'First steps': using rapid assessment and response methods to develop research, intervention and advocacy capacity for addressing drug use in Rosario City, Argentina

During the last decade, injecting drug use (IDU) has increased in Rosario City, Argentina, and more than half of all reported HIV cases are thought to be related to the sharing of injection equipment. Despite this, valid and systematic data on the extent and nature of injecting drug use are rare, and only a limited number of HIV prevention interventions currently operate in the city. In response, the Universidad Nacional de Rosario have used the Spanish translation of the Rapid Assessment and Response Guide on Injecting Drug Use (IDU-RAR) developed by the World Health Organization (WHO. The Rapid Assessment and Response Guide on Injecting Drug Use (draft for field testing). Geneva: WHO, 1998) as a first step in producing more detailed research data, identifying urgently needed interventions, and designing a long-term harm reduction strategy for Rosario. This paper describes this process and the outcomes of the assessment where key findings indicate that: 65% of those sampled were HIV positive; 70% shared injecting equipment; the majority were not in contact with drug treatment services; 13% were under the age of 20; and 62% of those injecting drug users with HIV had neither medical care or treatment for their condition.     

Decision making in general practice: the availability and use of a specific laboratory analysis

OBJECTIVES: The aim of this investigation was to study the effect of general practitioners' (GP's) characteristics on two decisions: whether to have the Helicobacter pylori rapid test (HPRT) in the office laboratory and whether to use this test or a similar hospital-based serological test in a typical clinical situation described in a vignette. METHODS: Discrete choice analysis with binary logit models were used to predict the probability that a general practice has the HPRT, as well as the GP's probability of using the HPRT or a similar test in this clinical situation. RESULTS: We found that the number of consultations per week has a positive effect on the probability of having the HPRT, indicating that the size of the practice affects the decision to have such a test in the repertoire. Furthermore, four variables significantly increased the probability of using one of the lab tests: more if located in urban practices, more by solo practitioners, more when the GP stated a high probability for H. pylori associated disease, and more when the GP had the rapid test available in the practice. In our analysis, the remuneration system is endogenous and does not have a significant effect on the two decisions. CONCLUSIONS: Our study demonstrates that characteristics of the GP affect the availability and use of a specific laboratory analysis.     

NOD B-cells are insufficient to incite T-cell-mediated anti-islet autoimmunity

Although it is well established that B-cells are required for the development of diabetes in the nonobese diabetic (NOD) mouse, the nature of their role remains unknown. Herein, we investigate the hypothesis that B-cells in this autoimmune background actively disrupt the tolerant state of those T-cells with which they interact. We demonstrate that NOD B-cells express elevated levels of crucial molecules involved in antigen presentation (including CD21/35, major histocompatibility complex class II, and CD40), alterations that invite the possibility of inappropriate T-cell activation. However, when chimeric animals are generated in which all B-cells are NOD-derived, a tolerant state is maintained. These data demonstrate that although B-cells are required for the development of autoimmunity, they are not sufficient to disrupt established tolerance. Moreover, non-B-cell antigen-presenting cells may be the critical actors in the establishment of the tolerant state; this function may be absent in NOD mice as they are characterized by deficient professional antigen-presenting cell function.     

Immunotoxin treatment targeted to the high-molecular-weight melanoma-associated antigen prolonging the survival of immunodeficient rats with invasive intracranial human glioblastoma multiforme

OBJECT: The aim of this study was to target immunotoxin treatment to the high-molecular-weight melanoma-associated antigen (HMW-MAA) and thereby examine any changes in the survival of immunodeficient rats with human glioblastoma multiforme (GBM). METHODS: To target treatment specifically to human glioma cells, Pseudomonas exotoxin A (PE) was conjugated to the 9.2.27 antibody, which recognizes the HMW-MAA. Treatment of the antigen-positive glioma cell line U87MG with the resulting 9.2.27-PE caused cytotoxicity with a median inhibitory concentration of 1 ng/ml. Intratumoral 9.2.27-PE treatment of intracranial U87MG tumors in nude rats prolonged the survival of these animals by 43% compared with controls. In additional studies on the use of this targeted treatment, the authors precultured freshly dissected glioblastoma multiforme (GBM) biopsy tissue for 1 to 2 weeks. Inoculation of this tissue into the rat brain resulted in diffuse infiltrative gliomas. The markers glial fibrillary acidic protein and S100 protein were found to be expressed in the original biopsy specimens, as well as in the glioma xenografts in nude rat brains. Intratumoral immunotoxin treatment of such established tumors with 9.2.27-PE was effective and prolonged survival time from 30% to as high as 90% in animals with tumors originating from four different GBM specimens. CONCLUSIONS: Targeted treatment of highly invasive GBMs proved effective, and these results emphasize the clinical relevance of this antigen as a target molecule for immunotoxin treatment of human GBMs.     

The clinical relevance of cytokeratin phenotyping in needle biopsy of liver metastasis

Although cytokeratin (CK) phenotyping of metastatic tumors is now routine in many laboratories, the clinical relevance of the procedure has seldom been addressed. We carried out a prospective clinical study of 134 consecutive cases of metastatic adenocarcinoma of the liver diagnosed by needle biopsies stained routinely for CK20 and CK7. The most probable localization of the primary tumor, deduced from this staining pattern, was stated in the original pathology report. The present study compared this assignment with the information available at the time of interpretation of the liver biopsy, to the results of the subsequent clinical investigation, and to the officially reported cause of death as outcome. As expected, the primary tumors were localized in the colon or in the rectum in 85% (34/40) of the CK20+/CK7- metastases. The definite diagnosis remained metastatic colorectal carcinoma in 83% (15/18) of the cases with diagnosed colorectal cancer before the liver biopsy. In the cases without a known primary tumor when the liver biopsy was interpreted, primary colorectal localization was accurately predicted in 86% (19/22) of the patients. Compared to the outcome, 77% (36/47) of the CK20+/CK7+ metastases had the expected pancreaticobiliary primary localization in 83% (30/36) without any primary tumor being known at the time of interpretation of the liver biopsy. In contrast, the majority of CK20- metastatic carcinomas had an unexpected primary localization, 50% (16/32) in the CK20-/CK7+ and 60% (9/15) in the CK20-/CK7- subgroup. In addition, the origin of the liver metastasis remained unknown in 37% (12/32) of CK20-/CK7+ cases. Thus, the CK20+/CK7- phenotype indicates a colorectal origin of the liver metastasis with considerable accuracy and independently of the available clinical information. The same is true for CK20+/CK7+ metastases, which indicate primary tumor localization in the pancreas or in the biliary tree. The results in the CK20- subgroups of the liver metastases are disappointing and cannot substantially help the clinical investigation.     

Recent progress in the design of selectin inhibitors

The selectins are a family of cell-adhesion proteins that mediate the early stages of leukocyte recruitment from the blood stream to sites of tissue damage through recognition of the carbohydrate epitope sialyl Lewis(x) (sLe(x)). Current development of small molecule based inhibitors of this process and their clinical potential to address numerous acute and chronic diseases are explored.