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Biomedical subjects

S Rajan

Publications and source records attributed to S Rajan.

At least 19 recordsLinked to original sources

TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor.

Tandem pore domain acid-sensitive K(+) channel 3 (TASK-3) is a new member of the tandem pore domain potassium channel family. A cDNA encoding a 365- amino acid polypeptide with four putative transmembrane segments and two pore regions was isolated from guinea pig brain. An orthologous sequence was cloned from a human genomic library. Although TASK-3 is 62% identical to TASK-1, the cytosolic C-terminal sequence is only weakly conserved. Analysis of the gene structure identified an intron within the conserved GYG motif of the first pore region. Reverse transcriptase-polymerase chain reaction analysis showed strong expression in brain but very weak mRNA levels in other tissues. Cell-attached patch-clamp recordings of TASK-3 expressed in HEK293 cells showed that the single channel current-voltage relation was inwardly rectifying, and open probability increased markedly with depolarization. Removal of external divalent cations increased the mean single channel current measured at -100 mV from -2.3 to -5.8 pA. Expression of TASK-3 in Xenopus oocytes revealed an outwardly rectifying K(+) current that was strongly decreased in the presence of lower extracellular pH. Substitution of the histidine residue His-98 by asparagine or tyrosine abolished pH sensitivity. This histidine, which is located at the outer part of the pore adjacent to the selectivity filter, may be an essential component of the extracellular pH sensor.

Amino Acid Sequence

Understanding dual enrollees' use of Medicare home health services: the effects of differences in Medicaid home care programs.

OBJECTIVES: Both the Medicare and Medicaid programs have experienced considerable growth in spending on home care in recent years. As policymakers adopt measures (such as those legislated in the Balanced Budget Act of 1997) to curb the rate of spending growth on home care services, it is important to understand interactions between the Medicare and Medicaid home care programs in serving the dually enrolled population. This study examines the potential effects of the Medicaid home care program on Medicare home health utilization using multivariate models. METHODS: The study relied on data from the Health Care Financing Administration's Medicare Current Beneficiary Survey (MCBS), a longitudinal survey of Medicare enrollees. The primary MCBS file used was from Round 1 of the survey, which was fielded between September and December 1991. The unit of analysis was individuals. The authors used descriptive and multivariate methods to explore the relationship between Medicare coverage and state home care program characteristics. Included were variables that have been found to be significant determinants of Medicare home health utilization in other studies as well as variables to indicate the availability and generosity of Medicaid home care services in each state represented in the survey. RESULTS: The findings were consistent with those of previous studies, in that dual enrollees were disproportionate users of Medicare home health services, accounting for only 16% of enrollees but receiving 40% of all visits. In addition, lower levels of Medicare home health use were observed in states with relatively higher Medicaid spending on home health and personal care services, but this relationship appeared to be heavily dominated by the inclusion of enrollees living in New York State. When individuals from New York were excluded from the analysis, we found a negative but statistically significant relationship between Medicaid outlays on home health and personal care services and Medicare home health utilization. CONCLUSIONS: Because the Medicare and Medicaid programs are interconnected through the sizable dual enrollee population, changes in one program are likely to have ramifications for the other. This study presents another step in exploring how the two programs interact and emphasizes the fact that costs can be shifted between the two programs as policy changes are made to control the rate of home care spending growth.

Aged

T2-weighted MRI of the uterus: fast spin echo vs. breath-hold fast spin echo.

This study compared one routine T2-weighted fast spin echo (T2FSE) sequence with a breath-hold T2FSE (BH T2FSE) sequence of the female pelvis for image quality, uterine anatomy, lesion detection, and signal intensity measurements. Thirty-two consecutive women (mean age 41.7 years) were imaged at 1.5 T with one high-resolution routine T2FSE sequence and one BH T2FSE sequence in the sagittal plane as part of comprehensive pelvic magnetic resonance imaging. The different image sets were rated separately for imaging characteristics (overall image quality, uterine anatomy definition, lesion detection, and free fluid conspicuity) and then compared side by side. The image sets were also compared for artifacts (ghosting, blurring, pulsatility, and chemical shift misregistration). Signal-to-noise (S/N) and signal difference-to-noise (SD/N) ratios were calculated for the different uterine zones, uterine abnormalities, free fluid, rectus abdominis muscle, and bladder. Contrast-to-noise ratios (CNRs) were calculated for uterine abnormalities. Twenty-eight uterine abnormalities were detected in 20 patients and included leiomyomata (13 patients), adenomyosis (7 patients), benign endometrial polyps (6 patients), endometrial carcinoma (1 patient), and pregnancy (1 patient). BH T2FSE was superior or equivalent to T2FSE for overall image quality in 23/32 patients (71.8%), uterine anatomy definition in 19/32 patients (59.3%), and lesion detection in 13/20 patients (65%). BH T2FSE performed less well than T2FSE for free fluid conspicuity in 5/5 (100%) patients. BH T2FSE was equivalent to or less affected than T2FSE for ghosting artifact in 24/32 patients (75%) and blurring artifact in 29/32 patients (90.6%). Pulsatility and chemical shift artifacts were not problematic for either image set. S/N and SD/N were higher for all BH T2FSE determinations compared with T2FSE. For the endometrium, junctional zone, myometrium, and bladder, these differences were statistically significant. There were no statistically significant differences for CNR between the two image sets, although BH T2FSE values for leiomyomata, adenomyosis, and abnormal endometria were higher than those calculated for T2FSE. All pathology detected with T2FSE was detected on BH T2FSE despite the breath-hold sequence's inherently poorer spatial resolution compared with the non-breath-hold sequence. BH T2FSE may be able to replace T2FSE for some uterine applications with a substantial time savings.

Adult

Transmyocardial laser revascularization: early results and 1-year follow-up.

BACKGROUND: Transmyocardial revascularization using a high-energy CO2 laser has emerged as a new therapeutic option for patients with severe diffuse coronary artery disease refractory to conventional modes of therapy. METHODS: From December 1994 to September 1997, 102 patients underwent isolated transmyocardial revascularization. The mean age was 56.7 +/- 9.2 years and 92.15% were men. Mean preoperative angina class and ejection fraction were 2.6 +/- 0.7 and 44.7% +/- 10.5%, respectively. Diabetes was present in 49.01% of patients, 32.3% had history of previous myocardial infarction, and 12.7% had undergone a previous coronary artery bypass graft procedure. An average number of 23 +/- 8 channels were created in each patient using an 800-W CO2 laser. RESULTS: The early mortality was 14.7% and univariate predictors of mortality were age more than 55 years, female sex, creatine kinase more than 1,600 IU, absence of intercoronary collaterals, and mean pulmonary artery pressure greater than 21 mm Hg. At 1-year follow-up there was significant improvement in angina class and effort tolerance but no significant change in left ventricular ejection fraction. CONCLUSIONS: We conclude that transmyocardial revascularization provides symptomatic benefit and improves exercise tolerance in a group of patients suffering from disabling angina not amenable to other modes of treatment. The high early mortality can be brought down with strict patient selection criteria. The mechanism of beneficial effects is uncertain and patency of laser channels is controversial, but laser-induced neoangiogenesis is being looked on as a possible explanation.

Adult

Hepatitis C lookback programme: a single hospital experience.

As part of the national Hepatitis C (HCV) Lookback Programme, HCV-infected donors donating blood after September 1991 were identified and the fate of their previous donations received at a single hospital were traced; 123 of 160 implicated blood components were traceable and transfused. Only 19 recipients were alive and traceable and were tested for HCV. Nine of the 14 recipients (64%) of HCV-positive donations and 2 of 5 recipients (40%) of HCV-indeterminate donations had evidence of HCV infection. Neither the number of donor exposures nor the type of component was predictive of recipient HCV status. Three recipients have chronic active hepatitis. The Hepatitis C Lookback Programme successfully identifies some but not all cases of transfusion-transmitted HCV. Transfusion records, particularly in the medical case notes, should be substantially improved. Many of the traced recipients are young, so that identification of HCV is of great importance.

Adolescent

The effects of aerosolized dextran in a mouse model of Pseudomonas aeruginosa pulmonary infection.

Airway infections initiated by the interaction of bacterial adhesins with carbohydrate receptors can be potentially prevented by nontoxic carbohydrate inhibitors. Intranasal inoculation of neonatal mice with Pseudomonas aeruginosa PAO1 caused pneumonia in 55% of control mice but in only 13% of mice inoculated 2 h after dextran inhalation (P<.001) and in 28% inoculated 4 h after dextran inhalation (P=.02). PAO1 adherence to epithelial cells was inhibited by 50% in the presence of dextran. Dextran was well distributed throughout the airways and stimulated tumor necrosis factor-alpha production in murine lungs but not interleukin-8 production by human epithelial cell lines. Phagocytosis of PAO1 was not affected by dextran nor was killing by human neutrophils diminished. Administration of dextran by aerosol may prevent murine pneumonia by impeding bacterial access to epithelial receptors and by stimulation of the immune functions of the epithelium.

Aerosols

An alternative approach to measuring the effects of insurance market reforms.

Reforms in the small group and individual insurance markets could make it easier for the currently insured to keep their coverage, and could expand coverage by making insurance more accessible to the currently uninsured. We use data from the 1989 through 1995 Current Population Survey to measure the impact of these reforms on state-level rates of uninsurance and private health insurance coverage. Instead of examining the effect of each of the various types of insurance marker reforms, we estimate the impact of packages of reforms on insurance coverage, reflecting how policies were implemented. We find that small group reforms have done little to affect insurance coverage. Individual market reforms, on the other hand, appear to increase uninsurance rates and reduce private coverage. Our findings suggest that small group reforms may have prevented erosion of private coverage, but have not reduced the numbers of uninsured people.

Employment

The National Survey of America's Families: an overview of the health policy component.

This report describes one aspect of "Assessing the New Federalism," a multi-year research project, started by the Urban Institute in 1996, to analyze the devolution of responsibility for social programs from the federal government to the states. The project combines case studies in 13 diverse states with analyses of data drawn from a wide range of sources, including a new household survey--the National Survey of America's Families (NSAF). The NSAF, which contains nationally representative data from almost 45,000 families, was fielded in 1997 and 1999, and is planned for 2001 and again at subsequent two-year intervals. In this paper, we provide an overview of the NSAF's purpose; the sampling approach and methods; the questionnaire content, with particular emphasis on questions of interest to health policy researchers; health policy research planned by Urban Institute staff; and the timetable for public release of the NSAF data.

Family Health

Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection.

Pseudomonas aeruginosa strains are opportunistic pathogens associated with infections in immunocompromised hosts and patients with cystic fibrosis. Like many other mucosal pathogens, P. aeruginosa cells express flagella which provide motility and chemotaxis toward preferred substrates but also provide a ligand for clearance by phagocytic cells. We tested the role of flagella in the initial stages of respiratory tract infection by comparing the virulence of fliC mutants in a neonatal mouse model of pneumonia. In the absence of fliC, there was no mortality, compared with 30% mortality attributed to the parental strain PAK or 15% mortality associated with infection due to a pilA mutant PAK/NP (P < 0.0001). The fliC mutants caused pneumonia in only 25% of the mice inoculated, regardless of whether there was expression of the pilus, whereas the parental strain was associated with an 80% rate of pneumonia. Histopathological studies demonstrated that the fliC mutants caused very focal inflammation and that the organisms did not spread through the lungs as seen in infection due to either PAK or PAK/NP. Purified flagellin elicited an intense inflammatory response in the mouse lung. 125I-labeled flagellin bound to the glycolipids GM1 and GD1a and to asialoGM1 in an in vitro binding assay. However, flagellin-mediated binding to epithelial gangliosides was a relatively unusual event, as quantified by binding assays of wild-type or fliC mutant organisms to CHO Lec-2 cells with membrane-incorporated GM1. Fla+ organisms but not fliC mutants were efficiently taken up by murine macrophages. P. aeruginosa flagella are important in the establishment of respiratory tract infection and may act as a tether in initial interactions with epithelial membranes. This function is offset by the contribution of flagella to host clearance mechanisms facilitating phagocytic clearance and the role of flagellar genes in mucin binding and clearance.

Animals

Prognostic significance of Bcl-2 and p53 protein expression in stage IIB and IIIB squamous cell carcinoma of the cervix.

Cervical cancer is the most common cancer among women in South India. More than 70% of the cases present in stage IIB and IIIB and of these more than 50% fail conventional treatment. The purpose of the present study was to determine the prognostic significance of Bcl-2 and p53 expression in squamous cell carcinomas of the cervix. Using immunohistochemistry, 40 cases of stage IIB and IIIB squamous cell carcinomas of the cervix treated with radiotherapy were studied for the expression of Bcl-2 and p53 protein and their prognostic value ascertained. Bcl-2 was expressed in 65% (n=26) of the tumours. There was a statistically significant association (p=<0.025) between Bcl-2 expression and poorer DFS and OS in stage IIB cases. In stage IIIB, these associations were not obvious probably due to additional genetic events overshadowing the significance of Bcl-2 expression. Only 4/40 (10%) of the cases were positive for p53 protein expression and there was an inverse correlation between p53 expression and Bcl-2 expression. This study suggests that Bcl-2 can be a useful marker to identify the poor prognostic group in stage IIB cases and needs to be confirmed in a larger series.

Biomarkers, Tumor

Neural networks as predictors of outcomes in alcoholic patients with severe liver disease.

We developed and evaluated neural networks as predictors of outcomes in alcoholic patients with severe liver disease using commonly available clinical and laboratory values. Hospital charts of 144 patients were reviewed. Nine variables (five laboratory, four clinical) were recorded along with in-hospital death or survival. Data were organized into separate development and validation sets. Neural network predictions of survival were compared with those of the Maddrey discriminant function and logistic regression models developed on the same data. Model performance was evaluated by comparing areas under receiver-operating characteristic (ROC) curves and the distributions of model scores. Survivors had significantly different laboratory and clinical characteristics, the most important being a higher prothrombin time, lower bilirubin, and lower incidence of encephalopathy. Neural network performance was significantly better than that of the Maddrey score (ROC areas, 81.5% vs. 73.8%; P = .04). The ROC area for neural networks was similar to that of logistic regression (ROC area 78.2%; P = .3), but the neural networks were more successful in classifying patients into low- and high-risk groups (P < .001). A neural network score with laboratory data from hospital-day 7 improved prognostic accuracy further to 84.3%. After adjusting for baseline risk, the neural network change in illness severity was still a significant predictor of mortality (P = .001). Neural networks using clinical and laboratory data showed a high prognostic accuracy for predicting mortality in alcoholic patients with severe liver disease.

Adult

A circulating, biologically inactive thyrotropin caused by a mutation in the beta subunit gene.

Mutation of a critical carboxy-terminal cysteine residue (C105V) in the thyrotropin-beta (TSH-beta) subunit gene was found in two related families with central hypothyroidism. Affected patients had low thyroid hormone levels and radioactive iodine uptake in the thyroid gland associated with measurable serum TSH. Thyrotropin-releasing hormone-stimulated TSH secretion did not increase thyroid hormone production in these patients as compared to their unaffected siblings, suggesting that the mutant TSH was biologically inactive in vivo. Recombinant TSH harboring this mutation was confirmed to be biologically inactive in an in vitro bioassay. Based on crystallographic structure of chorionic gonadotropin, a disulfide bond between C19 and C105 in the TSH-beta subunit is predicted to form the "buckle" of a "seat belt" that surrounds the common alpha subunit and maintains the conformation and bioactivity of the hormone. This natural mutation of the TSH-beta subunit confirms the importance of the seat belt in the family of pituitary and placental glycoprotein hormones.

Base Sequence

Surgical experience of total anomalous pulmonary venous connection with mid-term follow-up in a developing country.

OBJECTIVE: To illustrate the incidence, the different age group, varied clinical presentation, incremental risk factors for surgery and follow-up results from this part of the world. EXPERIMENTAL DESIGN: Retrospective study with follow-up from 3 months to 5 years. SETTING: Institutional practice with hospitalised care. SELECTION PROCEDURE: Hospitalised patients with a diagnosis of total anomalous pulmonary venous connection. INTERVENTIONS: All patients who were diagnosed to have total anomalous pulmonary venous connection underwent corrective surgery. RESULTS: There were 20 hospital deaths postoperatively. The mean follow-up was 1.9 year. Logistic regression analysis identified age group, timing of surgery, associated anomalies preoperative symptoms, anatomical type of lesion, pulmonary artery hypertension, duration of ventilation, low cardiac output as risk factors for surgery. The mean survival time was 4-8 years. CONCLUSION: Mortality continues to be higher from this part of the world due to severe malnourishment, late presentation. Sociodemographic factors also play a major role in affecting surgical outcome apart from the identified risk factors for surgery.

Cardiac Surgical Procedures

Surgical treatment of transposition of great arteries with interrupted pulmonary artery: a rare association of embryopathies.

The first case of TGA with VSD, ASD, and interrupted LPA and its successful surgical treatment is being reported along with a review of the relevant literature. The dominant presenting clinical features have been explained and an attempt has been made to explain the paucity of records in regard to this embryopathy. An arterial switch for TGA and a glutaraldehyde pretreated autologous pericardial roll for repair of interrupted LPA were carried out. Pre- and postoperative hemodynamics and angiography data are also presented.

Ductus Arteriosus, Patent

Insuring the poor through Section 1115 Medicaid waivers.

With the demise of health care reform at the national level, much of the attention has shifted to state-level efforts. Recently, several states have begun looking to the Medicaid program as a way to solve their health care problems. A principal way in which states are implementing health care reform is through the Section 1115 research and demonstration Medicaid waiver program. The 1115 waiver authority provides states considerable flexibility to restructure their Medicaid programs to offer health care to new populations and thus has great potential for covering large segments of the uninsured population. While it shows great promise, however, there are many obstacles states must overcome both in implementing and in maintaining an 1115 program.

Eligibility Determination