A survey of attitudes towards paediatric vaccinations amongst Canadian naturopathic students

Previous studies have suggested that providers of alternative medicine may harbour anti-vaccination attitudes and that these attitudes may develop at an early stage in their careers. We further explored this question by conducting a survey to determine the attitudes of students of naturopathic medicine, a growing alternative medicine discipline, towards recommended paediatric vaccines. We sampled all 4 years of students at the Canadian College of Naturopathic Medicine (CCNM) and obtained a response rate of 59.4% (312 of 525). We found that only 12.8% (40 of 312) of the respondents would advise full vaccination; however, 74.4% (232 of 312) of the respondents would advise partial vaccination. Importantly, both willingness to advise full vaccination and trust in public health and conventional medicine decreased in students in the later years of the programme. Our findings suggest that public health and conventional medical supporters of vaccination need to identify mechanisms for engaging in discussion with this population of complementary/alternative medical professionals at an early stage in their careers.     

Polyacetal-diethylstilboestrol: a polymeric drug designed for pH-triggered activation

Those polymer anticancer-drug conjugates currently undergoing clinical evaluation have a tripartite structure; a water-soluble polymer, an anticancer agent and a pendant linker. To simplify the construct it would be attractive to develop anticancer polymer therapeutics that contain the bioactive agent as an integral part of the polymer backbone. The aim of this study was to utilise the reaction between a divinyl ethers and diols, to synthesise polyacetals incorporating a drug with bis-hydroxyl functionality into the polymer backbone. Degradation of the polymer backbone in the acidic environment of the lysosome or the extracellular fluid of some tumours would then trigger drug release eliminating the need for a biodegradable linker. A tert-polymerisation approach was used to incorporate non-steroidal oestrogen diethylstilboestrol (DES) into the mainchain of water-soluble polyacetals synthesised using as co-monomer PEG of Mw 2900 or 3400 g/mol. When PEG2900 was used the resultant polymer had a Mw of 18,900 g/mol, a Mw/Mn of 1.9 and a DES loading 4.3 wt.%. With PEG3400 the polymer Mw was 43,000 g/mol, Mw/Mn=1.8 and it had a DES loading 4.7 wt.%. 1H-NMR confirmed the presence of two distinct sets of acetal peaks, which correspond to the two possible mainchain acetals; from PEG at 1.25-1.3(d) and 4.7-4.8(q) ppm and from DES at 1.55-1.6(d) and 5.4-5.5(q) ppm. These were consistent with the acetal signals observed for the non-water-soluble co-polymer DES: tri(ethylene glycol) divinyl ether (TEGDVE) (1 : 2, Mw=6859 g/mol, Mw/Mn=1.3). When evaluated in vitro, the DES-polyacetal displayed greater cytotoxicity than DES against human and murine tumour cell lines (IC50=48 and 420 microg/ml against MCF-7 human breast cancer cells and IC50=97 and 560 microg/ml against B16F10 murine melanoma cells, respectively). These polymers showed no significant haemolysis at concentrations up to 20 mg/ml confirming suitability for further in vivo evaluation. An enhanced rate of hydrolytic degradation of the polymer backbone was seen at pH 5.5, (65% trans-DES released in 96 h), compared to pH 7.4 (4% trans-DES released in 96 h). These bioresponsive DES-polyacetals tert-polymers are the first water-soluble anticancer polymeric drugs designed for acidic pH-triggered release of a drug incorporated into the polymer mainchain. Their in vitro characteristics suggest further in vivo evaluation is warranted.     

Practical aspects of sperm banking for cancer patients

Semen storage is now routinely offered to men of reproductive age who are diagnosed with malignant disease and who require surgical or chemotherapeutic treatments that have a significant risk of leaving them sterile or subfertile. There is a perception by the public at large and professionals in the field that this is a routine and simple process. Yet, semen storage for such men requires a number of unique skills from a multidisciplinary team of oncologists, nurses, counsellors and scientists (andrologists or embryologists) in order to provide a quality service to the patient. All too often it is seen as 'just another branch' of assisted conception treatment but there are sufficient unique issues for it to be considered a specialty in its own right. In the absence of professional guidelines to outline 'best practice', the British Andrology Society invited interested parties to attend a one-day workshop. This was designed as an interactive workshop for all those involved in the process of semen storage, be they clinicians, nurses, counsellors and scientific staff from either the disciplines of reproductive medicine or oncology. It was intended to examine the process of semen storage for such patients from the point of initial diagnosis, through the process of banking semen samples, to the point at which they are either used in treatment or are discarded. The programme was designed to promote maximum interaction between the speakers and the audience and between those from different specialties and disciplines so that they may learn from each other, developing and improving the service that is provided to these men.     

The apoptotic profile of human cumulus cells changes with patient age and after exposure to sperm but not in relation to oocyte maturity

OBJECTIVE: To determine the expression of apoptosis-associated molecules on cumulus cells removed from individual oocytes of different maturity, inseminated oocytes and to investigate the possibility of an age-dependent expression. DESIGN: Analysis of apoptosis in cumulus cells isolated from oocytes of different stages of maturity. SETTING: Assisted reproductive technology program of the Birmingham Women's Hospital, Birmingham, UK. PATIENT(S): Patients undergoing intracytoplasmic sperm injection or IVF cycles. MAIN OUTCOME MEASURE(S): Percentage of positive cumulus cells when assessed for nuclear DNA damage using the terminal deoxyuridine nucleotide end-labeling assay or stained with antibodies [Fas, Fas ligand, the antiapoptotic protein Bcl-xl, and the RNA-binding protein (TIAR)]. RESULT(S): Cumulus cells collected from mature oocytes showed no significant difference in the percentage of apoptotic markers compared to those recovered from immature oocytes, whereas those from patients >/=38 years differed significantly. When cumulus cells were exposed to sperm the levels of apoptotic markers altered significantly from those not exposed to sperm. CONCLUSION(S): The results show that the cumulus cells of human oocytes are equipped with a mechanism to undergo apoptosis and that patient age and the exposure of cumulus cells to sperm can alter their profiles of apoptotic markers.     

Ventricular rate stabilization for the prevention of pause dependent ventricular tachyarrhythmias: results from a prospective study in 309 ICD recipients

Reviews of stored electrograms from ICDs revealed a 5-30% incidence of short-long-short intervals preceding the onset of recurrent ventricular tachyarrhythmias. Rate stabilization by dedicated antibradycardia pacing algorithms has, therefore, been suggested to prevent onset of pause dependent tachyarrhythmias. However, the clinical efficacy of this approach has not been studied systematically. In a prospective multicenter crossover study, patients were randomized to activation or deactivation of an implemented ventricular rate stabilization algorithm (VRS) after first implant of a dual chamber ICD. After 3 months, all patients were crossed over to the alternate programming. The rate of appropriate spontaneous VA episodes was compared between VRS On and VRS Off. Stored electrograms were reviewed for evaluation of the mode of onset of tachyarrhythmias. Overall efficacy analysis was based on 309 patients enrolled in the study. Forty percent (124/309) of the patients experienced 4,973 VA episodes. Based on an intention-to-treat analysis, VRS Off and On arrhythmia incidence was 10.2 and 6.6 normalized to 3 months, respectively (risk reduction 35%; P = 0.18) On an on-treatment basis, a reduction from 9.0 episodes to 8.1 episodes (10% risk reduction, P = 0.24) was seen. In an extended Cox model adjusting for confounding variables, the relative risk for recurrent episodes was 0.92 during VRS On compared to Off (95% CI: 0.58-1.48; P = 0.74). During VRS Off, pause dependent onset was documented in only 36 (8%) of 427 visually analyzed episodes. There was no significant reduction in the incidence of recurrent ventricular tachyarrhythmias with VRS On compared to the Off programming in this prospective study.     

Linearity of canal-otolith interaction during eccentric rotation in humans

During natural behavior, the head may simultaneously undergo rotation, transduced by the semicircular canals, and translation, transduced by the otolith organs. It has been demonstrated in monkey that the vestibulo-ocular reflexes (VORs) elicited by both endorgans (i.e., the angular and linear VORs, or AVOR and LVOR) sum linearly during combined rotation and translation, but this finding has proven more elusive in humans. To investigate the combined AVOR/LVOR response, six human subjects underwent yaw eccentric rotation at 3 Hz in darkness while displaced from the axis of rotation. Responses to on-center yaw rotation (AVOR alone) and interaural translation (LVOR alone) were also recorded. During eccentric rotation with the subject facing away from the axis of rotation (i.e., nose out), in which a yaw to the right occurs simultaneously with a translation to the right (i.e., translation in phase with rotation), the AVOR and LVOR acted synergistically. Responses were always out of phase with rotation, and became larger in magnitude as vergence increased. For nose-in eccentric rotation, during which translation is out of phase with rotation, the LVOR acted antagonistically to the AVOR. During near viewing, the LVOR often dominated the overall response when eccentricity was sufficiently large, producing eye movements that were in phase with the rotational stimuli. As vergence decreased, the LVOR influence diminished, eventually resulting in responses that were out of phase with rotation at lowest vergence. When the response to pure yaw rotation was vectorially removed from the responses to eccentric rotation, the results proved statistically indistinguishable from the LVOR recorded during interaural translation, suggesting that the ocular response to combined angular and linear motion reflects the linear combination of the AVOR and LVOR.     

Physical activity and risk of renal cell carcinoma

The role of physical activity in the development of renal cell carcinoma was examined using a population-based case-control study conducted in the province of Ontario. Physical activity was examined in several ways, including by intensity and during various life periods. Frequency-matching by 5-year age groups and sex produced sets of 486 females (133 cases and 353 controls) and 447 males (172 cases, 275 controls). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). After adjusting for age, body mass index and smoking, women who performed relatively high amounts of recent recreational activity (OR = 0.41, 95% CI 0.21-0.82 for the highest vs. lowest quartile of activity, 2 years ago), as well as strenuous recreational activity (OR = 0.40, 95% CI 0.22-0.75), had a reduced risk of developing the disease. In general, moderate recreational activity did not appear to be associated with risk in females. In males, a relatively high frequency of total and moderate recreational activity was associated with reduced risk (total, OR = 0.49, 95% CI 0.27-0.87; moderate, OR = 0.49, 95% CI 0.27-0.89), especially during the teen years. Recreational activity during one's 30s was not associated with cancer risk. There was also no association between occupational activity and cancer risk in females or males. The results of our study, in general, suggest that physical activity may be associated with a decreased risk of developing renal cell carcinoma.     

Dose-response relationship and reproducibility of urinary salbutamol excretion during the first 30 min after an inhalation

AIMS: To determine the reproducibility and dose-response relationship for urinary salbutamol excretion post inhalation. METHODS: Fifteen volunteers inhaled either one, two, three, four or five doses of 100 micro g salbutamol on separate days and then seven of these also repeated each of the one, three and five doses on five occasions. After each study dose urine was collected 30 min post inhalation. RESULTS: The mean (SD) 30 min urinary salbutamol after one, two, three, four and five doses was 2.61 (1.0.), 5.47 (1.59), 8.68 (2.73), 12.34 (3.96) and 15.99 (4.50) micro g, respectively. Statistical analysis revealed a linear relationship (P < 0.001). Mean (SD) coefficient of variation after one, three and five doses was 10.5 (3.6), 10.1 (2.7) and 9.4 (2.3)%. CONCLUSIONS: The 30 min salbutamol urinary excretion post inhalation pharmacokinetic method, to compare inhaled products, is linear with inhaled dose and reproducible.