Wolbachia-mediated sperm modification is dependent on the host genotype in Drosophila

Estimates of Wolbachia density in the eggs, testes and whole flies of drosophilid hosts have been unable to predict the lack of cytoplasmic incompatibility (CI) expression in so-called mod(-) variants. Consequently, the working hypothesis has been that CI expression, although related to Wolbachia density, is also governed by unknown factors that are influenced by both host and bacterial genomes. Here, we compare the behaviour of the mod(-) over-replicating Wolbachia popcorn strain in its native Drosophila melanogaster host to the same strain transinfected into a novel host, namely Drosophila simulans. We report that (i) the popcorn strain is a close relative of other D. melanogaster infections, (ii) the mod(-) status of popcorn in D. melanogaster appears to result from its inability to colonize sperm bundles, (iii) popcorn is present in the bundles in D. simulans and induces strong CI expression, which demonstrates that the bacterial strain does not lack the genetic machinery for inducing CI and that there is host-species-specific control over Wolbachia tissue tropism, and (iv) infection of sperm bundles by the mod(-) D. simulans wCof strain indicates that there are several independent routes by which a strain can be a CI non-expressor.

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: A phase II trial for the Trans-Tasman Radiation Oncology Group

Purpose: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. Methods and Materials: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. Results: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. Conclusion: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications. (C) 2001 Elsevier Science Inc.

Maternal antecedents for cerebral palsy in extremely preterm babies: A case-controlled study

The study aimed to identify significant antenatal risk factors for cerebral palsy (CP) among extremely preterm infants with a matched case-control design. Infants born between 1989 and 1996 at 24 to 27 weeks' gestation who survived to hospital discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected for prematurity and 120 control children matched for gestational age without CP. Information on maternal obstetric risk factors and medication was obtained. Matched analyses were performed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while maternal administration of corticosteroids was associated with a reduced risk of CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was achieved but no relation between clinical or histological chorioamnionitis or funisitis and CP was demonstrated. Maternal preeclampsia was not associated with a statistically significant reduction in the risk of CP. It is concluded that a reduced risk of CP in extremely preterm infants is associated with the antenatal use of corticosteroids.

Mark-recapture may reveal more about ecology than about population trends: Demography of a threatened ghost bat (Macroderma gigas) population

Since European settlement in Australia, the geographical range of ghost bats (Macroderma gigas) has contracted northwards. Ghost bats are thought to occur in disjunct populations with little interpopulation migration, raising concerns over the current status and future viability of the southernmost colony, which has also been threatened by mining activity. To address these concerns, demographic parameters of the southernmost colony were estimated from a mark-recapture study conducted during 1975-1981. Female bats gave birth to a single young in late spring, but only 40% (22-70%, 95% CI) of females bred in their second year, increasing to 93% (87-97%, 95% CI) for females greater than or equal to 2 years old. Sixty-five percent of juveniles caught were female. Annual adult survival ranged between 0.57-0.77 for females and 0.43-0.66 for males, and was lowest over winter-spring and greatest in autumn-winter. Juvenile survival for the first year ranged between 0.35-0.46 for females and 0.29-0.42 for males. Adult survival varied among seasons, was negatively associated with rainfall, but was not associated with temperature beyond being lower in late winter. Poor survival may result from the inferior daytime roosts that bats must use if water seepage forces them to leave their normal roosts. Although these age-specific rates of fecundity and survival suggested a declining population, mark-recapture estimates of the population trend indicated stability over the study period. Counts at daytime roosts also suggested a population decline, but were considered unreliable because of an increasing tendency of bats to avoid detection. It is therefore likely that some assumptions in estimating survival were violated. These results provide a caution against the uncritical use of population projections derived from mark-recapture estimates of demographic parameters, and the use of untested indices as the basis for conservation decisions.

Genetic and environmental contributions to cannabis dependence in a national young adult twin sample

Background. This paper examines genetic and environmental contributions to risk of cannabis dependence. Method. Symptoms of cannabis dependence and measures of social, family and individual risk factors were assessed in a sample of 6265 young adult male and female Australian twins born 1964-1971. Results. Symptoms of cannabis dependence were common: 11(.)0% of sample (15(.)1% of men and 7(.)8% of women) reported two or more symptoms of dependence. Correlates of cannabis dependence included educational attainment, exposure to parental conflict, sexual abuse, major depression, social anxiety and childhood conduct disorder. However, even after control for the effects of these factors, there was evidence of significant genetic effects on risk of cannabis dependence. Standard genetic modelling indicated that 44(.)7% (95% CI = 15-72(.)2) of the variance in liability to cannabis dependence could be accounted for by genetic factors, 20(.)1% (95 CI = 0-43(.)6) could be attributed to shared environment factors and 35(.)3% (95% CI = 26(.)4-45(.)7) could be attributed to non-shared environmental factors. However, while there was no evidence of significant gender differences in the magnitude of genetic and environmental influences, a model which assumed both genetic and shared environmental influences on risks of cannabis dependence among men and shared environmental but no genetic influences among women provided an equally good fit to the data. Conclusions. There was consistent evidence that genetic risk factors are important determinants of risk of cannabis dependence among men. However, it remains uncertain whether there are genetic influences on liability to cannabis dependence among women.

Geographical variation in the penetrance of CDKN2A mutations for melanoma

Background: Germline mutations in the CDKN2A gene, which encodes two proteins (p16INK4A and p14ARF), are the most common cause of inherited susceptibility to melanoma. We examined the penetrance of such mutations using data from eight groups from Europe, Australia and the United States that are part of The Melanoma Genetics Consortium Methods: We analyzed 80 families with documented CDKN2A mutations and multiple cases of cutaneous melanoma. We modeled penetrance for melanoma using a logistic regression model incorporating survival analysis. Hypothesis testing was based on likelihood ratio tests. Covariates included gender, alterations in p14APF protein, and population melanoma incidence rates. All statistical tests were two-sided. Results: The 80 analyzed families contained 402 melanoma patients, 320 of whom were tested for mutations and 291 were mutation carriers. We also tested 713 unaffected family members for mutations and 194 were carriers. Overall, CDKN2A mutation penetrance was estimated to be 0.30 (95% confidence interval (CI) = 0.12 to 0.62) by age 50 years and 0.67 (95% CI = 0.31 to 0.96) by age 80 years. Penetrance was not statistically significantly modified by gender or by whether the CDKN2A mutation altered p14ARF protein. However, there was a statistically significant effect of residing in a location with a high population incidence rate of melanoma (P = .003). By age 50 years CDKN2A mutation penetrance reached 0.13 in Europe, 0.50 in the United States, and 0.32 in Australia; by age 80 years it was 0.58 in Europe, 0.76 in the United States, and 0.91 in Australia. Conclusions: This study, which gives the most informed estimates of CDKN2A mutation penetrance available, indicates that the penetrance varies with melanoma population incidence rates. Thus, the same factors that affect population incidence of melanoma may also mediate CDKN2A penetrance.

Pro re nata medication for psychoses: an audit of practice in two metropolitan hospitals

Objective: To examine the use of pro re nata (PRN) (as needed) medication in hospitalized patients with psychotic disorders. Methods: Retrospective chart reviews were conducted at two large public psychiatry units situated in inner city general hospitals. Pro re nata medication prescription, administration and outcomes were examined during inpatient episodes of care for 184 consecutive admissions of patients diagnosed with a psychotic disorder. Patient demographics, diagnoses, and regularly prescribed medication were also recorded. All admissions were drawn from a three-month period from December 1998-February 1999. Results: The most prevalent diagnoses were schizophrenia related disorders (n = 111) and mania (n = 34). Substance use disorders (n = 49) were the most common comorbid dis-orders. Pro re nata medication was administered during the acute phase of 82% of admissions. Drugs prescribed Pro re nata were mostly typical antipsychotics, benzodiazepines and/or anti-cholinergics. Coprescription of typical antipsychotics PRN with regularly scheduled atypical antipsychotics was common (64%). Pro re nata medications accounted for 31% of the total antipsychotic dose and 28% of the total anxiolytic dose administered during acute treatment. Higher daily doses of PRN medication were given to manic patients, males, younger patients and those with substance use disorders. Pro re nata prescriptions usually specified a maximum daily dose (87%) but rarely gave indications for use (6%). Adminis-tration records frequently lacked a specified reason for use (48%) or a notation of outcome (64%). Unit staff noted medication-related morbidity in 37% of patients receiving PRN medication, compared to 3% of patients receiving only regularly scheduled medication. Extrapyramidal symptoms (EPS) were most frequently associated with administration of PRN haloperidol (Relative Risk vs other PRN medications = 5.61, 95% CI = 2.36-13.73). Conclusions: Pro re nata medications comprised a significant part of the treatment which psychotic patients received. The common practice of coprescribing PRN typical antipsychotics with scheduled atypical antipsychotics is potentially problematical since administration of PRN medication is associated with significant medication related morbidity. Preferential use of benzodiazepines as PRN agents may minimize this morbidity and foster subsequent compliance with regularly prescribed antipsychotics.

Acute symptoms, not rectally administered sucralfate, predict for late radiation proctitis: Longer term follow-up of a phase III trial - trans-Tasman radiation oncology group

Image : To assess the potential for sucralfate administered rectally to reduce the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy (RT) for carcinoma of the prostate and to study the variables potentially contributing to late rectal morbidity and particularly to explore the relationship between acute and late toxicity. Image : Eighty-six patients with localized prostate carcinoma were randomized in a double-blind, placebo-controlled study to a daily enema of 3 g of sucralfate in a 15-mL suspension or the same suspension without sucralfate. The enema began the first day of RT and was continued for 2 weeks after treatment completion. The primary end point of the study was acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) toxicity; however, the patients were followed for an additional 5 years on a 6-month basis. The evaluation included late RTOG/EORTC toxicity and a patient self-assessment questionnaire. Image : With a median follow-up of 5 years, the Kaplan-Meier probability of late Grade 2 RTOG/EORTC toxicity was 12% (95% confidence interval [CI] 2–22%) for placebo and 5% (95% CI 0–12%) for sucralfate (p = 0.26). The probability of late rectal bleeding was 59% (95% CI 45–73%) for placebo and 54% (95% CI 40–68%) for sucralfate. No statistically significant difference was found between the treatment arms for the peak incidence of any of the other patient self-assessment variables. Cox proportional hazards modeling indicated acute RTOG/EORTC toxicity of Grade 2 or greater was associated with a hazard ratio of 2.74 (95% CI 1.31–5.73) for the development of late toxicity of Grade 1 or greater. Substituting the patient self-assessment variables for acute RTOG/EORTC toxicity revealed that rectal pain of a moderate or severe grade during RT was the best predictor of the subsequent development of late toxicity, with a hazard ratio of 3.44 (95% CI 1.68–7). Image : The results of this study do not support the use of sucralfate administered rectally as a method for reducing the late toxicity of nonconformal RT for prostate cancer. There appears to be an association between the development of acute and subsequent late toxicity, although the nature of this association remains to be determined

Increase in prevalence of nosocomial non-Candida albicans candidaemia and the association of Candida krusei with fluconazole use

Candida is an important nosocomial pathogen. This study was undertaken to provide information on the rate of candidaemia, to define the risks for candidaemia and to describe and account for the epidemiology of candidaemia at our institution between 1992 and 1999. The overall rate was 0.052 per 1000 patient days and 0.27 per 1000 discharges. The major risks for candidaemia were colonization at a non-sterile site (OR 3.85, 95%CI 1.80-9.09), total parenteral nutrition (TPN) in the absence of neutropenia (OR 11.8, 95%CI 4.5-35.4, P

Usefulness of clinical risk markers and ischemic threshold to stratify risk in patients undergoing major noncardiac surgery

The risk of cardiac events in patients undergoing major noncardiac surgery is dependent on their clinical characteristics and the results of stress testing. The purpose of this study was to develop a composite approach to defining levels of risk and to examine whether different approaches to prophylaxis influenced this prediction of outcome. One hundred forty-five consecutive patients (aged 68 +/- 9 years, 79 men) with >1 clinical risk variable were studied with standard dobutamine-atropine stress echo before major noncardiac surgery. Risk levels were stratified according to the presence of ischemia (new or worsening wall motion abnormality), ischemic threshold (heart rate at development of ischemia), and number of clinical risk variables. Patients were followed for perioperative events (during hospital admission) and death or infarction over the subsequent 16 10 months. Ten perioperative events occurred in 105 patients who proceeded to surgery (10%, 95% confidence interval [CI] 5% to 17%), 40 being cancelled because of cardiac or other risk. No ischemia was identified in 56 patients, 1 of whom (1.8%) had a perioperative infarction. Of the 49 patients with ischemia, 22 (45%) had 1 or 2 clinical risk factors; 2 (9%, 95% CI 1% to 29%) had events. Another 15 patients had a high ischemic threshold and 3 or 4 risk factors; 3 (20%, 95% Cl 4% to 48%) had events. Twelve patients had a low ischemic threshold and 3 or 4 risk factors; 4 (33%, 95% CI 10% to 65%) had events. Preoperative myocardial revascularization was performed in only 3 patients, none of whom had events. Perioperative and long-term events occurred despite the use of beta blockers; 7 of 41 eta blocker-treated patients had a perioperative event (17%, 95% CI 7% to 32%); these treated patients were at higher anticipated risk than untreated patients (20 +/- 24% vs 10 +/- 19%, p = 0.02). The total event rate over late follow-up was 13%, and was predicted by dobutamine-atropine stress echo results and heart rate response. (C) 2002 by Excerpta Medica, Inc.

Refinements in stress echocardiographic techniques improve inter-institutional agreement in interpretation of dobutamine stress echocardiograms

Aims To determine the degree of inter-institutional agreement in the assessment of dobutamine stress echocardiograms using modern stress echo cardiographic technology in combination with standardized data acquisition and assessment criteria. Method and Results Among six experienced institutions, 150 dobutamine stress echocardiograms (dobutamine up to 40 mug.kg(-1) min(-1) and atropine up to I mg) were performed on patients with suspected coronary artery disease using fundamental and harmonic imaging following a consistent digital acquisition protocol. Each dobutamine stress echocardiogram was assessed at every institution regarding endocardial visibility and left ventricular wall motion without knowledge of any other data using standardized reading criteria. No patients were excluded due to poor image quality or inadequate stress level. Coronary angiography was performed within 4 weeks. Coronary angiography demonstrated significant coronary artery disease (less than or equal to50% diameter stenosis) in 87 patients. Using harmonic imaging an average of 5.2+/-0.9 institutions agreed on dobutamine stress echocardiogram results as being normal or abnormal (mean kappa 0.55; 95% CI 0.50-0.60). Agreement was higher in patients with no (equal assessment of dobutamine stress echocardiogram results by 5.5 +/- 0.8 institutions) or three-vessel coronary artery disease (5.4 +/- 0.8 institutions) and lower in one- or two- vessel disease (5.0 +/- 0.9 and 5.2 +/- 1.0 institutions, respectively-, P=0.041). Disagreement on test results was greater in only minor wall motion abnormalities. Agreement on dobutamine stress echocardiogram results was lower using fundamental imaging (mean kappa 0.49; 95% CI 0.44-0.54; P

Viruses associated with outbreaks of equine respiratory disease in New Zealand

AIM: To identify viruses associated with respiratory disease in young horses in New Zealand. METHODS: Nasal swabs and blood samples were collected from 45 foals or horses from five separate outbreaks of respiratory disease that occurred in New Zealand in 1996, and from 37 yearlings at the time of the annual yearling sales in January that same year. Virus isolation from nasal swabs and peripheral blood leukocytes (PBL) was undertaken and serum samples were tested for antibodies against equine herpesviruses (EHV-1, EHV-2, EHV-4 and EHV-5), equine rhinitis-A virus (ERAV), equine rhinitis-B virus (ERBV), equine adenovirus 1 (EAdV-1), equine arteritis virus (EAV), reovirus 3 and parainfluenza virus type 3 (PIV3). RESULTS: Viruses were isolated from 24/94 (26%) nasal swab samples and from 77/80 (96%) PBL samples collected from both healthy horses and horses showing clinical signs of respiratory disease. All isolates were identified as EHV-2, EHV-4, EHV-5 or untyped EHV Of the horses and foals tested, 59/82 (72%) were positive for EHV-1 and/or EHV-4 serum neutralising (SN) antibody on at least one sampling occasion, 52/82 (63%) for EHV-1-specific antibody tested by enzyme-linked immunosorbent assay (ELISA), 10/80 (13%) for ERAV SN antibody, 60/80 (75%) for ERBV SN antibody, and 42/80 (53%) for haemagglutination inhibition (HI) antibody to EAdV-1. None of the 64 serum samples tested were positive for antibodies to EAV, reovirus 3 or PIV3. Evidence of infection with all viruses tested was detected in both healthy horses and in horses showing clinical signs of respiratory disease. Recent EHV 2 infection was associated with the development of signs of respiratory disease among yearlings [relative risk (RR) = 2.67, 95% CI = 1.59-4.47, p = 0.0171]. CONCLUSIONS: Of the equine respiratory viruses detected in horses in New Zealand during this study, EHV 2 was most likely to be associated with respiratory disease. However, factors other than viral infection are probably important in the development of clinical signs of disease.

Effects of paternal drinking, conduct disorder and childhood home environment on the development of alcohol use disorders in a Thai population

Aims To identify influences on the development of alcohol use disorders in a Thai population, particularly parental drinking and childhood environment. Design Case-control study. Setting A university hospital, a regional hospital and a community hospital in southern Thailand. Participants Ninety-one alcohol-dependents and 177 hazardous/harmful drinkers were recruited as cases and 144 non-or infrequent drinkers as controls. Measurements Data on parental drinking, family demographic characteristics, family activities, parental disciplinary practice, early religious life and conduct disorder were obtained using a structured interview questionnaire. The main outcome measure was the subject's classification as alcohol-dependent, hazardous/harmful drinker or non-/infrequent drinker. Findings A significant relationship was found between having a drinking father and the occurrence of hazardous/harmful drinking or alcohol dependence in the subjects. Childhood factors (conduct disorder and having been a temple boy, relative probability ratios, RPRs and 95% CI: 6.39, 2.81-14.55 and 2.21, 1.19-4.08, respectively) also significantly predicted alcohol dependence, while perceived poverty and ethnic alienation was reported less frequently by hazardous/harmful drinkers and alcohol-dependents (RPRS and 95% CIs = 0.34, 0.19-0.62 and 0.59, 0.38-0.93, respectively) than the controls. The relative probability ratio for the effect of the father's infrequent drinking on the son's alcohol dependence was 2.92 (95% CI = 1.42-6.02) and for the father's heavy or dependent drinking 2.84 (95% CI=1.31-6.15). Conclusions Being exposed to a light-drinking, father increases the risk of a son's alcohol use disorders exhibited either as hazardous-harmful or dependent drinking. However, exposure to a heavy- or dependent-drinking father is associated more uniquely with an increased risk of his son being alcohol-dependent. The extent to which this is seen in other cultures is worthy of exploration.

The efficacy of a psychosocial intervention for HIV/AIDS caregiving dyads and individual caregivers: a controlled treatment outcome study

The present study examined the comparative efficacy of intervening at the caregiver/care-recipient dyadic level, versus the individual caregiver level, for caregivers and their care-recipients with HIV/AIDS. Participants were randomly assigned to a Dyad Intervention (DI), a Caregiver Intervention (CI) or Wait List Control group (WLC), and assessed by interview and self-administered scales immediately before treatment and eight weeks later. Participants in the intervention groups also completed a four-month follow-up assessment. Dependent variables included global distress, social adjustment, dyadic adjustment, subjective health status, HIV/AIDS knowledge and target problem ratings. Results showed that caregivers in the DI group showed greater improvement from pre- to post-treatment on global distress, dyadic adjustment and target problems than the CI and WLC caregivers. The CI and DI caregivers showed greater improvement than the WLC group on all dependent variables except social adjustment. Care-recipients in the DI group improved significantly from pre- to post-treatment on dyadic adjustment, social adjustment, knowledge, subjective health status and Target Problem 1, whereas the CI and WLC care-recipients failed to improve on any of these measures. The treatment gains made by the DI caregivers and care-recipients on most dependent variables were maintained at a four-month follow-up. Findings support a reciprocal determinism approach to the process of dyadic adjustment and suggest that intervening at the caregiver/care-recipient level may produce better outcomes for both the caregiver and care-recipient than intervening at the individual caregiver level.

Combined physiotherapy and education is efficacious for chronic low back pain

Manual therapy, exercise and education target distinct aspects of chronic low back pain and probably have distinct effects, This study aimed to determine the efficacy of a combined physiotherapy treatment that comprised all of these strategies. By concealed randomisation, 57 chronic low back pain patients were allocated to either the four-week physiotherapy program or management as directed by their general practitioners, The dependent variables of interest were pain and disability. Assessors were blind to treatment group. Outcome data from 49 subjects (86%) showed a significant treatment effect. The physiotherapy program reduced pain and disability by a mean of 1.5/10 points on a numerical rating scale (95% CI 0.7 to 2.3) and 3.9 points on the 18-point Roland Morris Disability Questionnaire (95% CI 2 to 5.8), respectively. The number needed to treat in order to gain a clinically meaningful change was 3 (95% CI 3 to 8) for pain, and 2 (95% CI 2 to 5) for disability. A treatment effect was maintained at one-year follow-up. The findings support the efficacy of combined physiotherapy treatment in producing symptomatic and functional change in moderately disabled chronic low back pain patients.