The safety and efficacy of neuromodulation using percutaneous electrical nerve stimulation for the management of trigeminal-mediated headshaking in 168 horses.

BACKGROUND: Early results from the use of neuromodulation by percutaneous electrical nerve stimulation for the management of trigeminal-mediated headshaking in horses were promising but lacked sufficient case numbers and long-term follow-up. The neuromodulatory procedure has since been established as EquiPENS™. OBJECTIVES: The aim of this study was to report long-term results from a larger number of cases and to investigate for predictors of outcome. STUDY DESIGN: Prospective case series using international, multi-centre data. METHODS: Eligible cases were horses with a veterinary diagnosis of trigeminal-mediated headshaking, which received EquiPENS™ neuromodulation at trained centres between August 2013 and November 2017. The standard protocol was an initial three-procedure course, with additional procedures should a horse go into remission but then relapse. Data collected included signalment, history, diagnostic tests performed, details of any complications, whether horses had gone into remission and the length of remission. RESULTS: Results were obtained from 168 horses, with 530 procedures. The complication rate was 8.8% of procedures. In all but one case, complications were mild and transient, without self-trauma. Remission of headshaking following the initial course occurred in 53% (72/136) of horses. Median length of time recorded in remission was 9.5 weeks (range 2 days to 156 weeks ongoing). Where signs recurred, most horses went back into remission following additional procedures, usually for longer than from the previous procedure. No predictors for outcome were determined. MAIN LIMITATIONS: No placebo or control group, owner-assessed results. CONCLUSIONS: EquiPENS™ neuromodulation can be an effective and safe treatment for the management of trigeminal-mediated headshaking in some horses. An increased understanding of neuromodulation could help optimise the technique. Advances in treatment for trigeminal-mediated headshaking will remain limited until there is a greater understanding of the aetiopathogenesis of the condition.

The use of cinacalcet in pregnancy to treat a complex case of parathyroid carcinoma.

UNLABELLED: We present the case of a patient with metastatic parathyroid carcinoma whose hypercalcaemia was medically managed through two pregnancies. The diagnosis was made when the patient presented with chronic knee pain and radiological findings consistent with a brown tumour, at the age of 30. Her corrected calcium and parathyroid hormone (PTH) levels were significantly elevated. Following localisation studies, a right parathyroidectomy was performed with histology revealing parathyroid carcinoma, adherent to thyroid tissue. Aged 33, following biochemical recurrence of disease, the patient underwent a second operation. A subsequent CT and FDG-PET revealed bibasal pulmonary metastases. Aged 35, the patient was referred to our unit for treatment of persistent hypercalcaemia. The focus of treatment at this time was debulking metastatic disease using radiofrequency ablation. Despite advice to the contrary, the patient conceived twice while taking cinacalcet. Even though there are limited available data regarding the use of cinacalcet in pregnancy, both pregnancies continued to term with the delivery of healthy infants, using intensive medical management for persistent hypercalcaemia. LEARNING POINTS: Parathyroid carcinoma is a rare cause of primary hyperparathyroidism.Hypercalcaemia during pregnancy can result in significant complications for both the mother and the foetus.The use of high-dose cinacalcet in pregnancy has been shown, in this case, to aid in the management of resistant hypercalcaemia without teratogenicity.

Naturopaths and Western herbalists' attitudes to evidence, regulation, information sources and knowledge about popular complementary medicines.

BACKGROUND: The practice of naturopathy and Western herbal medicine (WHM) was built on traditional evidence but may be undergoing change with the advent of scientific evidence. The aims of this research were to provide a better understanding of practitioners' attitudes towards evidence, information sources, professional regulation and their knowledge about the evidence of commonly used complementary medicines (CMs). METHOD: Naturopaths and WHM practitioners were invited to participate in an anonymous, self-administered, on-line survey. Participants were recruited using the mailing lists and websites of CM manufacturers and professional associations. RESULTS: Four hundred and seventy nine practitioners participated; 95% currently in practice. The majority (99%) thought well documented traditional evidence was essential or important, 97% patient reports and feedback, 97% personal experience, 94% controlled randomised trials and 89% published case reports. Significantly more recent graduates (less than 5 years) rated randomised trials as essential compared to others. Most (82%) respondents want information sources containing both traditional and scientific evidence. They currently use several resources; 74% CM textbooks, 67% conferences/seminars, 57% CM journals, 48% databases and 40% manufacturers' information. The mean knowledge score was 61.5% with no significant differences between respondents with diploma or degree level education or by graduating year. Eighty-five percent of practitioners strongly agreed or agreed that practitioners should be formally registered to safeguard the public, 8% were unsure and 8% disagreed or strongly disagreed. CONCLUSION: Naturopaths and WHM practitioners accept the importance of scientific evidence whilst maintaining the importance and use of traditional evidence. The majority are in favour of professional registration.

Natural alternatives to in-feed antibiotics in pig production: can immunomodulators play a role?

As a result of the European ban of in-feed growth-promoting antibiotics, new strategies are being developed to increase the resistance to disease in farm animals. In pig production, this is of particular importance during the weaning transition when piglets are subjected to major stressful events, making them highly sensitive to digestive disorders. At this time, the development of both innate and adaptive immunity at the mucosal surface is critical in preventing the potential harmful effects of intestinal pathogenic agents. Strategies aiming at stimulating natural host defences through the use of substances able to modulate immune functions have gained increasing interest in animal research, and different bioactive components a priori sharing those properties have been the subject of in vivo nutritional investigations in pig. Among these, yeast derivates (ß-glucans and mannans) are able to interact with immune cells, particularly phagocytic cells. However, studies where they have been fed to pigs have shown inconsistent results, suggesting that their ability to target the sensitive immune cells through the oral route is questionable. The plant extracts, which would benefit from a positive image in the public opinion, have also been tested. However, due to a lack of data on the bioactive components of particular plants and the large diversity of species, it has proved difficult to prepare extracts of equivalent potency and thus, the literature on their influence on pig immunity remains inconclusive. In considering piglet immunity and health benefits, the most promising results to date have been obtained with spray-dried animal plasma, whose positive effects would be provided by specific antibodies and non-specific competition of some plasma components with bacteria for intestinal receptors. The major positive effect of spray-dried animal plasma is in reducing the infiltration of gut-associated lymphoid tissue by immune cells, which is likely to be the result of a decreased colonisation by potentially harmful bacteria. This review also highlights the limitations of some of the published in vivo studies on the immunomodulatory activity of certain feed additives. Among those, the lack of standardisation of extracts and the heterogeneity of piglet-rearing conditions (e.g. exposure to pathogens) are likely the most limiting.

Uncertainty analysis of doses from inhalation of depleted uranium.

Measurements of uranium excreted in urine have been widely used to monitor possible exposures to depleted uranium (DU). This paper describes a comprehensive probabilistic uncertainty analysis of doses determined retrospectively from measurements of DU in urine. Parametric uncertainties in the International Commission on Radiological Protection (ICRP) Human Respiratory Tract Model (HRTM) and ICRP systemic model for uranium were considered in the analysis, together with uncertainties in an alternative model for particle removal from the lungs. Probability distributions were assigned to HRTM parameters based on uncertainties documented in ICRP Publication 66 and elsewhere, including the Capstone study of aerosols produced after DU penetrator impacts. Uncertainties in the uranium systemic model were restricted to transfer rates having the greatest effect on urinary excretion, and hence retrospective dose assessments, over the measurement times considered (10-10(4) d). The overall uncertainty on dose (the ratio of the upper and lower quantiles, q0.975/q0.025) was estimated to be about a factor of 50 at 10 days after intake and about a factor of 10 at 10(3)-10(4) d. The dose to the lung dominated the committed effective dose, with the lung absorption parameters, particularly the slow dissolution rate, ss, dominating the overall uncertainty. The median dose determined from a measurement of 1 ng DU, collected in urine in a 24-h period, varied from 0.1 microSv at 10 d to about 1 mSv at 10(4) d. Despite the large uncertainties, the upper q0.975 quantile for the assessed dose was below 1 mSv up to 5,000 d.

Comparison of the potential for developmental toxicity of prenatal exposure to two dietary chromium supplements, chromium picolinate and [Cr3O(O2CCH2CH3)(6(H2O)3]+, in mice.

BACKGROUND: Chromium(III) is generally thought to be an essential trace element that allows for proper glucose metabolism. However, chromium(III) picolinate, Cr(pic)3, a popular dietary supplement form of chromium, has been shown to be capable of generating hydroxyl radicals and oxidative DNA damage in rats. The cation [Cr3O(O2CCH2CH3)(6(H2O)3]+, Cr3, has been studied as an alternative supplemental source of chromium. It has been shown to increase insulin sensitivity and lower glycated hemoglobin levels in rats, making it attractive as a potential therapeutic treatment for gestational diabetes. To date, no studies have been published regarding the safety of Cr3 supplementation to a developing fetus. METHODS: From gestation days (GD) 6-17, mated CD-1 female mice were fed diets delivering either 25 mg Cr/kg/day as Cr(pic)(3), 3.3 or 26 mg Cr/kg/day as Cr3, or the diet only to determine if Cr3 could cause developmental toxicity. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS: No signs of maternal toxicity were observed. No decrease in fetal weight or significantly increased incidence of skeletal defects was observed in the Cr3 or Cr(pic)3 exposed fetuses compared to the controls. CONCLUSION: Maternal exposure to either Cr(pic)3 or Cr3 at the dosages employed did not appear to cause deleterious effects to the developing offspring in mice.

Exposure of pregnant mice to chromium picolinate results in skeletal defects in their offspring.

BACKGROUND: Chromium(III) picolinate, [Cr(pic)(3)], is a widely marketed dietary supplement. However, Cr(pic)(3) has been associated with oxidative damage to DNA in rats and mutations and DNA fragmentation in cell cultures. In isolated case reports, Cr(pic)(3) supplementation has been said to cause adverse effects, such as anemia, renal failure, liver dysfunction, and neuronal impairment. To date, no studies have been published regarding the safety of chromium picolinate supplementation to a developing fetus, although Cr(pic)(3) has been recommended for pregnant women who are diagnosed with gestational diabetes. METHODS: From gestation days (GD) 6-17, pregnant CD-1 mice were fed diets containing either 200 mg/kg Cr(pic)(3), 200 mg/kg CrCl(3), 174 mg/kg picolinic acid, or the diet only to determine if Cr(pic)(3), CrCl(3), or picolinic acid could cause developmental toxicity. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS: The incidence of bifurcated cervical arches was significantly increased in fetuses from the Cr(pic)(3) group as compared to the diet-only group. Fetuses in the picolinic acid-treated group had an incidence double that of the control group; however, this increase was not statistically significant. Fetuses in the CrCl(3) group did not differ from the controls in any variable examined. No maternal toxicity was observed in any of the treatment groups. CONCLUSIONS: High maternal oral exposures to chromium picolinate can cause morphological defects in developing offspring of mice.

Treatment and outcome of 104 hospitalized patients with legionnaires' disease.

BACKGROUND: Large outbreaks of Legionella pneumonia are rare, but when they occur provide an opportunity to assess predictors of mortality and efficacy of drug therapy. Although erythromycin has been the treatment of choice for many years, newer antimicrobials with increased activity against Legionella are available. A large outbreak of legionnaires' disease associated with the Melbourne Aquarium occurred in April 2000. AIM: To describe the patterns and impact of Legionella therapy, and predictors of outcome in a large group of hospitalized patients with legionnaires' disease. METHODS: A 6-month retrospective audit of hospitalized patients with proven legionnaires' disease around the time of the Melbourne Aquarium outbreak was conducted. Statistical analysis was performed using SAS version 8.0 (SAS Institute Inc., NC, USA). RESULTS: Data were obtained on 104 patients (71 aquarium related, 33 not related). There were six deaths (mortality rate 5.8%), three of which were attributable directly to progressive legionnaires' disease. The major predictors of death were pre-existing cardiac failure (P = 0.0035) and renal disease (P = 0.026). Erythro-mycin is still the most commonly used antibiotic (80% received i.v. erythromycin) with clinicians prescribing more than one active Legionella drug in the majority of cases (76%). Choice of initial antibiotic therapy did not statistically affect outcome as measured by death, length of hospital stay or time to defervescence, although there was a trend towards improved survival with i.v. erythromycin (P = 0.063). Intravenous erythromycin was associated with a 19% rate of phlebitis, whereas side-effects from other antibiotics were uncommon. CONCLUSION: The most commonly used Legionella therapy in Australia remains erythromycin. This continues to be an effective agent, however, side-effects are common.

Comparison of genome screens for two independent cohorts provides replication of suggestive linkage of bone mineral density to 3p21 and 1p36.

Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Studies of BMD in families and twins have shown that this trait is under strong genetic control. To identify regions of the genome that contain quantitative trait loci (QTL) for BMD, we performed independent genomewide screens, using two complementary study designs. We analyzed unselected nonidentical twin pairs (1,094 pedigrees) and highly selected, extremely discordant or concordant (EDAC) sib pairs (254 pedigrees). Nonparametric multipoint linkage (NPL) analyses were undertaken for lumbar spine and total-hip BMD in both cohorts and for whole-body BMD in the unselected twin pairs. The maximum evidence of linkage in the unselected twins (spine BMD, LOD 2.7) and the EDAC pedigrees (spine BMD, LOD 2.1) was observed at chromosome 3p21 (76 cM and 69 cM, respectively). These combined data indicate the presence, in this region, of a gene that regulates BMD. Furthermore, evidence of linkage in the twin cohort (whole-body BMD; LOD 2.4) at chromosome 1p36 (17 cM) supports previous findings of suggestive linkage to BMD in the region. Weaker evidence of linkage (LOD 1.0-2.3) in either cohort, but not both, indicates the locality of additional QTLs. These studies validate the use, in linkage analysis, of large cohorts of unselected twins phenotyped for multiple traits, and they highlight the importance of conducting genome scans in replicate populations as a prelude to positional cloning and gene discovery.

Determination of the physical and chemical properties, biokinetics, and dose coefficients of uranium compounds handled during nuclear fuel fabrication in France.

The introduction of new ICRP recommendations, especially the new Human Respiratory Tract Model (HRTM) in ICRP Publication 66 led us to focus on some specific parameters related to industrial uranium aerosols collected between 1990 and 1999 at French nuclear fuel fabrication facilities operated by COGEMA, FBFC, and the CEA. Among these parameters, the activity median aerodynamic diameter (AMAD), specific surface area (SSA), and parameters describing absorption to blood f(r), s(r) and s(s) defined in ICRP Publication 66 were identified as the most relevant influencing dose assessment. This study reviewed the data for 25 pure and impure uranium compounds. The average value of AMAD obtained was 5.7 microm (range 1.1-8.5 microm), which strongly supports the choice of 5 microm as the default value of AMAD for occupational exposures. The SSA varied between 0.4 and 18.3 m2 g(-1). For most materials, values of the absorption parameters f(r), s(r), and s(s) derived from the in vitro experiments were generally consistent with those derived from the in vivo experiments. Using average values for each pure compound allowed us to classify UO2 and U3O8 as Type S, mixed oxides, UF4, UO3 and ADU as Type M, and UO4 as Type F based on the ICRP Publication 71 criteria. Dose coefficients were also calculated for each pure compound, and average values for each type of pure compound were compared with those derived using default values. Finally, the lung retention kinetics and urinary excretion rates for inhaled U03 were compared using material-specific and default absorption parameters, in order to give a practical example of the application of this study.

Review of drug-related legislation in the Republic of Fiji Islands.

The development of new drug-related legislation for Fiji commenced in 1996 when two draft Bills, namely the Pharmacy Bill and the Poisons and Therapeutics Goods Bill, which had been based on World Health Organisation (WHO) drafts, were prepared and circulated for comment. During a six-week period in 1998, the consultant analysed comments on the drafts, co-ordinated stakeholder meetings, and provided workshops for the identified major stakeholders. Implementation of the outcomes from the consultancy has been delayed by first, a democratic change in Government and the resulting establishment of new priorities, secondly by a coup with subsequent interim administration, and thirdly by return to democracy with priority reassessment by the new Government.

In vivo inhibition of renal 11beta-hydroxysteroid dehydrogenase in the rat stimulates collecting duct sodium reabsorption.

In order to test the proposal that the aldosterone specificity of mineralocorticoid receptors in the collecting duct depends on inactivation of glucocorticoids by the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD), we have assessed the effect of pharmacological inhibition of 11beta-HSD on collecting duct Na+ reabsorption in vivo. Adrenalectomized rats (n=14) were infused intravenously with high-dose corticosterone, and late-distal tubules were perfused orthogradely with artificial tubular fluid containing [14C]inulin and 22Na; urinary recoveries of the radioisotopes were monitored. Half of the rats received intravenous carbenoxolone to inhibit renal 11beta-HSD activity. The urinary recovery of [14C]inulin was complete in both groups of animals (101+/-2% versus 101+/-3%), but the recovery of 22Na was lower in carbenoxolone-treated rats (34+/-5%) than in the corticosterone-alone group (54+/-4%, P<0.01). These data, which provide the first demonstration of enhanced Na+ reabsorption in the distal nephron during inhibition of renal 11beta-HSD in vivo, strongly support the proposal that 11beta-HSD normally prevents endogenous glucocorticoid from exerting mineralocorticoid-like effects.

Reliable use of green fluorescent protein in fluorescent pseudomonads.

When fluorescent pseudomonads are cultured on standard solid media under iron limiting conditions, they produce fluorescent, pigmented iron collating agents (siderophores). Siderophores can be readily identified by strong fluorescence seen under UV/blue light. The application of the eukaryotic green fluorescent protein (GFP) as a bacterial marker in microbial ecology is increasingly being used, particularly as it is a powerful method for non-destructive monitoring in situ. As gfp expressing bacteria have to be detected under UV/blue light, the fluorescence of siderophore-producing Pseudomonas spp. masks normal levels of GFP fluorescence when colonies are viewed on standard bacterial agar. Here, we describe a simple but effective way of identifying gfp-expressing Pseudomonas fluorescens using media supplemented with 0.45 mM FeSO(4).7H(2)O. This is of relevance for the screening of insertion libraries and in the application of GFP transposons as promoter probes.

The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of Australian women. A randomised controlled trial.

OBJECTIVE: To evaluate the effects of a defined formula of Chinese medicinal herbs (CMH) on menopausal symptoms. DESIGN: A double-blind randomised placebo-controlled trial. METHODS: Between August 1998 and April 1999, 55 postmenopausal Australian women recruited from an urban population completed 12 weeks of intervention with either a defined formula of CMH (n = 28) or placebo (n = 27) taken twice daily as a beverage. MAIN OUTCOME MEASURES: The primary end-point was change in frequency of vasomotor events (hot flushes and night sweats). The secondary end-points were changes in score for the domains measured in the Menopause Specific Quality of Life (MENQOL) Questionnaire. RESULTS: There was a reduction in average weekly frequency of vasomotor events with CMH (-15%; 95% CI, -31% to +1%) and with placebo (-31%; 95% CI, -42% to -21%). The difference between groups favoured the use of placebo; however, this was not significant (P=0.09). Although significant reductions in scores for the various domains of the MENQOL Questionnaire were observed for both CMH and placebo, there were no significant differences between the two treatment groups for any domain. There was evidence for effect modification by previous use of natural therapies for the vasomotor, physical and sexual domains of the MENQOL Questionnaire: women with no prior use of natural therapies for their menopausal symptoms responded to therapy, whereas prior users did not. CONCLUSIONS: The defined formula of CMH was no more effective than placebo in reducing vasomotor episodes in Australian postmenopausal women, or in improving any of the four symptom domains in the MENQOL Questionnaire. Three of the MENQOL Questionnaire domains were modified by prior use of natural therapies. This finding has implications for future studies.

A clinical trial of the Buteyko Breathing Technique in asthma as taught by a video.

The Buteyko Breathing Technique (BBT) is promoted as a drug-free asthma therapy. It is based on the premise that raising blood PaCO2 through hypoventilation can treat asthma. Our study was designed to examine whether the Buteyko Breathing Technique, as taught by a video, is an efficacious asthma therapy. Thirty-six adult subjects with mild to moderate asthma were randomized to receive either a BBT or placebo video to watch at home twice per day for 4 weeks. Asthma-related quality of life, peak expiratory flow (PEF), symptoms, and asthma medication intake were assessed both before and after intervention. Our results demonstrated a significant improvement in quality of life among those assigned to the BBT compared with placebo (p = 0.043), as well as a significant reduction in inhaled bronchodilator intake (p = 0.008). We conclude that the BBT may be effective in improving the quality of life and reducing the intake of inhaled reliever medication in patients with asthma. These results warrant further investigation.

Transgenic avidin maize is resistant to storage insect pests.

Avidin is a glycoprotein found in chicken egg white, that sequesters the vitamin biotin. Here we show that when present in maize at levels of > or =100 p.p.m., avidin is toxic to and prevents development of insects that damage grains during storage. Insect toxicity is caused by a biotin deficiency, as shown by prevention of toxicity with biotin supplementation. The avidin maize is not, however, toxic to mice when administered as the sole component of their diet for 21 days. These dates suggest that avidin expression in food or feed grain crops can be used as a biopesticide against a spectrum of stored-produce insect pests.

Legal issues relating to telemedicine in Canada's publicly funded health-care system.

The advent of telemedicine poses new legal challenges for Canada's health-care system. Although telemedicine increases access, it does not fit easily into Canada's traditional one-tier approach to health-care. Cross-border telemedicine services may inadvertently contribute to a two-tier system. The current legal system will have to be adapted to accommodate changes instigated by cross-border telemedicine.

Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial.

OBJECTIVE: To assess neurological sequelae in patients with all grades of carbon monoxide (CO) poisoning after treatment with hyperbaric oxygen (HBO) and normobaric oxygen (NBO). DESIGN: Randomised controlled double-blind trial, including an extended series of neuropsychological tests and sham treatments in a multiplace hyperbaric chamber for patients treated with NBO. SETTING: The multiplace hyperbaric chamber at the Alfred Hospital, a university-attached quarternary referral centre in Melbourne providing the only hyperbaric service in the State of Victoria. PATIENTS: All patients referred with CO poisoning between 1 September 1993 and 30 December 1995, irrespective of severity of poisoning. Pregnant women, children, burns victims and those refusing consent were excluded. INTERVENTION: Daily 100-minute treatments with 100% oxygen in a hyperbaric chamber--60 minutes at 2.8 atmospheres absolute for the HBO group and at 1.0 atmosphere absolute for the NBO group--for three days (or for six days for patients who were clinically abnormal or had poor neuropsychological outcome after three treatments). Both groups received continuous high flow oxygen between treatments. MAIN OUTCOME MEASURES: Neuropsychological performance at completion of treatment, and at one month where possible. RESULTS: More patients in the HBO group required additional treatments (28% v. 15%, P = 0.01 for all patients; 35% v. 13%, P = 0.001 for severely poisoned patients). HBO patients had a worse outcome in the learning test at completion of treatment (P = 0.01 for all patients; P = 0.005 for severely poisoned patients) and a greater number of abnormal test results at completion of treatment (P = 0.02 for all patients; P = 0.008 for severely poisoned patients). A greater percentage of severely poisoned patients in the HBO group had a poor outcome at completion of treatment (P = 0.03). Delayed neurological sequelae were restricted to HBO patients (P = 0.03). No outcome measure was worse in the NBO group. CONCLUSION: In this trial, in which both groups received high doses of oxygen, HBO therapy did not benefit, and may have worsened, the outcome. We cannot recommend its use in CO poisoning.