Wegener's granulomatosis in childhood

The authors reviewed the medical histories and radiological examinations of five pediatric patients with a histologic diagnosis of Wegener's granulomatosis (WG) seen over a six year period in whom a total of 22 thoracic CT scans were performed. Involvement of both the upper and lower respiratory tracts was seen in all patients at presentation. One patient had subglottic stenosis necessitating tracheotomy. Pulmonary hemorrhage occurred in three patients at initial diagnosis. Classic cavitary lung nodules were seen in two patients — one at initial presentation, the other at relapse. The plain radiographic lower respiratory tract manifestations of pediatric WG were protean both at initial presentation and during follow up. Similarly, disease expression was highly variable on thoracic CT examinations but, overall, multifocal parenchymal infiltrates with or without small peripheral nodules were the commonest thoracic CT manifestations. As a consequence of cytotoxic and corticosteroid therapy the long-term prognosis of WG has improved considerably in recent years. Knowledge of the varied patterns of the primary disease and potential for iatrogenic complications are necessary for successful radiologic assessment of pediatric patients with WG.     

Chronic recurrent multifocal osteomyelitis: a noninfectious inflammatory process

We report seven patients with chronic recurrent multifocal osteomyelitis, an uncommon childhood disease of unknown etiology. These patients presented with insidious onset of bone pain at one or more sites associated with erythema, swelling and tenderness. Scintigraphy and radiography were consistent with osteomyelitis at multiple sites. Bone biopsies confirmed osteomyelitis but no organisms were consistently isolated. During a 1- to 3-year follow-up, most patients developed new symptomatic lesions. The disease was unaffected by antimicrobial therapy. Two of our patients had psoriasis and all were rheumatoid factor-, antinuclear factor- and HLA-B27-negative. We speculate that chronic recurrent osteomyelitis is a noninfectious inflammatory condition, a seronegative spondyloarthropathy. Chronic recurrent osteomyelitis is a clinical entity that should be recognized so that invasive diagnostic procedures and antimicrobial therapy are appropriately used. The patient may be reassured that this is not a malignant condition although there may be exacerbations over many years.     

Spinal cord dysfunction with quadriplegia complicating pneumococcal meningitis

A case of pneumococcal meningitis complicated by brain-stem herniation and flaccid quadriplegia is described, from which the patient, an 11 year old boy, made a partial recovery. The patient had suffered a head injury with skull fracture some years previously; this was his third episode of meningitis. The aetiology of the quadriplegia has not been fully established, but is presumed to be of vascular nature at spinal cord level, associated with an acute hypotensive episode. Preventative aspects of recurrent bacterial meningitis and brain-stem herniation following lumbar puncture are stressed.     

False positivity of Legionella serology in patients with cystic fibrosis

Respiratory deterioration accounts for the morbidity and mortality observed in patients with cystic fibrosis. The role of Legionella in this deterioration was determined in a 2-year prospective study of 49 patients with cystic fibrosis and 19 sibling controls. Sera were obtained from participants on enrollment and at quarterly intervals. Legionella antibodies were measured in parallel using an indirect fluorescent assay. No seroconversions were observed. Eleven of 49 patients with cystic fibrosis (22%) were seropositive compared to none of 19 siblings (P less than 0.05). Six of the 11 patients demonstrated high titers (greater than or equal to 1:512) that persisted throughout the study. Absorption with pools of various Pseudomonas species reduced the antibody titers such that only 3 remained positive after absorption. Legionella was not found to be an important cause of clinical deterioration during this study. The results of the absorption studies suggest that high titers to Legionella in this population are due to cross-reacting antibodies.     

Physical activity, body mass index, and ovulatory disorder infertility

Few studies have examined whether activity and adiposity levels typical of American women affect their risk of ovulatory disorder infertility, and none has examined moderate and vigorous intensity exercise separately. We investigated these associations in the Nurses' Health Study II, comparing prospectively collected data on adiposity and activity for 830 cases of incident ovulatory infertility and 26,125 pregnancies. We observed a U-shaped association between body mass index (BMI) and relative risk of ovulatory infertility, with increased risk for BMI below 20.0 or above 24.0 kg/m2. On the basis of the BMI distribution of U.S. women, these findings suggest that 12% (95% confidence interval = 7-20%) of ovulatory infertility in the U.S. may be attributable to underweight (BMI <20.0) and 25% (95% CI = 20-31%) to overweight (BMI > or = 25.0). An increase in vigorous activity (but not moderate activity) was associated with reduced relative risk of ovulatory infertility. Each hour per week of vigorous activity was associated with a 7% (95% CI = 4-10%) lower relative risk of ovulatory infertility. After adjustment for BMI, a 5% (95% CI = 2-8%) reduction in relative risk per hour of weekly activity remained. These data suggest that, among American women, more ovulatory infertility is attributable to overweight and a sedentary lifestyle than to underweight and overexertion.     

A sensitive,versatile microfluidic assay for bacterial chemotaxis

We have developed a microfluidic assay for bacterial chemotaxis in which a gradient of chemoeffectors is established inside a microchannel via diffusion between parallel streams of liquid in laminar flow. The random motility and chemotactic responses to L-aspartate, L-serine, L-leucine, and Ni(2+) of WT and chemotactic-mutant strains of Escherichia coli were measured. Migration of the cells was quantified by counting the cells accumulating in each of 22 outlet ports. The sensitivity of the assay is attested to by the significant response of WT cells to 3.2 nM L-aspartate, a concentration three orders of magnitude lower than the detection limit in the standard capillary assay. The response to repellents was as robust and easily recorded as the attractant response. A surprising discovery was that L-leucine is sensed by Tar as an attractant at low concentrations and by Tsr as a repellent at higher concentrations. This assay offers superior performance and convenience relative to the existing assays to measure bacterial tactic responses, and it is flexible enough to be used in a wide range of different applications.     

Physical activity and the prevention of cardiovascular disease

This article summarizes recent evidence on the role of physical activity in the prevention of overt and subclinical vascular disease. Epidemiologic data suggest that as little as 30 minutes per day of moderate-intensity physical activity, including brisk walking, reduces the incidence of clinical cardiovascular events in men and women. Regular exercise may also retard the progression of asymptomatic coronary and peripheral arteriosclerosis. Cardioprotective mechanisms of physical activity include reducing adiposity, blood pressure, diabetes incidence, dyslipidemia, and inflammation, and enhancing insulin sensitivity, glycemic control, fibrinolysis, and endothelial function. In a sedentary society such as the United States, public health initiatives that promote moderate increases in activity represent the optimal balance between efficacy and feasibility to achieve desired improvements in cardiovascular health.     

Glycemic index,glycemic load,and risk of type 2 diabetes

The possibility that high, long-term intake of carbohydrates that are rapidly absorbed as glucose may increase the risk of type 2 diabetes has been a long-standing controversy. Two main mechanisms have been hypothesized, one mediated by increases in insulin resistance and the other by pancreatic exhaustion as a result of the increased demand for insulin. During the past decade, several lines of evidence have collectively provided strong support for a relation between such diets and diabetes incidence. In animals and in short-term human studies, a high intake of carbohydrates with a high glycemic index (a relative measure of the incremental glucose response per gram of carbohydrate) produced greater insulin resistance than did the intake of low-glycemic-index carbohydrates. In large prospective epidemiologic studies, both the glycemic index and the glycemic load (the glycemic index multiplied by the amount of carbohydrate) of the overall diet have been associated with a greater risk of type 2 diabetes in both men and women. Conversely, a higher intake of cereal fiber has been consistently associated with lower diabetes risk. In diabetic patients, evidence from medium-term studies suggests that replacing high-glycemic-index carbohydrates with a low-glycemic-index forms will improve glycemic control and, among persons treated with insulin, will reduce hypoglycemic episodes. These dietary changes, which can be made by replacing products made with white flour and potatoes with whole-grain, minimally refined cereal products, have also been associated with a lower risk of cardiovascular disease and can be an appropriate component of recommendations for an overall healthy diet.     

American Indians/Alaska natives and dementia

Although the Native elder population continues to expand, very little is known about how dementia of any kind affects this group. This article reviews what and is known about dementia among American Indians/Alaska Natives. Specifically, it examines prevalence, assessment and diagnosis, cultural understandings, family caregiving, formal services, and abuse/neglect. It concludes that much work remains to be done on dementia in the Native population, and suggests directions for future research.     

Inflammatory biomarkers,hormone replacement therapy,and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study

Context  Postmenopausal hormone replacement therapy (HRT) has been shown to elevate C-reactive protein (CRP) levels. Several inflammatory biomarkers, including CRP, are associated with increased cardiovascular risk. However, whether the effect of HRT on CRP represents a clinical hazard is unknown. Objectives  To assess the association between baseline levels of CRP and interleukin 6 (IL-6) and incident coronary heart disease (CHD) and to examine the relationship between baseline use of HRT, CRP, and IL-6 levels as they relate to subsequent vascular risk. Design, Setting, and Participants  Prospective, nested case-control study of postmenopausal women, forming part of the Women's Health Initiative, a large, nationwide, observational study. Among 75 343 women with no history of cardiovascular disease or cancer, 304 women who developed incident CHD were defined as cases and matched by age, smoking status, ethnicity, and follow-up time with 304 study participants who remained event free during a median observation period of 2.9 years. Main Outcome Measure  Incidence of first myocardial infarction or death from CHD. Results  Median baseline levels of CRP (0.33 vs 0.25 mg/dL; interquartile range [IQR], 0.14-0.71 vs 0.10-0.47; P<.001) and IL-6 (1.81 vs 1.47 pg/mL; IQR, 1.30-2.75 vs 1.05-2.15; P<.001) were significantly higher among cases compared with controls. In matched analyses, the odds ratio (OR) for incident CHD in the highest vs lowest quartile was 2.3 for CRP (95% confidence interval [CI], 1.4-3.7; P for trend = .002) and 3.3 for IL-6 (95% CI, 2.0-5.5; P for trend <.001). After additional adjustment for lipid and nonlipid risk factors, both inflammatory markers were significantly associated with a 2-fold increase in odds for CHD events. As anticipated, current use of HRT was associated with significantly elevated median CRP levels. However, there was no association between HRT and IL-6. In analyses comparing individuals with comparable baseline levels of either CRP or IL-6, those taking or not taking HRT had similar CHD ORs. In analyses stratified by HRT, we observed a positively graded relationship between plasma CRP levels and the OR for CHD among both users and nonusers of HRT across the full spectrum of baseline CRP. Conclusions  These prospective findings indicate that CRP and IL-6 independently predict vascular events among apparently healthy postmenopausal women and that HRT increases CRP. However, use or nonuse of HRT had less importance as a predictor of cardiovascular risk than did baseline levels of either CRP or IL-6.