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Biomedical subjects

S K Gupta

Publications and source records attributed to S K Gupta.

At least 541 records · Page 30Linked to original sources
PubMed1990

Effect of food on the pharmacokinetics of cyclosporine in healthy subjects following oral and intravenous administration.

The pharmacokinetics of cyclosporine were studied in healthy subjects following administration of cyclosporine both orally (10 mg kg-1) and intravenously (4 mg kg-1) without and with high fat meals. Both blood and plasma samples (separated at 37 degrees C) were analyzed for cyclosporine concentration. Blood and plasma clearances of cyclosporine were calculated to be 0.36 and 0.47 L hr-1 Kg-1, respectively, and volume of distribution at steady state was calculated to be 1.21 L Kg-1, when cyclosporine was administered without a high fat meal. Using plasma analysis, the oral bioavailability of cyclosporine was estimated to be 21 and 79%, when administered without and with a high fat meal, respectively. When cyclosporine was administered intravenously together with a high fat meal, both clearance and volume of distribution increased significantly. Blood and plasma clearances of cyclosporine were 0.44 and 0.70 L hr-1 Kg-1, respectively, when cyclosporine was administered along with a high fat meal. We conclude that food not only enhances the absorption of cyclosporine but also enhances its clearance and volume of distribution. The observed variability in clearance, bioavailability, and volume of distribution values for cyclosporine across various pharmacokinetic studies can be partially accounted by the type of food administered and the sampling matrix used for analysis.

Administration, Oral↗
PubMed1990

Liquid chromatographic assay and pharmacokinetics of halazepam and its metabolite in humans.

A reversed-phase high-performance liquid chromatographic method is described for simultaneous quantification of halazepam and its major active metabolite, nordiazepam, in plasma. The method uses a solid-phase extraction procedure to prepare plasma samples. After extraction, the methanolic extract is evaporated, and the residue is then reconstituted in a small volume of mobile phase (a 40:60, v/v, mixture of 0.02 M phosphate buffer, pH 4.0, and methanol) and chromatographed. The total chromatography time for a single sample is approximately 10 min. A sensitivity of 1 ng/mL for halazepam and nordiazepam is attained when 1 mL of plasma is extracted. Analytical recovery of halazepam and nordiazepam added to the plasma ranged from 89 to 96%. The maximum within-day and day-to-day coefficients of variation for each compound at the concentration range of 2 to 100 ng/mL were 8.7 and 10.3%, respectively. Suitability of the method was assessed in a preliminary pharmacokinetic study in which three subjects were given a single 20-mg oral dose of halazepam following an overnight fast. It appeared from our kinetic analysis that halazepam is a drug with a fairly rapid absorption phase that is followed by a slow elimination phase. Mean oral plasma clearance of halazepam was 24 L/h. The mean apparent elimination half-life of nordiazepam (45.22 h) is considerably longer than that of halazepam (21.15 h).

Administration, Oral↗
PubMed1990

Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of benzodiazepines. I: Lorazepam.

This investigation compares the time course changes in the central nervous system (CNS) impairment effects on psychomotor and cognitive skills and relates these changes to the plasma lorazepam concentrations in a pharmacokinetic-pharmacodynamic (PK-PD) model. Six male subjects received a single oral dose of lorazepam or placebo. The CNS effects were measured by using computerized continuous tracking (TRKN), body sway with eyes open (SWAY OPEN), and digit symbol substitution (DSS) tests. Plasma lorazepam concentrations were best characterized by a two-compartment model with first-order absorption. Plotting the plasma lorazepam concentration and measured effect across time revealed a counterclockwise hysteresis loop. Fitting the time course of the effects in an integrated PK-PD model required an effect compartment with the equilibrium rate constant between it and the plasma compartment. The magnitude of the temporal lag was quantified by the half-time of equilibration between concentration in the hypothetical effect compartment and the plasma lorazepam level (t1/2keo). The CNS effect measured by TRKN was characterized by a mean estimate of maximum predicted effect (Emax) of 418 with a t1/2keo of 0.43 hr, an estimate of effect site drug level to produce 50% of Emax (EC50) of 35.8 ng/ml and a power parameter (gamma) of 6.29. Corresponding parameter mean estimates for SWAY OPEN and DSS as measures of drug CNS effect were quite similar.

Administration, Oral↗
PubMed1990

Improved strategies for secondary operations on infrainguinal arteries.

Secondary interventions play an important role in achieving the ultimate goal of limb salvage after primary infrainguinal interventions fail. By employing the described strategies and principles for secondary arterial reconstructions below the inguinal ligament, good results in terms of patency of the reoperated primary reconstruction or the secondary reconstruction can be obtained with significantly augmented limb salvage at a low cost in operative morbidity and mortality. These results mandate that vascular surgeons maintain an aggressive attitude toward the use of these secondary operations when a primary procedure fails to achieve or maintain its intended goal and a patient is faced with imminent limb loss because of distal ischemia.

Blood Vessel Prosthesis↗
PubMed1990

Age-related increase in CNS sensitivity to benzodiazepines as assessed by task difficulty.

The differential sensitivity of young and elderly healthy adults to the impairment effects of benzodiazepines was assessed by tasks with several levels of difficulty. Using a double-blind procedure, single doses of placebo, alprazolam (0.75 and 1.5 mg) and triazolam (0.25 and 0.5 mg) were ingested orally by 10 young men, 9 young women, 7 elderly men, and 10 elderly women. Order of drug administration was determined by a random Latin square design. Different versions of the subcritical tracking and digit symbol substitution tasks were characterized by three difficulty levels. Assessments of task performance were conducted at varying intervals for 7 h after drug administration. Both drugs induced a rapid initial onset of impairment in the two age groups. Evidence of increased drug sensitivity in the elderly was provided by the more prolonged duration of the pharmacologic effect in the older than young subjects, especially for the harder versions of the SCT and DSS tasks. In summary, the data provide support for the hypothesis of an age-related decline in the adaptive capacity to inhibit adverse drug effects.

Adult↗
PubMed1990

Pharmacokinetics of growth hormone secretion in humans induced by growth hormone releasing hormone.

This investigation compares the age- and sex-related changes in growth hormone (GH) response to growth hormone releasing hormone (GHRH) in normal subjects using an appropriate pharmacokinetic model. Twenty-five subjects (14 males and 11 females) aged 23-89 yr received a single intravenous bolus dose (1 microgram/kg) of GHRH-40 solution. Plasma GH concentration-time profiles are best characterized by a biexponential equation (or one-compartment model) with first-order release and disappearance rates and an equilibration lag time. The harmonic mean release rate half-life is similar for both sexes (males: 12.6 min vs. females; 11.4 min) but significantly different across age groups (23-35 yr: 7.2 min vs. 50-89 yr: 16.8 min). The mean disappearance rate half-life and GHRH-equilibration time lag for females (33.6 and 20.4 min, respectively) and the higher age group subjects (32.4 and 21.6 min, respectively) are significantly longer than those of males (22.8 and 9 min, respectively) and the lower age-group subjects (21.6 and 8.4 min, respectively). The mean metabolic clearance rate of GH is significantly lower (p less than 0.02) for females than for males (3.1 vs. 4.83 ml/hr.m2). However, the production rate and the amount of GH released by the pituitary for our subjects appear to be very similar for both males (8.7 micrograms/hr.m2 and 4.65 micrograms/m2) and females (9.33 micrograms/hr.m2 and 5.11 micrograms/m2).

Adult↗
PubMed1990

Sperm preparation affects reactivity of monoclonal antibodies.

The polyacrylamide gel electrophoresis (SDS-PAGE) patterns of extracts prepared from thrice-washed human sperm were compared with extracts of swim-up and non-rise sperm. For sperm extraction sodium deoxycholate (DOC), octylphenoxypolyethoxyethanol (NP-40), dithiothreitol (DTT), lithium 3,5-diiodosalicylate (LIS), or 3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulfonate (CHAPS) were used. A pellet of pooled thrice-washed semen was divided and extracted with these detergents. Similar gel electrophoresis profiles, as revealed by silver staining, were observed with the LIS, DOC, NP-40 and CHAPS extracts, whereas DTT extracts lacked the 150 and 200 kDa bands. Different thrice-washed semen pools varied in their protein pattern, probably due to the presence of sloughed germinal cells, white blood cells and sloughed cells from the reproductive tract. Swim-up sperm extracts had a different protein profile from that of thrice-washed pools but pools of swim-up sperm had a more constant protein pattern than those of thrice-washed semen pellets. Monoclonal antisperm antibodies did not always recognize antigens of the same molecular weights in western blots when extracts of swim-up sperm versus thrice-washed sperm were compared. In immunoblot studies with monoclonals (produced against thrice-washed sperm, cloned five times, reactive by ELISA and sperm function tests), 4/12 reacted with 0.3% NP-40 extracts of thrice-washed sperm and 5/12 with 0.3% NP-40 extract of swim-up sperm. These findings suggest that definition of antigens by monoclonal antisperm antibodies will be influenced by the nature of sperm extract employed.

Antibodies, Monoclonal↗
PubMed1990

Use of a piezoelectric film sensor for monitoring vascular grafts.

Detection of failing arterial reconstructions requires intensive surveillance by frequent physical examination and noninvasive laboratory testing. However, many grafts fail during the intervals between these examinations. For this reason, we have developed an implantable miniaturized piezoelectric flow detection device whose function can be monitored externally by radiotransmission across the skin. Sensors were constructed from ultrathin polyvinylidene fluoride (PVF2) with piezoelectric activity and attached with silicone fixative to 6-mm polytetrafluoroethylene grafts. Ten of these grafts were placed in mongrel dogs as iliofemoral bypasses. Real time data were acquired from the sensors at a rate of 200 Hz, using a DATAQ A/D data acquisition board and CODAS data acquisition software, while simultaneous blood flow (using an electromagnetic flowmeter) and intraluminal pressure were processed by using separate channels of the same data acquisition board. The data were stored on computer storage media and analyzed by the ASYST software, which allows simultaneous signal curves to be compared using regression analysis. In the resting state, the mean blood flow was 123 +/- 16 mL and the mean intraluminal pressure was 124/78 mm Hg, and there was perfect correlation between the PVF2 sensor and the flowmeter and between the sensor and the intraluminal pressure (correlation coefficient, r greater than or equal to 0.99 and r greater than or equal to 0.93, respectively). A tourniquet was applied to the iliac artery proximal to the graft to reduce the flow to approximately half of the resting state (mean flow after tourniquet: 66 +/- 6 mL/minute). Signal tracings from the three sources showed a remarkable similarity with a very high correlation coefficient (r greater than or equal to 0.99 between sensor and flowmeter and r greater than or equal to 0.92 between sensor and the pressure signal). These preliminary results show that the sensors made from low-profile and low-mass PVF2 material have the potential of being implanted around grafts for long-term, continuous monitoring of graft function. Further studies involving long-term implantation to assess the effect of tissue ingrowth and loss of compliance are necessary before this device can be used clinically.

Animals↗
PubMed1990

Pulmonary mechanics in healthy term neonates: variability in measurements obtained with a computerized system.

Using a commercially available computer-based analysis of ventilation and esophageal pressure (PeDs), we studied 11 healthy term neonates with serial pulmonary mechanics measurements during the first 3 days of life to determine the intrasubject variability of repeated measurements. Three consecutive pulmonary function tests were obtained before and after repositioning of the esophageal catheter, for a total of six measurements per day in each subject. The daily coefficient of variation for these 11 subjects ranged from 6% to 32% for respiratory rate; 6% to 27% for tidal volume; 3% to 28% for specific dynamic compliance, and 11% to 69% for pulmonary resistance. Repositioning the esophageal catheter did not produce significant differences in measurements of pulmonary mechanics (p greater than 0.05). We conclude that within a given subject, the maximum variability (mean + 2 SD) was 28% for specific dynamic compliance and 56% for pulmonary resistance. These intrasubject variability limits are important when one is interpreting pulmonary mechanics measurements in neonates before and after specific treatment, such as bronchodilators, diuretics, surfactant, or steroids.

Airway Resistance↗
PubMed1990

Production and characterization of a monoclonal antibody (P6) reactive to Mycobacterium tuberculosis.

The production and characterization of a murine monoclonal antibody (P6) to Mycobacterium tuberculosis is described. The specificity of the monoclonal antibody, an IgG1/K type, was tested against sonic extracts obtained from 27 mycobacteria and 39 bacteria by an enzyme-linked immunosorbent assay. Apparently it was highly specific for the virulent form of M. tuberculosis (H37Rv) and did not react with avirulent strains of M. tuberculosis (H37Ra) and M. bovis (BCG). It was devoid of reactivity with all other mycobacteria and bacteria except to a reaction of low extent with Nocardia asteroides (11.8%). The antibody recognized intact M. tuberculosis as well as the sonicate. Various pathogenic strains of M. tuberculosis collected from different geographical locations showed a range of reactivity with this monoclonal antibody. The antibody reacted strongly with M. tuberculosis South Indian (79112) and British strain (wild) and to varying extents with other strains of M. tuberculosis tested. In Western immunoblots, it recognized antigens of 45 and 96 KDa of M. tuberculosis (H37Rv).

Antibodies, Bacterial↗
PubMed1990

Limb loss with patent infra-inguinal bypasses.

To determine systemic and local risk factors that contribute to limb loss despite a patent infra-inguinal bypass graft and how to prevent it, we reviewed 987 patients who underwent infra-inguinal bypasses at our institution. Seventy-five (7.6%) patent grafts failed to achieve a healed foot despite exhaustive attempts to do so and these patients underwent major amputation either above the knee (AKA) or below the knee (BKA). In 525 femoro-popliteal bypasses, there were 38 major amputations (29 BKA; 9 AKA) with a patent graft; in 462 femoro-distal bypasses, there were 37 amputations (22 BKA; 15 AKA) with a patent graft. The remaining 912 patients with limb salvage as well as all the patients with limb loss were evaluated with regard to systemic risk factors, quality of the run-off from the popliteal artery, continuity of the tibial artery into the arch as demonstrated on arteriography, the haemodynamic improvement obtained postoperatively, and the presence and extent of necrosis in the foot. The presence of diabetes, extensive pedal necrosis and advanced infection predispose to limb loss despite a patent lower extremity bypass graft. Patients who lost their limbs despite a functioning bypass to an isolated popliteal segment had significantly less pronounced haemodynamic improvement postoperatively. An early graft extension to a reconstituted tibial or peroneal artery or a direct bypass to a distal tibial or peroneal artery may reduce the incidence of limb loss in this setting. When a patent bypass to an isolated tibial or peroneal artery segment failed to relieve foot ischaemia, limb salvage was achieved by a distal extension to plantar arteries.

Amputation, Surgical↗
PubMed1990

Short vein grafts in limb-saving arterial reconstructions.

In the management of limb-threatening infrainguinal arteriosclerosis, the short vein graft is a feature of distal-origin bypass procedures from the superficial femoral and popliteal arteries to more distal arteries. These procedures, which can only be performed in selected patients, have patency rates equivalent to those of comparable bypasses from the common femoral artery. Other advantages include the increased availability of the shorter vein graft segment that is required. Two newer operations that use short vein grafts are tibio-tibial bypasses and bypasses to isolated segments of infrapopliteal arteries. The authors' initial experience with these two procedures includes encouraging patency and limb salvage rates for periods up to 2 years in patients for whom there was no other therapeutic option short of amputation.

Arterial Occlusive Diseases↗
PubMed1990

Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of benzodiazepines. II. Triazolam.

This study compares the time course of triazolam effects on psychomotor and cognitive skills with triazolam plasma concentrations in a combined pharmacokinetic-pharmacodynamic (sigmoid-Emax) model. Ten male subjects received a single oral dose (1 mg) of triazolam or placebo. The CNS impairment effects were measured by using computerized tracking, body sway, and digit symbol substitution tests, and triazolam plasma concentration was measured by gas chromatography. The drug-induced effect changes lagged behind the plasma drug level changes. The magnitude of the time lag was quantified by the half-time of equilibration between concentrations in the hypothetical effect compartment and the plasma triazolam levels (t 1/2 keo). Essentially the same t 1/2 keo (approximately 6 min) was found for subcritical tracking, body sway, and digit symbol substitution tests. When using the predicted drug concentrations at the effect site, the hysteresis of the plasma concentration-effect disappears, suggesting that the hysteresis is not caused by drug induced tolerance. Moreover, the model allows for estimation of the effect site concentration that causes one-half of the maximal predicted effect (EC50, approximately 5 ng/ml) which is a measure of an individual's sensitivity to triazolam. On the basis of the EC50 values of the effect measures, body sway was slightly less sensitive to triazolam than subcritical tracking and digit symbol substitution tests.

Adult↗
PubMed1990

High-fat meals increase the clearance of cyclosporine.

High-fat meals increase the clearance and volume of distribution, but not the mean residence time, of cyclosporine in seven healthy volunteers when either plasma or blood analyses are used. This unexpected finding for a low-extraction ratio drug should not be explainable in terms of increased blood flow. We hypothesize that dietary fat can act as a carrier for cyclosporine and enhance both its volume of distribution and its clearance. We suggest that clearance then occurs following metabolism of lipids due to lipase activity within the hepatocyte, thereby releasing free drug for metabolism.

Biological Availability↗
PubMed1990

Safety of peripheral vascular surgery after recent acute myocardial infarction.

We have treated 30 patients requiring urgent or emergent vascular procedures in the first 6 weeks after a myocardial infarction (median 11 days) from 1977 through 1989. Forty operations were performed, including 28 lower extremity revascularizations, 10 major amputations and revisions, and two carotid endarterectomies. There were four postoperative deaths (three cardiac related) and two nonfatal reinfarctions. Cardiac complications did not correlate with age, interval from myocardial infarction to surgery within the initial 6 weeks, type of anesthesia, or complexity of operation. Twenty of 24 patients survived attempts at leg revascularization, with ultimate limb salvage in 16. Our cardiac complication rate of 17% (5/30 patients) was reasonably close to that predicted by the Goldman risk scale for classes II and III and significantly better than class IV and also better than that predicted by the Cooperman risk scale for vascular surgery, despite the more recent preoperative myocardial infarctions in our patients. We attribute our low morbidity and mortality to the extracavitary nature of the procedures and possibly to improvements in anesthetic and perioperative management. Patients requiring urgent revascularization for limb salvage should not be denied surgery on the basis of a recent myocardial infarction.

Adult↗
PubMed1990

Influence of vein size (diameter) on infrapopliteal reversed vein graft patency.

We reviewed 239 infrapopliteal reversed greater saphenous vein graft bypasses placed for critical ischemia over a 7-year period to determine the influence of vein diameter on graft patency and limb salvage. Grafts were assigned to four groups based on the minimum external diameter measured during operation: less than 3.0 mm, n = 18; 3.0 mm, n = 59; 3.5 mm, n = 67; and greater than or equal to 4.0 mm, n = 145. A pattern of increasing graft patency and limb salvage among the four groups was noted as the minimum external diameter increased from less than 3.0 mm to greater than or equal to 4.0 mm. When compared to the larger grafts greater than or equal to 4.0 mm, primary graft patency was significantly lower both for less than 3.0 mm grafts (0% for less than 3.0 mm vs 65% for greater than or equal to 4.0 mm at 3 years, p less than 0.001) and for long (greater than 45 cm) 3.0 mm grafts (38% for long 3.0 mm vs 75% for greater than or equal to 4.0 mm at 2 years, p less than 0.005). All 3.5 mm and short (less than 45 cm) 3.0 mm grafts had patency rates similar to greater than or equal to 4.0 mm veins. Thus long 3.0 mm and all less than 3.0 mm reversed saphenous vein grafts should be considered at high risk for failure. Veins with fibrotic, thick-walled segments identified during operation (n = 19) had patency rates significantly lower than nonfibrotic veins (n = 270; p less than 0.01), and this may play a role in the failure of some less than 3.0 mm minimum external diameter vein grafts.

Arteriovenous Shunt, Surgical↗
PubMed1990

Interruption of critical aortoiliac collateral circulation during nonvascular operations: a cause of acute limb-threatening ischemia.

In patients with aortoiliac occlusive disease interruption of critical collaterals during another nonvascular or cardiac operation may threaten limb viability. This occurred in four patients whose limb-threatening ischemia was precipitated by radical cystectomy with bilateral hypogastric artery ligation, left colon resection, or coronary artery revascularizations by means of the internal mammary artery. Important collateral pathways, the interruption of which may account for this phenomenon, are detailed, and approaches are outlined for prevention and management of acute ischemia in this setting.

Acute Disease↗