Introduction: Cervical Cancer is listed as the third commonest malignancy seen in women, worldwide. E-cadherin is a molecule with an important role in interaction of cell-cell and cell-extracellular matrix and its loss is important in tumor spread. This study was planned to evaluate the expression of E-Cadherin in precancerous and cancerous lesions of cervix. In this study 60 bi Methodology: opsies of cervical lesions were included. Cervical biopsies were taken in women with CIN II, CIN III, Well- differentiated squamous cell carcinoma, Moderately differentiated carcinoma, Poorly differentiated carcinoma, Undifferentiated carcinoma and Lymphoepithelioma. Immunohistochemical staining for E cadherin was done on all parafn blocks using monoclonal antibody. HPV DNA analysis was detected by PCR. Relevant personal and clinical data were documented. E– cadherin expression showed signicantly higher grade of expression in chronic Results: cervicitis as compared to premalignant and malignant lesions. Out of the 60 cases screened for HPV DNA by PCR, 26.6 % (10 cases) tested positive for HPV infection. Further investigation for HPV type 16/18 showed that 3 (18.7%) out of 16 cases tested for HR- HPV type 16 and 7(43.7%) for type 18. Conclusion: Expression of E-cadherin was observed to be inversely proportional to loss of cell differentiation. Loss of E-cadherin staining was closely related to grade of dysplasia. It can be used as a prognostic marker for cervical squamous premalignant and malignant lesions of cervix.
Older adults with depression frequently present with symptoms of mild cognitive impairment (MCI). In evaluating cognitive change after antidepressant treatment in such patients (Dep-MCI), demographic information such as gender and race are frequently included as covariates but their impact on cognitive change does not receive as much interest. The purpose of this study was to evaluate cognitive change after a 16-week open-trial antidepressant treatment using data from the Dep-MCI study (PI: Devanand; see Pelton, et al., 2015). Mood was assessed with the Hamilton Depression Rating Scale and cognition was assessed with a comprehensive neuropsychological battery. Participants (N=81) overall improved on the Mini Mental Status Exam (MMSE) and verbal memory. Females showed significantly greater improvement than males on the MMSE and WMS-R Visual Reproduction I. Caucasian participants showed significantly greater improvement than African American and Hispanic participants on WMS-R Visual Reproduction II, and significantly greater improvement than Hispanic participants on Trail Making Test - Trail B. Change in cognition did not depend on treatment response or remission. The effect sizes for these findings ranged from small (consistent with a practice effect) to medium (indicative of substantive change). The fact that males compared to females, and African American and Hispanic participants compared to Caucasian participants, showed significantly less improvement in cognitive functioning suggests they may benefit less from non-specific factors associated with participating in a medical center-based clinical trial.
Background This study is a randomized, prospective, investigation of the relationships between clinical trial design, patient expectancy and the outcome of treatment with antidepressant medication. Method Adult out-patients with major depressive disorder (MDD) were randomized to either placebo-controlled (PC, 50% probability of receiving active medication) or comparator (COMP, 100% probability of receiving active medication) administration of antidepressant medication. Independent-samples t tests and analysis of covariance (ANCOVA) were used to determine whether the probability of receiving active medication influenced patient expectancy and to compare medication response in the PC v. COMP conditions. We also tested the correlations between baseline expectancy score and final improvement in depressive symptoms across study groups. Results Subjects randomized to the COMP condition reported greater expectancy of improvement compared to subjects in the PC condition (t = 2.60, df = 27, p = 0.015). There were no statistically significant differences in the analyses comparing antidepressant outcomes between subjects receiving medication in the COMP condition and those receiving medication in the PC condition. Higher baseline expectancy of improvement was correlated with lower final depression severity scores (r = 0.53, p = 0.021) and greater improvement in depressive symptoms over the course of the study (r = 0.44, p = 0.058). Conclusions The methods described represent a promising way of subjecting patient expectancy to scientific study. Expectancy of improvement is affected by the probability of receiving active antidepressant medication and seems to influence antidepressant response.
Background Response to antidepressant medication is higher in comparator versus placebo-controlled randomized controlled trials (RCTs). Patient expectancy is an important influence on clinical outcome in the treatment of depression and may explain this finding. The results are reported from a pilot RCT studying expectancy and depression outcome in placebo-controlled versus comparator treatment conditions. Method Out-patients aged 18–65 years with major depressive disorder (MDD) were enrolled in this 8-week RCT. Subjects were randomized to placebo-controlled (escitalopram or placebo) or comparator (escitalopram or citalopram) administration of antidepressant medication. Subjects reported their expected likelihood and magnitude of depression improvement before and after randomization using questions from the Credibility and Expectancy Scale (CES). A regressed change model of post-randomization expectancy of improvement was fit to the data to determine whether subjects in the comparator group reported greater expectancies of improvement than subjects in the placebo-controlled group. Results Twenty subjects with mean age 56.5±11.7 years, a baseline Hamilton Depression Rating Scale (HAMD) score of 24.2±5.3, baseline Beck Depression Inventory (BDI) score of 24.9±6.4 and baseline Clinical Global Impressions (CGI) – Severity score of 4.0±0.3 were enrolled in the study. Adjusting for other factors, the effect of group assignment on expected magnitude of improvement was significant and large (effect size 1.5). No group differences in expected likelihood of improvement were found. Conclusions Randomization to comparator versus placebo-controlled administration of antidepressant medication produced greater expectancies of how much patients would improve during the trial. This expectancy difference may explain the higher response and remission rates that are observed in comparator versus placebo-controlled trials.
CONTEXT Lead is a major health hazard, especially in children. Impact of lead poisoning on our society is not known. Effectiveness of environmental interventions in reducing blood lead levels is not exactly known, though the Center for Disease Control and Prevention strongly advocates use of such means. AIMS We aimed at screening school children for blood lead levels (BLLs) and reducing the BLLs of children with preliminary BLL> 20 microg/dL by environmental intervention and intensive education. MATERIALS AND METHODS To assess the extent of lead poisoning, a screening of 106 children was done, which showed that children belonging to a particular government primary school had higher BLLs. A second screening program of 87 children conducted in that school showed that only 19% had BLL < 10 microg/dL; whereas 44% had BLL between 10 and 20 microg/dL, and 37% had BLL> 20 microg/dL. Thirty-eight children having BLL> 20 microg/dL were selected from the two screening programs. After removing all potential sources of lead from their environment and educating them about the ways to prevent exposure to lead, follow-up of their BLLs was carried out at an interval of 6 months for a period of 1 year. STATISTICAL ANALYSIS Values of the different follow-up studies were compared using repeated-measure ANOVA. RESULTS Our results showed that there was a significant (P < 0.0001) reduction in the BLLs in the first and second follow-up studies. CONCLUSIONS The study is a proof of the concept that a decline in the BLLs can be achieved by intense education and avoiding the potential environmental sources of lead.
Objectives The atypical subtype inpatients with major depressive disorder is characterized by mood reactivity, significant weight gain or increase in appetite, hypersomnia, leaden paralysis and a long-standing pattern of interpersonal rejection sensitivity. Though atypical depression is well documented in younger patients, little attention has been paid to the atypical subtype in samples of late-life depressed patients. This study reports the patient characteristics and treatment results of an eight-week open-label trial of venlafaxine in a sample of older depressed patients with atypical subtype.Methods Patients received fixed dosing schedule (up to 300 mg/day) of venlafaxine (Effexor XR) for 8 weeks.Results In this sample of 17 patients, the mean age was 65.6 years and 77% were female. Most strikingly, 53% of patients presented with late-onset atypical depression defined as first episode after the age of 50. Fifteen of the 17 patients (88%) completed the eight-week treatment trial. The mean score on the HRSD 24-item decreased from 22.2 +/- 5.1 at baseline to 11.8 +/- 8.9 (p < 0.001), and the mean total atypical item score decreased from 6.2 +/- 1.6 to 2.8 +/- 2.0 (p < 0.001). Remission was defined as a final HRSD < 10 and a 50% reduction in baseline HRSD score. The intent-to-treat remission rate was 65% and the completer remission rate was 73%.Conclusions In this sample of late-life patients with atypical depression venlafaxine treatment was reasonably effective and well tolerated. However, the effectiveness of venlafaxine in this study must be considered in the context that this was an open trial of antidepressant medication. Insufficient attention has been given to the atypical subtype in late-life depression. Whether late-onset atypical depression is significantly different from early-onset atypical depression, and whether late-onset patients with atypical depression are significantly different from late-onset patients with other depressive subtypes are questions of compelling interest. Copyright (C) 2004 John Wiley Sons, Ltd.
Background: Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results. Objective: To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD. Methods: Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years (mean 5.5 years) for development of delusions, illusions, hallucinations, behavioral symptoms, and depression. Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology (outcome) in relation to APOE genotype (predictor). Results: The presence of one epsilon4 allele carried a 2.5-fold risk, whereas the presence of two epsilon4 alleles carried a 5.6-fold risk for development of delusions. The associations remained significant even when age, ethnicity, sex, education, duration of disease, and cognitive and functional performance were controlled for. The presence Of two epsilon4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only. No significant associations were detected between APOE genotype and the incidence of illusions, behavioral symptoms, or depression. Conclusion: The presence of one or more epsilon4 alleles is a significant predictor for the incidence of delusions in the course of AD.
Depressed patients develop symptomatic and fatal ischemic heart disease at a higher rate than nondepressed patients, even after studies are controlled for known cardiovascular risk factors. Changes in sympathetic and parasympathetic tone appear to make depressed patients more vulnerable to ventricular fibrillation. Tricyclic antidepressants share the electrophysiologic profile of type 1A antiarrhythmic compounds and therefore may carry a risk of increased mortality when given to patients with ischemic heart disease. Serotonin reuptake inhibitors have shown no antiarrhythmic effect in depressed patients with serious cardiovascular disease, but studies to date have been small and short-term.
Objective. —To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies. Design. —Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed. Setting. —Three AD research centers. Patients. —All patients met National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit. Intervention. —Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features. Main Outcome Measures. —(1) Requiring the equivalent of nursing home placement and (2) death. Results. —Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted.Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients.When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients. Conclusions. —The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.
The "Predictors Study" is a prospective cohort study of the natural history of Alzheimer disease (AD), the aim of which is to identify milestones in disease progression and to develop a model to predict disease course in individual patients. The empirical background to this study is based on previous reports that the presence of extrapyramidal signs (EPS), myoclonus, and psychosis in AD may signify greater disease severity at any given stage and a more rapid course of the disease over time. The present analyses were conducted to determine whether these independent "predictor" variables were associated with greater disease severity at baseline within a new cohort of 224 mild AD patients recruited from three different medical centers (in New York, Baltimore, and Boston). Measures of disease severity were provided by the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale (BDRS), which measures functional capacity. Independent variables were EPS, delusions, and slowing of the posterior dominant EEG rhythm. The frequency of myoclonus and hallucinations was too low to permit adequate statistical assessment of their effects at this time. EPS and EEG slowing were associated with low mMMSE scores, whereas delusions were primarily associated with impaired functional capacity. These effects were independent of the influence of age and disease duration. These results indicate that the effects of these independent variables can be detected at mild stages of AD and that these effects can be generalized across different geographical regions.
Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The “Predictors Study,” a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed.