Cyclosporine A for the Prevention of Ocular Graft versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients Is Safe and Feasible.

PURPOSE: To evaluate the safety and efficacy of ocular cyclosporine in the prevention of the development of ocular graft versus host disease (oGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) in comparison with historic data. DESIGN: We developed a longitudinal, observational, prospective nonrandomized study. We evaluated the feasibility of prophylactic use of topical cyclosporine A (CsA) to prevent or decrease the incidence of oGVHD and compared this with historic data. METHODS: Patients undergoing AHSCT were treated with prophylactic topical CsA for 12 months after engraftment, followed by serial ophthalmic evaluations, including the Schirmer test. RESULTS: Twenty patients were included. No serious adverse effects were reported. Poor adherence was documented in 15% of patients. In spite of observing extra-ocular GVHD (acute and chronic GVHD incidence of 50 and 45%, respectively), only 1 in 20 patients developed oGVHD over the 20-month follow-up for the entire cohort. No statistically significant difference was observed in the incidence of oGVHD when compared to a historical cohort. CONCLUSIONS: Topical CsA as a prophylactic measure for oGVHD, administered over a period of 1 year after grafting, is safe and feasible and may decrease the incidence of ophthalmic manifestations of GVHD. These findings must be confirmed in a randomized trial.

More about low-dose rituximab and plasma exchange as front-line therapy for patients with thrombotic thrombocytopenic purpura.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, mainly as a consequence of autoimmunity. Plasma exchange (PEx) is standard, achieving complete remission (CR) in 77-83% of cases, but rates are variable depending on ADAMTS-13 activity and relapse is frequent in patients with <10%. Thus, an effective front-line immunosuppressive treatment is needed. MATERIALS AND METHODS: We administered PEx daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks to 10 patients with a first TTP episode and 1 relapsed patient (8 females (72%) and 3 males (28%)). Median age was 34 years (15-46) and laboratory parameters at diagnosis were as follows: platelets 11 × 10(9)/l (range 7-27.4 × 10(9)/l), lactate dehydrogenase 1822 U/l (range 705-8220 U/l, normal 70-180 U/l), and haemoglobin 6 g/dl (range 4.2-11.8 g/dl). ADAMTS-13 activity was determined in eight patients and was <10% in all. ADAMTS-13 autoantibody titre was determined in seven patients and was >15 units/ml in all (ref: negative <12, undetermined 12-15, positive >15 units/ml); Shiga toxin was negative in all patients. The median number of PEx until CR was 7 (range 4-12); prednisone 1 mg/kg was administered to six patients. RESULTS: The median follow-up was 22 months (range 4-49) and the estimated 2-year relapse-free survival was 89%; one HIV+ patient relapsed at 8 months follow-up. No complications related to PEx or rituximab were reported. CONCLUSIONS: Our study suggests that low-dose rituximab and PEx are effective as front-line treatment for acute TTP; however, a prospective trial is needed to demonstrate whether low-dose rituximab is as effective as the conventional dose.

Incidental identification of a thyroid hormone receptor beta (THRB) gene variant in a family with autoimmune thyroid disease.

BACKGROUND: Resistance to thyroid hormone (RTH) is a rare condition usually diagnosed in patients with classic thyroid function tests (TFTs) of elevated thyroid hormone levels with nonsuppressed TSH. The presence of autoimmune thyroid disease (AITD) can confound the clinical diagnosis of RTH. A family was evaluated because several members had elevated TSH and normal or low serum T4 concentrations with AITD. While these individuals were initially reported to have RTH, they were found to have a normal thyroid hormone receptor beta (THRB) gene sequence, and three other asymptomatic family members were found to harbor the variant TRß G339S. METHODS: The THRB gene was sequenced in 19 members of a large Mexican/Aztec family. In vitro expression of the mutant TRß protein was performed, as well as computer modeling of the variant compared to known mutations in the flanking codons. RESULTS: Investigation of an individual with AITD who was incorrectly diagnosed with RTH led to the fortuitous discovery of a THRB gene variant (G339S) in the proposita's father, paternal aunt, and cousin. This variant was not detected in analysis of 124 unrelated alleles. All individuals harboring G339S had normal TFTs. Normal in vitro expression and function of G339S and molecular modeling predicted that this variant would not have an effect on the hypothalamic-pituitary-thyroid axis as determined by thyroid hormone binding in vitro and thyroid function tests in vivo, despite profound effects seen in mutations in the adjacent codons 338 and 340. CONCLUSION: We report an individual with normal TFTs and AITD harboring a novel THRB gene variant. In addition to illustrating the importance of accurate diagnosis of thyroid disease so that proper treatment and counseling can be given, TRß codon 339 is not essential for normal TRß function.

[Metabolic syndrome in adults from 20 to 40 years old in a rural Mexican community]. / Síndrome metabólico en adultos de 20 a 40 años en una comunidad rural mexicana.

INTRODUCTION: Metabolic syndrome is the main health problem in Mexico. Its two principal complications (ischemic cardiopathy and type-2 diabetes) are the two main causes of death in Mexico since 2000. OBJECTIVE: To describe the prevalence of the metabolic syndrome in adults from 20 to 40 years old in a Mexican rural community (Senegal de Palomas, San Juan del Río, Querétaro) using the National Cholesterol Education Program (NCEP III) definition. MATERIAL AND METHODS: A descriptive study with a random sample was carried out. We present a univariate analysis with a 95% confidence interval. RESULTS: 73 cases were studied. The prevalence of the metabolic syndrome was 45.2% slightly higher in men (48.4%) than in women (42.8%). The prevalence of hypertension was 27.3%. The prevalence of obesity was 26.1% using the definition of the WHO and this prevalence rises up to 49.4% using the definition of the Mexican Official Norm. 90.5% of women and 93.5% of men had low HDLc. CONCLUSIONS: The prevalence of metabolic syndrome in adults from 20 to 40 years old in this Mexican rural community is much higher than the national mean for the same age cohort. The results show the necessity to increase the research of our rural communities in order to identify the possible causes to this problem and to create therapeutic programs for patients with metabolic syndrome.

Lípidos séricos en ejercitantes recreacionales / Lipids seric in recreacionals gyms

Se efectuó un estudio clínico-epidemiológico, prospectivo y correlativo para caracterizar las concentraciones séricas de colesterol (CT), triglicéridos (TG), colesterol de lipoproteínas de alta y baja densidad (C-LAD, C-LBD), y su relación con la composición corporal y capacidad física, en ejercitantes recreacionales de una región central de México. Se estudiaron 154 adultos jóvenes; 79 varones y 75 mujeres. Se sometieron a una evaluación integral de su estado de salud, antropometría y medición de capacidad en ambos sexos. Los niveles de CT (210 ñ 3 vs 197 ñ 1), TG (136 ñ 6 vs 105 ñ 3), C-LBD (150 ñ 3 vs 137 ñ 2) fueron más altos en hombres que en mujeres (p < 0.05), mientras que el C-LAD muestra valores similares y adecuados en ambos sexos. El nivel de aptitud física no se relacionó con los lípidos séricos (p> 0.05). Los datos indican la necesidad de establecer escrutinios periódicos en la población que opten por iniciar o continuar un programa de ejercicio físico

Variaciones biológicas día a día del colesterol sérico / Biologic variations day a day of seric cholesterol

El objetivo fue caracterizar la variación biológica semanal del colesterol sérico total (CT). Se analizaron muestras seriadas durante 7 días consecutivos para la determinación de CT en 38 universitarios; 21 varones y 17 mujeres, entre los 17 y 21 años de edad. A lo largo de la semana los valores fueron de (X ñ DE) 175 ñ 12 mg/dL y 177 ñ 13 mg/dL para los hombres y las mujeres respectivamente (p > 0.05). Se encontró una variación (coeficiente de variación, CV) del 7.16 por ceinto y 7.22 por ciento en ambos grupos, respectivamente. El CV intraensayo fue de 1.99 por ceinto. Por tanto, la variación no explicada por el método analítico fue de 5.17 por ciento en hombres y 5.23 por ciento en mujeres, atribuída a su variación biológica. El 40 por ciento de las mujeres y el 20 por ciento de los hombres presentaron una variación amplia (> 10 por ciento) en los niveles de CT. Concluimos que la caracterización del CT debe considera la variación biológica semanal que se presenta, además de la variación análitica