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Biomedical subjects

R Midha

Publications and source records attributed to R Midha.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cold preserved nerve allografts: changes in basement membrane, viability, immunogenicity, and regeneration.

Rat sciatic nerve graft segments were harvested and pretreated by either placement in the University of Wisconsin Cold Storage Solution at 5 degrees C and storage from 1 to 26 weeks, or repeatedly freezing (-40 degrees C) and thawing (20 degrees C). Following pretreatment, grafts were transplanted as either syngeneic or allogeneic nerve grafts. Storage and freeze-thawing did not affect the Schwann cell basal lamina or laminin distribution of the peripheral nerve. Graft cell viability decreased with increasing time of storage, with some viable cells detectable even after 3 weeks of storage. Freeze-thawed grafts were not viable. Increasing time of storage led to decreasing immune response and graft rejection, but improved regeneration. Freeze-thawed and 26-week stored allografts were nonimmunogenic and rejection was not seen, but regeneration was delayed compared to autografts. Graft storage may become a useful adjunct to clinical nerve allografting to permit elective scheduling of surgery, provide greater time for preoperative tissue testing, and possibly blunt the immune response.

Animals↗
PubMed1998

Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries.

BACKGROUND: The purpose of this study was to determine the prevalence, cause, severity, and patterns of associated injuries of limb peripheral nerve injuries sustained by patients with multiple injuries seen at a regional Level 1 trauma center. METHODS: Patients sustaining injuries to the radial, median, ulnar, sciatic, femoral, peroneal, or tibial nerves were identified using a prospectively collected computerized database, maintained by Sunnybrook Health Science Centre, and a detailed chart review was undertaken. RESULTS: From a trauma population of 5,777 patients treated between January 1, 1986, and November 30, 1996, 162 patients were identified as having an injury to at least one of the peripheral nerves of interest, yielding a prevalence of 2.8%. These 162 patients sustained a total of 200 peripheral nerve injuries, 121 of which were in the upper extremity. The mean patient age was 34.6 years (SEM +/- 1.1 year), and 83% of patients were male. The mean injury severity score was 23.1 (+/-0.90), and the mean length of hospital stay was 28 days (+/-1.8). CONCLUSIONS: Motor vehicles crashes predominated (46%) as the cause of injury. The most frequently injured nerve was the radial nerve (58 injuries), and in the lower limb, the peroneal nerve was most commonly injured (39 injuries). Diagnosis of a peripheral nerve injury was made within 4 days of admission to Sunnybrook Health Science Centre in 78% of the cases. Surgery was required to treat 54% of patients. Head injuries were the most common associated injury, occurring in 60% of patients. Other common associated injuries included fractures and dislocations. The present report aims to aid in identification and treatment of peripheral nerve injuries.

Adolescent↗
PubMed1998

Cervical myelopathy caused by hypoplasia of the atlas: two case reports and review of the literature.

OBJECTIVE AND IMPORTANCE: Congenital anomalies of the posterior arch of the atlas (C1) are uncommon. They range from partial clefts to total agenesis of the posterior arch. Developmental cervical canal stenosis is a congenital anomaly that may cause cervical myelopathy. Myelopathy caused by cervical stenosis at the level of the atlas has been reported in only three cases. We present two cases of nontraumatic cervical myelopathy caused by spinal stenosis at the level of the atlas associated with a hypoplastic but complete posterior arch of C1. CLINICAL PRESENTATION: Two elderly Chinese men developed cervical myelopathy gradually during months to years, without preceding trauma. Imaging revealed a hypoplastic but complete posterior C1 arch associated with changes of spondylosis in both patients, producing severe spinal stenosis and spinal cord compression. Posterior decompression was achieved in both by the removal of the posterior arch of C1 with its surrounding thickened posterior ligaments. Symptoms and clinical findings improved in the two patients during the follow-up period. CONCLUSION: The anomaly presented in our two cases differs from the established classification of congenital abnormalities of the posterior arch of the atlas, suggesting a different embryological defect. The hypoplastic posterior C1 arch created a congenitally narrowed spinal canal in our patients, rendering the spinal cord more susceptible to compression related to degenerative changes of the spine. Surgical removal of the shortened posterior C1 arch and surrounding degenerative ligaments is an effective treatment for symptomatic patients with this condition.

Aged↗
PubMed1998

Management and results of sciatic nerve injuries: a 24-year experience.

OBJECT: The purpose of this retrospective clinical study was to present results and provide management guidelines for various types of sciatic injuries. METHODS: Over a 24-year period, 380 patients with sciatic nerve injuries were managed. In 230 patients (60%), the injury was at the buttock level, with injection injuries comprising more than half of these cases. Thigh-level sciatic injury was evaluated in 150 cases (40%) and was usually secondary to one of four main causes: 1) gunshot wound; 2) femur fracture; 3) laceration; or 4) contusion. Patients with partial deficits uncomplicated by severe pain or with significant spontaneous recovery or late referral were managed medically. Surgical exploration was not indicated in 23% of injuries at the thigh level and almost 50% of those at the buttock level. Most of these patients achieved partial but good spontaneous recovery, especially in the tibial division distribution. Surgical intervention was required for more complete and persistent deficits in either the tibial or peroneal distribution. Divisions of the sciatic nerve were split apart and evaluated independently. Management was guided by nerve action potential (NAP) recordings, which indicated whether neurolysis or resection of the lesion was required. Repair was then made by using sutures or more frequently by graft placement. In most cases in which neurolysis was performed because a positive NAP was recorded distal to the lesion, useful function was found in the peroneal distribution. Unfortunately, significant recovery occurred in only 36% of patients who received suture or graft repairs of the peroneal division. Good-to-excellent outcome was common for the tibial division, even in cases in which repair was proximal and required lengthy grafts. The relatively favorable recovery of tibial as opposed to peroneal divisions of the sciatic nerve occurred regardless of the level or mechanism of injury. CONCLUSIONS: Surgical exploration and, when necessary, repair of sciatic nerve injuries is worthwhile in selected cases.

Action Potentials↗
PubMed1998

End-Organ reinnervation does not prevent axonal degeneration in nerve allografts following immunosuppression withdrawal.

Previous work indicated that appropriate end-organ reinnervation fails to influence axonal degeneration in nerve allografts following immunosuppression withdrawal. In the present study, we examined if differences existed in axonal degeneration when axons regenerated across nerve allografts are allowed or completely denied end-organ reinnervation. Two ACI rat nerve allografts (3 cm long) were sutured into gaps created in both peroneal nerves in Lewis rats. In the right leg, the distal end of the graft was connected to the distal host nerve stump to allow end-organ reinnervation. In the left leg, the distal end was turned back and double ligated (unconnected) to prevent end-organ reinnervation. Rats received Cyclosporin A daily for 12 weeks to allow for regeneration and were sacrificed at 16 (n = 5) or 18 (n = 5) weeks following engraftment to assess axonal degeneration following immunosuppression withdrawal. Five Lewis rats receiving autografts served as control and were sacrificed at 12 weeks. Morphometric analysis was performed. In the control group (autografts) the cross-sectional area of and the number of myelinated fibres in the unconnected grafts was double that of the connected grafts, suggesting a sprouting effect. There was a tenfold reduction in the mean number of fibres at weeks 16 and 18 in the allografts compared to controls, without any significant differences in the connected versus unconnected sides. End-organ reinnervation decreases sprouting of axons within the graft but does not protect axons from degeneration following immunosuppression withdrawal.

Journal Article↗
PubMed1997

Motor and sensory specificity of host nerve axons influence nerve allograft rejection.

Previous studies have shown both survival and loss of regenerated host axons within nerve allograft segments after withdrawal of Cyclosporin A (CsA) immunosuppression. We hypothesized that the nature of end-organ reinnervation may influence the response of the axon, with survival of axons for appropriate innervation vs degeneration for inappropriate innervation. The rat femoral nerve model was chosen, as it has approximately equal sensory (S) and motor (M) divisions. Four ACI rat peroneal nerve allografts were sutured in straight (right leg: MM and SS) or switched (left leg; MS and SM) orientation in each femoral nerve transection gap in each Lewis rat recipient. Rats received CsA for 8 weeks to allow end-organ reinnervation, after which immunosuppression was discontinued. Rats were killed at various times thereafter, and underwent histologic and morphometric analysis of the graft segment axons. The regenerated axon population in the allograft reflected the nerve of origin: significantly more but smaller fibers when the proximal nerve was sensory and fewer but larger fibers when the proximal nerve was motor. After CsA withdrawal, there was a marked decrease of host axons as part of an ensuing rejection episode. The overall proportional decrease of axons was similar across all nerve orientation groups and, therefore, did not appear to be influenced by the nerve of origin or by the end-organ. However, the sensory proximal groups (SS and SM) contained more mature, noninjured fibers, while the motor proximal groups (MM and MS) contained significantly more degeneration and newly regenerating axons. We conclude that the motor or sensory nerve origin of the host axon, rather than the end-organ, influences axon survival after immunosuppression cessation. It is hypothesized that sensory axons may be more resilient while motor axons are selectively vulnerable to this second injury.

Animals↗
PubMed1997

Epidemiology of brachial plexus injuries in a multitrauma population.

OBJECTIVE: The purpose was to identify the prevalence, causative factors, injury types, and associated injury patterns in multitrauma patients who sustained brachial plexus injuries. METHODS: A retrospective review of a prospectively collected and computerized database and a chart review were performed. RESULTS: Brachial plexus injuries were identified in 54 of 4538 (1.2%) patients presenting to a regional trauma facility. Young male patients predominated. Motor vehicle accidents were the most frequent cause overall, but only 0.67% of such accidents resulted in plexus injuries. Conversely, 4.2% of motorcycle accident victims and 4.8% of snowmobile accident victims suffered brachial plexus injuries. Injuries were supraclavicular for 62% of patients and infraclavicular for 38%. Supraclavicular injuries were more likely to be severe (Sunderland Grade 3 or 4), compared with infraclavicular injuries, which were neurapraxic in 50% of cases (P < 0.01). The former therefore required surgical exploration and reconstruction more often (52 versus 17%; P < 0.05). Associated injuries included closed head injuries with loss of consciousness in 72% of patients (coma in 19%), cervical spine fractures in 13%, and clavicle, scapular, or humeral fractures and shoulder dislocations or sprains in 15 to 22%. Rib fractures were observed in 41% and were complicated by internal thoracic injuries in a similar percentage of cases. The injury severity score ranged from 5 to 59, with a mean of 24, and two patients died. CONCLUSION: Brachial plexus injuries afflict slightly more than 1% of multitrauma victims. Motorcycle and snowmobile accidents carry especially high risks, with the incidence of injury approaching 5%. Head injuries, thoracic injuries, and fractures and dislocations affecting the shoulder girdle and cervical spine are particularly common associated injuries. Supraclavicular injuries are more common, are of more severe grade, more often require surgery, and are associated with worse prognosis, compared with infraclavicular injuries.

Accidents, Traffic↗
PubMed1996

Cyclosporine A inhibits lymphocyte migration into ovine peripheral nerve allografts.

Lymphocyte migration into nerve allografts was measured to estimate the cyclosporine A (CsA) dose required to suppress rejection. Twelve outbred sheep received daily subcutaneous CsA at 0, 5, 10, or 15 mg/kg/day for 2 weeks prior to implantation of multiple heterotopic subcutaneous nerve grafts. Lymphocyte migration was determined after 7 days by an intravenous pulse of autologous 111indium-labeled lymphocytes and subsequent quantitation of gamma radioactivity in nerve tissue (CPM/g, mean +/- SEM). Measurement by radioimmunoassay revealed a dose-dependent increase in blood cyclosporine levels. Lymphocyte migration into autografts (404+/-44) was significantly less than migration into allografts (16,554+/-2,049), in control animals (P < 0.01). A dose-dependent inhibition of lymphocyte migration into nerve allografts was observed with counts of 7,662+/-1,692, 4,083+/-1,112, and 1,561+/-232 in sheep receiving 5, 10, or 15 mg/kg/day of CsA, respectively. Daily CsA administration produced effective blood levels and immunosuppression sufficient to inhibit lymphocyte migration into nerve allografts.

Animals↗
PubMed1995

Regeneration across preserved peripheral nerve grafts.

The potential to store nerve grafts for a prolonged period of time was assessed in a rat sciatic nerve model. Three-centimeter syngeneic nerve grafts were stored in Belzer/University of Wisconsin cold storage solution at different temperatures (5 degrees C, 22 degrees C, or 37 degrees C) for varying time periods (6 h, 24 h, or 3 weeks) prior to transplantation. Functional assessment using serial walking track analyses revealed no difference between storage times and temperatures. At 14 months postengraftment, the conduction velocities and the number of myelinated fibers that had regenerated across all grafts stored at 5 degrees C for all time periods tested were superior to grafts stored at either 22 degrees C or 37 degrees C. Nerve grafts stored for up to 3 weeks at 5 degrees C acted as effective conduits for proximal regenerating fibers and resulted in histologic, electrophysiologic, and functional results equivalent to fresh nerve grafts. Nerve graft storage may be applicable to nerve allografts and potentially provide allograft material that requires reduced or no associated host immunosuppression.

Action Potentials↗
PubMed1995

Delayed myelopathy after trivial neck injury in a patient with a cervical neurenteric cyst.

BACKGROUND: Neurenteric cysts are rare spinal lesions of congenital origin. They usually present insidiously with a long history of local spinal pain, radiculopathy and myelopathy. We report a 14-year-old male with a high cervical neurenteric cyst who developed a progressive myelopathy after minor neck trauma. Full recovery followed a partial cyst excision and decompressive procedure. SIGNIFICANCE AND CONCLUSION: The possible pathogenic mechanisms for this unusual presentation include hemorrhage into the cyst, sudden mechanical compression from abnormal spinal movement of a chronically distorted and compressed spinal cord, or an increase in the size of the cyst secondary to accumulation of cyst fluid. In this case a small increase in the cyst size may have resulted in increased mechanical distortion and spinal cord dysfunction on a compressive and ischemic basis.

Adolescent↗
PubMed1995

Evaluation and quality-of-life assessment of amlodipine and enalapril in patients with hypertension.

In this multicentre, double-blind trial in 461 patients with essential hypertension, amlodipine (5-10 mg once daily) and enalapril (10-40 mg once daily) were compared in terms of quality of life, efficacy and tolerability after 1 year of treatment (part 1). In part 2, 177 patients successfully treated with amlodipine in part 1 continued in an open evaluation of efficacy and safety of antihypertensive treatment with amlodipine for a further 2 years. In part 1, both drugs were similarly effective in lowering blood pressure (BP) (although significantly more enalapril patients required a diuretic) while maintaining quality of life. Apart from class-typical effects, such as oedema 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 because of drug-related adverse events, demonstrating that the tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. The BP reduction seen in the amlodipine patients after part 1 was maintained during part 2. Also, blood lipids and safety variables remained virtually constant. It is concluded that, at similar BP reduction, quality of life is equally well maintained on amlodipine and enalapril therapy. Thus, amlodipine compares favourably with enalapril as an effective and well-tolerated anti-hypertensive agent over the first year. Additionally, amlodipine patients evaluated over a 2-year extension maintained good BP control and the drug was well tolerated.

Adult↗
PubMed1994

The fate of Schwann cells in peripheral nerve allografts.

The phenotype of Schwann cells, whether of host or donor origin, in nerve allografts has been a source of debate. The origin of Schwann cells in peripheral nerve allografts under conditions of no, temporary or continuous immunosuppression was assessed by immunohistochemistry. We hypothesized that host-derived Schwann cells would replace rejected foreign donor Schwann cells after withdrawal of immunosuppression. A murine model of nerve transplantation to normal (wild-type) hosts from donor Shiverer mice, a mutant whose Schwann cells are deficient in myelin basic protein, was used and antibody reactivity against myelin basic protein was employed to ascertain the identity of Schwann cells in the nerve allograft. Without immunosuppression, donor Shiverer Schwann cells were rejected and the nerve graft morphology was restored by host-derived Schwann cells. With continuous immunosuppression, donor Shiverer Schwann cells persisted in the graft segment, associated with a chronic rejection phenomenon. The latter allowed migration of host-derived Schwann cells, over time, into the graft segment in approximately half the cases. After withdrawal of finite (6 weeks) immunosuppression, a rejection response eliminated donor Schwann cells. Replacement by host Schwann cells ensured as was hypothesized.

Animals↗
PubMed1994

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

The efficacy, tolerability and impact on quality of life of amlodipine and enalapril were compared in a multicentre, double-blind, general practice study in 461 mild and moderate hypertensives over a 50-week active treatment period. Amlodipine (5-10 mg, once daily) and enalapril (10-40 mg, once daily) were found to be similarly effective in lowering blood pressure while not adversely affecting quality-of-life parameters. However, 20% of the enalapril group compared with 11% of the amlodipine group required the addition of hydrochlorothiazide for blood pressure control (P < 0.01). Diastolic blood pressure was normalised or reduced by 10 mmHg in 204 (90%) patients on amlodipine and in 190 (85%) patients on enalapril. Side-effects were, in general, mild or of little clinical significance. The major side-effects recorded were class-typical of ACE inhibitors and calcium antagonists, namely cough (enalapril) and oedema (amlodipine), respectively. Tolerability was very good, with only 17 patients (8 amlodipine, 4%; 9 enalapril, 4%) being withdrawn from the study due to side-effects definitely related to treatment. Amlodipine monotherapy produced a slightly beneficial effect on blood lipid concentration, and both drugs reduced the calculated 10-year risk of coronary heart disease. It was concluded that the calcium antagonist amlodipine compared favourably with the ACE inhibitor enalapril in terms of antihypertensive efficacy, tolerability and impact on quality of life.

Adult↗
PubMed1993

[Does antihypertensive treatment with amlodipine or enalapril affect quality of life? A multicenter study in general practice].

In this multicentre trial in general practice the effect of one year of therapy with amlodipine or enalapril on quality of life and blood pressure was studied in 461 hypertensive patients. Quality of life was evaluated by means of a questionnaire administered on five occasions during the study. A total of 125 questions were distributed between psychological general well-being, own perception of health, social relations, sexual and cognitive functioning, and a combined index for frequency and intensity of symptoms. Both drugs were equally effective in reducing blood pressure, from 162/106 to 142/91 mm Hg, and had the same effect on quality of life. Neither of the drugs reduced quality of life, and in some of the variables a slight improvement (2-5%) was observed. The two compounds were tolerated equally well. Apart from class-typical effects (coughing for enalapril and edema for amlodipine) no clinically significant side effects were experienced.

Adult↗
PubMed1993

Walking track analysis: utilization of individual footprint parameters.

Functional assessment of rat sciatic, tibial, and peroneal nerve injuries was performed using walking track analysis. Individual walking print length (PL), toe spread (TS), and intermediate toe spread (ITS) values were measured up to 24 weeks after specific nerve transection, with or without repair. Sciatic and tibial nerve manipulation initially affected all footprint measurements, consistent with loss of intrinsic and extrinsic motor function. After sciatic repair, TS demonstrated partial recovery without any substantial recovery in PL or ITS, compared with sciatic transection values. By contrast, after tibial repair, PL values recovered dramatically, between 16 and 24 weeks, to levels not significantly different from control subjects. This was not observed after tibial transection without repair. TS recovered partially, whereas ITS recovered to control levels by 20 weeks after tibial repair. Peroneal transection resulted in multiple contractures, rendering this group unmeasurable at 4 weeks. After peroneal repair, only the PL reflected significant loss of function at 2 weeks, recovering to control values by 8 weeks. Manual TS measurements in nonwalking rats did not reflect functional nerve regeneration. Thus, individual PL measurements alone can be used to characterize functional recovery after tibial and peroneal nerve injury, whereas TS reflected recovery after sciatic nerve injury.

Animals↗
PubMed1993

Double-blind, parallel, comparative study on quality of life during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicentre study.

OBJECTIVE: To compare tolerance, antihypertensive efficacy and impact on quality of life of amlodipine and enalapril in patients with mild or moderate hypertension. DESIGN: Multicentre, double-blind, double-dummy, comparative trial in general practice. Three phases were conducted: 4 weeks on placebo, 12 weeks of dose adjustment (amlodipine or enalapril) and a 38-week maintenance period. PATIENTS: Four hundred and sixty-one patients of both sexes were enrolled; 451 were available for efficacy evaluation at the end of the trial. TREATMENT: The patients were allocated to either amlodipine (231) or enalapril (230) treatment. If at the end of dose adjustment (amlodipine 5-10 mg/day, enalapril 10-40 mg/day) diastolic blood pressure was > or = 95 mmHg, hydrochlorothiazide (25-50 mg/day) was added (27 amlodipine patients and 45 enalapril patients). MAIN OUTCOME MEASURES: Blood pressure changes after 1 year of treatment; between- and within-group changes in quality of life as assessed by psychological general well-being, social and sexual functioning, health-risk perception, alertness, behaviour, and impact of symptom and side effects. RESULTS: Indices on quality of life were unchanged or increased (2-9%) in both groups. Blood pressure was normalized or reduced by > or = 10 mmHg in 204 (90%) and 190 (85%) patients on amlodipine and enalapril, respectively. Cough was the most frequently reported adverse event in the enalapril group (13%) and oedema in the amlodipine group (22%). Only eight (4%) patients on amlodipine and nine (4%) on enalapril were withdrawn because of drug-related adverse events. CONCLUSION: At similar blood pressure reduction in mild and moderate hypertension, quality of life is equally well maintained on amlodipine and enalapril therapy.

Adaptation, Psychological↗
PubMed1993

Effect of cold preservation on lymphocyte migration into peripheral nerve allografts in sheep.

Lymphocyte migration into fresh and preserved peripheral nerve allografts was quantitated to assess the effect of cold preservation and freeze-thawing pretreatment on the local immunological response to nerve allografts. Out-bred ewes received multiple 1.5-cm subcutaneous heterotopic peroneal nerve autografts, fresh allografts, and pretreated allografts, implanted within the same recipient. Lymphocyte migration was studied at 7 days by injecting autologous 111indium-labeled lymphocytes intravenously. After 3 hr of recirculation, lymphocyte migration into graft tissue was quantitated by a gamma counter (epm/g, mean +/- SEM). Lymphocyte traffic into fresh nerve allografts (21,623 +/- 3783) increased an average 9.4-fold over the autograft value (2918 +/- 377, P < 0.04). Histologic studies illustrated a marked lymphocytic infiltrate of CD4+ and CD8+ cells and enhanced class I and II MHC expression in fresh allografts, but not in autografts. Short-term cold preservation, for 6 and 12 hr (5 degrees C), enhanced lymphocyte entry into pretreated allograft tissue. Conversely, cold preservation for longer periods (1 and 3 weeks) dramatically reduced lymphocyte migration to values below corresponding autograft levels (783 +/- 100 and 1,252 +/- 120, respectively, P < 0.01). A comparable reduction in lymphocyte migration into nerve allografts was observed after freeze-thawing pretreatment (P < 0.01). Cold preservation of donor allogeneic lymphocytes inhibited their capacity to induce intradermal host lymphocyte migration, implicating passenger lymphocytes as a potential cold-sensitive allogeneic component of the nerve allograft. Assessment of the local response to ovine peripheral nerve allografts, utilizing radiolabeled autologous lymphocytes, demonstrated that cold preservation and freeze-thawing pretreatment significantly reduced lymphocyte migration into nerve allografts. The mechanism(s) of reduced lymphocyte migration may involve inactivation or death of antigen-presenting cells, including passenger lymphocytes.

Animals↗