Transmission of a newly characterized strain of varicella-zoster virus from a patient with herpes zoster in a long-term-care facility, West Virginia, 2004

We investigated a small outbreak of varicella in a long-term-care facility after a case of herpes zoster. Clinical specimens and environmental samples were collected from all case patients and from surfaces in the case patients' rooms and other common-use areas. Wild-type varicella-zoster virus (VZV) DNA was identified in all 3 varicella case patients, and high concentrations of VZV DNA were detected in environmental samples from the room of the herpes zoster case patient. Genotypic analysis showed that the identical VZV strain was present in all samples; moreover, the strain was a unique Mosaic genotype isolate that included a stable Oka vaccine marker that had hitherto never been observed in a wild-type strain of VZV. This study provides evidence for the value of including environmental sampling during the investigation of varicella outbreaks and illustrates the importance of evaluating multiple vaccine-associated markers for the discrimination of vaccine virus from wild-type VZV.     

Natural history of end-stage LV dysfunction: has it improved from the classic Franciosa and Cohn Graph?

The pathophysiology of heart failure is complex, and downstream effects cause decline in multiple systems. Medical therapies intended to slow or reverse disease progression have been shown to improve prognosis in prospective trials. Improvement in prognosis has also been observed in large cohorts across time strata. However, near-term mortality for those with advanced disease remains unacceptably high. Prognosis in advanced heart failure may be assessed with the appropriate use of clinical prediction tools. Optimal timing of evaluation for heart transplantation and/or mechanical circulatory support depends on an understanding of these issues.     

Differential association of retinal arteriolar and venular caliber with diabetes and retinopathy

Aims

To describe the relationship of retinal arteriolar and venular caliber with diabetes, retinopathy and hyperglycemia, in an Asian Indian population.

Methods

This was a population-based cross-sectional study of 3400 (75.6% response rate) Singapore ethnic Indians aged 40-80 years. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were obtained using a validated computer-assisted program. Diabetes mellitus was identified using standardized criteria. Diabetic retinopathy was graded based on the modified Airlie House Classification System.

Results

There were 980 (32.2%) participants with diabetes. Of these, 327 (33.4%) had diabetic retinopathy. After multivariate adjustment, diabetic persons had a wider CRAE (145.23 μm vs 142.38 μm, P < 0.001). This relationship was stronger in persons without hyperlipidemia (P-interaction < 0.1). Among diabetic participants, wider CRVE was related to increasing severity of retinopathy (P for trend < 0.05) and this association may be altered by hypertensive status. Retinal arteriolar caliber widened with increasing glucose (P < 0.001) and HbA1C (P < 0.001) levels.

Conclusions

In Indian adults, wider retinal arteriolar caliber is associated with diabetes and hyperglycemia, while wider retinal venular caliber is associated with diabetic retinopathy. This is consistent with white populations and confirms the differential systemic association of retinal vascular caliber in Asian Indians.     

The prevalence and associations of sleep disturbances in patients with systemic lupus erythematosus

The aim of this study was to analyze sleep complaints in patients with systemic lupus erythematosus (SLE) and to determine its prevalence and associations. Fifty outpatients with SLE and an equal number of age- and sex-matched controls were included in the study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) in both cases and controls. Depressed mood, functional disability and pain severity were assessed in patients using standardized questionnaires. Disease severity, cumulative damage and presence of fibromyalgia were determined by clinical examination. Bivariate associations between sleep quality and disease-related variables as well as demographic variables were calculated. A series of hierarchical regression analyses were computed to determine the independent determinant of sleep quality. PSQI scores were significantly higher in patients with SLE. Prevalence of sleep disturbance was 62%. Functional disability, disease activity and depressed mood correlated positively with sleep disturbances. 36% of the patients satisfied ACR criteria for fibromyalgia. In multiple regression analyses disease activity was found to be an independent determinant of sleep quality. The prevalence of poor sleep quality in patients with SLE was higher than it is generally perceived to be. Functional disability, disease activity and depressed mood contributed significantly to sleep disturbances in SLE.     

Reconstitution of deficient T cell receptor zeta chain restores T cell signaling and augments T cell receptor/CD3-induced interleukin-2 production in patients with systemic lupus erythematosus

OBJECTIVE: T cells from a majority of patients with systemic lupus erythematosus (SLE) display antigen receptor-mediated signaling aberrations associated with defective T cell receptor (TCR) zeta chain, a subunit of the TCR/CD3 complex. This study was undertaken to explore the possibility that forced expression of TCR zeta chain may reverse the known signaling abnormalities and defective interleukin-2 (IL-2) production in SLE T cells. METHODS: Freshly isolated SLE T cells were transfected with TCR zeta chain construct in a eukaryotic expression vector at high efficiency, by a recently developed nucleoporation technique. Restoration of TCR/CD3-mediated signaling was studied in the zeta chain-transfected cells. RESULTS: In SLE T cells transfected with TCR zeta chain, surface expression of TCR chain was increased and the TCR/CD3-induced increased free intracytoplasmic calcium concentration response was normalized, as was hyperphosphorylation of cellular substrates. Simultaneously, the previously noted increased expression of the Fc receptor gamma chain was diminished in SLE T cells transfected with the zeta chain expression vector, and the surface membrane clusters of cell signaling molecules were redistributed to a more continuous pattern. TCR zeta chain replacement also augmented the expression of diminished TCR/CD3-mediated IL-2 production in SLE T cells, associated with increased expression of the p65 subunit of nuclear factor kappaB in the nuclear fractions of these T cells. CONCLUSION: These results suggest that reconstitution of deficient TCR zeta chain can reverse the TCR/CD3-mediated signaling abnormalities as well as the defective IL-2 production in T cells of patients with SLE.     

Genetic signatures of high- and low-risk aberrant crypt foci in a mouse model of sporadic colon cancer

To determine whether cancer risk is related to histopathological features of preneoplastic aberrant crypt foci (ACF), gene expression analysis was performed on ACF from two mouse strains with differing tumor sensitivity to the colonotropic carcinogen, azoxymethane. ACF from sensitive A/J mice were considered at high risk, whereas ACF from resistant AKR/J mice were considered at low risk for tumorigenesis. A/J and AKR/J mice received weekly injections of azoxymethane (10 mg/kg body weight), and frozen colon sections were prepared 6 weeks later. Immunohistochemistry was performed using biomarkers associated with colon cancer, including adenomatous polyposis coli, beta-catenin, p53, c-myc, cyclin D1, and proliferating cell nuclear antigen. Hyperplastic ACF, dysplastic ACF, microadenomas, adjacent normal-appearing epithelium, and vehicle-treated colons were laser captured, and RNA was linearly amplified (LCM-LA) and subjected to cDNA microarray-based expression analysis. Patterns of gene expression were identified using adaptive centroid algorithm. ACF from low- and high-risk colons were not discriminated by immunohistochemistry, with the exception of membrane staining of beta-catenin. To develop genetic signatures that predict cancer risk, LCM-LA RNA from ACF was hybridized to cDNA arrays. Of 4896 interrogated genes, 220 clustered into six broad clusters. A total of 226 and 202 genes was consistently altered in lesions from A/J and AKR/J mice, respectively. Although many alterations were common to both strains, expression profiles stratified high- and low- risk lesions. These data demonstrate that ACF with distinct tumorigenic potential have distinguishing molecular features. In addition to providing insight into colon cancer promotion, our data identify potential biomarkers for determining colon cancer risk in humans.     

Influence of diabetes on macular thickness measured using optical coherence tomography: the Singapore Indian Eye Study

Purpose

To determine the influence of diabetes, diabetic retinopathy (DR), and other factors on macular thickness, measured using optical coherence tomography (OCT), in a population-based sample.

Methods

Data from the population-based Singapore Indian Eye Study were analyzed. We measured macular thickness using Stratus OCT Fast Macular Thickness scan protocol in 228 participants with diabetes mellitus (including 167 without DR, 44 with mild DR, 17 with moderate or severe DR) and 72 non-diabetic controls without macular oedema or other macular lesions. Analysis was done on right eyes.

Results

The mean age of participants was 60.1±10.1 years, with 53.8% men. Macular thickness measurements did not differ significantly between diabetic participants with no or mild DR and non-diabetic participants. Diabetic participants with moderate or severe DR had greater foveal and temporal outer macula thickness compared with those with no or mild DR (P=0.003). In a multivariate linear regression model, older age (P=0.009), male gender (P=0.005), and lower spherical equivalent (P=0.001) were other factors associated with greater foveal thickness in all participants after controlling for body mass index, glycosylated haemoglobin, total cholesterol, and mean systolic blood pressure.

Conclusion

This population-based study showed that diabetic participants with moderate or severe DR had thicker foveal measurements, even in the absence of diabetic macula oedema, than non-diabetic controls. Other factors that influenced macular thickness measurements were age, gender, and spherical equivalent. These data may aid the interpretation of OCT findings in persons with diabetes and DR.     

Splenic abscess.

Isolated splenic abscess is an uncommon condition. Seven cases seen between 1980 and 1990 are reviewed. The clinical presentation is non-specific and diagnosis is usually delayed. Computerized tomography allowed for accurate diagnosis in all cases. Pseudomonas species as a causative organism is reported to be rare, but were present in three of the present cases. Antibiotic therapy alone is insufficient and splenectomy remains the treatment of choice.