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Biomedical subjects

M Mumtaz

Publications and source records attributed to M Mumtaz.

11 recordsLinked to original sources

Remicade as TNF suppressor in patients with myelodysplastic syndromes.

Remicade, a chimeric human-murine monoclonal antibody capable of neutralizing tumor necrosis factor alpha was given to 37 low-risk myelodysplastic syndromes (MDS) patients in two cohorts; 5 and 10 mg/kg intravenously every 4 weeks for 4 cycles. Median age was 68 years, 33 had primary MDS, 14 had refractory anemia (RA), 14 RA with ringed sideroblasts, 9 RA with excess blasts. Nine patients stopped therapy prior to completing 4 cycles, 3 from cohort 1 and 6 from cohort 2 and response was evaluated using the International Working Group criteria in 28 patients who completed the 4 cycles. Six patients showed disease progression, 14 had stable disease and 8 showed hematologic responses, 3/15 (20%) in cohort 1 and 5/13 (38%) in cohort 2. Two patients had multi-lineage responses, 2 had > 100% increase in absolute neutrophils, 1 had > 1 gm/dl increase in hemoglobin, 1 had reduction in blasts from 7% to 1%, and 2 had minor cytogenetic responses (> 50% reduction in + 8 and 20q-metaphases respectively). We conclude that Remicade may have a variety of activities in low risk MDS patients, is well tolerated with a high patient compliance, and may be considered for combination therapy in the future.

Aged↗

Mixture component effects on the in vitro dermal absorption of pentachlorophenol.

Interactions between chemicals in a mixture and interactions of mixture components with the skin can significantly alter the rate and extent of percutaneous absorption, as well as the cutaneous disposition of a topically applied chemical. The predictive ability of dermal absorption models, and consequently the dermal risk assessment process, would be greatly improved by the elucidation and characterization of these interactions. Pentachlorophenol (PCP), a compound known to penetrate the skin readily, was used as a marker compound to examine mixture component effects using in vitro porcine skin models. PCP was administered in ethanol or in a 40% ethanol/60% water mixture or a 40% ethanol/60% water mixture containing either the rubefacient methyl nicotinate (MNA) or the surfactant sodium lauryl sulfate (SLS), or both MNA and SLS. Experiments were also conducted with 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (TCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB). Maximal PCP absorption was 14.12% of the applied dose from the mixture containing SLS, MNA, ethanol and water. However, when PCP was administered in ethanol only, absorption was only 1.12% of the applied dose. There were also qualitative differences among the absorption profiles for the different PCP mixtures. In contrast with the PCP results, absorption of TCB or PCB was negligible in perfused porcine skin, with only 0.14% of the applied TCB dose and 0.05% of the applied PCB dose being maximally absorbed. The low absorption levels for the PCB congeners precluded the identification of mixture component effects. These results suggest that dermal absorption estimates from a single chemical exposure may not reflect absorption seen after exposure as a chemical mixture and that absorption of both TCB and PCB are minimal in this model system.

Administration, Topical↗

Recurrent pyogenic cholangitis: 'sump syndrome' following choledochoduodenostomy.

An uncommon and late complication of side-to-side choledochoduodenostomy (CDD), the 'sump syndrome', developed in a patient 4 years after surgery. Recurrent right upper abdominal pain, fever with chills and rigors and latterly, mild jaundice made her seek repeated hospital admissions which were treated successfully with antibiotics. During the last admission, ultrasonography, endoscopic retrograde cholangiography (ERC), computerized scanning (CT) and hepatic iminodiacetic acid (HIDA) scan using Tc99m confirmed multiple intrahepatic calculi with proximal dilatation, debris in the distal blind segment and delayed excretion through the CDD. At surgery, the choledochoduodenostomy was taken down and a Rouxen-Y hepaticojejunostomy (RHJ) was fashioned after ductal clearance. The closed end of the Roux loop was placed subcutaneously for subsequent percutaneous access for cholangiography and removal of calculi. She is asymptomatic and well 28 months after surgery.

Adult↗

Stress and hypertension: role of serum, red cell and tissue electrolytes.

The role of stress in the precipitation of hypertension is often described in clinical studies, although the underlying mechanism remains unknown. The present study concerns the role of electrolytes in stress induced hypertension in rats. Acute immobilization stress of one hour elevated systolic blood pressure (SBP) in rats. Restraint induced blood pressure elevation was associated with increased sodium concentration in the red cells, heart and kidney, and decreased potassium in the red cells. Magnesium concentration increased and calcium concentration decreased in the serum. Increases of calcium and decreases of magnesium were also observed in the heart and kidney tissues. The results may help toward an understanding of the relationship between hypertension and electrolyte homeostasis. A possible role of Na(+)-K(+)-ATPase activity leading to observed changes of electrolytes or vice versa is discussed.

Animals↗

Electrolyte content of serum, erythrocyte, kidney and heart tissue in salt induced hypertensive rats.

The effect of salt load on the systolic blood pressure (SBP) and electrolyte levels of serum, erythrocyte, kidney and heart tissue was studied in rats. NaCl treatment increased sodium (5.69 +/- 0.4 mmol/L p < 0.001, 149.8 +/- 4.0 mEq/L, p < 0.001) and decreased potassium (112.6 +/- 2.4 mmol/L p < 0.001, 5.0 +/- 0.2 mEq/L, p < 0.001) in red cell and serum respectively. A decreased level of serum magnesium (1.4 +/- 0.3 mEq/L, p < 0.005) was observed. Sodium content was increased in both heart (39.93 +/- 2.9 mumol/g, p = n.s) and kidney tissues (44.39 +/- 0.5 mumol/g, p < 0.001). A pronounced increase in intracellular calcium (2.54 +/- 0.2 mumol/g, p < 0.001) and a decrease of magnesium content (6.05 +/- 0.8 mumol/g, p < 0.001) was observed in kidney tissue after treatment. The results suggested that marked changes in electrolyte levels of erythrocytes, serum, heart and kidney tissues in NaCl loaded rats may play a definite role in the development of salt induced hypertension.

Animals↗

The identification and testing of interaction patterns.

This paper presents a method for identifying and assessing the significance of interaction patterns among various chemicals and chemical classes of importance to regulatory toxicologists. To this end, efforts were made to assemble and evaluate experimental data on toxicologically significant interactions, to use this information to characterize the consistency of toxicological interactions, and to define classes of compounds that display similar toxicological interactions. The motivation for this effort is to be able to propose hypotheses, which can be validated by experimentation, on how 2 or more chemicals will interact.

Databases, Factual↗

Separation and quantitation of cis- and trans-thiothixene in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic procedure is described for the separation of cis and trans isomers of thiothixene, a thioxanthene derivative used as an antipsychotic agent. A radial compression module (RCM-100) was used with both silica and cyanopropyl cartridges. A fixed-wavelength UV detector (254 nm) was used in these studies for quantitation. Mesoridazine is used as an internal standard because of its separation characteristics and reproducible quantitation. C18 Sep-Pak cartridges are used for biological sample clean-up. Plasma samples from patients treated with thiothixene (Navane) were assayed for cis and trans-thiothixene. No trans-thiothixene was detectable and cis-thiothixene concentrations ranged from 0 to 22.5 ng/ml.

Chromatography, High Pressure Liquid↗

Evaluation of fluorometric assay methods for serotonin in platelets. Plasma and whole blood samples by comparison with GC-MS-SIM Technique.

Different methods have been used for the determination of serotonin (5HT) in human blood platelets, whole blood and plasma samples, but there have been very few reports on inter-method correlations. We now report the evaluation of fluorometric method using o-phthalaldehyde (OPT), with 3H-5HT as internal standard and GC-MS method using deuterated (d4-) 5-HT as internal standard. Basic extracts (pH 9.5) of sonicated platelet samples, hemolyzed blood or plasma samples are converted to trifluoroacetyl (TFA) or pentafluoropropionyl (PFP) derivatives. An aliquot of this derivatized sample (10%) was used for 3H count for determining the percent recovery, a second aliquot for GC-MS, and the rest for quantitation of OPT fluorescence (Emax360 millimicrons and Fmax 470 millimicrons). In another series, duplicate samples are extracted, one for fluorometry and the second for GS-MS with d4-5-HT as internal standard. Ions m/e 351 and 354 are monitored for the TFA and m/e 451 and 454 for PFP derivatives. The correlation between OPT fluorescence and GS-MS methods was good (0.95) for the platelets, but was poor (0.63) for whole blood and plasma samples. Thin layer chromatography of whole blood and plasma extracts showed multiple spots which yield characteristic fluorescence with OPT spray having same Emax or high background fluorescence. Serotonin levels in platelet samples of normal controls, and patients with different diagnoses of psychiatric disorders are presented.

Blood Platelets↗