Hypoxia-inducible factor-1alpha is an intrinsic marker for hypoxia in cervical cancer xenografts.

The hypoxia-inducible factor 1 (HIF-1) is known to induce the expression of several proteins linked to the maintenance of oxygen homeostasis, cellular energy metabolism, and tumor progression. Its alpha subunit (HIF-1alpha) is stabilized under hypoxic conditions and, therefore, might represent an intrinsic marker for tissue hypoxia. Here we report on the spatial relationship between HIF-1alpha and the nitroimidazole hypoxia marker EF5 in cervical carcinoma xenografts, and on their spatial relationship to tumor blood vessels. EF5 was administered to mice bearing ME180 and SiHa cervical cancer xenografts. Frozen tumor tissue sections, triple-stained for HIF-1alpha, the endothelial cell marker CD31, and EF5, were imaged using wide-field multiparameter immunofluorescence microscopy. Expression levels of EF5 and HIF-1alpha were similar in ME180 xenografts, but the percentage of tumor area stained with EF5 was significantly smaller than the percentage of HIF-1alpha-positive area in SiHa tumors. In both tumor types the EF5-HIF-1alpha overlap was statistically significant, thus confirming their spatial and temporal colocalization. Spatial distribution analysis of EF5 and HIF-1alpha is consistent with different pO2 value "thresholds" for EF5 binding and HIF-1alpha expression. Summarized, our results indicate that HIF-1alpha is a useful intrinsic marker for hypoxia in cervical carcinoma xenografts.

Formal total synthesis of (+/-)-alpha- and beta-cedrene by preparation of cedrone. Construction of the tricyclic carbon skeleton by the use of a highly efficient intramolecular Khand annulation.

The cedrene carbon skeleton was rapidly assembled from a simple monocyclic precursor by the strategic use of a high yielding intramolecular Khand cyclization reaction. Further synthetic manipulations provided a concise formal total synthesis of alpha- and beta-cedrene. Reaction: see text.

Comparison of therapeutic interchange with standard educational tools for influencing fluoroquinolone prescribing.

The abilities of therapeutic interchange (TI) and standard educational tools (SET) to change prescribing habits were compared. We evaluated the replacement of ciprofloxacin with levofloxacin in a four-hospital health system during a 14-month study period. Two hospitals used TI and two SET. The demographics, sites of infection, and severity of illness were analyzed for 554 patients treated at SET hospitals and 1323 patients treated at TI hospitals during a total of 2040 hospitalizations over a 14-month period. In TI hospitals, 97% of patients received levofloxacin, whereas 43% received levofloxacin in SET hospitals (p < 0.001). Clinical outcomes were not significantly different for the two groups, although more patients in the SET hospitals received combination antimicrobial therapy. Differences in savings per patient were significant between TI hospitals ($60) and SET hospitals ($37) (p < 0.001). The total annualized savings for all four hospitals was $156,444. TI was more effective than SET in facilitating changes in prescribing patterns in a health care system and resulted in significant cost savings to hospitals and payers.

Heat shock transcription factors and the hsp70 induction response in brain and kidney of the hyperthermic rat during postnatal development.

Heat shock transcription factor (HSF) 1 levels increase in brain regions and decline in kidney during postnatal rat development. In both neonatal and adult rats, levels of HSF1 protein in brain and kidney are proportional to the levels of HSF DNA-binding activity and the magnitude of heat shock protein hsp70 induction after thermal stress. There appears to be more HSF1 protein in adult brain than is needed for induction of hsp70 after thermal stress, suggesting that HSF1 may have other functions in addition to its role as a stress-inducible activator of heat shock genes. HSF2 protein levels decline during postnatal rat development in brain regions and kidney. Gel mobility shift analysis shows that HSF2 is not in a DNA-binding form in the neonatal brain and kidney, suggesting that HSF2 may not be involved in the constitutive expression of hsps in early postnatal development. There is no apparent relationship between levels of HSF2 protein and basal levels of hsp90, hsp70, heat shock cognate protein hsc70, and hsp60.

Antibiotic therapy of osteomyelitis in outpatients.

The therapy of osteomyelitis utilizing 481 courses of intravenous antibiotics in outpatients was analyzed to identify the types of bone infection most frequently treated by this form of therapy. The efficacy of this form of treatment is also discussed.

Gastroenteritis, sepsis, and osteomyelitis caused by Plesiomonas shigelloides in an immunocompetent host: case report and review of the literature.

We report the 11th human case of bloodstream infection with Plesiomonas shigelloides. This was the first case without any apparent underlying immunocompromising disease, and the patient was the first adult to survive the infection. We review all the extraintestinal cases associated with this organism, giving special attention to the clinical characteristics of the bloodstream infections reported previously.

A measurement of the efficacy of nosocomial infection control using the 95 per cent confidence interval for infection rates.

From 1981 through 1985, the authors studied the changes in monthly nosocomial infection rates at the University of Virginia Hospital in Charlottesville, Virginia using the 95% confidence interval for infection rates as a marker of the efficacy of infection control activities. For a 99-month baseline period, monthly infection rates were calculated and the 95% confidence interval was established. In the 60 study months, each monthly rate was compared with the 95% confidence interval for that particular month. At the end of each study year, the monthly infection rates were incorporated into the existing confidence interval. Of 60 monthly rates during the study period, 30 were below the confidence interval (p less than 0.00001), two were above the confidence interval (p = 0.23), and 28 were within the confidence interval. Since there was no reduction in surveillance activity, patient case-mix index, or laboratory sensitivity for organism recovery, these results suggest that monthly nosocomial infection rates at this hospital have decreased when compared with the baseline period. The use of the 95% confidence interval may provide a measure of the efficacy of infection control activities, suggest temporal intervals requiring more intensive infection surveillance, and provide a method for examining the variability in monthly infection rates.

Rabies pre-exposure prophylaxis using intradermal human diploid cell vaccine: immunologic efficacy and cost-effectiveness in a university medical center and a review of selected literature.

The authors studied the antigenicity of intradermal human diploid cell rabies vaccine administered to 40 laboratory workers considered to be at-risk at the University of Virginia Medical Center. A 1-year postvaccination serology was determined for 20 of those 40, all of whom demonstrated an antirabies titer greater than or equal to 1:50 by the raped fluorescent focus inhibition test. By 2 years' postvaccination, 5 of 40 subjects had "unprotective levels" (less than 1:5), whereas 35 had titers greater than or equal to 1:5, and none had a titer greater than or equal to 1:50. Booster doses given to four subjects whose titers had declined produced a 1-month postvaccination antirabies titer greater than or equal to 1:50 in all cases. Vaccine administration by the intradermal rather than the intramuscular route resulted in a cost savings of $120 (U.S.) per employee. This data indicate that the intradermal administration of human diploid cell vaccine for rabies pre-exposure prophylaxis achieves an immunologic response thought to be protective while providing a substantial cost savings when compared with the intramuscular route of administration. Those who receive primary pre-exposure rabies vaccination should have serologic confirmation of immunologic protection every 2 years with a booster dose given to subjects demonstrating a titer less than 1:5.

Nosocomial bloodstream infections: secular trends in a statewide surveillance program in Virginia.

Over a 7-year period (1978-1984) the authors studied the rates of nosocomial bloodstream infections in acute-care hospitals participating in a statewide surveillance network in Virginia. A total of 4,617 hospital-acquired bloodstream infections were documented among 1,807,989 patients at risk for an overall rate of 25.5 cases per 10,000 patient admissions/discharges (annual range = 22.1 to 30.7). Compliance of reporting for Virginia hospitals averaged 58% (1 to 5 monthly reports in a study year), and 39% (greater than or equal to 6 monthly reports annually). Significant changes in bloodstream infection rates (cases per 10,000 patient admissions/discharges) due to specific pathogens included the following: coagulase-negative staphylococci increased from a rate of 1.3 to 4.5 (P = .0003), and those due to all gram-positive cocci increased from a rate of 7.5 to 11.4 (P = .03). Candida species increased from a rate of 0.1 to 1.5 (P = .005). The data show a continuing rise of nosocomial Candida BSI and clearly document the re-emergence of gram-positive cocci as major nosocomial bloodstream pathogens.

Community-acquired bloodstream infection caused by Pseudomonas paucimobilis: case report and review of the literature.

Various sources of Pseudomonas paucimobilis bacterial infections have been documented. We report the third human case of bloodstream infection due to P. paucimobilis and review the literature in English regarding community-acquired and nosocomial infection due to this bacterium. Biochemical and genetic characteristics supporting the pathogenic potential of P. paucimobilis are presented, and the antibiotic susceptibility profile of the organism is summarized.

Peritonitis caused by Alcaligenes denitrificans subsp. xylosoxydans: case report and review of the literature.

We report the third human case of peritonitis caused by Alcaligenes denitrificans subsp. xylosoxydans and review the English literature regarding community-acquired and nonsocomial infection and colonization that results from this bacterium. The biochemical and genetic characteristics supporting the pathogenic potential of A. denitrificans subsp. xylosoxydans are reviewed, and the antimicrobial susceptibility profile of the organism is summarized.

Nosocomial urinary tract infections due to enterococcus. Ten years' experience at a university hospital.

From 1975 through 1984, 473 cases of enterococcal nosocomial urinary tract infection (UTI) were identified by prospective hospital-wide surveillance at the University of Virginia Hospital, Charlottesville. The rate of infection increased progressively from 12.3 to 32.2 cases per 10 000 patient discharges, and the proportion of nosocomial UTIs due to this organism increased from 6% to 16%. During the study period, crude mortality was 15%. Patients with the diagnosis of neurogenic bladder accounted for 26% of cases and had a crude mortality of 7.3%; all other cases (74%) had a crude mortality of 18.1%. Risk factors associated with fatal outcome in cases having a nosocomial enterococcal UTI included age of more than 50 years, concurrent acute respiratory failure, hospitalization on the internal medicine service, and concurrent gastrointestinal hemorrhage. Enterococcus is the second most frequent cause of nosocomial UTI in our hospital. The emergence of this pathogen may reflect, in part, its selective advantage imparted by resistance to cephalosporin antibiotics.

Associated mortality and clinical characteristics of nosocomial Pseudomonas maltophilia in a university hospital.

We studied the spectrum of clinical disease in 99 patients with nosocomial Pseudomonas maltophilia isolates at the University of Virginia Hospital from 1981 through 1984. The annual rate of isolation increased from 7.1 to 14.1 per 10,000 patient discharges. A crude mortality rate of 43% was documented in all patients from whom the organism was cultured, and the data include 12 patients with nosocomial bacteremia (four deaths). Risk factors associated with death for patients having a P. maltophilia isolate included the following: requirement for care in any intensive care unit during hospitalization (P = 0.0001), patient age over 40 years (P = 0.002), and a pulmonary source for the P. maltophilia isolate (P = 0.003). All P. maltophilia isolates were susceptible to trimethoprim-sulfamethoxazole, 60% of the isolates were resistant to all aminoglycosides (amikacin, tobramycin, and gentamicin), and more than 75% of the isolates were resistant to all beta-lactam antibiotics. The antibiotic susceptibility pattern allows for a niche exploitable in the hospital microbial environment by an organism with a marked associated mortality.

The efficacy of several new handwashing agents for removing non-transient bacterial flora from hands.

Forty subjects participated in a study of four handwashing agents evaluated for their efficacy in removing non-transient bacteria: 70% isopropanol, 0.05% stabilized iodine, 4% chlorhexidine gluconate, and 1% para-chloro-meta-xylenol. Each subject performed a non-medicated handwash to remove transient flora. Afterwards, three consecutive experimental handwashes were performed using a 10-second contact time, and a fourth handwash employed a 1-minute contact time. Quantitative post-handwash cultures were obtained using the sterile bag technique incorporating an effective agent neutralizer. Significant mean log10 reductions were documented for chlorhexidine gluconate, but only after the third (P = .05) and fourth (p = .004) handwash; however, the total log10 reduction was less than 1.0 for any single agent. Subsequently, three evaporative handwash agents, including 70% isopropanol, 0.5% chlorhexidine in 70% isopropanol, and a 60% isopropanol formulation containing evaporative retardants, were tested in 14 subjects. Contact time was prolonged to the point of evaporation prior to culturing. Four consecutive post-handwash cultures were obtained after performing a baseline pre-handwash culture. When compared with the other two evaporative agents, the 60% isopropanol formulation demonstrated significant mean log10 reductions for each handwash (p less than or equal to .03), with a total log10 reduction of 2.9 over all four handwashes (p = .0001). The brief contact time incorporated in our handwashing technique reflects clinical usage patterns. The marked bacterial reduction demonstrated by the 60% isopropanol formulation warrants further study.

Rabies: a review and current approach for the clinician.

Rabies is an acute viral encephalomyelitis with virtually a 100% case fatality rate. Only three cases of human survival after rabies have been documented. The current epizootic of raccoon rabies in the United States centered over the South Atlantic states mandates a working knowledge of rabies management and postexposure prophylaxis by health care professionals. Recently, important advances in rapid and accurate diagnosis and improvements in homologous vaccines make rabies a preventable disease in the United States.

Epidemiology of infections due to Pseudomonas aeruginosa.

Pseudomonas aeruginosa is responsible for an increasing proportion of infections acquired in the modern hospital setting. It accounts for 8.5% of all nosocomial infections and has an attack rate of 36 infections per 10,000 hospital discharges. P. aeruginosa represents the single most frequently isolated pathogen in patients with nosocomial pneumonia and burn-wound infections. The organism's bioepidemiology is linked to its ability to thrive in marginal econiches, and its ascendency as a nosocomial pathogen parallels the evolution of high-technology intensive care units, the large numbers of immunocompromised patients, and the liberal use of antibiotics. The reservoirs and modes of transmission for this organism are reviewed along with recent studies aimed at the prevention of both colonization and infection by this organism.

Common sense and consulting.

Three hundred and forty-two general practitioners in Scotland presented their views on content and training in relation to consulting with patients. Differences in responses from trainers, non-trainers, and trainees are examined and possible reasons for the divergences are discussed.