Fistula use after concurrent arteriovenous fistula formation and Tenckhoff catheter insertion

A significant proportion of peritoneal dialysis (PD) patients will have abrupt technique failure requiring conversion to haemodialysis, often using temporary vascular catheters as bridging access. However, vascular catheter use has been associated with increased mortality and great effort has been made to reduce their use. Just under two decades ago, a trial of dual arteriovenous fistula (AVF) formation and Tenckhoff catheter insertion reported only 4% of those in whom back‐up fistulae were formed ever used them. Patient demographic, surgical technique and fistula care over those decades have changed substantially, potentially making this practice feasible. Thirty‐five selected patients at Concord Repatriation and General Hospital had AVF formed at the time of Tenckhoff insertion and were entered prospectively into a vascular access database. We retrospectively examined this database with a median follow up of 345 days (interquartile range 183–658). Thirty‐one per cent of all patients used the preformed AVF, and a further 19% who were still on PD had clinically functioning AVF. The vast majority (62%) had abrupt PD technique failure. This is a marked difference to dated reports of AVF use after concurrent PD and AVF formation. It raises the possibility that the formation of back‐up fistula may be another method to reduce the need for vascular catheter use.     

A survey of current practices in the diagnosis of and interventions for inhalational injuries in Canadian burn centres

OBJECTIVE:

To summarize current Canadian practice patterns in the diagnosis of and interventions for inhalation injuries (INHI).

METHODS:

A 10-question survey regarding the diagnosis of and interventions for INHI was sent to the medical directors of all 16 burn centres across Canada.

RESULTS:

The response rate to the survey was 50%. Fibreoptic bronchoscopy is required for the diagnosis of INHI in only four centres (50%). The departments of intensive care, plastic surgery, otolaryngology and respirology are involved in performing fibreoptic bronchoscopy in 87.5%, 37.5%, 12.5% and 12.5% of Canadian burn centres, respectively. Intubation for INHI is most often based on physical examination results (87.5%) and clinical history (75%). The most common physical features believed to be most consistent with INHI are dyspnea (87.5%) and hoarseness (87.5%). Common treatments include intubation (87.5%), routine ventilatory support (87.5%) and chest physiotherapy (75%). None of the centres used nebulized heparin. A total of five centres (62.5%) routinely changed the fluid resuscitation protocol when INHI was diagnosed. Only two centres (25%) routinely used prophylactic antibiotics for INHI.

CONCLUSION:

Prospective, multicentre trials are needed to generate evidence-based consensus in the areas of diagnosis, grading and treatment for INHI in Canada.     

Intrahippocampal infusion of the Ih blocker ZD7288 slows evoked theta rhythm and produces anxiolytic‐like effects in the elevated plus maze

Hippocampal theta rhythm has been associated with a number of behavioral processes, including learning and memory, spatial behavior, sensorimotor integration and affective responses. Suppression of hippocampal theta frequency has been shown to be a reliable neurophysiological signature of anxiolytic drug action in tests using known anxiolytic drugs (i.e., correlational evidence), but only one study to date (Yeung et al. ( 2012 ) Neuropharmacology 62:155–160) has shown that a drug with no known effect on either hippocampal theta or anxiety can in fact separately suppress hippocampal theta and anxiety in behavioral tests (i.e., prima facie evidence). Here, we attempt a further critical test of the hippocampal theta model by performing intrahippocampal administrations of the I_h blocker ZD7288, which is known to disrupt theta frequency subthreshold oscillations and resonance at the membrane level but is not known to have anxiolytic action. Intrahippocampal microinfusions of ZD7288 at high (15 µg), but not low (1 µg) doses slowed brainstem‐evoked hippocampal theta responses in the urethane anesthetized rat, and more importantly, promoted anxiolytic action in freely behaving rats in the elevated plus maze. Taken together with our previous demonstration, these data provide converging, prima facie evidence of the validity of the theta suppression model. © 2012 Wiley Periodicals, Inc.     

The National Institutes of Health Chemical Countermeasures Research Program (NIH CCRP): A collaborative opportunity to develop effective and accessible chemical medical countermeasures for the American people

The United States Department of Health and Human Services (HHS) leads the nation in preventing, preparing for, and responding to the adverse health effects of public health emergencies and disasters. In addition to biological, radiological and nuclear agents, the risk of a high consequence public health emergency due to the intentional and/or accidental release of chemical agents is a major growing concern of the US government. As such, the federal government is fully committed to address public health security threats posed by chemicals. To enhance chemical emergency preparedness and response, HHS oversees the interdepartmental research, advanced development, regulatory review and approval, procurement, and stockpiling of medical countermeasures (MCMs). Within the National Institute of Health (NIH/HHS), the National Institute of Allergy and Infectious Diseases (NIAID) is responsible for the fundamental research and early development of MCMs to prevent deaths and/or treat injuries during and after emergencies due to large scale chemical exposure. This commentary provides an overview of the NIAID/NIH Chemical Countermeasures Research Program (CCRP) and resources to facilitate the research, discovery, and early development of chemical MCMs. Available product development resources include research funding opportunities, expert advice from the NIH, and preclinical and efficacy service support cores to reduce opportunity costs and entry barriers for prospective developers interested in entering or accelerating the development of chemical MCMs.     

Serum adiponectin is independently associated with the metabolic syndrome in Hong Kong,Chinese women with polycystic ovary syndrome

Objective: To evaluate the association of serum adiponectin level with the metabolic syndrome in Chinese women with polycystic ovary syndrome (PCOS).

Methods: This was a cross-sectional study carried out in Hong Kong Chinese women with PCOS at a university-affiliated tertiary hospital between January 2010 and January 2011. Clinical and biochemical parameters of the women were analysed. Prediction of the metabolic syndrome was determined by receiver–operator characteristic (ROC) curves, univariate and multivariate logistic regression analyses.

Results: A total of 116 women diagnosed to have PCOS were analysed. The area under the ROC curve of adiponectin for the prediction of metabolic syndrome was 0.820, 95% confidence interval (CI) 0.737–0.886. Univariate binary logistic regression showed that testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), waist circumference, body mass index (BMI), quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and adiponectin were significantly associated with the metabolic syndrome. On multivariate logistic regression analysis, adiponectin (p?= 0.020), HOMA-IR, age (p?= 0.011) and BMI (p?= 0.019) were independently associated with the metabolic syndrome, but not FAI (p?= 0.256).

Conclusions: Serum adiponectin is independently associated with the metabolic syndrome in Chinese women with PCOS. Further longitudinal follow-up studies are needed to determine whether serum adiponectin adds to the prediction of long-term cardiometabolic morbidity conferred by age, BMI and measures of insulin resistance.     

Compartmentalization of the broad-range phospholipase C activity to the spreading vacuole is critical for Listeria monocytogenes virulence

Listeria monocytogenes is a bacterial pathogen that multiplies in the cytosol of host cells and spreads directly from cell to cell by using an actin-based mechanism of motility. The broad-range phospholipase C (PC-PLC) of L. monocytogenes contributes to bacterial escape from vacuoles formed upon cell-to-cell spread. PC-PLC is made as an inactive proenzyme whose activation requires cleavage of an N-terminal propeptide. During infection, PC-PLC is activated specifically in acidified vacuoles. To assess the importance of compartmentalizing PC-PLC activity during infection, we created a mutant that makes constitutively active PC-PLC (the plcBDelta pro mutant). Results from intracellular growth and cell-to-cell spread assays showed that the plcBDelta pro mutant was sensitive to gentamicin, suggesting that unregulated PC-PLC activity causes damage to host cell membranes. This was confirmed by the observation of a twofold increase in staining of live infected cells by a non-membrane-permeant DNA fluorescent dye. However, membrane damage was not sufficient to cause cell lysis and was dependent on bacterial cell-to-cell spread, suggesting that damage was localized to bacterium-containing filopodia. Using an in vivo competitive infection assay, we observed that the plcBDelta pro mutant was outcompeted up to 200-fold by the wild-type strain in BALB/c mice. Virulence attenuation was greater when mice were infected orally than when they were infected intravenously, presumably because the plcBDelta pro mutant was initially outcompeted in the intestines, reducing the number of mutant bacteria reaching the liver and spleen. Together, these results emphasize the importance for L. monocytogenes virulence of compartmentalizing the activity of PC-PLC during infection.     

Localization and variable expression of G alpha(i2) in human endometrium and Fallopian tubes

BACKGROUND: Heterotrimeric G proteins take part in membrane-mediated cell signalling and have a role in hormonal regulation. This study clarifies the expression and localization of the G protein subunit G alpha(i2) in the human endometrium and Fallopian tube and changes in G alpha(i2) expression in human endometrium during the menstrual cycle. METHODS: The expression of G alpha(i2) was identified by Polymerase chain reaction (PCR), and localization confirmed by immunostaining. Cyclic changes in G alpha(i2) expression during the menstrual cycle were evaluated by quantitative real-time PCR. RESULTS: We found G alpha(i2) to be expressed in human endometrium, Fallopian tube tissue and in primary cultures of Fallopian tube epithelial cells. Our studies revealed enriched localization of G alpha(i2) in Fallopian tube cilia and in endometrial glands. We showed that G alpha(i2) expression in human endometrium changes significantly during the menstrual cycle, with a higher level in the secretory versus proliferative and menstrual phases (P < 0.05). CONCLUSIONS: G alpha(i2) is specifically localized in human Fallopian tube epithelial cells, particularly in the cilia, and is likely to have a cilia-specific role in reproduction. Significantly variable expression of G alpha(i2) during the menstrual cycle suggests G alpha(i2) might be under hormonal regulation in the female reproductive tract in vivo.     

A Multi-site In-depth Evaluation of the Quanterix Simoa from a User’s Perspective

An in-depth evaluation of the Quanterix© Simoa? platform was undertaken by scientists from the AAPS Emerging Technologies Focus Group to determine the overall performance of the technology as well as provide guidance to future users. In order to test the platform in a non-GLP bioanalytical setting, a cross-site evaluation of the Quanterix IL-6 biomarker kit was performed. Parameters tested during this evaluation included sensitivity, accuracy and precision, and parallelism in human serum from normal individuals. The results demonstrated improved sensitivity compared to the claimed sensitivity of other commercially available IL-6 kits and showed excellent site-to-site reproducibility. Observed issues included difficulties with system reliability and a lack of parallelism and specificity in a subset of samples. Overall, these results demonstrate that while there are challenges to the Simoa platform this technology offers automation capabilities and excellent sensitivity that enhance bioanalysis especially of low-abundance analytes.     

A randomised trial comparing conventional semen parameters,sperm DNA fragmentation levels and satisfaction levels between semen collection at home and at the clinic

The aim of the randomised trial was to compare conventional semen parameters, sperm DNA fragmentation levels and satisfaction levels between semen samples collected at home and at the clinic. We recruited 110 men with a history of infertility for at least 1 year from the outpatient andrology clinic. Each man collected two semen samples, one at home and one at the clinic. Men were randomly assigned into the home first (n = 55) or clinic first (n = 55) groups. The primary outcome was sperm concentration. There was no significant difference in sperm concentration, sperm DNA fragmentation levels or other conventional semen parameters between home first and clinic first samples (p > .05), while satisfaction levels were significantly higher for home first samples (p < .01). Consistent results were obtained when comparing home-collected and clinic-collected samples within individuals. Men can be offered the option to collect semen samples at home for examination or assisted reproduction without compromising semen quality, especially for those with difficulty in producing semen samples at the clinic.     

Evaluating the safety and efficacy of the 1,440‐nm laser in the treatment of photodamage in Asian skin

Background and Objective

As the demand for diminished procedure‐associated downtime continues to increase, nonablative fractional laser resurfacing is becoming a more popular intervention in the progression of photoaging. Patients with pigmented skin and a mild degree of photodamage may be particularly suited for a less intensive laser treatment. In this study, we have evaluated the safety and efficacy of a low energy, low density 1,440‐nm fractional laser in the treatment of multiple signs of photoaging including dyspigmentation, wrinkling, tissue laxity, enlarged pores, and skin roughness in Asians.

Study Design/Materials and Methods

Ten Chinese subjects with Fitzpatrick skin types III–V and visible signs of photodamage participated in this study. Patients received four treatments at 2‐week intervals with a 1,440‐nm diode‐based fractional laser. Photographs were taken at baseline, 2 weeks after each of the first three treatments and 4 weeks after the final treatment. Images were evaluated independently by two physicians. Clinical improvement and adverse events were analyzed. Discomfort, heat sensation and overall patient satisfaction associated with the procedure were also quantified.

Results

In this prospective single‐arm study, signs of photoaging were examined after treatment with the 1,440‐nm laser. Here we show that a series of four treatments with this device produced a mild improvement in skin texture, pigmentation, and wrinkling. Changes in pore size and skin laxity failed to reach statistical significance. Immediate after‐effects of the procedure included erythema and edema which were transient and left no permanent sequela. A significant proportion of patients reported some degree of discomfort during the procedure despite use of a topical anesthetic. One patient developed a discrete, localized area of post‐inflammatory hyperpigmentation which completely resolved by the final follow up visit.

Conclusion

The low energy, low density nonablative 1,440‐nm fractional laser produces a mild improvement in select signs of photodamage after four treatments without any long‐term adverse effects. Lasers Surg. Med. 46:375–379, 2014. © 2014 Wiley Periodicals, Inc.