Inhibition of advanced glycated end-products.
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Animals↗
Biomedical subjects
V Patel
Publications and source records attributed to V Patel.
Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis.
Flavopiridol (HMR 1275) has been identified recently as a novel antineoplastic agent in the primary screen conducted by the Developmental Therapeutics Program, National Cancer Institute. Flavopiridol inhibits most cyclin-dependent kinases (cdks) and displays unique anticancer properties. Here, we investigated whether this compound was effective against head and neck squamous cell carcinomas (HNSCC). Exposure of HNSCC cells to flavopiridol diminished cdc2 and cdk2 activity and potently inhibited cell proliferation (IC50 43-83 nM), which was concomitant with the appearance of cells with a sub-G1 DNA content. Moreover, DNA fragmentation and TUNEL (terminal deoxynucleotidyl transferase-mediated nick end labeling) reaction confirmed that flavopiridol induces apoptosis in all cell lines, even on certain HNSCC cells that are insensitive to apoptosis to DNA-damaging agents (gamma-irradiation and bleomycin). A tumorigenic HNSCC cell line was used to assess the effect of flavopiridol in vivo. Treatment (5 mg/kg per day, intraperitoneally) for 5 d led to the appearance of apoptotic cells in the tumor xenografts and caused a 60-70% reduction in tumor size, which was sustained over a period of 10 wk. Flavopiridol treatment also resulted in a remarkable reduction of cyclin D1 expression in HNSCC cells and tumor xenografts. Our data indicate that flavopiridol exerts antitumor activity in HNSCC, and thus it can be considered a suitable candidate drug for testing in the treatment of refractory carcinomas of the head and neck.
Animals↗
Reporting of gender-related information in clinical trials of drug therapy for myocardial infarction.
BACKGROUND: Concern has been expressed that women are not adequately represented in clinical trials evaluating treatments for medical conditions they commonly experience. This study was designed to assess the reporting of data on women in recently published trials of drug therapy for myocardial infarction, including those funded by an agency with a gender-related policy. METHODS: All randomized controlled trials and meta-analyses of drug therapies for myocardial infarction published in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, the Annals of Internal Medicine and the British Medical Journal from January 1992 to December 1996 were evaluated. On preliminary review 102 articles met the inclusion criteria; these were reviewed in detail, and 59 were excluded. Two reviewers independently extracted gender-related information from the 43 articles; discrepancies were resolved by consensus. RESULTS: Women presented up to 48% of the trial participants (mean 24.1%). In the trials funded by an agency with a gender-related policy, only 16.8% of participants, on average, were women. Of the 43 articles in the sample, only 14 (32%) provided gender-related results. Funding from an agency with gender-related policy did not affect the reporting of gender-related information. Subgroup analyses were provided for 14 (32%) of the 43 trials, including 2 (29%) of 7 trials funded by an agency with a gender-related policy. Of the 12 trials that included interaction analyses (excluding the 2 trials in which secondary analyses were conducted specifically to identify differences between women and men), 7 (58%) conducted an interaction analysis to determine if women responded differently than men; for one of these the interaction analysis was for a secondary outcome measure (drug safety). Only 5 (12%) of the 43 articles mentioned the differences between men and women in the Discussion section; 2 of these were studies that used secondary analyses to examine sex differences. Of the 5, only 1 was funded by an agency with a gender-related policy. INTERPRETATION: Women were poorly represented in the randomized controlled trials in this sample, regardless of whether the trials were funded by an agency with a gender-related policy. Structured reporting of gender-related information for clinical trials may improve the quality of information available about women and therefore facilitate the application of research findings to the care of women.
Angiotensin-Converting Enzyme Inhibitors↗
Reduced penetrance and variable expressivity of familial thoracic aortic aneurysms/dissections.
Autosomal dominant inheritance of thoracic aortic aneurysms and dissections occurs in subjects with Marfan syndrome, which results from mutations in the FBN1 gene on chromosome 15. A second chromosomal locus on 3p24-25 has been identified for a Marfan-like condition with thoracic aortic aneurysms. We describe here 6 families with multiple members with thoracic aortic aneurysms and dissections in the absence of the ocular and skeletal complications of Marfan syndrome. Medical records and autopsy reports on affected subjects in families with multiple members with thoracic aortic aneurysms and dissections were reviewed. Subjects in these families at risk for developing aortic disease underwent echocardiography to evaluate the aorta. The pattern of inheritance of thoracic aortic aneurysms and dissections was autosomal dominant in these families. Most affected subjects presented with aortic root dilatation or acute type I dissection, but the age of onset of disease was variable and there was decreased penetrance of the disorder. In 2 of the families, the syndrome was not linked to FBN1 or 3p24-25. Familial thoracic aortic aneurysm and dissection is an autosomal dominant condition with marked variability in the age of onset of aortic disease and decreased penetrance, making identification of affected subjects difficult. This condition is not due to mutations in the FBN1 gene or the unidentified gene on 3p24-25.
Aortic Dissection↗
The politics of alcoholism in india
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Journal Article↗
Acute directional coronary atherectomy prior to stenting in complex coronary lesions: ADAPTS Study.
The purpose of this study was to determine the results of directional coronary atherectomy (DCA) combined with stenting in a high-risk patient population. The use of stenting or DCA alone for aorto-ostial lesions, total chronic occlusions, long lesions, and lesions containing thrombus is associated with lowered success and a relatively high restenosis rate. Between July 1993 and October 1996, we treated 89 lesions with the combined approach of DCA and stenting in 60 consecutive patients. Thirty-one (51.7%) patients were treated because of unstable angina, 11 (18.3%) for post-myocardial infarction (MI) angina, 3 (5.0%) for acute MI, and 15 (25.0%) patients for stable angina. A total of 43 (71.7%) patients had multivessel disease, 19 (31.7%) had undergone previous coronary artery bypass graft (CABG), and 17 (28.3%) patients had undergone multivessel revascularization. The procedure was successful in all patients; and no postprocedural deaths or emergent CABG occurred. Two patients (3.3%) had non-Q-wave MI after the procedure and 1 patient (1.7%) experienced Q-wave MI due to subacute stent closure 7 days after the procedure. During follow-up ranging from 6 months to 3 years, 2 (3.3%) patients died, 2 (3.3%) required CABG surgery, 1 (1.7%) patient had an MI, and 6 patients (10.0%) required target vessel revascularization. By the quantitative coronary angiography, the initial minimal luminal diameter (MLD) averaged 0.91+/-0.45 mm (74.7+/-11.8% stenosis) increasing to 3.80+/-0.44 mm (-6.7+/-12.1%) after the combined approach procedure. Thirty patients (50.0%) met criteria for late (> or =6 months) angiographic follow-up. Late MLD loss averaged 1.13+/-1.07 mm, for a mean net gain of 1.61+/-1.23 mm. Available angiographic follow-up evaluation showed a restenosis rate of 13.3%. A combined approach, defined as the use of both DCA and stenting, is safe and yields a low restenosis rate in high-risk patients who have lesions known to respond less favorably to stenting or DCA alone.
Aged↗
Effect of angiotensin-converting enzyme inhibition with perindopril and beta-blockade with atenolol on retinal blood flow in hypertensive diabetic subjects.
The effect of angiotensin-converting enzyme (ACE) inhibitors on the diabetic retinal circulation has not been studied previously. The aim of this study was to evaluate the effect of ACE inhibition and beta-blockade on retinal blood flow (RBF) in a group of 45 hypertensive diabetic subjects using a randomized double-blind trial over a period of 12 months. Laser Doppler velocimetry and computed image analysis were used to measure RBF. The changes in blood pressure over 12 months were comparable (perindopril [PE]: systolic [SBP] 152.1 +/- 3.3 and diastolic [DBP] 97.2 +/- 1.7 mm Hg to SBP 136.8 +/- 3.4 and DBP 85.8 +/- 2.1; atenolol: SBP 158.9 +/- 5.1 and DBP 97.5 +/- 1.6 mm Hg to SBP 137.9 +/- 3.4 and DBP 85.1 +/- 1.6; P = .607, mean +/- SEM). RBF decreased from 17.19 +/- 2.21 microL x min(-1) to 14.18 +/- 1.50 microL x min(-1) in the PE group (n = 15, P = .208) while it increased with atenolol from 15.80 +/- 1.24 microL x min(-1) to 16.99 +/- 1.18 microL x min(-1) (n = 17, P = .399). The comparison of percentage changes in RBF (PE -7.16% +/- 11.49%; atenolol, +15.31% +/- 9.51%) reached statistical significance (P < .05). There was an increase in RBF in 33.3% of subjects receiving PE and in 70.6% of those receiving atenolol. Similar trends were found for retinal conductance. There were no significant changes in the parameters of retinal vascular permeability. Albuminuria decreased to a greater degree with PE, but did not reach significance (PE, 112.1 +/- 39.5 mg/24 h to 88.6 +/- 30.5 mg/24 h; atenolol, 87.3 +/- 51.7 mg/24 h to 82.1 +/- 47.7 mg/24 h). This suggests that ACE inhibition therapy may promote a hemodynamic milieu in the hypertensive diabetic retinal circulation that serves to protect against the progression of diabetic retinopathy, whereas beta-blockade has the opposite effect.
Adrenergic beta-Antagonists↗
The comparison of latent variable models of non-psychotic psychiatric morbidity in four culturally diverse populations.
BACKGROUND: Factor analysis has been employed to identify latent variables that are unifying constructs and that parsimoniously describe correlations among a related group of variables. Confirmatory factor analysis is used to test hypothesized factor structures for a set of variables; it can also, as in this paper be used to model data from two or more groups simultaneously to determine whether they have the same factor structure. METHOD: Non-psychotic psychiatric morbidity, elicited by the Revised Clinical Interview Schedule (CIS-R), from four culturally diverse populations was compared. Confirmatory factor analysis was employed to compare the factor structures of CIS-R data sets from Santiago, Harare, Rotherhithe and Ealing. These structures were compared with hypothetical one and two factor (depression-anxiety) models. RESULTS: The models fitted well with the different data sets. The depression-anxiety model was marginally superior to the one factor model as judged by various statistical measures of fit. The two factors in depression-anxiety model were, however, highly correlated. CONCLUSIONS: The findings suggest that symptoms of emotional distress seem to have the same factor structure across cultures.
Adolescent↗
Somatic and psychological models of common mental disorder in primary care in India.
BACKGROUND: Primary care attenders with a common mental disorder (CMD) frequently present with somatic symptoms. This study aimed to examine somatic and psychological models of CMD in primary care attenders in India. METHODS: Cross-sectional survey of attenders at two primary care clinics. Psychiatric caseness was determined on three criteria: standardized psychiatric interview (biomedical criterion), patients' self-assessment of emotional disorder (emic criterion) and health care provider diagnosis. The GHQ-12 and the PPQ, which emphasize psychological and somatic symptoms respectively, were used as screening instruments. RESULTS: Although somatic symptoms were the presenting complaints for 97% of subjects, 51% of subjects with a biomedically defined CMD had a psychological illness attribution. Patients with psychological attributions were more likely to be women, to have a longer duration of illness, to have higher CISR scores and were more likely to be recognized by the primary health care (PHC) physician. The GHQ-12 was superior to the PPQ in identifying cases of CMD against the biomedical criterion for both psychologizers and somatizers; both instruments performed equally well against the emic and care provider criteria. CONCLUSIONS: Psychological models may be acquired by patients as CMD becomes more chronic or severe, making them more likely to be detected by PHC physicians. Psychological symptoms are superior to somatic symptoms in detecting CMD. Shorter versions of the GHQ have comparable discriminating abilities to the 12-item version and offer the practical advantage of brevity, which may make them more acceptable to PHC physicians as a clinical screening tool.
Adolescent↗
The development of the Short Explanatory Model Interview (SEMI) and its use among primary-care attenders with common mental disorders.
BACKGROUND: Recent anthropological studies have documented the importance of understanding the relation of culture to the experience of mental illness. The use of interviews that elicit explanatory models has facilitated such research, but currently available interviews are lengthy and impractical for epidemiological studies. This paper is a preliminary report on the development of a brief instrument to elicit explanatory models for use in field work. METHOD: The development of the SEMI, a short interview to elicit explanatory models is described. The interview explores the subject's cultural background, nature of presenting problem, help-seeking behaviour, interaction with physician/healer and beliefs related to mental illness. RESULTS: The SEMI was employed to study the explanatory models of subjects with common mental disorders among Whites, African-Caribbean and Asians living in London and was also used in Harare, Zimbabwe. Data from its use in four different ethnic groups is presented with the aim of demonstrating its capacity to show up differences in these varied settings. CONCLUSIONS: The simplicity and brevity of the SEMI allow for its use in field studies in different cultures, data can be used to provide variables for use in quantitative analysis and provide qualitative descriptions.
Africa↗
Intraneuronal ApoE in human visual cortical areas reflects the staging of Alzheimer disease pathology.
Alzheimer disease (AD) is marked by progressive loss of cortical neurons with associated cognitive decline. Multiple genetic and environmental factors likely contribute to this progressive loss. Such genetic factors include the polymorphic locus (APOE) that encodes apolipoprotein E (apoE). In order to investigate a possible correspondence between cellular localization of apoE and the neuropathology of AD, we examined the distribution of apoE-immunoreactive neurons in visual cortical areas with different apparent susceptibility to AD neuropathology (areas 17-primary sensory, 18-secondary sensory, and inferior temporal-association cortex) at different stages of AD pathology as described by Braak and Braak. We found that intraneuronal apoE was present at all these stages, however, only in visual cortical regions known to be vulnerable to AD. In the late stages, the laminar distribution of apoE-immunoreactivity matched the distribution of other markers of AD pathology, especially modified tau. These data support previous findings that intraneuronal apoE in neocortex is common in aged, nondemented controls and demonstrate that it may be more common in regions at risk for AD pathology. Thus, intraneuronal accumulation of apoE may be an attribute of cortical neurons that are more vulnerable to age-related injury with the presence of apoE antedating the classical indices of late-onset AD pathology.
Aged↗
Predicting postnatal mental disorder with a screening questionnaire: a prospective cohort study from Zimbabwe.
BACKGROUND: Postnatal mental disorders are common causes of morbidity but are rarely diagnosed or treated in busy primary care clinics in developing countries. OBJECTIVE: To determine whether a brief psychiatric screening questionnaire used in the 8th month of pregnancy can predict postnatal mental disorder. STUDY DESIGN: Prospective cohort study. SITE: A peri-urban settlement in Zimbabwe. POPULATION: 500 women in the 8th month of pregnancy identified by traditional birth attendants and primary care clinics. SAMPLE: "High risk" cohort consisted of all women who scored 8 or more on the Shona Symptom Questionnaire (SSQ), an indigenous psychiatric questionnaire (n = 95). Low risk cohort consisted of 105 women randomly selected from the remainder of the sampling frame. OUTCOME MEASURE: Revised Clinical Interview Schedule at six to eight weeks postpartum; scores of 14 or more indicate psychiatric caseness. RESULTS: The prevalence of postnatal mental illness was 16%. Odds ratios (95% confidence intervals) for high risk women becoming cases in the postnatal period were 10.6, 4.8, 23.9, p < 0.0001 after adjustment for age, marital status, and occupation. CONCLUSIONS: A brief method of detecting women at high risk of developing a postnatal mental disorder can be used with reasonable accuracy in the 8th month of pregnancy. Further research is needed to determine whether interventions applied to this high risk group can reduce their postnatal morbidity.
Adult↗
Bipolar affective disorder, stress fractures, fungal dermopathy and 'tree frog fingers'.
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Adenoma, Chromophobe↗
Outcome of common mental disorders in Harare, Zimbabwe.
BACKGROUND: Little is known about the outcome of common mental disorders (CMD) in primary care attenders in low income countries. METHOD: Two and 12 month (T1 and T2) follow-up of a cohort of cases of CMD (n = 199) recruited from primary health, traditional medical practitioner, and general practitioner clinics in Harare, Zimbabwe. The Shona Symptom Questionnaire (SSQ) was the measure of caseness. RESULTS: The persistence of case level morbidity was recorded in 41% of subjects at 12 months. Of the 134 subjects interviewed at both follow-up points, 49% had recovered by T1 and remained well at T2 while 28% were persistent cases at both T1 and T2. Higher SSQ scores, a psychological illness model, bereavement and disability predicted a poor outcome at both times. Poorer outcome at T1 only was associated with a causal model of witch-craft and an unhappy childhood. Caseness at follow-up was associated with disability and economic deprivation. CONCLUSIONS: A quarter of cases of CMD were likely to be ill throughout the 12 month follow-up period. Targeting risk groups for poor outcome for interventions and policy interventions to reduce the impact of economic deprivation may provide a way of tackling CMD in primary care in low income countries.
Adult↗
Poverty, psychological disorder and disability in primary care attenders in Goa, India.
BACKGROUND: This study examined the association of common mental disorders in primary health clinic attenders with indicators of poverty and disability in Goa, India. METHOD: Adult attenders (n = 303) in two primary health clinics were recruited. RESULTS: There were 141 (46.5%) cases of common mental disorder. The following were associated with common mental disorder: female gender; inability to buy food due to lack of money; and being in debt. Cases scored significantly higher on all measures of disability. Primary health clinic staff recognised a third of the morbidity but used multiple oral drugs, injectable vitamins and benzodiazepines to treat common mental disorders. CONCLUSIONS: Poverty is closely associated with common mental disorder which in turn is associated with deprivation and despair. Primary mental health care priorities in low-income countries need to shift from psychotic disorders which often need specialist care to common mental disorders. Health policy and development agencies need to acknowledge the intimate association of female gender and poverty with these disorders.
Adolescent↗
Altered expression and activity of G1/S cyclins and cyclin-dependent kinases characterize squamous cell carcinomas of the head and neck.
Progressive deregulation of the cell-division cycle is thought to contribute to the establishment and progression of neoplasia. Previously, we have documented the in vivo inactivation of p16INK4A, an inhibitor of G1 cyclin-dependent kinases, in squamous cell carcinomas of the head and neck region. In the present study, we extend these findings by examining the expression and functional activity of cyclin-dependent kinases (CDKs) and their regulatory subunits using a model system of cell lines derived from squamous cell carcinomas. Increased activity of CDK4 and 6 was universal in tumor cells compared with normal keratinocytes, reflecting over-expression of either or both kinases. In contrast to other studies, over-expression of cyclin D1, a regulatory subunit of CDK4 and 6, was not observed. Increased activity of CDK2 was less frequent and was related to over-expression of cyclin A and/or E. All tumor cell lines showed increased expression of proliferating cell nuclear antigen compared to normal keratinocytes. Four SCC cell lines, including one tumor-metastasis pair derived from a single patient, failed to express the p15INK4B transcript. Western blot analysis of cell lysates revealed normal or reduced levels of p27KIP1 in tumor cells compared to normal keratinocytes. However, failure to express wild-type p53 was not reflected by lower levels of p21WAF1. Our data suggest that cell-cycle deregulation is likely to occur by multiple mechanisms during the genesis of head and neck squamous cell carcinomas. Furthermore, p16INK4A is likely to be the primary target for inactivation on chromosome 9p21 in these tumors as p15INK4B loss occurs less frequently.
Carcinoma, Squamous Cell↗
Novel technique for coil embolization of intercostal branch of internal mammary artery graft.
Coronary artery steal resulting from a large unligated intercostal or pericardial side branch of the internal mammary artery graft causing postoperative angina has been previously described. Transcatheter coil occlusion of internal mammary artery side branch has successfully been performed to treat coronary steal syndrome. Unsuccessful deployment of the microcoils can be due to inadequate guiding support in the LIMA or prolapse of the delivery catheter in the side branch. We report a new approach for the precise deployment of coils in the side branch of a LIMA graft, when inadequate guiding support is present.
Angina Pectoris↗
Etic and emic criteria for non-psychotic mental disorder: a study of the CISR and care provider assessment in Harare.
The paper describes the relationships between the Revised Clinical Interview Schedule (CISR) and the assessment of psychiatric status by primary care providers in Harare. Primary care clinic (PHC) and traditional medical practitioner (TMP) clinic attenders (n = 302) were interviewed with the Shona Symptom Questionnaire, the CISR and the Explanatory Model Interview. The PHC nurses and TMP were interviewed to elicit diagnostic formulation using the WHO Health Staff Rating codes. "Etic" cases were those who scored 12 or more on the CISR and "emic" cases were those whom the care provider had assessed as having a mental disorder. In all, 52% of subjects were classified as etic cases and 59% as emic cases. Overall agreement between the two criteria was 55%. Three-quarters of care provider "false-positives" were accounted for by a failure to take into account the varying reasons for consultation, such as social or spiritual problems. Most of the "false-negative" groups were symptomatic subjects, though with fewer symptoms than those who were "definite cases". One etic concept-phobia-was not considered as a mental disorder and appeared to lack concept validity in this setting.
Adult↗