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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 829 records · Page 46Linked to original sources

Catecholamines increase monocyte TNF receptors and inhibit TNF through beta 2-adrenoreceptor activation.

Postinjury deficits in monocyte tumor necrosis factor receptors (moTNFR) activity may alter beneficial functions during an inflammatory response. Several counter-regulatory hormones elicited during inflammation may modulate tumor necrosis factor (TNF) activity, but little is known about their influence on moTNFR. Also, catecholamines inhibit TNF production, but the adrenoreceptor mechanism of this effect has not been fully clarified. To determine the effect of catecholamines and corticosteroids on moTNFR, whole blood was coincubated for up to 8 (moTNFR) or 24 h (cytokines) in the presence of lipopolysaccharide (100 ng/ml) and 1) epinephrine (Epi, 10(-6) M), dexamethasone (Dex, 10(-6) M) or both (EpiDex, 10(-6) M) to assess the expression of total moTNFR, moTNFR-I, and moTNFR-II. 2) Epi and norepinephrine (EpiNE, 10(-6) M) and the alpha 1 + 2-, beta 1 + 2-, beta 1-, or beta 2-adrenergic antagonists were used to assess the role of such adrenoreceptors on total moTNFR and TNF production, and N6,2'-O-dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) alone or in combination with the phosphodiesterase inhibitor Ro-20-1724/000, to study the cAMP-dependent pathway on total moTNFR. We found that Epi upregulated total moTNFR and moTNFR-II. Dex did not significantly influence total moTNFR or moTNFR-II. Also, EpiNE increased total moTNFR and inhibited TNF by a beta 2-dependent mechanism. DBcAMP (10(-5) M) modestly enhanced total moTNFR. This suggests a common mechanism for acutely enhancing moTNFR and attenuation of soluble TNF appearance during conditions of severe stress.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Role of sympathetic nervous system in cardiovascular effects of centrally administered endothelin-1 in rats.

Centrally administered endothelin-1 (ET-1) produces a biphasic response, an initial increase followed by a decrease in blood pressure (BP). The pressor effect is due to stimulation of the sympathetic nervous system and/or release of vasopressin. The mechanism responsible for the depressor effect after central administration of ET-1 is still not known. Systemic and regional circulatory effects of intracerebroventricular (i.c.v.) administration of ET-1 (100 ng) were determined in anesthetized rats, using a radioactive microsphere technique. BP, cardiac output, and stroke volume were significantly decreased 30, 60, and 120 min after central administration of ET-1. Heart rate and total peripheral resistance were not altered. ET-1 produced a reduction in blood flow to the brain (83%), heart (62%), kidneys (53%), gastrointestinal tract (43%), portal system (46%), and musculoskeletal system (55%). To determine the role of the central nervous system in cardiovascular effects of centrally administered ET-1, experiments were performed in cervical-sectioned rats. The changes in systemic and regional blood circulation induced by centrally administered ET-1 in normal rats were not observed in cervical-sectioned rats. Pretreatment with a specific antagonist of ETA receptors, BQ-123 (10 micrograms i.c.v.), antagonized systemic and regional circulatory effects of ET-1. Centrally administered clonidine (1 microgram i.c.v.) produced hypotension and bradycardia, known to be mediated through the sympathetic nervous system. Pretreatment with an ETA receptor antagonist, BMS-182874 (50 micrograms/kg iv), blocked clonidine-induced hypotension and bradycardia. We conclude that centrally administered ET-1 stimulates ETA receptors to produce systemic and regional circulatory changes mediated by the sympathetic nervous system.

Animals↗

Renal artery stenosis in aortoarteritis: spectrum of disease in children and adults.

Nonspecific aortoarteritis is the commonest cause of renovascular hypertension (RVH) accounting for 87% of the patients in the present study. We compared the clinical and radiographic features and outcome in children (n = 16) and adult (n = 24) patients with aortoarteritis. Children have a shorter duration of disease and present more commonly with constitutional symptoms. All the patients were hypertensive; however, malignant hypertension and hypertensive encephalopathy were more common in children. Abdominal bruit and asymmetry of pulses were present only in 75 and 35% of the patients, respectively. Asymmetric kidney size on ultrasound was present in 15 of 24 adults, whereas 9 of 16 children had equal sized kidneys. Captopril renography had a better sensitivity for detection of RVH in children (13 of 16 in children vs. 12 of 24 in adults showing positive results). On intra-arterial digital substraction angiography, abdominal aortic involvement was invariable, whereas the thoracic aorta was involved less frequently in both age groups. Angiographic scores for the severity of vascular involvement was significantly lesser in children (6.87+/-4.8) as compared to adults (11.32+/-4.5). Thirteen of the 15 children were found suitable for revascularization, whereas 12 of 24 adults were not considered for revascularization as their kidneys were small and contributed to less than 10% of total function. Six of the adult patients underwent nephrectomy for the control of blood pressure. Results of angioplasty were also better in children than adults. We conclude that children present earlier with less severe vascular disease and respond better to revascularization, as compared to adults.

Adolescent↗

Role of preoperative donor-specific transfusion and cyclosporine in haplo-identical living related renal transplant recipients.

A prospective randomized trial of use of donor-specific transfusion and cyclosporine given 24 h before operation was performed in living related renal transplant recipients. The benefits, disadvantages and effect on graft and patient outcome was analyzed. Cyclosporine was started 72 h before operation and 48 h before donor-specific transfusion (DST). Fifteen patients received DST while another 15 age- and sex-matched living related renal allograft recipients on similar immunosuppression served as controls. Patient and donor demographics were similar in the two groups. The DST group had significantly fewer rejection episodes than the control group (0.26 vs. 1.1 rejection episode per patient, p < 0.01). There were fewer episodes of acute rejection in the first 3 months posttransplant in the DST group. Hyperresponder recipients (as tested by mixed lymphocyte cultures) also benefitted by DST which significantly reduced the number of acute rejection episodes (0.25 vs. 1 episode per hyperresponder patient, DST vs. control, p < 0.05). The need for dialysis, incidence of infections and other complications were similar in the two groups. Graft function at 3, 6, 9 and 12 months after transplant was significantly better in the DST group (p < 0.05). Graft survival at 1 year in DST group (85.5%) was not statistically different than control (74.8%). In conclusion, DST and cyclosporine given 24 h before live related renal transplantation is effective in improving graft function and reducing the number of acute rejection episodes which could have a beneficial effect on long-term graft survival.

Acute Disease↗

Mitrofanoff principle for continent urinary diversion.

In 1980 Mitrofanoff described a method to achieve continent urinary diversion by surgically closing the bladder neck and creating a continent catheterizable stoma from the appendix which had been implanted in a nonrefluxing manner into the bladder or from a nonrefluxing distal ureter. The Mitrofanoff principle (MP) serves well as a continence mechanism for either the native bladder or intestinal reservoirs. We review 17 patients, including 10 children, who were treated with the MP and received a continent catheterizable channel. For the MP, appendix was used in 16 patients and ureter in 1. The continuity between the urinary reservoir and urethra was maintained wherever possible. Bladder neck suspension was preferred to bladder neck closure in incontinent females and boys. Complications and their management have been discussed at length. Stable renal functions, ease of catheterization and urinary continence were achieved in 93.8% of the patients.

Adolescent↗

Remodeling with neointima formation in the mouse carotid artery after cessation of blood flow.

The ability of gene targeting in the mouse species presents a powerful tool to determine the role of specific molecules in vascular biology. Using a denuding-injury procedure, we recently reported that intimal lesions can be induced in the carotid artery of outbred mice. The technical challenge associated with achieving complete denudation and the relatively small size of the developing lesions prompted us to design the present model of neointima formation and vascular remodeling in the carotid artery of the inbred FVB mouse strain. Complete ligation of the vessel near the carotid bifurcation induced rapid proliferation of medial smooth muscle cells, leading to extensive neointima formation in the presence of an endothelial lining. Thrombus formation was not observed except in the most distal part of the vessel adjacent to the ligature. At 4 weeks after ligation, luminal area was reduced by approximately 80% through a combination of decreased vessel diameter and neointima formation. Ultrastructural analysis provided evidence for cell death in the developing neointima as well as the remodeling media. The present model might be useful in identifying those genes important for neointima formation and vascular remodeling.

Animals↗

Chronic, episodic, reversible airway obstruction after viral bronchiolitis in rats.

Viral bronchiolitis in human infants has been associated with persistent airway abnormalities, but not proven as a cause. Previously we observed some adult rats had airway obstruction and hyperresponsiveness following bronchiolitis at an early age. The purpose of this study was to determine, via serial measurements of lung mechanics, whether the postbronchiolitis airway obstruction was episodic or continuous, and to determine the magnitude and duration of glucocorticoid effects. Rats were either virus- (n = 14) or sham-inoculated (n = 8) at 3 wks of age. Lung mechanics were measured 6 times in each rat at postinoculation Weeks 11-18. Half the rats in each group were treated with dexamethasone for 3 d at Week 15. The virus group had higher lung resistance (p = 0.03) and lower dynamic compliance (p = 0.005) than control rats, with airway obstruction occurring in an episodic pattern. Dexamethasone treatment had a transient effect in postbronchiolitis rats; lung resistance normalized in Week 15 (p = 0.006), then returned to pretreatment levels by Weeks 16-18. We conclude that viral bronchiolitis in rats can result in a chronic syndrome of intermittent, reversible airway obstruction which has multiple parallels with human asthma over a prolonged time period.

Airway Resistance↗

Sudden unexplained death in a psychiatric patient--a case report: the role of phenothiazines and physical restraint.

Psychotropic drug use has long been associated with sudden unexplained and unexpected death in psychiatric patients despite controversies surrounding the issue. Physical restraint following violent episodes in psychiatric in-patients is also associated with neurally mediated sudden cardiac death. A case where these two mechanisms have jointly resulted in sudden death is reported. The literature on the subject is reviewed and the measures which may be useful in reducing the incidence of such deaths are discussed. The need for accurate and detailed reporting of such cases is emphasized.

Adult↗

Systemic lupus erythematosus in India.

The first case of systemic lupus erythematosus (SLE) was reported from India in 1995 followed by two more case reports and further, a series of eight cases, till 1969. Since the establishment of a clinical immunology laboratory at a major teaching institution in New Delhi in 1968, SLE was extensively studied and reported from that centre. From mid-1980 onwards several other centres in different regions in India including Chennai (old name Madras), Mumbai (old name Bombay), Calcutta and Hydrabad, also published their regional experience on SLE. Based on these data, the present report describes the clinical and laboratory characteristics of 1366 SLE patients seen in different regions of India. Arthritis, rash, photosensitivity, seizures and psychosis were seen in comparable proportions to other racial groups. Similarly, ANA and anti-DNA antibody positivity was also within the range seen in other racial groups. When compared with other series, however, alopecia, renal lupus, oral ulcers and neurological involvement was seen in higher proportions, reaching statistically significant figures in comparison to some racial groups. In contrast, haematological manifestations were seen in significantly less proportions in comparison to some of the racial groups. Serositis and discoid lesions were also seen in lower proportions than in most of other races. The proportion of those with anti-Sm antibodies was in between two extremes of highest among Africans and Israelis and lowest among Chinese and Europeans. Other manifestations were comparable to most other racial groups. Compared to North American and European reports, significantly low 5 and 10 year survival was observed among patients from India. This could be related to the general public health situation in the country including less than optimal management facilities in hospitals, delay in diagnosis due to lack of awareness of the disease, referral bias where only serious patients reach major city hospitals, or a truly severe disease among Indians, or a combination of these genetic, environmental and/or sociocultural factors. The Main causes of death were irreversible renal damage, infections and neurological involvement. Despite a comparable prevalence of anticardiolipin antibodies (aCL) and lupus anticoagulants (LAC), clinical antiphospholipid syndrome was significantly less common. Genetic studies showed appreciable increase of HLA DR4 (37.5%) among patients compared with controls (18%). Additionally the haplotype B8-DR3 was encountered frequently in the patient group.

Humans↗

Do the homeless get a fair deal from general practitioners?

Many studies have indicated the health status of homeless people to be typically poorer than that of the general population, with various studies indicating a high prevalence of psychiatric illness, drug or alcohol misuse and associated socio-medical problems. The Bristol Primary Healthcare Project is an agency which was established to provide a local health care service tailored to the needs of people who are homeless. The present study was carried out as part of an evaluation of the service offered locally to homeless people by General Practitioners (GPs). A postal questionnaire survey of 155 general practices within the Avon FHSA area was carried out. Both fundholding and non-fundholding practices were included, within an area including inner city, urban and rural/semi-rural locations. One hundred and seventeen completed questionnaires were returned, providing a response rate of 75%. Twenty-seven percent of practices would fully register a homeless person who seeks to register at the practice, 24% would treat as immediate and necessary and 33% would treat as a temporary resident. Four percent of fundholding practices surveyed would fully register homeless persons and 55% of inner city practices would do so. Seventy-nine percent of doctors indicated that homeless patients were more difficult to treat than other patients. The most frequent problems associated with registering homeless persons were perceived to be the associated social problems (90% of respondents agreed), the lack of medical records (88% agreed), the complex health problems (79% agreed) and the associated alcohol or substance misuse (78% agreed). The study has highlighted a need for government to consider providing incentives to GPs to register homeless people without resulting in adverse effects on their contract targets. The reluctance of some practices to register these patients varied by area and type of practice with doctors at fundholding practices being the most reluctant. There is an identified need for further health education and promotion work and initiatives exemplified by the Bristol Primary Healthcare Project for people who are homeless.

Attitude of Health Personnel↗

Tirofiban: an investigational platelet glycoprotein IIb/IIIa receptor antagonist.

The deposition of a platelet rich thrombus on an atherosclerotic plaque is a critical step in the development of unstable coronary syndromes. Currently available therapeutic agents such as aspirin and ticlopidine are relatively weak inhibitors of platelet aggregation. Recently, antagonists to platelet glycoprotein IIb/IIIa (GPIIb/IIIa), a platelet surface integrin whose activation and subsequent binding to fibrinogen is the final common step in the formation of platelet aggregates, have been utilised to treat unstable angina and myocardial infarction. Tirofiban is a novel, specific, low molecular weight GPIIb/IIIa receptor antagonist, which competitively inhibits the platelet fibrinogen receptor. Tirofiban is administered as an intravenous infusion with a mean half-life of 1.6 h. In healthy volunteers, the plasma concentration and half-life of tirofiban are unaffected by pre-treatment with aspirin, although aspirin increases the bleeding time prolongation caused by tirofiban. Tirofiban is excreted by both renal (37%) and non renal mechanisms. Three clinical trials, PRISM, PRISM PLUS, and RESTORE, have evaluated the safety and efficacy of tirofiban in unstable angina and in high-risk percutaneous transluminal coronary angioplasty (PTCA). When compared to heparin in the management of unstable angina, tirofiban decreased the odds of recurrent ischaemia, myocardial infarction, or death by 36% at 48 h, and death by 39% at 30 days. Similarly, the addition of tirofiban to heparin reduced the odds of recurrent ischaemic events for death at 7 days by 34%. RESTORE, a clinical trial evaluating the efficacy and safety of tirofiban in patients undergoing PTCA within 72 h of presentation with unstable angina or myocardial infarction, demonstrated a 38% reduction in a composite end-point at 48 h; the need for urgent PTCA and coronary artery bypass graft (CABG) at 30 days was reduced by 36%. Adverse side-effects, including major bleeding, were not significantly higher with tirofiban treatment. Tirofiban and other GPIIb/IIIa inhibitors represent a major advance in the treatment of unstable coronary syndromes and high-risk PTCA.

Journal Article↗

Density and the journey to work.

"This paper evaluates the influence of residential density on commuting behavior across U.S. cities while controlling for available opportunities, the technology of transportation infrastructure, and individual socio-economic and demographic characteristics. The measures of metropolitan and local density are addressed separately.... Regressions are conducted to predict commuting time, speed, and distance, by mode of travel on a cross-section of individuals nationally and city by city. The results indicate that residential density in the area around the tripmaker's home is an important factor: the higher the density the lower the speed and the shorter the distance.... The paper suggests a threshold density at which the decrease in distance is overtaken by the congestion effects resulting in a residential density between 7,500 and 10,000 persons per square mile (neither the highest nor lowest) with the shortest duration auto commutes."

Americas↗

Hantavirus pulmonary syndrome in Wisconsin.

In the spring of 1993 an outbreak of a new illness caused by a new pathogen was identified in the southwestern United States. This infection struck relatively young, healthy individuals, was characterized by fever, myalgias, respiratory failure, and a high mortality rate. This illness was caused by a new hantavirus and has been termed hantavirus pulmonary syndrome (HPS). The virus is carried by rodents, shed in saliva, urine, and feces. Human infection occurs through inhalation of aerosolized virus. The clinical syndrome has many non-specific signs and symptoms, but does follow a typical course with characteristic laboratory and radiographic findings. Early recognition of this infection is important so maximal supportive care can be initiated. We report the first documented case of hantavirus pulmonary syndrome in Wisconsin and Illinois.

Adult↗

Neuroimaging in late-life mood disorders.

Neuroanatomical and physiological imaging provide unprecedented opportunities to examine the biological substrates of major mental disorders such as late life major depression (MDD). Studies using positron emission tomography (PET) and single photon emission computed tomography (SPECT) demonstrate focal and global abnormalities in patients with MDD when compared with controls. Magnetic resonance imaging (MRI) allows us to examine specific neuroanatomical perturbations in depression and to study the impact of comorbid medical disorders on brain structure and function. These technologies have the potential to provide biological information critical to a better understanding and conceptualization of the neuroscientific basis and treatment of the major mental disorders in late life.

Aged↗

Assessment of radiolucent lines about the glenoid. An in vitro radiographic study.

UNLABELLED: A study was undertaken to investigate the precision of plain radiographs in the assessment of the width of radiolucent lines and to define parameters for more accurate measurement. A metal-backed glenoid component was inserted into fourteen cadaveric scapulae; the component had a radiolucent spacer at the central post to provide a gap with a known width at the component-bone interface. The specimens were mounted in a custom-designed jig, and initial radiographs were made with the glenoid in neutral version; sequential radiographs then were made, at 5-degree intervals, with the glenoid in 0 to 40 degrees of anteversion and retroversion. Four independent observers with various levels of experience measured the width of the radiolucent lines with use of digital microcalipers. Osteometric analysis demonstrated that normal glenoid version ranged from 3 degrees of anteversion to 13 degrees of retroversion; these values were similar to those reported in previous studies. Radiographic analysis showed that accurate measurement of the width of the gap was dependent on the position of the glenoid. The measured widths of the radiolucent lines were significantly smaller than the known width of the gap when retroversion was 10 degrees or more and when anteversion was 15 degrees or more (p < or = 0.05). Radiolucent lines were not consistently observed on radiographs that were made with the glenoid in more than 20 degrees of anteversion and retroversion. An analysis of interobserver error showed close agreement among the measurements made by the different observers when the glenoid was in 0 and 5 degrees of rotation, with decreased agreement when the glenoid was rotated more than 10 degrees from neutral. CLINICAL RELEVANCE: Inaccurate positioning of the patient and anatomical variation in glenoid version may explain the variability in the reported onsets, progressions, and frequencies of radiographic loosening of glenoid components. The findings of the present study also may help to explain the poor association between clinical and radiographic findings reported for patients who have pain at the site of a total shoulder prosthesis. Radiographs made within 10 degrees of neutral should allow accurate assessment of radiolucent lines about the glenoid.

Aged↗