Faculty Bibliography

David M. Oshinsky reviews the book "A Consumers' Republic: The Politics of Mass Consumption in Postwar America" by Lizabeth Cohen

Leukocyte adhesion deficiency type 2 (LADII) is characterized by defective selectin ligand formation, recurrent infection, and mental retardation. This rare syndrome has only been described in 2 kindreds of Middle Eastern descent who have differentially responded to exogenous fucose treatment. The molecular defect was recently ascribed to single and distinct missense mutations in a putative Golgi guanosine diphosphate (GDP)-fucose transporter. Here, we describe a patient of Brazilian origin with features of LADII. Sequencing of the GDP-fucose transporter revealed a novel single nucleotide deletion producing a shift in the open-reading frame and severe truncation of the polypeptide. Overexpression of the mutant protein in the patient's fibroblasts did not rescue fucosylation, suggesting that the deletion ablated the activity of the transporter. Administration of oral L-fucose to the patient produced molecular and clinical responses, as measured by the appearance of selectin ligands, normalization of neutrophil counts, and prevention of infectious recurrence. The lower neutrophil counts paralleled improved neutrophil interactions with activated endothelium in cremasteric venules of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, fucose supplementation induced autoimmune neutropenia and the appearance of H antigen on erythrocytes, albeit without evidence of intravascular hemolysis. The robust response to fucose despite a severely truncated transporter suggests alternative means to transport GDP-fucose into the Golgi complex.

Despite many advances in the treatment of hypertension, adequate blood pressure (BP) control in elderly patients continues to be a challenge. Optimal control of BP remains elusive because of issues relating to drug dosage and proper choice of therapeutic agents, including questions regarding the role of diuretics.We examined the effect of diuretic treatment on BP in 12 elderly hypertensive patients whose hypertension was poorly controlled on previous drug regimens. We also evaluated the relationship of systolic, diastolic, and mean arterial BP (SBP, DBP, MAP, respectively) to changes in plasma renin activity (PRA), serum aldosterone (SA), atrial natriuretic peptide (ANP), and serum chemistries both before and after adding furosemide to the prior antihypertensive agents.At baseline, 83% of patients had low PRA (< 1 ng/mL/h). After furosemide, in 67% of patients, decreases in SBP (166 +/- 5 to 134 +/- 5 mm Hg; P <.001), DBP (82 +/- 4 to 71 +/- 4 mm Hg; P =.004), and MAP (111 +/- 3 to 92 +/- 3 mm Hg; P <.001), were associated with increases in PRA (2.1 +/- 1.2 to 5.1 +/- 1.8 ng/mL/h; P =.01) and SA (4.8 +/- 1.0 to 9.4 +/- 1.4 ng/dL; P =.01) and with decreases in ANP (101 +/- 28 to 58 +/- 11 pg/mL; P =.01) and body weight (77.5 +/- 3.6 to 76.4 +/- 3.3 kg; P =.02), findings consistent with volume mediated/salt sensitive hypertension. In the remaining 33% of patients, BP also decreased significantly, but there was no increase in PRA (0.15 +/- 0.05 to 0.10 +/- 0 ng/mL/h) or SA (9.2 +/- 2.2 to 7.0 +/- 0.8 ng/dL) and no decrease in ANP (66 +/- 5 to 75 +/- 18 pg/mL) (P = ns for all), suggesting alternate mechanisms for their responses.Many of the elderly hypertensive patients in our study had decreased PRA levels and showed significant reductions in BP after furosemide administration. Despite the associated increases in PRA and SA and decreases in ANP in 67% of patients, diuretic use remains important in the control of hypertension in this population

The patient is at the center of clinical medicine. In order to effectively teach clinical skills a teacher must learn to involve patients in the educational process. It is through this process that learners acquire the skills of observation, communication, examination and professionalism. Despite the importance of teaching with the patient present, many clinical teachers are hesitant to teach at the bedside. This paper describes a workshop on bedside teaching. The authors present barriers and advantages discussed during the workshop as well as a 'Model of Best Bedside Teaching Practices', which emerged after conducting the workshop for over 135 medical educators. The model includes suggested skills for effective bedside teaching that are arranged into three domains: attending to patient comfort, focused teaching and group dynamics.

Bioterrorism is an area of increasing public health concern. The intent of this article is to review the air cleansing technologies available to protect building occupants from the intentional release of bioterror agents into congregate spaces (such as offices, schools, auditoriums, and transportation centers), as well as through outside air intakes and by way of recirculation air ducts. Current available technologies include increased ventilation, filtration, and ultraviolet germicidal irradiation (UVGI) UVGI is a common tool in laboratories and health care facilities, but is not familiar to the public, or to some heating, ventilation, and air conditioning engineers. Interest in UVGI is increasing as concern about a possible malicious release of bioterror agents mounts. Recent applications of UVGI have focused on control of tuberculosis transmission, but a wide range of airborne respiratory pathogens are susceptible to deactivation by UVGI. In this article, the authors provide an overview of air disinfection technologies, and an in-depth analysis of UVGI-its history, applications, and effectiveness

A probabilistic model of aging is considered. It is based on the assumption that a random resource, a stochastic process of aging (wear) and the corresponding anti-aging process are embedded at birth. A death occurs when the accumulated wear exceeds the initial random resource. It is assumed that the anti-aging process decreases wear in each increment. The impact of environment (lifestyle) is also taken into account. The corresponding relations for the observed and the conditional hazard rate (force of mortality) are obtained. Similar to some demographic models, the deceleration of mortality phenomenon is explained via the concept of frailty. Simple examples are considered

PURPOSE: We examined the relationships among urethral hypermobility, intrinsic sphincter deficiency and incontinence in women. MATERIALS AND METHODS: A total of 65 consecutive women with stress urinary incontinence and 28 with lower urinary tract symptoms not associated with stress urinary incontinence were evaluated with videourodynamics, 24-hour voiding diaries and pad tests, vesical leak point pressure measurement and the cotton swab test. RESULTS: A total of 93 patients with a mean age +/- SD of 63 +/- 13 years were studied, including 65 who presented with stress urinary incontinence and 28 who presented with lower urinary tract symptoms without stress urinary incontinence. The incidence of urethral hypermobility was 32% in the stress urinary incontinence group and 36% in the lower urinary tract symptoms group (p = 0.46). When stress urinary incontinence cases were stratified according to a vesical leak point pressure of 0 to 60, 60 to 90 and greater than 90 cm. H2O, urethral hypermobility was noted in 25%, 31% and 41%, respectively, a difference that was not statistically significant (p = 0.6). Overall incontinent patients with and without urethral hypermobility had the same median number of incontinence episodes (5, range 1 to 13 versus 7, range 1 to 15, p = 0.39) and median pad weight (39.5 range 1 to 693 gm. versus 33.5, range 1 to 751, p = 0.19). When patients with intrinsic sphincter deficiency, defined as vesical leak point pressure less than 60 cm. H2O, were divided into those with and without urethral hypermobility, there were no differences in the mean number of incontinence episodes (9.4 +/- 3 versus 6 +/- 3.6, p = 0.17) or median pad weight (90 gm., range 10 to 348 versus 86, range 30 to 81, p = 0.76). The degree of change in the urethral angle did not correlate with vesical leak point pressure (r = 0.16, p = 0.24) or with pad weight (r = -0.23, p = 0.1). CONCLUSIONS: Urethral hypermobility was equally common in this group of women with lower urinary tract symptoms and stress urinary incontinence. Intrinsic sphincteric deficiency and urethral hypermobility may coexist and they do not define discrete classes of patients with stress urinary incontinence. Urethral hypermobility did not appear to have an independent effect on the frequency or severity of incontinence. Patients with stress urinary incontinence can still be characterized by vesical leak point pressure and change in the urethral angle, although these variables do not always define discrete classes.

The new quinolone garenoxacin (BMS-284756), which lacks a C-6 fluorine, was examined for its ability to block the growth of Staphylococcus aureus. Measurement of the MIC and the mutant prevention concentration (MPC) revealed that garenoxacin was 20-fold more potent than ciprofloxacin for a variety of ciprofloxacin-susceptible isolates, some of which were resistant to methicillin. The MPC for 90% of the isolates (MPC(90)) was below published serum drug concentrations achieved with recommended doses of garenoxacin. These in vitro observations suggest that garenoxacin has a low propensity for selective enrichment of fluoroquinolone-resistant mutants among ciprofloxacin-susceptible isolates of S. aureus. For ciprofloxacin-resistant isolates, the MIC at which 90% of the isolates tested were inhibited was below serum drug concentrations while the MPC(90) was not. Thus, for these strains, garenoxacin concentrations are expected to fall inside the mutant selection window (between the MIC and the MPC) for much of the treatment time. As a result, garenoxacin is expected to selectively enrich mutants with even lower susceptibility

Cardiovascular disease, an equal opportunity killer that actually affects more women than men is a shock to many women who believe this disease does not affect them as much as men. A healthy heart can be achieved through diet, weight control, and exercise. Furthermore, using Pycnogenol, an antioxidant, is powerful in reducing inflammation in the body, strengthening the vascular system, lowering high blood pressure and cholesterol, and fighting the effects of smoking, stress and other environmental risk factors on the heart

The findings suggest in effect that the vaccine failed in its prime objective. The vaccine showed virtually no effectiveness overall, making it extremely unlikely that it could be approved for use without further trials. But the data offers intriguing clues to possibly productive avenues of research. Dr. Jose Esparza, the leading vaccine expert at the UN AIDS agency in Geneva, said he was very encouraged by the results. This is the first demonstration of protection in humans, and one of the most significant findings in HIV vaccine research in many years, he said. Though the vaccine is not the final product that we need for public health use and is not ready to be licensed for sale, he said, it should give encouragement to all vaccine developers. Esparza said it was imperative to conduct more vaccine trials, especially in Africa. VaxGen was formed to carry the vaccine forward after the U.S. National Institutes of Health, and the company that invented the vaccine, Genentech, decided it was not worthy of clinical trials. The fact that the vaccine advanced to such large trials was largely the result of the doggedness of the company co-founder and president, Dr. Donald Francis, a former epidemiologist and virologist at the Centers for Disease Control and Prevention who was one of the first medical experts to see the dangers of AIDS when the disease became known more than 20 years ago. The vaccine, known as Aidsvax, is made from a protein called gp120, the same protein that protrudes from the surface of HIV and helps the virus dock with cells of the body's immune system. The protein in the vaccine is made in genetically engineered hamster ovary cells