Ovarian hormone loss impairs excitatory synaptic transmission at hippocampal CA3-CA1 synapses.

Premature and long-term ovarian hormone loss following ovariectomy (OVX) is associated with cognitive impairment. This condition is prevented by estradiol (E2) therapy when initiated shortly following OVX but not after substantial delay. To determine whether these clinical findings are correlated with changes in synaptic functions, we used adult OVX rats to evaluate the consequences of short-term (7-10 d, OVXControl) and long-term (∼5 months, OVXLT) ovarian hormone loss, as well as subsequent in vivo E2 treatment, on excitatory synaptic transmission at the hippocampal CA3-CA1 synapses important for learning and memory. The results show that ovarian hormone loss was associated with a marked decrease in synaptic strength. E2 treatment increased synaptic strength in OVXControl but not OVXLT rats, demonstrating a change in the efficacy for E2 5 months following OVX. E2 also had a more rapid effect: within minutes of bath application, E2 acutely increased synaptic strength in all groups except OVXLT rats that did not receive in vivo E2 treatment. E2's acute effect was mediated postsynaptically, and required Ca(2+) influx through the voltage-gated Ca(2+) channels. Despite E2's acute effect, synaptic strength of OVXLT rats remained significantly lower than that of OVXControl rats. Thus, changes in CA3-CA1 synaptic transmission associated with ovarian hormone loss cannot be fully reversed with delayed E2 treatment. Given that synaptic strength at CA3-CA1 synapses is related to the ability to learn hippocampus-dependent tasks, these findings provide additional insights for understanding cognitive impairment-associated long-term ovarian hormone loss and ineffectiveness for delayed E2 treatment to maintain cognitive functions.

Review of mobile communication devices as potential reservoirs of nosocomial pathogens.

Innovation in mobile communication technology has provided novel approaches to the delivery of healthcare and improvements in the speed and quality of routine medical communication. Bacterial contamination of mobile communication devices (MCDs) could be an important issue affecting the implementation of effective infection control measures and might have an impact on efforts to reduce cross-contamination. This review examines recent studies reporting bacterial contamination of MCDs, most demonstrating that 9-25% of MCDs are contaminated with pathogenic bacteria. We examine previously investigated risk factors for MCD contamination in addition to work on surface decontamination of the device. Recommendations to reduce contamination risks include staff education, strict hand hygiene measures, guidelines on device cleaning and consideration of the restrictions regarding use of mobile phone technology in certain high risk areas, for example, operating theatres, intensive care units and burns units. Further work is required to evaluate the benefit of such interventions on MCD contamination and to determine whether a link exists between contamination and subsequent patient infection.

PI3K signaling effects in hypothalamic neurons mediated by estrogen.

Multiple mechanisms mediate the effects of estrogen in the central nervous system, including signal transduction pathways such as protein kinase A, protein kinase C, and phosphatidylinositol 3-kinase (PI3K) pathways. Previously we demonstrated that estrogen regulates a number of PI3K-related genes in the hypothalamus, including the PI3K p55gamma regulatory subunit. We hypothesized that PI3K activation is critical for the effects of estrogen and that the p55gamma subunit may be more prevalent than the p85alpha regulatory subunit in the hypothalamus. Therefore, in the present study, we compared the mRNA distribution of the p55gamma and p85alpha regulatory subunits by using in situ hybridization in guinea pig. Expression level of p55gamma mRNA was greater than p85alpha in most hypothalamic nuclei. Twenty-four hours of estrogen treatment increased p55gamma mRNA expression in the paraventricular, suprachiasmatic, arcuate, and ventromedial nuclei, and little or no change was observed for p85alpha mRNA. Quantitative real-time PCR confirmed the in situ hybridization results. Next, we investigated the general role of PI3K signaling in the estrogen-mediated changes of arcuate proopiomelanocortin (POMC) neuronal excitability by using whole-cell recording. One cellular mechanism by which estrogen increases neuronal excitability is to desensitize (uncouple) gamma-aminobutyric acid type B (GABA(B)) receptors from their G-protein-gated inwardly rectifying K(+) channels in hypothalamic neurons. We found that the PI3K inhibitors wortmannin and LY294002 significantly reduced the estrogen-mediated GABA(B) receptor desensitization in POMC arcuate neurons, suggesting that PI3K signaling is a critical downstream mediator of the estrogen-mediated rapid effects. Collectively, these data suggest that the interplay between estrogen and PI3K occurs at multiple levels, including transcriptional and membrane-initiated signaling events that ultimately lead to changes in homeostatic function.

Bacterial contamination of hospital bed-control handsets in a surgical setting: a potential marker of contamination of the healthcare environment.

INTRODUCTION: Patients undergoing colorectal surgical resections have a high incidence of surgical site infection (SSI). Many patient-specific risk factors have been recognised in association with SSI in such patients, but environmental contamination is increasingly recognised as a contributor to hospital-acquired infection (HAI). This study set out to describe the bacterial contamination of the patient environment, using hospital bed-control handsets, as they are frequently handled by both staff and patients and represent a marker of environmental contamination. PATIENTS AND METHODS: On two unannounced sampling events, 1 week apart, 140 bacteriological assessments were made of 70 hospital bed control handsets within a specialist colorectal surgical unit. RESULTS: Of the handsets examined, 67 (95.7%) demonstrated at least one bacterial species (52.9% grew 1, 30% grew 2 and 12.9% grew 3 or more bacterial species). Of these, 29 (41.4%) bed-control handsets grew bacteria known to cause nosocomial infection, including 22 (31.4%) handsets which grew Enterococcus spp., 9 (12.9%) which grew MRSA, 2 (2.9%) which grew MSSA, 2 (2.9%) which grew coliforms, and 1 (1.4%) handset which grew anaerobes. At 1-week follow-up, 31 bed-control handsets showed evidence of contamination by the same bacterial species. CONCLUSIONS: This study revealed high levels of bacteria known to cause HAI, contaminating hospital bed-control handsets in a surgical setting. Further study is now required to confirm whether hospital environmental contamination is causally involved in SSI.

Device-associated nosocomial infection rates in intensive care units of seven Indian cities. Findings of the International Nosocomial Infection Control Consortium (INICC).

We sought to determine the rate of healthcare-associated infection (HCAI), microbiological profile, bacterial resistance, length of stay (LOS) and excess mortality in 12 ICUs of the seven hospital members of the International Infection Control Consortium (INICC) of seven Indian cities. Prospective surveillance was introduced from July 2004 to March 2007; 10 835 patients hospitalized for 52 518 days acquired 476 HCAIs, an overall rate of 4.4%, and 9.06 HCAIs per 1000 ICU-days. The central venous catheter-related bloodstream infection (CVC-BSI) rate was 7.92 per 1000 catheter-days;the ventilator-associated pneumonia (VAP) rate was 10.46 per 1000 ventilator-days; and the catheter-associated urinary tract infection (CAUTI) rate was 1.41 per 1000 catheter-days. Overall 87.5% of all Staphylococcus aureus HCAIs were caused by meticillin-resistant strains, 71.4% of Enterobacteriaceae were resistant to ceftriaxone and 26.1% to piperacillin-tazobactam; 28.6% of the Pseudomonas aeruginosa strains were resistant to ciprofloxacin, 64.9% to ceftazidime and 42.0% to imipenem. LOS of patients was 4.4 days for those without HCAI, 9.4 days for those with CVC-BSI, 15.3 days for those with VAP and 12.4 days for those with CAUTI. Excess mortality was 19.0% [relative risk (RR) 3.87; P < or = 0.001] for VAP, 4.0% (RR 1.60; P=0.0174) for CVC-BSI, and 11.6% (RR 2.74; P=0.0102) for CAUTI. Data may not accurately reflect the clinical setting of the country and variations regarding surveillance may have affected HCAI rates. HCAI rates, LOS, mortality and bacterial resistance were high. Infection control programmes including surveillance and antibiotic policies are a priority in India.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the preoperative staging of thoracic oesophageal and gastro-oesophageal junction cancer: a prospective study.

BACKGROUND: The pre-operative staging in oesophageal cancer is often challenging and underestimation of the extent of the disease may lead to unnecessary surgery. AIM: To audit the use and assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) as a staging tool for thoracic oesophageal and gastro-oesophageal junction (GOJ) cancers in our oncological surgical practice. PATIENTS AND METHODS: Over a 3 year period, between 2002 and 2004, 134 patients with thoracic oesophageal or GOJ cancer were referred to our unit for treatment. The standard preoperative staging investigation in all cases was CT (thorax, abdomen and pelvis). A preoperative FDG-PET scan was further requested in 22 patients. The case notes of all the patients that underwent a FDG-PET scan were reviewed and compared with the preoperative imaging, the operative findings and the histopathology of the resected tumours. RESULTS: Eighteen men and 4 women with a median age of 65 (range 43-79) years were studied. After FDG-PET, 13 out of 22 patients (59%) were deemed suitable for tumour resection. Twelve of the 13 patients were fit to undergo surgery. At laparotomy, 2 of those (17%) were found inoperable due to widespread disease. The sensitivity of CT versus FDG-PET to detect infiltrated lymph nodes was 29% (95% CI: 3-70) versus 71% (95% CI: 29-96) (P=0.0412), whereas both tests had 67% specificity (95% CI: 9-99) in detecting lymph nodes. The sensitivity and the specificity of CT versus FDG-PET to detect distant organ metastases (M1b) were 33% (95% CI: 4-77) and 88% (95% CI: 47-99) versus 50% (95% CI: 6-93) and 100% (95% CI: 69-100), respectively (P>0.05). The FDG-PET regarding the N and M status differed from the CT in 11 patients and led to modification of the planned management in 5 of them. CONCLUSIONS: FDG-PET is more accurate than CT in defining N and M status. It can result in a reduction of unnecessary surgery in a significant number of patients. The combined PET-CT scan as a single imaging modality is expected to further improve diagnostic accuracy of FDG-PET.

Multiple pathways transmit neuroprotective effects of gonadal steroids.

Numerous preclinical studies suggest that gonadal steroids, particularly estrogen, may be neuroprotective against insult or disease progression. This paper reviews the mechanisms contributing to estrogen-mediated neuroprotection. Rapid signaling pathways, such as MAPK, PI3K, Akt, and PKC, are required for estrogen's ability to provide neuroprotection. These rapid signaling pathways converge on genomic pathways to modulate transcription of E2-responsive genes via ERE-dependent and ERE-independent mechanisms. It is clear that both rapid signaling and transcription are important for estrogen's neuroprotective effects. A mechanistic understanding of estrogen-mediated neuroprotection is crucial for the development of therapeutic interventions that enhance quality of life without deleterious side effects.

Intratesticular cysts and malignant potential: conservative management is an option.

Benign intratesticular cysts are rare, but recognition is essential to prevent unnecessary surgical intervention. The diagnostic dilemma is to differentiate these cysts from testicular malignancy. As they are extremely uncommon, experience of their management is limited and controversial. We present a case of a simple intratesticular cyst and discuss the diagnostic and management principles.

Nongynecologic applications of transvaginal US.

Transvaginal ultrasonography (US) is a noninvasive, readily available imaging technique that has greatly enhanced diagnostic sensitivity and accuracy for both gynecologic and nongynecologic disease. High-frequency US probes placed in the vagina allow high-resolution assessment of all the pelvic viscera, including portions of the gut and urinary tract. In addition, they allow visualization of the peritoneum of the pelvic pouch and the pelvic side walls without interference from bowel gas or adipose tissue. Evaluation of these areas requires a modified US technique that includes the use of the highest-frequency probes with angulation of the transducer to allow assessment of the region of interest. In women of childbearing age, the similarity of symptoms in gynecologic and gastrointestinal tract disease in particular underscores the potential utility of transvaginal US, which may, for example, help differentiate appendicitis in a pelvic appendix from pelvic inflammatory disease. Transvaginal US may also help determine the correct course of therapy, thereby improving patient management. Other indications for transvaginal US include assessment for pelvic appendicitis and diverticulitis, rectal and perianal complications of Crohn disease, and ureteric and bladder calculi and tumors as well as evaluation of the anal sphincters in women with fecal incontinence. Transvaginal US is also superior to routine US in the detection and characterization of ascites and peritoneal disease. Transvaginal US examination should include the entire pelvic cavity and contents, especially in women at risk for pelvic sepsis or peritoneal disease.

Retention, antimicrobial activity, and clinical outcomes following use of a bioerodible tetracycline gel in moderate-to-deep periodontal pockets.

This randomized, examiner masked, split mouth study evaluated a new model to test periodontal therapy involving a novel bioerodible copolymer gel containing tetracycline hydrochloride. Responses to the tetracycline gel and untreated control were compared for product tolerance and 3 different measures of effectiveness (drug retention, changes in microbial levels, and clinical status). The test gel was administered by syringe into the periodontal pockets of 18 systemically healthy adult volunteers, each of whom presented with 3 or more sites with 6 mm probing depths. Gingival crevicular fluid samples were used to monitor daily drug levels over 7 days, while clinical responses were assessed at day 30. Overall, the test gel was well-tolerated by all patients. For the 3 effectiveness measures, tetracycline was released throughout the observation period and mean levels exceeded 100 microg/mL over 6 days, statistically significant reductions in selected periodontal pathogens were evident at day 7 but not at day 30, and mean probing depth reductions at test sites were 1.12 mm at 30 days versus 0.36 mm at untreated control sites (P=0.012). The safety profile, longer-term drug retention, antimicrobial activity, and clinical response in this Phase I study suggest that this tetracycline-containing copolymer gel platform may represent a safe and effective bioerodible therapy for periodontitis. The experimental model also shows merit for early phase clinical testing of novel therapeutic agents.

Gingival fluid tetracycline release from bioerodible gels.

Intracrevicular antimicrobial therapy is consistent with the site-specific nature of periodontitis. Considerable research has focused on the use of nonresorbable fibers. However, a bioerodible system is desirable. The purpose of this study was to assess tetracycline release and safety following a single application of a syringable 35% tetracycline hydrochloride in a lactic-glycolic acid gel. 31 generally healthy adult volunteers (mean age = 59 years) were enrolled in and completed this randomized, double-blind eight day study. 2, 6-10 mm non-adjacent interproximal pockets that bled on pocket probing were chosen as experimental sites in each subject. I experimental site and the surrounding gingival crevice received small particle size tetracycline in gel while the other site received larger particle size tetracycline in gel. Gingival crevicular fluid (GCF) was collected prior to treatment and 15 min, 1, 2, 3, 4 and 8 days post-treatment. GCF tetracyline concentrations were determined by agar diffusion bioassay and GCF volume measurements. 61% and 71% of sites had > or = 100 micrograms/ml tetracycline 3 days following application of large (mean concentration = 430 +/- 92 micrograms/ml) and small particle gels (mean concentration = 418 +/- 70 micrograms/ml), respectively. 37% and 55% of sites had measurable tetracycline 8 days after placement of large (mean concentration = 86 +/- 31 micrograms/ml) and small particle gels (mean concentration = 293 +/- 79 micrograms/ml), respectively. The most common adverse event was "bitter taste" (10% of subjects). Based upon the reduction in probing depths and % of sites bleeding on probing at 8 days relative to pretreatment, and the absence of any serious adverse events, it is concluded that these bioerodible gels are safe, and since the bacteriostatic range for most putative periodontopathogens is in the 2-10 micrograms/ml range, the tetracycline levels observed at days 3 and 8 likely represent significant antimicrobial efficacy.

Immunological detection of Bacteroides fragilis in clinical samples.

A monospecific polyclonal antiserum, prepared against Bacteroides fragilis common polysaccharide antigen purified by polyacrylamide gel immunoblot detected B. fragilis, B. thetaiotaomicron, B. ovatus and Prevotella melaninogenica in pus samples from various anatomical sites by immunofluorescence microscopy of the pus. With standard clinical laboratory culture methods, 36% of 147 samples were positive for one or more of the above bacteria. Of these, B. fragilis accounted for 33%. By immunofluorescent labelling of pus with the common antigen antiserum the detection of these bacteria in the samples increased to 50%. All nine of the blood cultures in which B. fragilis was detected by culture contained bacteria positive for the common antigen. Immunofluorescent labelling of pus samples with a selection of monoclonal antibodies specific for surface polysaccharides which are known to be antigenically variable in culture in vitro and in an animal model of infection showed that these polysaccharides are also variable in natural infection. The results indicate that the common polysaccharide antigen, in contrast to the variable surface polysaccharides, is a suitable target for the immunodetection of B. fragilis in clinical samples from a range of anatomical sites.