Increased dopaminergic activity in socially isolated rats: An electrophysiological study

The development of animal models mimicking symptoms associated with schizophrenia has been a critical step in understanding the neurobiological mechanisms underlying the disease. Long-term social isolation from weaning in rodents, a model based on the neurodevelopmental hypothesis of schizophrenia, has been suggested to mimic some of the deficits seen in schizophrenic patients. We confirm in the present study that socially isolated rats display an increase in both spontaneous and d-amphetamine-induced locomotor activity, as well as deficits in sensorimotor gating as assessed in a pre-pulse inhibition paradigm. In addition, in vivo electrophysiological studies revealed changes in dopaminergic cell firing activity in the ventral tegmental area of isolated rats when compared to group-housed controls. These alterations include an increase in the number of spontaneously active dopaminergic neurons, and a change of firing activity towards a more irregular and bursting firing pattern. Taken together, our findings suggest that the behavioral phenotype induced by social isolation may be driven by an overactive dopamine system.     

Conversion of oral alfacalcidol to oral calcitriol in the treatment of secondary hyperparathyroidism in chronic hemodialysis patients

International Urology and Nephrology - The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent...     

Proxy‐reported health‐related quality of life of patients with juvenile idiopathic arthritis: The pediatric rheumatology international trials organization multinational quality of life cohort study

Objective

To investigate the proxy‐reported health‐related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA).

Methods

In this multinational, multicenter, cross‐sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. Potential determinants of HRQOL included demographic data, physician's and parent's global assessments, measures of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate.

Results

A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean ± SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 ± 10.6 versus 54.6 ± 4.0, P < 0.0001; psychosocial: 47.6 ± 8.7 versus 51.9 ± 7.5, P < 0.0001), with the physical well‐being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score >1 and a pain intensity rating >3.4 cm on a 10‐cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively.

Conclusion

We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well‐being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health.     

RV Fractional Area Change and TAPSE as Predictors of Severe Right Ventricular Dysfunction in Pulmonary Hypertension: A CMR Study

Background

The right ventricular ejection fraction (RVEF) is a surrogate marker of right ventricular function in pulmonary hypertension (PH), but its measurement is complicated and time consuming. The tricuspid annular plane systolic excursion (TAPSE) measures only the longitudinal component of RV contraction while the right ventricular fractional area change (RVFAC) takes into account both the longitudinal and the transversal components. The aim of our study was to evaluate the relationship between RVEF, RVFAC, and TAPSE according to hemodynamic severity in two groups of patients with PH: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Methods and Results

Fifty-four patients with PAH (n?=?15) and CTEPH (n?=?39) underwent right heart catheterization and cardiac magnetic resonance (CMR). The ventricular volumes and areas, TAPSE, and eccentricity index were measured. The RVFAC was more strongly correlated with the RVEF (r?=?0.81, p?<?0.0001) than the TAPSE (r?=?0.63, p?<?0.0001). RVEF?<?35% was better predicted by the RVFAC than the TAPSE (TAPSE: AUC?=?0.77 and RVFAC: AUC?=?0.91; p?=?0.042). In the group with the worse hemodynamic status, the RVFAC correlated much better with the RVEF than the TAPSE. There were no significant differences in the CMR data analyzed between the groups of PAH and CETPH patients.

Conclusions

The RVFAC is a good index to estimate RVEF in PH patients; even better than the TAPSE in patients with more severe hemodynamic profile, possibly for including the transversal component of right ventricular function in its measurement. Furthermore, RVFAC performance was similar in the two PH groups (PAH and CTEPH).

     

Effectiveness of diabetes mellitus screening recommendations

Screening guidelines proposed by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus have been endorsed by several medical societies. However, one-third of cases are undiagnosed, and complications at the time of diagnosis indicate that disease may have been present for several years before diagnosis. This study evaluates the effectiveness of the guidelines for detecting new cases of diabetes mellitus. By using a cross-sectional, representative sample of the United States (National Health and Nutritional Examination Survey, NHANES III), the guidelines are tested on adults, 20 years and older without a prior diagnosis of diabetes. Individuals are classified as nondiabetics (n = 6,241) or as having undiagnosed diabetes (n = 274) based on their blood glucose. Screening when one risk factor is present, as stated in the guidelines, has a true-positive rate of 100% and would require that 83% of the population be tested. Screening when two risk factors are present is more efficient, with a comparable true-positive rate (98%), but requires that only 59% of the population be tested. A notable finding is the earlier age of onset among minorities, which may be associated with other health disparities. Because diabetes occurs at younger ages in minorities, screening whites who are > or =40 and minorities > or =30 years of age has a high true-positive rate (95%) and also reduces testing (60%). The screening guidelines would be effective, if followed, and would essentially eliminate undiagnosed cases of diabetes.     

Quantitative study of digestive enzyme secretion and gastrointestinal lipolysis in chronic pancreatitis.

BACKGROUND & AIMS: The contribution of human gastric lipase (HGL) to the overall lipolysis process in chronic pancreatitis (CP), as well as the relative pancreatic enzyme levels, rarely are addressed. This study was designed to quantify pancreatic and extrapancreatic enzyme output, activity, and stability in CP patients vs. healthy volunteers. METHODS: Healthy volunteers (n = 6), mild CP patients (n = 5), and severe (n = 7) CP patients were intubated with gastric and duodenal tubes before the administration of a test meal. HGL, human pancreatic lipase (HPL), chymotrypsin, and amylase concentrations were assessed in gastric and duodenal samples by measuring the respective enzymatic activities. Intragastric and overall lipolysis levels at the angle of Treitz were estimated based on quantitative analysis of lipolysis products. Similar analyses were performed on duodenal contents incubated ex vivo for studying enzyme stability and evolution of lipolysis. RESULTS: Although HPL, chymotrypsin, and amylase outputs all were extremely low, HGL outputs in patients with severe CP (46.8 +/- 31.0 mg) were 3-4-fold higher than in healthy controls (13.3 +/- 13.8 mg). Intragastric lipolysis did not increase, however, in patients with severe CP, probably because of the rapid decrease in the pH level of the gastric contents caused by a higher gastric acid secretion. HGL remains active and highly stable in the acidic duodenal contents of CP patients, and, overall, can achieve a significant lipolysis of the dietary triglycerides (30% of the control values) in the absence of HPL. CONCLUSIONS: Although all pancreatic enzyme secretions are simultaneously reduced in severe CP, gastric lipase can compensate partly for the loss of pancreatic lipase but not normalize overall lipolytic activity.