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Biomedical subjects

P K Sen

Publications and source records attributed to P K Sen.

At least 19 recordsLinked to original sources

Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model.

OBJECTIVE: To develop a model to predict transmission of HIV-1 from men to women. DESIGN: HIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated with epidemiological studies of HIV-1 transmission to develop a probabilistic model. SETTINGS: Semen samples were collected from patient subjects in Seattle Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocervical biopsy specimens were obtained from women in Chicago, Illinois. PARTICIPANTS: Eighty-six men (not receiving antiretroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the number of endocervical CCR5 receptors were determined. MAIN OUTCOME MEASURES: Prediction of transmission of HIV-1 from men to women per episode of vaginal intercourse based on the absolute burden of HIV (volume x HIV RNA copies/ml seminal plasma). RESULTS: The model suggests efficient heterosexual transmission of HIV-1 when semen viral burden is high. When semen contains 100 000 copies of non-syncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen, transmission probability is 3 per 10 000 episodes of intercourse. CONCLUSIONS: This model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.

Cervix Uteri↗

Characteristics of iron ore tailing slime in India and its test for required pond size.

The physical and chemical nature of the tailing slime depends on milling operations and water content in the effluent. The characteristics of the tailings dictate the type of disposal facility required. Characteristics of the tailings, transportation from beneficiation plants and disposal system are described. Studies on tailing slime have been carried out at iron ore mines in Orissa and the results are discussed. The tailings contain toxic elements and find their way into the water environment. Sedimentation test was carried out on tailings and the area required for tailing pond was found to be 3155 m2 in comparison to 10000 m2 obtained from the use of an empirical equation. Provision of tailing pond for the disposal of tailings is a conservation of resources in addition to pollution control, and sedimentation test is essential for required pond size calculation.

India↗

The long-term outcome after central cord syndrome: a study of the natural history.

We studied 32 patients with central cord syndrome who were managed conservatively. Six were under 50 years of age (group 1), 16 between 50 and 70 years (group 2) and ten over 70 years (group 3). At the time of discharge all patients in group 1 could walk independently and had good bladder control compared with 11 (69%) and 14 (88%) in group 2 and four (40%) and two (20%) in group 3, respectively. At follow-up after a mean of 8.6 years (4 to 15), ten patients had died leaving 22 in the study. All those in group 1 were alive, could walk independently and had bladder control. In group 2, 13 were alive of whom ten (77%) could walk independently and nine (69%) had bladder control. In group 3 only three were alive of whom only one was independent and none had bladder control. Function at discharge as measured by the ASIA motor scoring system was usually maintained or improved at follow-up, but patients over 70 years of age at injury did poorly.

Activities of Daily Living↗

Glaucoma after pars plana vitrectomy and silicone oil injection for complicated retinal detachments.

OBJECTIVE: To determine the incidence and associations of glaucoma after pars plana vitrectomy (PPV) and silicone oil injection (SOI) for complicated retinal detachments and the response to treatment. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: A total of 150 eyes of 150 patients who had completed a minimum of 6 months of follow-up were included in this study. Analysis included clinical records of all consecutive cases of complicated retinal detachment that underwent PPV with SOI between July 1991 and February 1996. INTERVENTION: Surgical intervention for vitreoretinal pathology included standard three-port PPV and additional procedures as appropriate for the retinal pathology, and SOI. Procedures for the control of glaucoma were silicone oil removal (SOR), trabeculectomy with mitomycin C, cyclocryotherapy, semiconductor diode laser contact transscleral cyclophotocoagulation (TSCPC) and anterior chamber tube shunt to encircling band (ACTSEB). MAIN OUTCOME MEASURES: Presence of glaucoma (predefined as intraocular pressure [IOP] > or = 24 mmHg, which also was > or = 10 mmHg over the preoperative level, sustained for > or = 6 weeks) and the result of medical and surgical management were the main outcome measures. Demographic, preoperative, intraoperative, and postoperative parameters including the age of the patient, etiology of retinal detachment, refractive status, pre-existing glaucoma, aphakia, diabetes mellitus, presence of silicone oil (SO) in the anterior chamber, emulsification of SO, rubeosis iridis, and anatomic success were evaluated by univariate and multivariate logistic regression analyses to assess their predictive value in the causation of glaucoma and to determine factors prognosticating response to treatment. RESULTS: The main indications for PPV+SOI were proliferative vitreoretinopathy (57%; 85 of 150), proliferative diabetic retinopathy (15%; 23 of 150), and trauma (14%, 21 of 150). Glaucoma occurred in 60 eyes (40%) at 14 days median (range, 1 day-18 months). Elevation of IOP could be attributed directly to SO in 42 (70%) eyes. Glaucoma was controlled in 43 (72%) of 60 eyes on treatment (with medicines alone in 30%; SOR and medicines in 25%; trabeculectomy with mitomycin C/ACTSEB/cyclocryotherapy or TSCPC in 17%); 28% (17 of 60) remained refractory. Independent predictive factors for glaucoma on multivariate analysis were rubeosis iridis (odds ratio, 10.76), aphakia (odds ratio, 9.83), diabetes (odds ratio, 6.03), SO in anterior chamber (odds ratio, 4.74), and anatomic failure (negative risk factor; odds ratio, 0.11). Poor prognostic factors for the control of glaucoma were SO emulsification (odds ratio, 15.34) and diabetes (odds ratio, 6.03). CONCLUSION: Glaucoma is a frequent and often a refractory complication of PPV with SOI and has a multifactorial etiology. Aggressive medical and surgical management with SOR, trabeculectomy with mitomycin C, glaucoma shunts, and cyclodestructive procedures shows modest success in controlling IOP.

Adolescent↗

A random effects model for multivariate failure time data from multicenter clinical trials.

A random effects model for analyzing multivariate failure time data is proposed. The work is motivated by the need for assessing the mean treatment effect in a multicenter clinical trial study, assuming that the centers are a random sample from an underlying population. An estimating equation for the mean hazard ratio parameter is proposed. The proposed estimator is shown to be consistent and asymptotically normally distributed. A variance estimator, based on large sample theory, is proposed. Simulation results indicate that the proposed estimator performs well in finite samples. The proposed variance estimator effectively corrects the bias of the naive variance estimator, which assumes independence of individuals within a group. The methodology is illustrated with a clinical trial data set from the Studies of Left Ventricular Dysfunction. This shows that the variability of the treatment effect is higher than found by means of simpler models.

Angiotensin-Converting Enzyme Inhibitors↗

A marginal mixed baseline hazards model for multivariate failure time data.

In multivariate failure time data analysis, a marginal regression modeling approach is often preferred to avoid assumptions on the dependence structure among correlated failure times. In this paper, a marginal mixed baseline hazards model is introduced. Estimating equations are proposed for the estimation of the marginal hazard ratio parameters. The proposed estimators are shown to be consistent and asymptotically Gaussian with a robust covariance matrix that can be consistently estimated. Simulation studies indicate the adequacy of the proposed methodology for practical sample sizes. The methodology is illustrated with a data set from the Framingham Heart Study.

Biometry↗

Genetic evidence that Neisseria gonorrhoeae produces specific receptors for transferrin and lactoferrin.

Transferrin (TF) and lactoferrin (LF) are probably the major sources of iron (Fe) for Neisseria gonorrhoeae in vivo. We isolated mutants of N. gonorrhoeae FA19 that were unable to grow with Fe bound to either TF (TF-) or LF (LF-) or to both TF and LF ([TF LF]-). The amount of Fe internalized by each of the mutants was reduced to background levels from the relevant iron source(s). The wild-type parent strain exhibited saturable specific binding of TF and LF; receptor activity was induced by Fe starvation. The TF(-)-specific or LF(-)-specific mutants were almost completely lacking in receptor activity for TF or LF, respectively, whereas the [TF LF]- mutants bound both TF and LF as well as the wild-type strain. All mutants utilized citrate and heme normally as Fe sources. These results demonstrate that ability to bind TF or LF is essential for gonococci to scavenge appreciable amounts of Fe from these sources in vitro. In addition, the TF and LF Fe acquisition pathways are linked by the mutual use of a nonreceptor gene product that is essential to Fe scavenging from both of these sources; this gene product is not required for Fe acquisition from other sources.

Binding, Competitive↗

Effects of chlorothiazide on 1,25-dihydroxyvitamin D3, parathyroid hormone, and intestinal calcium absorption in the rat.

Previous studies have shown that thiazide diuretic agents reverse secondary hyperparathyroidism and reduce circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and intestinal calcium absorption rates in patients with idiopathic hypercalciuria of the renal-leak variety. We have investigated whether thiazides can reverse the secondary increase in serum parathyroid hormone (PTH) and 1,25(OH)2D3 levels or intestinal calcium absorption induced by feeding rats a diet low in calcium (LCD, 0.02% calcium) but adequate in phosphorus and vitamin D. We found that LCD increased circulating immunoreactive PTH [chow vs. LCD, 0.52 +/- 0.06 vs. 1.06 +2- 0.1 (SE) ng/ml, P less than 0.001], 1,25(OH)2D3 (chow vs. LCD, 101 +/- 15 vs. 325 +/- 38 pg/ml, P less than 0.001), calcium uptake by everted gut sacs from duodenum, ileum, and descending colon, and net calcium absorption by descending colon studied in Ussing chambers in vitro. Chlorothiazide (CTZ) prevented the increase in PTH during LCD (chow + CTZ vs. LCD + CTZ, 0.69 +/- 0.07 vs. 0.73 +/- 0.06, NS) but not the increase in 1,25(OH)2D3 (chow + CTZ vs. LCD + CTZ, 88 +/- 10 vs. 277 +/- 31, P less than 0.002) or intestinal calcium transport. The drug caused no change in serum 1,25(OH)2D3 or intestinal calcium absorption in rats fed normal chow. In rats given exogenous 1,25(OH)2D3 to stimulate intestinal calcium absorption, CTZ reduced urine calcium excretion greatly but did not alter intestinal calcium absorption.

Administration, Oral↗

Effects of metabolic acidosis on PTH and 1,25(OH)2D3 response to low calcium diet.

To study the effects of chronic metabolic acidosis on the metabolism of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] rats were given either a low calcium diet (LCD) (0.002% calcium) or chow (1.2% calcium); ammonium chloride (NH4Cl) was added (1 or 1.5%) to the drinking water of some rats eating LCD or chow while others served as nonacidotic controls. LCD increased circulating 1,25(OH)2D3 levels from 46 +/- 14 to 204 +/- 24 pg/ml (P less than 0.001) in the absence of NH4Cl; 1.5% NH4Cl prevented the increase in 1,25(OH)2D3 (25 +/- 6 vs. 27 +/- 8 pg/ml (P, NS) but 1% NH4Cl did not (50 +/- 12 vs. 161 +/- 23 pg/ml; P less than 0.001). Acidosis suppressed neither serum immunoreactive parathyroid hormone (PTH) nor urine cAMP response to LCD. Although total serum calcium and phosphorus showed no regular changes with NH4Cl, acidosis raised blood ionized calcium in rats fed either chow or LCD, and serum 1,25(OH)2D3 levels were inversely correlated with ionized calcium (r = 0.714; P less than 0.001) during LCD. Chronic NH4Cl acidosis prevented serum 1,25(OH)2D3 from rising during LCD, independent of changes in PTH secretion, cAMP generation, or serum phosphorus. The absence of a 1,25(OH)2D3 response may be due to increased ionized calcium produced by acidosis.

Acidosis↗

The stereochemistry of beta-lactam formation in penicillin biosynthesis.

1. (2R,3S)-[U-14C,3-3H1]- and (2R,3R)-[U-14C,2,3-3H2] Cysteine hydrochlorides have been separately synthesised. The latter compound has been shown to have uniform distributions of tritium between C-2 and C-3. 2. The abvoe cysteines and (2R)-[U-14C,3,3,3',3'-3H4]cystine have been converted to samples of penicillin G by Penicillium chrysogenum. 3. Incorporation results indicate that all but 14% of the tritium is lost from the (2R,3S)-[3-3H1]isomer; that 42% of tritium is retained by the non-stereospecifically C-3 tritiated cystine; and that 58% of tritium is retained by the (2R,3R)-[2,3-3H2]isomer on conversion to penicillin G. 4. Degradation of the penicillin G derived from (2R,3R)-[U-14C,2,3-3H2]cysteine hydrochloride has indicated that in fact about 87% of the original C-3 tritium of cysteine is retained at C-5 of penicillin G. 5. The results indicate stereospecificity in the cyclisation giving rise to the beta-lactam ring in penicillin G in nature with loss of the 3-pro-S-hydrogen and rentention of the 3-pro-R-hydrogen of cysteine. Thus there is net retention of stereochemistry in the cyclisation.

Carbon Radioisotopes↗