Addition of the effects of norepinephrine and acetazolamide to decrease formation of cerebrospinal fluid

In a system for ventriculocisternal perfusion of the choroid plexus, the rate of formation of new cerebrospinal fluid was measured by changes in dilution of an impermeant dye in the perfusate. Norepinephrine added to the perfusate decreased formation of cerebrospinal fluid in rats as was previously demonstrated in rabbits. The dose-response relationship for rats was determined. The formation rate was decreased 42% by 10(-3) M norepinephrine. Acetazolamide, 50 mg/kg i.v., caused a decrease of 46%. Given together, these drugs decreased formation 79%, demonstrating essentially full addition between the regulatory mechanisms involved. Addition of equal magnitude occurred when intraventricular nialamide, an inhibitor of monoamine oxidase, and i.v. acetazolamide were given together. This demonstrates addition between acetazolamide and endogenous norepinephrine (or other catecholamines present) in which metabolic breakdown is prevented by the inhibitor. The degree of reduction in cerebrospinal fluid formation seen in these experiments exceeds that reported for numerous other trials of single drugs.     

Potential sperm donors', recipients' and their partners' opinions towards the release of identifying information in Western Australia

BACKGROUND: The aim of this study was to examine Western Australian potential sperm donors' and recipients' opinions towards the release of identifying information and their intentions to disclose. METHODS: Forty-five potential sperm donors, 33 recipients and 12 partners completed an anonymous questionnaire regarding their opinions on the release of identifying information, whether a child should be told about the manner of their conception, the level of expected contact of donor with future donor offspring and the importance of anonymity in their decision to donate. RESULTS: Slightly less than one-half (48.9%) of potential donors indicated that they would still donate if their identity was revealed to future offspring. When asked whether they would consider contact with offspring, 80% responded positively, with 42% favouring one-off contact. The majority of recipients (82%) and partners (92%) were planning to inform their offspring about the manner of their conception, with 69% of recipients believing that the offspring should receive identifying information about the donor. Recipients were ambivalent about the level of contact between their offspring and the donor. CONCLUSION: These results suggest that the move to an open-identity donor system in Western Australia will benefit the majority of recipient parents who are intending to disclose; however, it also suggests a 50% decline in the number of potential sperm donors.     

Off-label use of pentazocine and the associated adverse events among pediatric surgical patients in a tertiary hospital in Northern Nigeria: a retrospective chart review

Background and aims: Pentazocine remains a widely used opioid pre-anesthetic medication and post-operative analgesic in low- and middle-income countries despite concerns. We assessed the adverse events (AEs) associated with off-label use of pentazocine in pediatric surgical patients and determined the possible risk factors associated with slow respiratory AEs.

Method: Children ≤18?years old were administered pentazocine IM/IV as a pre-anesthetic medication or post-operative analgesic. Pertinent data including total daily dose and duration of use of pentazocine and its associated AEs were obtained from patients’ case files. Risk factors associated with slow respiratory AEs were determined using logistic regression analyses.

Results: One hundred and fifty-nine patients were included with a median age of 2?years; they were mainly males (52.8%). Pentazocine was administered off-label to all patients for post-operative pain management (96.2%) or pre-anesthetic medication (3.8%). All patients experienced at least one AE with most experiencing 2–7 AEs. Rapid breathing (120; 18.7%), followed by fast pulse (101; 15.7%) and sleepiness/sedation/drowsiness (81; 12.6%) were the most common AEs. None of the demographics and clinical variables significantly predicted the risk of slow respiratory AEs.

Conclusion: Off-label use of pentazocine is common and associated with multiple AEs. Care is needed as no predictors of slow respiratory AEs were observed.     

Feasibility of using point prevalence surveys to assess antimicrobial utilisation in public hospitals in South Africa: a pilot study and implications

Objectives: There is currently a lack of data regarding antimicrobial use among public hospitals in South Africa. This is a concern given their growing use and increasing antimicrobial resistance rates in South Africa. Consequently, the objectives of this study were to firstly determine the appropriateness of point prevalence survey (PPS) data collection instruments for performing antimicrobial utilization studies among public sector hospitals in South Africa; secondly, to determine current antimicrobial utilization in a public sector hospital, and thirdly evaluate the prescribing of antimicrobials with those contained within the national Essential Medicines List and Standard Treatment Guidelines (EML/STGs). The findings will be used to guide future activities in South Africa.

Methods: A PPS was conducted in Dr George Mukhari Academic Hospital. For each in-patient ward, all patients’ files were completely surveyed on a single day. The number of patients who were on antimicrobials served as the numerator and the denominator comprised the total number of patients in the ward.

Results: 39 wards and 512 patient files were surveyed. The overall prevalence of antimicrobial use was 37.7%, highest in the ICUs. Beta lactamase inhibitors and antimicrobials for tuberculosis were the most prevalent antimicrobials. More than two thirds (83%) of antimicrobial treatment was modified following culture sensitivity test results when requested, and 98% of antimicrobials prescribed were contained within the current EML/STGs. In 10.8% of occasions, antimicrobials appear to have been prescribed other than for treatment, i.e. no systemic infection. There were concerns though with the lack of IV to oral switching.

Conclusion: The PPS method offers a standardized tool that can be used to identify targets for quality improvement. However, there were concerns with the time taken to conduct PPS studies, which is an issue in resource limited settings. This is being addressed alongside concerns with the lack of IV to oral switching.     

Membranous glomerulonephritis induced in the pig by antibody to angiotensin-converting enzyme: considerations on its relevance to the pathogenesis of human idiopathic membranous glomerulonephritis.

In the course of studies on the humoral consequences of swine to primate xenotransplantation, the investigators induced formation of glomerular subepithelial immune deposits and tubular lesions in pigs injected with heterologous antibody to angiotensin-converting enzyme. This study describes the morphology of the lesions, discusses their mechanism, explains their relevance for understanding the pathogenesis of human idiopathic membranous glomerulonephritis, and proposes future directions for investigations.     

The 'wise list'- a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm

The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.     

Vitamin D resistance and colon cancer prevention

Observational studies have been largely consistent in showing an inverse association between vitamin D and an individual's risk of developing colorectal cancer. Vitamin D protection is further supported by a range of preclinical colon cancer models, including carcinogen, genetic and dietary models. A large number of mechanistic studies in both humans and rodents point to vitamin D preventing cancer by regulating cell proliferation. Counterbalancing this mostly positive data are the results of human intervention studies in which supplemental vitamin D was found to be ineffective for reducing colon cancer risk. One explanation for these discrepancies is the timing of vitamin D intervention. It is possible that colon lesions may progress to a stage where they become unresponsive to vitamin D. Such a somatic loss in vitamin D responsiveness bears the hallmarks of an epigenetic change. Here, we review data supporting the chemopreventive effectiveness of vitamin D and discuss how gene silencing and other molecular changes somatically acquired during colon cancer development may limit the protection that may otherwise be afforded by vitamin D via dietary intervention. Finally, we discuss how understanding the mechanisms by which vitamin D protection is lost might be used to devise strategies to enhance its chemopreventive actions.