Adjunctive treatment with mianserin enhances effects of raclopride on cortical dopamine output and, in parallel, its antipsychotic-like effect

Clinical studies indicate that adjunctive treatment with the antidepressant drug mianserin, a 5-hydroxytryptamine (5-HT)_2A/C receptor antagonist and an α₂- and α₁-adrenoceptor antagonist, may enhance the effect of conventional antipsychotic drugs in schizophrenia, in particular on negative symptoms such as withdrawal retardation, akathisia, and some aspects of cognitive impairment. Here, we have examined the effect of mianserin in combination with the selective dopamine (DA) D_2/3 receptor antagonist raclopride on conditioned avoidance response (CAR), a preclinical test of antipsychotic efficacy with high predictive validity; catalepsy, a preclinical test of extrapyramidal side effect liability; and DA output in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), respectively. Mianserin (5 mg/kg intraperitoneal) significantly enhanced the suppressant effect of a low dose of raclopride (0.1 mg/kg subcutaneous) on CAR without any increase in catalepsy. Administration of raclopride to rats pretreated with mianserin resulted in a large enhancement of DA output in the mPFC and, at the same time, a small but significant reduction in the raclopride-induced DA output in the NAC. These experimental results indicate that adjunctive treatment with mianserin to a typical D₂ antagonist generates an atypical antipsychotic profile.     

Simultaneous mutations in the CLCNKB and SLC12A3 genes in two siblings with phenotypic heterogeneity in classic Bartter syndrome

Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical findings were different: the boy, who also presented syndromic signs, developed glomerular proteinuria and renal biopsy revealed focal segmental glomerular sclerosis; the girl showed the typical signs of classic Bartter syndrome. As described in a previous paper, a heterozygous mutation (frameshift 2534delT) was demonstrated in the gene encoding the thiazide-sensitive NaCl co-transporter (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene in both subjects, inherited in trans from the parents. The children were finally diagnosed as having classic Bartter syndrome. These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred.     

The management of HCV infected pregnant women and their children European paediatric HCV network

BACKGROUND/AIMS: As evidence accumulates relating to mother-to-child (vertical) transmission of hepatitis C virus (HCV), it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children. METHODS: A review of evidence from the European Paediatric HCV Network (EPHN) prospective study of HCV infected women and their children and other published studies. Meeting of EPHN clinical experts to reach a consensus on recommendations for management. Each recommendation was graded according to the level of evidence. RESULTS/CONCLUSIONS: Although several risk factors for mother-to-child transmission have been identified, none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV. Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women. Based on the current evidence, routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV. HCV/HIV co-infected women should follow existing HIV guidelines.     

Symptoms and diagnosis of borderline, early and advanced epithelial ovarian cancer

OBJECTIVE: To document symptoms associated with borderline, early and advanced ovarian cancer and identify personal characteristics associated with early versus late diagnosis. METHODS: Information concerning symptoms and diagnosis history was available from 811 women with ovarian cancer who took part in an Australian case-control study in the early 1990s. Women were classified into three groups for comparison based on their diagnosis: borderline, early (stage I-II) and advanced (stage III-IV) invasive cancer. RESULTS: Sixteen percent of women with borderline tumors, 7% with early cancer and 4% with advanced cancer experienced no symptoms before diagnosis (P < 0.0001). Among women with symptoms, abdominal pain (44%) or swelling (39%) were most frequently reported; an abdominal mass (12%) and gynecological symptoms (12%) were less common. Compared to advanced stage cancer, women with early stage cancer were more likely to report an abdominal mass or urinary symptoms but less likely to report gastrointestinal problems or general malaise. General malaise and 'other' symptoms were least common in borderline disease. Older women, and those with higher parity or a family history of breast or ovarian cancer, were more likely to be diagnosed at an advanced stage of disease. CONCLUSIONS: Women who experience persistent or recurrent abdominal symptoms, particularly swelling and/or pain should be encouraged to seek medical attention and physicians should be alert to the possibility of ovarian cancer even in the absence of an abdominal mass. Further information about the prevalence of these symptoms in the general population is essential to assist physicians in patient management.     

Incidence and significance of cardiac troponin I release in severe trauma patients

BACKGROUND: The incidence and significance of troponin I release and its mechanism are unknown in severe trauma patients. The characteristics of this release were prospectively studied in such patients and correlated with presence of shock, existence of myocardial contusion, and outcome. METHODS: During a 24-month period, serial electrocardiogram recordings and troponin I measurements were performed in all trauma patients admitted at a surgical intensive care unit. The diagnosis of a significant myocardial contusion was made on electrocardiographic criteria. According to the time course of troponin I, three groups of patients were defined a priori: very transient (/= 2 microg/l), and sustained (> 36 h) and significant release (troponin I > 2 microg/l). In the last group, coronary artery angiography was performed. RESULTS: The incidence of troponin I release was 12% (95% confidence interval [CI], 9.6-14.4%) in 728 patients. A significant myocardial contusion was found in 35 patients (5%; 95% CI, 3.4-6.6%) and may occur in the absence of chest trauma and without troponin I release. Sensitivity, specificity, and positive and negative predictive values of troponin I for the diagnosis of myocardial contusion were 63, 98, 40, and 98%, respectively. Troponin I release was observed in 54 early (> 48 h) survivors (7%; 95% CI, 5.6-9.6%) without preexisting coronary artery disease. A sustained and significant release of troponin I (17 patients) was frequently associated with chest trauma (82%) and constantly with electrocardiographic abnormalities. A coronary artery injury was found in 7 patients (2 major and 5 minor vascular injuries) (1% of the whole group; 95% CI, 0.4-2.0%). Mortality was similar in early survivors with (15%; 95% CI, 7-27%) or without (12%; 95% CI, 9-14%) troponin I release. The odds ratio for late mortality was 1.32 (95% CI, 0.61-2.85) in patients with troponin I release. CONCLUSIONS: Serial electrocardiogram recordings and troponin I assessments may be proposed for initial screening in high-risk trauma patients to detect anatomical cardiac injuries through the time course of circulating protein. Troponin I release does not have a prognosis value in trauma patients.     

Attenuation compensation in cerebral 3D PET: effect of the attenuation map on absolute and relative quantitation

It is generally well accepted that transmission (TX)-based non-uniform attenuation correction can supply more accurate absolute quantification; however, whether it provides additional benefits in routine clinical diagnosis based on qualitative interpretation of 3D brain positron emission tomography (PET) images is still the subject of debate. The aim of this study was to compare the effect of the two major classes of method for determining the attenuation map, i.e. uniform versus non-uniform, using clinical studies based on qualitative assessment as well as absolute and relative quantitative volume of interest-based analysis. We investigated the effect of six different methods for determining the patient-specific attenuation map. The first method, referred to as the uniform fit-ellipse method (UFEM), approximates the outline of the head by an ellipse assuming a constant linear attenuation factor (=0.096 cm^–1) for soft tissue. The second, referred to as the automated contour detection method (ACDM), estimates the outline of the head from the emission sinogram. Attenuation of the skull is accounted for by assuming a constant uniform skull thickness (0.45 cm) within the estimated shape and the correct value (0.151 cm^–1) is used. The usual measured transmission method using caesium-137 single-photon sources was used without (MTM) and with segmentation of the TX data (STM). These techniques were finally compared with the segmented magnetic resonance imaging method (SMM) and an implementation of the inferring attenuation distributions method (IADM) based on the digital Zubal head atlas. Several image quality parameters were compared, including absolute and relative quantification indexes, and the correlation between them was checked. The qualitative evaluation showed no significant differences between the different attenuation correction techniques as assessed by expert physicians, with the exception of ACDM, which generated artefacts in the upper edges of the head. The mean squared error between the different attenuation maps was also larger when using this latter method owing to the fact that the current implementation of the method significantly overestimated the head contours on the external slices. Correlation between the mean regional cerebral glucose metabolism (rCGM) values obtained with the various attenuation correction methods and those obtained with the gold standard (MTM) was good, except in the case of ACDM (R ²=0.54). The STM and SMM methods showed the best correlation (R ²=0.90) and the regression lines agreed well with the line of identity. Relative differences in mean rCGM values were in general less than 8%. Nevertheless, ANOVA results showed statistically significant differences between the different methods for some regions of the brain. It is concluded that the attenuation map influences both absolute and relative quantitation in cerebral 3D PET. Transmission-less attenuation correction results in a reduced radiation dose and makes a dramatic difference in acquisition time, allowing increased patient throughput.     

The expected number of hospitalisations and beds needed due to pandemic influenza on a regional level in the Netherlands

In order to minimise the effects of a potential influenza pandemic on the population, regional authorities in the Netherlands are in the process of development of a plan to be prepared to cope with mass illness and to ensure health care services. The objective of this study is to calculate the expected numbers of hospitalisations and the maximum number of beds needed per day on a regional level. As many uncertainties are involved in this type of studies, we have performed a scenario analysis of the expected number of hospitalisations and beds needed during an influenza pandemic. The analysis gives insight into the impact of the pandemic in terms of how many will be hospitalised, how many beds are needed during the pandemic and in the effect of a possible intervention by therapeutic use of antivirals in terms of hospitalisations and beds needed. It can be concluded that our scenario analysis will be helpful in designing and planning on a regional level.     

The interrelationship of psychosocial risk factors for coronary artery disease in a working population: do we measure distinct or overlapping psychological concepts?

There is growing evidence that psychosocial factors contribute to the risk of coronary artery disease. Commonly used psychometric scales share several features leading to questions about whether they reflect distinguishable concepts. Study participants were 822 employees of the Augsburg Cohort Study (mean age 40 years, 89% men). The authors analyzed the interrelationship between the following psychosocial measures by applying Pearson correlations and factor analysis to the Hospital Anxiety and Depression Scale (HADS), Type D Personality (DS14), the Maastricht Vital Exhaustion Questionnaire (VE), Social Support (F-SozU), the SF12 Health Survey, and Effort-Reward Imbalance. Although the full correlation matrix revealed low to medium associations supporting the notion that the applied psychometric scales show some conceptual overlap, factor analyses resulted in 13 distinguishable and interpretable factors, considerably reflecting the original psychometric scales. This strengthens the assumption that the psychometric scales used constitute distinct psychological concepts, in particular, depressive symptomatology and negative affectivity versus vital exhaustion.     

Epidemiology of eye injuries in Abidjanian children

Eye injuries, most of them preventable, are particularly severe in Africa, because of the risks of infection and delay in treatment. We report a 16-month (March 1997-June 1998) prospective observational survey of eye injuries in children up to the age of 15 years at Treichville-Abidjan University Hospital. During this period, 62 children were treated for these injuries. Ocular traumas represented 4% (n = 245) of new admissions in ophthalmology, and 29% of these injuries occurred in children. The sex ratio was 5:2 boys to girls, and their mean age was 8.66 +/- 3.56 years. Eye injuries occurred most often during play (84%, n = 52). More than 85% (n = 53) of children were alone or without adult supervision at the time of the injury. The causal agent was most often wood (35%) followed by metal (29%). The mean time from injury to hospital admission was 1.8 +/- 0.77 day. Only 19% of patients were admitted the day of injury. Most patients (66%) first sought treatment in a primary care centre. More than 70% (n = 44) of injuries necessitated hospitalisation. Open eyeball wounds were the most common injury (53%) and were associated with endophthalmitis in 16%. The mean recovery of visual acuity was 0.1. At admission, 40 of the injured eyes (64.5%) had monocular blindness; six recovered, for a final blindness rate of 55%. Injuries associated with wooden objects had a final blindness rate of 77% and play-related injuries 63%. The primary posttraumatic sequelae were corneal scars. Eyeball phthysis (14.5%) was secondary to 8 open wounds of the eyeball and one postcontusion retinal detachment. Eye injuries remain a major cause of monocular blindness in children in Cote d'Ivoire. Most of them can be prevented by relatively simple measures including supervision of children and rapid hospitalisation when injury occurs.