Lipid-lowering therapy for patients with or at risk of coronary artery disease

Several studies have shown that effective lipid-lowering therapy slows the progression of atherosclerotic lesions in the coronary and carotid arteries. Recent clinical trials have confirmed and extended previous work showing that lowering cholesterol reduces the risk of coronary events. A clear reduction in major coronary events during treatment for 5 years with the hydroxymethylglutaryl-coenzyme A reductase inhibitor pravastatin was observed in the West of Scotland study and in the preliminary results of the Cholesterol and Recurrent Events study. The Scandinavian Simvastatin Survival Study has provided the first unequivocal demonstration of improved survival as a result of lipid-lowering therapy. These three trials, which together included over 15,000 patients studied for 5 years, have provided good evidence that noncardiovascular mortality is not affected by substantial reductions in blood cholesterol.     

Identification of patients with autosomal dominant polycystic kidney disease at highest risk for end-stage renal disease

To identify those potential factors that, early in the course of disease, mark a population of patients with autosomal dominant polycystic kidney disease (ADPKD) who have worse renal survival, survival analysis and risk ratio calculation for 1215 ADPKD patients were performed. Survival times were calculated as time to dialysis, transplantation, or death. Risk ratios were calculated using the Cox proportional hazards model. Three hundred eighty-eight patients entered end-stage renal disease and 205 patients died. ADPKD2 subjects had longer renal survival than ADPKD1 subjects (median survival, 68 versus 53 yr; P < 0.0005; risk ratio, 2.5). Women had significantly better renal survival than men (56 versus 52 yr; P < 0.0001; risk ratio, 1.6). Subjects who were diagnosed before age 30 and those who developed hypertension before age 35 had worse renal survival than those subjects who were diagnosed after age 30 or those who remained normotensive after age 35, respectively (age of diagnosis: 49 versus 59 yr; P < 0.0001; risk ratio, 3.2; hypertension: 51 versus 65 yr; P < 0.0001; risk ratio, 4.4). Similarly, those who had an episode of gross hematuria before age 30 had a worse renal outcome than those who did not (49 versus 59 yr; P < 0.0001; risk ratio, 2.6). We have also calculated risk ratios for a combined model. When therapeutic interventions become available for this disease, these populations with high risk ratios should be considered for such interventions.     

Long-term predictive value of a single cytomegalovirus (CMV) DNA PCR assay for CMV disease in human immunodeficiency virus-infected patients

Universal prophylaxis with oral ganciclovir is not cost-effective for the prevention of cytomegalovirus (CMV) disease in human immunodeficiency virus infection. For a preemptive strategy to be considered, patients at highest risk for CMV disease need to be easily and accurately identified. In this study, the sensitivity, specificity, positive predictive value, and negative predictive value of a single CMV DNA PCR assay for the subsequent development of CMV disease were 0.75, 0.89, 0.75, and 0.89, respectively.     

Predictive value of cytomegalovirus (CMV) antigenemia and digene hybrid capture DNA assays for CMV disease in human immunodeficiency virus-infected patients

Oral ganciclovir prophylaxis decreases the incidence of cytomegalovirus (CMV) disease among persons infected with the human immunodeficiency virus (HIV), but universal prophylaxis is not cost-effective. We evaluated urine and peripheral blood mononuclear cell cultures, a qualitative and quantitative antigenemia assay, and a commercially available CMV DNA hybridization assay for their ability to predict CMV disease in 138 HIV-infected patients. During a median follow-up of 10 months, 23 patients (17%) developed CMV disease. The sensitivity, specificity, positive predictive value, negative predictive value, and mean lead times for the antigenemia assay (with use of a threshold of 8 positive cells per 10(5) peripheral blood mononuclear cells as a positive) were 74%, 91%, 63%, 95%, and 95 days, respectively. Corresponding figures for the DNA hybridization assay were 91%, 64%, 34%, 97%, and 152 days. These assays can identify patients at increased risk of CMV disease and should allow a strategy of preemptive therapy to be tested.     

T cell receptor heterogeneity in gamma delta T cell clones from intestinal biopsies of patients with celiac disease

In celiac disease large numbers of gamma delta T lymphocytes infiltrate the intestinal epithelia. We have isolated intestinal gamma delta T cell clones from patients with celiac disease and have analyzed their T cell receptor repertoire. T cell lines and clones were obtained from jejunal biopsies of 14 celiac patients and 12 individuals without celiac disease. These were analyzed by staining with monoclonal antibodies against CD3, alpha beta and gamma delta T cell receptor, by Southern blot with gamma- and delta-specific probes and by polymerase chain reaction using V delta-specific oligonucleotides. Intestinal gamma delta cells from patients with celiac disease differed from those of controls with normal jejunal histology in that V delta 1+ cells and V delta 1-V delta 2- cells were significantly increased. There was no evidence of the expansion of one or more clones expressing particular types of gamma delta T cell receptor.     

Semiquantitative Epstein-Barr virus (EBV) polymerase chain reaction for the determination of patients at risk for EBV-induced lymphoproliferative disease after stem cell transplantation

Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a serious and potentially fatal complication after allogeneic stem cell transplantation (SCT). To evaluate levels of EBV DNA in SCT patients, a semiquantitative polymerase chain reaction (PCR) assay was developed. DNA was extracted from peripheral blood leukocytes and diluted, and PCR was performed by using a primer set specific for a well-conserved sequence of the internal repeat 1 region of the EBV genome. Forty-one SCT patients were screened with this method. Thirty-seven patients received allogeneic transplants, of which 18 were T-cell-depleted marrow. Four additional patients received autologous SCT, one of which was T-cell depleted. The mean time of follow-up by EBV PCR was 147 days (range, 47 to 328 days) posttransplant. The range of EBV copies/microg DNA from normal EBV sero-positive donors was 40 to 4,000. Seven patients had >/=40,000 copies of EBV DNA/microg DNA, all of whom were recipients of T-cell-depleted SCT. Five of the seven patients with elevated levels of EBV DNA developed EBV-LPD. Four of these five patients with EBV-LPD had elevated levels of EBV DNA from 1 to 8 weeks before diagnosis. Two patients with EBV-LPD had normal levels of EBV DNA, and two patients with >/=40,000 copies EBV/microg DNA did not develop EBV-LPD. In one patient, clinical resolution of disease correlated with a decrease in EBV DNA and an increase in the level of EBV-specific cytotoxic T-cell precursors. These data indicate that the measurement of EBV viral load with semiquantitative PCR is useful in detecting EBV-LPD in high-risk patients before the onset of clinical symptoms. Because not all patients with elevated levels of EBV DNA develop EBV-LPD, semiquantitative PCR results cannot substitute for clinical, radiographic, and pathological confirmation of this diagnosis.     

Susceptibility to peer influence: Using a performance-based measure to identify adolescent males at heightened risk for deviant peer socialization.

A substantial amount of research has suggested that adolescents' attitudes and behaviors are influenced by peers; however, little is known regarding adolescents' individual variability, or susceptibility, to peer influence. In this study, a performance-based index from an experimental paradigm was used to directly measure adolescents' susceptibility to peers. A total of 36 adolescent boys participated in a “chat room” experiment in which they ostensibly were exposed to deviant or risky social norms communicated either by high-peer-status (i.e., popular, well-liked) or low-peer-status (i.e., unpopular, disliked) grade mates who actually were electronic confederates. Changes in adolescents' responses before and after exposure to peer norms were used as a measure of peer influence susceptibility. These same adolescents completed a questionnaire assessment at the study outset and again 18 months later to assess their actual engagement in deviant behavior and their perceptions of their best friend's engagement in deviant behavior. Only among adolescents with high levels of susceptibility to high-status peers was a significant longitudinal association revealed between their best friend's baseline deviant behavior and adolescents' own deviant behavior 18 months later. Findings support the predictive validity of a performance-based susceptibility measure and suggest that adolescents' peer influence susceptibility may generalize across peer contexts. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Age at onset and gender of schizophrenic patients in relation to neuroleptic resistance

PURPOSE: To characterize the network structure of Poly(Acryloyl Hydroxyethyl Starch) (Ac-HES) microspheres and test the theoretical model and the hypothesis that the rate of swelling of microspheres is inversely related to the extent of crosslinking. METHODS: Microspheres were prepared with varying degrees of derivatization (DD) and molar ratios (MR) and subjected to the characterization of matrix structure by dynamic and equilibrium swelling studies utilizing direct microscopic observation and the Flory-Rehner equation. The dependence of average molecular weight between crosslinking Mc, on DD and MR were compared to test the validity of the model. RESULTS: Study of the dependence of Mc on the microspheres preparation parameters, DD and MR, showed that at constant MR, the Mc decreased with DD, while at constant DD, the Mc initially decreased with MR to a minimum, and then increased with MR, complying with the model prediction. Dynamic swelling of microspheres showed a monotonical increase to equilibrium size featured by two time variables, Tp and Teq, that were dependent on Mc; this permitted a conceptual view of the general structure of the Ac-HES microspheres. The Mc, which was more accurately determined by the weight method (as opposed to volume method), was independent of the size of microspheres although there was evidence of variation among particles within a batch. CONCLUSIONS: The results validated the model in describing the polymerization/crosslinking reaction of the Ac-HES microsphere system and suggested that Mc is the principal factor in controlling release.     

Profile of some risk factors for coronary heart disease in a developing country: Nigeria

We examined visual evoked potentials and pattern electroretinograms in a patient with Tolosa-Hunt syndrome associated with optic nerve involvement. The 82-year-old woman developed unilateral painful ophthalmoplegia and visual loss in the right eye. Magnetic resonance imaging showed an abnormal soft-tissue area in the right cavernous sinus and the right orbital apex. Symptoms responded rapidly to treatment with corticosteroid. Visual evoked potentials to flash and pattern stimuli were both remarkably reduced and delayed in the right eye in the acute stage; however they improved to almost normal after steroid therapy. The pattern electroretinogram recorded in the acute stage was normal bilaterally. These results indicate that optic nerve involvement in Tolosa-Hunt syndrome can be mild and reversible.     

Identification of naturally processed T cell epitopes from glutamic acid decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of recent onset IDDM patients

Glutamic acid decarboxylase (GAD) has been defined as a major target antigen in insulin-dependent diabetes mellitus (IDDM). To identify the molecular ligands triggering a T cell response to GAD, a panel of human GAD65-specific T lymphocyte lines was generated from peripheral blood of three recent onset IDDM patients. All lines derived from a patient expressing the high-risk-conferring HLA-DR*0301/ *0401 haplotypes recognized a single epitope localized between amino acid positions 270 and 283 of GAD65, a stretch that is located in close proximity to the homology region shared with Coxsackie virus P2-C protein. All lines with this specificity were restricted to the DRA, B1*0401 product of the DR4 haplotype. Analysis of the GAD-specific T cell response in a second patient homozygous for DR4 haplotypes demonstrated that the same DRA, B1*0401 allele selected T cells specific for a different determinant. The T cell response profile in a third patient showed that DR*1501/ *1601-encoding haplotypes could present at least three different epitopes to GAD65-specific T lymphocytes. One of these epitopes was presented by a DR allele associated with the resistance-conferring DRB1*1501 haplotype. GAD-specific T cell lines could not be isolated from HLA class II-matched normal individuals. Our data reveal that (a) the T cell response to GAD65 is quite heterogenous in recent onset IDDM patients; (b) HLA-DR, not DQ, seems to be the principal restriction element used by T cells present at the onset of the disease; and (c) T cells responding to epitopes containing identical sequences to Coxsackie virus P2-C protein were not detected.     

Early and late postinfarct dilatation of the left ventricle: the connection to electrophysiological disorders and the risk of developing ventricular tachyarrhythmias

The aim of the study was to discover determinants of the onset of life threatening ventricular tachyarrhythmia. 102 patients with acute myocardial infarction and 32 patients with postinfarction cardiosclerosis were examined. The data gained at programmed ventricular stimulation, high resolution ECG, Holter ECG monitoring, spectral analysis of cardiac rhythm variability and two-dimension echocardiography proved the importance of early postinfarction left ventricular dilatation in the onset of electrical cardiac instability, establishment of anatomic substrate of monomorphic ventricular tachycardias, low variability of cardiac rhythm. The findings evidence that MI patients with late ventricular potentials and end-diastolic left ventricular index above 100 ml/m2 in subacute period may be considered as a group of high risk in need of individual approach and further therapy. The discovered lowering of informative value of non-invasive methods in patients late after MI dictates the necessity of new approaches to detection of electrophysiological disturbances and sudden death risk in registration of postinfarction dilatation of the heart.     

Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy

The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92-558).     

The product of proliferation disrupter is concentrated at centromeres and required for mitotic chromosome condensation and cell proliferation in Drosophila

Homozygosity for a null mutation in the proliferation disrupter (prod) gene of Drosophila causes decreased mitotic index, defects of anaphase chromatid separation, and imperfect chromosome condensation in larval neuroblasts and other proliferating cell populations. The defective condensation is especially obvious near the centromeres. Mutant larvae show slow growth and massive cell death in proliferating cell populations, followed by late larval lethality. Loss of prod function in mitotic clones leads to the arrest of oogenesis in the ovary and defective cuticle formation in imaginal disc derivatives. The prod gene encodes a novel 301-amino-acid protein that is ubiquitously expressed and highly concentrated at the centric heterochromatin of the second and third mitotic chromosomes, as well as at > 400 euchromatic loci on polytene chromosomes. We propose that Prod is a nonhistone protein essential for chromosome condensation and that the chromosomal and developmental defects are caused by incomplete centromere condensation in prod mutants.     

Long-term depletion of naive T cells in patients treated for Hodgkin's disease

We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8alphaalpha homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4-, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.     

Notifying patients exposed to blood products associated with Creutzfeldt-Jakob disease: theoretical risk for real people

BACKGROUND: In July 1995 the Canadian Red Cross Society recalled blood products because of the hypothetical risk of transmission of Creutzfeldt-Jakob disease (CJD) through those blood products. The authors undertook a survey to determine the views of patients and parents of patients about being notified that they or their child had received such blood products. METHODS: The study population consisted of 528 transfusion recipients, of whom 453 (85.8%) were under 16 years of age, notified by the Hospital for Sick Children, Toronto, of the CJD recalls in 1995 and 1996. Families attending an information session were asked to complete a self-administered questionnaire (85 cases). Ninety-seven families randomly selected from those who did not attend the session were interviewed by telephone. The questionnaire was adapted from a questionnaire used to evaluate families' responses to notification of transfusion and risk of HIV infection. RESULTS: More than 80% of the respondents said they wanted to be notified and would want to be notified if there were another recall. On initial receipt of the notification about two-thirds of the respondents had been anxious, fearful or angry. There was no one method of conveying the information that suited all, but a personalized letter was seen as the most acceptable method. INTERPRETATION: Most parents of children who have received blood products are in favour of being informed about the risk of CJD, despite the uncertainty of the information on risk and the anxiety that such information causes.     

Underutilization of warfarin in older persons with chronic nonvalvular atrial fibrillation at high risk for developing stroke

OBJECTIVE: To investigate the prevalence of the use of warfarin to maintain an international normalized ratio (INR) between 2.0 and 3.0 in older persons with chronic nonvalvular atrial fibrillation (AF), and without contraindications to warfarin, who are at high risk for developing new thromboembolic (TE) stroke. DESIGN: A retrospective analysis of charts from all older persons seen during 1997 at an academic hospital-based geriatrics practice. SETTING: An academic hospital-based geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians. PATIENTS: Three hundred eighty men and 1183 women, mean age 80+/-8 years (range 59 to 103 years), were included in the study. MEASUREMENTS AND MAIN RESULTS: Of 1563 persons studied, 141 (9%) had chronic nonvalvular AF. Of 141 persons with AF, 127 (90%) were at high risk for developing TE stroke because they had either a previous thromboembolism, congestive heart failure, or echocardiographic evidence of abnormal left ventricular systolic function; a systolic blood pressure >160 mm Hg; or they were women older than 75 years of age. Of the 127 persons with AF at high risk for developing TE stroke, three (2%) had contraindications to warfarin. Of the 124 persons with AF at high risk for developing TE stroke and no contraindications to warfarin, 61 (49%) were treated with warfarin to maintain an INR between 2.0 and 3.0, and 45 (36%) were treated with 325 mg aspirin daily. Of 14 persons with AF at low risk for developing TE stroke, one (7%) was treated with warfarin to maintain an INR between 2.0 and 3.0, and six (43%) were treated with 325 mg aspirin daily. CONCLUSIONS: Warfarin is underutilized as a treatment to maintain an INR between 2.0 and 3.0 in older persons with chronic nonvalvular AF at high risk for developing TE stroke.     

Behaviors of heterosexual sexually, transmitted disease clinic patients with sex partners at increased risk for human immunodeficiency virus infection

BACKGROUND AND OBJECTIVES: From March 1989 through December 1992, the Centers for Disease Control and Prevention conducted annual, voluntary surveys of human immunodeficiency virus (HIV) risk behavior in sentinel sexually transmitted disease (STD) clinics in 25 cities in the United States. GOAL: Describe behaviors of heterosexual participants who reported as their only risk for HIV infection sexual contact with persons at increased risk for HIV. STUDY DESIGN: Participants responded to a standard questionnaire that collected demographic data and medical, drug use, and sexual histories. RESULTS: Sex with an injection drug user was the most common risk behavior. Fewer than 5% of participants always used condoms in the preceding year; 38% never used condoms. Multivariate analyses identified three independent predictors of HIV infection in men: living in the Northeast (odds ratio [OR] = 3.6; P < 0.001), sex with an HIV-infected woman (OR = 3.6; P < 0.01), and black race (OR = 2.7; P < 0.01). For women, sex with an HIV-infected man was the strongest predictor (OR = 12.0; P < 0.001) followed by Northeast residence (OR = 5.4; P < 0.001) and black race (OR = 3.4; P < 0.01). CONCLUSION: Sexually transmitted disease clinic patients throughout the United States knowingly engaged in sexual activities with partners at increased risk for HIV infection. HIV prevention activities need to be targeted to all sexually active persons, particularly in areas where injection drug use and HIV are prevalent.     

The role of risk factors for periodontal disease in patients with rheumatoid arthritis

This paper summarises the methods and some of the findings of a large cohort study of dementia and cognitive decline in subjects aged over 75 years in Cambridge, particularly regarding the incidence wave. From a sample of 1968 subjects previously studied in a prevalence study in 1985-1987, survivors were restudied at 2.4 years, in a two-stage design employing the Mini; Mental State Examination (MMSE) and the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). High incidence rates of dementia were found, which rose steeply with age, particularly for Alzheimer's disease. New minimal dementia and milder cognitive impairment were also common. Cognitive decline on the MMSE showed a near normal, non-bimodal distribution. The sample has since been restudied at intervals for a total of up to 9 years to document longitudinal cognitive change. Brains have been obtained for post mortem neuropathological and molecular biological study, particularly of the early sequential changes associated with cognitive decline and dementia.