Dualism and its place in a philosophical structure for psychiatry

Medicine, Health Care and Philosophy - It is often claimed in parts of the psychiatric literature that neuroscientific research into the biological basis of mental disorder undermines dualism in...     

Variceal hemorrhage and cystic fibrosis: outcomes and implications for liver transplantation.

Autopsy and imaging studies show that liver involvement is common in cystic fibrosis. However, complications of chronic liver disease including portal hypertension and variceal bleeding are infrequently encountered, and the degree to which variceal hemorrhage affects prognosis in cystic fibrosis is unclear. This uncertainty has lead to debate as to whether liver transplantation is indicated in these patients. We describe a case series of 18 patients and compare their survival with a control group of cystic fibrosis patients without liver disease. The median age at first bleed was 20.0 years (range 9.7-30.9). The median survival after first bleed was 8.4 years, compared to 13.0 years in the control group (P = 0.15). A total of 14 patients have died, 9 from respiratory disease with no discernable contribution from their liver disease. Liver disease contributed to 4 deaths. Only 1 patient suffered a fatal hemorrhage, which may have been either variceal or bronchial in origin. Long-term survival is a frequent occurrence in patients with cystic fibrosis who suffer variceal hemorrhage, and age at death is comparable to the general cystic fibrosis population. In conclusion, this suggests that liver transplantation is not indicated in these patients without additional features of liver decompensation.     

High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity

It has been reported that hepatitis B virus (HBV) mutants carrying mutations in the pre-S region can be found in infected patients. In this study, we investigated the prevalence of the HBV variant with the pre-S mutant in different geographic regions, including countries with low and high levels of endemic HBV infection, and analyzed the correlation with clinical findings. We examined 387 HBV DNA-positive serum samples from individuals among 12 countries, consisting of Vietnam, Myanmar, Thailand, China, Korea, Nepal, Japan, Russia, Spain, United States, Bolivia, and Ghana. HBV pre-S mutants were detected in 71 (18.3%) of 387 serum samples tested. This mutant was the most prevalent in Vietnam (36%), followed by Nepal (27.3%), Myanmar (23.3%), China (22.4%), Korea (14.3%), Thailand (10.5%), Japan (7.7%), and Ghana (4.3%). In contrast, no case with this mutation was found in Russia, Spain, United States, and Bolivia. Among the HBV deletion mutations, 15.5% (11 of 71) occurred in the pre-S1 and 46.5% (33 of 71) in the pre-S2 regions. Eight (11.3%) cases had a mutation in both the pre-S1 and pre-S2 regions. In addition, a point mutation at the pre-S2 starting codon was observed in 19 (26.7%) cases. The detection rate of the HBV mutant in patients with hepatocellular carcinoma was significantly higher than in other patients (P < 0.05). Furthermore, these mutants were found more frequently in genotype B (25%) and genotype C (24.5%) than in the other genotypes (P < 0.05). Our results indicated that there was a high prevalence of HBV pre-S mutation in regions of endemic HBV infection in Asia. Furthermore, the pre-S mutation appeared to be correlated with hepatocellular carcinoma and HBV genotypes.     

Genetic testing for inherited eye conditions in over 6,000 individuals through the eyeGENE network

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross‐referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.     

Clinical and Epidemiological Relevance of Quantitating Hepatitis E Virus-Specific Immunoglobulin M

Diagnosis of acute hepatitis E by detection of hepatitis E virus (HEV)-specific immunoglobulin M (IgM) is an established procedure. We investigated whether quantitation of HEV IgM and its ratio to HEV total Ig furnished more information than conventional IgM tests that are interpreted as positive or negative. A previously described indirect immunoassay for total Ig against a baculovirus-expressed HEV capsid protein was modified to quantitate HEV-specific IgM in Walter Reed (WR) antibody units by using a reference antiserum and the four-parameter logistic model. A receiver-operating characteristics curve derived from 197 true-positive specimens and 449 true-negative specimens identified 30 WR units/ml as an optimum cut point. The median HEV IgM level in 36 patients with acute hepatitis E fell from 3,000 to 100 WR units/ml over 6 months, suggesting that 100 WR units/ml would be a more appropriate cut point for distinguishing recent from remote IgM responses. Among three hepatitis E case series, determination of the HEV IgM-to-total-Ig ratio in acute-phase serum revealed that most patients had high ratios consistent with primary infections whereas a few had low ratios, suggesting that they had sustained reinfections that elicited anamnestic antibody responses. The diagnostic utility of the new IgM test was similar to that of a commercially available test that uses different HEV antigens. In conclusion, we found that HEV IgM can be detected specifically in >95% of acute hepatitis E cases defined by detection of the virus genome in serum and that quantitation of HEV IgM and its ratio to total Ig provides insight into infection timing and prior immunity.     

Fibrous hamartoma of infancy

Fibrous hamartoma of infancy is an uncommon fibroproliferative lesion that occurs only in infancy and childhood. The present case is unusual for the presence of two separate lesions, infiltration into the superficial muscle, infiltration and entrapment of nerves, and rapid recurrence after initial surgery. Despite these unusual and suspicious features, follow-up evaluations over the 15 months subsequent to the last resection showed no evidence of recurrence.     

Differential immunohistochemical reactions of carcinoid tumors

Neuron-specific enolase, S-100 protein, and Leu 7 are present in cells showing neuroendocrine differentiation. Leu 7 recognizes myelin-associated glycoprotein, and recent evidence suggests that it further recognizes a subset of neurosecretory granules. Forty-six primary and metastatic carcinoid tumors from various sites were evaluated immunohistochemically with antisera to neuron-specific enolase, S-100, and Leu 7. Only one tumor, a rectal carcinoid, failed to stain with neuron-specific enolase. The remaining cases showed four patterns of staining: nuclear, diffuse cytoplasmic, globular cytoplasmic, or mixed. The pattern of reaction did not correlate with either the embryonic origin or histologic pattern of the tumor. Two patterns of staining were obtained with anti-Leu 7: diffuse cytoplasmic, or dot or ring-like deposition of reaction product. The latter pattern was entirely confined to appendiceal carcinoids. Reactivity with S-100 was in the form of dense positivity in individual cells having a stellate outline. Less intense cytoplasmic positivity and, uncommonly, a mixture of both types of staining were also seen. These histochemical results may lend support to recent evidence suggesting the existence of identifiable subsets of neurosecretory granules in neuroendocrine tumors, including carcinoids.     

Mast cell desensitization to IgE fails to induce a parallel adenosine receptor desensitization

Desensitization induced by challenge of mast cells with antigen is specific for IgE-dependent signals. During the secretory process mast cells release adenosine, which can induce a desensitization of adenosine receptors. To determine whether adenosine receptors may de desensitized from a previous antigen challenge, mast cells were sensitized with anti-DNP IgE antibody, challenged with DNP-BSA antigen, returned to culture overnight, resensitized, and rechallenged. Previously challenged cells exhibited increased spontaneous -hexosaminidase release, but adenosine retained its ability to augment -hexosaminidase release. Adenosine enhanced A23187-stimulated release of -hexosaminidase in control and previously challenged cells. Leukotriene C₄ generation followed a similar pattern. Mastoparan, a direct G protein activator and mast cells secretogogue, produced a doubling of -hexosaminidase release in previously challenged cells. Results using other G protein activators were equivocal. Degranulation alone is insufficient to induce adenosine receptor hyposensitization. Whether the hyperresponsiveness to mastoparan is a consequence of uncoupling of IgE receptors from G proteins remains uncertain.