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Biomedical subjects

K Pandya

Publications and source records attributed to K Pandya.

At least 19 recordsLinked to original sources
PubMed2006

Effect of oral administration of bismuth compounds on Campylobacter colonization in broilers.

Bismuth compounds have been used since the 18th century to treat gastrointestinal ailments in man. Colloidal bismuth subcitrate (De-Nol) is currently used in combination with antibiotics to reduce enteric Helicobacter pylori colonization as a treatment of stomach ulcers. We investigated whether bismuth citrate or its parent compound, colloidal bismuth subcitrate, would reduce colonization of the closely related foodborne pathogen, Campylobacter jejuni in chickens. In 2 studies, birds were either fed 0, 50, or 200 ppm bismuth citrate or bismuth subcitrate (De-Nol) for 10 or 21 d and were orally challenged with 7 combined strains of C. jejuni (n = 6 birds/treatment). For both treatment groups, cecal Campylobacter colonization was reduced when birds were fed 200 ppm for 10 d but not 21 d. For the 50 ppm treatment group, only birds dosed with bismuth citrate for 21 d demonstrated any reduction in cecal Campylobacter concentrations when compared with controls. These data suggest that bismuth citrate and colloidal bismuth subcitrate may reduce cecal colonization by Campylobacter in broilers, but these effects are inconsistent.

Administration, Oral↗
PubMed2003

Marek's disease virus reactivation from latency: changes in gene expression at the origin of replication.

Marek's disease is a contagious lymphoma of chickens caused by Marek's disease virus (MDV). MDV replicates in chicken lymphocytes and establishes latency within and transforms chicken CD4+ T-cells. Transformed T-cells are seen as skin leukosis or as lymphomas in visceral organs. A major focus of our laboratory is the functional study of genes flanking the origin of replication. This origin (OriLyt) is contained within the repeats flanking the unique long (UL) region of the genome (IRL and TRL). To the left of this Ori are genes associated with MDV latent/transforming infection [1.8-kb RNA family, pp14, Meq), and to the right (UL) are genes associated with early stages of MDV lytic infection [BamHI-H-encoded protein (Hep), pp38/pp24, Mys]. During latency, MDV suppresses lytic gene expression and has evolved mechanisms for blocking the apoptosis of latently-infected CD4+ T-cells. Of the genes expressed during MDV latency and in the transformed cell, the Meq (Marek's EcoRI-Q-encoded protein) has been shown to block apoptosis and transactivate gene expression. Upon reactivation to lytic infection, we have found that splice variants of Meq predominate and that these forms lack several of the domains important to Meq trans-activation and trans-repression. We have found that rightward from the origin of replication, a family genes, including phosphoprotein 38 (pp38) are expressed during early stages of reactivation. Three separate open reading frames (Hep, Mys, and pp38) are encoded by distinct transcripts from this region. We are now determining the kinetics of expression of these transcripts and their relative abundance during reactivation.

Animals↗
PubMed2001

Extension of a tuned log spiral of revolution fluorescence XAFS detector, designed for optimal detection of a particular element Z, to XAFS of elements other than Z.

Recently, it has been demonstrated that an x-ray detector in the form of a log spiral of revolution, covered with highly oriented pyrolytic graphite, is an excellent device for obtaining the fluorescence XAFS of an element of interest in the presence of competing fluorescence from other elements. In the present work we investigate the capabilities of a log spiral of revolution (LSR) detector, with a geometry optimized for one element (in this case Cr), if used for XAFS of other elements.

Journal Article↗
PubMed2001

Schedule-dependent pulsed paclitaxel radiosensitization for thoracic malignancy.

The objective of this study was to apply preclinical research of paclitaxel radiosensitization to the treatment of thoracic malignancy. Human lung cancer cell line NCI520 and epidermoid cell line A431 were investigated in vitro for radiosensitizing effects of paclitaxel. Optimal schedule of paclitaxel treatment was applied to a clinical protocol as well as off-protocol treatment of thoracic malignancy. Pulsed paclitaxel with concurrent once-daily radiation was delivered every 48 hours during the week using doses of 15 mg/m2, 20 mg/m2, or 25 mg/m2 in a phase I clinical trial of dose escalation. Preclinical data support the finding that low-dose paclitaxel is sufficient for radiosensitization. Data also support that delaying radiation is better than immediate radiation after drug treatment. Twenty-three patients have enrolled in the phase I clinical trial. Seventeen patients completed treatment (6 at 15 mg/m2; 5 at 20 mg/m2; and 6 at 25 mg/m2). Mean tumor shrinkage at 4 to 6 weeks after therapy was 82%, 84%, and 84% for dose levels I, II, and III, respectively [average primary tumor shrinkage was 83% +/- 8% (95% C.I.)]. Locoregional tumor response rate was 100% [12% (2/17) complete response and 88% (15/17) partial response] with low rates of toxicity. It is concluded that pulsed low-dose paclitaxel and radiation is a very effective and well-tolerated regimen for thoracic malignancy.

Adult↗
PubMed2000

Novel transactivation domain in erythroid Kruppel-like factor (EKLF).

Erythroid Kruppel-like Factor (EKLF) is an erythroid-specific transcription factor that plays a critical role in gamma- to beta-globin gene switching during development. To identify essential domains required for EKLF transactivation function, we cotransfected a human erythroleukemia cell line (K562) with a locus control region gamma/Luc-beta/Cat reporter and an EKLF expression vector. In this assay EKLF mediates a 500-fold induction of beta/CAT expression compared with controls. To map essential transactivation domains, progressive NH(2)-terminal and internal deletion mutants of EKLF were constructed. All EKLF mutants were expressed at wild-type levels, localized to the nucleus, and bound DNA. When mutant EKLF proteins were tested for beta/CAT activation, a novel transactivation domain was identified. This novel domain, encompassing amino acids (aa) 140-358, is sufficient for maximal beta/CAT activation. An 85-amino acid subdomain within this region (aa 140-225) is essential for its activity. Interestingly, this central transactivation subdomain is functionally redundant with the amino-terminal domain (aa 1-139). Thus, EKLF possesses at least two potent transactivation domains that appear to function in a redundant manner.

Animals↗
PubMed1998

Interferon alpha-2b and megestrol acetate in the treatment of advanced renal cell carcinoma: a phase II study.

Interferon-alpha has been used to treat advanced renal cell carcinoma, and megestrol acetate has been shown to improve the quality of life of patients who have cancer. We combined interferon alpha-2b, 10 million IU/m2 subcutaneously 5 consecutive days per week, with megestrol acetate, 80 mg orally twice a day, in 15 patients who had advanced renal cell carcinoma. Only 6 (40%) had a prior nephrectomy, and most had disease in the lung and other sites. There were no complete or partial responders to this treatment, although stable disease was achieved in 5 (33%) patients. The treatment was excessively toxic, with 12 (86%) patients requiring dose modification or discontinuation of treatment due to fatigue. We conclude that interferon alpha-2b and megestrol acetate is an excessively toxic, inactive regimen, at least in a group of patients who have advanced disease with a poor prognosis.

Aged↗
PubMed1998

Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: an Intergroup study.

PURPOSE: The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, doxorubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features greater doxorubicin and 5-FU dose-intensity than CAF and improved scheduling of antimetabolites with sequential methotrexate and 5-FU, as well as infusion 5-FU. PATIENTS AND METHODS: A total of 646 node-positive, receptor-negative patients were randomly assigned to receive either the 1 6-week regimen or six cycles of CAF. Breast cancer outcomes included recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. The trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditional two-sided tests of significance. RESULTS: At a median follow-up of 3.9 years, the estimated 4-year recurrence-free survival rate was 67.5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided; P = .095, one-sided). The estimated 4-year survival rate was 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukopenia, granulocytopenia, and thrombocytopenia, as well as liver and cardiac toxicity, whereas the 16-week regimen produced significantly higher grades of anemia, nausea, stomatitis, and weight loss, as well as skin and neurotoxicity. There were three treatment-related deaths with CAF but none with the 16-week regimen. During treatment, quality of life declined significantly more with the 16-week regimen than CAF, but by 4 months posttreatment, there was no difference. CONCLUSION: The 16-week regimen produced marginally better breast cancer outcomes than CAF with similar toxicity but a greater reduction in during-treatment quality of life. The 16-week regimen should not be used instead of a standard-dose regimen without careful consideration of the 16-week regimen's pros and cons, which include its complicated schedule. It should probably not be tested further, but its antimetabolite schedules and frequent drug administration (ie, dose density) should be considered in the development of new regimens.

Adult↗
PubMed1995

Near fatal gas embolism during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has been greeted with enthusiasm by surgeons and patients alike. However, with the passage of time reports of complications related to this new approach are being published. We report an unusual complication of gas embolism in laparoscopic cholecystectomy. A high index of suspicion along with vigilant intraoperative monitoring will help in the early diagnosis and reduction of morbidity associated with gas embolism.

Cholecystectomy, Laparoscopic↗
PubMed1994

Differential modulation of astrocyte cytokine gene expression by TGF-beta.

In this study, we demonstrate that TGF-beta inhibits TNF-alpha expression, and induces/enhances IL-6 expression by primary rat astrocytes. Treatment of astrocytes with TGF-beta alone had no effect on TNF-alpha mRNA or protein expression; however, TGF-beta suppressed induction of TNF-alpha expression by three different stimuli (IFN-gamma/LPS, IFN-gamma/IL-1 beta, TNF-alpha) at both the protein and mRNA level. The extent of TGF-beta-mediated inhibition was greatest when astrocytes were pretreated with TGF-beta for 6 to 24 h, then exposed to the inducing stimuli. Inhibition of TNF-alpha mRNA steady-state levels by TGF-beta was a result of inhibition of TNF-alpha gene transcription, rather than degradation of the TNF-alpha message. In contrast, TGF-beta alone induced expression of IL-6 by astrocytes and synergized with two other cytokines, IL-1 beta and TNF-alpha, for enhanced IL-6 expression. TGF-beta-induced/enhanced IL-6 expression was mediated by transcriptional activation of the IL-6 gene. These results indicate that TGF-beta is an important regulator of cytokine production by astrocytes under inflammatory conditions in the brain.

Animals↗
PubMed1994

Amenorrhea following chemotherapy for breast cancer: effect on disease-free survival.

Adjuvant chemotherapy, which is known to be a cause of premature ovarian failure, is now recommended for most women diagnosed with breast cancer, and it has been postulated that the effects of chemotherapy are of the same order as those of ovarian ablation. Thus, it is important to correlate disease-free survival with induction of early menopause. We examined the literature for papers reporting the effects of chemotherapy on menstruation and ovarian changes in premenopausal women. Few studies reported such effects, but of those papers reviewed here, no such benefits in terms of disease-free survival were found. Thus, the benefits of adjuvant chemotherapy must be carefully weighed against the risk of early menopause in premenopausal women with good prognosis breast cancer.

Adult↗
PubMed1994

Effect of simultaneous low level exposure of Pb and Cd on delta-ALAD and acetylcholinesterase activity in rats.

Dose dependent study was performed to identify subcritical level of Pb and Cd. Blood delta-ALAD activity was inhibited by (0.1 mg/kg body wt) of both lead and cadmium in isolation and combination, the extent of which increases with duration of exposure. Hepatic delta-ALAD activity however is less affected by Cd and Pb-Cd together than Pb alone. Erythrocyte acetylcholinesterase activity though decrease in all groups, is not significant.

Acetylcholinesterase↗
PubMed1993

Accuracy of fecal occult blood screening for colorectal neoplasia. A prospective study using Hemoccult and HemoQuant tests.

OBJECTIVES: To define the validity of fecal blood as a marker for colorectal neoplasia in the screening setting and to compare yields by Hemoccult and HemoQuant fecal occult blood screening tests. DESIGN: A multicenter masked comparison of fecal blood test results against structural colorectal evaluations and longitudinal follow-up, serving as criterion standards, in nonreferred subjects at risk for colorectal neoplasia. SETTING: Communities, primary care centers, referral centers. PARTICIPANTS: Two groups: (1) 1217 patients aged at least 18 years undergoing routine structural surveillance evaluations following curative resection of a colorectal tumor and (2) 12312 relatives of colorectal cancer patients aged at least 50 years. INTERVENTIONS: Blinded Hemoccult II and HemoQuant testing on three mailed-in stool samples per subject. MAIN OUTCOME MEASURE: Sensitivity of fecal blood tests for colorectal neoplasia. RESULTS: In the postresection group, surveillance evaluations revealed 46 malignant colorectal neoplasms and 402 polyps. At matched specificity, sensitivity of either test for cancer was 26% (95% confidence interval, 13% to 39%). Hemoccult was positive in 21% of intraluminal recurrences, 33% of all new primary tumors, and 29% of Dukes A or B cancers; HemoQuant was elevated in 24%, 28%, and 29%, respectively. Sensitivity for polyps 1.0 cm or larger was 13% by Hemoccult and 11% by HemoQuant. In the group of relatives, estimated sensitivity for cancer at 1 to 3 years of follow-up was 25% to 33% by Hemoccult, not significantly different from the 29% to 43% by HemoQuant. CONCLUSIONS: Based on our observations in the screening setting, fecal blood appears to be a poor marker for colorectal neoplasia. Most cancers and the vast majority of polyps will be missed. Hemoccult and HemoQuant are similarly insensitive.

Adult↗
PubMed1993

Control of ventilation, respiratory muscle strength, and granulomatous involvement of skeletal muscle in patients with sarcoidosis.

Granulomatous involvement of skeletal muscle occurs in 50 to 80 percent of patients with sarcoidosis. How this may affect respiratory muscle function in sarcoidosis is not known. To attempt to answer this question, we compared respiratory function and muscle force generation, and control of ventilation in 12 untreated patients with 12 healthy, nonsmoking subjects. While seated, room air breathing, measurements included expiratory reserve volume (ERV), components of breathing pattern, and occlusion pressure at 1 s (P0.1). Three of nine patients who consented to muscle biopsy demonstrated granulomatous involvement on histologic examination, and Pmax values less than the group mean; however, some patients without muscle granulomas also demonstrated low Pmax values. Breathing pattern in the sarcoid patients was rapid and shallow, but not related to the degree of radiographic infiltration or respiratory elastance. Mean inspiratory flow (VT/TI), minute ventilation, and P0.1 were, in general, greater than in the control subjects, indicating an increase in central drive. There was a significant inverse correlation between FVC and P0.1, and a weak inverse relationship between ERV and P0.1. With no significant difference between group "effective impedances" (P0.1/(VT/TI)), findings indicate that in the sarcoidosis group, decreased muscle force generation was compensated for by an increase in central drive. Granulomatous infiltration may be one of many factors contributing to respiratory muscle weakness in sarcoidosis.

Adult↗
PubMed1992

Comparing the effectiveness of behavioral treatment for chemotherapy-induced nausea and vomiting when administered by oncologists, oncology nurses, and clinical psychologists.

Adequate control of side effects during medical treatment of cancer increases patient compliance and quality of life. Antiemetic drugs are not an effective treatment for the one in three cancer patients on chemotherapy who experience anticipatory nausea and vomiting (ANV); the behavioral treatment of systematic desensitization has been found effective for ANV when delivered by clinical psychologists. This study examined the effectiveness of systematic desensitization when delivered by medical personnel versus clinical psychologists. Seventy-two consecutive cancer patients with ANV were randomly assigned to no-treatment control or to systematic desensitization from 5 behaviorally trained clinical psychologists, 6 clinical oncologists, or 10 oncology nurses. The treatment was found effective in reducing anticipatory nausea, anticipatory vomiting, posttreatment nausea, and posttreatment vomiting compared to control patients, with no significant differences in effectiveness found between clinical psychologists and oncology staff. Although medical personnel should not engage patients in psychotherapy or other interventions that cannot be completed successfully, they can treat patients effectively with systematic desensitization and should be encouraged to learn and use this and other behavioral intervention techniques to benefit total patient care.

Behavior Therapy↗
PubMed1989

Perforation of esophagus after endoscopic variceal sclerotherapy. Incidence and clues to pathogenesis.

To determine the true incidence of endoscopic variceal sclerotherapy (EVS)-related esophageal perforation, a retrospective analysis of 900 EVS procedures using sodium tetradecyl sulfate performed on 170 patients during a five-year period (1980-1985) was carried out. Autopsy data of all patients who received EVS and who died (32 patients, 100%) during this period were available to confirm the diagnosis of perforation. Esophageal perforation was confirmed in 5 (2.9%) and was seen in patients with advanced alcoholic liver disease. Importantly, most patients did not manifest features of an esophageal leak, but presented instead as a deterioration in condition and died after a mean (+/- SD) 14 +/- 5.2 days. Analysis of the clinical and EVS data reveals that the risk of developing perforation is high when EVS is performed during active bleeding. The extravariceal location of sclerosant and microabscesses may be important predisposing factors. In our experience large-dose injection, deep ulceration, and balloon tamponade are less likely predisposing factors of this complication.

Adult↗