The effect of high-flow nasal oxygen flow rate on gas exchange in apnoeic patients: a randomised controlled trial.

High-flow nasal oxygen can be administered at induction of anaesthesia for the purposes of pre-oxygenation and apnoeic oxygenation. This intervention is claimed to enhance carbon dioxide elimination during apnoea, but the extent to which this occurs remains poorly quantified. The optimal nasal oxygen flow rate for gas exchange is also unknown. In this study, 114 patients received pre-oxygenation with high-flow nasal oxygen at 50 l.min-1. At the onset of apnoea, patients were allocated randomly to receive one of three nasal oxygen flow rates: 0 l.min-1; 70 l.min-1; or 120 l.min-1. After 4 minutes of apnoea, all oxygen delivery was ceased, tracheal intubation was performed, and oxygen delivery was recommenced when SpO2 was 92%. Mean (SD) PaCO2 rise during the first minute of apnoea was 1.39 (0.39) kPa, 1.41 (0.29) kPa, and 1.26 (0.38) kPa in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.16. During the second, third and fourth minutes of apnoea, mean (SD) rates of rise in PaCO2 were 0.34 (0.08) kPa.min-1, 0.36 (0.06) kPa.min-1 and 0.37 (0.07) kPa.min-1 in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.17. After 4 minutes of apnoea, median (IQR [range]) arterial oxygen partial pressures in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups were 24.5 (18.6-31.4 [12.3-48.3]) kPa; 36.6 (28.1-43.8 [9.8-56.9]) kPa; and 37.6 (26.5-45.4 [11.0-56.6]) kPa, respectively; p < 0.001. Median (IQR [range]) times to desaturate to 92% after the onset of apnoea in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, were 412 (347-509 [190-796]) s; 533 (467-641 [192-958]) s; and 531 (462-681 [326-1007]) s, respectively; p < 0.001. In conclusion, the rate of carbon dioxide accumulation in arterial blood did not differ significantly between apnoeic patients who received high-flow nasal oxygen and those who did not.

Expression of RcrB confers resistance to hypochlorous acid in uropathogenic Escherichia coli.

To eradicate bacterial pathogens, neutrophils are recruited to the sites of infection, where they engulf and kill microbes through the production of reactive oxygen and chlorine species (ROS/RCS). The most prominent RCS is the antimicrobial oxidant hypochlorous acid (HOCl), which rapidly reacts with various amino acid side chains, including those containing sulfur and primary/tertiary amines, causing significant macromolecular damage. Pathogens like uropathogenic Escherichia coli (UPEC), the primary causative agent of urinary tract infections, have developed sophisticated defense systems to protect themselves from HOCl. We recently identified the RcrR regulon as a novel HOCl defense strategy in UPEC. Expression of the rcrARB operon is controlled by the HOCl-sensing transcriptional repressor RcrR, which is oxidatively inactivated by HOCl resulting in the expression of its target genes, including rcrB. The rcrB gene encodes a hypothetical membrane protein, deletion of which substantially increases UPEC's susceptibility to HOCl. However, the mechanism behind protection by RcrB is unclear. In this study, we investigated whether (i) its mode of action requires additional help, (ii) rcrARB expression is induced by physiologically relevant oxidants other than HOCl, and (iii) expression of this defense system is limited to specific media and/or cultivation conditions. We provide evidence that RcrB expression is sufficient to protect E. coli from HOCl. Furthermore, RcrB expression is induced by and protects from several RCS but not from ROS. RcrB plays a protective role for RCS-stressed planktonic cells under various growth and cultivation conditions but appears to be irrelevant for UPEC's biofilm formation. IMPORTANCE Bacterial infections pose an increasing threat to human health, exacerbating the demand for alternative treatments. Uropathogenic Escherichia coli (UPEC), the most common etiological agent of urinary tract infections (UTIs), are confronted by neutrophilic attacks in the bladder, and must therefore be equipped with powerful defense systems to fend off the toxic effects of reactive chlorine species. How UPEC deal with the negative consequences of the oxidative burst in the neutrophil phagosome remains unclear. Our study sheds light on the requirements for the expression and protective effects of RcrB, which we recently identified as UPEC's most potent defense system toward hypochlorous acid (HOCl) stress and phagocytosis. Thus, this novel HOCl stress defense system could potentially serve as an attractive drug target to increase the body's own capacity to fight UTIs.

Multistate outbreaks of Salmonella infections linked to imported Maradol papayas - United States, December 2016-September 2017.

Foodborne salmonellosis causes approximately 1 million illnesses annually in the United States. In the summer of 2017, we investigated four multistate outbreaks of Salmonella infections associated with Maradol papayas imported from four Mexican farms. PulseNet initially identified a cluster of Salmonella Kiambu infections in June 2017, and early interviews identified papayas as an exposure of interest. Investigators from Maryland, Virginia and Food and Drug Administration (FDA) collected papayas for testing. Several strains of Salmonella were isolated from papayas sourced from Mexican Farm A, including Salmonella Agona, Gaminara, Kiambu, Thompson and Senftenberg. Traceback from two points of service associated with illness sub-clusters in two states identified Farm A as a common source of papayas, and three voluntary recalls of Farm A papayas were issued. FDA sampling isolated four additional Salmonella strains from papayas sourced from Mexican Farms B, C and D. In total, four outbreaks were identified, resulting in 244 cases with illness onset dates from 20 December 2016 to 20 September 2017. The sampling of papayas and the collaborative work of investigative partners were instrumental in identifying the source of these outbreaks and preventing additional illnesses. Evaluating epidemiological, laboratory and traceback evidence together during investigations is critical to solving and stopping outbreaks.

Clinically meaningful efficacy of a non-estrogen agent: re-analysis of phase-2 data evaluating MF101.

OBJECTIVE: To evaluate the level of reduction in hot flushes among a cohort of postmenopausal women randomized to a phase-2 clinical trial evaluating MF101, a selective estrogen receptor ß modulator, for treatment of vasomotor symptoms to determine clinically meaningful efficacy. METHODS: We performed a re-analysis of data from a double-blinded, placebo-controlled trial of 217 postmenopausal women randomized to treatment with MF101 or placebo for 12 weeks. At study termination, participants were asked if they were satisfied enough with medication to continue therapy. RESULTS: Of the women treated, 73% with ≥50% reduction in hot flush frequency and 77% with ≥60% reduction in hot flush frequency were willing to continue treatment. CONCLUSION: A 50-60% reduction in hot flushes is clinically meaningful among postmenopausal women who are being treated with a non-estrogen agent such as MF101.

Application of multiple locus variable number of tandem repeat analysis (MLVA), phage typing and antimicrobial susceptibility testing to subtype Salmonella enterica serovar Typhimurium isolated from pig farms, pork slaughterhouses and meat producing plants in Ireland.

Salmonella enterica subsp. enterica serovar Typhimurium is a common zoonotic pathogen encountered in Irish pigs and the pork industry and its characterisation using highly discriminatory typing methods is necessary for epidemiological studies, outbreak investigation and control. Multiple locus variable number of tandem repeat analysis (MLVA), phage typing and antimicrobial susceptibility testing were applied to characterise 301 S. typhimurium isolates of porcine origin isolated from farms, slaughterhouses and pork meat producing plants in Ireland over a four-year period. 154 MLVA patterns were obtained compared to 19 phage types and 38 AMR patterns, and MLVA was particularly useful for discriminating isolates of the same phage type, e.g. DT104 and DT104b, or isolates that were Untypable or in the category of "react with phage but does not conform to a recognised phage type" (RDNC) by the phage typing method. Cluster analysis of MLVA profiles using a minimum spanning tree (MST) demonstrated two major clusters (I and II), which showed to have a clear association with phage types, cluster I associated to phage types DT104, U302 and DT120 and cluster II associated to DT193 and U288. The results of this present study showed that MLVA is highly discriminatory and permitted the identification of identical profiles among isolates obtained at different points of the pork food chain. The same MLVA profile was observed in some cases among isolates with different phage types. While this can be explained by the fact that some phage types are closely related, it also indicates that combining phage typing and MLVA enhances strain typing of S. typhimurium.

Relationships between clinical signs, pathological changes and tissue distribution of Mycobacterium avium subspecies paratuberculosis in 21 cows from herds affected by Johne's disease.

Twenty-one cows from eight herds affected by Johne's disease were assigned to four groups: seven were not thriving and had persistent diarrhoea, six were not thriving and had intermittent diarrhoea, four were not thriving but did not have diarrhoea, and four were clinically normal. Postmortem, macroscopic lesions consistent with Johne's disease were identified in 17 of the cows and Mycobacterium avium subspecies paratuberculosis (MAP) was isolated from all of them. However, except for the fact that diarrhoea was correlated with the presence of lesions in the large intestine there was little correlation between the presence or absence of clinical signs and the lesions associated with Johne's disease. The tissue distribution of MAP was also poorly correlated with either the clinical signs or the lesions. The organism was widely distributed in 17 of the 21 cows, including three of the clinically normal animals, and was present in the mammary tissues of seven cows including two of the clinically normal animals. Three distinct histopathological patterns were observed in the affected intestines: infiltration of the lamina propria with giant cells, tuberculoid lesions, and lepromatous lesions; the lepromatous lesions were associated with extensive pathological changes.

Gastric bypass for morbidly obese patients with established cardiac disease.

BACKGROUND: Bariatric surgery has often been avoided in patients with known cardiac disease because of the risks inherent in this patient population. This study was done to evaluate both the risks and benefits of Roux-en-Y gastric bypass (RYGBP) in morbidly obese patients with established cardiac disease. METHODS: Data were analyzed to compare preoperative with postoperative co-morbid cardiac risk factors, peri-operative and postoperative complications, and change in body mass index (BMI) in 77 consecutive patients who had a preoperative diagnosis of cardiac disease and underwent RYGBP between March 1998 and January 31, 2006. Findings were compared to a concomitant control group without cardiac disease. RESULTS: The preoperative presence of cardiac disease was manifested primarily as coronary artery disease (CAD) (45 patients) or as congestive heart failure (CHF) (32 patients). Of the patients with CAD, 60% had diabetes, 91% had hypertension and 39% had hyperlipidemia. 58% had one or more prior invasive cardiac procedures. In the CHF group, 50% had diabetes, 71% had hypertension and 44% had hyperlipidemia. The average length of stay was 3.7 days for CAD patients and 3.3 days for CHF compared to 3.0 days for controls. All co-morbid conditions were improved, and no patient died from cardiac disease. However, one patient died as a complication of GI bleeding, one patient subsequently underwent revascularization and another underwent stenting. Other complications up to 5 years postoperatively were frequent but seldom life-threatening. CONCLUSION: RYGBP surgery in patients with existing cardiac disease appears to have acceptable risk and is effective in reducing the co-morbid conditions of diabetes, hypertension, hyperlipidemia, sleep apnea and arthritis, but longer term data are needed.

Comparison of risk factors for ductal carcinoma in situ and invasive breast cancer.

BACKGROUND: Ductal carcinoma in situ (DCIS) accounts for approximately 12% of newly diagnosed breast cancers. Knowledge of the factors that predict who will be diagnosed with DCIS is very limited. PURPOSE: The goal of this study was to determine risk factors associated with DCIS and whether these risk factors are similar to those associated with invasive breast cancer. METHODS: We conducted a cross-sectional study of 39,542 women aged 30 years and older who underwent a screening mammographic examination at the University of California San Francisco Mobile Mammography Screening Program from April 1985 through September 1995. A breast cancer risk profile and clinical history were obtained for each woman. Follow-up after abnormal mammography was performed to determine the presence of DCIS or invasive breast cancer by contacting the women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results cancer registry. Multivariate analysis was performed by the use of polytomous logistic regression. Two-sided statistical tests were used to determine P values. RESULTS: Among women aged 30-49 years, a family history of breast cancer (i.e., at least one affected first degree relative) was associated with an increased risk of DCIS (Odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.1-4.9) and body mass index greater than or equal to 25 kg/m2 was associated with a decreased risk of DCIS (OR = 0.4, 95% CI = 0.2 to 0.9). For each of these factors, there was a trend in the same direction bordering on statistical significance for invasive cancer (ORs = 1.7 [95% CI = 0.9-3.4] and 0.6 [95% CI = 0.3-1.1], respectively). Report of a palpable mass was associated with an increased risk of invasive cancer among women aged 30-49 years (OR = 12.0; 95% CI = 7.1-20.0); there was a trend in the same direction for DCIS (OR = 2.0; 95% CI = 0.8-5.1), but the association was much stronger for invasive disease than for DCIS (OR = 6.0; 95% CI = 2.1-18.0; P = .001). Among women aged 50 years and older, family history of breast cancer and nulliparity or age at birth of first child of 30 years or older increased the risk of both DCIS (ORs = 2.2 [95% CI = 1.0-4.2] and 2.3 [95% CI = 1.3-3.8], respectively) and invasive breast cancer (ORs = 1.5 [95% CI = 1.0-2.2] and 1.6 [95% CI = 1.2-2.1], respectively). Report of a palpable mass was not associated with an increased risk of DCIS among women 50 years and older, but it was strongly associated with an increased risk of invasive cancer (OR = 9.3; 95% CI = 6.0-14.0). Increasing age was associated with an increased risk of both DCIS and invasive cancer among women aged 30-49 years, but the association was stronger for invasive disease; a trend in the same direction bordering on statistical significance was observed for women aged 50 years and older. CONCLUSION: Risk factors for DCIS are similar to those for invasive breast cancer. IMPLICATIONS: More research is needed to better understand the malignant potential of DCIS lesions and factors that predict which lesions will become invasive breast cancer if left untreated.

Variability and accuracy in mammographic interpretation using the American College of Radiology Breast Imaging Reporting and Data System.

BACKGROUND: Several studies, which were limited by their small sample size and selection of difficult cases for review, have reported substantial variability among radiologists in interpretation of mammographic examinations. We have determined, in the largest study to date, intraobserver and interobserver agreement in interpreting screening mammography and accuracy of mammography by use of the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS). METHODS: The mammographic examinations were randomly selected on the basis of original mammographic interpretation and cancer outcome from 71,713 screening examinations performed by the Mobile Mammography Screening Program of the University of California, San Francisco, during the period from April 1985 through February 1995. The final sample included 786 abnormal examinations with no cancer detected, 267 abnormal examinations with cancer detected, and 1563 normal examinations. Films were read separately by two radiologists according to BI-RADS. Cancer status was determined by contacting women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results Program. RESULTS: There was moderate agreement between radiologists in reporting the presence of a finding when cancer was present (kappa = 0.54) and substantial agreement when cancer was not present (kappa = 0.62). Agreement was moderate in assigning one of the five assessment categories but was statistically significantly lower when cancer was present relative to when cancer was not present (kappa = 0.46 versus 0.56; two-sided P = .02). Agreement for reporting the presence of a finding and mammographic assessment was two-fold more likely for examinations with less dense breasts. Agreement was higher on repeat readings by the same radiologists than between radiologists. The sensitivity of mammography was lower with BI-RADS than with the original system for mammographic interpretation, but the positive predictive value of mammography was higher. CONCLUSION: Considerable variability in interpretation of mammographic examinations exists; this variability and the accuracy of mammography are neither improved nor diminished with use of BI-RADS.

Genotyping of Mycobacterium bovis isolates from badgers in four areas of the Republic of Ireland by restriction fragment length polymorphism analysis.

An analysis of the molecular epidemiology of Mycobacterium bovis in badgers was made in four selected areas of the Republic of Ireland in which an intensive badger removal programme was being carried out over a period of five years. Tissue samples from 2310 badgers were cultured. Restriction fragment length polymorphism (RFLP) analysis with IS6110, polymorphic GC-rich sequence (PGRS) and direct repeat sequence (DR) probes was applied to the isolates from 398 badgers, and 52 different rflp types were identified. Most of the isolates belonged to seven predominant types, and the other 45 types were represented by few isolates. An analysis suggests that some of these 45 types may have been introduced by the inward migration of badgers and others may have been the result of genetic changes to one of the prevalent types. The badgers were divided into groups on the basis of the sett at which they were captured, and RFLP typing was applied to isolates from two or more badgers from 85 groups. Multiple RFLP types were identified among isolates from 50 of these groups, suggesting that badgers probably moved frequently between group territories.

Temporal acquistion of enhanced fibrinolytic activity by syrian hamster embryo cells following treatment with benzo(a)pyrene.

Following treatment of Syrian hamster embryo cells with benzo(a)pyrene, the time required for the expression of enhanced fibrinolytic activity was examined. For this study, the fibrin-agarose overlay method was developed to distinguish the activity of normal and transformed colonies of hamster cells. Colonies possessing enhanced fibrinolytic activity were not observed one passage (2 weeks after treatment). Morphologically transformed colonies, which exhibited no enhanced fibrinolytic activity, were observed 8 days following treatment. In contrast to these two early changes, cells capable of growth in soft agar were observed much later (6 to 8 weeks after treatment). Untreated Syrian hamster embryo cells generally senesced and did not exhibit enhanced fibrinolytic activity. Approximately 1 of 10 untreated cultures escaped senescence and evolved as a continuous cell line; such cultures frequently exhibited enhanced fibrinolytic activity. These results suggest that the acquisition of enhanced fibrinolytic activity, while perhaps not a cause of neoplastic transformation, may reflect a loss of control of the normal function of the cellular genetic apparatus during the process of transformation.

Hormone therapy and in-hospital survival after myocardial infarction in postmenopausal women.

BACKGROUND: Although postmenopausal hormone therapy (HRT) commonly is used in hope of preventing coronary heart disease, the effect of HRT on case fatality of myocardial infarction has never been studied. We evaluated HRT as a predictor of survival after MI in postmenopausal women. METHODS AND RESULTS: The present study was performed with 114 724 women of age >/=55 years with confirmed myocardial infarction who presented between April 1998 and January 2000 to 1 of 1674 hospitals participating in the National Registry of Myocardial Infarction-3. Presenting characteristics, treatment, and clinical outcome data were obtained by chart review. At time of hospitalization, 7353 (6.4%) women reported current use of HRT, defined as use of estrogen, progestin, or estrogen/progestin for reasons other than contraception. Unadjusted mortality was 7.4% in users of HRT and 16.2% in nonusers (odds ratio 0.41, 95% confidence interval 0.36 to 0.43). After adjustments were made for prior medical history, clinical characteristics, treatments received in-hospital, and likelihood of receiving HRT, HRT remained associated with an improved rate of survival (odds ratio 0.65, 95% confidence interval 0.59 to 0.72). Significant association of HRT with decreased mortality after myocardial infarction was observed in all age strata. CONCLUSIONS: Postmenopausal HRT appears to be associated with reduced mortality after myocardial infarction. This finding could be caused by therapeutic effect of HRT, selection and adherence bias, or some combination of both.

Left ventricular pseudoaneurysm.

Left ventricular (LV) pseudoaneurysms form when cardiac rupture is contained by adherent pericardium or scar tissue. Although LV pseudoaneurysms are not common, the diagnosis is difficult and they are prone to rupture. We evaluated the clinical presentation, diagnostic accuracy of imaging modalities, results of therapy and prognosis of 290 patients with LV pseudoaneurysms. Most cases of LV pseudoaneurysm were related to myocardial infarction (particularly inferior wall myocardial infarction) and cardiac surgery. Congestive heart failure, chest pain and dyspnea were the most frequently reported symptoms, but >10% of patients were asymptomatic. Physical examination revealed a murmur in 70% of patients. Almost all patients had electrocardiographic abnormalities, but these were usually nonspecific ST segment changes; only 20% of patients had ST segment elevation. Although radiographic findings were also usually nonspecific, the appearance of a mass was present in more than one half of patients and may be an important clue to the correct diagnosis. Left ventricular angiography was the most definitive test and can be useful in planning surgery since concomitant coronary angiography can be performed. Regardless of treatment, patients with LV pseudoaneurysms had a high mortality rate, especially those who did not undergo surgery. Because the symptoms, signs, electrocardiographic abnormalities and radiographic findings seen in patients with LV pseudoaneurysms can be indistinguishable from those in patients with coronary disease alone, a high clinical index of suspicion is needed to avoid missing the diagnosis.

Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease.

OBJECTIVES: This study sought to determine the independent association of renal insufficiency with cardiovascular risk among women with known coronary heart disease (CHD). BACKGROUND: Although patients with end-stage renal disease and proteinuria are at high risk for cardiovascular events, little is known about the cardiovascular risk associated with moderate renal insufficiency. METHODS: The Heart and Estrogen/progestin Replacement Study (HERS) was a clinical trial among 2,763 women with coronary disease who were randomized to conjugated estrogen plus progestins or identical placebo and followed for a mean of 4.1 years. Women were categorized as having normal renal function (creatinine < 1.2 mg/dl; n = 2,012), mild renal insufficiency (1.2 mg/dl to 1.4 mg/dl; n = 567) and moderate renal insufficiency (>1.4 mg/dl; n = 182). We examined the independent association of renal function with incident cardiovascular events including CHD death, nonfatal myocardial infarction, hospitalization for unstable angina, stroke and transient ischemic attacks. RESULTS: Compared with women with normal renal function, those with mild and moderate renal insufficiency were older, more likely to be black, have a history of hypertension and diabetes and have higher serum levels of triglycerides and lipoprotein(a). After multivariate adjustment, both mild (relative hazards [RH] = 1.24; 95% confidence interval [CI]: 1.0 to 1.5) and moderate renal insufficiency (RH = 1.57; 95% CI: 1.2 to 2.1) were independently associated with increased risk for cardiovascular events compared with women with normal renal function. CONCLUSIONS: Renal insufficiency is an independent risk factor for cardiovascular events in postmenopausal women with known coronary artery disease. Renal function may add helpful information to CHD risk stratification.

Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women.

OBJECTIVES: We examined the association of hormone therapy (HRT) with hemorrhagic and ischemic stroke among postmenopausal women with acute myocardial infarction (AMI). BACKGROUND: Hemorrhagic and ischemic strokes are common complications of AMI, and women are at increased risk for hemorrhagic stroke after thrombolytic therapy. This risk may be related to female hormones. METHODS: Using data from the National Registry of Myocardial Infarction-3, we studied 114,724 women age 55 years or older admitted to the hospital for AMI, of whom 7,353 reported HRT use on admission. We determined rates of in-hospital hemorrhagic and ischemic stroke stratified by HRT use and estimated the independent association of HRT with each stroke type using multivariable logistic regression. RESULTS: The HRT users were younger than non-users, had fewer risk factors for stroke including diabetes and prior stroke, and received more pharmacologic and invasive therapy including cardiac catheterization. A total of 2,152 (1.9%) in-hospital strokes occurred, with 442 (0.4%) hemorrhagic, 1,017 (0.9%) ischemic and 693 (0.6%) unspecified. Among HRT users and non-users, the rates of hemorrhagic stroke (0.40% vs. 0.42%, p = 1.00) and ischemic stroke (0.80% vs. 0.96%, p = 0.11) were similar. Among 13,328 women who received thrombolytic therapy, the rate of hemorrhagic stroke was not significantly different for users and non-users (1.6% vs. 2.1%, p = 0.22). After adjustment for baseline and treatment differences, HRT was not associated with hemorrhagic (odds ratio [OR], 0.88; 95% confidence intervals [CI], 0.58 to 1.35) or ischemic stroke (OR, 0.89; CI, 0.66 to 1.18). CONCLUSIONS: Acute myocardial infarction is a high-risk setting for stroke among postmenopausal women, but HRT does not appear to modify that risk. Clinicians should not alter their approach to thrombolytic therapy based on HRT use.

Risk stratification of ambulatory patients suspected of Pneumocystis pneumonia.

To determine whether aspects of clinical history, physical examination, and laboratory studies improve the diagnostic accuracy of the chest roentgenogram in the diagnosis of Pneumocystis carinii pneumonia (PCP), we followed up 302 consecutive patients with respiratory symptoms and risk factors for human immunodeficiency virus. Of the 279 patients (92%) with follow-up information available, 31 (11%) were diagnosed with PCP. Only 68% of patients with PCP had typical chest roentgenograms. Regression analysis identified four independent predictors of PCP: diffuse or perihilar infiltrates, presence of mouth lesions, lactate dehydrogenase level more than 220 U/L, and erythrocyte sedimentation rate 50 mm/h or more. Using these four predictors, patients could be stratified into low-, intermediate-, and high-risk groups for PCP. We suggest that examination of the mouth, chest roentgenogram, lactate dehydrogenase level, and erythrocyte sedimentation rate be part of the evaluation of ambulatory patients with respiratory symptoms at risk for human immunodeficiency virus.

Is postmenopausal estrogen therapy associated with neuromuscular function or falling in elderly women? Study of Osteoporotic Fractures Research Group.

BACKGROUND: Muscle strength declines with advancing age; the causes of this are uncertain. In women, strength begins to decline around the time of menopause, suggesting that hormonal changes might influence strength. To determine the effect of postmenopausal estrogen use on muscle strength, neuromuscular function, and the risk of falling, we examined 9704 participants aged 65 years or more enrolled in the Study of Osteoporotic Fractures. METHODS: We measured hip abductor, triceps extensor, and hand-grip muscle strength, balance, gait speed, and self-reported functional disability. Falls during the first year of follow-up were determined from postcards that participants mailed every 4 months indicating whether they had fallen in the previous 4 months (> 99% complete follow-up). RESULTS: After adjusting for age, medications, medical history, and personal habits, current estrogen users did not differ in a clinically meaningful way from those who had never used estrogen on tests of hip abductor strength (mean difference, 0.15 kg; 95% confidence interval, -0.05 to 0.34 kg), triceps extensor strength (0.005 kg; -0.17 to 0.18 kg), or grip strength (0.30 kg; 0.00 to 0.59 kg). Gait speed, time to stand five times from a chair, balance, self-reported disability, and incidence of falls (odds ratio, 1.12; 95% confidence interval, 0.87 to 1.44) also did not differ between current users and never users. In addition, current users were similar to past users on all measures. CONCLUSION: We found no evidence that postmenopausal estrogen use has beneficial effects on muscle strength or neuromuscular function or that it reduces the risk of falling.

1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial.

An unexplained loss of muscle strength occurs with aging. Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [1,25-(OH2)D3] to persons with low serum concentrations can improve strength. To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [1,25-(OH2)D3], we conducted a randomized, controlled, double blinded trial in 98 men and women volunteers over 69 yr old. Treatment consisted of 0.25 micrograms 1,25-(OH)2D3, orally, twice per day or identical placebo for 6 months. Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer. There was no difference between the two groups at 1 week, 1 month, or 6 months of treatment in any of the measures of muscle strength. We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons. Further research is needed to determine the etiology of the decline in muscle strength associated with aging.

Integrated physical and transcript map of 5q31.3-qter.

We have constructed a physical and transcript map of 5q31.3-qter. The contig comprises 173 yeast artificial chromosomes (YACs) to which 159 sequence tagged sites (STSs), 47 expressed sequence tags (ESTs), and 32 genes were assigned. Previously published partial YAC contigs of the region have been refined and integrated. Given that the region contains 25 Mbp of DNA the average spacing of markers is approximately 100 kb.

Afferent innervation of outer and inner hair cells is normal in neonatally de-efferented cats.

It has been hypothesized that normal pruning of exuberant branching of afferent neurons in the developing cochlea is caused by the arrival of the olivocochlear efferent neurons and the resulting competition for synaptic sites on hair cells. This hypothesis was supported by a report that afferent innervation density on mature outer hair cells (OHCs) is elevated in animals deefferented at birth, before the olivocochlear system reaches the outer hair cell area (Pujol and Carlier [1982] Dev. Brain Res. 3:151-154). In the current study, this claim was evaluated quantitatively at the electron microscopic level in four cats that were de-efferented at birth and allowed to survive for 6-11 months. A semiserial section analysis of 156 OHCs from de-efferented and normal ears showed that, although de-efferentation essentially was complete in all four cases, the number and distribution of afferent terminals on OHCs was indistinguishable from normal, and the morphology of afferent synapses was normal in both the inner hair cell area and the OHC area. Thus, the postnatal presence of an efferent system is not required for the normal development of cochlear afferent innervation, and the synaptic competition hypothesis is not supported.