21 years of Wiskott-Aldrich syndrome in Spain: incidence, mortality, and gender bias.

BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder considered to predominantly affect males. OBJECTIVE: This study aims to investigate the incidence and intrahospital death associated with WAS in Spain as well as the gender bias. METHODS: A population-based retrospective epidemiological study of 97 WAS patients that were diagnosed in Spanish hospitals between 1997 and 2017 was conducted by using data from the National Surveillance System for Hospital Data. RESULTS: Our results revealed that the mean annual incidence of WAS in Spain was 1.1 per 10,000,000 inhabitants (IC95% 0,45-2,33). The relative risk was higher in male than female (2.42). WAS diagnosis occurs at later ages in women (median age of 47 years) compared to men (median age of 5.5 years). Only male were admitted to the hospital at least in 10 different occasions and all deaths were detected in men. The intra-hospital death rate was of 9.28% in WAS, being most of the deaths associated with brain hemorrhage or infection. CONCLUSIONS: WAS, a rare disease, is diagnoses at later ages in women and the mortality was found in males mostly associated with brain hemorrhage and infection.

Angiogenesis determines blood flow, metabolism, growth rate, and ATPase kinetics of tumors growing in an irradiated bed: 31P and 2H nuclear magnetic resonance studies.

Experimental tumors growing in irradiated tissue have been used to study the biological differences characteristic of locally recurrent tumors. Since the hypoxic cell fraction of tumors growing in irradiated tissue is increased and growth rate is slowed, these tumors are assumed to be metabolically deprived with hypoperfusion. In this study, we directly measured the effect of tumor bed irradiation on blood flow, growth rate, rate of nucleoside triphosphate (NTP) turnover, and metabolic state using 31P and 2H nuclear magnetic resonance, and an intradermal assay for angiogenesis. (NTP turnover refers to ATP-synthetase mediated NTP turnover that is visible to 31P nuclear magnetic resonance using the technique of saturation transfer.) A decrease in the number of small blood vessels perfusing tumors in a preirradiated bed was found. Most of the decrease was due to a loss of vessels with diameters less than 0.04 mm. When tumors growing in preirradiated tissue reached approximately 100 mm3 in volume, a high frequency of gross and microscopic necrosis and hemorrhage was already observed in most tumors. Consistent with these observations, the phosphocreatine/inorganic phosphate and nucleoside triphosphate/inorganic phosphate ratios were significantly lower in the tumors growing in a preirradiated bed compared with tumors in a nonirradiated bed. The blood flow rate was similar to control for tumors less than 100 mm3 (45.8 versus 40.5 ml/100 g/min, P = not significant), but was significantly lower than control for tumors greater than 100 mm3 (40.4 versus 12.2 ml/100 g/min, P less than 0.01). The NTP turnover rates correlated (P less than 0.005, r = 0.66) with the volume doubling rate (1/tumor volume doubling time), but for tumors approximately 100 mm3 in size neither the volume doubling rate nor the NTP turnover rate of tumors growing in an irradiated bed was statistically lower than control [NTP turnover: 14 +/- 3%/s versus 9 +/- 2%/s; volume doubling rate: 0.47 +/- 0.07/day versus 0.33 +/- 0.04/day (mean +/- SE)]. A large intertumor variability of all metabolic parameters was observed.

Isolated rat cardiomyocytes as an experimental model for studying acute cardiotoxicity of cyclosporin A.

The acute cardiotoxicity of cyclosporin A was studied in isolated cardiac myocytes from adult rats. In an initial series of 7 animals, myocytes were incubated with concentrations of cyclosporin A ranging from 1 microgram/ml to 50 micrograms/ml. Shape changes of untreated cells, cells treated with cyclosporin A and cells treated with the solvent of cyclosporin A, Tween 80/ethanol, were evaluated. After 8 hours and 16 hours, respectively, of incubation 92 +/- 4.3% and 72 +/- 8.7% of the non-treated control cells were still rod-shaped. Cyclosporin A, however, in a concentration of 5 micrograms/ml decreased the number of rod-shaped cells (79 +/- 3.2% at 8 hours and 51 +/- 3.5% at 16 hours) in comparison to the solvent (94 +/- 3.5% at 8 hours and 76 +/- 5.8% at 16 hours, P less than 0.02). This effect became more pronounced with higher concentrations of cyclosporin A. On the other hand, Tween 80/ethanol alone in higher concentrations also led to a reduced number of rod-shaped cells. In a second series of 7 animals using Tween 80/ethanol and methanol as drug vehicles, myocytes were incubated for 16 hours with 15 micrograms/ml of cyclosporin A in a calcium containing medium (1 mM) or a calcium free medium (10(-4) M ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid). The number of remaining rod-shaped cells was higher in the calcium free medium as opposed to the medium containing calcium when the cells were exposed to cyclosporin A. It is concluded that in the applied model cyclosporin A at high concentrations has an acute cardiotoxic effect which in part appears to be calcium related.

Priorities and satisfaction on the help needed and provided in a first episode of psychosis. A survey in five European Family Associations.

In the case of a first episode of psychosis among members of different associations of families of mentally ill people, little is known about their priorities and how satisfied they are with the help provided to them. A survey was conducted in five European family associations. Respondents emphasized the need for early (ambulant) intervention through outreach with very practical goals directed at creating stability and social functioning. About one-third of the respondents are unsatisfied or very unsatisfied. The highest percentage of unsatisfied respondents was in the following five areas of care: advice on how to handle specific problems; help with preserving or regaining social functioning; help with regaining structure and routine; information; prompt assistance preferably in patients own environment. The agreement of these findings with findings from earlier studies underlines the importance of suggesting specific changes in the delivery of care.

[Risk behaviours and seroprevalence to HIV, HBV and HCV in patients of the AIDS information and prevention center in Valencia, Spain]. / Prácticas de riesgo y seroprevalencia al VIH, VHB y VHC en los pacientes del Centro de Información y Prevención del SIDA de Valencia.

OBJECTIVE: The purpose of this study was to describe the sociodemographic and serologic profiles in a first time consultant population at the Information and AIDS Prevention Center of Valencia (Spain). In addition, the HIV infection risk factors were analyzed. METHOD: A cross-sectional study was performed on 1,573 persons who consulted during the year 1995. Sociodemographic and infection risk practices data were recorded and serologic information about HIV, HBV and HCV infection were obtained. Exact binomial method with a 95% interval confidence was used to calculate infection prevalence and the chi square test to make comparisons between qualitative variables. RESULTS: Sex distribution was 66,1% males and 31,9% females; mean age was 29,01 (SD: 9.2) years. Sexual intercourse without condom (25.2%) and parenteral drug abusers (22.6%) were the more frequent risk groups seeking consultation about HIV infection. Global HIV infection prevalence was 12.7% (95% CI= 11,2-14,5%). Among HIV seropositive patients, sexual transmission accounted for 30.8% of cases, of which 69.4% were heterosexual relations. The HIV infection prevalence for different risk groups were the following: parenteral drug abusers 36.8% (95% CI= 31,7-42%), heterosexual intercourse with an HIV-infected partner 24.1% (95% CI= 17,1-32,2%) and homosexual intercourse between men 9,5% (95% CI= 5,8-14,5%). HCV antibody prevalence for parenteral drug abusers was 81.2% (95% CI= 76,7-85,1%). Risk practices with a statistically significant association with HIV infection were: being an injecting drug abuser, as well as having an HIV infected and/or a injecting drug abuser partner. CONCLUSIONS: Drug parenteral abusers are still the target population for prevention programs. Data suggest that prevention and sexual education programs must continue. The main effort should be focused on the young population and on sexual partners of injecting drug abusers and/or HIV seropositive partners.

Hypothermic coagulopathy in trauma: effect of varying levels of hypothermia on enzyme speed, platelet function, and fibrinolytic activity.

BACKGROUND: The coagulopathy noted in hypothermic trauma patients has been variously theorized to be caused by either enzyme inhibition, platelet alteration, or fibrinolytic processes, but no study has examined the possibility that all three processes may simultaneously contribute to coagulopathy, but are perhaps triggered at different levels of hypothermia. The purpose of this study was to determine whether, at clinically common levels of hypothermia (33.0-36.9 degrees C), there are specific temperature levels at which coagulopathic alterations are seen in each of these processes. METHODS: Of 232 consecutive adult trauma patients presenting to a Level I trauma center, 112 patients met the inclusion criteria of an Injury Severity Score of 9 or greater and time since injury of less than 2 hours. Of the included patients, 40 were normothermic and 72 were hypothermic (> or =37 degrees C, n = 40; 36.9-36 degrees C, n = 29; 35.9-35 degrees C, n = 20; 34.9-34 degrees C, n = 16; 33.9-33 degrees C, n = 7). Included patients were prospectively studied with thrombelastography adjusted to core body temperature. Additionally, PT, aPTT, platelets, CO2, hemoglobin, hematocrit, and Injury Severity Score were measured. RESULTS: Analysis by multivariate analysis of variance of the relationship between coagulation and temperature demonstrated that in hypothermic trauma patients, 34 degrees C was the critical point at which enzyme activity slowed significantly (p < 0.0001), and at which significant alteration in platelet activity was seen (p < 0.001). Fibrinolysis was not significantly affected at any of the measured temperatures (p > 0.25). CONCLUSIONS: Patients whose temperature was > or =34.0 degrees C actually demonstrated a significant hypercoagulability. Enzyme activity slowing and decreased platelet function individually contributed to hypothermic coagulopathy in patients with core temperatures below 34.0 degrees C. All the coagulation measures affected are part of the polymerization process of platelets and fibrin, and this process may be the mechanism by which the alteration in coagulation occurs.

Usefulness of thrombelastography in assessment of trauma patient coagulation.

OBJECTIVE: Thrombelastography (TEG) is used to rapidly assess coagulation abnormalities in cardiac and transplant surgery. The purpose of this study was to investigate TEG in the initial assessment of trauma patient coagulation. METHODS: TEG was performed on 69 adult blunt trauma patients during their initial evaluation. Demographics, history of inherited coagulopathies, medications, TEG parameters, platelet count, prothrombin time/partial thromboplastin time, Revised Trauma Score (RTS), Injury Severity Score (ISS), use of blood products, and outcome were recorded. RESULTS: Mortality was 4.3%. Fifty-two patients demonstrated coagulation abnormalities by TEG; of these, 45 were hypercoagulable (mean ISS 13.1), and seven were hypocoagulable (mean ISS 28.6). Six of the seven hypocoagulable patients received blood transfusions within the first 24 hours. Mean ISS of the 17 patients with normal TEG parameters was 3.7. Logistic regression of ISS, Revised Trauma Score, prothrombin time/partial thromboplastin time, and TEG on use/nonuse of blood products within the first 24 hours demonstrates that only ISS (p < 0.001) and TEG (p < 0.05) are predictive of early transfusion. CONCLUSIONS: The majority of blunt trauma patients in this series were hypercoagulable. TEG is a rapid, simple test that can broadly determine coagulation abnormalities. TEG is an early predictor of transfusion in blunt injury patients.