The triple flash electroretinogram and its significance in macular diseases

Purpose: The purpose of this study was to evaluate recovery data for the b-wave of the electroretinogram (ERG) elicited using multiple flash stimulation with increasing stimulus intervals in normal controls and in patients with macular diseases. The results will describe effects of age and macular disease and define indexes characterizing the recovery process. Methods: Scotopic Ganzfeld flash ERGS were elicited using interstimulus intervals of 140, 280, and 560 ms. Relative b-waves were calculated as the ratio b_{140 ms}/ b_{560 ms} and b_{280 ms}/b_{560 ms}, respectively. Responses obtained in 134 eyes of 134 normal controls served as reference data. Fifty-four patients with different macular diseases were also examined and their data compared to the reference data. Results: Relative b-wave amplitudes correlated with interstimulus interval and with flash luminance, but not with age. All patients had a normal ERG when recorded following the standard of clinical electroretinography. A sigmoidal model was suggested, providing three indexes characterizing the b-wave recovery process. Relative b-waves and recovery indexes varied in age-related macular degeneration, central serous retinopathy, vitelliform macular degeneration, Stargardt's disease, and pattern dystrophy. Conclusion: The triple flash ERG reflects energy-yielding and -utilizing mechanisms. It proved to be more sensitive in detecting functional lesions in macular diseases than the standardized explorating procedure. The b-wave recovery model allows differentiation between two independent mechanisms contributing to the b-wave recovery process. One or more of the three characterizing indexes are affected in different macular diseases.     

Changes in newspaper coverage of cardiovascular health issues in conjunction with a community-based intervention

Numerous community-based prevention projects, with significant media components, have been conducted over the past decade. Multiple evaluation strategies have been used to document the effectiveness of these interventions, including intermediate measures of community impact such as assessment of media coverage. As part of the evaluation of a community-based intervention (the Bootheel Heart Health Project), dissemination of information on cardiovascular disease (CVD) was measured through a media content analysis of newspapers. Data were analyzed from 23 newspapers in six rural counties in southeastern Missouri for the period October 1988 through August 1993. An increase was observed in CVD-related coverage in the pre-intervention period (mean articles per month = 31.5) compared with the post-intervention period (mean articles per month = 50.7) (F = 10.2; P = 0.003). In supporting data from a separate randomized risk factor survey of 1510 residents in the same area, respondents reported hearing of heart health coalitions primarily through local newspapers. The current study documents increasing print media coverage of cardiovascular health issues in a high-risk, rural area and shows that media content analysis can be a useful evaluation tool in community-based interventions.     

AZATHIOPRINE INDUCED BONE MARROW SUPPRESSION IN LIVE RELATED RENAL ALLOGRAFT RECIPIENTS

Over a follow-up period of 6 years, 4 out of 31 live related renal allograft recipients (12.9%) developed azathioprine induced bone marrow suppression. Presentation in 3 patients was with fever and 2 patients also had associated graft dysfunction. All patients had leucopenia, 2 patients in addition had anaemia and one patient had pancytopenia. Bone marrow suppression developed 9.6 months (3.5-16.0 months) following transplantation and recovery followed over a period of 30 (18-49 days) days after withdrawal of the drug. One patient succumbed during the phase of bicytopenia.KEY WORDS: Azathioprine, Bone marrow suppression, Kidney transplantation     

Characteristics of optic disc changes in Taiwanese patients with primary angle-closure glaucoma.

BACKGROUND AND PURPOSE: Primary angle-closure glaucoma (PACG) is the predominant form of glaucoma among Asians. Although numerous studies have been done to describe the characteristic optic disc changes in patients with primary open angle glaucoma (POAG) which is the predominant form of glaucoma among Western populations, few studies have evaluated the optic disc changes in patients with PACG. The aim of this study was to elucidate the characteristic intrapapillary and parapapillary disc changes in PACG in a cross-sectional study and to develop a practical approach to the detection of glaucomatous optic disc changes in PACG by ophthalmoscopic examination. METHODS: A total of 103 eyes in 103 PACG patients were studied. Forty one eyes of 41 age- and sex-matched healthy subjects served as controls. Three glaucoma-trained subspecialists examined stereophotographs of optic discs to evaluate the intrapapillary and parapapillary changes. The differences in PACG and control group eyes were compared. RESULTS: Concentric steep enlargement of the optic disc was found in 99 PACG eyes (96%). Local notching was noted in only 3 eyes, and vertically oval-shaped cupping of the optic disc in only 1 eye. Disc hemorrhage was not detected in any eye. Parapapillary atrophy of the alpha zone involving both temporal and nasal side of the optic disc and parapapillary atrophy of beta zone were significantly more frequent in the PACG group. The presence of an alpha zone or a beta zone simultaneously involving both the temporal and nasal side of the optic disc was associated with more severe optic nerve head damage. CONCLUSIONS: The intrapapillary change in the PACG group eyes reflected the development of cupping in PACG patients with small and compact optic discs. The parapapillary atrophy paralleled the intrapapillary optic disc cupping in eyes of the PACG group.     

Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians.

Exposure to heterocyclic amines may increase prostate cancer risk. Human sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and the risk of prostate cancer in a population based case-control study. Prostate cancer patients (n = 464) and control individuals (n = 459), frequency matched on age and ethnicity, provided informed consent, answered a survey, and provided a blood sample. Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. Meat consumption was assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1 high activity allele were at increased risk for prostate cancer [odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele. The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile. A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively). When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption.     

Inhibition of the allograft response by donor specific blood transfusion: association with reduced local TH1 cytokines and nitric oxide but enhanced prostaglandin E2 production

BACKGROUND: Donor-specific blood transfusion (DST) may improve allograft survival in human and animal models, but the mechanisms for this graft protective effect are incompletely understood. The sponge matrix allograft model was used to determine if DST induces regulatory factors within the allograft. METHODS: C57BL/6 (H-2b) recipients received donor-specific (DBA/2J, H-2d) or syngeneic (C57BL/6) blood 7 days before sponge matrix allograft (DBA/2J) implantation. Fourteen days postgrafting, the sponge infiltrating cells (SIC) were examined for cytotoxic T cell (CTL) and natural killer (NK) activity, and sponge exudate fluid (SEF) was assessed for nitric oxide (.N=O) and prostaglandin E2 (PGE2) content. Interleukin- (IL) 2, IL-4, IL-10, and interferon-gamma (IFN-gamma) production by SIC was also determined. Recipient splenocytes were simultaneously assessed for anti-donor cytotoxic and proliferative responses and .N=O production. RESULTS: SIC from mice receiving syngeneic transfusions (ST) acquired both CTL and NK activity postgrafting, with maximal activity by day 14. DST suppressed both CTL and NK activity throughout the postgrafting period. Limiting dilution analysis (LDA) of SIC to determine precursor and native CTL frequency showed significantly lower responder cell frequency after DST compared with ST. SEF .N=O levels and SIC production of IL-2 and IFN-gamma in grafted DST mice were significantly lower than in grafted mice receiving ST. No significant amounts of IL-4 and very low levels of IL-10 were produced by SIC from grafted mice after either ST or DST. Conversely, PGE2 content of sponge fluid and serum from DST mice was higher than in mice receiving ST. Antigen stimulated splenocyte proliferation and CTL development assessed by LDA were also inhibited by DST. CONCLUSIONS: Reduction in local TH1 cytokines, absence of detectable TH2 cytokines, with enhanced PGE2 and depressed .N=O were observed in the local graft environment after DST. These data support the hypothesis that DST induces donor-specific intragraft suppressor factors, accompanied by reduced local and systemic immune activation.     

Hormone-refractory breast cancer remains sensitive to the antitumor activity of heat shock protein 90 inhibitors.

PURPOSE: The antiestrogen tamoxifen (Tam) has been used as therapy against estrogen receptor (ER)-positive breast cancer for decades. Most tumors respond initially, but resistance frequently develops. The ER exists in a multiprotein complex containing the molecular chaperone heat shock protein (Hsp) 90, which is known to regulate the stability and activity of this receptor. Therefore, we investigated a ligand-independent approach to hormonal therapy that depletes cellular levels of the receptor by inhibiting the function of Hsp90. EXPERIMENTAL DESIGN: The activity of the Hsp90 inhibitor geldanamycin (GA) and its clinically relevant derivative, 17-allylamino-17-demethoxygeldanamycin (17AAG), was examined at the molecular and cellular levels using Tam-resistant MCF-7 breast cancer cells both in vitro and in tumor xenografts. RESULTS: The ER was depleted by GA in several Tam-resistant cell lines, as were other Hsp90 client proteins such as Akt and Raf-1. Unexpectedly, Tam inhibited ER depletion by GA but had no effect on destabilization of Akt or Raf-1. When SCID mice supplemented with Tam were treated with 17AAG, their tumors also showed no decrease in ER levels as measured by immunofluorescent staining and laser scanning cytometry. In these same tumors, however, decreased Akt and Raf-1 levels were observed. Drug administration also led to inhibition of tumor xenograft growth. The mechanism by which Tam inhibits GA-mediated ER depletion is unclear, but immunoprecipitation experiments showed that Tam does not inhibit the ability of GA to alter the ER-chaperone complex. CONCLUSIONS: Based on its ability to deplete the ER as well as other critical signaling molecules in Tam-resistant breast cancer, 17AAG may provide a useful alternative treatment for patients with recurrent, hormone-refractory breast cancer that should be explored further in Phase II trials. In this context, combined treatment with 17AAG and Tam should be avoided because Tam may inhibit the ability of 17AAG to deplete the ER, potentially reducing its anticancer activity.