An ecological momentary assessment study of age effects on perceptive and non-perceptive clinical high-risk symptoms of psychosis.

Among individuals with clinical high risk for psychosis (CHR), perceptive symptoms are more frequent but have less clinical significance in children/adolescents compared to adults. However, findings are based on clinical interviews relying on patient's recall capacity. Ecological momentary assessment (EMA) can be used to explore experiences in real-time in the subject's daily life. The aim of this study was to assess frequency and stability of (perceptive and non-perceptive) CHR symptoms and to explore potential age effects. EMA was used in a sample of an early detection for psychosis service in Bern, Switzerland (N = 66; 11-36 years). CHR symptoms were recorded in random time intervals for seven days: eight assessments per day per subject, minimum time between prompts set at 25 min. CHR symptoms were additionally assessed with semi-structured interviews including the 'Structured Interview for Psychosis-Risk Syndromes' and the 'Schizophrenia Proneness Instruments'. Mixed-effects linear regression analysis on the frequency of CHR symptoms revealed a significant effect of age group, and the interaction CHR symptoms x age group for both perceptive and non-perceptive symptoms. Further, regarding stability of CHR symptoms, there was a significant effect of the interaction CHR symptoms x age group for perceptive symptoms only. Based on EMA, perceptive CHR symptoms were more frequently reported but less stable in children/adolescents compared with adults. Together with previous findings, our finding of higher instability/variability of perceptive symptoms in younger persons might suggest that with advancing age and more stability of CHR symptoms, clinical relevance (reduced psychosocial functioning) may increase.

Bone density in youth with prediabetes: results from the National Health and Nutrition Examination Survey, 2005-2006.

Youth with type 2 diabetes might have suboptimal peak bone mass, but it is unknown whether similar effects are evident in youth with prediabetes. Results from this study suggest that diabetes-related effects on peak bone mass likely occur before disease onset, and involve the muscle-bone unit. INTRODUCTION: Type 2 diabetes might adversely influence bone health around the age of peak bone mass, but it is unknown whether diabetes-related effects on areal bone mineral density (aBMD) are evident in youth with prediabetes. We compared age-related trends in aBMD and associations between lean body mass (LBM) and aBMD between children and adolescents with prediabetes vs. normal glucose regulation. METHODS: Cross-sectional analysis of data from the National Health and Nutrition Examination Survey (2005-2006) in youth ages 12-20 years (49% female, 34% black) with prediabetes (n = 267) and normal glucose regulation (n = 1664). Whole body aBMD and LBM were assessed via DXA. LBM index (LBMI) and Z-scores for aBMD and LBMI were computed. RESULTS: Unadjusted between-group comparisons revealed greater mean weight and LBMI Z-scores in youth with prediabetes vs. normal glucose regulation, but similar bone Z-scores between the two groups. While accounting for differences in BMI Z-score, there was a significant interaction between prediabetes status and age with respect to whole body aBMD Z-score (P < 0.05), such that children with prediabetes tended to have increased aBMD but adolescents and young adults with prediabetes tended have lower aBMD. Furthermore, the positive association between LBMI and whole body aBMD was moderated in youth with prediabetes (P < 0.001), who had slightly lower whole body aBMD for a given LBMI (P = 0.068). Lumbar spine bone measures did not differ between the two groups. CONCLUSIONS: Type 2 diabetes-related threats to peak bone mass might occur prior to disease onset, therefore potentially impacting a considerable proportion of US youth.

Whole egg consumption and cortical bone in healthy children.

Eggs contain bioactive compounds thought to benefit pediatric bone. This cross-sectional study shows a positive link between childhood egg intake and radius cortical bone. If randomized trials confirm our findings, incorporating eggs into children's diets could have a significant impact in preventing childhood fractures and reducing the risk of osteoporosis. INTRODUCTION: This study examined the relationships between egg consumption and cortical bone in children. METHODS: The cross-sectional study design included 294 9-13-year-old black and white males and females. Three-day diet records determined daily egg consumption. Peripheral quantitative computed tomography measured radius and tibia cortical bone. Body composition and biomarkers of bone turnover were assessed using dual-energy X-ray absorptiometry and ELISA, respectively. RESULTS: Egg intake was positively correlated with radius and tibia cortical bone mineral content (Ct.BMC), total bone area, cortical area, cortical thickness, periosteal circumference, and polar strength strain index in unadjusted models (r = 0.144-0.224, all P < 0.050). After adjusting for differences in race, sex, maturation, fat-free soft tissue mass (FFST), and protein intakes, tibia relationships were nullified; however, egg intake remained positively correlated with radius Ct.BMC (r = 0.138, P = 0.031). Egg intake positively correlated with total body bone mineral density, BMC, and bone area in the unadjusted models only (r = 0.119-0.224; all P < 0.050). After adjusting for covariates, egg intake was a positive predictor of radius FFST (ß = 0.113, P < 0.050) and FFST was a positive predictor of Ct.BMC (ß = 0.556, P < 0.050) in path analyses. There was a direct influence of egg on radius Ct.BMC (ß = 0.099, P = 0.035), even after adjusting for the mediator, FFST (ß = 0.137, P = 0.020). Egg intake was positively correlated with osteocalcin in both the unadjusted (P = 0.005) and adjusted (P = 0.049) models. CONCLUSION: If the positive influence of eggs on Ct.BMC observed in this study is confirmed through future randomized controlled trials, whole eggs may represent a viable strategy to promote pediatric bone development and prevent fractures.

Ethnic differences in vitamin D status, bone and body composition in South Asian indian and caucasian men.

Background: High prevalence of metabolic abnormalities and poor bone health in ethnic minorties may stem from differences in body composition and alterations in endocrine milieu. South Asian Indians (SAIs) are at greater risk for metabolic syndrome (MetS) and poor bone health than Caucasians. Often these differences are reported later in life and/or in a resident immigrant population compared to a Caucasian population. In this study, we determined whether vitamin D status, bone, body composition differed in young SAIs and Caucasians. Notably we compared differences amongst recent SAI immigrants and Caucasians. Methods: We examined differences in bone density, body composition, serum 25-hydroxy vitamin D (s25(OH)D), parathyroid hormone (sPTH), vitamin D binding protein (sDBP), osteocalcin (sOC), and dietary intakes in young healthy SAI and Caucasian men. Results: Sixty men (N = 30 SAIs and N = 30 Caucasians) with a mean age of 27.8 ± 7.4 years completed the study. Compared to the Caucasians, SAIs had statistically significantly lower s25(OH)D and higher sPTH (p < 0.05). We also found that s25(OH)D was negatively associated with sPTH only among the SAIs (r = - 0.389, p = 0.037). Also, lean mass% (LM%) and fat-free mass% (FFM%) were lower in SAIs (p < 0.05) compared to caucasians. s25(OH)D correlated with nearly all body composition parameters, while sPTH correlated negatively with LM% and FFM%, and positively with FM% (all p < 0.05) in the Caucasian group. Bone mineral density at most sites were also significantly lower (p < 0.05) in the SAI's compared to caucasians. Conclusion: Young SAIs have a poor vitamin D status and less favorable bone and body composition parameters compared to Caucasians. These findings highlight the possible complex interplay between skeletal and metabolic health in different ethnicities which may be evident early on in life. Interventions to improve bone and metabolic health should therefore target younger ethnic minorities.

Elevated bilirubin in acute and transient psychotic disorder.

INTRODUCTION: Mild unconjugated hyperbilirubinemia seems to be more common in patients with disorders from the schizophrenic spectrum than in other psychiatric patients or in the general population and has been linked to brain alterations. This spectrum however contains a number of diagnostic entities that might not share the same etiological and environmental factors. METHODS: 325 hospital admissions were analysed over a one-year period. RESULTS: We found an association of acute and transient psychotic disorders (ATPD) with total bilirubin level and rate of elevated total bilirubin that was increased compared to paranoid schizophrenia and schizoaffective disorder, all patients, and was higher than in the general population. Concomitant increased direct bilirubin might suggest that reduced UGT activity, causing Gilbert's syndrome in the general population, is not the reason for elevated bilirubin in ATPD. CONCLUSIONS: The difference between ATPD and schizophrenia/schizoaffective disorder might be due to disorder severity, aetiology, or environmental factors that influence enzyme activity.

Preliminary findings of four-week, task-based anodal prefrontal cortex transcranial direct current stimulation transferring to other cognitive improvements in schizophrenia.

Most transcranial Direct Current Stimulation (tDCS) trials of schizophrenia administer few sessions and do not assess transfer effects to other cognitive domains. In a randomized, double-blind, sham-controlled, parallel groups trial, we determined the extent to which 4-weeks of 2 mA tDCS at 20 min/day totalling 20 tDCS sessions administered during a spatial working memory test, with anodal right dorsolateral prefrontal cortex (DLPFC) and cathodal left tempo-parietal junction (TPJ) placement, as an adjunct to antipsychotics reduced auditory hallucinations and improved cognition in 12 outpatients with schizophrenia. Anodal tDCS significantly improved language-based working memory after 2 weeks and verbal fluency after 2 and 4 weeks. Thus, four weeks of tDCS appears to be safe and elicits transfer benefits to other prefrontal-dependent cognitive abilities in schizophrenia.

Adjunctive selective estrogen receptor modulator increases neural activity in the hippocampus and inferior frontal gyrus during emotional face recognition in schizophrenia.

Estrogen has been implicated in the development and course of schizophrenia with most evidence suggesting a neuroprotective effect. Treatment with raloxifene, a selective estrogen receptor modulator, can reduce symptom severity, improve cognition and normalize brain activity during learning in schizophrenia. People with schizophrenia are especially impaired in the identification of negative facial emotions. The present study was designed to determine the extent to which adjunctive raloxifene treatment would alter abnormal neural activity during angry facial emotion recognition in schizophrenia. Twenty people with schizophrenia (12 men, 8 women) participated in a 13-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment (120 mg per day orally) and performed a facial emotion recognition task during functional magnetic resonance imaging after each treatment phase. Two-sample t-tests in regions of interest selected a priori were performed to assess activation differences between raloxifene and placebo conditions during the recognition of angry faces. Adjunctive raloxifene significantly increased activation in the right hippocampus and left inferior frontal gyrus compared with the placebo condition (family-wise error, P<0.05). There was no significant difference in performance accuracy or reaction time between active and placebo conditions. To the best of our knowledge, this study provides the first evidence suggesting that adjunctive raloxifene treatment changes neural activity in brain regions associated with facial emotion recognition in schizophrenia. These findings support the hypothesis that estrogen plays a modifying role in schizophrenia and shows that adjunctive raloxifene treatment may reverse abnormal neural activity during facial emotion recognition, which is relevant to impaired social functioning in men and women with schizophrenia.

Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls.

CONTEXT: IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship. OBJECTIVE: We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years. MAIN OUTCOME MEASURES: Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height. RESULTS: In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P < .001). IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047). CONCLUSIONS: Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.

Antihypertensive effects of captopril and saralasin in essential and renal hypertension.

The antihypertensive effect of captopril and its mechanism of action were studied in patients with essential and renal hypertension. In mild essential hypertension (n = 12), during monotherapy with captopril (50 to 450 mg, 4 to 12 weeks) blood pressure was normalized in seven, improved in two and remained unchanged in three patients, plasma levels of active and acid-activatable inactive renin significantly increased and angiotensin II decreased, whereas no consistent changes in urinary kallikrein excretion occurred. In severe renal (n = 14) and essential (n = 9) hypertension, blood pressure was normalized in eight (seven with renal hypertension), improved in seven and unchanged in eight patients, when captopril (50 to 450 mg, 3 to 15 months) was added to the antihypertensive medication. In one patient with stenosis in a transplanted renal artery reversible renal failure occurred during captopril therapy possibly because of a steep initial decrease in blood pressure, although a toxic effect of the drug cannot be excluded. In another series of 12 renal and 8 essential hypertensive patients, a significant correlation between the acute effect of captopril (within 90 minutes) an saralasin on blood pressure was demonstrated (r=0.71, p less than 0.001). The change in blood pressure after either drug was significantly related to the initial plasma renin concentration. In conclusion, captopril seems to be an effective antihypertensive agent in essential and renal hypertension. Renal function should be monitored during captopril therapy. Our studies suggest that captopril decreases blood pressure by inhibiting the vasopressor action of the renin-angiotensin system.

Coronary vasculopathy in polycythemia vera.

Thrombosis is a common complication in polycythemia often causing death. In coronary artery occlusion, thrombosis due to hyperviscosity and thrombocytosis is mostly discussed as the origin of the infarction. We discuss the case of a 30-year-old male patient, with polycythemia, who died of myocardial infarction. On autopsy the vessels showed neither ateriosclerotic changes nor thrombotic occlusions. Instead, a marked intima proliferation was found leading to multiple occlusions whereas media and adventitia were unchanged. This pattern of a coronary vasculopathy has not been described before, and can be interpreted as an alternative mechanism for vascular occlusion in polycythemia. Similar histopathological changes have already been found in skin lesions in erythromelalgia, a common symptom in polycythemia.

Long-term ciclosporine A treatment in adults with minimal change nephrotic syndrome or focal segmental glomerulosclerosis.

To evaluate the efficacy and safety of long-term ciclosporine A (CSA) treatment in idiopathic nephrotic syndrome, we prospectively followed immunosuppressive therapy in 22 nephrotic adults for a median of 32 months (range 7-91 months) and obtained repeat renal biopsies. CSA induced complete remission in 60.0% and 14.3% of patients with minimal change nephrotic syndrome (MCNS) (n = 7), respectively. In addition, partial remissions were achieved in 20.0% of patients with MCNS and in 42.9% of patients with FSGS. Resolution of proteinuria was strictly CSA-dependent and no sustained remission occurred following withdrawal, thereby requiring long-term treatment in 18 patients. In 10 patients CSA was administered for more than 43 months. During maintenance therapy the antiproteinuric effect of CSA was preserved and renal function as well as blood pressure remained stable in patients with MCNS, whereas renal function deteriorated in two patients with FSGS due to progression of the underlying renal disease. Renal biopsies revealed slight signs of CSA toxicity in four patients. However, in no case loss of renal function was attributable to these lesions. In conclusion, the present data suggest that long-term maintenance treatment of MCNS with CSA is efficacious and safe at least for a period of up to 43 months. In contrast, CSA has some effect on proteinuria in FSGS, but the results are less favorable.

Cerebral blood flow identifies responders to transcranial magnetic stimulation in auditory verbal hallucinations.

Auditory hallucinations comprise a critical domain of psychopathology in schizophrenia. Repetitive transcranial magnetic stimulation (TMS) has shown promise as an intervention with both positive and negative reports. The aim of this study was to test resting-brain perfusion before treatment as a possible biological marker of response to repetitive TMS. Twenty-four medicated patients underwent resting-brain perfusion magnetic resonance imaging with arterial spin labeling (ASL) before 10 days of repetitive TMS treatment. Response was defined as a reduction in the hallucination change scale of at least 50%. Responders (n=9) were robustly differentiated from nonresponders (n=15) to repetitive TMS by the higher regional cerebral blood flow (CBF) in the left superior temporal gyrus (STG) (P<0.05, corrected) before treatment. Resting-brain perfusion in the left STG predicted the response to repetitive TMS in this study sample, suggesting this parameter as a possible bio-marker of response in patients with schizophrenia and auditory hallucinations. Being noninvasive and relatively easy to use, resting perfusion measurement before treatment might be a clinically relevant way to identify possible responders and nonresponders to repetitive TMS.

Resting-state EEG in schizophrenia: auditory verbal hallucinations are related to shortening of specific microstates.

OBJECTIVE: Abnormal perceptions and cognitions in schizophrenia might be related to abnormal resting states of the brain. Previous research found that a specific class (class D) of sub-second electroencephalography (EEG) microstates was shortened in schizophrenia. This shortening correlated with positive symptoms. We questioned if this reflected positive psychotic traits or present psychopathology. METHODS: Resting-state EEGs of frequently hallucinating patients, indicating on- and offset of hallucinations by button press, were analyzed. Microstate class D duration was related to spontaneous within-subject fluctuations of auditory hallucinations. RESULTS: Microstate D was significantly shorter in periods with hallucinations. CONCLUSIONS: Microstates of class D resemble topographies associated with error monitoring. Its premature termination may facilitate the misattribution of self-generated inner speech to external sources during hallucinations. SIGNIFICANCE: These results suggest that microstate D represents a biological state marker for hallucinatory experiences.

[Septic shock with purpura fulminans after a dog bite]. / Sepsis mit Purpura Fulminans nach Hundebiss.

HISTORY AND CLINICAL FINDINGS: A 61-year-old man presented with a four-day history of back pain and nonspecific abdominal pain. His condition had significantly worsened since the day before admission with generalized weakness and dyspnea. His temperature was 39.1 C, he had tachycardia and was tachypneic. Peripheral cyanosis was noted. The abdomen was soft with mild epigastric tenderness. A diffuse skin rash developed with increasing petechial bleeding and central necrosis. It was revealed that he had been bitten by a dog several weeks before admission. INVESTIGATIONS: Laboratory data indicated an acute inflammatory process with a marked increase in white blood cells and C-reactive protein. An elevated procalcitonin level suggested a systemic bacterial infection. Chest X-ray and abdominal CT scan were unremarkable. Echocardiography revealed a globally hypokinetic heart with no evidence of valvular vegetations. One set of blood cultures grew micro-aerophilic, Gram-negative rods. Gene sequencing identified the slow growing, fastidious bacillus as CAPNOCYTOPHAGA CANIMORSUS. TREATMENT AND COURSE: The patient was admitted to the intensive care unit and initially treated with intravenous piperacillin/tazobactam and hydrocortisone for septic shock. Transfusions of platelets and blood products were given because of disseminated intravascular coagulation. The patient developed multi-organ failure requiring ventilation and hemodialysis; he died four days after admission. CONCLUSIONS: As a rare cause of septicemia, especially in immunocompromised patients, Capnocytophaga canimorsus infection should be considered after an animal bite. Given the slow growth of this bacterium in culture, Gram-staining of a peripheral blood smear may provide an early diagnosis and avoid delay before appropriate antibiotic therapy, which may favorably influence the potentially fatal course, is started.