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Biomedical subjects

V Chaudhry

Publications and source records attributed to V Chaudhry.

At least 19 recordsLinked to original sources
PubMed1998

Electrophysiological studies in the Guillain-Barré syndrome: distinguishing subtypes by published criteria.

Guillain-Barré syndrome (GBS) is recognized clinically by the presence of acute, rapidly progressive weakness, areflexia, and albuminocytological dissociation in cerebrospinal fluid. Although GBS was initially considered to be primarily an acute inflammatory demyelinating polyneuropathy (AIDP), several other subtypes have been recognized: acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN), and Fisher syndrome (FS). Because each of these subtypes may have an independent immunopathogenesis and, therefore, may require selective treatments in the future, recognition of these subtypes is important. When using nerve conductions to classify the subtypes, the most easily and confidently identified subtype is AIDP. Therefore, most electrodiagnostic criteria have attempted to identify demyelination in this acute setting, in which physiology is constantly changing. In a single well-defined GBS population, we compared the various published criteria for demyelination in GBS. We reviewed charts of 43 patients with GBS between 1991 and 1996. Applying six available criteria sets, the number of patients categorized as having AIDP ranged from 21% to 72%. Until investigators can agree on a single set of criteria, considerable variability will continue to exist when identifying cases of AIDP.

Adolescent↗
PubMed1998

Multifocal motor neuropathy.

Multifocal motor demyelinating neuropathy is an acquired immune-mediated neuropathy with distinctive clinical and electrophysiologic manifestations, and response to treatment. Clinically, it is characterized by slowly progressive asymmetrical predominantly distal weakness; unilateral wrist drop, grip weakness, and foot drop are the commonest initial manifestations. Electrophysiologic testing reveals multifocal motor demyelinating features. Persistent, localized, partial motor conduction block is the hallmark of the disorder. Results of sensory nerve conduction studies are generally normal, consistent with the lack of sensory symptoms and signs. Most patients show marked improvement in strength after treatment with intravenous human immunoglobulin or cyclophosphamide. The pathogenesis of the disease is not completely understood. An autoimmune pathogenesis is considered likely based on the beneficial response to immunomodulatory treatment and the presence of serum anti-GM1 ganglioside antibodies in affected patients.

Adult↗
PubMed1998

Colonoscopy: the initial test for acute lower gastrointestinal bleeding.

Despite literature showing safety, accuracy, and therapeutic capability of emergency colonoscopy for acute lower gastrointestinal (LGI) bleeding, surgical literature suggests that this examination is difficult to perform in the acute setting. In contrast to currently accepted protocols, we believe that unprepared colonoscopy within 24 hours of presentation can be performed safely with a high rate of success in localizing and often treating the specific cause of LGI bleeding. We report results over a 7-year period in our institution using early colonoscopy as the primary investigative method for the diagnosis and treatment of LGI bleeding. We analyzed 85 consecutive patients suspected of LGI bleeding referred to the surgical service between 1989 and 1996. LGI bleeding was defined as the passage of blood per rectum, distal to the ligament if Trietz. We excluded patients who were only hemoccult positive or had an upper gastrointestinal source by nasogastric aspirate or upper gastrointestinal endoscopy. All patients underwent urgent unprepped colonoscopy by surgical endoscopists relying on the cathartic effect of blood and liberal suction/irrigation to cleanse the colon. Therapeutic maneuvers included Nd:YAG laser or BICAP coagulation. Studies in which active bleeding was found or lesions with endoscopic evidence of recent hemorrhage were considered positive. A total of 126 colonoscopies were performed in 85 patients, 44 males and 41 females, with a median age of 75 years (range, 12-91 years). Fifty-three patients (62%) had hematocrit drops of greater than 5 per cent. Thirty-four patients were transfused an average of 4.5 units of blood per patient. The source of bleeding was correctly identified in 82 of 85 (97%) patients. Ninety-one per cent of sources were colonic, and 9 per cent were small bowel. Fecal residue prevented initial adequate examination in only two patients. Diverticulosis (20%), ischemic colitis (18%), hemorrhoids (14%), and arteriovenous malformations (11%) were the predominant sources of bleeding. Spontaneous cessation of bleeding occurred in 58 (68%) patients. Control of active hemorrhage was achieved endoscopically in 17 of 27 acutely bleeding patients. Significant therapeutic interventions were performed in 26 additional patients, including fulgration, polypectomy, relief of obstruction, and removal of foreign body. One patient with asymptomatic free air was observed nonoperatively, for a complication rate of 0.8 per cent. In-hospital mortality was 3.5 per cent (three patients), all secondary to multisystem organ failure and underlying disease. In-hospital rebleeding rate was 3.5 per cent (three). We conclude that, using colonoscopy, it is possible to identify the source of acute LGI bleeding in more than 95 per cent of cases. Diagnostic and therapeutic capability with colonoscopic intervention to control active hemorrhage is especially appealing. Additionally, the pattern, amount, and location of blood in the unprepared colon all give clues as to source and rate of bleeding. In experienced hands, morbidity and mortality of emergent colonoscopy is very low. High accuracy, safety, and therapeutic capability makes colonoscopy the initial diagnostic test of choice for acute LGI hemorrhage.

Acute Disease↗
PubMed1997

Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: absence of structural mutations in five patients with Brody disease.

Sarcolipin (SLN) is a low-molecular-weight protein that copurifies with the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase (SERCA1). Genomic DNA and cDNA encoding human sarcolipin (SLN) were isolated and characterized and the SLN gene was mapped to chromosome 11q22-q23. Human, rabbit, and mouse cDNAs encode a protein of 31 amino acids. Homology of SLN with phospholamban (PLN) suggests that the first 7 hydrophilic amino acids are cytoplasmic, the next 19 hydrophobic amino acids form a single transmembrane helix, and the last 5 hydrophilic amino acids are lumenal. The cytoplasmic and transmembrane sequences are not well conserved among the three species, but the lumenal sequence is highly conserved. Like SERCA1, SLN is highly expressed in rabbit fast-twitch skeletal muscle, but it is expressed to a lower extent in slow-twitch muscle and to an even lower extent in cardiac muscle, where SERCA2a and PLN are highly expressed. It is expressed in only trace amounts in pancreas and prostate. SLN and PLN genes resemble each other in having two small exons, with their entire coding sequences lying in exon 2 and a large intron separating the two segments. Brody disease is an inherited disorder of skeletal muscle function, characterized by exercise-induced impairment of muscle relaxation. Mutations in the ATP2A1 gene encoding SERCA1 have been associated with the autosomal recessive inheritance of Brody disease in three families, but not with autosomal dominant inheritance of the disease. A search for mutations in the SLN gene in five Brody families, four of which were not linked to ATP2A1, did not reveal any alterations in coding, splice junction or promoter sequences. The homozygous deletion of C438 in the coding sequence of ATP2A1 in Brody disease family 3, leading to a frameshift and truncation following Pro147 in SERCA1, is the fourth ATP2A1 mutation to be associated with autosomal recessive Brody disease.

Amino Acid Sequence↗
PubMed1997

Entrapment of motor nerves in motor neuron disease: does double crush occur?

OBJECTIVE: To investigate whether "diseased nerves" are more prone to entrapment neuropathy than normal nerves. Nerve conduction studies of human neuropathies have shown that electrophysiological abnormalities are often most prominent at potential sites of nerve entrapment, and entrapments are more common in patients with radiculopathies--a concept designated as "double crush". As entrapment neuropathies commonly occur in otherwise healthy subjects, it is unclear whether this relation is coincidental or whether peripheral nerves affected by disease are rendered more susceptible to effects of repeated minor trauma, traction, or mechanical compression. METHODS: Sequential ulnar nerve conduction studies were prospectively performed at baseline and at four, eight, and 12 month intervals in 16 patients with amyotrophic lateral sclerosis. Ulnar nerve entrapment was defined as a focal reduction (> 10 m/s) in conduction velocity in the across-elbow segment. RESULTS: Ulnar sensory and motor nerve fibres showed similar findings of ulnar nerve entrapment at baseline and at follow up over the period of the study. Nerves with ulnar nerve entrapment showed a significantly greater reduction in distal motor amplitudes than nerves without entrapment, even though distal ulnar sensory amplitudes remained unchanged. CONCLUSIONS: Motor nerves in motor neuron disease do not seem to be more susceptible to entrapment at the elbow than do healthy sensory nerves, thus casting doubt on the double crush hypothesis. Nerves with double pathology (amyotrophic lateral sclerosis and ulnar nerve entrapment), however, seem to undergo more rapid axonal loss than do nerves with single pathology (amyotrophic lateral sclerosis or ulnar nerve entrapment alone).

Adult↗
PubMed1996

Sensory nerve pathology in multifocal motor neuropathy.

The nosological status of multifocal motor neuropathy remains controversial. The clinical and electrodiagnostic hallmarks suggest selective motor fiber involvement. In this study, we asked to what extent sensory nerves might be involved pathologically in multifocal motor neuropathy. Examination of sensory nerve biopsy specimens from 11 patients did reveal pathological findings in all, but they were very mild. An increased number of thinly myelinated, large-caliber fibers was the unifying feature common to each specimen. By electron microscopy, each biopsy specimen had thinly myelinated fibers surrounded by minor onion bulbs. Active demyelination, though scant, was seen in 3 nerves. Myelinated fiber density was normal. Subperineurial edema and inflammation were not present. We conclude that multifocal motor neuropathy is not an exclusively motor abnormality, although it appears to be so clinically and electrophysiologically. The frequent, albeit mild, pathological abnormalities in sensory fibers suggest that the demyelinating pathophysiology also affects sensory fibers, but to a lesser degree than motor fibers. Some investigators maintain that multifocal motor neuropathy is within the spectrum of chronic inflammatory demyelinating polyneuropathy. The very mild degree of sensory fiber involvement, the absence of inflammation or edema, and the distinctive clinical features support the concept of multifocal motor neuropathy as distinct from chronic inflammatory demyelinating polyneuropathy.

Adult↗
PubMed1996

A prospective study of suramin-induced peripheral neuropathy.

Suramin is an investigational drug that has shown therapeutic activity in hormone-refractory metastatic prostate cancer in Phase I/II trials. Dose-limiting neurotoxicity remains the most serious complication of suramin treatment. We performed a prospective study to define the incidence, severity, characteristics, and dose relationships of suramin-induced peripheral neuropathy. Twenty-two patients who received suramin in a Phase-I trial underwent baseline and serial follow-up neurological evaluations consisting of history, examination, nerve conduction studies and quantitative sensory testing (QST). Suramin was administered intravenously in escalating dosages by using a 5-day schedule (repeated monthly), with the dose, determined by a population pharmacokinetic model, to accomplish 30-min post-infusion concentrations of 300 micrograms ml-1 (cohort I), 350 micrograms m-1 (cohort II) and 400 micrograms ml-1 (cohort III). Twelve patients developed a mild, axonal, length-dependent, sensory-motor poly-neuropathy. Three other patients developed a subacutely progressive, functionally disabling, demyelinating neuropathy; sural nerve biopsy in two patients showed lymphocytic inflammation. These three patients improved after drug discontinuation and plasmapheresis. Although there was no apparent correlation between the cumulative dose and the severity of the neuropathy, no patient from cohort I, but 88% of patients from cohorts II and III, developed neuropathy. We conclude that when suramin is used at peak concentrations of > or = 350 micrograms ml-1 its administration is associated with two patterns of neuropathy, a distal axonal neuropathy and an inflammatory demyelinating neuropathy that is partially reversible. Neurological monitoring for development of neuropathy will improve the safety of suramin use in future clinical studies.

Aged↗
PubMed1996

Nerve conduction studies in adrenomyeloneuropathy.

OBJECTIVE: Adrenomyeloneuropathy (AMN) is an X linked metabolic disorder presenting with progressive spastic paraparesis in the third to fifth decade of life. Although peripheral neuropathy is also present in most patients, prominent pyramidal signs may make its clinical recognition difficult. The objective was to characterise the peripheral neuropathy in patients with AMN by nerve conduction studies. METHODS: Nerve conduction studies were performed in 99 men known to have AMN and in 38 heterozygous women, all of whom had neurological disabilities. RESULTS: Of the 13 variables obtained, at least one was abnormal in 82% of patients. The abnormalities were more common in men than in women (87% v 67%); in legs than in arms (77% v 38%); in motor than in sensory conduction (80% v 39%); and in latency (distal and F wave) and velocity compared with amplitude (80% v 29%). Twenty six patients had at least one nerve variable value in the demyelinating range. Four variables (sural velocity, peroneal amplitude, peroneal velocity, and peroneal F wave) were correlated with the expanded disability status scale; five variables (peroneal velocity, tibial H reflex, median distal latency, median conduction velocity, and median F wave latency) were correlated with serum very long chain fatty acids (VLCFAs); and two variables (sural amplitude and peroneal distal latency) were more likely to be abnormal in patients with normal adrenal function than in patients with Addison's disease. CONCLUSIONS: Nerve conduction studies in patients with AMN are often abnormal and suggest a mixture of axonal loss and multifocal demyelination. Their correlation with disability status and serum VLCFAs suggests that measures from nerve conduction studies may be useful in evaluating future treatments.

Adrenoleukodystrophy↗
PubMed1996

Wallerian degeneration in peripheral nerve disease.

Wallerian-like degeneration can be regarded as the final shared pathway of the most prevalent diseases of the peripheral nervous system, including many degenerative, metabolic, heritable, toxic, inflammatory and ischaemic disorders. The cellular responses that take place during Wallerian degeneration, including the elaboration of neurotrophins, are increasingly recognized to set the stage for the success or failure of subsequent regeneration, and manipulations of Wallerian degeneration are being investigated as a potential means of altering the outcome of nerve regeneration.

Axons↗
PubMed1994

Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation.

Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, recent studies have suggested an autoimmune mechanism of pathogenesis. Previous trials of immunosuppressive treatment have yielded inconclusive results. Our study was designed to determine whether more powerful and prolonged immunosuppression, produced by total lymphoid irradiation (TLI), would alter the course of ALS. In a double-blind, randomized, placebo-controlled study, 30 patients with classic ALS were treated with TLI, and 31 were given sham radiation. Quantitative measurements of muscle strength, functional motor activity, and humoral and cellular immune status were followed for 2 years, or until death or respirator dependence. Motor function in the TLI-treated and control groups showed no significant differences throughout the study. Overall survival was not significantly different in the TLI-treated and control groups. TLI effectively suppressed cellular and humoral immune function throughout the 2-year study period. Analysis of the relationship between immunosuppression and motor functions showed no consistent effect of treatment. We conclude that powerful and prolonged immunosuppression produced by TLI did not benefit patients with ALS. This fails to support the concept of an autoimmune mechanism of pathogenesis of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies.

Taxol is a novel antineoplastic agent that has demonstrated impressive clinical activity in breast, ovarian, lung, and head and neck cancers. This broad antitumor activity of taxol in cisplatin-sensitive tumors suggests that the combination of taxol and cisplatin may become one of the most commonly used taxol-based chemotherapeutic regimen in the treatment of solid tumors. Both taxol and cisplatin, however, are neurotoxic. To study the neurotoxic effects of these two agents when used in combination, we prospectively evaluated neurological function at baseline, during, and following treatment, in 21 cancer patients treated with taxol (135-350 mg/m2), cisplatin (75-100 mg/m2), and granulocyte-colony stimulating factor (5 micrograms/kg). Twenty of the 21 patients (95%) developed a sensory-motor neuropathy 1 to 21 weeks after the initiation of therapy, that was progressive with each additional course of chemotherapy. The neuropathy was symmetrical, length dependent, axonal in nature by physiological studies, and more pronounced in those patients who received higher doses of taxol. The neuropathy appeared earlier and at lower taxol doses in those patients with preexisting neuropathies. We conclude that sensory-motor neuropathy is a frequent dose-dependent toxicity of combined cisplatin and taxol use. Peripheral neuropathy is likely to become the major dose-limiting toxicity of taxol-cisplatin combination chemotherapy when higher doses of these agents are administered with granulocyte-colony stimulating factor.

Adult↗
PubMed1994

The effect of systemically administered recombinant human nerve growth factor in healthy human subjects.

This phase I double-masked, randomized, placebo-controlled study evaluated the safety of single intravenous or subcutaneous doses of recombinant human nerve growth factor (rhNGF) in healthy human volunteers at doses ranging from 0.03 to 1 micrograms/kg. No life-threatening adverse events were seen at any dose. At doses above 0.1 microgram/kg, subjects reported mild to moderate muscle pain, primarily in the bulbar and truncal musculature. The duration and severity of these myalgias varied in a dose-dependent manner, and women appeared to be more susceptible than men. Intravenous rhNGF produced earlier and more pronounced systemic effects than did identical subcutaneous doses. Subjects receiving subcutaneous rhNGF noted hyperalgesia at the injection site, a local effect persisting up to 7 weeks, that also varied in a dose-dependent manner. Antibodies to NGF were not detected in any subject. These results indicate that systemically administered rhNGF exerts a characteristic and reproducible biological effect in healthy subjects at very low doses and in a dose-dependent manner.

Adolescent↗
PubMed1994

Multifocal motor neuropathy: electrodiagnostic features.

Diagnosis of multifocal motor neuropathy (MMN), a syndrome characterized by progressive asymmetric weakness with intact sensation, is important because the disorder often responds to treatment. Multifocal partial motor conduction block (PMCB) has been emphasized as a cardinal feature in the diagnosis of this syndrome, but detailed nerve conduction studies are not available. Nine patients, ages 28-58, had chronic, progressive, asymmetric, predominantly distal limb weakness for 5-18 years. Sensation was normal and reflexes were reduced asymmetrically. Although all 9 demonstrated PMCB localized to short nerve segments, additional features of multifocal motor demyelination were present, including temporal dispersion (5 patients), segmentally reduced motor nerve conduction velocity (7 patients), prolonged distal motor latency (4 patients), and prolonged F-wave latency (9 patients). The strength of all patients improved after treatment with human immune globulin. A reduction in the degree of PMCB or an increase in the distal motor amplitude or both accompanied the clinical improvement. These studies suggest that patients with MMN demonstrate widespread evidence of motor demyelination in addition to the well-described PMCB, and that reduction of PMCB accounts for the increase in strength following therapy.

Adult↗
PubMed1994

Inter- and intraexaminer reliability of nerve conduction measurements in patients with diabetic neuropathy.

We determined the inter- and intraexaminer reliability of nerve conduction measurements in six patients with diabetic peripheral neuropathy. Each patient was examined by six electromyographers on two separate occasions at least 1 week apart. We obtained attributes of nerve conduction at each examination and analyzed the data by analysis of variance. Intraexaminer reliability was high for 11 of 12 measurements, and interexaminer reliability was high for eight of twelve. Three of the four measurements that varied between examiners were either sensory or motor amplitudes, attributes frequently used to measure disease progression or to assess the result of therapeutic intervention. Our results suggest that longitudinal nerve conduction measurements used to assess worsening or improvement over time should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.

Analysis of Variance↗
PubMed1993

Multifocal motor neuropathy: response to human immune globulin.

Multifocal motor neuropathy (MMN) is a progressive disorder producing asymmetrical weakness and muscle wasting. Case reports suggest that patients with MMN improve after cyclophosphamide therapy, but not after prednisone or plasmapheresis. Because MMN is likely to be immune mediated, we investigated the therapeutic response to human immune globulin (HIG) in an open, uncontrolled trial. Nine patients, ages 28 to 58 years, had chronic, progressive, asymmetrical, predominantly distal, limb weakness for 5 to 18 years. Sensation was normal, and reflexes were reduced asymmetrically. All had physiological evidence of multifocal motor demyelination with partial motor conduction block, and 7 had elevated serum titers of anti-GM1 IgM antibody. All patients were treated with HIG, 1.6 to 2.4 gm/kg, given intravenously over 3 to 5 days. Strength improved in all patients 3 to 10 days after treatment, with improvement peaking at 2 weeks and lasting for an average of 2 months. The range of functional improvement varied from dramatic to mild. The degree of partial motor conduction block was reduced, at least partially, in 7 of 8 patients. The serum anti-GM1 antibody titers did not change. Repeated courses of HIG resulted in similar improvements. We conclude that HIG may be an effective therapy for patients with MMN.

Adult↗
PubMed1993

Thermal sensitivity in demyelinating neuropathy.

An 8-year-old girl with demyelinating peripheral neuropathy was observed to get markedly weak coincident with a febrile illness. With return of body temperature to normal over 24 hours, her strength improved back to baseline. Subsequently, we studied the effect of temperature on CMAP amplitude of two motor nerves in the patient and two control subjects. Both temperature, measured orally, was raised by immersing the subjects in hot water and lowered by passive cooling. With increase in temperature to 39.5 degrees C, the CMAP amplitudes were reduced by 80% in the patient's nerves compared to only 48% in the control nerves. These changes recovered with cooling to 36.9 degrees C. We conclude that demyelinated peripheral nerves are more susceptible to temperature-induced impulse blocking than healthy nerves and provide the first published evidence of the clinical consequences of this phenomenon in a demyelinating disease other than multiple sclerosis.

Action Potentials↗