Distal Proctocolitis and n-3 Polyunsaturated Fatty Acids (n-3 PUFAs): The Mucosal Effect In Situ

It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis.     

Cost-effectiveness of community psychiatric nurse or out-patient psychiatrist care of neurotic patients

In a prospective controlled investigation chronic patients, the majority with neurotic conditions, were randomly allocated either to community psychiatric nurses (CPN) as the main therapist or to routine out-patient psychiatrist follow-up. There was no statistically significant difference in the mean public expenditure for the two modes of care. The direct costs of psychiatric care comprised a small proportion of total public expenditure and were initially greater in the nursing group. Subsequently, and over the whole 18-month study period, nursing was the cheaper option in terms of these direct costs. Clinical and social outcomes were comparable in both follow-up groups. Consumer satisfaction was significantly greater among CPN patients. On balance, these results confirm the benefit of community psychiatric nursing for this patient group.     

Effect of RGD coating on osteocompatibility of PLGA-polymer disks in a rat tibial wound

Osteocompatibility of porous polylactic-glycolic acid (PLGA) disks coated with synthetic peptides was assessed in 5-mm diameter unicortical tibial osseous wounds in rats. The coatings consisted of various ratios of peptides including the tripeptide arginine-glycine-aspartic acid (RGD) and the inactive arginine-glycine-glutamic acid (RGE). When left empty, the tibial wounds healed spontaneously with proliferation of intramedullary woven bone within 1 week. The reactive bone was resorbed, and by 3 weeks, the cortical wound was healed with lamellar bone, and the medullary space was repopulated with marrow. When PLGA disks were implanted there was a delay in repair with reduced bone fill and no bone bridging at 3 weeks. When disks were coated with increasing amounts of RGD peptide, there was a biphasic effect on osteocompatibility and on osseous ingrowth. Evaluation at 10 days showed a dose-dependent increase, with 1.5-fold greater osteocompatibility (p < 0.05) and 1.6-fold more osseous ingrowth into the polymer (p < 0.01) than uncoated disks. With more RGD and with undiluted RGE, osteocompatibility and osseous ingrowth were the same as with uncoated disks. At 3 weeks, there were no significant differences among all the groups. These data indicate that RGD coating enhanced early stages of osteocompatibility and ingrowth.     

Performance of a commercial, type-specific enzyme-linked immunosorbent assay for detection of herpes simplex virus type 2-specific antibodies in Ugandans

Two hundred forty-eight human immunodeficiency virus (HIV)-positive and 496 HIV-negative subjects in Uganda were tested by HerpeSelect herpes simplex virus type 2 enzyme-linked immunosorbent assay (ELISA) and Western blotting to optimize the ELISA for use in this population. A higher index cutoff value was required for optimal sensitivity and specificity, and overall performance of the assay was not affected by HIV status.     

Aspergillus fumigatus empyema, arthritis, and calcaneal osteomyelitis in a lung transplant patient successfully treated with posaconazole

A 64-year-old male with Aspergillus fumigatus infection that had disseminated from the lung to the ankle and adjacent bone was treated successfully with posaconazole after therapy with itraconazole and amphotericin B lipid complex failed. Marked clinical improvement occurred within 6 weeks of initiation of posaconazole therapy; after 6 months, infection had resolved at all sites. The patient has had no recurrence of infection.     

Investigation of de novo variation in pediatric cardiomyopathy

Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal dominant manner with variable expressivity. De novo variants have been reported, however their overall frequency is largely unknown. We sought to determine the rate of de novo, pathogenic and likely pathogenic (P/LP) variants in children with a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy (HCM, DCM, or RCM), and to compare disease outcomes between individuals with and without a de novo variant. A retrospective record review identified 126 individuals with HCM (55%), DCM (37%), or RCM (8%) ≤18 years of age who had genetic testing. Overall, 50 (40%) had positive genetic testing and 18% of P/LP variants occurred de novo. The rate of de novo variation in those with RCM (80%) was higher than in those with HCM (9%) or DCM (20%). There was evidence of germline mosaicism in one family with RCM. Individuals with de novo variants were more likely than those without to have a history of arrhythmia (p = .049), sudden cardiac arrest (p = .024), hospitalization (p = .041), and cardiac transplantation (p = .030). The likelihood of de novo variation and impact on family risk and screening should be integrated into genetic counseling.     

Inbred guinea pig model of intrauterine infection with cytomegalovirus.

Outbred guinea pigs have previously been utilized in an experimental model for the study of congenital infection with cytomegalovirus (CMV). Development of an inbred model of intrauterine CMV infection would allow analysis of the cells involved in CMV immunity, studies of transplacental CMV transfer, and investigation of the cellular immune factors that participate in intrauterine CMV infections. This study was therefore designed to assess the inbred guinea pig as a model for the study of congenital CMV infection. Intrauterine fetal and placental infection with CMV was demonstrated in inbred Strain 2 guinea pigs, and the maternal factors influencing transplacental transmission of CMV were evaluated. Infectious virus was recovered from placentas and offspring of mothers that experienced primary CMV infection during pregnancy, but not from placentas and offspring of mothers that were inoculated with CMV prior to pregnancy. However, histologic lesions consisting of focal necrosis and inflammation were seen in tissues of offspring from both groups of mothers. Inoculation of seronegative pregnant Strain 2 animals with low doses of virus (2.5 to 3.5 log10 TCID50) resulted in both placental and fetal CMV infection without significant maternal death. Infection of placentas and offspring occurred in utero regardless of the stage of pregnancy. In addition, infectious virus was detectable in fetal tissues at the time of maternal viremia but also later during the course of maternal infection, ie, 4 weeks after inoculation. These findings indicate that the inbred guinea pig model can be used to investigate the pathogenesis of intrauterine CMV infections.     

Longitudinal reliability of focus glycoprotein G-based type-specific enzyme immunoassays for detection of herpes simplex virus types 1 and 2 in women

Serologic assays that utilize herpes simplex virus (HSV) type-specific glycoproteins G-1 (HSV-1) and G-2 (HSV-2) to discriminate between antibodies against HSV-1 and HSV-2 are sensitive and specific. However, the high rates of seroreversion, defined as the change in an individual's antibody status from positive to negative over time, previously reported in longitudinal evaluations of glycoprotein G type-specific tests suggests that their use in HSV acquisitional studies would be problematic. To further explore the reliability of the glycoprotein G-based serologic tests, we evaluated HSV-1 and HSV-2 enzyme immunoassays from Focus Technologies in a longitudinal cohort of 1207 young women from Pittsburgh, Pa. On enrollment of the women in the study, HSV-1 and HSV-2 antibodies were detected in 46.6 and 24.9% of the women, respectively. Among the women with at least three visits, 3.4% (15 of 447) of those who were HSV-1 antibody positive had a subsequent negative result while fewer than 1% (2 of 227) of those who were HSV-2 antibody positive seroreverted. The median of mean positive index values for women who seroreverted to HSV-1 antibody was lower than that for women who remained seropositive (1.25 versus 7.06; P < 0.001). Similarly, the median of mean positive index values for women whose HSV-2 antibody status reverted from positive to negative was lower than that for those women who did not serorevert (1.83 versus 7.46; P = 0.02). Comparative Western blot analysis demonstrated that the lower positive index values, seen more often among the HSV seroreverters, often signified false-positive immunoassay results. Overall, the seroreversion rates were low; the use of glycoprotein G-based serologic tests for the measurement of HSV-1 and HSV-2 antibodies in incidence studies therefore appears warranted.