Martin Luther King, Jr. Multi-Service Ambulatory Care Center

AD (Alzheimer's disease) is linked to Abeta (amyloid beta-peptide) misfolding. Studies demonstrate that the level of soluble Abeta oligomeric forms correlates better with the progression of the disease than the level of fibrillar forms. Conformation-dependent antibodies have been developed to detect either Abeta oligomers or fibrils, suggesting that structural differences between these forms of Abeta exist. Using conditions which yield well-defined Abeta-(1-42) oligomers or fibrils, we studied the secondary structure of these species by ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy. Whereas fibrillar Abeta was organized in a parallel beta-sheet conformation, oligomeric Abeta displayed distinct spectral features, which were attributed to an antiparallel beta-sheet structure. We also noted striking similarities between Abeta oligomers spectra and those of bacterial outer membrane porins. We discuss our results in terms of a possible organization of the antiparallel beta-sheets in Abeta oligomers, which may be related to reported effects of these highly toxic species in the amyloid pathogenesis associated with AD.

This review chronicles the synergistic growth of the fields of fatty acid and polyketide synthesis over the last century. In both animal fatty acid synthases and modular polyketide synthases, similar catalytic elements are covalently linked in the same order in megasynthases. Whereas in fatty acid synthases the basic elements of the design remain immutable, guaranteeing the faithful production of saturated fatty acids, in the modular polyketide synthases, the potential of the basic design has been exploited to the full for the elaboration of a wide range of secondary metabolites of extraordinary structural diversity.

Viral infections and clinical complications were studied during hemodialysis and after renal transplantation. Active cytomegalovirus infection developed in 96% of patients after renal transplantation; reactivation of herpes simplex, varicella-zoster, and Epstein-Barr viruses was found in 35%, 24%, and 0% of patients, respectively. Cytomegalovirus viremia developed in 42% of patients an average of two months after renal transplantation, lasted 1.75 (+/- 1.5) months (except in one patient with chronic viremia), and was followed by chronic viruria. Higher titers of infectious cytomegalovirus were found in the polymorphonuclear than in the mononuclear leukocyte fraction. Reactivation of a latent infection and, less likely, respiratory infection appear to be the most probable mechanisms of cytomegalovirus infection after renal transplantation. One to three months after transplant, cytomegalovirus infection may be related to fever, arthralgia, pneumonitis, and leukopenia; three to four months after transplant, the virus may be related to hepatitis; and 12-30 months after transplant, it may be related to retinitis in patients with chronic viremia. Although other causes of these complications are possible, herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, measles virus, adenovirus, hepatitis B virus, and Toxoplasma gondii appear to be of lesser importance than cytomegalovirus in this respect.

BACKGROUND: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes. Women with atypical breast ductal epithelial cells have an increased relative risk of breast cancer. In this study, ductal lavage, a new procedure for collecting ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. METHODS: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by lavage of fluid-yielding ducts. All statistical tests were two-sided. RESULTS: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7% or more. Nipple aspirate fluid (NAF) samples were evaluated cytologically for 417 women, and ductal lavage samples were evaluated for 383 women. Adequate samples for diagnosis were collected from 111 (27%) and 299 (78%) women, respectively. A median of 13,500 epithelial cells per duct (range, 43-492,000 cells) was collected by ductal lavage compared with a median of 120 epithelial cells per breast (range, 10-74,300) collected by nipple aspiration. For ductal lavage, 92 (24%) subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%). For NAF, corresponding percentages were 6%, 3%, and fewer than 1%. Ductal lavage detected abnormal intraductal breast cells 3.2 times more often than nipple aspiration (79 versus 25 breasts; McNemar's test, P<.001). No serious procedure-related adverse events were reported. CONCLUSIONS: Large numbers of ductal cells can be collected by ductal lavage to detect atypical cellular changes within the breast. Ductal lavage is a safe and well-tolerated procedure and is a more sensitive method of detecting cellular atypia than nipple aspiration.

The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans.

• We prospectively tested the effect of the early postinjury attainment of supranormal values of cardiac index (≥4.52 L/min per square meter), oxygen delivery (≥670 mL/min per square meter), and oxygen consumption (≥166 mL/min per square meter) on outcome in traumatized patients with an estimated blood loss of 2000 mL or more. The goals in control patients were to attain normal values for all hemodynamic measurements. During the 6-month period, 33 protocol patients and 34 control patients with similar vital signs, estimated blood losses, and severity of injuries were enrolled in the study. Eight (24%) protocol patients died, while 15 (44%) control patients died. The protocol patients had fewer mean (±SEM) organ failures per patient (0.76±1.21 vs 1.59±1.60), shorter stays in the intensive care unit (5±3 vs 12±12), and fewer mean days requiring ventilation (4±3 vs 11±10) than did the control patients (<i>P</i>&lt;.05 for each). We conclude that attaining supranormal circulatory values improves survival and decreases morbidity in the severely traumatized patient. (<i>Arch Surg.</i>1992;127:1175-1181)

Despite the World Health Organization's declaration that the spread of tuberculosis is a global emergency and despite the implementation of strong tuberculosis-control initiatives, this highly infectious disease continues to affect all vulnerable populations, including the elderly population (age ⩾65 years). Tuberculosis in aging adults remains a clinical and epidemiological challenge. Atypical clinical manifestations of tuberculosis in older persons can result in delay in diagnosis and initiation of treatment; thus, unfortunately, higher rates of morbidity and mortality from this treatable infection can occur. Underlying illnesses, age-related diminution in immune function, the increased frequency of adverse drug reactions, and institutionalization can complicate the overall clinical approach to tuberculosis in elderly patients; maintenance of a high index of suspicion for tuberculosis in this vulnerable population is, thus, undoubtedly justifiable.

SCOPUS: re.j

One hundred fifty-two strains of Clostridium were isolated from 144 patients over a 14-month-peroid. These included 23 recognized species and 23 strains that were unclassified. Soft tissues or abscesses yielded 84 strains of Clostridium. Intraabdominal sites predominated, but clostridia were recovered from empyema, carcinoma, frostbite with gas gangrene, muscle abscess, aortic graft, and brain abscess. Blood cultures yielded 65 strains of Clostridium from 49 patients, representing 0.3% of 16,314 blood cultures (or 2.6% of 2,168 positive cultures). Clostridium perfringens was most common in blood, accounting for 37 isolates (57%). Clostridial bacteremia was often unrelated to the clinical setting and was found in alcoholics with aspiration or Streptococcus pneumoniae pneumonia, pulmonary tuberculosis, empyema, meningococcemia, and infantile gastroenteritis. In 20 of the 49 patients (41%), aerobic or other anaerobic bacteria were cultured concurrently from the blood. Thus, clostridial bacteremia should be interpreted with caution since there may be little correlation with the patient's clinical condition.

The reaction of oxygen with protein diiron sites is important in bioorganic syntheses and biomineralization. An unusually short Fe-Fe distance of 2.53 angstroms was found in the diiron (mu-1,2 peroxodiferric) intermediate that forms in the early steps of ferritin biomineralization. This distance suggests the presence of a unique triply bridged structure. The Fe-Fe distances in the mu-1, 2 peroxodiferric complexes that were characterized previously are much longer (3.1 to 4.0 angstroms). The 2.53 angstrom Fe-Fe distance requires a small Fe-O-O angle (approximately 106 degrees to 107 degrees). This geometry should favor decay of the peroxodiferric complex by the release of H2O2 and mu-oxo or mu-hydroxo diferric biomineral precursors rather than by oxidation of the organic substrate. Geometrical differences may thus explain how diiron sites can function either as a substrate (in ferritin biomineralization) or as a cofactor (in O2 activation).

Both human lung surfactant protein, SP-B, and its amino-terminal peptide, SP-B1-25, inhibit the formation of condensed phases in monolayers of palmitic acid, resulting in a new fluid phase. This fluid phase forms a network, separating condensed-phase domains at coexistence. The network persists to high surface pressures, altering the nucleation, growth, and morphology of monolayer collapse structures, leading to lower surface tensions on compression and more reversible respreading on expansion. The network is stabilized by the low line tension between the fluid phase and the condensed phase as confirmed by the formation of "stripe" phases.

Cardiac catheterization studies have demonstrated that Doppler-derived flow velocities in the ductal flow jet and the left pulmonary artery accurately predict the aortopulmonary pressure difference and left-to-right shunt size in newborns. To assess the presence of persistent pulmonary hypertension in premature newborns with various degrees of respiratory distress syndrome (RDS) severity, we estimated pulmonary artery pressure from the aortopulmonary pressure difference and pulmonary blood flow from the left pulmonary artery flow velocity with color-flow-directed, pulsed Doppler echocardiography. Seventy-nine premature neonates were divided into three groups—no or mild RDS (n = 27), severe RDS (n = 38), and fatal RDS (n = 14)—and compared with a group of healthy term neonates (n = 34). In premature and term neonates with no/mild RDS the mean ± SEM aortopulmonary pressure difference increased from 7.3 ± 0.4 and 6.6 ± 0.5 mm Hg to 22.8 ± 1.4 and 21.4 ± 1.1 mm Hg over the first 24 hours (P &amp;lt; .001). The mean aortopulmonary pressure difference was 0.9 ± 0.3 mm Hg during the first 72 hours in neonates with fatal RDS, but increased from 1.5 ± 0.3 mm Hg at 4 hours to 7.4 ± 0.6 at 24 hours and 21.5 ± 0.7 mm Hg at 72 hours of age in neonates with severe RDS. Left pulmonary artery velocity time integrals were 18.3 ± 0.5 cm in premature and 18.8 ± 0.5 cm in term neonates with no/mild RDS at 12 hours vs 11.2 ± 0.4 cm in neonates with severe and 9.9 ± 0.5 cm in neonates with fatal RDS (P &amp;lt; .001). At 36 hours of age pulmonary blood flow velocity in neonates with severe RDS had caught up with that of those with no/mild RDS, but was only 11.6 ± 0.6 cm in neonates with fatal RDS (P &amp;lt; .001). These data indicate that persistent pulmonary hypertension and large right-to-left shunts via the ductus are common findings in small premature neonates with severe RDS and are predictive of early demise.

<b><i>Background:</i></b> It has been suggested that a zone of perihematomal ischemia analogous to an ischemic penumbra exists in patients with primary intracerebral hemorrhage (ICH). Diffusion-perfusion MRI provides a novel means of assessing injury in perihematomal regions in patients with ICH. <b><i>Objective:</i></b> To characterize diffusion-perfusion MRI changes in the perihematomal region in patients with hyperacute intracerebral hemorrhage. <b><i>Method:</i></b> Twelve patients presenting with hyperacute, primary ICH undergoing CT scanning and diffusion-perfusion MRI within 6 hours of symptom onset were reviewed. An automated thresholding technique was used to identify decreased apparent diffusion coefficient (ADC) values in the perihematomal regions. Perfusion maps were examined for regions of relative hypo- or hyperperfusion. <b><i>Results:</i></b> Median baseline NIH Stroke Scale score was 17 (range, 6 to 28). Median hematoma volume was 13.3 mL (range, 3.0 to 74.8 mL). MRI detected the hematoma in all patients on echo-planar susceptibility-weighted imaging and in all seven patients imaged with gradient echo sequences. In six patients who underwent perfusion imaging, no focal defects were visualized on perfusion maps in tissues adjacent to the hematoma; however, five of six patients demonstrated diffuse ipsilateral hemispheric hypoperfusion. On diffusion imaging, perihematomal regions of decreased ADC values were identified in three of 12 patients. All three subsequently showed clinical and radiologic deterioration. <b><i>Conclusions:</i></b> A rim of perihematomal decreased ADC values was visualized in the hyperacute period in a subset of patients with ICH. The presence of a rim of decreased ADC outside the hematoma correlated with poor clinical outcome. Although perfusion maps did not demonstrate a focal zone of perihematomal decreased blood flow in any patient, most patients had ipsilateral hemispheric hypoperfusion.

Exercise training increases exercise capacity of maintenance hemodialysis patients, but the cellular mechanisms responsible for this effect are unclear. We studied the effects of different forms of exercise training (endurance, strength, or a combination where patients underwent about one-half each

In order to evaluate a new thoracic electrical bioimpedance (TEB) system for measurement of stroke volume based on the Sramek-Bernstein equation, 391 paired values of cardiac output were measured simultaneously with the standard thermodilution method. These values were obtained from 16 patients selected for having the most severe illness during a 6-month period; the intent was to evaluate the bioimpedance method in the worst possible situations. The correlation coefficient (r) was 0.83, slope was 0.87, intercept was 1.53, and the mean difference between the two methods was 16.2 +/- 11.8 (SD)% in the total series. In 285 paired samples where satisfactory conditions were met, r was 0.90, slope was 0.98, intercept was 0.34, and the mean difference was 11.8 +/- 8.9%. The data indicate satisfactory correlations between these two methods. When the TEB waveform is satisfactory, the agreement between TEB and thermodilution is as good as the agreement between serial thermodilution methods. Difficulties may arise with dysrhythmias, tachycardia (heart rate greater than 150 beat/min), metal in the chest or chest wall, sepsis, hypertension, and extremely oily skin. Mechanical ventilation did not appear to be a problem.

We recently introduced a series of stimuli-responsive, mechanically adaptive polymer nanocomposites. Here, we report the first application of these bio-inspired materials as substrates for intracortical microelectrodes. Our hypothesis is that the ideal electrode should be initially stiff to facilitate minimal trauma during insertion into the cortex, yet become mechanically compliant to match the stiffness of the brain tissue and minimize forces exerted on the tissue, attenuating inflammation. Microprobes created from mechanically reinforced nanocomposites demonstrated a significant advantage compared to model microprobes composed of neat polymer only. The nanocomposite microprobes exhibit a higher storage modulus (E' = ~5 GPa) than the neat polymer microprobes (E' = ~2 GPa) and can sustain higher loads (~12 mN), facilitating penetration through the pia mater and insertion into the cerebral cortex of a rat. In contrast, the neat polymer microprobes mechanically failed under lower loads (~7 mN) before they were capable of insertion into cortical tissue. Further, we demonstrated the material's ability to morph while in the rat cortex to more closely match the mechanical properties of the cortical tissue. Nanocomposite microprobes that were implanted into the rat cortex for up to eight weeks demonstrated increased cell density at the microelectrode-tissue interface and a lack of tissue necrosis or excessive gliosis. This body of work introduces our nanocomposite-based microprobes as adaptive substrates for intracortical microelectrodes and potentially for other biomedical applications.

Abstract Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1 − / − mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1 − / − only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease.

OBJECTIVE: This review examines herbs commonly used for psychiatric symptoms-St. John's wort, kava, ginkgo biloba, and valerian. METHODS: MEDLINE was searched for articles related to the use of herbs in psychiatry published after 1990. A secondary search examined sources cited in articles obtained from the MEDLINE search. RESULTS: Of nine controlled and standardized trials of St. John's wort, five showed the herb's superiority to placebo, and four found no differences in effectiveness when compared with antidepressant drugs. The pharmacologically active components are not known. Several double-blind, placebo-controlled trials have demonstrated the anxiolytic efficacy of kava, but these studies had ill-defined patient populations, small sample sizes, and short treatment duration. All but one of 40 controlled trials of ginkgo extracts in the treatment of dementia found clinically significant improvement in memory loss, concentration, fatigue, anxiety, and depressed mood. Most studies of gingko had poorly defined patient populations and small sample sizes and used nonstandard measures. A recent well-designed multicenter study showed significantly less decline in cognitive function among patients with dementia receiving gingko. Valerian has been shown to decrease sleep latency and nocturnal awakenings and improve subjective sleep quality, but placebo effects were marked in some studies, and in some cases the beneficial effects were not seen until two to four weeks of therapy. CONCLUSIONS: Although evidence of the efficacy of herbal preparations in treating psychiatric conditions is growing, translating the results of efficacy studies into effective treatments for patients is hampered by the chemical complexity of the products, the lack of standardization of commonly available preparations, and the paucity of well-controlled studies.

OBJECTIVE: Reduced intake of sweetened caloric beverages (SCBs) is recommended to lower total energy intake. Replacing SCBs with non-caloric diet beverages does not automatically lower energy intake, however. Compensatory increases in other food or beverages reportedly negate benefits of diet beverages. The purpose of this study was to evaluate drinking water as an alternative to SCBs. RESEARCH METHODS AND PROCEDURES: Secondary analysis of data from the Stanford A TO Z intervention evaluated change in beverage pattern and total energy intake in 118 overweight women (25 to 50 years) who regularly consumed SCBs (>12 ounces/d) at baseline. At baseline and 2, 6, and 12 months, mean daily beverage intake (SCBs, drinking water, non-caloric diet beverages, and nutritious caloric beverages), food composition (macronutrient, water, and fiber content), and total energy intake were estimated using three 24-hour diet recalls. Beverage intake was expressed in relative terms (percentage of beverages). RESULTS: In fixed effects models that controlled for total beverage intake, non-caloric and nutritious caloric beverage intake (percentage of beverages), food composition, and energy expenditure [metabolic equivalent (MET)], replacing SCBs with drinking water was associated with significant decreases in total energy intake that were sustained over time. The caloric deficit attributable to replacing SCBs with water was not negated by compensatory increases in other food or beverages. Replacing all SCBs with drinking water was associated with a predicted mean decrease in total energy of 200 kcal/d over 12 months. DISCUSSION: The results suggest that replacing SCBs with drinking water can help lower total energy intake in overweight consumers of SCBs motivated to diet.

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. It is a medically and socially complex, multisystem illness that affects individuals throughout the lifespan. Given improvements in care, most children with SCD survive into adulthood. However, access to adult sickle cell care is poor in many parts of the United States, resulting in increased acute care utilization, disjointed care delivery, and early mortality for patients. A dearth of nonmalignant hematology providers, the lack of a national SCD registry, and the absence of a centralized infrastructure to facilitate comparative quality assessment compounds these issues. As part of a workshop designed to train health care professionals in the skills necessary to establish clinical centers focused on the management of adults living with SCD, we defined an SCD center, elucidated required elements of a comprehensive adult SCD center, and discussed different models of care. There are also important economic impacts of these centers at an institutional and health system level. As more clinicians are trained in providing adult-focused SCD care, center designation will enhance the ability to undertake quality improvement and compare outcomes between SCD centers. Activities will include an assessment of the clinical effectiveness of expanded access to care, the implementation of SCD guidelines, and the efficacy of newly approved targeted medications. Details of this effort are provided.