Choroidal melanoma with secondary glaucoma

The case of a 40-year-old female patient with choroidal melanoma with secondary glaucoma presenting as a painful blind right eye is reported. Liver metastasis was detected by ultrasonography. The choroidal tumor measured 2 x 2.1 x 1.5 cm; histopathology showed that it was of the spindle cell (spindle A) variety. Such tumors are rare in non-white races and secondary glaucoma is an uncommon presentation.     

Human prion diseases

Prion diseases is another name for a group of 'transmissible spongiform encephalopathies'. Creutzfeldt-Jakob disease, the first prion disease described in humans, occurs in sporadic, familial or iatrogenic form. Other transmissible spongiform encephalopathies in humans such as familial Creutzfeldt-]akob disease, Gerstmann-Str?ussler-Scheinker disease and fatal familial Insomnia have been shown to be associated with specific prion protein gene mutations. In 1996, a new variant of Creutzfeldt-Jakob disease was reported in the United Kingdom among young patients with unusual clinical features and unique neuropathological findings. This new form could be due to transmission to humans of the agent causing bovine spongiform encephalopathy. While examination of brain tissue is the key to making a diagnosis, it is not always possible antemortem. Immunological tests such as ELISA or western blot assays along with tests for 1 4-3-3 protein in the cerebrospinal fluid remain the main tools of diagnosis. Conventional disinfection and sterilization practices are Ineffective for these agents. The unusual properties of prions pose a challenge for treatment, surveillance and control of these diseases.     

Integration of service systems for homeless persons with serious mental illness through the ACCESS program. Access to Community Care and Effective Services and Supports

OBJECTIVE: The aim of this study was to evaluate the first of the two core questions around which the ACCESS (Access to Community Care and Effective Services and Supports) evaluation was designed: Does implementation of system-change strategies lead to better integration of service systems? METHODS: The study was part of the five-year federal ACCESS service demonstration program, which sought to enhance integration of service delivery systems for homeless persons with serious mental illness. Data were gathered from nine randomly selected experimental sites and nine comparison sites in 15 of the nation's largest cities on the degree to which each site implemented a set of systems integration strategies and the degree of systems integration that ensued among community agencies across five service sectors: mental health, substance abuse, primary care, housing, and social welfare and entitlement services. Integration was measured across all interorganizational relationships in the local service networks (overall systems integration) and across relationships involving only the primary ACCESS grantee organization (project-centered integration). RESULTS: Contrary to expectations, the nine experimental sites did not demonstrate significantly greater overall systems integration than the nine comparison sites. However, the experimental sites demonstrated better project-centered integration than the comparison sites. Moreover, more extensive implementation of strategies for system change was associated with higher levels of overall systems integration as well as project-centered integration at both the experimental sites and the comparison sites. CONCLUSIONS: The ACCESS demonstration was successful in terms of project-centered integration but not overall system integration.     

The kinetics of deregulation of expression by de novo methylation of the h19 imprinting control region in cancer cells

Epigenetic lesions are common in neoplasia and range from hypermethylation of subsets of CpG islands to loss of imprinting. By exploiting an episomal model system and the strong de novo methylation capacity of a human cancer cell line, we show that an H19 minigene rapidly becomes methylated and silenced, mimicking the inactivation of the maternal H19 allele in a range of cancers. Although the H19 imprinting control region (ICR) initially displayed methylation protection, it eventually succumbed to the pressure mounted by the de novo methylation machinery of the JEG-3 cells. Importantly, we were able to visualize the kinetics of the loss of the H19 ICR chromatin insulator function in association with chromatin compaction. Our results document that a strong de novo methylation machinery leads to loss of methylation privilege states of H19 ICR to functionally manifest loss of insulator function in a matter of only a few days in human cancer cells.     

Increasing social capital via local networks: analysis in the context of a surgical practice

The relationship between social capital (support, trust, patient awareness, and increased practice revenue) and local networks (university hospital) in communities has received little attention. The development of computer-based communication networks (social networks) has added a new dimension to the argument, posing the question of whether local networks can (re-)create social capital in local communities. This relationship is examined through a review of the literature on local networks and social capital and a surgeon's practice management from 1990 to 2001 with respect to repair of pectus chest deformities. With respect to pectus repair there was a consistent but small number of new referrals (15-20 new patients/year), lack of patient awareness (eight to 12 self-referred patients/year), and modest practice revenue. Since the inception of an Internet website (social network) dedicated to pectus repair in 1996 there has been increased social participation (n = 630 hits/year to the website); facilitation of spread of information through E-mail messages (n = 430 messages/year); and a greater participation of groups such as women, minorities, adults, and those with disability (n = 120 patients/year). The dissemination of information via the local network has also allowed an "outward movement" with increased participation by interconnecting communities (n = 698,300 global Internet participants based on statistical ratios). We conclude that local networks have enhanced social networks providing new grounds for the development of relationships based on choice and shared interest.     

A receptor-specific peptide for imaging infection and inflammation

The chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP), when radiolabelled, continues to be an attractive agent for imaging infection or inflammation. Previously, several analogues of fMLP have been prepared and radiolabelled using a bifunctional chelating agent conjugation procedure that was relatively long and complex. We have prepared a new analogue of fMLP, TP765, by the addition of 4-aminobutyric acid (4-ABA) and a group of four amino acids, Gly-Gly-d-Ala-Gly, to the carboxy terminus (i.e. to the phenylalanine) of fMLP. The adduct -(4-ABA)-Gly-Gly-d-Ala-Gly- serves as a chelating moiety for strong chelation with 99Tcm. The use of a peptide as a chelating moiety greatly simplified the synthetic procedure and rendered the analogue ready for instant chelation with 99Tcm. HPLC analysis revealed that 99Tcm-TP765 was a single chemical entity that retained biological activity and neutrophil specificity. 99Tcm-TP765 was stable when challenged with strong chelating agents in vitro and had rapid but biphasic blood clearance (alphat1/2 = 7 min, betat1/2 = 45 min). Approximately 90% of the radioactivity had cleared from circulation within 45 min post-injection and the agent had accumulated in experimental bacterial or sterile abscesses in significantly (P<0.05) higher quantities than the analogues evaluated previously. Generally, the biodistribution pattern of 99Tcm-TP765 was similar to that of other analogues examined and its abscess uptake was independent of the abscess age. In conclusion, a new analogue of fMLP, 99Tcm-TP765, was prepared by a simple procedure. This new analogue has properties similar to those of previously examined analogues used as agents for imaging infection or inflammation.     

A prospective randomized, comparative, open-label trial of the safety and efficacy of paromomycin (aminosidine) plus sodium stibogluconate versus sodium stibogluconate alone for the treatment of visceral leishmaniasis

Response to treatment with organic pentavalent antimonials, the standard first-line treatment for visceral leishmaniasis (VL), has been decreasing since their introduction into India. Combining sodium stibogluconate (SB) with paromomycin (PM) may be an efficient alternative to single-agent therapy. This trial was designed to assess the safety and efficacy of PM 12 or 18 mg/kg daily plus SB 20 mg/kg daily for 21 days compared to SB alone for 30 days. One hundred and fifty patients were randomly assigned in 1996 to 1 of the 3 treatments and followed-up for 180 days. At the end of treatment, 49 of 52 patients receiving PM12 + SB, 46 of 48 receiving PM18 + SB, and 27 of 49 patients receiving SB alone, were cured. During follow-up there was 1 relapse in each of the treatment groups, giving final cure rates of 48 of 52 (92.3%) for PM12 + SB, 45 of 48 (93.8%) for PM18 + SB, and 26 of 49 (53.1%) for SB. PM plus SB for 21 days at either 12 or 18 mg/kg daily was significantly more effective than SB alone for 30 days (chi 2 P < 0.001). One patient (SB alone) had experienced a serious adverse event: cardiotoxicity at day 8 (myocarditis and ECG changes) which caused withdrawal from the study. Only 19 of 100 patients enrolled in the PM treatment arms had a complete audiogram series conducted thus making it difficult to assess oto-toxicity. PM 12 or 18 mg/kg daily plus a standard dose of SB for 21 days was statistically more effective than SB in producing a final cure for patients with VL in Bihar, India.