First Spanish Trauma Registry: analysis of 1500 cases.

OBJECTIVES: To develop the first Spanish Pediatric Trauma Registry to collect and evaluate infomation concerning aspects of injuries in our pediatric population. METHODS: From January 1995 to August 1998, 35,946 children younger than 16 years were treated in our hospital for acute injury: 1500 were admitted and included in our database. Our file registry consists of 108 data points including: patient identification, type, place and mechanism of injury, pre-hospital care, transport, assessment on admission, severity scores, diagnostic studies, injuries, treatment morbidity and mortality. RESULTS: Accidents were more frequent in males (68%) than in females. The predominant age group was 12-15 years of age (34%). Accidents were more frequent in the street (35.1%) than at home (18.9%) or school (13%). Falls and traffic-related accidents were the leading cause of injury (39% and 21.2%, respectively). Two hundred and thirty-five (15.7%) had a Pediatric Trauma Score < or = 8. Fifty of these sustained multiple trauma (33%) (Injury Severity Score > or = 15). Musculoskeletal and head trauma were the most frequent injuries (48.5% and 42.0%, respectively). Surgical or orthopedic procedures were performed in 906 patients (56.5%). The average length of stay was 4.5 days (range 1-93 days). Functional impairment in children older than 4 years of age was found in 413 children (33.3%). We encountered 7 deaths in the 1500 patients, or an overall mortality of 0.5%. These 7 deaths were only seen in the I.S.S. > or = 15 group (50 patients) with 14% mortality. CONCLUSIONS: The goals of this Registry are to establish the epidemiology of our injured pediatric population, to review patient care, to develop prevention programs and to compare results with other centers so that potential deficiencies can be corrected.     

Vascular Reactivity Profile of Novel KCa3.1‐Selective Positive‐Gating Modulators in the Coronary Vascular Bed

Opening of intermediate‐conductance calcium‐activated potassium channels (K_Ca3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new K_Ca3.1‐selective positive‐gating modulators, SKA‐111 and SKA‐121, to (1) evoke porcine endothelial cell K_Ca3.1 membrane hyperpolarization, (2) induce endothelium‐dependent and, particularly, endothelium‐derived hyperpolarization (EDH)‐type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole‐cell patch‐clamp experiments on endothelial cells of PCA (PCAEC), K_Ca currents evoked by bradykinin (BK) were potentiated ≈7‐fold by either SKA‐111 or SKA‐121 (both at 1 μM) and were blocked by a K_Ca3.1 blocker, TRAM‐34. In membrane potential measurements, SKA‐111 and SKA‐121 augmented bradykinin‐induced hyperpolarization. Isometric tension measurements in large‐ and small‐calibre PCA showed that SKA‐111 and SKA‐121 potentiated endothelium‐dependent relaxation with intact NO synthesis and EDH‐type relaxation to BK by ≈2‐fold. Potentiation of the BK response was prevented by K_Ca3.1 inhibition. In Langendorff‐perfused rat hearts, SKA‐111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive‐gating modulation of K_Ca3.1 channels improves BK‐induced membrane hyperpolarization and endothelium‐dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive‐gating modulators of K_Ca3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease.     

Inhibition of human immunodeficiency virus type 1 infection in macrophages by an alpha-v integrin blocking antibody

Macrophages are key cells for HIV infection and HIV spreading inside the organism. Macrophages cultured in vitro can be successfully infected after differentiation with cytokines such as macrophage colony stimulating factor (M-CSF). In the monocyte to macrophage differentiation process with M-CSF, alphav-integrins are upregulated concomitantly with the capacity of HIV to generate a productive virus infection. In the present study we show that an anti-alphav antibody, 17E6, inhibited HIV-1 infection of primary macrophages. The effect of 17E6 on HIV-1 BaL replication in acutely infected macrophages was dose-dependent, with a 50% effective concentration (EC50) of 17+/-2 microg/ml in the absence of cytotoxicity. Similarly, a monoclonal antibody targeting the alphavbeta6 integrin (14D9.F8) also inhibited HIV-1 BaL infection in this cell type. 17E6 reduced the detection of HIV-1 BaL proviral DNA in acutely infected macrophages, but was completely ineffective against HIV-1 BaL production in chronically infected macrophages, suggesting that 17E6 inhibited HIV infection at an early stage of the virus cycle. Finally, a small molecular weight antagonist of the alphavbeta6 integrin, EMD 409849, reduced HIV replication at subtoxic concentrations. Therefore, our results suggest that alphav-containing integrins could play a role in HIV replication in macrophages and suggest that small-molecular-weight compounds might interfere with HIV replication in macrophages through the interaction with alphav integrins.     

Novel targets for HIV therapy

There are currently 25 drugs belonging to 6 different inhibitor classes approved for the treatment of human immunodeficiency virus (HIV) infection. However, new anti-HIV agents are still needed to confront the emergence of drug resistance and various adverse effects associated with long-term use of antiretroviral therapy. The 21st International Conference on Antiviral Research, held in April 2008 in Montreal, Canada, therefore featured a special session focused on novel targets for HIV therapy. The session included presentations by world-renowned experts in HIV virology and covered a diverse array of potential targets for the development of new classes of HIV therapies. This review contains concise summaries of discussed topics that included Vif-APOBEC3G, LEDGF/p75, TRIM 5α, virus assembly and maturation, and Vpu. The described viral and host factors represent some of the most noted examples of recent scientific breakthroughs that are opening unexplored avenues to novel anti-HIV target discovery and validation, and should feed the antiretroviral drug development pipeline in the near future.     

Phase II of doxorubicin/taxol in metastatic breast cancer

Purpose. To assess the response rate, survival, and toxicity of Taxol®(paclitaxel) as 1h infusion plus doxorubicin as firstline treatment for patients with metastatic breast cancer (MBC).Patients and methods. Seventysix patients with untreated MBC were recruited. All of them had measurable disease and were evaluable for toxicity. Fiftyfive percent of the patients had visceral involvement. The dose of doxorubicin was fixed at 50mg/m² as a short intravenous infusion, followed by 200mg/m² of Taxol as a 1h intravenous infusion. Doxorubicin was administered during the first seven cycles, continuing with Taxol only up to a maximum of ten cycles.Results. Neutropenia was the most important toxicity: 30% grade 3 and 18% grade 4. Only 2 patients showed a decrease in the left ventricular ejection fraction (LVEF) which caused discontinuing the treatment. No clinical congestive heart failure (CHF) was observed. Seventyfour patients were eligible for response evaluation: 10 (14%) achieved complete response (CR) and 46 (62%) achieved partial response (PR). The mean duration of response was 13.47± 1.35 months (95% confidence interval (CI): 10.82; 16.12) and the mean survival was 21.50± 1.42 months (95% CI: 18.72; 24.29).Conclusion. The overall response (OR) rate was 76%. No CHF was assessed and 2 patients stopped treatment due to LVEF decrease. Although doxorubicin 50mg/m² followed by Taxol 200mg/m² in 1h intravenous infusion presents a toxicity profile which demands a close followup, it represents a convenient outpatient schedule with similar activity rate compared to longer Taxol infusions.     

Interpretation module for screening normal ECG

This work concerns the development of a module for automatic recognition of normal ECGs, i.e. those whose waves morphology do not suggest physiopathological or structural heart alterations. Such a unit constitutes the central part of an administrative system under development which will aid in the management of ECG testing in the primary care delivery level in Chile. This system greatly contributes to the optimal allocation of resources in order to increase the test delivery coverage and to reduce the social and private costs involved. A main feature of the system is that it operates through the screening of normal ECG. This process is performed in a computerized unit whose core is the interpretation module. The design of such a module uses concepts and methods previously developed for the general problem of medical diagnosis, based on fuzzy set theory. The interpretation module parameters were adjusted considering hypothetical and real data covering a wide variety of normal and pathological cases. Then its performance was tested using more than one hundred patients' records chosen at random. Results of this test are given and a discussion, including a comparison with similar commercial equipment, is provided.     

Aseptic meningitis due to varicella-zoster virus: serum antibody levels and local synthesis of specific IgG, IgM, and IgA

We used an indirect enzyme immunoassay to describe the evolution of serum levels and the intrathecal production of IgG, IgA, and IgM antibodies to varicella-zoster virus (VZV) in eight patients with a syndrome of acute aseptic meningitis (AAM) and evidence of intrathecal production of VZV-specific IgG antibodies. Four of the eight patients showed no cutaneous zoster while hospitalized. Our results suggested an etiologic relation between VZV and AAM in all cases. Furthermore, we observed some differences in the pattern of evolution of antibodies in serum and cerebrospinal fluid in relation to the presence or absence of cutaneous lesions in our patients. These differences could reflect different pathogenic mechanisms in the spread of VZV to the central nervous system and in the production of the AAM syndrome.