Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.

BACKGROUND: The coagulation protein von Willebrand Factor (VWF) is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood. OBJECTIVES: To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies. METHODS: We measured VWF antigen (VWF:Ag), VWF propeptide (VWFpp), Factor VIII (FVIII), and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF) of VWF in two pregnancies which had samples from multiple trimesters. RESULTS: VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation. CONCLUSIONS: These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.

Modulation of the BP response to diet by genes in the renin-angiotensin system and the adrenergic nervous system.

BACKGROUND: Essential hypertension results from the interaction of several genetic and environmental factors. Identification of genetic factors that modulate blood pressure (BP) response to interventions can lead to improved strategies for prevention and control. The purpose of this study was to identify genes that modulate BP response to dietary interventions. METHODS: We used data and samples collected in two randomized feeding studies to determine the extent to which genetic architecture is associated with the effect on BP of sodium intake and the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. Participants in both trials were adults with above-optimal BP or unmedicated stage 1 hypertension. Genomic DNA was typed for several candidate genes. RESULTS: The effect of sodium intake on BP differed by genotype at the angiotensinogen, ß2-adrenergic receptor, and kallikrein loci. The effect of DASH dietary pattern on BP differed by genotype at the ß2-adrenergic receptor locus. CONCLUSIONS: These findings have implications for understanding the mechanism(s) through which diet affects BP, the heterogeneity of these effects, and the extent to which dietary interventions can modulate genetic predisposition.

Determining nursing faculty development needs.

Although faculty members often come to a university school of nursing with little or no experience in teaching, research, or other forms of scholarship, few schools of nursing have a comprehensive, formalized faculty development program. In considering the need to find and retain the best faculty in this competitive market, the University of North Carolina at Chapel Hill School of Nursing appointed a task force to develop a formal faculty development program for the School. After reviewing the literature and contacting 24 schools of nursing, the task force concluded that most do not offer a systematic approach to faculty development. The task force developed and distributed a needs assessment and received responses from 53% of the faculty. Based on the needs assessment the task force made eight recommendations to the faculty for an ongoing, comprehensive faculty development program.

Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis.

Four pneumococcal genes (phtA, phtB, phtD, and phtE) encoding a novel family of homologous proteins (32 to 87% identity) were identified from the Streptococcus pneumoniae genomic sequence. These open reading frames were selected as potential vaccine candidates based upon their possession of hydrophobic leader sequences which presumably target these proteins to the bacterial cell surface. Analysis of the deduced amino acid sequences of these gene products revealed the presence of a histidine triad motif (HxxHxH), termed Pht (pneumococcal histidine triad) that is conserved and repeated several times in each of the four proteins. The four pht genes (phtA, phtB, phtD, and a truncated version of phtE) were expressed in Escherichia coli. A flow cytometry-based assay confirmed that PhtA, PhtB, PhtD and, to a lesser extent, PhtE were detectable on the surface of intact bacteria. Recombinant PhtA, PhtB, and PhtD elicited protection against certain pneumococcal capsular types in a mouse model of systemic disease. These novel pneumococcal antigens may serve as effective vaccines against the most prevalent pneumococcal serotypes.

Improvement in mood, physical symptoms, and function with nortriptyline for depression in patients with chronic obstructive pulmonary disease.

Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients, detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate. The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression. Thirty patients completed a 12-week, randomized controlled trial of nortriptyline. Nortriptyline was clearly superior to placebo for treatment of depression. Nortriptyline treatment was accompanied by marked improvements in anxiety, certain respiratory symptoms, overall physical comfort, and day-to-day function; placebo effects were negligible. Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment. These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients.

Psychosocial and ethical issues of AIDS health care programs.

The psychiatric, psychosocial, and ethical considerations in the design and evaluation of health care programs for AIDS patients and others with HIV infection are described in this article. The responsibilities of health care providers are considered in the context of the history and epidemiology of AIDS, previous responses of the health care delivery system, and the concerns of the general public. General guidelines for program development are set forth; these guidelines embody ethical principles, the role of education in altering the behavior and attitudes of patients and health care workers, the optimal levels of and precautions for infection control, and the evaluation of a patient's competency and judgement. Several examples of the use of these guidelines to resolve difficult policy issues arising in the treatment of patients with AIDS or HIV infection are also provided.