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Biomedical subjects

V Chaudhry

Publications and source records attributed to V Chaudhry.

At least 55 records · Page 3Linked to original sources
PubMed1993

Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting.

PURPOSE: To determine the maximum-tolerated doses (MTD), the principal toxicities, and the pharmacologic behavior of high doses of Taxol (paclitaxel; Bristol-Myers Squibb, New York, NY) combined with cisplatin and granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: Untreated and minimally pretreated solid-tumor patients received 24-hour infusions of Taxol on day 1 followed by cisplatin on day 2 and G-CSF, 5 micrograms/kg/d subcutaneously (SC), beginning on day 3. Treatment was repeated every 3 weeks. Starting doses of Taxol and cisplatin were 135 and 75 mg/m2, respectively. RESULTS: The development of a severe peripheral neuropathy and/or severe myalgias precluded the chronic administration of Taxol and cisplatin with G-CSF at doses greater than 250 mg/m2 and 75 mg/m2, respectively. At this dose, the mean Taxol steady-state plasma concentration (Css) exceeds concentrations capable of inducing pertinent antimicrotubule effects in vitro. The severity of the neuropathy was related to the cumulative dose of Taxol, the magnitude of the dose administered during each treatment, and the presence of a pre-existing medical disorder associated with peripheral neuropathy. A proximal myopathy of modest severity also was documented. Although severe neutropenia occurred frequently, especially at the MTD, it was rarely associated with fever (8% of courses), and absolute neutrophil counts (ANCs) less than 500/microL never persisted for more than 5 days. Responses were noted in non-small-cell lung cancer (NSCLC) and head and neck, breast, and esophageal cancers. CONCLUSION: Taxol and cisplatin doses of 250 mg/m2 and 75 mg/m2, respectively, can be administered repetitively with G-CSF to untreated and minimally pretreated patients. However, these doses are not recommended for patients with pre-existing neuropathies until additional experience in high-risk patients is obtained. Although this Taxol dose is nearly 85% higher than the dose that can be combined with cisplatin in the absence of G-CSF, this high-dose regimen should not be used outside the investigational setting until a dose-response relationship has been demonstrated for Taxol in randomized clinical trials.

Adult↗
PubMed1993

Relapse in Guillain-Barré syndrome after treatment with human immune globulin.

Seven adult patients received human immune globulin intravenously as initial therapy for Guillain-Barré syndrome. Although all patients initially stabilized or improved, five patients deteriorated 1 to 16 days after completion of treatment. In all five patients, clinical worsening included loss of at least one functional grade together with a decreased forced vital capacity. We subsequently treated each patient with a course of plasma exchange, which led to varying degrees of clinical improvement in four. In contrast to previously reported relapse rates for Guillain-Barré syndrome, our experience suggests that clinically significant relapses may occur in patients more often following human immune globulin therapy than after either plasma exchange or no therapy.

Adolescent↗
PubMed1993

Neurotoxicity of Taxol.

Neurotoxicity, manifested primarily by a motor and sensory polyneuropathy, is the principal nonhematological side effect of Taxol. Available evidence suggests that Taxol produces a toxic effect involving either axons or ganglion cell bodies, or both, rather than a myelinopathy. As with other toxic polyneuropathies, patients with preexisting peripheral neuropathies, such as those caused by diabetes mellitus or ethanol, appear to be particularly predisposed to developing neurological toxicity. The incidence and severity of the neuropathic manifestations also appear to be related to the Taxol dose level, the cumulative dose of Taxol, and possibly to the use of Taxol in combination with cisplatin. Rarely, manifestations of autonomic and central nervous system dysfunction occur. Taxol also induces myalgias in the peri-treatment period, especially when used in high doses, and a myopathy has been noted in patients treated with high doses of Taxol administered alone and in combination with cisplatin. Although dose-response relationships for Taxol have not been clearly established, these neuromuscular effects are likely to become a significant clinical problem if higher doses of Taxol are used with hematopoietic colony-stimulating factors. The neuromuscular effects of Taxol, including symptoms, physical and electrophysiological manifestations, and predisposing factors, as well as agents that may be used for neuroprotection, are discussed in this report.

Humans↗
PubMed1993

Clinical toxicities encountered with paclitaxel (Taxol).

Although paclitaxel (TAXOL) appears to be one of the most promising antineoplastic agents of the last decade, with demonstrated activity in advanced and refractory ovarian, breast, lung, and head and neck cancers, most clinical oncologists have had little experience with the agent. This is largely the result of the initially limited supply of paclitaxel and other obstacles encountered during early clinical development that restricted the drug's availability to a few investigational centers. Although a high incidence of major hypersensitivity reactions due to the Cremophor EL vehicle used in formulation disrupted and almost terminated the clinical development of paclitaxel, hypersensitivity reactions are no longer a serious problem consequent to the advent of effective premedication regimens and longer administration schemes. Instead, neutropenia is the principal toxicity of paclitaxel. At clinically relevant doses, absolute neutrophil count nadirs are severely depressed in most patients. The duration of severe neutropenia, however, is usually brief; treatment delays for unresolved hematologic toxicity are rare, and absolute neutrophil count nadirs are constant with repetitive dosing, suggesting that neutropenia is not cumulative. Asymptomatic sinus bradycardia has occurred in up to 29% of patients in phase II trials, and other cardiac disturbances, including atrioventricular conduction and bundle branch blocks, ventricular tachycardia, and possible ischemic manifestations, have been reported in approximately 3% of patients. Cardiac disturbances have primarily been noted in studies that used cardiac monitoring to more effectively detect and manage major hypersensitivity reactions. Although sinus bradycardia and conduction blocks appear to represent true toxicities, ventricular tachycardia and ischemic manifestations, which have largely been observed in patients with preexisting cardiac disease, may not be due to paclitaxel. In view of the lack of clinical significance of the cardiac effects and their infrequent occurrence, cardiac monitoring during paclitaxel is not recommended for patients without cardiac risk factors. However, until precise risk factors can be defined, patients with a significant antecedent cardiac history are generally not considered to be good candidates for paclitaxel therapy. Neurotoxicity, characterized principally by peripheral neurosensory manifestations, has generally been of mild to moderate severity, even in heavily pretreated patients at paclitaxel doses < or = 200 mg/m2. However, some patients have developed a severe sensory-motor polyneuropathy at higher doses of paclitaxel (given as a single agent or in combination with cisplatin). Patients with an antecedent peripheral neuropathy or coexisting medical illnesses associated with peripheral neuropathy (such as diabetes mellitus and substantial prior alcohol use) appear to be especially prone to developing peripheral neuropathy.(ABSTRACT TRUNCATED AT 400 WORDS)

Alopecia↗
PubMed1992

Wallerian degeneration in human nerves: serial electrophysiological studies.

After nerve transection, the distal stump undergoes Wallerian degeneration (WD). Little information is available concerning sequential changes in nerve conduction measurements during WD in humans. Five patients with nerve injuries were studied temporally. Motor-evoked amplitudes were reduced by 50% at 3 to 5 days after injury; the response was absent by day 9. Sensory-evoked amplitudes were reduced by 50% at 7 days after injury; the response was absent by day 11. Sensory and motor nerves with shorter distal stumps showed earlier loss of amplitude than did those with longer distal stumps. Denervation potentials were seen 10 to 14 days after injury. Our results suggest that WD occurs earlier if the distal stump is shorter, and that motor-evoked responses are affected earlier than sensory-evoked responses. The time-lag between the loss of the motor-evoked response and the appearance of denervation potentials, the latter coinciding with reduction of sensory evoked responses, suggests that failure of neuromuscular transmission precedes axonal loss during WD.

Action Potentials↗
PubMed1992

Different patterns of glycolipid antibody reactivity: lower motor neuron syndromes vs. immunization.

High titers of serum antibodies against GM1 ganglioside occur frequently in patients with lower motor neuron (LMN) syndromes. We compared the specificities of the antiganglioside antibody reactivities in LMN patients with those arising after immunization of Lewis rats with several ganglioside containing preparations including purified GM1, human central nervous system (CNS) grey matter and white matter. Serums with high titers of anti-GM1 antibodies from patients with LMN syndrome usually showed limited cross-reactivity to other glycolipids but often bound to a Gal(beta 1-3)GalNAc-containing neoglycoprotein. In contrast, serums with anti-GM1 antibody arising after immunization showed broad cross-reactivity with other glycolipids but did not bind to the neoglycoprotein. We conclude that the serum patterns of antiganglioside antibody reactivity secondary to immunization with gangliosides and CNS components are different from the natural autoantibodies found in LMN patients. The antiganglioside antibodies seen in LMN patients are unlikely to be a result of autoreactivity to gangliosides after nervous tissue damage.

Animals↗
PubMed1992

Chronic demyelinating polyneuropathy associated with eosinophilia-myalgia syndrome.

Eosinophilia-myalgia syndrome (EMS) is a newly described syndrome associated with use of L-tryptophan. A neuropathy with features of axonal degeneration has also been described in conjunction with EMS. Demyelinating polyneuropathy is not a well recognised association of the syndrome. The two patients with EMS reported presented with profound weakness and sensory loss and were found to have clinical, electrophysiological and pathological evidence of a chronic demyelinating polyneuropathy. The concurrence of this neuropathy with EMS, as well as several other features of their illness, is suggestive of an immune mediated mechanism in the pathophysiology of EMS.

Aged↗
PubMed1992

Wallerian degeneration in peripheral nerve disease.

This article first reviews the different classes of nerve injury. The temporal evolution of electrophysiologic changes occurring during Wallerian degeneration in humans is then described, followed by a description of sequential structural changes and cellular responses that occur after nerve transection. The final section focuses on the basis for resurgent research interest in Wallerian degeneration and the different research approaches being taken to answer basic science and clinical questions.

Animals↗
PubMed1991

Treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulin.

Chronic inflammatory demyelinating polyneuropathy is an immune-mediated demyelinating peripheral neuropathy usually treated with immunosuppressants. We reviewed our experience treating 15 patients (9 men, 6 women) with intravenous immunoglobulin. Six patients were on other therapies at the time of intravenous immunoglobulin infusions (4, prednisone; 2, prednisone and azathioprine). The dose of intravenous immunoglobulin was either 0.3 or 0.4 gm/kg/day for 4 to 5 days. Transient fever occurred in 1 patient. Subjective improvement in sensory symptoms was reported by almost all patients. Objective improvements in strength or functional tasks occurred in only 3 patients, a man with human immunodeficiency virus infection, a 14-year-old girl, and a woman with an immunoglobulin G kappa paraprotein. Our results suggest that individual patients may respond to intravenous immunoglobulin therapy. A multicenter controlled trial is needed to assess properly the role of intravenous immunoglobulin therapy in patients with chronic inflammatory demyelinating polyneuropathy.

Adolescent↗
PubMed1991

Inter- and intra-examiner reliability of nerve conduction measurements in normal subjects.

Nerve conduction studies are widely employed in evaluating patients with peripheral nerve disease and are often used serially to measure disease progression or to assess a therapeutic intervention. We determined the inter- and intra-examiner reliability of electrophysiological data by performing serial nerve conduction studies on 7 normal subjects. A high degree of intra-examiner reliability was present, but significant inter-examiner differences were found. Our results suggest that if nerve conduction studies are to be used longitudinally, they should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.

Electromyography↗
PubMed1991

Conduction block in diabetic neuropathy.

Symmetric sensorimotor polyneuropathy is a common complication of diabetes. Sensory and motor evoked amplitudes and conduction velocities are reduced. Both demyelination and axon loss have been reported in pathologic studies. Conduction block (CB), a manifestation of segmental demyelination, has not been previously studied in diabetic neuropathy. We determined the prevalence of conduction block in patients with diabetes by analyzing electrodiagnostic data from 24 diabetics. Conduction block was defined as a greater than 20% drop in peak-to-peak amplitude, and a less than 15% change in negative-peak duration between proximal and distal stimulation sites. A total of 76 nerve segments were studied. The criteria for conduction block were met in only 6 segments in 6 patients. The mean decrease in peak-to-peak amplitude between stimulation sites was 28% (range 21% to 40%). We conclude that conduction block over long nerve segments is uncommon in diabetic neuropathy, and, if present, suggests that other causes for neuropathy in diabetic patients should be sought.

Demyelinating Diseases↗
PubMed1991

Stimulated single-fiber electromyography in Lambert-Eaton myasthenic syndrome.

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Electrodiagnosis is confirmed by an increase in compound muscle action potential amplitude during high-frequency repetitive nerve stimulation or following brief exercise. We describe the results of stimulated single-fiber electromyography in 4 patients with disorders of neuromuscular transmission: LEMS (2), LEMS/myasthenia gravis (MG) overlap (1), and MG (1). Stimulated SFEMG was performed in the extensor digitorum communis muscle with axonal intramuscular suprathreshold stimulation at low and high rates. In all 4 patients, a rate dependence of jitter was found. In LEMS and LEMS/MG, jitter and blocking improved with high stimulation rates, as compared with the opposite effect in MG. We conclude that stimulated SFEMG is a valuable technique in the diagnosis of LEMS.

Aged↗
PubMed1991

Caroli disease: computed tomographic diagnosis.

Computed tomographic (CT) scan findings in patients with cavernous ectasia of the biliary tract (Caroli disease) have been described. Our patient had the isolated form of Caroli disease characterized by saccular dilatation of intrahepatic bile ducts and no evidence of portal hypertension. CT scan of the liver showed tiny dots with strong contrast enhancement within dilated intrahepatic bile ducts (the central dot sign). This finding when correlated with sonogram indicated portal radicles surrounded by dilated intrahepatic bile ducts.

Adolescent↗
PubMed1990

Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies.

We studied 74 patients with progressive, asymmetrical lower motor neuron syndromes. Clinical features of these patients, including age, sex, disease duration, patterns of weakness, and reflex changes, were evaluated by review of records. In each patient the clinical features were compared to the type of nerve conduction abnormalities and to the specificities of high-titer serum antiglycolipid antibodies. Antibody specificities were determined by an enzyme-linked immunosorbent assay using purified glycolipids and carbohydrates as substrates. Our results show that high titers of antibodies to glycolipids are common in sera of patients with lower motor neuron syndromes. Selective patterns of reactivity indicate that specific carbohydrate epitopes on the glycolipids are the targets of the high-titer antibodies in individual patients with lower motor neuron syndromes. Several distinct lower motor neuron syndromes can be identified based on clinical, physiological, and antiglycolipid antibody characteristics. These syndromes include multifocal motor neuropathy with evidence of multifocal conduction block on motor, but not sensory, axons and frequent (84%) high titers of anti-GM1 ganglioside antibodies; a lower motor neuron syndrome with predominantly distal weakness early in the disease course, no conduction block, and a high incidence (64%) of anti-GM1 antibodies; and a lower motor neuron syndrome with predominant early weakness in proximal muscles and serum antibodies to asialo-GM1 that do not cross-react with GM1 ganglioside.

Adult↗
PubMed1989

Anti-GM1 ganglioside antibodies with differing fine specificities in patients with multifocal motor neuropathy.

Antibodies to gangliosides were detected in sera from three of 19 patients with chronic inflammatory polyneuropathy (CIP) by a thin-layer chromatogram overlay technique. All three of the patients fell into a clinical subset of the group that had multifocal motor neuropathy, and in all three patients the antibodies reacted with GM1 ganglioside. However, the fine specificities of the antibodies differed as demonstrated by cross-reactivity with different gangliosides in each of the three patients. The antibodies in patient 1 reacted with GM1, GD1b, and asialo-GM1 suggesting that the terminal Gal(beta 1-3)GalNAc moiety that is common to these three glycolipids is an important part of the epitope(s). This was confirmed by showing reactivity of the antibodies with Gal(beta 1-3)GalNAc conjugated to bovine serum albumin. Patient 2 had antibodies that did not react with GD1b, but cross-reacted with GM2 ganglioside suggesting that the epitope(s) involved the inner portion of the oligosaccharide moiety that is shared between GM1 and GM2. Patient 3 had antibodies that reacted with GM1 and asialo-GM1, but they did not cross-react with either GD1b or GM2. These results provide further evidence for a relationship between motor nerve syndromes and anti-GM1 antibodies and also suggest that GM1 could be a principal target antigen since other reactive gangliosides differed among the patients. However, the possible pathogenic effects of anti-GM1 antibodies on motor nerves remain to be established.

Antibodies↗
PubMed1987

Symptomatic atlantoaxial dislocation in Down's syndrome.

Four patients with Down's syndrome suffered compression of the spinal cord secondary to atlantoaxial dislocation. All four developed inability to walk and quadriparesis, with signs of cervical myelopathy. It is important to recognize this potentially fatal complication of the syndrome. Immediate immobilization of the neck, followed by cervical roentgenograms, should be done in any patient with Down's syndrome who presents with neck pain, torticollis, urinary incontinence, or loss of ambulation. Surgical repair with fusion of the first and second cervical vertebrae can be carried out later.

Adolescent↗
PubMed1977

Adrenal testis inter-relationship in male Indian palm squirrel Funambulus pennanti Wroughton.

The present work attempts to study adrenal-testes relationship in a seasonal breeder, Indian palm squirrel, Funambulus pennanti. To assess the functional status of the adrenals, its two major components i.e. cholesterol and ascorbic acid were estimated biochemically and the results related with testicular functioning and its cholesterol concentration. In addition, histological studies of the above tissues were also carried out. Variation in adrenal function is clearly manifested by fluctuations in its cholesterol and ascorbic acid contents. However, no alteration in adrenal histology was discernible. Testicular recrudescence starts in January and peak activity is reached in April and May when adrenals are most inactive. End of June markes the beginning of testicular regression and maximal regression is reached in October.

Adrenal Glands↗