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Biomedical subjects

G Choudhary

Publications and source records attributed to G Choudhary.

At least 19 recordsLinked to original sources
PubMed2001

Carvedilol titration in patients with congestive heart failure receiving inotropic therapy.

BACKGROUND: Carvedilol has been shown to improve morbidity and mortality in patients with congestive heart failure (CHF). There are limited data of carvedilol use in patients on inotrope therapy. We present our experience with carvedilol titration in New York Heart Association (NYHA) class IIIb/IV patients stabilized on milrinone therapy, as a nonrandomized study with a parallel control group of patients never on inotropes. These patients achieved volume control and stabilization of their symptoms during the course of milrinone therapy. METHODS AND RESULTS: Seventeen patients in class IIIb/IV CHF (group 1) on intermittent intravenous milrinone therapy and 15 patients in class II/IIIa compensated CHF (group 2) on standard triple heart failure therapy were titrated on carvedilol. Success and adverse events during titration were compared between the 2 groups. Fifteen (88%) patients in group 1 and 14 (93%) patients in group 2 were successfully titrated on carvedilol over 8.1 +/- 1.8 weeks and 6.7 +/- 2.8 weeks, respectively. The target dose of carvedilol (25 or 50 mg twice daily) was achieved in 13 (87%) patients (group 1) and 14 (93%) patients (group 2). Seven (47%) patients in group 1 and 4 (28%) patients in group 2 had adverse events during carvedilol titration. Eight (53%) patients in group 1 were weaned off milrinone over a period of 8.4 weeks after carvedilol titration, whereas the rest of the patients had reduction in the frequency of infusion. Ten (63%) patients in group 1 improved by one or more functional classes. CONCLUSIONS: Patients in NYHA class IIIb/IV who are treated with inotropic therapy can be titrated on carvedilol after reaching a stable state while on milrinone and standard oral drugs. Most of these patients can be successfully weaned off of milrinone or have decreased frequency of infusions and demonstrate improved functional status. Prospective randomized trials are required to evaluate these observations made in a limited number of patients in class IIIb and IV CHF because the combination of milrinone and beta-blockers has never been adequately evaluated.

Adrenergic beta-Antagonists↗
PubMed2000

Use of on-line mass spectrometric detection in capillary electrochromatography.

Capillary electrochromatography (CEC) is a liquid phase analytical separation technique that is generally carried out with packed capillary columns by electroosmotically driven mobile phase at high electric field strength. The analytes are separated by virtue of the differences in their distribution between the mobile and stationary phases and, if charged in their electrophoretic mobilities as well. It is thus considered a hybrid of liquid chromatography and capillary electrophoresis and is expected to combine the high peak efficiency of capillary zone electrophoresis (CZE) with the versatility and loading capacity of HPLC. This review explores the potential use of on-line mass spectrometric detection for CEC. It discusses key design issues that focus on the physical and electrical arrangement of the CEC column with respect to the electrospray orifice inlet. The salient features of the sheathless, sheath flow and liquid junction interfaces that are frequently employed while coupling a CEC column to an electrospray ionization mass spectrometry system are also highlighted. Possible configurations of the CEC column outlet that would obviate the need for pressurizing the capillary column are also presented. While coupling CEC with MS both the nature of the interface and the configuration of the column outlet will determine the optimal arrangement. The review also discusses bandspreading that occurs when a connecting tube is employed to transfer mobile phase from the column outlet to the atmospheric region of the electrospray source with a concomitant loss in sensitivity. Selected examples that highlight the potential of this technique for a wide range of applications are also presented.

Electrophoresis, Capillary↗
PubMed2000

Apoptosis of lung epithelial cells in response to TNF-alpha requires angiotensin II generation de novo.

Recent work from this laboratory demonstrated that apoptosis of pulmonary alveolar epithelial cells (AEC) in response to Fas requires angiotensin II (ANGII) generation de novo and binding to its receptor (Wang et al., 1999b, Am J Physiol Lung Cell Mol Physiol 277:L1245-L1250). These findings led us to hypothesize that a similar mechanism might be involved in the induction of AEC apoptosis by TNF-alpha. Apoptosis was detected by assessment of nuclear and chromatin morphology, increased activity of caspase 3, binding of annexin V, and by net cell loss inhibitable by the caspase inhibitor ZVAD-fmk. Purified human TNF-alpha induced dose-dependent apoptosis in primary type II pneumocytes isolated from rats or in the AEC-derived human lung carcinoma cell line A549. Apoptosis in response to TNF-alpha was inhibited in a dose-dependent manner by the nonselective ANGII receptor antagonist saralasin or by the nonthiol ACE inhibitor lisinopril; the inhibition of TNF-induced apoptosis was maximal at 50 microgram/ml saralasin (101% inhibition) and at 0.5 microgram/ml lisinopril (86% inhibition). In both cell culture models, purified TNF-alpha caused a significant increase in the mRNA for angiotensinogen (ANGEN), which was not expressed in unactivated cells. Transfection of primary cultures of rat AEC with antisense oligonucleotides against ANGEN mRNA inhibited the subsequent induction of TNF-stimulated apoptosis by 72% (P < 0.01). Exposure to TNF-alpha increased the concentration of ANGII in the serum-free extracellular medium by fivefold in A549 cell cultures and by 40-fold in primary AEC preparations; further, exposure to TNF-alpha for 40 h caused a net cell loss of 70%, which was completely abrogated by either the caspase inhibitor ZVAD-fmk, lisinopril, or saralasin. Apoptosis in response to TNF-alpha was also completely inhibited by neutralizing antibodies specific for ANGII (P < 0.01), but isotype-matched nonimmune immunoglobulins had no significant effect. These data indicate that the induction of AEC apoptosis by TNF-alpha requires a functional renin/angiotensin system (RAS) in the target cell. They also suggest that therapeutic control of AEC apoptosis in response to TNF-alpha is feasible through pharmacologic manipulation of the local RAS.

Angiotensin II↗
PubMed2000

Should the definition of preeclampsia include a rise in diastolic blood pressure of >/=15 mm Hg to a level <90 mm Hg in association with proteinuria?

OBJECTIVE: This study was undertaken to compare baseline characteristics and pregnancy outcomes between normotensive women who did and those who did not have a rise in diastolic blood pressure of >/=15 mm Hg in association with proteinuria. STUDY DESIGN: We studied 4302 healthy nulliparous women from the Calcium for Preeclampsia Prevention trial who were delivered at >/=20 weeks' gestation. We selected as the study group normotensive women who developed proteinuria within 7 days of a rise in diastolic blood pressure of >/=15 mm Hg with respect to baseline on 2 occasions 4 to 168 hours apart. Baseline blood pressure was the mean of measurements at 2 clinic visits before 22 weeks' gestation. Other normotensive women used for comparison were those who did not develop gestational hypertension or a rise in diastolic blood pressure of >/=15 mm Hg in association with proteinuria. RESULTS: Except for greater weight (P <.001), body mass index (P <.001), and systolic blood pressure (P =.05) the baseline characteristics of the 82 women with a rise in diastolic blood pressure of >/=15 mm Hg in association with proteinuria did not differ significantly from those of the other normotensive women. Although they had a greater rate of weight gain (P <.005), larger babies (P =.06), and a 2-fold increase in abdominal delivery (P <.001), there was little other evidence of adverse pregnancy outcomes among these women. CONCLUSION: During normotensive pregnancy a rise in diastolic blood pressure of >/=15 mm Hg in association with proteinuria appears to be benign and is not a useful clinical construct.

Birth Weight↗
PubMed1999

Integrated approach to the multidimensional analysis of complex biological samples by microseparation techniques. Analysis of glycoprotein factor associated with cancer cachexia.

Microanalytical separation techniques including capillary liquid chromatography, capillary electrophoresis and capillary electrochromatography are suitable for detection of diagnostically important changes in the metabolic profiles of biological fluids. A prototype instrument was employed to serve as an integrated platform for the analysis of urine sample from patients suffering from cancer cachexia. The instrument provides for convenient, rapid and efficient multidimensional approach towards method development which would facilitate simultaneous analysis of complex biological mixtures by the above techniques.

Cachexia↗
PubMed1999

Investigation of the potential of capillary electrophoresis with off-line matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for clinical analysis: examination of a glycoprotein factor associated with cancer cachexia.

The potential of capillary electrophoresis (CE) with offline matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry has been demonstrated for the examination of a glycoprotein factor associated with cancer cachexia. A comparison of CE profiles of a healthy volunteer and a cancer patient shows the presence of additional peaks in the electropherogram of the cancer patient that could be associated with cachexia. Micropreparative CE was performed with 180-micron fused silica capillary columns with tapered ends to collect CE fractions for further identification by MALDI-TOF-MS. The analysis of crude urine samples of cancer patients exhibiting cachexia, as well as CE fractions, with MALDI-TOF-MS using ferulic acid as the matrix shows a number of characteristic ions at m/z values of approximately 24 and approximately 67 kDa. The 24-kDa peak may be identified as the cachectic factor, a glycoprotein, whereas the peak at 67 kDa is identified as albumin, which is present in urine of most patients, and to which the cachectic factor is noncovalently bound. The combined use of CE and MALDI-TOF-MS was successful in detecting cachexia in all of the patients in this study, including one patient that was in an early phase of the disease.

Blood Proteins↗
PubMed1998

Capillary electrochromatography of biomolecules with on-line electrospray ionization and time-of-flight mass spectrometry.

Capillary electrochromatography (CEC) is considered a hybrid of liquid chromatography and capillary electrophoresis. It is expected to combine the high peak efficiency of capillary zone electrophoresis with the versatility and loading capacity of HPLC to bring about another high-performance MS-compatible chromatographic system. This paper explores the potential of CEC coupled with the electrospray ionization and time-of-flight mass spectrometry in biochemical analysis. The packed columns used in this study were tapered at the outlet to retain the packing material, thereby obviating the need for an outlet frit. Electrosmotically driven solvent gradients were employed for the separation of phenylthiohydantoin (PTH)-amino acids by reversed-phase chromatography, and a time-of-flight (TOF) mass spectrometer was employed as the detector for the CEC column effluent. The effect of CEC operating parameters, such as gradient shape, column length, and electric field, on the analytical results from the separation and MS detection of a standard mixture of PTH-amino acids was investigated. Particular attention was paid to the effect of sheath flow-rate, sheath composition and mass spectra acquisition rate on the performance of the electrospray TOF-MS.

Amino Acids↗
PubMed1998

Human health perspective on environmental exposure to hydrazines: a review.

Hydrazines are colorless liquid compounds that have been found at various Department of Defense hazardous waste sites. They are designated as environmental contaminants causing adverse effects to public health and have been identified at many National Priorities List (NPL) hazardous waste sites and federal facilities sites in the United States. Three chemically similar hydrazines-hydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine--occur in the environment and cause adverse health effects to persons living near hazardous waste sites. Humans are exposed to hydrazines by drinking contaminated, water, by inhaling contaminated air, or by swallowing or touching contaminated dust. Human occupational data and studies in laboratory animals suggest that people exposed to hydrazines may develop adverse systemic health effects or cancer. Hydrazines have caused cancer in animals following acute- or intermediate- duration exposure by the oral and inhalation routes. The U.S. Environmental Protection Agency, the U.S. Department of Health and Human Services, the International Agency for Research on Cancer, and the World Health Organization have classified hydrazines as possible cancer-causing environmental contaminants.

Animals↗
PubMed1997

Capillary electrochromatography with gradient elution.

A capillary electrochromatograph incorporating a gradient-forming system generally employed in HPLC is described, and the use of gradient elution in reversed phase electrochromatography is demonstrated by the separation of PTH-amino acids and steroid hormones. The gradient former employs two reciprocating displacement pumps to control the composition of the eluent in the reservoir at the column inlet with time in a controlled manner. Thus, the composition of the mobile phase flowing through the column and driven by electrosmotic forces can be changed with time in a controlled fashion as customary in HPLC with gradient elution. The design of the system allows also for isocratic elution by pumping the eluent of constant composition through the cavity at the column inlet and thus continuously supplying fresh buffer. The eluent gradient is generated by the two pumps and a 10 microL mixer. From there the liquid passes at a flow rate of 0.1-0.2 mL/min through the 17 microL cavity housing the column inlet and an electrode. The flow of the mobile phase was electrosmotic at an effective overall electric field strength of 500-1500 V/cm through a 50 microns x 20/12 cm capillary column packed with 3.5 microns octadecylated silica particles. Gradient profiles generated in this manner were highly reproducible. The same-day and day-today reproducibilities of the electrosmotic flow were found to be better than 3%. The use of the capillary electrochromatographic system was demonstrated with isocratic and gradient elution for the separation of complex mixtures of biologically interesting substances. The influence of the column temperature on the electrosmotic flow velocity and retention of PTH-amino acids was also investigated.

Chromatography, High Pressure Liquid↗
PubMed1997

Dynamics of capillary electrochromatography experimental study on the electrosmotic flow and conductance in open and packed capillaries.

For capillary electrochromatography (CEC) to become an analytical separation technique of high speed and resolution the factors determining the conductivity of the column as well as the generation and control of electrosmotic flow (EOF) in porous media have to be understood. In the present study the conductance of capillaries packed with a variety of stationary phases was evaluated with respect to the conductance of the open capillary and the data were interpreted in the light of the Tobias equation. However, the consistently observed reduction of the EOF when a capillary having a charged inner wall is packed with particles having charges of the same sign and the dependence of the EOF velocity on the particle size needs further explanation. The data suggests that, due to the employment of relatively long columns packed with small particles, CEC may offer peak capacities much higher than HPLC or micro-HPLC. The CEC columns are unique as they consist of a packed and an open capillary segment having different conductances and consequently different voltage gradients and electrical field strengths. Therefore, any sufficiently detailed study on CEC systems requires also the characterization of the individual column segments. EOF velocities of 6-7 mm/s could be realized at 60 kV applied voltage with a 23/32 cm x 50 microns raw fused-silica capillary packed with 6-micron Zorbax ODS particles. The current was a linear function of the field strength up to 1.8 kV/cm, but at high field strengths the EOF increased with squared field strength. Data on band spreading indicate that with a given column the plate height at high EOF velocities is smaller in CEC than in micro-HPLC and it is weakly dependent on the velocity.

Acetonitriles↗
PubMed1996

Human health perspectives on environmental exposure to benzidine: a review.

Benzidine, an odorless, white to slightly reddish-white crystalline organic compound, is an environmental contaminant that has been identified at about 30 National Priorities List (NPL) hazardous waste sites in the United States. In the environment, it is usually found attached to suspended particles either in its "free" state or as chloride or sulfate salts. In the past, U.S. industries used large quantities of benzidine to produce dyes for paper, clothes, and leather. Since the ban on its production and use in the United States in the 1970s, this compound is imported for specialty uses. People living near hazardous waste sites might be exposed to benzidine by drinking contaminated water, by inhaling contaminated air, or by swallowing or touching contaminated dust. People can also be exposed by using benzidine dyes on paper, clothes, and other materials. Human occupational data and studies of laboratory animals suggest that people exposed to benzidine may develop adverse systemic health effects or cancer. The U.S. Environmental Protection Agency (EPA), the U.S. Department of Health and Human Services, the International Agency for Research on Cancer (IARC), and the World Health Organization (WHO) have classified benzidine as a carcinogen. Urinary bladder cancer is the most common form of cancer caused by exposure to benzidine. The stomach, kidneys, brain, mouth, esophagus, liver, and gallbladder might also be targets. The information presented in the article may help public health officials, physicians, and toxicologists evaluate and develop the health information materials on the nature of benzidine in the environment and its potential impact on public health.

Animals↗
PubMed1987

Determination of 2,3-dibromopropanol in air.

One of the starting materials for the preparation of TRIS-BP (tris-2,3-dibromopropanol phosphate), which is used in the treatment of fabrics and various materials to make them nonflammable, is 2,3-dibromopropanol. Because of the reported toxic nature of its parent phosphate compound, 2,3-dibromopropanol recently has been used by itself as a fire retardant. The manufacture and use of 2,3-dibromopropanol as a fire retardant, however, have been a matter of great concern in the workplace because of its mutagenic, carcinogenic and nephrotoxic nature. A sensitive air sampling and analytical method has been developed as part of a complete field survey protocol. This paper describes the development of an air sampling and gas-liquid chromatographic analysis procedure for 2,3-dibromopropanol. The detection limit for the method is 5 microg per sample and the relative standard deviation for the method is 5%.

1-Propanol↗
PubMed1980

Gas-liquid chromatographic determination of toxic diamines in permanent hair dyes.

A rapid, simple and sensitive analytical method has been developed for the simultaneous determination of 1,4-diaminobenzene, 2,5-diaminotoluene and 2,4-diaminoanisole in permanent (oxidation type) hair dyes. The method utilizes an ethyl acetate extraction in the presence of NaCl followed by direct injection into a gas liquid chromatograph equipped with a flame-ionization detector. The detection limits are 5 ng/microliter each for 1,4-diaminobenzene and 2,5-diaminotoluene and 20 ng/microliter for 2,4-diaminoanisole. The relative standard deviations at 5 tims the detection limits are 5.6, 5.8 and 4.6% for these three compounds, respectively. Recovery of diamines from "spiked" dyes was generally found to be greater than 85%.

Carcinogens↗
PubMed1979

Gas chromatography/mass spectrometry: its application to industrial hygiene analytical problems.

The mass spectrometer (MS), when used as a detector for the gas chromatography yields a system (GC/MS) which is compatible, sensitive, and provides specific information, suitable for qualitative or quantitative analyses for industrial hygiene samples. Examples of the use of two GC/MS/Data Systems utilizing industrial hygiene samples as encountered during the health hazard evaluation efforts of NIOSH (National Institute for Occupational Safety and Health) are presented. A quadrupole unit has been used as a service tool to analyze industrial field samples and a high resolution double focussing unit has been used in the areas of method development research.

Acetylene↗