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Biomedical subjects

A Khan

Publications and source records attributed to A Khan.

At least 253 records · Page 14Linked to original sources

Phase Equilibria and Structure of the 1-Dodecylpyridinium Bromide-Dodecane-Water System.

The isothermal ternary phase diagram for the 1-dodecylpyridinium bromide/dodecane/water system was determined at 40 degreesC by 2H NMR and polarizing microscopy methods. Two liquid crystalline phases, a large cubic area and a normal hexagonal phase, and one isotropic normal micellar solution phase were characterized, and their ranges of existence were determined. The micelles were found to be probably small and spherical at lower concentrations of surfactant, and were found to grow at higher concentrations and on addition of oil. The two-phase areas, L1 + HI and HI + I, are both very narrow. The comparatively large cubic area, containing 43-63 wt% surfactant and 3-10 wt% dodecane, is probably consistent of more than one structure. SAXS experiments indicate two different structures built of discrete micellar aggregates. Copyright 1998 Academic Press.

Journal Article↗

Effects of 3-mercaptopicolinic acid and a derivative of chlorogenic acid (S-3483) on hepatic and islet glucose-6-phosphatase activity.

Glucose-6-phosphatase activity was measured in hepatic microsomes and in pancreatic islets from ob/ob mice. In hepatic microsomes vanadate, phlorizin, 3-mercaptopicolinic acid and a derivative of chlorogenic acid (S-3483) inhibited the translocase activity of the enzyme, vanadate in addition inhibited hydrolase activity. In islets, vanadate inhibited both components of the enzyme, phlorizin inhibited only hydrolase activity while 3-mercaptopicolinic acid and compound S-3483 were without effect. Similarly, when islets were incubated with 3H2O and unlabeled glucose, the incorporation of 3H into medium glucose was inhibited by vanadate and phlorizin, but not by 3-mercaptopicolinic acid and S-3483. These findings suggest that, as with glucokinase, different isoenzymes of glucose-6-phosphatase are present in islets and liver.

Animals↗

The influence of patient-related factors on ex vivo retroviral-mediated gene transfer into mobilized peripheral blood myeloid progenitors.

Mobilized human peripheral blood progenitor cells are potential alternatives to bone marrow cells as targets for ex vivo gene transfer. We report the transduction efficiency of retroviral-mediated gene transfer into myeloid progenitors of peripheral blood progenitor cell (PBPC) harvests, mobilized by high-dose cyclophosphamide and GM-CSF, compared with nonmobilized bone marrow (BM). Eleven PBPC samples were enriched for CD34+ cells, preincubated with IL-3 (10 ng/ml), IL-6 (50 ng/ml), and 10% autologous plasma for 42 hr, and transduced over a 6-hr incubation with IL-3 + IL-6 and a retroviral vector carrying the NeoR gene. NeoR-specific sequences were detected by polymerase chain reaction in 10 cell pellets (91%). Gene expression in CFU-GM colonies was found in nine transduced samples (82%), with a mean transduction efficiency of 5.2% (95% CI, 1.3-11.8%) CFU-GM per PBPC sample. In univariate analysis, a higher transduction efficiency into CFU-GM correlated significantly with a higher CFU-GM concentration in the CD34+-enriched sample (p = 0.009), a shorter interval from diagnosis (p < 0.001), and fewer months of prior cytotoxic treatment (p = 0.001); correlation with younger age was of borderline statistical significance (p = 0.077). In multivariate analysis a shorter interval from diagnosis and, to a lesser degree, a higher CFU-GM concentration in the CD34+-enriched sample were independent predictors of higher transduction efficiency. Twelve BM samples were similarly transduced; 11 pellets were PCR positive. CFU-GM NeoR gene expression was 4.2% (95% CI, 2.0-7.2%) CFU-GM per BM sample, which was not significantly different from the transduction efficiency into PBPC cells. No correlation was found between the transduction efficiency of CFU-GM in BM samples and CFU-GM concentration in the CD34+-enriched sample, time from diagnosis, months of prior cytotoxic treatment, and/or patient age. Our data suggest that the transduction efficiency ex vivo may be influenced by time from diagnosis, CFU-GM concentration in the sample, and possibly by the extent of prior cytotoxic administration.

Adult↗

Increased glucocorticoid sensitivity in islet beta-cells: effects on glucose 6-phosphatase, glucose cycling and insulin release.

Glucose-6-phosphatase (G6Pase) activity and the rate of glucose cycling are increased in islets from animal models of Type II (non-insulin-dependent) diabetes mellitus. Glucocorticoid treatment further stimulates these processes and inhibits glucose-induced insulin release. To determine whether these effects result from a direct action of glucocorticoids on the beta-cells, we used isolated islets. The islets were from transgenic mice overexpressing the glucocorticoid receptor in their beta-cells to increase the cells' sensitivity to glucocorticoid. Islets from transgenic and non-transgenic control mice utilized and oxidized the same amount of glucose. In contrast, islet G6Pase activity was 70 % higher, glucose cycling was increased threefold and insulin release was 30 % lower in islets from transgenic mice. Hepatic G6Pase activity was the same in transgenic and control mice. Dexamethasone administration increased G6Pase activity and glucose cycling and decreased insulin release in both transgenic and control mouse islets. We conclude that glucocorticoids stimulate islet G6Pase activity and glucose cycling by acting directly on the beta-cell. That activity may be linked to the inhibition of insulin release.

Animals↗

PROFILE: River Dolphins in Bangladesh: Conservation and the Effects of Water Development

/ Ganges river dolphins (Platanista gangetica) are threatened in Bangladesh from the effects of dams, large embankment schemes, dredging, fisheries bycatch, directed hunting, and water pollution. Visual surveys of the section of the Jamuna River located between the divergence of the Old Brahmaputra River and the confluence of the Padma River and the section of the Kushiyara River located between the Bangladesh-India border and the confluence of the Korangi River recorded a sighting rate of 0.13 sightings/km (mean group size = 1.8 dolphins) and 0.08 sightings/km (mean group size = 3.8 dolphins), respectively. These sections of river were considered to be priority areas for investigation because several water development projects have already been constructed and more are planned for the areas. During the surveys we examined the remains of dolphins caught accidentally in plastic gillnets and observed fishermen catching the fish species Clupisoma garua using dolphin oil and body parts as a fish attractor. Additional studies are needed to assess the status of dolphins and effects of water development and fisheries bycatch. Feasibility studies should be conducted on designating dolphin/fish sanctuaries and creating artificial habitat or enhancing existing habitat in eddy countercurrent scour pools to mitigate deleterious impacts. The environmental requirements of river dolphins reflect the needs of productive and biotically diverse tropical rivers.KEY WORDS: Bangladesh; River dolphins; Water development; Platanista; Fisheries bycatch; Flood Action Plan; Dams; Embankments; Barrages

Journal Article↗

CD57 (Leu-7) expression is helpful in diagnosis of the follicular variant of papillary thyroid carcinoma.

CD57 (HNK-1) is a oligosaccharide antigen that is expressed by cells of several lineages. It is present on multipotential neuroepithelial cells during embryogenesis, and tumours of epithelial, neuroectodermal and nerve sheath origin also express CD57. Its role in the diagnosis of thyroid tumours is controversial. We have studied CD57 expression by immunohistochemistry to determine its utility in the classification of thyroid follicular lesions. Study material included 114 normal thyroid sections, 77 benign thyroid lesions (29 colloid nodules, 22 follicular adenomas, 20 cases of Hashimoto's thyroiditis and 6 of Grave's disease) and 83 thyroid carcinomas, including 31 follicular variants of papillary carcinoma. We observed CD57 positivity in 95% of thyroid carcinomas, 27% of follicular adenomas and 10% of colloid nodules. It was not expressed in the normal thyroid. CD57 expression in thyroid carcinomas was significantly different from that in normal and benign thyroid lesions (P < 0.0001). The follicular variant of papillary thyroid carcinoma also showed significantly higher CD57 expression than colloid nodules (P < 0.0009) or follicular adenomas (P < 0.0009). No significant difference was seen between colloid nodules and follicular adenomas. We conclude that CD57 immunohistochemistry is valuable in the classification of thyroid follicular lesions into benign and malignant groups and is also helpful in the diagnosis of the follicular variant of papillary thyroid carcinoma.

Adenoma↗

Glucose-6-phosphatase activity in the hypothalamus of the ob/ob mouse.

The hypothalamus and cortex from ob/ob mice and their lean littermates were sonicated and then incubated with glucose-6-phosphate (glucose-6-P) and glycerol phosphate (glycerol-P). The difference between the rates of hydrolysis of glucose-6-P and glycerol-P was taken as the measure of glucose-6-phosphatase activity. The activity was much higher in the hypothalamus from ob/ob mice versus their lean littermates. Activity was undetected in the cortex. These findings raise the possibility that a defect in the regulation of glucose-6-phosphatase activity in a portion of the hypothalamus may relate to the mechanism underlying obesity in the ob/ob mouse. However, obese gene product administration to ob/ob mice, while reducing the body weight, did not alter the glucose-6-phosphatase activity.

Animals↗

The role of cell cycle regulatory proteins, cyclin D1, cyclin E, and p27 in thyroid carcinogenesis.

The cell cycle is controlled in part by cyclin-dependent kinases (CDKs), which are activated by forming complexes with cyclins. CDKs phosphorylate certain substrates to facilitate the proliferating cells through the cell cycle. CDK inhibitors (CDKIs) such as p27 inhibit cyclin-CDK complexes and function as a negative cell cycle regulator. The overexpression of the positive regulators (cyclins) or the underexpression of the negative regulators including p27 has been seen in a variety of neoplasms, but their role and interaction in thyroid carcinogenesis is yet to be established. We studied the expression of cyclins D1 and E, and the CDKI, p27 by immunohistochemistry in 116 cases, including 59 cases of follicular variant of papillary carcinoma (FVPC) and 57 cases of follicular adenoma (FA). The positive staining was divided into four grades: 1+ if less than 10%, 2+ if 11% to 25%, 3+ if 26% to 50%, and 4+ if greater than 50% of the nuclei of tumor cells stained positively. Cyclin D1 expression was seen in 37 (63%) FVPC and 34 (60%) FA. Cyclin E-positive cells were seen in 51 (86%) FVPC and 47 (82%) FA. No significant differences in the grade of cyclins D1 (P = .261) and E (P = .284) staining was seen between FVPC and FA. Of the 59 FVPC, 53 (89%) showed p27-positive cells; of these, 33 were 1+, nine were 2+, seven were 3+ and only four were 4+ positive. Conversely, all 57 FA were p27 positive, 53 were 4+, and four were 3+ positive. This difference in the grade of p27 staining between FVPC and FA was statistically significant (P < .001). This study shows a significant underexpression of p27 in FVPC compared with FA, suggesting that a decrease in p27 expression plays a more important role than overexpression of cyclins D1 and E alone in thyroid carcinogenesis and that p27 immunostaining may be helpful in the diagnosis of FVPC.

Adenocarcinoma, Follicular↗

Plasma and tonsillar tissue pharmacokinetics of teicoplanin following intramuscular administration to children.

The population pharmacokinetics of teicoplanin in plasma and tonsillar tissue in children was determined following intramuscular administration. Thirty seven patients in all received either a single 5 mg/kg dose; 2 doses of 5 mg/kg, 12 h apart; 3 doses of 5 mg/kg, 12 h apart; or, a single 10 mg/kg dose. Limited data, comprising a maximum of 2 blood samples and 1 tonsillar sample were taken from each patient, with the maximum time being 48 h after the first dose of teicoplanin (in the 3 x 5 mg/kg dosing schedule). All plasma data were analyzed simultaneously by a maximum likelihood method employing a modified EM algorithm. A first-order absorption, one-compartment disposition model was fitted to the data. Mean parameter values (with lower and upper 95% confidence intervals) were: clearance/bioavailability, 0.024 L h(-1) kg(-1) (0.020-0.027); volume of distribution/bioavailability, 0.61 L kg(-1) (0.54-0.70); absorption rate constant, 0.43 h(-1) (0.31-0.61). A first-order transfer model for distribution of teicoplanin between plasma and tonsillar tissue was fitted to the tonsil data. The mean parameter values (95% confidence intervals) were: transfer rate constant between plasma and tonsils 0.49 h(-1) (0.35-0.67); transfer rate constant between tonsils and plasma 0.73 h(-1) (0.52-1.03). These rate constants correspond to a distribution half-life of 0.95 h and an equilibrium distribution concentration ratio between tonsillar tissue and plasma of 0.67. After normalising clearance and volume of distribution for body weight, there was no further influence of body weight on the pharmacokinetic parameters. Also, there was no effect of dose, and as two formulations were used, one for the 5 mg/kg dose and the other for the 10 mg/kg dose, no effect of formulation on the pharmacokinetics of teicoplanin after im (intramuscular) administration was found.

Algorithms↗

Reduction in vancomycin-resistant Enterococcus and Clostridium difficile infections following change to tympanic thermometers.

OBJECTIVE: To contain a nosocomial outbreak of vancomycin-resistant Enterococcus (VRE). DESIGN: Intervention study, with comparison of incidence rates before and after intervention to assess whether changes in incidence followed the intervention and were greater than expected based on trends observed before the intervention. SETTING: A 343-bed acute-care hospital serving a predominantly elderly population referred from nursing homes, as well as patients admitted from the community. METHODS: Interventions strategies were tested on three high-risk nursing stations. These included enhanced environmental sanitation; intensive staff retraining in Universal Precautions, body substance isolation, and proper use of gloves; and the use of tympanic thermometers to avoid possible rectal or oral VRE transmission during temperature taking. RESULTS: Nosocomial VRE infections were reduced by 48% 9 months after switching to tympanic thermometers; incidence of Clostridium difficile infections also was reduced. As a result, tympanic thermometers were introduced facilitywide; additional observation for 20 months showed a risk reduction of 60% for VRE and 40% for C difficile. CONCLUSION: Cross-transmission of VRE and C difficile during temperature taking may result in bowel colonization, placing the patient at increased risk for infection. This risk may be reduced by the use of tympanic thermometers.

Anti-Bacterial Agents↗

Sources of error in bioimpedance spectroscopy.

Two different makes of bioimpedance spectrometer (UniQuest-SEAC SFB-3 and Xitron 4000B) were used for a series of measurements on volunteers and patients in intensive care. Although each machine was accurate over the frequency range 5 to 500 kHz when bench tested on model resistor-capacitor circuits, significant differences in their recorded impedance parameters appeared when used in vivo, especially on intensive care patients. A series of laboratory tests was performed on each machine simulating the situation in vivo to identify possible reasons for these differences. Whilst stray capacitance in the environment was identified as the major contributor to variability in high-frequency performance, interaction between electrode impedance and lead positioning was also a factor. The observed phase shift with frequency or time delay (Td) used in the Xitron modeling software appears to be the result of a time constant caused by stray capacitance and so is unlikely to have any biological meaning. Significant differences in the in vivo numerical values produced by bioimpedance spectrometers may be attributed to instrument design, data processing and, in particular, the clinical environment.

Adult↗

Changes in arterial-mixed venous oxygen content difference (CaO2 - CvO2) and the effect on shunt calculations in critically ill patients.

Many commonly used indices of pulmonary oxygen transfer assume that CaO2 - CvO2 is constant. We studied changes in CaO2 - CvO2 in critically ill patients to determine the effect on calculated shunt of assuming a fixed CaO2 - CvO2. Two hundred pairs of arterial and mixed venous blood gas measurements were obtained retrospectively from 43 patients, each providing four or five pairs from a period of 48 h. CaO2 - CvO2 range from 13 to 74 ml l-1. The mean within-patient sd was 6.8 ml l-1 and the overall between-patient sd was 10.9 ml l-1. Our results show that assuming a fixed CaO2 - CvO2 leads to errors in quantifying pulmonary oxygen transfer.

Critical Care↗

Low-dose spiral computed tomography of the thorax: comparison with the standard-dose technique.

RATIONALE AND OBJECTIVES: This study was conducted to determine whether significant reduction in radiation dose (250 mAs-->50 mAs), in chest computed tomography (CT) using volume acquisition affects image quality or the detectability of pathologic findings in the lung and mediastinum. METHODS: Phantom studies were conducted to evaluate resolution and noise level, then a patient study was then done. Fifty consecutive patients (10 normal and 40 abnormal) cases were examined. After a scan (250 mAs, 120OkVp) of the entire thorax, five additional slices (50 mAs, 120kVp) at the level of the abnormality were obtained. Three independent observers evaluated the visibility of normal lung and mediastinal structures, as well as image noise. The mean score was compared between the standard and low doses. In a second study, an independent evaluation of the presence or absence of pathologic findings was made by four observers. RESULTS: Lucite phantom studies demonstrated diminished low-contrast resolution and increased noise level for the low-dose technique. Observers assessed more noise in the low-dose images (P < 0.001). The normal structures were judged to be more visible with standard dose (P < 0.01), but the magnitude of the judged differences was small especially in the lung. No differences were found in the detection of lung and mediastinal abnormalities (P > 0.10). CONCLUSIONS: The low-dose technique was effective in demonstrating pathologic findings for the lung and mediastinum. Low-dose spiral CT should be considered as a viable alternative to standard-dose spiral CT.

Adult↗

The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group.

This 12-week, double-blind, placebo-controlled study evaluated the efficacy and safety of venlafaxine as first-line therapy for the treatment of major depression and major depression associated with anxiety in 384 adult outpatients. Fixed total daily dosages of 75, 150, and 200 mg of venlafaxine were administered in a twice-a-day regimen. Primary efficacy parameters were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D Depressed Mood Item, the Montgomery-Asberg Depression Rating Scale total score, and the Clinical Global Impressions Scale. Overall, a higher percentage of patients responded to venlafaxine than to placebo. Efficacy data indicated a dose-related response, most evident in the onset of clinical improvement; statistically significant improvements in some primary parameters were seen as early as 1 to 2 weeks after initiation of treatment, especially in the 150-and 200-mg/day groups. These dose-related clinical improvements continued through week 12. Venlafaxine-treated patients who had depression associated with anxiety showed significant dose-related improvements compared with placebo-treated patients; improvement was noted by scores on the HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor. Few clinically significant changes were observed in laboratory values, vital signs, or electrocardiogram tracings. Venlafaxine was generally well tolerated at all dosages. The most common study events included nausea, dizziness, somnolence, insomnia, dry mouth, and asthenia, which are consistent with findings of previous studies. The current study demonstrated that 75 to 200 mg/day of venlafaxine twice daily produced a dose-related improvement in the primary efficacy parameters and in the onset of significant antidepressant effects, which was noted at weeks 1 to 2 with the highest dosage tested (200 mg/day). The study also demonstrated that these dosages of venlafaxine were safe and effective as first-line therapy for major depression and depression associated with anxiety.

Adult↗