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Biomedical subjects

P Kelkar

Publications and source records attributed to P Kelkar.

At least 19 recordsLinked to original sources
PubMed2005

Effects of (R)- and (S)-isomers of beta-adrenergic agonists on eosinophil response to interleukin-5.

BACKGROUND: Racemic beta2-adrenergic receptor agonists (beta2-agonists) are used frequently to treat patients with asthma. Potential differences in the biological activities and clinical efficacies among racemic beta2-agonists and their isomers are controversial, and research into these possible differences is limited. OBJECTIVE: We hypothesized that the (S)- and the (R)-isomers of beta2-agonists have opposing effects on the activation of inflammatory cells. METHODS: Isolated human eosinophils were pretreated with 1:1 racemic (R,S)-, (R)- or (S)-albuterol, isobutyl methylxanthine (IBMX), and stimulated with IL-5. The kinetics of superoxide production were examined by reduction of cytochrome c, and the effects of pharmacological agents on superoxide production were monitored for 180 min. RESULTS: (R,S)-albuterol inhibited IL-5-induced superoxide production. This inhibition was enhanced by a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, IBMX, and was reversed by the selective beta2-adrenergic receptor antagonist, ICI 118, 551, verifying the involvement of both cAMP and the beta2-adrenergic receptor. In addition, (R)-albuterol alone, similarly to (R,S)-albuterol, significantly inhibited IL-5-induced superoxide production up to 60 min (P<0.05, n=4), but the inhibition was lost with longer incubation. In contrast, (S)-albuterol with IBMX did not inhibit IL-5-induced superoxide production before 60 min, but it significantly enhanced IL-5-mediated superoxide production after 60 min (P<0.05, n=4). When both were present as racemic (R,S)-albuterol, the inhibitory effect of (R)-albuterol was not affected by (S)-albuterol. CONCLUSION: When incubated with IL-5-activated eosinophils, (R)-albuterol shows anti-inflammatory effects and (S)-albuterol shows pro-inflammatory effects in the presence of IBMX. The kinetics of these effects are different, and when used simultaneously, (R)-albuterol predominates. When marked usage of the (S)-isomer is anticipated, racemic (R,S)-albuterol should be used clinically with caution.

1-Methyl-3-isobutylxanthine↗
PubMed2003

Mononeuritis multiplex in diabetes mellitus: evidence for underlying immune pathogenesis.

Four patients with type 2 diabetes mellitus developed mononeuritis multiplex subacutely. Sural nerve biopsies showed multifocal axonal loss in all patients, with epineurial perivascular inflammation affecting small calibre vessels in three. Three patients improved with immunotherapy. These observations suggest that mononeuritis multiplex in diabetes may be caused by an immune mediated vasculopathy and that it is pathogenetically akin to the more common and better recognised diabetic amyotrophy.

Aged↗
PubMed2003

Para-aminosalicylic acid (PAS) desensitization review in a case of multidrug-resistant pulmonary tuberculosis.

SETTING: Tertiary care hospital in the Upper Midwest, United States. OBJECTIVE: Rapid desensitization to para-aminosalicylic acid (PAS) in a patient with previous hypersensitivity reaction and a review of published PAS desensitization protocols. DESIGN: Composition and implementation of a short-course PAS desensitization protocol for a 34-year-old woman with multidrug-resistant (MDR) pulmonary tuberculosis, incorporating published experiences of PAS desensitization over the past 50 years. RESULTS: We composed a protocol and successfully desensitized our patient to PAS (Paser granules). By starting with a low dose (50 mg), then doubling the PAS dose on each successive day, our patient was able to tolerate full dose in 1 week. No steroids were required and no adverse reactions were encountered. Previous published PAS desensitization protocols used starting doses of 10-500 mg, desensitization time ranges from 7 to 54 days and commonly used steroids or corticotropin. CONCLUSION: Rapid desensitization to PAS can be successfully conducted within 1 week without the use of steroids or corticotropin. Given the limited number of drugs available for many patients with MDR-TB, desensitization to PAS is a valid alternative to drug discontinuation for patients with hypersensitivity reactions.

Adult↗
PubMed2001

Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis.

BACKGROUND: Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial. METHODS: Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations. RESULTS: Two hundred four patients enrolled, 196 had two or more evaluations, and 128 patients completed the study. The mean rate of decline of the arm muscle strength was not significantly different between the groups. Moreover, there was no beneficial effect upon the rate of decline of other secondary measures (vital capacity, survival, ALS functional rating scale, timed walking) nor was there any symptomatic benefit. In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin. CONCLUSION: These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS.

Acetates↗
PubMed2000

Distinctive pathologic findings in proximal diabetic neuropathy (diabetic amyotrophy).

OBJECTIVE: To investigate the pathogenesis of proximal diabetic neuropathy (PDN) with nerve and muscle biopsies. BACKGROUND: Recent evidence suggests that nerve ischemia secondary to immune-mediated vasculopathy rather than diabetic microangiopathy may be responsible for PDN. METHOD: - Fifteen patients with PDN and two diabetic controls underwent nerve and muscle biopsy and clinical, electrophysiologic, and laboratory evaluation. There were eight men and seven women between 49 and 79 years of age with type II diabetes. All had progressive, painful, asymmetric, proximal weakness with duration of 5 weeks to 12 months. None had evidence of systemic autoimmune disorder. RESULTS: Four patients showed the distinctive findings of polymorphonuclear small-vessel vasculitis affecting epineurial vessels with transmural infiltration of postcapillary venules with polymorphonuclear leukocytes. Immunoglobulin M (IgM) deposits were found along the endothelium and intramurally in affected vessels. IgM staining was seen in the subperineurial space and in the endoneurium. Activated complement deposition was seen along endothelium of small vessels. Three of these four patients were evaluated within 6 seeks of onset of PDN, and the fourth patient during acute flare of PDN 6 months after the initial onset. Six patients showed "perivasculitis" with mononuclear cell infiltrates around small epineurial vessels without vasculitis (fibrinoid necrosis or transmural inflammation). One patient showed recanalized vessels with transmural lymphocytes without fibrinoid necrosis, possibly suggesting healed vasculitis. CONCLUSION: These distinctive pathologic findings support that proximal diabetic neuropathy has an immune-mediated inflammatory basis and suggest that polymorphonuclear vasculitis with immune complex and complement deposition may be the primary event in the acute phase of proximal diabetic neuropathy.

Aged↗
PubMed2000

Isolated posterior column dysfunction: an unusual presentation of spondylotic myelopathy.

Two patients with previously unreported clinically evident myelopathy caused by herniated intervertebral disks are described. These patients had isolated posterior column dysfunction in the lower extremities without motor deficits, abnormal reflexes, spinothalamic sensory abnormalities, or sphincter changes. The level of cord compression was significantly more cranial than suggested by clinical localization, and the results of initial radiographic studies were unremarkable. Study of posterior column dysfunction using somatosensory evoked potentials was helpful in localizing the lesions and guiding appropriate neuroradiologic studies.

Adult↗
PubMed1998

Asymptomatic grotesque deformities of the cervical spine. An occupational hazard in railway porters.

STUDY DESIGN: A case report. OBJECTIVE: To illustrate an extremely rare occurrence of chronic, occupational, low-grade trauma leading to asymptomatic grotesque cervical spine deformities in railroad station porters. SUMMARY OF BACKGROUND DATA: Occupational trauma causing spinal deformities has been described in relation to thoracic and lumbar spines in miners. To the authors' knowledge, this is the first reported case of asymptomatic cervical spinal deformity in railway porters as a result of chronic occupational trauma. METHODS: A magnetic resonance imaging study was performed on both patients. RESULTS: The magnetic resonance images showed advanced degenerative changes in the cervical spine causing obvious deformities, along with apparently normal cord signal intensity. CONCLUSIONS: Chronic, occupational, low-grade trauma of the cervical vertebral region is extremely unusual in industrialized countries. Nevertheless, in view of the increasing mobility of people in general and of the labor force in particular, this complication of an occupational exposure deserves attention as an unusual cause of cervical spinal deformity.

Adult↗
PubMed1998

Pure methotrexate encephalopathy presenting with seizures: CT and MRI features.

With the advent of chemotherapy, mortality rates in acute lymphoblastic leukaemia (ALL) have decreased, but complications in the central nervous system have appeared. These include direct involvement of the brain itself and the development of chemotherapy-related encephalopathy as a delayed reaction. In most reported cases, this encephalopathy is believed to be due to necrotising angiitis arising from the combination of chemotherapy with adjuvant radiotherapy. We report the cases of four children with ALL who had been treated with high-dose intravenous and intrathecal chemotherapy but no radiation therapy, and who were admitted to hospital because of seizures. CT of the brain revealed the presence of diffuse periventricular white matter hypodensities in all cases and subcortical hyperdense foci in three cases. MRI showed diffuse hyperintense white matter lesions on T2-weighted images in all four patients; hypointense changes were observed on susceptibility-sensitive FLASH sequences in the hyperdense foci seen on CT as well as changes that were hyperintense on T1-weighted images. It was, therefore, concluded that the lesions corresponded to a leukoencephalopathy with calcific deposits. These findings are of a pure form of methotrexate encephalopathy causing seizures.

Antineoplastic Agents↗
PubMed1997

Differentiation of benign and malignant breast lesions: MR imaging versus Tc-99m sestamibi scintimammography.

PURPOSE: To compare the accuracies of magnetic resonance (MR) imaging and scintimammography in differentiating benign from malignant breast lesions. MATERIALS AND METHODS: MR imaging was performed in 66 women with 75 lesions during intravenous administration of gadopentetate dimeglumine. Planar and single photon emission computed tomographic (SPECT) scintimammography were performed (with 740 MBq technetium-99m sestamibi administered intravenously) in all 66 patients with 75 lesions and in 64 patients with 73 lesions, respectively. MR imaging and scintimammographic studies were independently evaluated by using signal intensity measurements versus time or focal tracer uptake to differentiate benign from malignant lesions. Histopathologic proof was obtained in 63 lesions. Twelve lesions were monitored with follow-up. RESULTS: MR imaging was false-negative in one and false-positive in nine lesions. Planar scintimammography was false-negative in 10 and false-positive in six lesions. SPECT scintimammography was false-negative in four and false-positive in 10 lesions. Sensitivities and specificities for malignancy were, respectively, 96% and 82% for MR imaging, 62% and 88% for planar scintimammography, and 83% and 80% for SPECT scintimammography. CONCLUSION: Both MR imaging and scintimammography are useful in the evaluation of breast cancer. MR imaging is more sensitive and as specific as scintimammography.

Adult↗
PubMed1997

Coaxial technique: approach to breast core biopsies.

PURPOSE: To assess the feasibility of the coaxial core breast biopsy technique performed under stereotactic and ultrasound (US) guidance in vitro and in vivo. MATERIALS AND METHODS: Biopsies were performed in vitro and in vivo with a coaxial technique. In vitro, the true needle-tip deviation was measured with a breast phantom on a stereotactic device with alteration of x and y axes. In vitro US studies were performed to evaluate the optimal technique for harvesting sufficient material for histologic work-up. In 205 patients, coaxial biopsy was performed in 210 suspicious lesions under US (61 lesions) or stereotactic (patient in the sitting position, n = 67; patient in the prone position, n = 82) guidance. In addition, the coaxial system was used for preoperative localization. Surgery and histologic work-up were performed in all cases. RESULTS: In vitro, the true needle-tip deviation was found to be less than indicated on the stereotactic device. A factor was introduced to correct this error. For US guidance, angulation or rotation of the coaxial needle within the lesion proved to be the best technique to increase the size of histologic specimen. Of the 210 lesions, 112 were benign and 98 were malignant. Agreement between biopsy results and final postsurgical histologic analysis was found in 205 cases (98%). CONCLUSION: The coaxial breast biopsy technique is an accurate, simple, and time-saving method performed under stereotactic or US guidance.

Adult↗