PABPN1 gene therapy for oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment.

A histological study of the transit of Cryptosporidium parvum oocysts through clams (Tapes decussatus).

A histological study was carried out to investigate the transit of Cryptosporidium parvum oocysts through the clam Tapes decussatus. Spat of approximately 5-7 mm shell length were maintained in a tank of natural sea water contaminated with purified C. parvum oocysts. The experiment lasted 240 h and, every 24 h, five specimens were killed, placed in Bouin's fixative, and processed routinely for histological examination. Sections (3 mum) cut from the all body tissues were stained with modified Gomori's trichrome for their accurate identification; the oocysts were detected by a direct immunofluorescence procedure. Oocysts were detected in siphons, gills, stomach, digestive diverticula, and intestine. The oocysts present in the intestine were free or mixed with the intestinal contents; therefore release of these oocysts with the feces should favour dissemination of contamination. Oocysts were found in branchial mucus and within the interfilamentary spaces, which suggests the occurrence of repeated filtrations and the possibility that the retained oocysts maintain their infective capacity.

Diagnosis of malaria by polymerase chain reaction.

Malaria is no longer endemic in Puerto Rico, however, imported cases of the disease are occasionally reported to the Health Department of the Island. This is a report of a 45-year-old female patient who traveled to Kenya and Niger and was admitted to a San Juan area hospital with an 8 day history of daily chills and fever, myalgia, nausea and vomiting. Upon admission, peripheral blood displayed multiple intra-erythrocytic ring-shape trophozoites, highly suggestive of Plasmodium falciparum. The polymerase chain reaction was used as a complementary method for the detection of malaria parasites and confirmation of post-treatment parasite clearance. This report presents an imported case of malaria in Puerto Rico and showed the use of a molecular technique to diagnose Plasmodium.

Comparing easy and accessible parameters of glycemic control in type 2 diabetes.

BACKGROUND: HbA1c is considered the gold standard of long-term glycemic control and is recommended as a routine test for every diabetic patient. However, its common use in clinical practice has some problems related to lack of standardization and its relative cost. Recent studies have suggested, that postprandial blood glucose could be better than a fasting sample, as a marker of diabetes control. The objective of the present study was to evaluate the relative value of plasma glucose samples at different times of the day, and easy and accessible programs for home blood and urinary glucose measurements compared with HbA1c in assessing the mean glycemic control of type 2 diabetic patients. METHODS: Sixty type 2 diabetic patients were instructed to do home blood and urine glucose monitoring for two months, at the end, plasma glucose profiles were obtained. RESULTS: The mean of all the capillary BG measurements had the best correlation with the HbA1c (r = 0.84, p < 0.001), followed by the mean of the capillary BG measurements before breakfast and supper (r = 0.82, p < 0.001), and the 2 hr. postbreakfast plasma glucose (r = 0.79 p < 0.001). The fasting PG had a low correlation (r = 0.65, p < 0.001), but a good sensitivity to predict a fair or a poor metabolic control. Diabetes duration and type of treatment explained 17% and 28% of variance in HbA1c levels. CONCLUSIONS: A bimonthly fasting PG correlated well with the glycosylated hemoglobin and is the easiest and cheapest way of monitoring glycemic control in type 2 diabetic patients with some preserved insulin reserve (diabetes for less than 10 years and on treatment with only one hypoglycemic agent). A sample of capillary BG, fasting, once per week correlates better with the HbA1c than a fasting PG every 2-3 months. The 2 hr and 5 hr postbreakfast PG have a good correlation with the HbA1c, but are not a substitute for doing BG monitoring. Glycosuria may be a useful parameter to rule out a fair or poor metabolic control in some patients.

Cáncer de ovario con metástasis a piel. Reporte de un caso y revisión de la bibliografía / Ovarian cancer with skin metastases. A case report and literature review

Resumen ANTECEDENTES: en 80% de las ocasiones el cáncer de ovario epitelial se diagnostica en etapas III y IV, la recurrencia locorregional es una característica frecuente en esta neoplasia maligna. La mortalidad asociada es una de las más importantes de todas las neoplasias malignas en la mujer, en todo el mundo. OBJETIVO: documentar las metástasis de cáncer de ovario a piel, la incidencia, presentación clínica, y pronóstico. CASO CLÍNICO: paciente de 67 años, con un carcinoma seroso papilar etapa IIIC de ovario; se efectuaron cirugía óptima y cuatro ciclos de quimioterapia (carboplatino y paclitaxel), con 21 meses de intervalo libre de enfermedad. La paciente tenía: pápulas y nódulos inexplicables en la piel del abdomen y las piernas. La biopsia incisional documentó la recaída a la piel, sin otro sitio de metástasis a distancia. La paciente recibió tratamiento sistémico paliativo. CONCLUSIONES: las metástasis cutáneas de cáncer de ovario tienen una presentación clínica pleomórfica y distribución amplia en todo el organismo, con frecuencia afectan la región abdominal o torácica; las metástasis cutáneas de ovario tienen una expectativa de vida limitada, a pesar del tratamiento sistémico.

Abstract BACKGROUND: 80% of the cases of epithelial ovarian cancer are diagnosed in stages III and IV, locoregional recurrence is a frequent feature of this malignant neoplasm. Associated mortality is one of the most important of all malignant neoplasms in women, all over the world. OBJECTIVE: To document the metastasis of ovarian cancer to skin, incidence, clinical presentation, and prognosis. CLINICAL CASE: 67-year-old patient with papillary serous carcinoma stage IIIC of ovary; Optimal surgery and four cycles of chemotherapy (carboplatin and paclitaxel) were performed, with a 21-month disease-free interval. The patient had unexplained papules and nodules on the skin of the abdomen and legs. Incisional biopsy documented relapse to the skin, with no other site of distant metastases. The patient received systemic palliative treatment. CONCLUSIONS: Cutaneous metastases from ovarian cancer have a pleomorphic clinical presentation and widespread distribution throughout the body, often affecting the abdominal or thoracic region; cutaneous ovarian metastases imply a limited life expectancy, despite systemic treatment.

Respuesta inmunologica en pacientes con uveitis. / Immunological response in patients with uveitis

Se estudio la respuesta inmunologica del compartimiento humoral en el suero sanguineo y humor acuoso en tres grupos de pacientes: Grupo I: pacientes con uveitis; Grupo II con enfermedad sistemica autoinmune sin uveitis, y Grupo III: control.Los resultados senalan alteraciones locales en este sentido encontrandose elevacion de la IgG e IgA en los pacientes del Grupo I asi como la presencia del factor B y C3, los cuales se reportan en forma original; los complejos inmunologicos fueron detectados por dos metodos, siendo significativos los resultados en el Grupo I