Neisseria subflava endocarditis. Case report and review of the literature

Neisseria subflava is a rare cause of bacterial endocarditis. Only seven cases have been identified in the world literature if strict criteria as to organism classification and of endocarditis are applied to individual case reports. The first reported case in an intravenous drug user is described. In addition, findings on serial two-dimensional and M-mode echocardiography performed during and after the treatment period are presented. This patient's recovery with anti-microbial therapy alone despite evidence of aortic and significant mitral valve involvement is in accord with results of other antibiotic-treated cases.     

2002 update to the ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: implications for emergency department practice

The publication of comprehensive evidence-based guidelines for the management of non-ST-segment elevation acute coronary syndrome by the American College of Cardiology and the American Heart Association in September 2000 marked a sentinel event in the evolution of managing this challenging patient population. Many of the recommendations included in the guidelines have relevance to the emergency department care of patients with non-ST-segment elevation acute coronary syndrome and were summarized in Annals of Emergency Medicine in September 2001. New clinical data in this area continue to accumulate at a remarkably rapid rate, prompting the American College of Cardiology and the American Heart Association to publish an update of the 2000 guidelines in October 2002. Several of the modified and new recommendations again potentially affect ED management. These are presented and discussed here.     

Body fat content and 25-hydroxyvitamin D levels in healthy women

Obesity is associated with alterations in the vitamin D endocrine system. Lower levels of serum 25-hydroxyvitamin D (25-OHD) in morbidly obese individuals may be secondary to an alteration in tissue distribution resulting from an increase in adipose mass. Therefore, morbidly obese individuals are expected to need higher doses of vitamin D supplementation than the general population. However, it is still unknown whether adiposity (or percentage body fat) should be taken into consideration while assessing vitamin D requirements in the general population. To study the relationship between 25-OHD levels and percentage body fat content in healthy women, we studied 410 healthy women between 20 and 80 yr of age with body mass index ranging from 17 to 30 kg/m2. We analyzed the correlation between serum 25-OHD level and percentage body fat measured by dual energy x-ray absorptiometry. We also analyzed the influence of season, dietary vitamin D intake, age, and race on this relationship. The levels of serum 25-OHD inversely correlated with percentage body fat. The correlation was -0.13 (P = 0.013) after adjusting for race, age, season, and dietary vitamin D intake. In a multiple stepwise regression, race and season were found to have a major influence on serum 25-OHD (cumulative R2 = 0.34), and percentage body fat, although modest (additional R2 = 0.02), also had an independent statistically significant influence on serum 25-OHD levels. We conclude, percentage body fat content is inversely related to the serum 25-OHD levels in healthy women.     

Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors

Genomic DNA copy number alterations are key genetic events in the development and progression of human cancers. Here we report a genome-wide microarray comparative genomic hybridization (array CGH) analysis of DNA copy number variation in a series of primary human breast tumors. We have profiled DNA copy number alteration across 6,691 mapped human genes, in 44 predominantly advanced, primary breast tumors and 10 breast cancer cell lines. While the overall patterns of DNA amplification and deletion corroborate previous cytogenetic studies, the high-resolution (gene-by-gene) mapping of amplicon boundaries and the quantitative analysis of amplicon shape provide significant improvement in the localization of candidate oncogenes. Parallel microarray measurements of mRNA levels reveal the remarkable degree to which variation in gene copy number contributes to variation in gene expression in tumor cells. Specifically, we find that 62% of highly amplified genes show moderately or highly elevated expression, that DNA copy number influences gene expression across a wide range of DNA copy number alterations (deletion, low-, mid- and high-level amplification), that on average, a 2-fold change in DNA copy number is associated with a corresponding 1.5-fold change in mRNA levels, and that overall, at least 12% of all the variation in gene expression among the breast tumors is directly attributable to underlying variation in gene copy number. These findings provide evidence that widespread DNA copy number alteration can lead directly to global deregulation of gene expression, which may contribute to the development or progression of cancer.     

Diagnosis of intra-abdominal and mediastinal sarcoidosis with EUS-guided FNA

BACKGROUND: In the presence of a compatible clinical picture, the diagnosis of sarcoidosis requires pathologic confirmation of noncaseating epithelioid granuloma in affected tissues. The standard procedure of choice for most patients is a bronchoscopy with transbronchial biopsy (TBB), which has a diagnostic yield of 40% to 90%. The lowest yield with TBB is in cases that present with predominant mediastinal or intra-abdominal lymphadenopathy (LN) and minimal parenchymal lung involvement. OBJECTIVE: To study the diagnostic yield of EUS-guided FNA in diagnosing sarcoidosis with predominant LN or masses. DESIGN: Retrospective chart review. SETTING: Teaching university hospital. PATIENTS: Analysis of 21 consecutive patients with sarcoidosis and predominant mediastinal and/or intra-abdominal LN or masses who underwent EUS-guided FNA. RESULTS: EUS-guided FNA diagnosed sarcoidosis in 18 of 21 patients (86%). In 3 patients, EUS-guided FNA was either not diagnostic or inconclusive, and patients underwent mediastinoscopy with lymphadenectomy, which established the diagnosis of sarcoidosis. Seven of the 21 patients (33%) had intra-abdominal LN and/or masses, and EUS-guided FNA of the intra-abdominal pathology was diagnostic of sarcoidosis in 4 of the 7 patients (57%). Four of the 21 patients (19%) had a history of malignancy, and use of EUS-guided FNA helped in ruling out the recurrence of malignancy in 3 of the 4 patients (75%). LIMITATIONS: Mycobacterial and fungal culture was not obtained in all patients. CONCLUSIONS: EUS-guided FNA offers a practical, minimally invasive technique for the diagnosis of sarcoidosis in patients who present with predominant mediastinal and/or intra-abdominal LN or masses.     

Mechanism of inositol monophosphatase, the putative target of lithium therapy.

myo-Inositol monophosphatase (myo-inositol-1-phosphate phosphohydrolase, EC 3.1.3.25) is an attractive target for mechanistic investigation due to its critical role in the phosphatidylinositol signaling pathway and the possible relevance of its inhibition by Li+ to manic depression therapy. The x-ray crystallographic structure of human inositol monophosphatase in the presence of the inhibitory metal Gd3+ showed only one metal bound per active site, whereas in the presence of Mn2+, three ions were present with one being displaced upon phosphate binding. We report here modeling, kinetic, and mutagenesis studies on the enzyme, which reveal the requirement for two metal ions in the catalytic mechanism. Activity titration curves with Zn2+ or Mn2+ in the presence or absence of Mg2+ are consistent with a two-metal mechanism. Modeling studies based on the various x-ray crystallographic structures (including those with Gd3+ and substrate bound) further support a two-metal mechanism and define the positions of the two metal ions relative to substrate. While the first metal ion may activate water for nucleophilic attack, a second metal ion, coordinated by three aspartate residues, appears to act as a Lewis acid, stabilizing the leaving inositol oxyanion. In this model, the 6-OH group of substrate acts as a ligand for this second metal ion, consistent with the reduced catalytic activity observed with substrate analogues lacking the 6-OH. Evidence from Tb3+ fluorescence quenching and the two-metal kinetic titration curves suggests that Li+ binds at the site of this second metal ion.     

Onset of ovulation after menarche in girls: a longitudinal study

INTRODUCTION: Hypothalamic-pituitary axis maturity has been believed to be the rate-limiting step in the development of ovulatory menstrual cycles. We hypothesized that, given current nutritional conditions, hypothalamic-pituitary axis maturation would be relatively rapid in menarcheal girls. METHODS: Daily urine and menstrual records were collected for 2 yr each from 10 girls aged 11-13 yr at study entry. Urinary excretion of LH, FSH, estradiol (E1c), and progesterone (Pdg) metabolites was measured using established ELISAs. An objective algorithm detected rises of LH, FSH, E1c, and Pdg consistent with follicular maturation and/or ovulation. RESULTS: Nine of 10 girls enrolled into the study experienced the onset of menarche prior to or during the 2-yr collection period. LH and FSH surges, as well as small amplitude Pdg increments, were observed prior to menarche. Regular, ovulatory-appearing cycles with LH surges and gradually increasing and more sustained Pdg rises were observed over time after menarche, although duration of Pdg elevations remained shorter than in adult women (8.9 +/- 1.0 vs. 12.1 +/- 0.8 d, P = 0.043). E1c levels leading to LH/FSH surges were lower in perimenarcheal girls than adult controls, and bleeding episodes did not uniformly correlate with hormone patterns. Progressive increases in FSH and Pdg, but not LH or E1c, were observed in association with menarche. CONCLUSION: Mature hormone patterns are established within several months of and even prior to menarche in normal-weight perimenarcheal girls. Factors determining menstrual bleeding in perimenarcheal girls may not be solely dependent on reproductive hormones or the neuroendocrine axis.     

Validation of data from electronic data warehouse in diabetic ketoacidosis: Caution is needed

Aims

This study validated enterprise data warehouse (EDW) data for a cohort of hospitalized patients with a primary diagnosis of diabetic ketoacidosis (DKA).