Cyprinid herpesvirus 3 as a potential biological control agent for carp (Cyprinus carpio) in Australia: susceptibility of non-target species.

Carp (Cyprinus carpio L.) is a pest species in Australian waterways, and cyprinid herpesvirus 3 (CyHV-3) is being considered as a potential biological control (biocontrol) agent. An important consideration for any such agent is its target specificity. In this study, the susceptibility to CyHV-3 of a range of non-target species (NTS) was tested. The NTS were as follows: 13 native Australian, and one introduced, fish species; a lamprey species; a crustacean; two native amphibian species (tadpole and mature stages); two native reptilian species; chickens; and laboratory mice. Animals were exposed to 100-1000 times the approximate minimum amount of CyHV-3 required to cause disease in carp by intraperitoneal and/or bath challenge, and then examined clinically each day over the course of 28 days post-challenge. There were no clinical signs, mortalities or histological evidence consistent with a viral infection in a wide taxonomic range of NTS. Furthermore, there was no molecular evidence of infection with CyHV-3, and, in particular, all RT-PCRs for viral mRNA were negative. As a consequence, the results encourage further investigation of CyHV-3 as a potential biocontrol agent that is specific for carp.

Intestinal epithelial Toll-like receptor 4 prevents metabolic syndrome by regulating interactions between microbes and intestinal epithelial cells in mice.

Little is known about the pathogenesis of metabolic syndrome, although Toll-like receptor 4 (TLR4) has been implicated. We investigated whether TLR4 in the intestinal epithelium regulates metabolic syndrome by coordinating interactions between the luminal microbiota and host genes that regulate metabolism. Mice lacking TLR4 in the intestinal epithelium (TLR4ΔIEC), but not mice lacking TLR4 in myeloid cells nor mice lacking TLR4 globally, developed metabolic syndrome; these features were not observed in TLR4ΔIEC mice given antibiotics. Metagenomic analysis of the fecal microbiota revealed differences between TLR4ΔIEC and wild-type mice, while meta-transcriptome analysis of the microbiota showed that intestinal TLR4 affected the expression of microbial genes involved in the metabolism of lipids, amino acids, and nucleotides. Genes regulated by peroxisome proliferator-activated receptors (PPARs) and the antimicrobial peptide lysozyme were significantly downregulated in TLR4ΔIEC mice, suggesting a mechanism by which intestinal TLR4 could exert its effects on the microbiota and metabolic syndrome. Supportingly, antibiotics prevented both downregulation of PPAR genes and the development of metabolic syndrome, while PPAR agonists prevented development of metabolic syndrome in TLR4ΔIEC mice. Thus, intestinal epithelial TLR4 regulates metabolic syndrome through altered host-bacterial signaling, suggesting that microbial or PPAR-based strategies might have therapeutic potential for this disease.

Intermittent medication cessation in the treatment of Tourette syndrome.

Long-term use of neuroleptic medications has been associated with many undesirable effects. Intermittent medication cessation may reduce the risk of exposure to these side effects. Six school age male Tourette Syndrome (TS) patients who were on medication for TS (haloperidol) were monitored closely over a six-month period. Four patients withdrew from haloperidol for the middle two-month period then returned to medication use. Other subjects remained on medication throughout the study. Results indicated that withdrawal from haloperidol is likely to result in an increase in TS symptoms, particularly simple motor tics, which is quite dramatic but rarely lasts more than 4 weeks. Physical symptoms of withdrawal from haloperidol include irritability, nervousness, moodiness, oppositional behaviours, stomach pains, indigestion, skin irritations, diaphoresis, visual acuity problems, oculogyria, and symptom instability. Results of psychometric tests also indicated, however, that subjects were less depressed, experienced fewer obsessive-compulsive symptoms, and were less hyperactive and socially withdrawn when they were medication free as compared to on haloperidol.

An evaluation of Tourette syndrome and medication use in Canada.

Self-report data were gathered from a national sample of over 200 Canadian Tourette Syndrome (TS) patients. Information regarding symptom severity both on and off medication was gathered along with an analysis of different medications in use, and patient ratings of effectiveness of those medications. Patients also rated their own mental health. Results indicated that approximately 60% of TS patients take some form of medication for relief from their symptoms. Of these, over 80% reported that symptoms are less severe when medicated. The most commonly prescribed medications in order of popularity are haloperidol, pimozide, clonidine and benztropine mesylate (Cogentin). Patient ratings of effectiveness of these medications places haloperidol first, pimozide second and clonidine third although all were found to be "somewhat" to "very" effective. Of those TS patients on medications, 50% rated their own mental health as good to excellent and 50% rated it as fair to poor.

Tourette syndrome and social functioning in a Canadian population.

Two hundred and ten patients with Tourette Syndrome (TS) and/or their parents completed a survey, answering questions about the frequency and disruptiveness of vocal and motor tics, behaviour problems and sleep disturbances. Respondents also rated the impact of TS symptoms on social relationships and level of personal and social functioning. Motor tics were reported to be more problematic than were vocal tics. Disruptive behavioural problems included obsessive-compulsive rituals, hyperactivity, anxiety, temper tantrums, mood swings, aggressiveness and coprolalia. Respondents also reported problems getting to sleep, bad dreams, somnambulism and enuresis. More than 40% of respondents reported problems in dating, and problems in making and keeping friends. Family members, friends and physicians were reported to be the most understanding and tolerant of TS symptoms; employers were rated as being the least understanding. More than 30% of respondents reported some problems in coping, but more than 50% of respondents also rated their mental health as good or excellent.

Tourette syndrome and educational problems in Canada.

A comprehensive survey of known Tourette Syndrome patients was conducted on a national basis in Canada. In addition to in-depth historical background information, symptomatology, geography and demographics, data were collected regarding educational issues. Approximately 70% of the sample were receiving some sort of education. The most commonly cited educational problems were with concentration, paying attention, and performance on time-limited tasks. In almost all cases the school had been informed of the Tourette Syndrome diagnosis, but in 78% of respondents the school personnel were rated as not at all knowledgeable regarding TS. Despite problems, 66% of TS patients reported being generally satisfied with the education being received. Patients made recommendations regarding how educational experiences could be made better. Of these suggestions, educating educators was the most frequent recommendation.

Tourette syndrome and medical treatment in Canada.

Self-report data were gathered from a national sample of over two hundred Canadian Tourette Syndrome (TS) patients. Included was previous use of stimulant medication and prior extended use of antihistamines for allergies or sinus condition. Patients were also asked information on Tourette Syndrome-precipitated hospitalization or boarding school placement, the type of physician treating them and on a five-point scale their level of satisfaction with their medical care. Results indicate that over 20% of TS patients have used stimulant medications and 30% have used antihistamine for extended periods. Many patients have spent time in psychiatric settings and most are under the care of psychiatrist or neurologist. Approximately 40% of TS patients reported being satisfied to very satisfied with the medical care they were receiving, and 20% having mixed feelings. Few patients receiving medical care were dissatisfied with their treatment.

Tourette syndrome: impact on Canadian family functioning.

An evaluation of the impact of Tourette Syndrome on the family. Self-report data were gathered from a Canadian sample of over two hundred Tourette Syndrome patients and/or their families regarding the effects of TS on family life. Patients rated the extent to which having TS interfered with the family's day-to-day activities. Also indicated was whether marital difficulties or difficulties with alcohol or drugs arose since the Tourette diagnosis was made. Data were also gathered on the number of TS patients or other family members who sought professional counselling and the extent to which counselling was found helpful.

Electrical stimulation of the brain in treatment of chronic pain. Experience over 5 years.

Forty-eight patients underwent electrical stimulation of the brain for treatment of chronic pain between 1978 and 1983. Average pain duration prior to treatment was 4.5 years. Before selection for this procedure patients underwent pain treatment in a multidisciplinary pain center, intensive psychological and psychiatric evaluation, and assessment of pain responsiveness to intravenous administration of placebo, morphine, and naloxone. A total of 71 electrodes were placed in the 48 patients at a variety of stimulating targets, including the periaqueductal gray matter, periventricular gray matter, thalamus, and internal capsule. Seventy-two percent of patients experienced complete or partial pain relief. In addition, 59% of patients were able to discontinue narcotic usage. Twenty-five percent of patients returned to normal physical activities and another 33% showed marked improvement in functional capacity. Follow-up periods ranged from 2 to 60 months; with a mean follow-up period of 20 months. A variety of relatively minor complications occurred, but no mortality or permanent sequelae were experienced. No patient's pain was made worse as a result of electrical stimulation. Electrical stimulation of the brain offers a safe and relatively effective method for the treatment of chronic pain in appropriately selected patients, who are unresponsive to other forms of therapy.

Re-examination of the role of the Brucella melitensis HtrA stress response protease in virulence in pregnant goats.

Based on previously reported studies describing the experimental infection of pregnant goats with B. melitensis strain RWP5, we proposed that the HtrA protease plays an important role in the virulence of B. melitensis in its natural ruminant host. Subsequent studies, however, have shown that RWP5 is actually an htrA cycL double mutant. In order to definitively evaluate the role of the B. melitensis htrA in virulence, we constructed an authentic htrA mutant and examined this strain in pregnant goats. The findings of these studies indicate that the contribution of the htrA gene product to the virulence of B. melitensis in its natural host is not as great as was previously proposed.

Pathogenicity and protective activity in pregnant goats of a Brucella melitensis Deltaomp25 deletion mutant.

The Brucella melitensis mutant BM 25, which lacks the major 25 kDa outer membrane protein Omp25, has previously been found to be attenuated in the murine brucellosis model. In the present study, the capacity of the Deltaomp25 mutant to colonise and cause abortions in the caprine host was evaluated. The vaccine potential of BM 25 was also investigated in goats. Inoculation of nine pregnant goats in late gestation with the B. melitensis mutant resulted in 0/9 abortions, while the virulent parental strain, B. melitensis 16M, induced 6/6 dams to abort (P<0.001, n=6). BM 25 also colonised fewer adults (P<0.05, n=6) and kids (P<0.01, n=6) than strain 16M. The Deltaomp25 mutant was found capable of transient in vivo colonisation of non-pregnant goats for two weeks post-infection. Owing to the ability of BM 25 to colonise both non-pregnant and pregnant adults without inducing abortions, a vaccine efficacy study was performed. Vaccination of goats prior to breeding with either BM 25 or the current caprine vaccine B. melitensis strain Rev. 1 resulted in 100 per cent protection against abortion following challenge in late gestation with virulent strain 16M (P<0.05, n=7). However, unlike strain Rev. 1, BM 25 does not appear to cause abortions in late gestation based on this study with a small number of animals. The B. melitensis Deltaomp25 mutant, BM 25, may be a safe and efficacious alternative to strain Rev. 1 when dealing with goat herds of mixed age and pregnancy status.

Attenuation of a Brucella abortus mutant lacking a major 25 kDa outer membrane protein in cattle.

OBJECTIVE: To determine the virulence of a Brucella abortus mutant, BA25, lacking a major 25 kd outer membrane protein (Omp25) in cattle. ANIMALS: 20 mixed-breed heifers in late gestation. PROCEDURE: 10 heifers were inoculated with 1 x 10(7) colony-forming units of the Omp25 mutant via the conjunctival sac, and an equal number were infected with the virulent parental strain B. abortus 2308. The delivery status of the dams was recorded, and colonization was assessed following necropsy. The ability of BA25 to replicate inside bovine phagocytes and chorionic trophoblasts was also evaluated in vitro because of the propensity of virulent brucellae to replicate inside these cells in vivo. RESULTS: The parental strain induced abortions in 5 of 10 inoculated cattle, whereas only 1 of 10 dams exposed to BA25 aborted. Brucella abortus strain 2308 colonized all of the cow-calf pairs and induced Brucella-specific antibodies in 100% of the dams. In contrast, BA25 was isolated by bacteriologic cultural technique from 30% of the calves and 50% of the inoculated dams (n = 10). Of the 10 heifers inoculated with BA25, 4 did not develop Brucella-specific antibodies nor were they colonized by the mutant strain. In bovine macrophages and chorionic trophoblasts, BA25 replicated in significantly lower numbers than the virulent parental strain (n = 3). CONCLUSIONS AND CLINICAL RELEVANCE: The 25 kd outer membrane protein may be an important virulence factor for B. abortus in cattle. The attenuation of the Omp25 mutant in cattle may involve the inability of BA25 to replicate efficiently in bovine phagocytes and chorionic trophoblasts.

Mathematics anxiety and its effect on drug dose calculation.

Eighty learners were randomly selected from 160 first-year nursing students enrolled in an urban community college nursing program in Ontario. They were subsequently divided into control and treatment groups to investigate the effects of different teaching methods on mathematics anxiety and the students' ability to accurately calculate fractional drug doses. The results obtained in this study indicated that there were no statistically significant differences between the control and treatment groups in either mathematics anxiety levels or in arithmetic test performance. These findings counter many of those found in previous investigations. Reasons for these discrepancies are provided along with recommendations for present practice and future research.

Intracoronary thrombolytic therapy performed within a coronary care unit: one year's experience.

Acute myocardial infarction is associated with a high incidence of occluding coronary arterial thrombi. Thrombolytic therapy has been advocated to restore coronary artery blood flow and to reduce myocardial damage. Coronary arteriography and intracoronary thrombolytic therapy was administered to 61 patients admitted to a Coronary Care Unit within eight hours of symptoms. Successful reperfusion was obtained in 38 of 46 single vessel occlusions associated with a first coronary attack. Failure of reperfusion occurred in patients with two vessel occlusions or with cardiogenic shock. This study demonstrates the feasibility of applying this technique within a Coronary Care Unit with low capital and running costs, and suggests that its widespread application is possible even within the setting of a District General Hospital.

Atropine treatment modifies LPS-induced inflammatory response and increases survival.

OBJECTIVE: To explore the effect that Atropine, a competitive antagonist for the muscarinic acetylcholine receptor (mAChR), has on the response to LPS. SUBJECTS: Eight-week-old, male, B6 mice. TREATMENT: Mice were treated with Atropine prior to, or after LPS challenge. METHODS: Survival was monitored and analyzed via Kaplan-Meier analysis using the log-rank test. The effects of atropine on the inflammatory response (TNF-alpha, IL-6 and IL-10) were monitored at various time intervals following LPS injection in mice that were treated and not treated with atropine. RESULTS: Atropine administration prior to LPS induction of the inflammatory response resulted in reduced TNF-alpha and elevated IL-10 plasma levels without affecting the production of IL-6. This reduction in TNF-alpha levels was independent of the increase in IL-10 production. Atropine pretreatment improved the rate of survival from endotoxic shock in mice. The improved survival of mice after endotoxic shock could still be observed when atropine was administered several hours after LPS injection. CONCLUSION: The administration of atropine after injury may have a beneficial clinical effect.