Oral levofloxacin 500 mg once daily in the treatment of chronic bacterial prostatitis.

The aim of this study was to confirm further the efficacy and safety of levofloxacin in patients with chronic bacterial prostatitis (CBP) in Europe. Men with a history of CBP were enrolled in a prospective, multinational (eight countries), open-label study to receive levofloxacin 500 mg once daily per os (p.o.) for 28 days. Patients were followed for 6 months. A total of 117 patients were treated. Gram-negative bacteria were identified in 57/106 patients (mainly Escherichia coli (n=37)) and Gram-positive bacteria in 60/106 patients (mainly Enterococcus faecalis (n=18) and Staphylococcus epidermidis (n=14)). Among the intention-to-treat population (n=116), the clinical success rate (cured and improved patients) was 92% (95% confidence interval (CI) 84.8-96.5%), 77.4% (95% CI 68.2-84.9%), 66.0% (95% CI 56.2-75.0%) and 61.9% (95% CI 51.9-71.2%) at 5-12 days, 1 month, 3 months and 6 months post treatment. The microbiological eradication rate according to evaluation scheme II was 82/98 (83.7%, 95% CI 74.8-90.4%) at 1 month and the continued eradication rate was 52/57 (91.2%, 95% CI 80.7-97.1%) at 6 months post treatment. Comparison of four classification schemes showed similar results. Thus, the present investigation is suitably comparable in methods and results to previous studies. Levofloxacin was well tolerated. Four patients (3.4%) discontinued therapy due to adverse events and 15 patients (12.8%) experienced at least one adverse event. Levofloxacin 500 mg p.o. once daily for 28 days is clinically and microbiologically effective in the treatment of CBP caused by susceptible pathogens and is well tolerated.

Evaluation and validation of a new risk score (CLEOPATRA score) to predict the probability of premature delivery for patients with threatened preterm labor.

OBJECTIVE: To develop a clinically useful tool to predict the probability of preterm delivery in patients with threatened preterm labor. METHODS: One hundred and seventy patients with preterm labor between 24 and 34 weeks of gestation were included. Preterm delivery < 37 weeks of gestation was the main endpoint of the study. The data were randomized and split into an evaluation set (n = 85) and a validation set (n = 85). The evaluation set was subjected to stepwise backward logistic regression analysis to quantify the relative impact of four potential risk factors, including individual patient factors, results of a rapid fetal fibronectin assay, and sonographic measurement of cervical length. Using the constant of the logistic regression analysis and the beta-coefficients for the identified risk factors the individual probability of preterm delivery for each woman of the validation dataset was calculated. The area under a receiver-operating characteristics curve (AUC) was used to evaluate the discriminating power of the score. RESULTS: The overall rate of preterm delivery was 27.1%. The logistic regression analysis was performed for the potential predictors of spontaneous preterm delivery, identified by univariate analysis. These were positive fetal fibronectin, cervical length, previous preterm delivery and maternal age. Two risk factors were independent predictors of preterm delivery and were included in the CLEOPATRA I (clinical evaluation of preterm delivery and theoretical risk assessment) score: cervical length measurement and previous preterm delivery were associated with a higher risk of preterm delivery (odds ratio, 7.65 and 6.74, respectively). Since fetal fibronectin assay is not available at all institutions worldwide, it was excluded from the initial model. In the CLEOPATRA II model the risk factors fetal fibronectin and previous preterm delivery were associated with higher risk of preterm delivery, with odds ratios of 17.9 and 4.56, respectively. The discrimination power (AUC) obtained from the models were: CLEOPATRA I, 0.69 (95% CI, 0.56-0.82); CLEOPATRA II, 0.81 (95% CI, 0.69-0.93). CONCLUSION: In symptomatic women the risk for preterm delivery can be predicted best with the CLEOPATRA II score based on fetal fibronectin and previous preterm delivery.

Meningitis due to multiple-resistant penicillin- and cefotaxime-intermediate Streptococcus pneumoniae in a German child after bone marrow transplantation.

The incidence of infection with penicillin-non-susceptible Streptococcus pneumoniae is increasing rapidly worldwide. Spain and France are highly affected, whereas the level of penicillin resistance in Germany, Italy, The Netherlands and Scandinavia is low. We report a lethal episode of meningitis due to penicillin- and cefotaxime-intermediate S. pneumoniae in a 7-year-old, allogene bone marrow transplanted German boy, 5 weeks after a holiday in Spain. Three days prior to the infection the patient showed good performance status. He was in complete remission without signs of graft-versus-host disease (GVHD). He died on day 341 post bone marrow transplant (BMT), 2 days after the onset of meningitis. Penicillin-non-susceptible S. pneumoniae should be regarded as a potential infectious agent even in countries with a low prevalence of resistance.

Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)thieno[2,3-c]pyridines with fine-tuning at C-2 carbamides.

The elevated expression of cell adhesion molecules (CAMs) on the lumenal surface of vascular endothelial cells is a critical early event in the complex inflammatory process. The adhesive interactions of these CAMs that include E-selectin, ICAM-1, and VCAM-1 with their counter-receptors on leukocytes, such as integrins of the alpha(L)beta(2) family, result in migration of the leukocytes to the site of inflammation and cause tissue injury. Pharmaceutical agents that could suppress the induced expression of one or more of these cell adhesion molecules would provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A-205804 (1), a potent and selective inhibitor of the induced expression of E-selectin and ICAM-1 over VCAM-1, was further modified with emphasis at the C-4 and C-2 positions to identify a more potent drug candidate with a good pharmacokinetic profile and physical properties. Replacement of the C-4 sulfur linkage in 1 with an oxygen atom eliminated one of the two major metabolites for this lead molecule. The para-position of the 4-phenoxy group of the thieno[2,3-c]pyridine lead is found to be very critical for a higher in vitro potency and selectivity of E-selectin and ICAM-1 over VCAM-1 expression. This position is presumably close to the solvent-accessible region of the target protein-inhibitor complex. An attempt to install a water-solubilizing group at the para-position of the phenoxy group to increase the aqueous solubility of this lead series through various linkages failed to provide an ideal inhibitor. Only small substituents such as fluorine are tolerated at the meta- and ortho-positions of the 4-phenoxy to retain a good in vitro potency. Bromo, trifluoromethyl, pyrazol-1-yl, and imidazol-1-yl are among the better substituents at the para-position. With fine-tuning at the C-2 position we discovered a series of very potent (IC(50) < 5 nM for ICAM-1) and selective (>200-fold vs VCAM-1) inhibitors with a good pharmacokinetic profile. Demonstrated efficacy in a rat rheumatoid arthritis model and in a mice asthma model with selected compounds is also reported.

Expression, purification, and characterization of human recombinant thrombopoietin in Chinese hamster ovary cells.

Thrombopoietin (TPO) is a primary regulator of megakaryocytopoiesis, a process through which megakaryocytes proliferate and mature into platelets. Recombinant human TPO (rhTPO) was expressed in Chinese hamster ovary (CHO) cells and purified from the culture medium. The cDNA encoding full-length TPO, including the native signal peptide sequence, was amplified by PCR from a human fetal liver cDNA library. The product was cloned into a mammalian expression vector under the control of the SV40 early promoter and enhancer. Secreted rhTPO was purified in three conventional chromatography steps. It migrates on SDS-PAGE as a broad band, characteristic of a heavily glycosylated protein, with an average molecular mass of 85 kDa. rhTPO expressed in CHO cells is biologically active in vitro as demonstrated by its ability to stimulate the proliferation of a megakaryocytic cell line and to trigger the JAK/STAT signal transduction pathway. rhTPO also shows activity in vivo as judged by the elevation of platelet count in treated mice.

Clinical practice guidelines for bipolar disorder from the Department of Veterans Affairs.

BACKGROUND: For the last several years, the Department of Veterans Affairs (VA) has been involved in the development of practice guidelines for major medical, surgical, and mental disorders. This article describes the development and content of the VA-Clinical Practice Guidelines for Bipolar Disorder, which are available in their entirety on the Journal Web site (http://www. psychiatrist.com). METHOD: A multidisciplinary work group composed of content experts in the field of bipolar disorder and practitioners in general clinical practice was convened by the VA's Office of Performance and Quality and the Mental Health Strategic Health Group. The work group was instructed in algorithm development and methods of evidence evaluation. Draft guidelines were developed over the course of 6 months of meetings and conference calls, and that draft was then sent to nationally prominent content experts for final critique. RESULTS: The Bipolar Guidelines are part of the family of the VA Clinical Guidelines for Management of Persons with Psychosis and consist of explicit algorithms supplemented by annotations that explain the specific decision points and their basis in the scientific literature. The guidelines are organized into 5 modules: a Core Module for diagnosis and assignment to mood state plus 4 treatment modules (Manic/Hypomanic/Mixed Episode, Bipolar Depressive Episode, Rapid Cycling, and Bipolar Disorder With Psychotic Features). The modules specify particular diagnostic and treatment tasks at each step, including both somatotherapeutic and psychotherapeutic interventions. CONCLUSION: The VA Bipolar Guidelines are designed for easy clinical reference in decision making with individual patients, as well as for use as a scholarly reference tool. They also have utility in training activities and quality improvement programs.

Povidone-iodine to prevent mucositis in patients during antineoplastic radiochemotherapy.

In an open study, the efficacy of povidone-iodine in the prophylaxis of mucositis during antineoplastic radiochemotherapy was determined. 40 patients were randomly assigned to a treatment or control group (each 20 patients). All patients received standard prophylaxis of mucositis with nystatin, dexpanthenol, rutoside and immunoglobulin. In addition, the patients of the treatment group performed 4 times daily rinsing with povidone-iodine, the control patients with sterile water. Clinical examination of the oral mucosa was performed weekly during the radiation period and up to 6 weeks after the end of therapy. Oral mucositis was observed in 14 patients of the treatment group (mean grading: 1.0) and in all 20 patients of the control group (mean grading: 3.0). The mean onset of mucositis was after 2.25 weeks in treatment patients and 1.5 weeks in control patients. The mean total duration of mucositis was 2.75 weeks in treatment patients and 9.25 weeks in control patients. The mean AUC values were 2.5 in treatment patients and 15.75 in control patients. All findings were statistically significantly different between the two groups. It is concluded that rinsing with povidone-iodine reduces the incidence, severity and duration of oral mucositis during antineoplastic radiochemotherapy.

Incremental lines in root cementum of human teeth: an approach to their ultrastructural nature by microscopy.

In ground sections of human teeth, root cementum shows under the light microscope as alternating, almost concentric, dark and light rings. In paleontology and forensic medicine, the number of these incremental lines or annulations is used to derive the age-at-death of the individual. To find the ultrastructural features underlying these cemental annulations, we used bright-field light microscopy (LM), confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM), and electron-dispersive x-radiation (EDX) in a scanning electron microscope (SEM). Annulations visible in ground sections of about 100-micron thickness were no longer visible in semi-thin sections (thickness, 1-2 microns) of the same specimen in the same area. The assumption that annulations could be caused by super-imposing structures in the depth of field of the light microscope's objective lens was not verified by CLSM. Fiber bundles of higher density than the surrounding matrix in TEM micrographs could not be connected unambiguously with annulations in LM micrographs. After all, the ultrastructural nature of cemental annulations remains an open question.

Serum prostate-specific antigen and digital rectal examination for early detection of prostate cancer in a national community-based program. The Prostate Cancer Education Council.

OBJECTIVES: This study analyzed methods of prostate cancer early detection in community settings throughout the United States against standards and findings of earlier studies conducted at academic medical centers. METHODS: The study was conducted at 148 clinical centers during Prostate Cancer Awareness Week in September 1993 and continued through June 1994. A total of 31,953 eligible subjects were tested by both digital rectal examination (DRE) and prostate-specific antigen (PSA). PSA was tested with the Abbott IMx PSA assay and reported by Roche Biomedical, Inc. RESULTS: The study confirmed that elevated PSA levels (greater than 4.0 ng/mL) aid in the detection of organ-confined prostate cancer when used in conjunction with the DRE. Reflecting more conservative biopsy decision-making practices, study results nonetheless are comparable to earlier reports. Among 1307 subjects who underwent biopsy, 322 cancers were detected. The cancer detection rate was 3.6% for PSA, 3.0% for DRE, and 4.7% if either test result was positive. The positive predictive value (PPV) for elevated PSA levels (greater than 4.0 ng/mL) was 3l.6%, significantly better (P < 0.0001) than the PPV for abnormal DRE results (25.5%). Nearly 90% (88.9%) of staged cancers were diagnosed as localized. Elevated PSA levels detected more localized cancers (76 of 105 [72.4%]) than the DRE (72 of 105 [68.6%]). Of localized tumors, 33 (31.4%) were missed by DRE and detected solely by PSA, and 29 (27.6%) were missed by PSA and detected solely by DRE. The combined use of the two methods detected 33 additional localized tumors. CONCLUSIONS: Community practice throughout the United States demonstrates that PSA and DRE are consistently effective and efficient in the early detection of prostate cancer.

The effect of exercise training on cold tolerance in adult and old C57BL/6J mice.

In order to ascertain the effect of aging on cross-adaptation between exercise training and cold tolerance, we studied cold tolerance in adult and old C57BL/6J male mice before and after 6 weeks of an exercise regimen of moderate intensity. There were two age groups of 32 mice each, including 12-month-old (adult) and 24-month-old (aged) mice equally divided into control and exercise groups. The exercise consisted of daily runs on a treadmill (1 hr/day, 5 days/week) for 6 weeks, while the control mice spent the same time on a stationary treadmill. All mice were subjected to a cold stress test (3-hr partial restraint at 6 degrees C) prior to and following the designated regimen. The results revealed a statistically significant interaction between age and exercise training. In adult mice, exercise resulted in a reduction of cold-induced heat production and weakening of cold tolerance, while in aged mice, the opposite effect was observed; i.e., an increase in cold-induced heat production accompanied by greater cold tolerance. However, only the attenuating effect on cold tolerance of adults was statistically significant. The results of our experiments do not support the existence of cross-adaptation between exercise training and cold tolerance. They indicate, however, that exercise training affects the cold tolerance in adult and old mice through different physiological mechanisms.

A bi-modal transfer of antibiotic resistance by conjugation and transduction from an imipenem-resistant strain of Pseudomonas aeruginosa.

A strain of Pseudomonas aeruginosa No. 76/17224 resistant to carbenicillin (CAR), kanamycin (KAN), cefalotin (CLO), cefotaxime (CTX), ceftazidime (CAZ), aztreonam (AZA), imipenem (IMI) and ofloxacin (OFL) was isolated at the Frankfurt University Hospital. This strain transferred, by conjugation, antibiotic resistance determinants to CAR, CLO, CTX, CAZ and AZA. In addition, we isolated a wild-type phage from this strain. We used this phage to transduce the resistance determinants to four susceptible recipient strains of P. aeruginosa. The phage designated AP-76 transduced the resistance determinants to KAN, CAR, CTX and CAZ to all four recipient strains. Imipenem and aztreonam resistance determinants were directly transduced to two recipient strains only, i.e. to PAO-1670 and ML-1008. The IMI resistance determinant was not co-transduced with any other resistance determinant(s) selected directly. Our results indicated that IMI resistance determinant was not associated with other resistance determinants. IMI was actively hydrolysed by IMI-resistant transductants and this hydrolysis was inhibited by clavulanate but not by EDTA.

Evaluations of wasted mouse fibroblasts and SV-40 transformed human fibroblasts as models of ataxia telangiectasia in vitro.

Fibroblast cultures from wasted mice have been derived and the responses of these cultures to bleomycin treatment or gamma-irradiation have been examined. No differences were observed between wasted fibroblasts and littermate controls in the post-treatment inhibition of DNA replication. In contrast, a human SV-40 transformed ataxia telangiectasia fibroblast line mimicked the abnormal response of primary ataxia telangiectasia fibroblasts to gamma-rays or bleomycin and thus appears to be a useful in vitro model of ataxia telangiectasia.

Air quality of American homes.

In a survey of particulate fallout in homes it was found that there is a relation between pollution inside and outside a home. The level inside the home also depends on the location of the home (urban, suburban, or rural). Bathrooms and kitchens show heavier particle fallout than living rooms or bedrooms.

Condensation nuclei: production of very large numbers in country air.

When relatively clean country air is exposed to the saturated vapor of iodine or turpentine, very large numbers of condensation nuclei develop. It is believed that such air contains clusters of molecules that are polymerized by the vapor of turpentine or iodine to form nuclei.

Time lapse photography of clouds.

The equipment and procedures used in preparing more than 15,240 m of 16-mm time lapse movies of atmospheric clouds is described. Such photographic records are of great value in establishing a dynamic cloud census of a specific area. Operational techniques, the support diagrams, and the optimum time intervals in use for different types of records are presented.

Ice nuclei from automobile exhaust and iodine vapor.

When exposed to a trace of iodine vapor, the submicroscopic particles of lead exhausted by automobiles produce nuclei for the formation of ice crystals. Concentrations of particles exceeding 10(6) per liter can be directly sampled from the exhaust pipe of an idling motor. Concentrations of from 10(4) to 10(5) per liter have been found in rural air downwind of auto roads; the concentration at one rural site has increased by an order of magnitude in 13 years. The phenomenon may provide a method of modifying clouds, and of determining ( and monitoring) the percentage of automobile exhaust in a polluted atmosphere. It may be an important factor in inadvertent modification by man of the climate.