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Biomedical subjects

A Khan

Publications and source records attributed to A Khan.

At least 325 records · Page 18Linked to original sources
PubMed1996

Intraductal papillary mucinous neoplasm of the pancreas presenting as acute pancreatitis.

Intraductal papillary mucinous neoplasms are rare pancreatic exocrine tumors with distinct clinicopathologic features. They usually present with a long history of chronic pancreatitis-like symptoms, which are often associated with weight loss, diarrhea, and malabsorption. We report a case of benign intraductal papillary mucinous neoplasm with focal squamous metaplasia presenting as acute necrotizing pancreatitis. The clinicopathologic features are discussed in a brief review of the literature.

Acute Disease↗
PubMed1996

Giant gastric ulceration associated with antiphospholipid antibody syndrome.

The anticardiolipin or antiphospholipid antibody syndrome is characterized by an increased incidence of venous and arterial thromboses. This syndrome may occur in association with systemic lupus erythematosus or independently. Gastroenterological manifestations have included Budd-Chiari syndrome, hepatic infarction, esophageal necrosis with perforation, intestinal ischemia and infarction, pancreatitis, and colonic ulceration. We report a 39-yr-old man with antiphospholipid antibody syndrome complicated by adrenal insufficiency secondary to bilateral adrenal infarction who presented with severe epigastric pain. Endoscopic evaluation disclosed progressive gastric ulceration with necrosis in the distal body. Angiography revealed no vasculitis. Because of intractable pain despite intravenous anticoagulation and narcotic analgesia, the patient was taken to surgery, and an antrectomy with Billroth II gastrojejunostomy was performed. Histological examination revealed widespread vascular occlusive disease involving veins, small arteries, and arterioles present in all layers of the stomach and the perigastric fat consistent with the vasculopathy of the antiphospholipid antibody syndrome. Treatment with high intensity oral anticoagulation and corticosteroids resulted in clinical and endoscopic improvement. This case report extends the gastroenterological manifestations of the antiphospholipid antibody syndrome to include giant gastric ulceration and emphasizes the importance of anticoagulation in treatment.

Adult↗
PubMed1996

Myasthenia Gravis.

Explore the source record for details and available documents.

Fatal Outcome↗
PubMed1996

Angiographically documented coronary artery disease in asymptomatic middle aged men suspected of silent ischaemic heart disease.

One hundred and fourteen asymptomatic middle aged men, with a positive stress test, underwent coronary angiography at Armed Forces Institute of Cardiology/National Institute of Heart Diseases (AFIC/NIHD), Rawalpindi. Of these, 66 (58%) were found to have significant disease (> 50% luminal narrowing in at least one of the major epicardial arteries) while 48 (42%) had normal coronary arteries. Of the former, 27 (41%) had 1-vessel CAD, 18 (27%) had 2-vessel CAD and 21 (32%) had 3-vessel CAD. There were significantly more hypertensives, hyperlipidaemics and diabetics in CAD group, while other risk factors were the same. The overall risk factor prevalence was low. The major reasons for performing coronary angiography were a positive stress test done as part of routine annual medical checkup and resting ECG changes of enough significance to warrant further investigations. It is concluded that the presence of significant coronary artery disease can be silent in a large number of asymptomatic middle aged men, especially those who have conventional risk factors.

Adult↗
PubMed1995

Ventricular remodeling following infant-pediatric cardiac transplantation. Does age at transplantation or size disparity matter?

Early left ventricular (LV) remodeling following pediatric cardiac transplantation has not been described. To identify patterns and determinants of change in left ventricular mass and volume posttransplant, we studied 125 consecutive children who underwent cardiac transplantation between January 1, 1989 and July 31, 1993. Two-dimensional imaging-directed M-mode echocardiograms were studied weekly until 26 weeks post-transplant. LV mass and volume (indexed to BSA1.5) were measured. LV mass index increased until 3 weeks post-transplant, and then decreased. The mean decrement in LV mass index after 8 weeks post-transplant (relative to baseline) was significantly larger in patients with donor-recipient weight ratio > 1.5 compared with patients with donor-recipient weight ratio < or = 1.5 (-2.2 g/m3 compared with 33.4 g/m3, respectively, P < 0.01). Multiple linear regression was performed employing donor-recipient weight ratio, time since transplantation, ischemic time, and age at transplant as prognostic variables. Donor-recipient weight ratio (P < 0.0001), time since transplant (P < 0.01), and age at transplant (P = 0.02) were identified as independent predictors of change in LV mass index. Donor-recipient weight ratio (P = 0.001) and time since transplantation (P = 0.02) were independent predictors of change in LV volume index. There was an interaction between donor-recipient weight ratio and time since transplantation, suggesting that donor-recipient weight ratio has an independent effect as well as a time-dependent effect on change in LV mass and volume indices. LV mass and volume indices increased early posttransplant and then decreased; this pattern was temporally predictable, and dependent on donor-recipient weight ratio and age at transplant.

Child, Preschool↗
PubMed1995

Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma.

BACKGROUND: Treatment with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) resulted in responses in some patients with advanced renal cell carcinoma (RCC). However, the relative therapeutic benefit of the addition of LAK to IL-2 was unknown. METHODS: A randomized Phase III trial was conducted in patients with RCC comparing continuous intravenous infusion (CI) IL-2 alone with CI IL-2 plus LAK. Interleukin-2 was administered at 3 x 10(6) U/m2/day on days 1-5, 13-17, 21-24, and 28-31. Patients on the LAK treatment arm underwent leukapheresis on days 8-10 and LAK cell reinfusion on days 13-15. The results are reported with long-term follow-up. The published experience with IL-2 alone or with the addition of LAK was investigated in a quantitative literature survey. The response proportions were studied by schedule (high dose bolus, moderate dose, low dose) and by concomitant administration of LAK. RESULTS: Seventy-one patients were treated, 36 on the IL-2 arm and 35 on the IL-2 plus LAK arm. Four patients (6%) had major responses (two complete, two partial). The median survival of all patients was 13 months (95% confidence interval [CI], 9-18 months). There were no differences between treatment arms with regard to response (P = 0.61) and survival (P = 0.67). More patients on the LAK arm experienced pulmonary toxicity (P = 0.008). The overall weighted response proportion was 16% (95% CI, 8%-24%) for the 39 published series of 1291 patients treated with IL-2. The 95% confidence intervals for response proportion overlapped when compared by schedule and by administration of LAK. CONCLUSIONS: The dose and schedule of IL-2 used in this study resulted in a low level of antitumor activity and the addition of LAK did not improve the response rate against RCC. Given the infrequent, but reproducible, responses with IL-2 and interferon-based regimens, continued investigation of these agents is warranted as is the study of new cytokines. Alternative treatment strategies should be studied in RCC and new agents and treatment regimens that appear promising in Phase II studies must be studied in randomized trials.

Adult↗
PubMed1995

Dissociation between exocytosis and Ca(2+)-channel activity in mouse pancreatic beta-cells stimulated with calmidazolium (compound R24571).

Calmidazolium, a calmodulin inhibitor, suppressed influx of Ca2+ through voltage-gated Ca2+ channels in mouse pancreatic beta-cells. Despite this fact, calmidazolium stimulated insulin release from beta-cells at basal glucose concentration. This effect was not mediated by protein kinase C (PKC), since it persisted in PKC-depleted cells. RpcAMPS significantly attenuated the calmidazolium-stimulated insulin secretion, indicating that calmidazolium acts, at least partly, through PKA. The compound also stimulated insulin secretion from electropermeabilized beta-cells, indicating effects on distal steps in the stimulus-secretion coupling. The use of calmidazolium offers possibilities to investigate the mechanisms activating exocytosis under conditions where the cytoplasmic-free Ca2+ concentration does not increase.

Animals↗
PubMed1995

Sequence of the bphD gene encoding 2-hydroxy-6-oxo-(phenyl/chlorophenyl)hexa-2,4-dienoic acid (HOP/cPDA) hydrolase involved in the biphenyl/polychlorinated biphenyl degradation pathway in Comamonas testosteroni: evidence suggesting involvement of Ser112 in catalytic activity.

The nucleotide sequence of bphD, encoding 2-hydroxy-6-oxo-(phenyl/chlorophenyl)hexa-2,4-dienoic acid hydrolase involved in the biphenyl/polychlorinated biphenyl degradation pathway of Comamonas testosteroni strain B-356, was determined. Comparison of the deduced amino-acid sequence with published sequences led to the identification of a 'lipase box', containing a consensus pentapeptide sequence GlyXaaSerXaaGly. This suggested that the mechanism of action of this enzyme may involve an Asp-Ser-His catalytic triad similar to that of classical lipases and serine hydrolases. Further biochemical and genetic evidence for the active-site involvement of Ser112 was obtained by showing that a semipurified enzyme was inhibited by PMSF, a classic inhibitor of serine hydrolases, and by site-directed Ser112-->Ala mutagenesis.

Amino Acid Sequence↗
PubMed1995

Effect of nibbling versus gorging on cardiovascular risk factors: serum uric acid and blood lipids.

Nibbling has been reported to decrease serum cholesterol under fasting conditions, as well as the incidence of cardiovascular disease. It has been suggested that these effects are partly attributable to reduced concentrations of serum insulin, which are also observed. However, data on the effects of nibbling on serum lipids throughout the day are not available, nor is it known how nibbling affects serum uric acid as a further insulin-related risk factor for cardiovascular disease. We have attempted to address these issues. Seven healthy men consumed identical diets in a randomized crossover design either as three meals daily (control) or as 17 meals daily (nibbling) for 2 weeks. On day 13, serum lipid levels were measured over the course of the day (12 hours) together with the 24-hour urinary excretion of mevalonic acid as an indicator of hepatic cholesterol synthesis. Concentrations of uric acid in serum and 24-hour urinary excretion of uric acid were also determined. Mean (+/- SE) percent treatment differences in day-long total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B were significant, with lower values on the nibbling diet as compared with the control diet (8.1% +/- 1.6%, P = .002; 12.2% +/- 2.6%, P = .005; 10.1% +/- 1.6%, P < .001; and 9.9% +/- 2.6%, P = .008, respectively). No significant difference was seen in the total to HDL cholesterol ratio or in urinary mevalonic acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ethanol-induced single-strand DNA breaks in rat brain cells.

Male Sprague-Dawley rats were intubated with 4 g/kg body weight of ethanol (in a 20%, v/v, water solution). Brain cells were analyzed for single-strand DNA breaks at various post-ethanol administration time points using an alkaline microgel electrophoresis assay. Results showed a significant increase in single-strand DNA breaks in brain cells that peaked at approx. 4 h and returned to control level within 6 h after ethanol administration.

Administration, Oral↗
PubMed1995

Acetaldehyde: genotoxicity and cytotoxicity in human lymphocytes.

We evaluated the DNA damaging effects of ethanol and its major metabolite, acetaldehyde. Freshly isolated human lymphocytes from two healthy donors were incubated with 0, 1.56, 6.25, 25, and 100 mM of ethanol or acetaldehyde in complete medium for 1 h. We used a newly developed, sensitive, alkaline microgel electrophoresis technique to quantitate single- and double-strand DNA breaks or alkali-labile sites in individual cells. Ethanol did not induce DNA strand breaks. However, acetaldehyde induced both single-strand (even at the lowest concentration of 1.56 mM) and double-strand breaks (only at the highest concentration of 100 mM). Following exposure to acetaldehyde, cells were incubated in complete medium for 30, 60, and 120 min. During this incubation period, most cells were unable to repair DNA single- and double-strand breaks caused by acetaldehyde. We also observed a significant cell loss after exposure to acetaldehyde. To our knowledge, this is the first study demonstrating DNA single- and double-strand breaks by acetaldehyde.

Acetaldehyde↗
PubMed1995

Comprehensive pharmacokinetics of urinary human follicle stimulating hormone in healthy female volunteers.

PURPOSE: The study determined the pharmacokinetics of urinary human follicle stimulating hormone (u-hFSH) in 12 down-regulated healthy female volunteers. METHODS: Following pituitary desensitization, baseline FSH serum levels were measured over a 24-hour period. Then each subject received, in random order, single doses of u-hFSH (Metrodin), 75 IU, 150 IU and 300 IU iv, and 150 IU im on four occasions separated by washout periods of one week. Blood and urine samples were collected at preset times. FSH levels were measured by a immuno-radiometric assay and an in vitro rat granulosa cells aromatase bioassay. RESULTS: All doses of u-hFSH were well tolerated. After an iv bolus, the pharmacokinetics of FSH were well described by a two-compartment open model. Immunoassay data showed that the total exposure to FSH was proportional to the administered dose. Mean total clearance of FSH was approximately 0.5 L.h-1 and renal clearance was 0.14 L.h-1. The volume of distribution at steady-state was around 8 liters. The distribution half-life was 2 h and the terminal half-life nearly one day. After im injection, almost two thirds of the administered dose was available systemically. The in vitro bioassay confirmed this pharmacokinetic analysis. CONCLUSIONS: The estimation of the elimination half-life of around one day indicates that the maximal effect of a given dose of u-hFSH administered daily cannot be observed until 3 to 4 days of repeated administration. This indicates that, on a pure pharmacokinetic basis, physicians should wait at least 4 days to assess the efficacy of a given dose of u-hFSH and that they should not modify dosage too frequently.

Adult↗
PubMed1995

Induction of DNA single-strand breaks in human lymphocytes by low doses of gamma-rays.

We hypothesized that very low doses of gamma-rays have a genotoxic effect as measured by DNA single-strand breaks (ssbs). To test our hypothesis we used a newly developed alkaline microgel electrophoretic technique to quantitate DNA ssbs in freshly isolated human lymphocytes. An enhanced sensitivity to detect low levels of DNA damage was made possible by this method due to an additional step of DNA precipitation by ethanol in agarose microgels. We exposed lymphocytes from three subjects for 1 h at 4 degrees C to 740 MBq of technetium 99-m at a distance of 20 cm (0.25 mGy), 10 cm (1.02 mGy), and 5 cm (4.08 mGy) from the source vial. Doses of 1.02 and 4.08 mGy induced a significant dose-dependent increase in DNA ssbs in human lymphocytes from three subjects, each examined on three different days.

DNA Damage↗
PubMed1995

Radiation-induced lung injury using a pig model. Evaluation by high-resolution computed tomography.

RATIONALE AND OBJECTIVES: To assess the early phase of radiation-induced lung injury using high-resolution computed tomography (CT) under experimental conditions and to perform precise CT-pathologic correlation. METHODS: Five Yorkshire pigs received a single dose of 12.5 Gy to the right lower lung. Computed tomographic images were obtained at 2-week intervals. The animals were killed after follow-up periods of 4-16 weeks. The lungs were removed, inflated, fixed, dried, and sliced corresponding to the CT sections. Computed tomography, specimen radiography, and histologic findings were correlated. RESULTS: Various CT findings were observed during the first 16 weeks, including ground-glass opacity, discrete consolidation, patchy consolidation, thickened interlobular septum, and bronchovascular bundle. Ground-glass opacity was associated with thickened alveolar wall and scattered tiny fibrotic foci. Thickened interlobular septum and bronchovascular bundle were the results of fibrosis adjacent to these structures. Discrete consolidation correlated with intraalveolar edema with hemorrhage and infiltration of inflammatory cells. CONCLUSIONS: High-resolution CT correlated well with pathology of the lung due to radiation injury as verified by precise radiologic-pathologic correlation.

Animals↗
PubMed1995

Combination treatment of intraocular lymphoma.

BACKGROUND: Primary intraocular lymphoma is an uncommon clinical entity with poor visual and systemic prognosis. Optimal management of intraocular lymphoma remains uncertain. METHODS: Three patients with intraocular lymphoma, two of whom had documented CNS involvement, were treated based on a modification of the Sloan-Kettering Cancer Center protocol for primary CNS lymphoma. All patients underwent diagnostic pars plana vitrectomy and histopathologic confirmation of primary intraocular large B-cell lymphoma. Treatment involved systemic chemotherapy with methotrexate and high-dose ARA-C, radiation therapy of the brain and orbits, and intrathecal methotrexate delivered via an Ommaya reservoir. RESULTS: Resolution of the ocular lymphoma was seen in all three patients, and resolution of the intracranial disease also was seen in the two patients with CNS involvement. All patients have remained disease free, with lymphoma in remission for at least 24 months after completion of treatment. CONCLUSION: The Sloan-Kettering protocol for the treatment of primary CNS lymphoma also appears to be effective in some cases of primary intraocular large cell lymphoma. Furthermore, the Ommaya reservoir works well for intrathecal delivery of methotrexate in patients with CNS or leptomeningeal spread.

Aged↗