRP). HRP was similarly administered to 9 normal rats. Longitudinal sections of the spinal cord encompassing the injury site were stained with Luxol fast blue, and coronal sections from the cerebrum and midbrain were processed for HRP reactivity with tetramethylbenzidine. Labelled corticospinal and rubrospinal neurons were counted in every 6th section to derive a cortical score (CS) and a red nucleus score (RNS) for each animal. The CS reflected the extent of the pathological changes at the site of cord injury and the ln CS decreased linearly with increasing injury severity (P less than 0.0001). In contrast, the RNS was only reduced in animals with severe (53.0 g) cord injuries (P less than 0.0006). The degree of preservation of the dorsal columns including the corticospinal tracts at the injury site correlated with the CS, whereas the RNS was related to the degree of preservation of the lateral columns. Counts of rubrospinal neurons, but not corticospinal neurons, correlated closely (r = 0.96, P less than 0.001) with the inclined plane results, suggesting the importance of non-pyramidal tracts in controlling gross motor function. Thus, counting corticospinal and rubrospinal neurons is an objective, reliable test of the severity of experimental spinal cord injury.

Animals↗
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↗