Anemia associated with pegylated interferon-alpha2a and alpha2b therapy in hemodialysis patients.

AIMS: Anemia is a well-known side effect of interferon therapy since interferons are potent inhibitors of erythropoiesis. The aim of this study was to compare the anemia associated with pegylated interferon (PEG-IFN) (alpha2a versus alpha2b therapy in hemodialysis patients (HD) with chronic hepatitis C. METHODS: In order to study the anemia, doses of erythropoietic growth factors (EGF), hemoglobin (Hb) and erythropoietin resistance index (ERI) were compared at baseline and after PEG-IFN-alpha2a or alpha2b therapy in 16 HD patients with chronic C hepatitis. Pharmacokinetic studies were performed in 4 of those treated with PEG-IFN-alpha2b and 2 patients treated with PEG-IFN-alpha2a. Secondary end-points were viral response and serious adverse events. RESULTS: At 4-6 months after the beginning of therapy, both PEG-IFN-alpha induced a significant increment in the erythropoietin resistance index. This increment was significantly higher in patients treated with PEG-IFN-alpha2a when compared with alpha2b (45 vs 9.9, p = 0.012). The pharmacokinetics of PEG-IFN-alpha2a and alpha2b in HD patients were different, the C(max), C(min) and the area under the serum concentration time curve, were all higher in patients treated with PEG-IFN-alpha2a compared with PEG-INF-alpha2b. Discontinuation of therapy occurred in 2 (28.5%) of the 7 patients in the PEG-IFN-alpha2a group and in 4 (44%) of the 9 patients in the PEG-IFN-alpha2b group. Three (42%) subjects in the alpha2a group and 5 (55%) in the alpha2b group had a response at the end of the 48 weeks of therapy. In 4 (44.4%) of the 9 patients treated with alpha2b the viral response was sustained. CONCLUSIONS: In summary, patients treated with PEG-IFN-alpha2a have a major inhibitory effect on erythropoiesis. This could be explained by the different pharmacokinetic properties of PEG-IFN-alpha2a and alpha2b. Further studies are needed to clarify how these findings influence the efficacy, safety and cost-effectiveness of the PEG-IFN-alpha2.

[Usefulness of procalcitonin as an early diagnostic test of neonatal sepsis in newborns with risk factors for infection]. / Utilidad de la procalcitonina como prueba diagnóstica precoz de sepsis neonatal en recién nacidos con factores de riesgo de infección.

OBJECTIVE: To investigate the reliability of serum procalcitonin (PCT) as an early diagnostic test (within the first 12 hours of life) of neonatal sepsis in newborns with maternal or neonatal risk factors for infection. MATERIAL AND METHODS: We performed a prospective study of 123 newborns consecutively admitted to neonatal unit over a 2-year period with at least one risk factor for infection. We constructed a 2x2 table between the validated test (serum PCT by semi-quantitative assay, with several cut-off points: 0.5, 2 and 10 ng/ml) and the reference assay (blood culture or clinical, laboratory and microbiological confirmation of sepsis). The validity (sensitivity, specificity), safety [positive predictive value (PPV) and negative predictive value (NPV)] and likelihood ratios (LR+ and LR-) of the test were calculated. RESULTS: Serum PCT was measured within the first 12 hours of life in 95% of the patients (mean and median=6 hours). The best cut-off point for serum PCT was 2 ng/ml, and, taking subsequent clinical-laboratory-microbiological confirmation of sepsis as the best reference assay, showed a sensitivity of 100% (95% CI 65-100), specificity of 82% (95% CI 74-88), PPV of 25% (95% CI 13-44), NPV of 100% (95% CI 96-100), LR+ of 5.5 (95% CI 3.7-8.1), and LR- of 0. CONCLUSIONS: Serum PCT levels<2 ng/ml within the first 6-12 hours of life in newborns with risk factors for infection are useful as a screening assay to rule out neonatal sepsis with a sensitivity of 100% (false negatives=0% and NPV=100%). However, for subsequent confirmation a more specific assay (with a low false positive rate and high PPV) should be used, such as C-reactive protein. The higher cost of the serum PCT test should be weighed against shorter admissions as a result of its use.

[Markers of airway remodeling in induced sputum from healthy smokers]. / Marcadores de remodelado bronquial en el esputo inducido de fumadores sanos.

OBJECTIVE: Airway remodeling in chronic obstructive pulmonary disease (COPD) has been linked to the equilibrium between matrix metalloproteinase (MMP) 9 and its inhibitor, tissue inhibitor of metalloproteinase (TIMP) 1. However, that equilibrium has not been analyzed in healthy smokers. The aim of this study was to assess the equilibrium between MMP-9 and TIMP-1 in induced sputum from healthy smokers, healthy nonsmokers (controls), and patients with COPD. PATIENTS AND METHODS: Samples of induced sputum were obtained from 35 individuals: 12 healthy smokers, 12 controls, and 11 patients with COPD. In each sample, a differential cell count was performed and enzyme-linked immunosorbent assays were used to analyze the concentrations of MMP-9 (total and active fraction) and TIMP-1. RESULTS: Compared with controls, healthy smokers were found to have a higher mean (SD) concentration of total MMP-9 (273 [277] ng/mL vs 128 [146] ng/mL) and a higher ratio of total MMP-9 to TIMP-1 (0.16 [0.14] vs 0.08 [0.06]). However, the ratio of active MMP-9 to TIMP-1 was similar in the 2 groups. Samples from patients with COPD had the highest concentrations of total MMP-9 (477 [262] ng/mL) and active MMP-9 (178 [126] ng/mL) and the lowest concentrations of TIMP-1 (1.044 [1.036] microg/mL). When all groups were considered together, there was an inverse relationship between the MMP-9/TIMP-1 ratio and the forced expiratory volume in the first second (FEV1). The relationship between the active MMP-9/TIMP-1 ratio and FEV1 was even stronger, and the relation of both ratios with FEV1 became stronger still when smoking was considered. CONCLUSIONS: Healthy smokers had a higher concentration of total MMP-9 and that concentration was correlated with their exposure to tobacco smoke. Maintenance of the active MMP-9/TIMP-1 ratio in healthy smokers may explain the absence of progressive airway obstruction. Measurement of active MMP-9 concentration could be useful for assessment of airway remodeling.

[Anemia management in haemodialysis. EuCliD database in Spain]. / Control de la anemia en hemodiálisis. Base de datos EuCliD (European Clinical Database) en España.

We present the results on Anaemia Management in Fresenius Medical Care Spain dialysis centres as reported by EuCliD (European Clinical Database), evaluating a population of 4,426 patients treated in Spain during the year 2001. To analyse the erythropoietin dose and the haemoglobin levels we divided the population in two groups according to the time with dialysis treatment: patients treated less than six months and patients between six months, and four years on therapy. We compared our results with the evidence based recommendations Guidelines: the European Best Practice Guidelines (EBPG) and the US National Kidney Foundation (NKF-K/DOQI). We also compared our results with those presented by the ESAM2 on 2,618 patients on dialysis in Spain carried out in the second half of the year 2000. We observed that 70% of the population reaches an haemoglobin value higher that 11 g/dl, with a mean erythropoietin (rHu-EPO) dose of 111.9 Ul/kg weight/week (n = 3,700; SD 74.9). However, for those patients on treatment for less than six months, the mean Haemoglobin only reaches 10.65 g/dl (n = 222; SD 1.4). The rHu-EPO was administrated subcutaneously in 70.2% of the patients. About the iron therapy, 86% of the patients received iron treatment and the administration route was intravenous in 93% of the population. The ferritin levels were below 100 micrograms/dl in 10% of the patients and 26.4% showed a transferrin saturation index (TSAT) below 20%. The erythropoieting resistance index (ERI), as rHu-EPO/haemoglobin, has been used to evaluate the response to rHu-Epo, according to different variables. It was observed that the following factors lead to a higher rHu-EPO resistance: intravenous rHu-EPO as administration route, the presence of hypoalbuminemia, increase of protein C reactive, Transferrin saturation below 20% and starting dialysis during the last six months.

Evaluación de la reproducción inducida de nicuro Pimelodus blochii (Telostei: Pimelodidae) utilizando diferentes inductores hormonales / Evaluation of induced breeding of Pimelodus blochii nicuro (telostei, pimelodidae) using different inducing hormone

Objetivo. Evaluar el efecto de dos inductores hormonales en la reproducción inducida de nicuro Pimelodus blochii. Materiales y métodos. Para los procesos experimentales fueron utilizados adultos sexualmente maduros, sometidos a tres tratamientos aplicados vía intramuscular, en dosis única de 0.25 mL/kg Ovaprim® (OVAP) (T1), 0.5 mL/kg de OVAP (T2) y 6.25 mg/kg de Extracto de Hipófisis de Carpa (EHC) (T3), para este último tratamiento la inyección fue dividida en 20 y 80%, con un intervalo de 12 h entre aplicaciones. Previo a la extracción de los gametos, los animales fueron tranquilizados por inmersión en una solución de Metanosulfonato de Tricaina (90 mg/L). El desempeño reproductivo fue evaluado mediante el índice de ovulación (hembras ovuladas/hembras tratadas), fecundidad absoluta (Fa) (ovocitos/hembra), fecundidad relativa (Fr) en función del número de ovocitos desovados por gramo de peso. La fecundación se realizó en seco y seis horas post-fecundación (HPF) se determinó la tasa de fertilidad. Resultados. La ovulación (ºh) para el T1 fue a las 297.1±30.0, T2 294.6±32.9 y T3 247.3±13.1 ºh. En todos los tratamientos se obtuvieron hembras ovuladas, donde los mayores índices de ovulación fueron obtenidos con Ovaprim® (T1 y T2) con 36.4 y 50%, respectivamente. Las tasas de fecundación obtenidas fueron mayores a un 50%, para el tratamiento 1 y 2, con valores de 74.5 y 32.7%, respectivamente. Conclusiones. El uso de inductores hormonales puede ser efectivo para garantizar la reproducción inducida del nicuro, en dosis única de 0.25 y 0.5 mL/kg de Ovaprim®.

Objective. Evaluate the effect of two hormonal inducers in induced breeding of nicuro Pimelodus blochii. Materials and methods. The experimental process used sexually mature adults exposed to three intramuscular treatments, a single dose of 0.25 mL/g Ovaprim® (OVAP) (T1), 0.5 mL/kg of OVAP (T2) and 6.25 mg/kg of pituitary carp extract (EPC) (T3), for the latter treatment the injection was divided into 20 and 80%, with an interval of 12 hours between applications. Prior to the removal of gametes, the animals were tranquilized by immersion in a Tricaine Methanesulfonate (90 mg/L) solution. Reproductive performance was evaluated using ovulation rates (females ovulated/treated females), fertility (Fa) (eggs/female), relative fertility (Fr) depending on the number of eggs spawned per gram of weight. The dry method of fertilization was used and the fertility rate was determined six hours post-fertilization (HPF). Results. The Ovulation (ºh) was: for T1 297.1±30.0, T2 294.6±32.9 and T3 247.3±13.1ºh. Ovulated females were obtained in all treatments, where the highest rates of ovulation were obtained with Ovaprim ® (T1 and T2) with 36.4 and 50% respectively. Fertilization rates were higher than 50% for treatments 1 and 2, with values of 74.5 and 32.7% respectively. Conclusions. The use of hormonal inducers may be effective to ensure nicuro induced reproduction with a single dose of 0.25 and 0.5 mL/kg Ovaprim®.