Efficacy of ECT in Psychotic and Nonpsychotic Depression

The authors examined reports addressing the question of whether electroconvulsive therapy (ECT) is more effective in psychotic or nonpsychotic depressive disorders. Most ECT studies did not consider the issue directly, and those that did had varying methodologies and results. The authors then analyzed the data of 33 depressed patients to clarify the differential response to ECT in 13 psychotic and 20 nonpsychotic patients. The subjects were also examined as to type of electrode placement. ECT produced a greater reduction in Hamilton Depression Rating Scale scores in the psychotic depressives as compared to the nonpsychotics after an average of 9.2 treatments. The two patients who were nonresponders to ECT were both nonpsychotic.     

Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk

Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of visual impairment in developed countries. Risk factors include environmental components and genetic determinants. The complement factor H (CFH) has been the first major susceptibility gene for AMD identified within 1q32. Here, we focused on a second region of interest in 10q26 where a recent meta-analysis revealed strongest evidence for linkage to AMD at a genome-wide significance level. Within an interval of 22 Mb, we have analyzed 93 single nucleotide polymorphisms for allelic association with AMD in two independent case-control cohorts of German origin (AMD(combined) n=1166; controls(combined) n=945). Significant association was found across a 60 kb region of high linkage disequilibrium harboring two genes PLEKHA1 and hypothetical LOC387715. The strongest association (P=10(-34)) centered over a frequent coding polymorphism, Ala69Ser, at LOC387715, strongly implicating this gene in the pathogenesis of AMD. Besides abundant expression in placenta, we demonstrate weak expression of LOC387715 in the human retina. At present, however, there is no functional information on this gene, which appears to have evolved recently within the primate lineage. The joint contribution of the common risk allele at LOC387715, Ala69Ser, and at CFH, Tyr402His, was assessed in our case-control population, which suggests an additive model indicating an independent contribution of the two gene loci to disease risk. Our data show a disease odds ratio of 57.6 (95% CI: 37.2, 89.0) conferred by homozygosity for risk alleles at both CFH and LOC387715 when compared with the baseline non-risk genotype.     

An ELISA serum assay for autoantibodies to HSP70 in immune-mediated hearing loss

A Western blot to detect anti-HSP70 autoantibodies has been reported to be of diagnostic value for immune-mediated hearing loss patients. While setting up this Western blot in our lab, we detected two main problems. First, some patients were positive for antibodies to a 70-kDa protein when tested against a whole cell lysate, but negative if the antigen used was purified HSP70. Second, if high amounts of purified HSP70 were loaded on the gel, both patients and healthy controls were positive. We have developed and optimized an ELISA as an alternative to the Western blot. This assay is more appropriate to identify positive and negative individuals because it is semi-quantitative. The ELISA is also more sensitive, requiring very low concentrations of the antigen and thus minimizing false positives. Finally, we demonstrated that immune-mediated hearing loss patients recognize mainly the native form of HSP70, a fact that potentially leads to false negatives when a denaturing Western blot assay is used for diagnosis. To test the diagnostic value of the ELISA, we performed a blind test with 70 hearing loss patients, as well as 30 healthy controls. A sensitivity of 84% and a specificity of 93% were obtained, superior to what has been reported so far for the Western blot.     

Speech characteristics in the Kabuki syndrome

Six children with Kabuki syndrome were studied to investigate speech patterns associated with the syndrome. Each child's speech was characterized with regard to articulation (types of errors and intelligibility), pitch (high or low), loudness (volume of speech), and prosody (general quality of speech that combines rate and inflection). All six children had a history of delayed speech and language acquisition and were receiving speech services. All individuals had articulation errors and abnormal oral resonance, which appeared to be due to poor oral-motor coordination and hypotonia and were not felt to be due to structural abnormalities such as velopharyngeal insufficiency, dental malocclusion, or cleft palate. An intriguing finding, noted in the two individuals followed from childhood into adolescence with serial speech evaluations, was that pitch, loudness, and prosody did not mature over time and what was age appropriate performance at younger ages became inappropriate in adolescence. This raises a challenge for speech services, as by adolescence, while articulation had improved, the pitch and loudness of these individuals' speech had not and so was noticeably different from peers. Distinctive speech characteristics with a lack of normal maturation during childhood can be added to the extensive list of clinical features associated with the Kabuki syndrome and hopefully will lead to improved speech/language treatment for individuals with this syndrome.     

Association of DLG5 R30Q variant with inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system known as the inflammatory bowel diseases (IBD). Recently, Stoll and colleagues reported a novel finding of genetic variation in the DLG5 gene that is associated with IBD (CD and UC combined). We present here a study of the genetic variation described in that report in two well-powered, independent case-control cohorts and one family-based collection, and confirm the proposed association between IBD and the R30Q variant of DLG5 in two of the three studies. We are, however, unable to replicate the other proposed association to the common haplotype described in Stoll et al and suggest that this other finding could conceivably have been partially a statistical fluctuation and partially a result of LD with the replicated R30Q association. This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect.     

Hepatitis B virus transmission in Brazilian hemodialysis units: serological and molecular follow-up

A serological and molecular study of hepatitis B virus (HBV) infection was carried out in dialysis units in Central Brazil. Between 1995 and 1999, serum samples from all HBsAg-positive hemodialysis patients (n = 43) were tested for HBeAg/anti-HBe and subtyping by monoclonal ELISA. HBV DNA was detected by PCR and positive samples were genotyped by restriction fragment polymorphism pattern (RFLP) methodology. TheHBsAg prevalence declined in this population during the survey period (12-5.8%). HBeAg and anti-HBe were detected in 23 (53.5%) and 18 (41.9%) sera, respectively. Thirty-six samples could be HBsAg subtyped: 21 were subtype ayw(3), 14 belonged to adw(2) and one was identified as adw(4). HBV DNA was present in 30 serum samples. Of these, 20 (66.7%) were genotype D, 9 (30%) genotype A, and 1 (3.3%) genotype F. In addition, the RFLP pattern could be determined in samples from 18/20 genotype D patients: D3 (10 strains), D7 (7 strains) and D4 (1 strain); from 8/9 genotype A patients: A1 (6 strains) and A3 (2 strains); and from the patient infected with genotype F: F1. Patterns D3 and D7 were associated closely with HBV infection in the two largest hemodialysis units studied. These findings confirm the value of the RFLP method as an effective molecular epidemiological tool for elucidating HBV transmission in hemodialysis units.     

Fulminant disseminated Varicella Zoster virus infection without skin involvement.

BACKGROUND: Varicella Zoster virus (VZV) infection is potentially very serious in bone marrow transplant recipients, and may manifest as a disseminated visceral infection. This condition is generally accompanied by a vesicular rash. OBJECTIVES: We review here a case of fulminant fatal disseminated VZV infection, not accompanied by skin involvement, and the laboratory approaches currently available to diagnose this disease. STUDY DESIGN: Post mortem tissue samples were subjected to histopathological examination, and tested for herpesviruses by electron microscopy and PCR. RESULTS: Intranuclear inclusions were noted by histological examination in the lungs, liver, kidneys and bone marrow. Particles with a herpesvirus morphology were visualized in liver tissue. VZV DNA was detected in liver and bone marrow by PCR followed by sequencing of the amplicons. Viremia was documented by retrospective testing of the serum by PCR. CONCLUSIONS: A disseminated VZV infection which proved rapidly fatal was demonstrated in a case without skin manifestations. This rare presentation of VZV infection is potentially underdiagnosed. Testing for VZV viremia by PCR can at the very least suggest the diagnosis although whether plasma-associated viremia is truly pathognomonic of visceral disseminated infection remains to be established.