Oxidative coupling reactions of pyridine

Abstract available: p.i

The role of vitamin C deficiency in chronic alcoholism

Gastric erosions caused by home-brewed lager. A 22 year old male was admitted to hospital because of melaena due to acute gastric erosions. In the three weeks prior to his admission, he had drunk several gallons of home-brewed lager. Investigations revealed that this was contaminated with acetaldehyde and acetic acid which had been produced by an acetobacter organism present in the yeast. Experiments were carried out on the effect of home-brewed lager and beer on the stomachs of the guinea pigs. The incidence of erosive gastritis was significantly increased when the animals were given similarly contaminated home-brewed lager. This observation is of importance since the home-brewing of beer and lager has become common since its legalisation in 1964. A clinical study was carried out to determine the leucocyte ascorbic acid levels and the iron status of fifty alcoholics admitted to medical and psychiatric wards. In addition, the dietary intake of vitamin C and iron was estimated. The age range of the group was 24-70 years and this included nine females, age range years. None of the patients had overt liver disease and none were intoxicated at the time the blood sample was taken. All the alcoholic patients had an inadequate intake of iron (15 mg/day) but the haemoglobin, erythrocyte protoporphyrin and serum iron levels showed, that over 55% of the patients showed no signs of anaemia. In the absence of liver disease, the incidence of anaemia in alcoholics was lower than expected. L.A.A. was estimated by the 2,4-dinitrophenyl method and the average daily intake of vitamin C was calculated from the diet history. The alcoholic group was matched with a normal group of patients according to age. (within five years) and sex. The results show that, as a group, alcoholics are sub-clinically scorbutic. Their vitamin C levels, 18.8 +/- 11.01 (mean +/- S.D,) mug/108 WBC are significantly lower (p 0.0005) than those of the matched group, 27.41 +/- 7.59 (mean +/- S.D.) mug/108 WBC. The L.A.A. levels in different age groups are not significantly different from each other but in every age group the alcoholic group has a significantly lower vitamin C level when compared with the control group. When the diet histories were studied, it was clear that the main reason for low L.A.A. levels was inadequate intake of vitamin C. Having established that alcoholics are generally deficient in vitamin C, an investigation was carried out to ascertain if this condition could directly affect the metabolism of ethanol. An experiment was designed to measure the induction of hepatic alcohol dehydrogenase by alcohol in sub-clinically scorbutic guinea pigs. However, the criteria of sub-clinical scurvy (i.e. a state where there is a diminished level of ascorbic acid in the body without apparent manifestations of scurvy) had to be established at the outset. The leucocyte ascorbic acid levels and the vitamin C levels in the liver, stomach and upper small intestine of guinea pigs were measured by the usual 2,4 dinitrophenyl hydrazine method. These levels show that guinea, pigs are sub-clinically scorbutic after two weeks on a scorbutic diet. Only male guinea pigs were used in the experiments. The levels of ADH were measured in the guinea pig livers after daily injections of 2 ml of 30% ethanol in saline for two days, one week, two weeks and three weeks. The guinea pigs in the scorbutic groups were always maintained on the scorbutic diet for two weeks. The results show that ADH is maximally induced within two days and that there is a highly significant increase in ADH levels in sub-clinically scorbutic guinea pigs fed ethanol. The potentiation of ADH induction in sub-clinically scorbutic states could explain the increased tolerance of alcoholics for alcohol since sub-clinical scurvy was present in the majority of the cases of chronic alcoholism. The level of NAD was measured in guinea pigs injected with 30% alcohol for two weeks and fed the scorbutic diet. The levels of NAD are higher in sub-clinically scorbutic animals fed ethanol than in normal animals fed ethanol

Leydig Cell Hyperplasia Mimicking a Testicular Tumour in a Patient with Klinefelter Syndrome

Background: Klinefelter syndrome (KS) is the most common sex-chromosomal disorder in males. Frequently under-recognized, it occurs in 1 in 500–600 male births. It is caused by the inheritance of at least one additional X chromosome from either parent. Patients often have uncommon or atypical malignancies. Patient: We describe the case of a 35-year-old man with 47XXY KS and previous cryptorchidism, presenting with a painful testicular mass. Histology confirmed Leydig cell hyperplasia. Discussion: Cryptorchidism is an established risk factor for testicular tumours and occurs six times more commonly in KS than in the general population. Despite this, large epidemiological studies have shown a reduced burden of testicular cancer in these patients. The presentation of a hypoechoic lesion on ultrasound will prompt consideration of testicular tumours, however orchalgia represents an atypical presentation. In patients with KS, Leydig cell hyperplasia is a much more common entity and should be considered early in the differential diagnosis

Developmental Model of Depression Applied to Prenatal Depression: Role of Present and Past Life Events, Past Emotional Disorders and Pregnancy Stress

Several risk factors for depression during pregnancy have already been established. However, very few studies have conducted a multivariate analysis incorporating both the major predictors of depression in women, in accordance with comprehensive developmental models of depression, and specific stressors associated with the biological and psychosocial state of the mother-to-be.We used a cross-sectional cohort design to analyze the associations between prenatal depression and potential risk factors. 693 French-speaking women with singleton pregnancies at 20-28 weeks' gestation were consecutively recruited at Caen University Hospital. Fifty women with missing values were subsequently excluded from the analysis. Depressive symptoms were assessed on the Edinburgh Postnatal Depression Scale. Risk factors were either extracted from the computerized obstetric records or assessed by means of self-administered questionnaires. The associations between prenatal depression and the potential risk factors were assessed using log-binomial regression models to obtain a direct estimate of relative risk (RR). The following factors were found to be significant in the multivariate analysis: level of education (p<0.001), past psychiatric history (adjusted RR=1.8, 95% confidence interval (CI): 1.1;2.8, p=0.014), stress related to the health and viability of the fetus (adjusted RR=2.6, 95% CI: 1.6;4.1, p<0.001), and stress related to severe marital conflicts (adjusted RR=2.4, 95% CI: 1.5;3.9, p<0.001) or to serious difficulties at work (adjusted RR=1.6, 95% CI :1.04;2.4, p=0.031). An association was also found with the previous delivery of a child with a major or minor birth defect (adjusted RR=2.0, 95% CI: 1.04;4.0, p=0.038). Univariate analyses revealed a strong association with childhood adversity (parental rejection: RR=1.8, 95% CI: 1.2;2.8, p=0.0055 and family secrets: RR=2.0, 95% CI: 1.2;3.1, p=0.0046) and with lack of partner support (RR=0.50, 95% CI: 0.30;0.84, p=0.0086).Our study identifies several risk factors that could easily be assessed in clinical practice. It draws attention to the impact of previously delivering a child with a birth defect. The association with childhood adversity warrants further study

An observational treatment study of metacognition in anxious-depression

Prior studies have found metacognitive biases are linked to a transdiagnostic dimension of anxious-depression, manifesting as reduced confidence in performance. However, previous work has been cross-sectional and so it is unclear if under-confidence is a trait-like marker of anxious-depression vulnerability, or if it resolves when anxious-depression improves. Data were collected as part of a large-scale transdiagnostic, four-week observational study of individuals initiating internet-based cognitive behavioural therapy (iCBT) or antidepressant medication. Self-reported clinical questionnaires and perceptual task performance were gathered to assess anxious-depression and metacognitive bias at baseline and 4-week follow-up. Primary analyses were conducted for individuals who received iCBT (n=649), with comparisons between smaller samples that received antidepressant medication (n=82) and a control group receiving no intervention (n=88). Prior to receiving treatment, anxious-depression severity was associated with under-confidence in performance in the iCBT arm, replicating previous work. From baseline to follow-up, levels of anxious-depression were significantly reduced, and this was accompanied by a significant increase in metacognitive confidence in the iCBT arm (β=0.17, SE=0.02, p<0.001). These changes were correlated (r(647)=-0.12, p=0.002); those with the greatest reductions in anxious-depression levels had the largest increase in confidence. While the three-way interaction effect of group and time on confidence was not significant (F(2, 1632)=0.60, p=0.550), confidence increased in the antidepressant group (β=0.31, SE = 0.08, p<0.001), but not among controls (β=0.11, SE = 0.07, p=0.103). Metacognitive biases in anxious-depression are state-dependent; when symptoms improve with treatment, so does confidence in performance. Our results suggest this is not specific to the type of intervention

An observational treatment study of metacognition in anxious-depression

Prior studies have found metacognitive biases are linked to a transdiagnostic dimension of anxious-depression, manifesting as reduced confidence in performance. However, previous work has been cross-sectional and so it is unclear if under-confidence is a trait-like marker of anxious-depression vulnerability, or if it resolves when anxious-depression improves. Data were collected as part of a large-scale transdiagnostic, four-week observational study of individuals initiating internet-based cognitive behavioural therapy (iCBT) or antidepressant medication. Self-reported clinical questionnaires and perceptual task performance were gathered to assess anxious-depression and metacognitive bias at baseline and 4-week follow-up. Primary analyses were conducted for individuals who received iCBT (n=649), with comparisons between smaller samples that received antidepressant medication (n=82) and a control group receiving no intervention (n=88). Prior to receiving treatment, anxious-depression severity was associated with under-confidence in performance in the iCBT arm, replicating previous work. From baseline to follow-up, levels of anxious-depression were significantly reduced, and this was accompanied by a significant increase in metacognitive confidence in the iCBT arm (β=0.17, SE=0.02, p<0.001). These changes were correlated (r(647)=-0.12, p=0.002); those with the greatest reductions in anxious-depression levels had the largest increase in confidence. While the three-way interaction effect of group and time on confidence was not significant (F(2, 1632)=0.60, p=0.550), confidence increased in the antidepressant group (β=0.31, SE = 0.08, p<0.001), but not among controls (β=0.11, SE = 0.07, p=0.103). Metacognitive biases in anxious-depression are state-dependent; when symptoms improve with treatment, so does confidence in performance. Our results suggest this is not specific to the type of intervention

High power, low frequency ultrasound: meniscal tissue interaction and ablation characteristics

This study evaluates high power low frequency ultrasound transmitted via a flat vibrating probe tip as an alternative technology for meniscal debridement in the bovine knee. An experimental force controlled testing rig was constructed using a 20kHz ultrasonic probe suspended vertically from a load cell. Effect of variation in amplitude of distal tip displacement (242-494µm peak-peak) settings and force (2.5-4.5N) on tissue removal rate (TRR) and penetration rate (PR) for fifty-two bovine meniscus samples was analyzed. Temperature elevation in residual meniscus was measured by embedded thermocouples and histological analysis. As amplitude or force increases, there is a linear increase in TRR (Mean: 0.9 to 11.2mg/s) and PR (Mean: 0.08 to 0.73mm/s). Maximum mean temperatures of 84.6°C and 52.3°C were recorded in residual tissue at 2mm and 4mm from the ultrasound probe-tissue interface. There is an inverse relationship between both amplitude and force, and temperature elevation, with higher settings resulting in less thermal damage

Vagus nerve stimulation for depression: efficacy and safety in a European study

Background Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. Method An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. Results The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). Conclusions VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European stud

Expression of glucocorticoid inducible genes is associated with reductions in cornu ammonis and dentate gyrus volumes in patients with major depressive disorder

Alterations of the glucocorticoid system and of hippocampal volumes have consistently been reported in patients with major depressive disorders (MDD). The aim of the present study was to investigate whether the messenger RNA (mRNA) expression of glucocorticoid inducible genes is associated with changes in the cornu ammonis (CA) and dentate gyrus subfields. Forty-three patients with MDD and 43 healthy controls were recruited and investigated with high resolution magnetic resonance imaging. Hippocampal subfields were measured using freesurfer. Measurement of whole blood mRNA expression of glucocorticoid inducible genes serum and glucocorticoid-regulated kinase 1 (SGK1), FK506 binding protein 5 (FKBP5), and glucocorticoid induced leucine zipper (GILZ) was performed. Patients with MDD had significantly smaller volumes of CA1, CA2/3, CA4/DG, and subiculum compared to healthy controls. In the regression analysis, the factor diagnosis had a significant moderating effect on the association of SGK1 and hippocampal volumes. Patients with low expression of SGK1 had significantly smaller CA2/3 and CA4/DG volumes compared to patients with high expression of SGK1 mRNA and to healthy controls with low/high expression of SGK1, respectively. Therefore, a lack of mRNA expression of glucocorticoid inducible genes in patients with MDD that seems to correspond to a blunted cortisol response is associated with smaller hippocampal CA and dentate gyrus volumes. SGK1 seems to be particularly relevant for stress-related mental disorders

A meta-analysis of prevalence estimates and moderators of low bone mass in people with schizophrenia

Objective: To assess the prevalence and moderators of low bone mass, osteopenia and osteoporosis in schizophrenia patients. Method: Major electronic databases were searched from inception till December 2013 for studies reporting the prevalence of low bone mass (osteopenia + osteoporosis = primary outcome), osteopenia or osteoporosis in schizophrenia patients. Two independent authors completed methodological appraisal and extracted data. A random effects meta-analysis was utilized. Results: Nineteen studies were included (n = 3038 with schizophrenia; 59.2%male; age 24.5–58.9 years). The overall prevalence of low bone mass was 51.7%(95% CI = 43.1–60.3%); 40.0%(CI = 34.7–45.4%) had osteopenia and 13.2%(CI = 7.8–21.6%) had osteoporosis. Compared with controls, schizophrenia patients had significantly increased risk of low bone mass (OR = 1.9, CI = 1.30–2.77, P < 0.001, n = 1872) and osteoporosis (OR = 2.86, CI = 1.27–6.42, P = 0.01, n = 1824), but not osteopenia (OR = 1.33, CI = 0.934–1.90, P = 0.1, n = 1862). In an exploratory regression analysis, older age (P = 0.004) moderated low bone mass, while older age (P < 0.0001) and male sex (P < 0.0001) moderated osteoporosis. The subgroup analyses demonstrated high heterogeneity, but low bone mass was less prevalent in North America (35.5%, CI = 26.6–45.2%) than Europe (53.6%, CI = 38.0–68.5%) and Asia (58.4%, CI = 48.4–67.7%), and in mixed in-/out-patients (32.9%, CI = 49.6–70.1%) vs. in-patients (60.3%, CI = 49.6–70.1%). Conclusion: Reduced bone mass (especially osteoporosis) is significantly more common in people with schizophrenia than controls