Post-mortem toxicology in the diagnosis of sudden death in young and middle-aged victims.

OBJECTIVE: We aimed to investigate the impact of the toxicological results found in cases of sudden death (SD) and to correlate the clinical, autopsy and genetic findings with the toxicology results. MATERIALS AND METHODS: Consecutive SD in people aged between 16 and 50 years with medico-legal autopsies and toxicology studies were included over a 3-year period. The comparison between the toxicological data and demographic characteristics, clinical circumstances, autopsy, and genetic results were taken into account. RESULTS: 101 cases were finally included. They were predominately males (84%) and the mean age was 39.8 years. 52 (51.5%) cases had positive toxicological findings and in 25 cases (24.8%), toxic compounds were considered the first cause of death. Ethanol was the most frequently identified agent (69%), following by licit drugs (56%) and drugs of abuse (39%). Cases with positive toxicology were younger than those with negative results (37.9±9.1 vs. 41.9±7.8; p=0.02). Patients with more than 3 comorbidities showed an association with positive toxicological results (n=14 vs. n=3; p=0.017). The genetic study was performed in 70 (69.3%) SD cases. We identified pathogenic or likely pathogenic variants in 17.1% cases and uncertain significance variants in 42.8% cases. 58% of these variants were probably related to the cause of death. CONCLUSIONS: A large fraction of SD victims had positive toxicological findings and a quarter of deaths were directly caused by toxic substances. The identification of the factors that trigger SD provides a good approach to contribute in avoiding future episodes.

Relationships between Serum Levels of Atazanavir and Renal Toxicity or Lithiasis.

The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV) at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were evidenced in urine. Cumulative incidence of renal colic was 9.2 per 100 patients. The variables related to having renal colic were the presence of alkaline urine pH and lower basal creatinine clearance. The mean serum level of ATV was slightly higher in patients with renal colic-1,303 µg/L versus 1,161 µg/L-but did not reach statistical significance. Neither were any significant differences detected by analysing the levels according to the timetable for ATV dosage. Cumulative incidence of renal colic was high in patients being treated with ATV, in 33% of whom the presence of ATV crystals was evidenced in urine. We were unable to demonstrate a relationship between ATV serum levels and renal colic or progression towards renal failure.

Prognostic value of serum CA125 levels in diffuse large B-cell lymphoma: potential role of a new sex- and age-adjusted reference value.

CA125, a tumor marker normally used to follow the clinical course of ovarian cancer, also may have a role in lymphoma. All available series were analyzed using the standard reference value 35 U/ml, but age and sex may influence serum CA125 (sCA125) levels. We aim to study the prognostic value of serum CA125 (sCA125) levels in diffuse large B-cell lymphoma (DLBCL), considering the influence of age and sex on sCA125 levels. We investigated the relationship between sCA125 and clinical outcome after treatment in 42 patients with DLBCL, comparing both the standard (35 U/ml) and a new age and sex adjusted (sex/age-adjusted) reference value proposed by our group. We found that patients with elevated sCA125 levels had significantly more adverse prognostic factors at diagnosis, lower CR rates, higher relapse rates and worse survival. In the low-risk IPI categories, the presence of elevated sCA125 defined a particularly high-risk subgroup with poorer 3-year PFS when compared with patients with normal sCA125 levels. The use of a sex/age-adjusted reference value for sCA125 may increase the sensitivity to identify those patients with elevated sCA125 levels truly related to DLBCL activity.

Revisión de las intoxicaciones graves por insecticidas organofosforados atendidas en un período de 11 años (1996-2006) / Review of severe organophosphate poisonings over a period of 11 years (1996-2006)

Objetivo: Revisar las intoxicaciones por organofosforados (OF) en un período de 11años atendidas en nuestro hospital que requirieron ingreso de 7 días o más. Método: Estudio retrospectivo descriptivo de pacientes intoxicados por insecticidas OF atendidos entre 1996 y 2006 con una estancia hospitalaria igual o mayor de 7 días. Se analizan las siguientes variables: la edad, el sexo, el tipo de producto, el destino del ingreso y la duración de las estancias hospitalarias que generaron, el hábitat de residencia(rural o urbano), la causa de la intoxicación, la sintomatología clínica, las medidas terapéuticas aplicadas, la presencia de antecedentes psiquiátricos y las determinaciones seriadas de colinesterasas sérica. Resultados: Se han incluido 8 pacientes, el 50% de los cuales eran hombres, con una edad media de 49 años. El producto un OF puro (50%), un OF más herbicida (25%) y un OF más carbamato (25%). La estancia media hospitalaria fue de 40 días y en los 6pacientes que requirieron unidad de cuidados intensivos (UCI) su estancia en ella fue de 23 días. Cinco casos procedían del medio rural (62,5%) y 3 del urbano (37,5%), yen 5 casos (62,5%) exitió intención suicida. Todos los pacientes presentaron síndrome colinérgico, el 25% síndrome muscarínico leve el 75% sintomatología muscarínica, nicotínicay central. En el 50% de casos se produjo un síndrome intermedio y en el 50%hubo recidiva colinérgica. Hubo hipotermia severa en 2 casos e insuficiencia respiratoria en 6 pacientes, los cuales requirieron intubación orotraqueal. Se realizó descontaminación gástrica en 6 casos, en 2 se administró el carbón sin lavado previo, en 5 la atropina,en 4 la pralidoxima y en 1 el carbón activado y la hemofiltración. La colinesterasasérica fue determinada en 6 casos. Conclusión: Las intoxicaciones graves por OF presentan una gran riqueza sintomática, la cual es mayor cuando las medidas iniciales adoptadas no son enérgicas y/o si se produce una retirada precoz del tratamiento (AU)

Objective: To review all the organophosphate poisonings (OP) over a 11-year period which required at least seven days of admission at our hospital. Methods: Descriptive retrospective study of patients with OP attended at the hospital from 1996 to 2006. The variables age, sex, type of poisonous compound, destination at admission, length of stay, environment (rural or urban), cause of poisoning, clinical symptoms, therapeutic measures, acetyl cholinesterase measurement, and history of psychiatric disorders were assessed. Results: Eight patients were included, mean age 49 years (range: 26-65), 50% female. Poisonous compound were pure OP (50%), OP plus herbicide (25%) and OP plus carbamate (25%). Mean hospital stay was 40,5 days. Mean stay in the ICU in 6 patients who required intensive care was 23 days. Five (63.5%) patients were from rural origin and 3 (27.5%) were urban cases. Five cases (62.5%) were suicide attempts, 2 (25%) were accidents and the reason was not clear in one case. 100% presented with cholinergic syndrome, 2 cases (25%) mild muscarinic syndrome and 6 cases (75%) muscarinic, nicotinic and central symptoms. Four cases (50%) presented intermediate syndrome and 4 cases relapse of cholinergic symptoms. Severe hypothermia was present in 2 cases. Respiratory insufficiency was seen in 6 patients, which required orotracheal intubation. Gastrointestinal decontamination was performed in 6 cases. Two patients received activated charcoal without lavage. Atropine was usedin 5 cases (62.5%) and pralidoxime in 4. Hemoperfusion with activated carbon and hemofiltration was used inone case. Serum cholinesterase activity was measured in 6 cases. Conclusion: Severe organophosphate poisonings has multiple symptoms. If general measures adopted are not enough and/or treatment is withdrawn early they can increase significantly (AU)

Proposed reference value of the CA 125 tumour marker in men. Potential applications in clinical practice.

INTRODUCTION: CA 125 is a tumour marker usually used to monitor the clinical course of the patients with ovary cancer. The frequently used reference value of this marker is 35 U/mL. However, some arguments to allow us to question us the validity of the classical reference value: i) a second generation of immunoassays, ii) diverse studies related to the factors that influence in the CA 125 serum concentrations and iii) the new applications of CA 125 in pathologies different to the ovary cancer. OBJECTIVES: 1) To propose a reference value of CA 125 in men; 2) To evaluate the CA 125 serum concentration according to different variables, some of which can be altered in pathologies where CA 125 level can be monitored and/ or altered. MATERIAL AND METHODS: 65 healthy men were included (age: 40.21+/-10.60 years). A survey containing different parameters and an analytic that contained a hemogram, hepatic, renal, pancreatic profile, ionogram, thyroid function, tumour markers and NT-Pro-BNP was carried out to exclude the presence of a pathological situation. The percentile 95 (P(95)) was calculated to obtain the reference value. Correlations among the CA 125 and the different variables were analyzed by the Spearman test. RESULTS: The median [ranges] and the P(95) were: 7.50 [3.00-25.00] and 20.17 U/mL, respectively. 78% of the values of CA 125 were < or =10 U/mL, 94% were < or =15 U/mL and 95% were < or =20 U/mL. Furthermore, the studied variables don't seem to influence in the concentrations of this marker. CONCLUSIONS: The proposed reference value obtained in healthy male subjects is significantly lower than the one used in the clinical practice. This value should be kept in mind when extending the use of this marker to other pathologies which was not used up to now.

Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco smoking.

Tobacco smoking induces an inflammatory response in the lungs of all smokers but, for reasons that are still poorly understood, only a proportion of them develop chronic obstructive pulmonary disease (COPD). Recent evidence indicates that this inflammatory response persists after smoking cessation, suggesting some type of auto-perpetuation mechanism similar to that described in autoimmune disorders. T-lymphocytes (CD4+ and CD8+) have been implicated in the pathogenesis of both COPD and several autoimmune processes. A subtype of regulatory CD4+ T-cells expressing CD25 (Tregs) plays a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity, but their potential role in COPD has not been explored. The present study sought to evaluate maturation (CD45RA/CD45R0) and activation markers (CD28) of T-lymphocytes and to explore potential Treg abnormalities in COPD. Flow cytometry was used to characterise T-lymphocytes obtained from blood and bronchoalveolar lavage fluid (BALF) in 23 patients with moderate COPD, 29 smokers with normal lung function and seven never-smokers. The main findings were that in BALF: patients with COPD showed higher CD8+CD45RA+ and lower CD8+CD45R0+ than smokers with normal lung function; and compared with never-smokers, smokers with preserved lung function showed a prominent upregulation of Tregs that was absent in patients with COPD. These observations indicate a final maturation-activation state of CD8+ T-lymphocytes in chronic obstructive pulmonary disease and, for the first time, identify a blunted regulatory T-cell response to tobacco smoking in these patients, further supporting a potential involvement of the acquired immune response in the pathogenesis of the disease.

Intracellular cytokine profile of T lymphocytes in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by an excessive inflammatory response to inhaled particles, mainly tobacco smoking. T lymphocytes are important regulatory cells that secrete several cytokines and participate actively in this inflammatory response. According to the pattern of cytokines secreted, the immune response is classified as cytotoxic or type 1 [interferon (IFN)-gamma-, interleukin (IL)-2-dependent] and humoral or type 2 (IL-4-, IL-5-, IL-10- and IL-13-dependent). This paper sought to compare the intracellular profile of cytokine expression determined by flow cytometry in T lymphocytes harvested from bronchoalveolar lavage (BAL) and peripheral blood in patients with COPD, smokers with normal lung function and never smokers. We found that BAL T lymphocytes from COPD patients had a higher percentage of positive stained cells for most of the cytokines analysed when compared to never smokers or smokers with normal lung function. Differences reached statistical significance for IL-4, IL-10 and IL-13, particularly in CD8(+) T cells. Furthermore, the expression of most of these cytokines was related inversely to the degree of airflow obstruction present suggesting local activation and/or selective homing of T lymphocytes to the lungs in COPD patients. These observations were not reproduced in circulating T lymphocytes. These results suggest that BAL T lymphocytes in patients with COPD produce more cytokines than in controls and tend to show a type 2 pattern of intracellular cytokine expression, particularly a Tc-2 profile. This is related inversely to the degree of airflow obstruction present.

Variabilidad de las concentraciones séricas de CA 125 en mujeres sanas en función de la edad, situación hormonal y otras condiciones / Variability of CA 125 serum concentrations in healthy women according to age, hormonal status and other factors

Los conocimientos relativos a los factores que influyen en las concentraciones de CA 125 ha conducido a cuestionarse la validez de un único valor límite. Los objetivos del trabajo fueron valorar los valores de CA 125 en función de la edad, presencia o ausencia de menopausia, índice de masa corporal (IMC), hábito tabáquico, paridad, variabilidad durante el ciclo menstrual, variabilidad biológica, índice de individualidad y diferencia crítica. Se incluyó a 65 mujeres sanas distribuidas en 2 grupos: sin y con menopausia. Los principales resultados demuestran que existe una clara relación entre las concentraciones de CA 125 y la edad, que en mujeres sin menopausia la concentración de CA 125 fue superior respecto a las mujeres con menopausia, con p95 de 30,52 y 18,30 U/ml, respectivamente. No encontramos variaciones durante el ciclo menstrual, aunque existe la probabilidad de encontrar valores superiores al valor límite convencional durante la fase folicular. La variabilidad biológica intra e interindividual en mujeres sin menopausia fue del 14,23 y el 43,57%, respectivamente, mientras que la variabilidad biológica interindividual en mujeres con menopausia fue del 36,25%. La diferencia crítica fue del 42,73% y el índice de individualidad de 0,11. No encontramos diferencias en función de la paridad ni del hábito tabáquico. Tampoco encontramos una relación respecto al IMC. En conclusión, el conocimiento de factores que influyen en las concentraciones séricas de CA 125, así como la adaptación de valor límite en función de diferentes situaciones fisiológicas y clínicas puede permitir una mejor interpretación e identificación de subgrupos con un riesgo de presentar cáncer de ovario (AU)

Knowledge of the factors influencing serum concentrations of CA 125 have led the validity of a single cut-off value to be questioned. The aims of the present study were to evaluate CA 125 levels according to age, menopause, body mass index (BMI), smoking, parity, variability during the menstrual cycle, biological variation, index of individuality (II), and critical difference (CD). Sixty-five healthy women distributed in 2 groups, non-menopausal and menopausal, were included. The main results of the study demonstrate that there is a clear relationship between CA 125 levels and age: serum levels of CA 125 were significantly lower in menopausal women than in non-menopausal women, with 95th percentiles of 30.52 U/ml and 18.30 U/ml, respectively. No variations were found during the menstrual cycle, although a CA 125 value higher than the conventional cut-off value was observed during the follicular phase. In non-menopausal women, intra- and interindividual biological variations were 14.23% and 43.57%, while in menopausal women interindividual biological variation was 36.25%. CD was 42.73% and II was 0.11. No significant differences were found between smokers and nonsmokers or according to parity. No relationship was found between CA 125 levels and BMI. In conclusion, knowledge of the factors influencing serum concentrations of CA 125 according to different physiologic and clinical factors and careful adjustment of cut-off values could improve interpretation and identification of subgroups at risk for ovarian carcinoma (AU)

Evaluación de dos ensayos quimioluminiscentes automatizados para la medida de Insulin-like growth factor I (IGF-I) y Insulin- like growth factor binding protein 3 (IGFBP-3) / Evaluation of two automated chemiluminiscent immunoassays for Insulin-like growth factor I (IGF-I) and Insulin-like growth factor binding protein 3 (IGFBP-3)

Realizamos un estudio de comparación entre dos métodospara la medida de Insulin-like growth factor I (IGF-I) e Insulin-likegrowth factor binding protein 3 (IGFBP-3). La IGF-I y la IGFBP-3 se midieron por un método inmunoquímico quimioluminiscenteen un analizador IMMULITE 2000 y por un método inmunoradiométrico(IRMA). En el IMMULITE 2000 se evaluó el límitede detección, imprecisión, inexactitud y concordancia, errortotal (ET) y practicabilidad. Límites de detección: IGF-I: 20ng/mL y IGFBP-3: 0,02 µg/mL. La imprecisión del ensayo de IGF-I se mantuvo parcialmente dentro de los límites establecidos(<6,95%) y para la IGFBP-3 se mantuvo dentro de loslímites aceptables (<4.85%). El ensayo de IGF-I respecto alIRMA no presentó ningún error sistemático mientras que elensayo de IGFBP-3 presentó un error sistemático proporcional.El ET con ambos métodos fue de 17,09 % y 11,92%, respectivamente.Los ensayos de IGF-I y IGFBP-3 en el IMMULITE2000 son sensibles, precisos, rápidos y automáticos lo querepresenta claras ventajas. Concluimos que los métodos estudiadosson satisfactorios para la determinación de estas magnitudes

Perform an analytical evaluation of two methods for Insulinlikegrowth factor I (IGF-I) and Insulin-like growth factor bindingprotein 3 (IGFBP-3). IGF-I and IGFBP-3 Immulite 2000 methodswere evaluated for detection limit, precision, correlation, totalerror (TE) and practicability. Detection limit of IGF-I and IGFBP-3 methods were 20 ng/mL and 0,02 µg/mL, respectively. Precisionfor IGF-I assay was partiality within acceptable limits(<6,95%); for IGFBP-3 assay, was within acceptable limits (<4.85%). IGF-I respect to the IRMA method had not a systemtic bias and IGFBP-3 had a proportional systematic bias. TE forIGF-I and IGFBP-3 was 17,09 % and 11,92%, respectively.IMMULITE 2000 IGF-I and IGFBP-3 assays have performancecharacteristics suitable for the monitoring of these analytes

Decreased macrophage release of TGF-beta and TIMP-1 in chronic obstructive pulmonary disease.

The present study tested the hypothesis that alveolar macrophages (AM) from patients with chronic obstructive pulmonary disease (COPD) release more pro-inflammatory and/or less anti-inflammatory mediators than those from smokers with normal lung function and never-smokers. AM were sorted by flow cytometry from bronchoalveolar lavage fluid in 13 patients with COPD (mean+/-SEM 67+/-2 yrs, forced expiratory volume in one second (FEV1) 61+/-4% reference), 16 smokers with normal lung function (55+/-2 yrs, FEV1 97+/-4% reference) and seven never-smokers (67+/-7 yrs, FEV1 94+/-4% reference). After sorting, AM were cultured (with and without lipopolysaccharide stimulation) after 4 h and 24 h, and the concentrations of leukotriene B4 (LTB4), transforming growth factor (TGF)-beta1 and tissue inhibitor of metalloproteinase (TIMP)-1 were quantified in the supernatant by ELISA. The production of reactive oxygen intermediates (ROI) in freshly isolated AM was determined by flow cytometry. LTB4 secretion and ROI production were not different between groups. In contrast, AM from COPD patients released significantly less TGF-beta1 and TIMP-1 than those from smokers with normal lung function and nonsmokers. In conclusion, these observations are compatible with reduced anti-inflammatory and anti-elastolytic capacity in chronic obstructive pulmonary disease, which is likely to contribute to the pathogenesis of the disease.

Experience in management of 51 non-functioning pituitary adenomas: indications for post-operative radiotherapy.

OBJECT: The indications for additional radiotherapy (RT) after surgery for non-functioning pituitary adenoma are controversial. The goal of this retrospective study was to evaluate the outcome of surgically treated patients, with or without post- operative irradiation. METHODS: Review of cases treated for non-functioning pituitary adenoma. Fifty-one patients were identified, with a mean post-operative follow-up of 6.4+/-3.5 yr. Twenty-nine patients showed residual tumor after surgery and 22 did not. Serial endocrine, visual and radiological evaluations were made after treatment to assess the efficacy and toxicity of surgery and RT. Twenty-seven patients with residual tumor after surgery received RT (22 of them during the post-operative period and 5 after an interval of several yr: 3 because of increased tumor size and 2 with stable residual lesion); tumors in 14 of these patients decreased in size, 11 appeared to be stable on imaging and one patient showed some increase in tumor size (one patient was not followed-up). The residual tumors of the 2 non-irradiated patients remained stable after 5 and 7 yr, respectively. Twenty-two patients without residual disease after surgery (11 with post-operative irradiation, 1 with RT 5 yr after transsphenoidal surgery because of tumor recurrence, and 10 without RT) have shown no evidence of tumor regrowth on serial images. CONCLUSIONS: Radiotherapy can be avoided in patients with complete macroscopic resection and absence of residual tumor in post-operative images; they must be carefully followed using imaging techniques and, in the case of recurrence, they should be re-operated and/or irradiated.

[Comparison of the effectiveness of pentobarbital and thiopental in patients with refractory intracranial hypertension. Preliminary report of 20 patients]. / Comparación de la eficacia del pentobarbital y el tiopental en el control de la hipertensión intracraneal refractaria. Resultados preliminares en una serie de 20 pacientes.

OBJECTIVE: To assess the effectiveness of pentobarbital and thiopental to control raised intracranial pressure (ICP), refractory to first level measures, in patients with severe traumatic brain injury. MATERIAL AND METHODS: Prospective, randomized study to compare the effectiveness between two treatments: pentobarbital and thiopental. The patients will be selected from those admitted to the Intensive Care Unit with a severe traumatic brain injury (postresuscitation Glasgow Coma Scale equal or less than 8 points) and raised ICP (ICP>20 mmHg) refractory to first level measures according to the Brain Trauma Foundation guidelines. The adverse effects of both treatments were also collected. RESULTS: We present the results of the first 20 patients included. Ten received pentobarbital and the other ten thiopental. There were no statistically significance differences in patients'characteristics (age, sex, severity of the trauma at admission and comorbilities). There were no differences between both groups neither in the Glasgow Coma Scale at admission (thiopental six points; pentobarbital seven points; P=0.26) nor in the admission Cranial Tomography, according to the Traumatic Coma Data Bank Classification. Thiopental treatment controlled raised ICP in five cases and pentobarbital in two cases (P=0.16). Five patients in the thiopental group died and eight in the pentobarbital group (P=0.16). There were no statistically differences between both groups regarding to the presence of hypotension (P=1) or infectious complications. CONCLUSIONS: These preliminary results indicate that thiopental could be more effective than pentobarbital in patients with refractory intracranial hypertension. These results support previous experimental findings that show that both treatments are not equal and justify to continue this study.

Blunted gamma delta T-lymphocyte response in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by an excessive inflammatory response to inhaled particles, mostly tobacco smoking. Although inflammation is present in all smokers, only a percentage of them develop COPD. T-lymphocytes are important effector and regulatory cells that participate actively in the inflammatory response of COPD. They comprise the T-cell receptor (TCR)-alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes. The latter represent a small percentage of the total T-cell population, but play a key role in tissue repair and mucosal homeostasis. To investigate TCR-alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes in COPD, the present authors determined, by flow cytometry, the distribution of both subpopulations in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from patients with COPD, smokers with normal lung function and never-smokers. The present study found that: 1) the distribution of CD4+ and CD8+ lymphocytes in blood and BAL was similar in all three groups; 2) compared with nonsmokers, gamma delta T-lymphocytes were significantly increased in smokers with preserved lung function; and 3) this response was blunted in patients with COPD. These results highlight a novel, potentially relevant, pathogenic mechanism in chronic obstructive pulmonary disease.

Comparación de la eficacia del pentobarbital y el tiopental en el control de la hipertensión intracraneal refractaria. Resultados preliminares en una serie de 20 pacientes / Comparison of the effectiveness of pentobarbital and thiopental in patients with refractory intracranial hypertension. Preliminary report of 20 patients

Objetivo. Comparar la eficacia del pentobarbital y tiopental en el control de la hipertensión intracraneal (HIC) refractaria a las medidas de primer nivel, según las Guías de Práctica Clínica de la "Brain Trauma Foundation", en pacientes con traumatismo craneoencefálico (TCE) grave. Material y métodos. Estudio prospectivo de cohorte, aleatorizado, de intervención terapéutica comparativa entre dos fármacos: pentobarbital y tiopental. La muestra fue seleccionada a partir de los pacientes que sufrieron un TCE grave (Glasgow Coma Scale GCS, postresucitación, 20 mmHg) refractaria al tratamiento convencional, de acuerdo con las Guías de Práctica Clínica de la "Brain Trauma Foundation". Además de comprobar la eficacia en el control de la PIC, también se recogieron los efectos secundarios del tratamiento. Resultados. Se presentan los resultados de los primeros 20 pacientes reclutados, de los cuales diez recibieron tiopental y diez pentobarbital. No hubo diferencias estadísticamente significativas en las características basales de los pacientes (edad, sexo, índices de gravedad y comorbilidades). Tampoco hubo diferencias respecto al GCS de ingreso (tiopental seis puntos; pentobarbital siete puntos; P=0,26) ni en la tomografía craneal computarizada de ingreso, según la clasificación del "Traumatic Coma Data Bank". En el grupo de tiopental se controló la PIC en cinco casos y en el grupo de pentobarbital en dos pacientes (P=0,16). Cinco pacientes tratados con tiopental fallecieron y ocho en el grupo de pentobarbital (P=0,16). No hubo diferencias significativas entre ambos grupos respecto a la incidencia de hipotensión arterial (P=1) o complicaciones infecciosas. Conclusiones. los resultados preliminares de este estudio indican que el tiopental podría ser más eficaz que el pentobarbital en el control de la HIC refractaria a las medidas de primer nivel. Dichos resultados confirman la evidencia experimental que indica que los mecanismos neuroprotectores de ambos fármacos son distintos y justifican el continuar aumentando el tamaño muestral de nuestro estudio para poder definir mejor la eficacia de ambos fármacos

Objective. To assess the effectiveness of pentobarbital and thiopental to control raised intracranial pressure (ICP), refractory to first level measures, in patients with severe traumatic brain injury. Material and methods. Prospective, randomized study to compare the effectiveness between two treatments: pentobarbital and thiopental. The patients will be selected from those admitted to the Intensive Care Unit with a severe traumatic brain injury (postresuscitation Glasgow Coma Scale equal or less than 8 points) and raised ICP (ICP>20 mmHg) refractory to first level measures according to the Brain Trauma Foundation guidelines. The adverse effects of both treatments were also collected. Results. We present the results of the first 20 patients included. Ten received pentobarbital and the other ten thiopental. There were no statistically significance differences in patients’characteristics (age, sex, severity of the trauma at admission and comorbilities). There were no differences between both groups neither in the Glasgow Coma Scale at admission (thiopental six points; pentobarbital seven points; P=0.26) nor in the admission Cranial Tomography, according to the Traumatic Coma Data Bank classification. Thiopental treatment controlled raised ICP in five cases and pentobarbital in two cases (P=0.16). Five patients in the thiopental group died and eight in the pentobarbital group (P=0.16). There were no statistically differences between both groups regarding to the presence of hypotension (P=1) or infectious complications. Conclusions. These preliminary results indicate that thiopental could be more effective than pentobarbital in patients with refractory intracranial hypertension. These results support previous experimental findings that show that both treatments are not equal and justify to continue this study

Transferibilidad de resultados entre dos ensayos para la medida del Antígeno Prostático Específico total y libre / Compatibility of results between two immunoassays for the measure of the total and free Prostate Specific Antigen

Objetivo: evaluar la transferibilidad de los resultados de PSA total y libre medidos en dos inmunoensayos y las consecuencias prácticas que puede tener la elección de un ensayo. Material y métodos: 151 pacientes con sospecha de hiperplasia benigna de próstata (HBP) y/o con carcinoma prostático. El PSA total se determinó mediante los ensayos de ADVIA Centaur e Immulite 2000 y el PSA libre en el ACS 180 e Immulite 2000. Resultados: La media de los resultados del PSA total es mayor en el Immulite 2000 (p<0.0001); la media de PSA libre )p<0.0001) y del por cientoPSA libre (p<0.0001) es menor en el Immulite 2000. Conclusiones: a) Los resultados de los dos ensayos evaluados no son intercambiables y demuestran la necesidad de realizar estudios de transferibilidad de resultados cuando se produce un cambio de método en el laboratorio. 2) Las discrepancias entre los ensayos podrían traducirse en diferencias clínicamente significativas (AU)

Varying additive effects of bromocriptine with two somatostatin analogs in cultures of GH-secreting adenomas.

In this study, we have investigated the effect of combined treatment using two somatostatin analogs, lanreotide or octreotide, with bromocriptine on GH release in cultures of GH-secreting pituitary tumors. Sixteen acromegalic patients were included in the study. All patients had been treated with lanreotide prior to the surgery. Five patients (31.2 %) reached GH levels below 2.0 microg/l and normal IGF-I levels according to age and sex after lanreotide treatment. A positive correlation was observed between the lanreotide-induced inhibition of GH release in vitro and serum GH decrease after lanreotide treatment (r = 0.52; p = 0.03). Combined treatment significantly inhibited GH release in vitro in 8 of the 16 tumors (50 %). However, only 5 (31.2 %) of the respective patients had been resistant to presurgical treatment with lanreotide. Three of these 5 patients (18.7 %) responded to a BC concentration similar to that achieved with therapeutic doses, and in 2 patients only when a pharmacological dose of BC was used in the combined treatment. The additive effect was observed with the combination of lanreotide and BC in 6 tumors and with octreotide and BC in 3. Only one tumor showed simultaneous response to both types of combination. These results suggest that the additive effect under the combined treatment might be found between 18 and 30 % of patients who are resistant to these drugs, and that different combinations of somatostatin analogs and dopamine agonists should be tested in resistant patients.

The complete normalization of the adrenocortical function as the criterion of cure after transsphenoidal surgery for Cushing's disease.

Transsphenoidal microsurgery is the standard treatment for patients with Cushing's disease. However, there is general lack of agreement regarding the definition of cure. We studied 58 patients with corrected hypercortisolism after transsphenoidal surgery for Cushing's disease. Plasma and urinary cortisol levels were measured after surgery. After the postsurgical hypocortisolism stage (or periodically in patients without hypocortisolism), urinary free cortisol, plasma cortisol at 0800 h and 2300 h, morning cortisol after 1 mg dexamethasone, and cortisol response to insulin-induced hypoglycemia were performed. Patients were classified in 3 groups: group I, patients with transient hypocortisolism and normal hypothalamus-pituitary-adrenal axis afterwards; group II, patients with transient hypocortisolism and abnormalities in the circadian rhythm or the stress response afterwards; and group III, patients without postoperative hypocortisolism. Thirty-three patients were included in group I, 8 in group II, and 17 in group III. Groups I and II were similar in postsurgical plasma cortisol (46.9 +/- 30.3 vs. 60.7 +/- 38.6 nM) and mean follow-up (69.8 vs. 68.8 months) but were significantly different in their recurrence rate (3.4% vs. 50%, P < 0.001). Patients in group III had normal postsurgical plasma and urinary cortisol but persistent abnormalities in circadian rhythm and stress response. After a mean follow-up of 39.1 months, their recurrence rate was similar to that of group II (64.7% vs. 50%). The complete normalization of the adrenocortical function, which is always preceded by postsurgical hypocortisolism, is associated with a very low recurrence risk and should be considered, in our opinion, the main criterion of surgical cure in Cushing's disease.

Apparent cure of Graves-Basedow disease after sibling allogeneic bone marrow transplantation.

Evidence that allogeneic bone marrow transplantation (BMT) can cure or alter the course of intractable autoimmune diseases comes from both extensive experimental work in animal models and anecdotal case reports in humans. We describe a female patient diagnosed as having severe aplastic anaemia (SAA), hyperthyroidism and ophthalmopathy of Graves-Basedow disease who received a BMT from her histocompatible sister. Fifty-three months after BMT, complete remission of hyperthyroidism and ocular signs persists. The SAA is cured and she is free of any chronic graft-versus-host disease (GVHD). In the early post-BMT period, PCR analysis of bone marrow and peripheral blood cells confirmed a complete chimerism of donor origin. Thus, it is plausible to attribute the resolution of the patient's thyroid hyperfunction and opththalmopathy to the replacement of the host immune system.