Use-effectiveness of oral and intrauterine contraception

The use-effectiveness of oral contraception and intrauterine contraception was studied in 3 family planning centers in the United States: Grady Memorial Hospital in Atlanta, Georgia; State University of New York, Downstate Medical Center, in Brooklyn; and the Planned Parenthood Center in Buffalo, New York. In each locality 1000 women were selected for the study. 2900 women accepted intrauterine devices (IUDs) or oral contraceptives (OCs) as their first method of contraception. In Brooklyn 3 out of 4 women chose OCs; in Atlanta and Buffalo roughly equal numbers selected each method. The mean age of admission was 25.7 years in Buffalo, 24 years in Brooklyn, and 23.8 years in Atlanta. IUD acceptors were older than those choosing OCs. The difference was greatest in Buffalo (3.3 years) and smallest in Atlanta (.8 years). A special one-page, self-coding questionnaire was designed to collect the information required. In all 3 clinics contraceptive termination rates were markedly lower for the IUDs than for OCs. At 1 year of use for the first method only about one-fourth the women who chose the IUD had discontinued its use. Women on OCs terminated at rates from 10-20% higher. Termination rates for all contraception, both first-method and substitution, were lower than for first-method alone and lower for IUDs than for OCs. The highest continuation rate for all contraception was 92.5% for IUD users in Brooklyn while OC users in Atlanta were at the lowest level at 60.5%. Pregnancy rate studies demonstrated higher failure rates with OCs than with IUDs in all 3 clinics. Statistics by age showed that termination rates for both IUD and OC users declined with age. Women who selected IUDs as their method of contraception were more persistent users of contraception. Even after discontinuing IUD use, they were more likely to adopt another contraceptive method.     

Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing

Human mesenchymal stem cells (hMSC) are adult stem cells with multipotent capacities. The ability of mesenchymal stem cells to differentiate into many cell types, as well as their high ex vivo expansion potential, makes these cells an attractive therapeutic tool for cell transplantation and tissue engineering. hMSC are thought to contribute to tissue regeneration, but the signals governing their mobilization, diapedesis into the bloodstream, and migration into the target tissue are largely unknown. Here we report that hepatocyte growth factor (HGF) and the cognate receptor HGFR/c-met are expressed in hMSC, on both the RNA and the protein levels. The expression of HGF was downregulated by transforming growth factor beta. HGF stimulated chemotactic migration but not proliferation of hMSC. Therefore the HGF/c-met signaling system may have an important role in hMSC recruitment sites of tissue regeneration. The controlled regulation of HGF/c-met expression may be beneficial in tissue engineering and cell therapy employing hMSC.     

Synthesis, radiofluorination, and in vitro evaluation of pyrazolo[1,5-a]pyridine-based dopamine D4 receptor ligands: discovery of an inverse agonist radioligand for PET

A series of fluoro-substituted analogs structurally derived from the aminomethyl-substituted pyrazolo[1,5- a]pyridine lead compounds 9 (FAUC 113) and 10 (FAUC 213) were synthesized and evaluated as high-affinity D 4 receptor (D 4R) ligands ( 3a- 3h, K i = 1.3-28 nM). The para-fluoroethoxy-substituted derivatives 3f and 3h revealed an outstanding D 4 subtype selectivity of more than 3 orders of magnitude over both congeners D 2 and D 3 combined with inverse agonism at D 4R. The corresponding (18)F-labeled radioligands revealed high serum stability in vitro and log P values of 2-3. In vitro rat brain autoradiography showed specific binding of [ (18)F]3h in distinct brain regions, including the gyrus dentate of the hippocampus, that were inhibited by both eticlopride (65-80%) and the selective D 4R antagonist 10 (78-93%). The observed binding pattern was mainly consistent with the known D 4R distribution in the rat brain. Thus, [(18)F]3h (FAUC F41) represents a potential radioligand for studying the D 4R in vivo by positron emission tomography (PET).     

1,25-dihydroxyvitamin D resistance, rickets, and alopecia: analysis of receptors and bioresponse in cultured fibroblasts from patients and parents

To investigate further the cellular defects of vitamin D-dependent rickets type II with alopecia, we studied 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors and the response to 1,25-(OH)2D3 in cultured skin fibroblasts from rachitic patients. Our studies included cells from four affected patients from three kindreds and their parents and cells from five normal subjects. We measured total 1,25-(OH)2D3 receptor binding in cell extracts and the capacity of 1,25-(OH)2D3 to induce the enzyme 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) as a marker of functional response. In normal fibroblasts, the 1,25-(OH)2D3 maximal binding capacity was 52 +/- 5 fmol/100 micrograms DNA (mean +/- SE), and the apparent dissociation constant (Kd) was 0.05 +/- 0.01 nM. The maximal induced 24-hydroxylase activity after 1,25-(OH)2D3 treatment was 11.5 +/- 1 fmol/10(6) cells X 30 min, and the dose of 1,25-(OH)2D3 that achieved half-maximal induction was 2.3 +/- 0.3 nM. Fibroblasts from all four rachitic patients had the same defect: no measurable 1,25-(OH)2D3 receptor binding and no detectable response above basal activity even after high doses of 1,25-(OH)2D3. Cells from all parents except one had normal 1,25-(OH)2D3 binding characteristics and normal 24-hydroxylase bioresponse to 1,25-(OH)2D3. One parent despite a normal phenotype had only half the normal level of binding sites and only half the normal bioresponse. In summary, the cultured fibroblasts from four affected children representing three different kindreds with 1,25-(OH)2D3 resistance failed to exhibit detectable 1,25-(OH)2D3 receptors. We postulate that this biochemical defect produced both the inability to respond to 1,25-(OH)2D3 in vitro and the 1,25-(OH)2D3 resistance in vivo. The obligate heterozygotic parents were normal, except for one who had both half the normal number of receptors and half the normal response to 1,25-(OH)2D3. The data confirm the critical role of the receptor in 1,25-(OH)2D3 action and the close coupling of receptor content and functional responsiveness.     

Deep vein thrombosis/pulmonary embolism: a survey of self-reported prevention practices among hospitals

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major causes of preventable complications for hospitalized patients worldwide. The National Quality Forum (NQF) recommends that all patients be assessed for DVT/PE risk upon admission, periodically thereafter, and receive evidence-based pharmacologic prophylaxis. Objectives of this study were to capture information about hospital practices related to detection, prevention, and treatment of DVT/PE and to explore relationships between hospital characteristics and an applicable patient safety indicator (PSI) #12 postoperative DVT/PE. Two study phases were conducted in the south-central region of the United States. First, a survey tailored to gather information about the study objectives from subject matter experts was administered, and then, using the subject matter expert results, an online survey of performance improvement professionals was deployed. Using this 5-point Likert scale online survey, respondents at each hospital reflected their DVT/PE prevention practices approach and status. Results provided insight for trends in hospital-based DVT/PE prevention practice, associated hospital characteristics, relationship among domains of prevention practice, and how electronic DVT/PE order sets related to DVT/PE outcomes. Relationship of all these characteristics to hospital overall PSI #12 postoperative DVT/PE rates were compared. Future study and survey development recommendations were discussed.     

Clonal dissemination of Salmonella enterica serovar Infantis in Germany

Salmonella enterica serovar Infantis (Salmonella Infantis) is consistently isolated from broiler chickens, pigs, and humans worldwide. This study investigated 93 epidemiologically unrelated Salmonella Infantis strains isolated in Germany between 2005 and 2008 in respect to their transmission along the food chain. Various phenotypic and genotypic methods were applied, and the pathogenicity and resistance gene repertoire was determined. Phenotypically, 66% of the strains were susceptible to all 17 antimicrobials tested, while the others were almost all multidrug-resistant (two or more antimicrobial resistances), with different resistance profiles and preferentially isolated from broiler chickens. A number of phage types (PTs) were shared by strains from pigs, broiler chickens, and humans (predominated by PT 29). One, PT 1, was only detected in strains from pigs/pork and humans. Pulsed-field gel electrophoresis (PFGE) subdivided strains in seven different clusters, named A-G, consisting of 35 various XbaI profiles with coefficient of similarity values of 0.73-0.97. The majority of XbaI profiles were assigned to clusters A and C, and two predominant XbaI profiles were common in strains isolated from all sources investigated. Multi-locus sequence typing (MLST) analysis of selected strains representing the seven PFGE clusters revealed that they all belonged to ST32. The pathogenicity gene repertoire of 37 representative Salmonella Infantis strains analyzed by microarray was also identical. The resistance gene repertoire correlated perfectly with the phenotypic antimicrobial resistance profiles, and multidrug-resistant strains were associated with class 1 integrons. Overall, this study showed that two major closely related genotypes of Salmonella Infantis can transmit in Germany to humans through contaminated broiler meat or pork, and consequently presents a hazard for human health.     

External validation of the diagnostic value of perihematomal edema characteristics in neoplastic and non-neoplastic intracerebral hemorrhage

Background and purpose

Neoplastic intracerebral hemorrhage (ICH) may be incorrectly identified as non-neoplastic ICH on imaging. Relative perihematomal edema (relPHE) on computed tomography (CT) has been proposed as a marker to discriminate neoplastic from non-neoplastic ICH but has not been externally validated. The purpose of this study was to evaluate the discriminatory power of relPHE in an independent cohort.

Methods

A total of 291 patients with acute ICH on CT and follow-up magnetic resonance imaging (MRI) were included in this single-center retrospective study. ICH subjects were dichotomized into non-neoplastic or neoplastic ICH based on the diagnosis on the follow-up MRI. ICH and PHE volumes and density values were derived from semi-manually segmented CT scans. Calculated PHE characteristics for discriminating neoplastic ICH were evaluated using receiver-operating characteristic (ROC) curves. ROC curve-associated cut-offs were calculated and compared between the initial and the validation cohort.

Results

A total of 116 patients (39.86%) with neoplastic ICH and 175 (60.14%) with non-neoplastic ICH were included. Median PHE volumes, relPHE, and relPHE adjusted for hematoma density were significantly higher in subjects with neoplastic ICH (all p values <0.001). ROC curves for relPHE had an area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.66–0.78) and an AUC of 0.81 (95% CI 0.76–0.87) for adjusted relPHE. The cut-offs were identical in the two cohorts, with >0.70 for relPHE and >0.01 for adjusted relPHE.

Conclusions

Relative perihematomal edema and adjusted relPHE accurately discriminated neoplastic from non-neoplastic ICH on CT imaging in an external patient cohort. These results confirmed the findings of the initial study and may improve clinical decision making.