Prevalence of typus melancholicus in healthy germans

BACKGROUND: There have been few studies concerning the prevalence of Typus melancholicus (TM) in healthy volunteers based on age or sex. To our knowledge, no such studies have been performed in healthy Germans, but several in healthy Japanese people. Therefore, it is necessary to also determine the prevalence of TM in healthy Germans, in order to know whether the prevalence of TM is cross-culturally constant. SUBJECTS AND METHODS: We examined the prevalence of TM in 121 healthy German volunteers (62 men and 59 women with a mean age +/- SD of 43.9 +/- 16.8 years and 47.4 +/- 15.9 years, respectively). Kasahara's Inventory for the Melancholic Type Personality (KIMTP) and von Zerssen's F-List (F-List) were used to identify TM. The subjects were divided by age into three groups: those aged 40 years or less (group A), those aged 41-60 years (group B), and those aged 61 years or more (group C). Mean total KIMTP and F-List scores were calculated. In addition, we also calculated mean scores of the two KIMTP TM factors ['harmony in personal relationships' (factor 1) and 'social norms' (factor 2)]. Differences in scores between men and women were analyzed by Student's t test. Differences in scores between the three age groups were evaluated by one-way analysis of variance and Scheffé's test. RESULTS: The KIMTP and F-List scores increased with age in both men and women. In the women, the KIMTP and F-List scores were significantly higher in groups B and C than in group A. In the women, the group C KIMTP factor 1 score was significantly higher than the group A KIMTP factor 1 score. The KIMTP and F-List scores tended to be higher for the women than for the men. Within groups B and C, the KIMTP and F-List scores and the KIMTP factor 1 score were significantly higher for the women than for the men. CONCLUSION: Overall, the sex and age distributions of scores for both questionnaires were similar to those obtained in previous studies in Japanese people. It is of note that our German subjects and previous Japanese subjects were not demographically controlled and, clearly, cultural backgrounds differed. Thus, KIMTP and the F-List may discriminate the TM personality with some degree of universality despite cultural differences and might be useful in cross-cultural comparisons of TM.     

No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia

We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30 ± 11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia.     

Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma

The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-1B (ADH1B, previously called ADH2), and ADH1C (previously called ADH3) affect the metabolism of alcohol. The inactive ALDH2 encoded by ALDH2*1/*2 and the less-active ADH1B encoded by ADH1B*1/*1 increase the risk of esophageal squamous cell carcinoma in East Asian drinkers. This case-control study involved 96 Japanese men with oral and pharyngeal squamous cell carcinoma (hypopharyngeal cancer in 43 patients and oral/oropharyngeal cancer in 53) and 642 cancer-free Japanese men. The risk of the cancers overall and of hypopharyngeal cancer was increased 3.61- and 10.08-fold, respectively, by ALDH2*1/*2 among moderate-to-heavy drinkers (9+ units/week; one unit = 22 g of ethanol), but the risk of oral/oropharyngeal cancer was not significantly affected by the ALDH2 genotype. The results obtained with a simple alcohol flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping. Among moderate-to-heavy drinkers, men with the less-active ADH1B*1/*1 had a significantly higher risk of the cancers overall, of hypopharyngeal cancer, and of oral/oropharyngeal cancer (OR = 5.56, 7.21 and 4.24, respectively). In view of the linkage disequilibrium between ADH1B and ADH1C, the ADH1C genotype does not significantly affect cancer risk. The significant independent risk factors for oral and pharyngeal cancer overall among moderate-to-heavy drinkers were inactive ALDH2*1/*2, less-active ADH1B*1/*1, frequent drinking of strong alcohol beverages straight, smoking, and lower intake of green-yellow vegetables. Educating these risks for cancer of the upper aerodigestive tract could be a useful new strategic approach to the prevention of these cancers in Japanese.     

A virtual bronchoscopic navigation system under X-ray fluoroscopy for transbronchial diagnosis of small peripheral pulmonary lesions

We had reported the utility of virtual bronchoscopic navigation system under CT-guidance for the diagnosis of small peripheral pulmonary lesions (PPLs). This study investigated the efficacy of virtual bronchoscopic navigation system for the diagnosis of small PPLs under X-ray fluoroscopy. We performed bronchoscopy with this system for 94 consecutive patients with 96 PPLs (< or =30mm in longest diameter; mean longest diameter, 16.2mm). A standard bronchoscope was used in 38 cases, and an ultrathin bronchoscope in 58 cases. Virtual bronchoscopic images were reconstructed from helical CT data. All the examinations were performed under X-ray fluoroscopy with virtual bronchoscopic navigation system, we referred both virtual bronchoscopic images and actual bronchoscopic images simultaneously to navigate the bronchoscopic pathway to the PPLs. Specimens for pathological examination were collected by transbronchial biopsy (TBB) and/or brushing. Virtual images accorded well with actual bronchoscopic images. The average total examination time was 24.1+/-7.4min (mean+/-S.D.). The overall diagnostic yields were 62.5% (60 of 96 PPLs), 71.1% (27 of 38 PPLs) with the standard bronchoscope, and 56.9% (33 of 58 PPLs) with the ultrathin bronchoscope. Diagnostic rates were 35%, 61.4% and 94.7% for lesions < or =10, 10-20, and >20mm, respectively. There were eight ground glass opacity (GGO) lesions confirmed only on CT scans; seven cases were pathologically diagnosed. All the examinations were performed safely with no complications. Bronchoscopy with virtual bronchoscopic navigation under X-ray fluoroscopy is useful for the diagnosis of small PPLs.     

Endoplasmic Reticulum Stress in Diabetic Hearts Abolishes Erythropoietin-Induced Myocardial Protection by Impairment of Phospho�CGlycogen Synthase Kinase-3�¨CMediated Suppression of Mitochondrial Permeability Transition

OBJECTIVE

Alteration in endoplasmic reticulum (ER) stress in diabetic hearts and its effect on cytoprotective signaling are unclear. Here, we examine the hypothesis that ER stress in diabetic hearts impairs phospho–glycogen synthase kinase (GSK)-3β–mediated suppression of mitochondrial permeability transition pore (mPTP) opening, compromising myocardial response to cytoprotective signaling.

RESEARCH DESIGN AND METHODS

A rat model of type 2 diabetes (OLETF) and its control (LETO) were treated with tauroursodeoxycholic acid (TUDCA) (100 mg · kg⁻¹ · day⁻¹ for 7 days), an ER stress modulator. Infarction was induced by 20-min coronary occlusion and 2-h reperfusion.

RESULTS

Levels of ER chaperones (GRP78 and GRP94) in the myocardium and level of nonphoshopho–GSK-3β in the mitochondria were significantly higher in OLETF than in LETO rats. TUDCA normalized levels of GRP78 and GRP94 and mitochondrial GSK-3β in OLETF rats. Administration of erythropoietin (EPO) induced phosphorylation of Akt and GSK-3β and reduced infarct size (% risk area) from 47.4 ± 5.2% to 23.9 ± 3.5% in LETO hearts. However, neither phosphorylation of Akt and GSK-3β nor infarct size limitation was induced by EPO in OLETF rats. The threshold for mPTP opening was significantly lower in mitochondria from EPO-treated OLETF rats than in those from EPO-treated LETO rats. TUDCA restored responses of GSK-3β, mPTP opening threshold, and infarct size to EPO receptor activation in OLETF rats. There was a significant correlation between mPTP opening threshold and phospho–GSK-3β–to–total GSK-3β ratio in the mitochondrial fraction.

CONCLUSIONS

Disruption of protective signals leading to GSK-3β phosphorylation and increase in mitochondrial GSK-3β are dual mechanisms by which increased ER stress inhibits EPO-induced suppression of mPTP opening and cardioprotection in diabetic hearts.Despite recent progress in coronary intervention strategies, diabetes is associated with higher mortality after acute myocardial infarction due to more extensive atherosclerotic lesions and hypertrophied and dysfunctional left ventricle (1–3). Therefore, diabetic patients with coronary artery diseases are patients who most require novel protective strategies against myocardial ischemia reperfusion injury. However, diabetes is known to impair responses of the myocardium to protective interventions. Protection afforded by preinfarct angina is lost in diabetic patients (4). In animal models, ischemic preconditioning (IPC) and some pharmacological agents failed to reduce infarct size in diabetic hearts (5–8). Recently, Gross et al. (7) have reported that responses of Akt, extracellular signal–related kinase (ERK), and glycogen synthase kinase (GSK)-3β to opioid receptor stimulation were blunted in streptozotocin-induced diabetes. GSK-3β has been shown to regulate a variety of cellular functions (9,10), and recent studies (10–14) have indicated that inactivation of GSK-3β by phosphorylation at Ser9 enhances myocardial tolerance against ischemia reperfusion injury. Furthermore, accumulating evidence indicates that phospho–GSK-3β–mediated cytoprotection is achieved by elevation of the threshold for opening of the mitochondrial permeability transition pore (mPTP), a probable final common step in stress-induced cell necrosis (11,15–17). However, derangements in GSK-3β regulation and its downstream targets in type 2 diabetes have not yet been clarified.The endoplasmic reticulum (ER) has received much attention recently for its role in signal transduction relevant to cell survival and death. Various pathophysiological conditions induce Ca²⁺ overload and/or accumulation of unfolding or misfolding proteins within the ER, a condition referred to as ER stress (18). ER stress induces multiple responses, including adaptive changes in translation, protein folding, secretion, and degradation. Prolonged ER stress can trigger apoptosis by induction of C/EBP homologous protein (CHOP), activation of c-JUN NH₂-terminal kinase (JNK), or caspase 12–dependent pathways. ER stress has been reported to be involved in the pathogenesis of diabetes (18–20), neurodegenerative disease, immune response, atherosclerosis, ischemia reperfusion injury, and heart failure (18,21–25).We hypothesized that ER stress is increased in the diabetic myocardium and that increased ER stress in diabetic hearts impairs phospho–GSK-3β–mediated suppression of mPTP opening, leading to loss of myocardial response to cytoprotective signaling. The rationale for this hypothesis is threefold. First, increased ER stress has been observed in epididymal fat tissue in obese diabetic mice (26). Second, an increase in GSK-3β activity induced by ER stress through dephosphorylation of phospho-Ser9 has been reported in noncardiac cells (27). Finally, elevated levels of GSK-3 protein and activity were observed in skeletal muscle of type 2 diabetic patients (28). To test our hypothesis, we investigated changes in anti-infarct tolerance, myocardial ER stress, cytoprotective signaling, and mPTP opening threshold in a rat model of type 2 diabetes. ER stress modulators, sodium tauroursodeoxycholic acid (TUDCA), and 4-phenylbutyric acid (4-PBA) (29) were used to suppress ER stress. Erythropoietin (EPO) was used to induce GSK-3β phosphorylation in this study, since we have characterized signaling pathways from the EPO receptor leading to myocardial protection and modification of the pathways by concurrent pathological conditions (13,30,31).     

Irregularity of medial femoral condyle on MR imaging serves as a possible indicator of objective severity of medial-type osteoarthritic knee—a pilot study

Irregularly described contour of the femur and the tibia on magnetic resonance (MR) imaging is commonly seen in osteoarthritic (OA) knees. The aim of this study is to examine the relationship between irregularity of contour of medial femoral condyle (tentatively named I-index) and severity of OA. Twenty-six medial-type OA knees with a mean age of 63.8 were studied. All patients had undergone MR imaging to measure the I-index using image analysis software, and its relationship to Lysholm score was examined. The I-index negatively correlated with Lysholm score (r = −0.55, p < 0.01). The I-index for each Kellgren and Lawrence grade was significantly different. We have concluded that the I-index is a potent indicator to objectively describe the severity of OA especially for the advanced stage OA.