Coinfections by HIV, hepatitis B and hepatitis C in imprisoned injecting drug users

In order to know the prevalence and risk factors for coinfections by human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among injecting drug users (IDUs), a cross-sectional study was carried out in two prisons of the province of Cantabria, northern Spain. Three hundred and sixty-two IDU inmates were recruited. All inmates were interviewed and their blood tested for HIV, HBV and HCV. Crude and multiple risk factor adjusted for (by polychotomous logistic regression) odds ratios were calculated. Prevalence of HBV-HCV coinfection (42.5%) was higher than HIV-HBV-HCV coinfection (37.3%), whereas monoinfections were very uncommon (overall: 13%). Long-term injectors and reincarceration were the foremost risk factors for both coinfections, showing a trend between the degree of association and the number of viruses infecting a patient. No significant relationship between coinfection status and sexual practices was observed. The results related to coinfections are consistent with previous studies of prevalence and risk factors for HIV, HBV and HCV, in indicating that the high rates of coinfections among IDU inmates emphasise the need to harm-reduction policy across prisons in Spain.     

Cyclosporin A induced internalization of the bile salt export pump in isolated rat hepatocyte couplets.

Isolated rat hepatocyte couplets were used to perform the comparative study of two widely used immunosuppressors, cyclosporin A (CsA) and tacrolimus (FK506) on hepatocanalicular function. We assessed canalicular function by counting the percentage of couplets that were able to accumulate the fluorescent cholephile, cholyl-lysyl-fluorescein (CLF), into the canalicular vacuole between the two cells, i.e., canalicular vacuole accumulation (CVA) of CLF. Compared to controls (DMSO-treated cells), CsA, in the approximate range of concentrations used therapeutically, caused inhibition of CVA of CLF, disorganization of the bile salt export pump (Bsep) localization at canalicular level resulting in its relocation into the cell, and disruption of the pericanalicular F-actin cytoskeleton. In contrast, FK506, at both approximately therapeutic and supratherapeutic concentrations, had no deleterious effect upon CVA of CLF, upon the localization of the bile salt transporter at the canalicular membrane, or on the organization of the pericanalicular F-actin cytoskeleton. These results point to transporter and cytoskeletal disorganization as contributors or determinants of CsA-induced cholestasis at canalicular level, whereas FK506 does not appear to produce these cholestasis-determining responses even at supratherapeutic concentrations.     

Acute cardiopulmonary alterations induced by fine particulate matter of S?o Paulo, Brazil.

The mechanisms involved in the association between air pollution and increased cardiovascular morbidity are not fully understood. The objective of this study was to test the hypothesis that fine particulate matter (PM(2.5)) induces systemic inflammation and vasoconstriction of small arteries in the lung and heart of rats. Thirty-eight healthy Wistar rats were anesthetized, intubated, and submitted to the instillation of 1 ml of distilled water diluted in the following solution: blank filter, 100 microg and 500 microg of PM(2.5). PM(2.5) was collected in glass fiber filters with a high-volume sampler. The animals were sacrificed 24 h after instillation when blood, heart, and lung samples were collected for morphological and wet-to-dry weight ratio analysis. PM(2.5) consisted of the following elements: sulphur, arsenic, bromine, chlorine, cobalt, iron, lanthanum, manganese, antimony, scandium, and thorium. Total reticulocytes significantly increased at both PM(2.5) doses (p < 0.05) while hematocrit levels increased in the 500 microg group (p < 0.05). Quantification of segmented neutrophils and fibrinogen levels showed a significant decrease, while lymphocytes counting increased with 100 microg of PM(2.5) (p < 0.05). A significant dose-dependent decrease of intra-acinar pulmonary arteriole lumen/wall ratio (L/W) was observed in PM groups (p < 0.001). Peribronchiolar arterioles L/W showed a significant decrease in the 500 microg group (p < 0.001). A significant increase in heart wet-to-dry weight ratio was observed in the 500 microg group (p < 0.001). In conclusion, fine environment particles in the city of S?o Paulo promote pulmonary and cardiac histological alterations. Pulmonary vasculature was markedly affected by particle instillation, resulting in significant vasoconstriction in healthy rats.     

Role of the CDKN2A locus in patients with multiple primary melanomas.

PURPOSE: We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. PATIENTS AND METHODS: One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included. RESULTS: Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM. CONCLUSION: MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.     

Radioquimioterapia de la enfermedad limitada del carcinoma pulmonar de célula pequeña. ¿Tratamiento concomitante en protocolos asistenciales?

Purpose We retrospectively reviewed our institution’s database to investigate the outcome and impact of combined radiochemotherapy (RT/CT; concomitant or in sequence) in localised small-cell lung cancer (L-SCLC). Material and methods Between January 1995 to November 1999, 79 patients with L-SCLC received combined RT/CT at our Institution. RT was delivered concurrently or sequentially following the CT. Patients with treatment response received additional prophylactic cranial irradiation (PCI). Results Of the patients treated, 54% had received concurrent CT/RT compared to 46% receiving RT following the CT. PCI was administered to 80% of the patients. Complete response was observed in 66% of patients. With a median follow up of 30 months, median overall survival was 15.9 months; 14.3 months for patients who received RT following CT and 21.6 months for those receiving concurrent CT/RT. The type of schedule of combined radiochemotherapy was an independent prognostic factor for survival free of local recurrence, as was additional PCI for distant metastasis-free survival. Conclusions Our results are similar to those reported previously in the literature. The main point of interest is that our patients were non-selected. We strongly support the use of concurrent CT/RT so as to achieve results comparable to the best in the literature.

     

Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-).

PURPOSE: To evaluate the efficacy of reduced intensity conditioning (RIC) allogeneic transplant in 30 patients with poor-prognosis chronic lymphocytic leukemia (CLL) and/or high-risk molecular/cytogenetic characteristics. EXPERIMENTAL DESIGN: Eighty-three percent of patients had active disease at the moment of transplant. That is, 14 of the 23 patients analyzed (60%) had unmutated immunoglobulin variable heavy-chain gene (IgV(H)) status; 8 of 25 patients (32%) had 11q-, with four of them also displaying unmutated IgV(H); and six (24%) had 17p- (five were also unmutated). RESULTS: After a median follow-up of 47.3 months, all 22 patients alive are disease free; overall survival and event-free survival (EFS) at 6 years were 70% and 72%, respectively. According to molecular/cytogenetic characteristics, overall survival and EFS for unmutated CLL and/or with 11q- aberration (n = 13) were 90% and 92%, respectively, not significantly different to those with normal in situ hybridization, 13q- and +12, or mutated CLL (n = 7). All six patients with 17p deletion were transplanted with active disease, including three with refractory disease; all except one reached complete remission after the transplant and two are alive and disease free. Nonrelapse mortality (NRM) was 20%; more than two lines before transplant is an independent prognostic factor for NRM (P = 0,02), EFS (P = 0.02), and overall survival (P = 0.01). Patients older than 55 years have a higher risk of NRM (hazard ratio, 12.8; 95% confidence interval, 1.5-111). Minimal residual disease was monitored by multiparametric flow cytometry in 21 patients. Clearance of CD79/CD5/CD19/CD23 cells in bone marrow was achieved in 68% and 94% of the patients at days 100 and 360, respectively. CONCLUSION: According to these results, RIC allogeneic transplant could overcome the adverse prognosis of patients with unmutated CLL as well as those with 11q- or 17p-.     

Diagnóstico y seguimiento de los pacientes con hipotiroidismo congénito diagnosticados por cribado neonatal

The screening program of congenital hypothyroidism (CH) is probably one of the best achievements in paediatrics. Thyroid hormones are essential for brain development and brain maturation that continue through the neonatal period. Hypothyroidism that begins in the first months of life causes irreversible damage to the central nervous system, and is one of the most frequent and preventable causes of mental retardation. As children with congenital hypothyroidism are born with a normal appearance, analytical studies are required to immediately start the appropriate therapy.This article analyses the aims, diagnostic procedures, tests required, aetiology, and differential diagnosis in this disorder. Especially relevant is to perform frequent monitoring to ensure dose adjustments of L-Thyroxine therapy, avoiding infra- or supra-dosing that negatively affects neurosensory functions. Re-evaluation of the aetiology permanent vs transient hypothyroidism is always recommended after 3 years of chronological age.The relevance of this screening program should be widely discussed in paediatrics. The main objective is to avoid cerebral damage in these patients, and has been highly successful and economically beneficial.Other aspects are required to optimise patient outcomes, to perform all the controls according to the recommendations and to include, in the near future, the diagnosis of central hypothyroidism. Implementation of this program is necessary to progress in accordance with current scientific knowledge.     

Estudio de intervención formativa con miniensayos para mejorar la atención de las urgencias médicas en un centro de salud

ObjectiveTest effectiveness and acceptability of interventions short essay-type training in health emergency management (EM).DesignCombined case series and controlled study before and after training sessions.LocationHealth Center (HC).ParticipantsTeam on duty, two monitors-facilitators, and a mannequin.Main measuresVariables: response times, staff performance, resource usage and opinion. Structure: scenarios and key messages. Instrument development: 1. Initial/final questionnaire and events. 2. Essential/non-essential times; 3. Post-test opinion questionnaire. Performance of six consecutive 15 min tests fortnightly (including corrections) and poll after each test. A month later, repeat in random order and under similar conditions. Analysis: repeated measures.ResultsA total of 93 (2/3) workers completed the initial survey, and 74 the final, with 46 participants (25 doctors, 7 nurses, 21 non-health completed 95 direct interventions. Matching participants > 80% between series. A reduction was seen in the “detection of collapse to first defibrillation” interval (10 to 4 min). EM events improved 2-3 fold and “sense of security during a real EM” increased from 23% to 71% among participants. The vast majority of participants said “useful corrections made by the facilitator.” The proportions of those who “would like to see tests introduced” and those who said “re-training was needed in EM” were moderately increased (67.4% vs 85% in health care workers). The “would like to attempt basic life support” was unchanged.ConclusionDespite being reduced in number and duration, this model of intervention has shown positive trends in terms of use and acceptability for implementation in the HC.