Biomedical subjects

R Midha

Publications and source records attributed to R Midha.

At least 19 recordsLinked to original sources

PubMed2006

Undiagnosed dysglycaemia and inflammation in cardiovascular disease.

BACKGROUND: Cardiovascular (CV) disease is associated with increased levels of glucose, but the prevalence of dysglycaemia in CV diseases is not fully known. The study examined the prevalence of unknown dysglycaemia and its association with inflammation in Caucasian patients with ischaemic vascular complications, i.e. coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). MATERIALS AND METHODS: This case-controlled study involved 149 patients (mean age 68 years) hospitalized for CAD, PAD or CVD and 59 control-subjects (CTR) free from CV-disease. The prevalence of dysglycaemia according to WHO/ADA criteria (impaired fasting glycaemia, impaired glucose tolerance or diabetes mellitus) was assessed by a 75-g oral glucose tolerance test. Inflammatory parameters were analyzed in fasting samples. RESULTS: Dysglycaemia was found in 49%, 55% and 57% of patients with CAD, CVD and PAD, respectively; all were significantly higher than among the controls (29%). The odds ratio (95% CI) for being dysglycaemic were 1.7 (1.04-2.77), 1.9 (1.19-3.06) and 2.0 (1.25-3.19) for CAD, CVD and PAD, respectively. Inflammatory markers (the total leucocyte count, soluble tumour necrosis factor-receptor type I, C-reactive protein) were elevated in patient groups and tended to increase with increasing blood glucose levels in all groups. The levels of the anti-inflammatory cytokine transforming growth factor-beta1 and insulin-like growth factor binding protein 3 were lowered in patients with CAD and, in patients with PAD, the former was inversely related to the levels of the blood glucose. CONCLUSIONS: Undiagnosed dysglycaemia was common in patients with ischaemic CV manifestations regardless of vascular bed involved. Inflammation was associated in a dosage-related manner to glucose levels.

Adult↗

PubMed2003

Lymphatic cerebrospinal fluid absorption pathways in neonatal sheep revealed by subarachnoid injection of Microfil.

There is mounting evidence that a significant portion of cerebrospinal fluid drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. To characterize these pathways further, yellow Microfil was infused into the cisterna magna of 2-7-day-old lambs post mortem to perfuse either the cranial or spinal subarachnoid compartments. In some animals, blue Microfil was perfused into the carotid arteries simultaneously. Microfil was observed in lymphatic networks in the nasal mucosa, covering the hard and soft palate, conchae, nasal septum, the ethmoid labyrinth and the lateral walls of the nasal cavity. Many of these lymphatics drained into vessels located on the lateroposterior wall of the nasopharynx and from this location drained to the retropharyngeal lymph nodes. Additionally, lymphatics containing Microfil penetrated the lateral wall of the nasal cavity and joined with superficial lymphatic ducts travelling towards the submandibular and preauricular lymph nodes. In two cases, lymphatic vessels were observed anastomosing with deep veins in the retropharyngeal area. Microfil was also distributed within the nerve trunks of cranial and spinal nerves. The contrast agent was located in longitudinal channels within the endoneurial space and lymphatics containing Microfil were observed emerging from the mesoneurium. In summary, Microfil distribution patterns in neonatal lambs illustrated the important role that cranial and spinal nerves play in linking the subarachnoid compartment with extracranial lymphatics.

Absorption↗

PubMed2001

MR properties of rat sciatic nerve following trauma.

T(1) and T(2) relaxation times, magnetization transfer (MT), and diffusion anisotropy of rat sciatic nerve were measured at different time intervals following trauma. The nerve injury was induced by either cutting (irreversible nerve degeneration) or crushing (degeneration followed by regeneration). The MR properties were measured for proximal and distal portions of the injured nerve. The portions of the nerve proximal to the induced injury exhibited MR characteristics similar to those of normal nerves, whereas the distal portions showed significant differences in all MR parameters. These differences diminished in the regenerating nerves within approximately 4 weeks post injury. In the case of irreversible nerve damage, the differences in the distal nerves were slightly larger and did not resolve even 6 weeks after induced trauma. The MR measurements were correlated with histopathology exams. Observed changes in tissue microstructure, such as demyelination, inflammation, and axonal loss, can result in a significant increase in the average T(1) and T(2) relaxation times, reduction in the MT effect, and decrease in diffusion anisotropy. MR parameters, therefore, are very good indicators of nerve damage and may be useful in monitoring therapies that assist nerve regeneration. Magn Reson Med 45:415-420, 2001.

Animals↗

PubMed2001

Prospective analysis of relationships of outcome measures for ulnar neuropathy at the elbow.

BACKGROUND: We undertook a prospective study to investigate relationships between outcome measures of ulnar neuropathy at the elbow. METHODS: Thirty-one patients (mean age 52.6, range 20-80), with clinically and electrically verified ulnar neuropathy at the elbow, were seen independently by a neurosurgeon and a physiotherapist. All tests were administered to all patients on each visit. Data collected included measures of sensory (monofilament, two-point discrimination, vibration) and motor function (grip, key-pinch, muscle atrophy), pain (visual analogue scale (VAS)) and impact on lifestyle (Levine's questionnaires (function status score--FSS, symptom severity score--SSS)), disability of the arm, shoulder and hand module (DASH) and patient-specific measures (PSM). Parametric and non-parametric correlation and factor analysis were done. RESULTS: Outcome analysis was available for 63 patient visits, with follow-up obtained for 20 patients (mean 8.5 months). Lifestyle and pain instruments (FSS, SSS, DASH, PSM and VAS) all correlated well with each other (r > 0.6, p < .01). DASH was moderately to highly correlated to nine of the 11 measures. Some tests correlated poorly, for example, Semmes-Weinstein monofilament with other sensory measures and muscle atrophy with almost all measures. Factor analysis revealed that there are two principal factors, accounting for 77% of the variance. Factor 1 relates to impact on lifestyle and pain while Factor 2 relates to strength and function. DISCUSSION/CONCLUSIONS: Intraclass measures, particularly ones assessing lifestyle and pain instruments are strongly correlated. Factor analysis revealed two principal factors that account for the majority of the variance; future studies with a larger sample size are needed to validate this analysis.

Adult↗

PubMed2001

Subacute femoral compressive neuropathy from iliacus compartment hematoma.

BACKGROUND: Traumatic retroperitoneal hematoma in the iliacus muscle is an unusual but potentially serious cause of femoral compression neuropathy. CASE REPORT: We describe the clinical, imaging, and management features of a case of traumatic iliacus retroperitoneal hematoma with delayed manifestation of femoral neuropathy. DISCUSSION: The anatomical substrate for hematoma formation with subacute compression of the femoral nerve is emphasized. A subacute compartment syndrome with progressive edema, swelling and ischemia of iliacus compartment is suggested as the underlying cause. Early fasciotomy with or without hematoma evacuation should be considered in order to provide rapid decompression and to minimize the chance of permanent nerve injury.

Adolescent↗

PubMed2001

Epithelioid hemangioendothelioma of the spine presenting as cervical myelopathy: case report.

OBJECTIVE AND IMPORTANCE: We report the first case in the literature of cervical myelopathy caused by progressive cord compression as a result of epithelioid hemangioendothelioma of the cervical vertebra. CLINICAL PRESENTATION: A 58-year-old man presented with progressive cervical myelopathy. Imaging revealed a vascular, expansile lesion of contiguous cervical vertebrae causing cord compression. The surgical pathology revealed epithelioid hemangioendothelioma, a rare tumor not previously reported to present in such a fashion. INTERVENTION: Preoperative embolization and a two-stage anterior and posterior surgical decompression and fusion procedure were performed. The high vascularity of this lesion makes surgery a formidable surgical challenge. Adjuvant radiotherapy was administered to the residual tumor because of its potential for low-grade malignancy. CONCLUSION: The diagnosis relied on accurate histopathological assessment. The general principles of achieving cord decompression and tumor control are important. The literature on epithelioid hemangioendothelioma involving the spine is reviewed, and the tumor biology and the role of adjuvant therapy are discussed.

Angiography, Digital Subtraction↗

PubMed2001

Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics.

Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur through the cribriform plate into the nasal submucosa, where it is absorbed by cervical lymphatics. We tested the hypothesis that sealing the cribriform plate extracranially would impair the ability of the CSF pressure-regulating systems to compensate for volume infusions. Sheep were challenged with constant flow or constant pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of the cribriform plate was sealed. With both infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships were shifted significantly to the left when the cribriform plate was blocked. This indicated that obstruction of the cribriform plate reduced CSF clearance. Sham surgical procedures had no significant effects. Estimates of the proportional flow through cribriform and noncribriform routes suggested that cranial CSF absorption occurred primarily through the cribriform plate at low ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways) appeared to be recruited only when intracranial pressures were elevated. These data challenge the conventional view that CSF is absorbed principally via arachnoid villi and provide further support for the existence of several anatomically distinct cranial CSF transport pathways.

Animals↗

PubMed2001

Comparison of cerebrospinal fluid transport in fetal and adult sheep.

We quantified cerebrospinal fluid (CSF) transport (conductance) and CSF outflow resistance in late-gestation fetal and adult sheep using two methods, a constant pressure infusion method and a bolus injection technique into the lateral ventricles. No significant differences in CSF conductance (fetus 0.013 +/- 0.002, adult 0.014 +/- 0.003 ml x min(-1) x cm H(2)O(-1)) or CSF outflow resistance (fetus 83.7 +/- 9.8, adult 84.7 +/- 19.7 cm H(2)O x ml(-1) x min) were observed. To confirm CSF transport to plasma in fetal animals, (125)I- or (131)I-labeled human serum albumin (HSA) was injected into the lateral ventricles. The tracer entered fetal plasma with an average mass transport rate of 1.91 +/- 0.47% injected/h (n = 9). In two fetuses, we monitored the tracer appearance in plasma and cervical and thoracic duct lymph after injection of radioactive HSA into the ventricular CSF. As was the case in adult animals, fetal tracer concentrations increased in all three compartments over time, with the highest concentrations measured in lymph collected from the cervical lymphatics. These results 1) indicate that global CSF transport parameters in the late-gestation fetus and adult sheep are similar and 2) suggest an important role for extracranial lymphatic vessels in CSF transport before birth.

Animals↗

PubMed2001

Differential response of sensory and motor axons in nerve allografts after withdrawal of immunosuppressive therapy.

OBJECT: Rejection of nerve allografts and loss of regenerated host axons after withdrawal of immunosuppressive therapy poses an ongoing challenge in peripheral nerve repair. The present report is of a blinded prospective controlled study in which an established rat model of nerve allotransplantation is used to examine the effect of fiber type on survival and degeneration of nerve allografts after discontinuation of immunosuppression. The authors hypothesized that sensory axons will selectively resist a rejection response, whereas motor axons will degenerate. METHODS: Four-centimeter nerve segments from ACI rats were grafted into peroneal and sural (mixed) or saphenous (sensory) nerve gaps in Lewis rats. In some rats, L4-6 dorsal root ganglia were ablated before grafting, creating pure motor sural and peroneal nerves. All rats received 12 weeks of immunosuppressive therapy to support nerve regeneration into allografts. Immunosuppression with cyclosporin was then withdrawn. At planned death (12-18 weeks postsurgery), graft tissue was subjected to histomorphometric analysis for evaluation of axon survival and loss. Graft rejection led to loss of all axons in approximately 60% of the allograft segments. The mixed nerve group was most prone to complete rejection, with significantly lowered axon counts at Weeks 16 and 18 compared with the Week 12 baseline. Axons from the sensory nerve were least likely to degenerate. The pure motor nerve group axons demonstrated intermediate sensitivity, with a selective loss of larger axons at Week 16 and a significant decrease in axon counts from the Week 12 baseline at Week 18. CONCLUSIONS: Whereas the majority of axons are lost after withdrawal of immunosuppressive therapy from nerve allografts, there is a selective survival of axons from cutaneous sensory nerves and smaller-diameter motor fibers. The biological and molecular mechanisms that make some axons impervious to injury remain to be determined.

Animals↗

PubMed2000

Split cord malformation with diastematomyelia presenting as neurogenic claudication in an adult: a case report.

STUDY DESIGN: This is a report of a rare presentation of a split cord malformation with diastometamyelia. OBJECTIVES: This report draws attention to the fact that the only manifestation of diastmetamyelia in the adult patient may be neurogenic claudication. SUMMARY OF BACKGROUND DATA: Patients with split cord malformations and diastometamyelia rarely have symptomatic onset in adulthood. When present, a traumatic event leading to an acute neurologic change is the usual presentation. METHODS: An adult patient presented with symptoms of neurogenic claudication in the left leg. Magnetic resonance imaging examination showed a split cord malformation and diastometamylia at L3-L4 with spinal stenosis of the left hemicord. Decompressive laminectomy and subtotal resection of the bony spur were performed. RESULTS: Two years after decompression, the patient has complete resolution of his leg symptoms and is back to work. CONCLUSIONS: Neurogenic claudication without any objective neurologic deficit or neurocutaneous stigmas of an underlying spinal cord abnormality may be the only presentation in the adult with diastometamyelia. Decompression to relieve both clinical and radiologic evidence of spinal stenosis obtained excellent outcome.

Adult↗

PubMed2000

Detection of host and donor cells in sex-mismatched rat nerve allografts using RT-PCR for a Y chromosome (H-Y) marker.

The donor and host source of support cells, such as Schwann cells, in nerve allograft segments have been the subject of debate. The objective of the present study was to assess the utility of a molecular technique that probes for a Y chromosome expressed gene (H-Y) in distinguishing host from donor tissue in sex-mismatched nerve allograft segments. Forty-two Lewis rats received bilateral syngeneic Lewis or allogeneic ACI rat peroneal nerve grafts, with or without cyclosporin A (CsA) treatment. At different times thereafter animals were sacrificed and samples were harvested. We transplanted males and females reciprocally, to study both survival of donor cells (persisting H-Y mRNA in male grafts by transcription polymerase chain reaction (RT-PCR), and graft infiltration by host cells (detectable H-Y mRNA in female grafts). A kinetic analysis revealed a progressive loss of viable donor cells (loss of H-Y mRNA signal) from allografts, beginning 2-3 weeks, and culminating at 4 weeks, with little detectable H-Y in the absence of CsA treatment. CsA treatment led to prolonged survival of allograft cells, confirmed by detectable H-Y mRNA. By studying female grafts in male rats we could confirm that loss of viable donor tissue in allografts was accompanied by infiltration of host (H-Y mRNA positive) cells, whereas no H-Y mRNA signal was seen in males receiving autografts from females or in immunosuppressed allograft segments. These data suggest that reverse RT-PCR analysis for a Y chromosome gene product can be a valuable tool to assess the origin of viable cells in sex-mismatched nerve allotransplantation tissue.

Animals↗

PubMed2000

Long nerve allografts in sheep with Cyclosporin A immunosuppression.

Rodent studies of nerve allografts are limited by a relatively short length of graft segment. The authors attempted to establish an outbred sheep model that would allow the study of longer, more clinically relevant nerve gaps. Using outbred ewes, two 8-cm long radial sensory nerves were grafted into gaps (5 cm) in the median nerve. Sheep received an autograft and an allograft. Four sheep were immunosuppressed with Cyclosporin A (CsA) and four were controls. Blood CsA levels greater than 1000 microg/L were obtained. Systemic immunosuppression resulted in severe opportunistic infections, and the sheep were sacrificed between 35 and 47 days following surgery. Histologically, in the autografts and CsA-treated allografts, evidence of nerve regeneration was seen. Non-immunosuppressed allografts were clearly rejected. While clear differences in the histology of experimental and control grafted nerve tissues were seen, the sheep allograft model presents considerable challenges due to immunosuppression-related infectious complications.

Animals↗

PubMed2000

Axillary nerve injuries in children.

Isolated axillary nerve injury is uncommon, particularly in children. The motor deficit of shoulder abduction may not recover spontaneously and can be a substantial handicap. Detection may be difficult initially, as the injury is masked by trauma such as head injury, and concomitant shoulder injury requiring immobilization. After mobilization, patients learn to partially compensate by using alternate muscles. There are few reports of surgical management of this nerve injury. Most concern predominantly adults, and the results are mixed with on average slightly greater than half having a good recovery (defined as grade 4-5 Medical Research Council muscle power). We present our experience with 4 pediatric patients who had axillary nerve injury. Three patients had an interposition nerve graft, and 1 patient underwent neurolysis. All patients recovered to grade 4-5 deltoid muscle power. Children with an axillary nerve injury which fails to recover spontaneously by 4-6 months should strongly be considered for surgical exploration.

Adolescent↗

PubMed2000

Peripheral nerve repair and grafting techniques: a review.

In this review, various conventional nerve repair techniques including direct epineurial repair, grouped fascicular repair, fascicular repair, and nerve grafting are described. The indications for use, as well as the relative advantage and disadvantage, of each technique are discussed. The experimental and clinical evidence from a review of the pertinent literature does not demonstrate a significant difference in outcome of one method over the others. Surgical decisions should be made by a thorough evaluation of all aspects of the nerve injury and surgical methods. All nerve injuries cannot be repaired using only one type of nerve repair method. The surgeon should be familiar with all the techniques described and be prepared to use them under appropriate circumstances.

Humans↗

PubMed1999

Regeneration across cold preserved peripheral nerve allografts.

The feasibility of peripheral nerve allograft pretreatment utilizing cold storage (5 degrees C in the University of Wisconsin Cold Storage Solution) or freeze-thawing to prevent rejection was investigated. Regeneration across cold-stored (3 or 5 weeks) or freeze-thawed (FT), 3.0-cm sciatic nerve allografts were compared to fresh auto- and allografts in an inbred rat model. At 16-week post-engraftment, only FT allografts appeared similar to autografts on gross inspection; FT grafts were neither shrunken nor adherent to the surrounding tissue as seen in the other allograft groups. Qualitatively, the pattern of regeneration in the graft segments of the fresh allograft and to a lesser extent of pretreated allografts was inferior to that of autografts as evidenced by a disruption in the perineurium, more extrafascicular axons, smaller and fewer myelinated axons, increased intrafascicular collagen deposition, and the persistence of perineurial cell compartmentation and perivascular infiltrates. Distal to these grafts, the regeneration became more homogenous between groups, although areas of ongoing Wallerian degeneration, new regeneration as well as compartmentation, were more prevalent in fresh and pretreated allografts. Although the number of myelinated fibres was equivalent to autografts, the fibre diameters, the number of large diameter fibres, and the G-ratio were significantly decreased in the allograft groups, which, in part, accounted for the significant decrease in conduction velocity in the 3-week stored and fresh allograft, and the slight decrease in the 5-week stored and FT allograft groups. There was a small return in the Sciatic Function Index towards normal, but no consistent differences between groups were found. Prolonged cold storage and freeze-thawing of nerve allografts resulted in regeneration that was better than fresh allografts, but inferior to autografts. With the concomitant use of host immunosuppression or other immunotherapies, these storage techniques can provide a means of transporting nerve allografts between medical centres and for converting urgent into elective procedures.

Action Potentials↗

PubMed1999

Peripheral nerve revascularization: histomorphometric study of small- and large-caliber grafts.

The revascularization of nerve grafts was investigated using histologic and morphometric techniques. Small-diameter nerve grafts (sciatic in the rat and sural in adult ewes) were studied, as was a large-diameter peroneal nerve graft in the ewe. Ninety-six hours after sciatic nerve engraftment, rats were injected with an intravascular fluorescent tracer. Evans blue albumin (EBA). Specimens were observed for the number of vessels perfused. Analysis showed no difference in vascular pattern between the grafted nerves and their control nerves, suggesting that spontaneous revascularization had occurred to establish a vascular tree essentially identical to the native nerve. Sural and peroneal nerve grafts were evaluated in adult ewes at 7 or 40 days post-nerve grafting. Similar to the rat sciatic nerve, the small-diameter sural nerve grafts were completely revascularized, with an equal number of perfused vessels at both time periods, with respect to control specimens. In contrast, the larger-caliber peroneal nerve grafts were not perfused at 7 days, and very poorly perfused at 40 days. This correlated with scant neural regeneration at 40 days. The finding suggests that small-diameter nerve grafts spontaneously revascularize, and revascularization using microvascular techniques is not necessary. In contrast, the larger-diameter nerve graft did not revascularize well. Such a large-diameter nerve graft would provide a suitable model to investigate the potential merits of a vascularized nerve graft.

Animals↗

PubMed1999

Revascularization of peripheral nerve autografts and allografts.

The timing and mechanisms of peripheral nerve revascularization were investigated using a 2-cm sciatic nerve graft model in 58 rats. Epineurial perfusion was consistently established by 48 hours and endoneurial perfusion by 72 hours. The pattern of endoneurial perfusion was "all-or-none"--either all or none of the vessels in a fascicle exhibited blood flow. Conventional allografts exhibited similar revascularization dynamics and patterns. Capping the ends of the autograft with Silastic significantly delayed revascularization; no flow was observed at 4 days, and only a peripheral rim of perfused fascicular vessels was observed at 7 days. These patterns suggested that the primary method of revascularization in the conventional graft was longitudinal inosculation; no evidence of peripheral neovascularization or dependence on the graft bed as a source of revascularization was observed. The introduction of a major histocompatibility complex barrier between the grafted tissue and the recipient animal did not alter the timing or the mechanics of blood flow reestablishment.

Animals↗

PubMed1998

Lack of association between outcome measures of nerve regeneration.

Studies of nerve regeneration in rodents utilize at least one of three classes of outcome measures: electrophysiology, morphometry, and functional tests. The assumption that these measures are correlated was tested utilizing a data set of 16 variables. Significant correlations (Spearman's rho, P < or = 0.05) were found within variable classes; however, none were found between classes. The three commonly utilized outcome measures do not measure the same phenomenon but rather discrete aspects of nerve regeneration.

Animals↗