The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

Body pain and treatment response in late-life depression.

OBJECTIVE: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.     

Developing a Peer Review Process for Web-based Curricula

The World Wide Web creates new challenges and opportunities for medical educators. Prominent among these are the lack of consistent standards by which to evaluate web-based educational tools. We present the instrument that was used to review web-based innovations in medical education submissions to the 2003 Society of General Internal Medicine (SGIM) national meeting, and discuss the process used by the SGIM web-based clinical curriculum interest group to develop the instrument. The 5 highest-ranked submissions are summarized with commentary from the reviewers.     

Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.     

Cytologic findings in stage I adenocarcinoma of the lung: Implications for the detection of early lung cancer

Preoperative cytologic examinations were performed on bronchial material from 92 patients with postsurgical (pathologic) stage I (American Joint Committee) adenocarcinoma of the lung. All patients were followed up for at least 5 years or until death; thus, cases of adenocarcinoma metastatic to the lungs were virtually excluded. Only 22 patients (24%) had abnormal preoperative cytologic findings. This low cytologic sensitivity is ascribed to the small size and peripheral location of the tumors. Large lesions of high histologic grades were more likely to have positive preoperative cytologic findings than small, well-differentiated ones.     

Advances in the use of nucleic acid probes in diagnosis of viral diseases of man

Summary A variety of methods are now available for the preparation and labelling of viral nucleic acids for use as probes in diagnostic virology. Some of these are assessed including the use of synthetic oligonucleotides in place of molecularly cloned nucleic acids, and alternatives to labelling with radioactive isotopes such as biotin, enzymes and fluorochromes. Dot blot, sandwich, indirect sandwich and in situ hybridization are covered, and examples given of the current use of nucleic acid probes in detection of human viral infections. The potential and limitations of nucleic acid hybridization are discussed in the light of these new methods.     

Season of birth in infantile autism

Existing evidence suggests an excess of winter births in schizophrenia and inconsistent results for other psychiatric conditions. The present study examined seasonal effects of birth among autistic individuals. Results revealed an excess of spring and carly summer births and an underrepresentation of winter and fall births. However, this pattern was obtained only for the male, nonverbal, and lower-functioning autistic subgroup.This project was supported in part by the Ontario Mental Health Foundation Grant #988-84/86.     

Satisfaction with Team Midwifery Care for Low‐ and High‐Risk Women: A Randomized Controlled Trial

ABSTRACT:Background: In 1996 a new model of maternity care characterized by continuity of midwifery care from early pregnancy through the postpartum period was implemented for women attending Monash Medical Centre, a tertiary level obstetric service, in Melbourne, Australia. This study's purpose was to assess the impact of this model on women's views and experiences of care during the antenatal, intrapartum, and postpartum periods compared with views of women receiving standard maternity care. Methods: One thousand low‐ and high‐risk women who booked at the antenatal clinic and met the eligibility criteria were randomly allocated to continuity of midwifery care from a group of seven midwives in collaboration with medical staff, or to standard care from a variety of midwives and medical staff. Women's views of care were measured by means of a postal questionnaire at four months after the birth. Results: Team midwifery care was associated with increased satisfaction with antenatal, intrapartum, and some aspects of postpartum care. The differences were most obvious for antenatal care. Conclusions: Continuity of midwifery care is realistically achievable in a tertiary obstetric referral service and is associated with increased satisfaction. (BIRTH 30:1 March 2003)     

Evaluating the effectiveness of interventions: exploration of two statistical methods.

Repeated measures designs are often used to evaluate the effectiveness of interventions. In these designs, the outcomes are measured on several occasions before and after implementation of the intervention. Two statistical methods, the repeated measures analysis of variance (RM-ANOVA) and hierarchical linear models (HLM), can be used to analyze the data. The authors provide an overview of the statistical models underlying RM-ANOVA and HLM and discuss the strengths and limitations of each. They propose that the 2 methods are complementary in determining the effectiveness of interventions.