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Biomedical subjects

A Bhatnagar

Publications and source records attributed to A Bhatnagar.

At least 19 recordsLinked to original sources

Effective heart disease prevention: lessons from a qualitative study of user perspectives in Bangladeshi, Indian and Pakistani communities.

OBJECTIVES: Coronary heart disease (CHD) has a high mortality, incidence and prevalence among Indian, Pakistani and Bangladeshi communities in the UK, indicating the need for effective heart disease prevention initiatives for these communities. This paper considers how service user perspectives can be used to develop effective, culturally focused CHD prevention interventions for these target groups by addressing identified barriers, including deeply held cultural beliefs. STUDY DESIGN: A qualitative research study, using a longitudinal action research approach. METHODS: This was a community-based study in Edinburgh. Six focus group discussions--two for each community--were organized with participants from these communities at the beginning of the project. A further six focus group discussions for the same communities were organized six months later. RESULTS: Over the period examined, participants reported varying changes in levels of knowledge relating to the nature, causes and symptoms of CHD. Some participants reported taking slight to significant steps to reduce or prevent heart disease, while others did not. The project was viewed as helpful in increasing knowledge about CHD and preventive measures and encouraging healthier lifestyles. However, persistent barriers to change were also identified, requiring changes to the project that involved not only matching intervention materials and messages to observable, superficial characteristics of the target population, but more fundamental changes that address the cultural, social, historical, environmental and psychological forces that influence health behaviour. CONCLUSION: CHD prevention initiatives need to identify and respond to deep-rooted influences on health-behaviour in 'at-risk' groups, in addition to superficial characteristics of the target populations. It is important for specific prevention initiatives to be linked into wider CHD frameworks to ensure transferability of learning and integration within wider service provision.

Asia, Western↗

Acrolein generation stimulates hypercontraction in isolated human blood vessels.

Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H(2)O(2) exposure (1 microM-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 microM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca(2+) to hypercontraction. Acrolein or allylamine but not H(2)O(2), benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca(2+)-free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension.

Acrolein↗

Acrolein induces vasodilatation of rodent mesenteric bed via an EDHF-dependent mechanism.

Acrolein is generated endogenously during lipid peroxidation and inflammation and is an environmental pollutant. Protein adducts of acrolein are detected in atherosclerotic plaques and neurons of patients with Alzheimer's disease. To understand vascular effects of acrolein exposure, we studied acrolein vasoreactivity in perfused rodent mesenteric bed. Acrolein induced endothelium-dependent vasodilatation that was more robust and more sensitive than dilation induced by 4-hydroxy-trans-2-nonenal, trans-2-hexenal, or propionaldehyde. Acrolein-induced vasodilatation was mediated by K(+)-sensitive components, e.g., it was abolished in 0 [K(+)](o) buffer or in 3 mM tetrabutylammonium, inhibited 75% in 50 microM ouabain, and inhibited 64% in 20 mM K(+) buffer. Moreover, combined treatment with the Ca(2+)-activated K(+) channel inhibitors 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34, 100 nM) and apamin (5 microM) significantly reduced vasodilatation without altering sensitivity to acrolein. However, acrolein-induced % dilation was unaffected by l-NAME or indomethacin pretreatment indicating mechanistic independence of NO and prostaglandins. Moreover, acrolein induced vasodilatation in cirazoline-precontracted mesenteric bed of eNOS-null mice confirming eNOS independence. Pretreatment with 6-(2-propargyloxyphenyl) hexanoic acid (PPOH 50 microM), an epoxygenase inhibitor, or the superoxide dismutase mimetic Tempol (100 microM) significantly attenuated acrolein-induced vasodilatation. Collectively, these data indicate that acrolein stimulates mesenteric bed vasodilatation due to endothelium-derived signal(s) that is K(+)-, ouabain-, PPOH-, and Tempol-sensitive, and thus, a likely endothelium-derived hyperpolarizing factor (EDHF). These data indicate that low level acrolein exposure associated with vascular oxidative stress or inflammation stimulates vasodilatation via EDHF release in medium-sized arteries--a novel function.

Acrolein↗

'Fast-tracking' cancer referrals: application for periocular basal cell carcinoma.

AIM: To study the feasibility of a modified fast-track protocol for periocular basal cell carcinoma (BCC). METHODS: A modified protocol was set up with an aim to examine all periocular BCCs within 6 weeks of referral to our oculoplastic clinic. An audit of this protocol was performed over a 2-year period. RESULTS: A total of 65 patients were referred as a 'possible BCC' over the 2-year period. In all, 32 of these patients were referred by dermatologists (49%), followed by fellow consultant ophthalmologists (20 patients, 31%) and general practitioners (11 patients, 17%). The clinical suspicion in the oculoplastic clinic agreed with the referral diagnosis in 71% (46 of the 65) of patients. This figure was particularly high for referrals from dermatologists (84%). In all, 44 out of the 46 'clinically suspected BCC' underwent surgical excision. Histopathology confirmed BCC in 39 of these 44 patients, a diagnostic accuracy of 89%. Among the subgroup of patients referred by the dermatologists, the largest source of referrals, 24 out of 30 patients that underwent surgical excision had histologically proven BCC; a diagnostic accuracy of 80%. CONCLUSION: Our study shows that the modified fast-track protocol for periocular BCCs is practical and feasible. Such a practice is highly desirable since it prevents a long wait for patients who are aware of a possible malignant periocular lesion.

Basal Cell Carcinoma↗

Late-onset visual decline following successful treatment of subfoveal choroidal neovascularisation with photodynamic therapy.

Photodynamic therapy (PDT) has been shown in large studies to be capable of achieving closure of choroidal neovascularization (CNV), thereby resulting in stabilization of visual acuity. We report a series of four patients with classic CNV treated with PDT with good initial result but subsequent severe visual loss that may be related to a change in the morphology of the subretinal scar.

Choroidal Neovascularization↗

Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer.

BACKGROUND: The monoclonal antibody 3H1 mimics the external structure of the carcinoembryonic antigen (CEA). It therefore has the potential, via the anti-idiotypic network, to stimulate immune responses to CEA that may benefit colorectal cancer patients. PATIENTS AND METHODS: A total of 630 patients with previously untreated metastatic colorectal cancer were randomised in a 2:1 fashion to receive bolus 5-fluorouracil (5-FU) and leucovorin (LV) plus either 3H1 (n = 422) or placebo (n = 208). RESULTS: The addition of 3H1 to 5-FU and LV did not result in increased toxicity. Survival for the full intent-to-treat population was 14.7 months for the 3H1 arm and 15.2 months for the placebo arm (P = 0.80). Anti-CEA antibody responses were observed in 70% of patients treated with 3H1. Patients with a negative CEA response had a median survival of 8.3 months (95% CI 7.5-11.0) compared with patients with a strong response: median survival not reached (P <0.001). CONCLUSION: 3H1 is safe and effectively induces immune responses to CEA. Addition of 3H1 to 5-FU and LV was not shown to improve overall patient outcomes. However, improved survival in patients developing anti-CEA responses to 3H1 are provocative and should be studied in further clinical trials.

Adult↗

Disposable devices for measuring intraocular pressure: a clinical study to assess their accuracy.

AIMS: We conducted a study to compare the accuracy of two commercially available disposable tonometry devices (the acrylic biprism, Tonosafe and the silicone shield, Tonoshield) with the standard Goldmann applanation tonometer (GAT). METHODS: A total of 80 eyes of 40 patients were randomly assigned to two groups. Group A (40 eyes) had the intraocular pressure IOP measured using GAT and the acrylic biprism (Tonosafe), while Group B (40 eyes) had IOP measured using GAT and the disposable silicone shield (Tonoshield). IOP was measured using the GAT both before and after the disposable device and average of the two standard Goldmann readings was compared with the IOP measured using the disposable devices. RESULTS: The mean difference in IOP in Group A was 0.29 mmHg (SD 0.54) (P=0.0018) while in Group B the mean difference in IOP was 2.09 mmHg (SD 1.23) (P<0.0001). The Altman-Bland method was used to assess the agreement between two methods of clinical measurement. This shows a positive bias of 0.29 (95% confidence interval (CI) 0.11-0.46) when using the disposable acrylic biprism and a positive bias of 2.09 (95% CI 1.69-2.48) with the silicone shield. CONCLUSION: The IOP recorded using the disposable acrylic biprism (Tonosafe) was in close agreement with the standard GAT. However, IOP readings obtained with the silicone shield (Tonoshield) tend to be higher than with the standard GAT. These facts should be kept in mind when recording IOP in clinical situations.

Disposable Equipment↗

Cytomorphological study of soft tissue neoplasms: role of fluorescent immunocytochemistry in diagnosis.

OBJECTIVES: Exact categorization of soft tissue tumours (STTs) on smears requires application of various ancillary techniques. This study was aimed at evaluating the role of fluorescent immunocytochemistry (FICC) in cyto-diagnosis of 30 STT cases. METHODS: Thirty cases of soft tissue tumours were included in the present study. All cases were subjected to routine Giemsa and Papanicolaou stain. Extra smears were made and kept for fluorescent immunostaining. A panel of cytoskeletal antibodies, tagged with FITC (Fluorescein isothyocynate), was employed in all these cases. Fluorescent immunostained smears were examined under Zeiss Confocal Laser scanning microscope, using double immunofluorescence (red-green). Finally, all cases were subjected to biopsy and again immunoperoxidase staining. RESULTS: Among the 30 cases in the present study, unaided cytological diagnoses ranged from 'spindle cell' tumour in four (13.3%) cases, benign and malignant spindle cell tumour in 17 (56.6%) cases, to malignant mesenchymal tumour in nine (30%) cases. FICC helped in further correct categorization of 25/30 (83.3%) cases viz. leiomyoma (three), benign neurogenic tumour (six), schwannoma (one), dermatofibrosarcoma protuberans (three), synovial sarcoma (two), rhabdomyosarcoma (two), malignant fibrous histiocytoma (five) and malignant peripheral nerve sheath tumour (three). Aggressive fibromatosis was found to be a missed diagnosis in two cases. Overall concordance between cyto-diagnosis with FICC, and histopathology results was 83.3% (P < 0.05). CONCLUSION: Fluorescent immunocytochemistry is a significant ancillary technique for making a rapid and specific diagnosis of STT, as required for their timely management. Incorporation of a wide panel of antibody markers with clinico-cytological correlation is recommended in forming an exact diagnosis in these cases.

Biopsy, Fine-Needle↗

Physiology of Anabaena khannae and Chlorococcum humicola under fluoride stress.

Sodium fluoride showed pH-dependent physiological responses in the two test microalgae Anabaena khannae and Chlorococcum humicola. A. khannae showed severe membrane damage with fluoride at low pH with leakage of pigments and electrolytes. Annihilation of photosynthesis along with inhibition in 14C uptake was observed at pH 6 with 50 mg/L fluoride. While respiration was less affected in the cyanobacterium, C. humicola showed 30 % inhibition in respiratory activity. Resistance of C. humicola to fluoride toxicity has been attributed to the hindrance provided by the thick cell envelope, intracellular compartmentation and increase in extracellular pH as a consequence of its metabolism.

Anabaena↗

Removal of 2-fluoro and 2-iodophenol from aqueous solutions using industrial wastes.

A comparative study of the adsorbents prepared from several industrial wastes for the removal of 2-fluorophenol and 2-iodophenol has been carried out. The results show that maximum adsorption on carbonaceous adsorbent prepared from fertilizer industry waste has been found to be 35.3 and 235.3 mg g(-1) for 2-fluorophenol and 2-iodophenol, respectively. Compared to carbonaceous adsorbent, the other three adsorbents (viz., blast furnace sludge, dust, and slag) adsorb phenols to a much smaller extent. This has been attributed to the carbonaceous adsorbent having a larger porosity and consequently higher surface area. The adsorption of phenols on this adsorbent has been studied as a function of contact time, concentration and temperature. The adsorption has been found to be endothermic, and the data conform to the Langmuir equation. The further analysis of data indicates that adsorption is a first order process and pore diffusion controlled. A comparative study of adsorption results with those obtained on standard activated charcoal sample shows that prepared adsorbent is about 45% as efficient as standard activated charcoal and therefore, can be fruitfully employed for the removal of phenolic pollutants from wastewaters.

Adsorption↗

Ethnic differences in patient perceptions of heart failure and treatment: the West Birmingham heart failure project.

OBJECTIVE: To investigate further the hypothesis that ethnic groups would have different levels of knowledge and perceptions of congestive heart failure (CHF) and treatments for this condition, a cross sectional survey was conducted of patients who were attending the heart failure clinics in two teaching hospitals of Birmingham, UK, that serve a multiethnic population. METHODS: 103 patients with CHF (66 men, 37 women) were surveyed by standard questionnaire: 42 were white, 34 Indo-Asian, 22 Afro-Caribbean, and 5 Oriental. RESULTS: When asked about their beliefs about control of one's health, 22 (64.7%) of Indo-Asians felt that God/fate controlled their health. The majority of white patients tended to believe that the greatest factor influencing their health was the doctor (15 (35.7%)). Of the total study cohort, only 68 (66%) of patients were aware of their primary diagnosis of heart failure; the majority of Indo-Asians (21 (61.8%)) were not aware of their diagnosis. Half of Indo-Asians (17 (50%)) felt that heart failure was not severe, in contrast to 40.9% (n = 9) of Afro-Caribbeans and only 19.1% (n = 8) of white patients. Of the study cohort, 38 (36.9%) were taking their drugs because their doctor told them to, a response most common among the Indo-Asians. The majority of Indo-Asians (22 (64.7%)) and Afro-Caribbeans (14 (63.6%)) stated that they did not have, or did not know whether they had enough, information about their drug. The corresponding figure for white patients was 21.4% (n = 9). When asked whether they took their medication regularly as prescribed, 7 (31.8%) of Afro-Caribbeans reported that they did not take their drugs regularly. CONCLUSIONS: Our study has highlighted deficiencies in the knowledge of CHF among patients from ethnic minority groups, as well as deficiencies in the information being given to these patients. There is a clear need to invest more in patient education for CHF, with special emphasis on certain high risk subgroups.

Aged↗

Beta2 microglobulin as a surrogate marker for HIV infection: good correlation with CD4 counts.

To determine if beta-2 microglobulin (beta2M) levels were elevated in our HIV infected patient population and if it could be used as a surrogate marker for disease progression. Thirty-eight HIV infected individuals and 26 age and sex-matched controls were studied. Measurement of CD4 cell count was carried out on a flowcytometer using anti-human CD4 monoclonal antibody and beta2M was measured by an enzyme immunoassay. Mean levels of HIV infected individuals were 1.29 +/- 0.52 mg/L and were significantly higher than 0.74 +/- 0.07 mg/L, the value of controls (p value <0.01). There was a negative correlation between CD4 counts and beta2M levels (r-value-0.79, p value <0.001). Beta2M levels in HIV infected individuals who have no opportunistic infection are elevated and these levels correlate with the CD4 counts. Beta2M can be used for the clinical follow-up of patients with HIV infection.

Adult↗

Utilization of industrial waste products as adsorbents for the removal of dyes.

A number of low cost adsorbents from steel and fertilizer industries wastes have been prepared and investigated for the removal of anionic dyes such as ethyl orange, metanil yellow and acid blue 113 from aqueous solutions. The results indicate that inorganic wastes, i.e. blast furnace dust, sludge and slag from steel plants are not suitable for the removal of organic materials, whereas a carbonaceous adsorbent prepared from carbon slurry of fertilizer industry was found to adsorb 198, 211 and 219mg/g of ethyl orange, metanil yellow and acid blue 113, respectively. The adsorption of dyes on this adsorbent was studied as a function of contact time, concentration, particle size and temperature by batch method. The adsorption isotherm conformed to Langmuir model and the adsorption was found to be exothermic and physical in nature. Kinetic data conforms to Lagergren's equation with good correlation coefficients varying from 0.9998 to 0.9999 indicating that the adsorption is a first-order process. The adsorption data on carbonaceous adsorbent was compared to a standard activated charcoal sample and it was found that the prepared adsorbent is about 80% as efficient as standard activated charcoal and therefore, can be used as low cost alternative ( approximately 100 US dollars per ton) for colour removal from effluents.

Adsorption↗

Reduced apoptosis by pentoxiphylline among patients with HIV infection.

BACKGROUND: Apoptosis is a significant cause of CD4(+) T cell death. Caspase 8 (FLICE) is involved in apoptosis mediated by Fas and p55 tumor necrosis factor (TNF) receptor ligation. It is also partially mediated by interleukin-1beta (IL-1beta)-converting enzyme (ICE; caspase 1). We and others have shown that pentoxiphylline inhibits TNF-alpha. We used it among patients with HIV infection to determine if 24 weeks of therapy altered the levels of caspase 1 and caspase 8. PATIENTS AND METHODS: Nineteen HIV-infected patients having no opportunistic infection at the time of recruitment were administered pentoxiphylline 400 mg thrice daily for 24 weeks. Caspase levels were measured using a single-step ELISA using commercially available monoclonal antibodies against caspase 1 and caspase 8. RESULTS: Mean CD4 counts of the patients were 202.6+/-111.6 (/mm(3)). Mean OD value of caspase 1 among patients before therapy was 0.302+/-0.197 and was higher than that of controls (0.287+/-0.064), but this was not statistically significant. Following 24 weeks of therapy with pentoxiphylline, the OD value declined significantly to 0.164+/-0.028 among patients (p<0.001). Mean OD value of caspase 8 among patients prior to therapy was 0.927+/-0.249. This was significantly higher than that of controls, whose level was 0.0074+/-0.004 (p<0.001). Following 24 weeks of therapy with pentoxiphylline, the OD value declined to 0.199+/-0.064 among patients and this was significantly lower than the value at the start of treatment (p<0.001). CONCLUSION: Therapy with pentoxiphylline for 24 weeks is associated with a decline in the levels of caspase 1 and caspase 8. Since the drug is known to produce TNF inhibition, this might result in reduced apoptosis and an improved CD4 lymphocyte survival.

Adult↗

Influence of Mycobacterium tuberculosis on differential activation of helper T-cells.

Host defence against tuberculosis infection involves T-lymphocyte mediated cellular immune responses. In this study we assessed T-cell activation by studying the early signal transduction events and production of cytokines by human CD4+ T-cells. The study constituted of five groups of subjects: (a) untreated acid fast bacilli (AFB)+ve TB patients who have not started anti-tuberculosis therapy (ATT) [New]; (b) patients who have taken ATT for two months [2T]; (c) patients who have taken ATT for six months [6T]; (d) mantoux positive healthy controls [T+ve]; (e) mantoux negative healthy controls [T-ve]. We found that mantoux positive healthy controls produced significantly higher levels of IP3, intracellular Ca2+ and presented increased PKC activity when CD4+ T-cells were stimulated with M. tuberculosis H37Rv cell lysate as compared to mantoux negative controls. Furthermore, decreased expression of CD54 (ICAM-1) and reduced [Ca2+]i were seen in TB patients as compared to T+ve healthy controls. TB patients showed significantly lower levels of IL-2 and IFNgamma and higher levels of IL-4 as compared to normal healthy controls, suggesting a diminished Th1 response. Thus, the reciprocal changes in cytokines, reduced [Ca2+]i levels, and CD54 expression in patients imply phenotype shifting of Th precursors to Th2 type in TB patients.

Adult↗

Effect of different aspirin doses on platelet aggregation in patients with stable coronary artery disease.

BACKGROUND: Aspirin is widely used as an antiplatelet agent in the primary and secondary prevention of cardiovascular disease. In order to spare prostacyclin formation and reduce gastrointestinal side-effects, very low doses of aspirin have been introduced. However, it remains unclear whether these low doses are equally effective with respect to inhibition of platelet aggregation. AIMS: In a randomized, controlled study in 60 patients with stable coronary artery disease, the effects on platelet aggregation of five doses (50, 80, 100, 162.5 and 325 mg) of aspirin, which are widely used in clinical practice, given for 70 days, were investigated. Two reagents, adenosine diphosphate (ADP) and epinephrine, were used to induce platelet aggregation in platelet-rich plasma. An age- and sex-matched group of people without coronary artery disease served as the control. RESULTS: ADP- and epinephrine-induced platelet aggregation was 78.2 +/- 12.8% and 76.7 +/- 15.5% of maximum aggregation in the control group. Aspirin inhibited platelet aggregation in a dose-dependent manner. Minimum platelet aggregation was observed at a dose of 325 mg aspirin (27.5 +/- 17.4% with ADP). Doses of 50 and 80 mg aspirin were much less effective in inhibiting platelet aggregation (59.1 +/- 11.4% and 50.3 +/- 12.1% with ADP, respectively). Doses of 100 and 162.5 mg aspirin produced significantly greater inhibition of platelet aggregation than lower doses (36.2 +/- 11.7% and 38.5 +/- 19.8% platelet aggregation with ADP, respectively). CONCLUSION: Our results demonstrate that doses of aspirin less than 100 mg are not as effective at inhibiting platelet aggregation as doses greater than 100 mg.

Adenosine Diphosphate↗