Autosomal dominant cone-rod dystrophy due to a missense mutation (R838C) in the guanylate cyclase 2D gene (GUCY2D) with preserved rod function in one branch of the family

Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disorder of photoreceptors. Mutations in several genes encoding different proteins of the visual cascade are described. The inheritance of two intragenic markers within the interstitial retinol binding protein (IRBP) gene was established in 45 Spanish families with a history of ARRP. Homozygosity mapping and cosegregation analyses were positive in 19 families. Only one heterozygous T-C transition at position 3024 (exon 1) was detected in one consanguineous family. This variant was identified as a rare polymorphism and was present in 5% of the chromosomes analyzed.     

Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial

OBJECTIVE: To compare unilateral and bilateral neck exploration for primary hyperparathyroidism in a prospective randomized controlled trial. SUMMARY BACKGROUND DATA: Based on the assumption that unilateral neck exploration for a solitary parathyroid adenoma should reduce operating time and morbidity, a variety of minimally invasive procedures have challenged the idea that bilateral neck exploration is the gold standard for the surgical treatment of primary hyperparathyroidism. However, to date, no open prospective randomized trial has been published comparing unilateral and bilateral neck exploration. METHODS: Ninety-one patients with the preoperative diagnosis of primary hyperparathyroidism were randomized to unilateral or bilateral neck exploration. Preoperative scintigraphy and intraoperative parathyroid hormone measurement guided the unilateral exploration. Gross morphology and frozen section determined the extent of parathyroid tissue resection in the bilateral group. The primary end-point was the use of postoperative medication for hypocalcemic symptoms. RESULTS: Eighty-eight patients (97%) were cured. Histology and cure rate did not differ between the two groups. Patients in the bilateral group consumed more oral calcium, had lower serum calcium values on postoperative days 1 to 4, and had a higher incidence of early severe symptomatic hypocalcemia compared with patients in the unilateral group. In addition, for patients undergoing surgery for a solitary parathyroid adenoma, unilateral exploration was associated with a shorter operative time. The cost for the two procedures did not differ. CONCLUSIONS: Patients undergoing a unilateral procedure had a lower incidence of biochemical and severe symptomatic hypocalcemia in the early postoperative period compared with patients undergoing bilateral exploration. Unilateral neck exploration with intraoperative parathyroid hormone assessment is a valid surgical strategy in patients with primary hyperparathyroidism with distinct advantages, especially for patients with solitary parathyroid adenoma.     

Renal Uptake,Excretion, and Retention of Mercury

A modification is proposed for the conventional pH stat assay for human plasma and erythrocyte cholinesterases. Principal advantages for the micromodification are smaller sample size afforded by collection of specimens in microhematocrit tubes and reduction in subsequent sample-handling time. Red blood cell (RBC) washing and recentrifugation steps are eliminated. Although the basic assay procedure remains unchanged, titration parameters are changed to accommodate smaller sample volumes. Results from either assay procedure are comparable, as shown by statistically significant regressions of micromodification assay data upon those of conventional pH stat procedure.     

The boston qualitative scoring system for the rey-osterrieth complex figure: A study of children with attention deficit hyperactivity disorder

Abstract

The Boston Qualitative Scoring System (BQSS) for the Rey-Osterrieth Complex Figure (ROCF) was utilized to examine the qualitative features of ROCF performance of children with Attention Deficit Hyperactivity Disorder (ADHD). Thirty-nine children with ADHD were compared to age-matched controls (n = 39) on their reproduction of the ROCF. ADHD children performed more poorly than did control children on measures of attention to detail, expansion, accuracy, and neatness. Sensitivity and specificity of individual BQSS measures for discriminating ADHD from control subjects were determined, and a logistic regression model was derived, yielding an overall sensitivity of 64% and specificity of 97% for the classification of ADHD. Eighty-one percent of all children were correctly classified. Cross-validation of this model on an independent sample of ADHD and control subjects revealed good predictive accuracy. These findings suggest that the BQSS may be a useful measure in the neuropsychological evaluation of children with suspected ADHD.     

Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis

Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60-65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.     

Electrophysiological studies on rat dorsal root ganglion neurons after peripheral axotomy: Changes in responses to neuropeptides

The effect of three peptides, galanin, sulfated cholecystokinin octapeptide, and neurotensin (NT), was studied on acutely extirpated rat dorsal root ganglia (DRGs) in vitro with intracellular recording techniques. Both normal and peripherally axotomized DRGs were analyzed, and recordings were made from C-type (small) and A-type (large) neurons. Galanin and sulfated cholecystokinin octapeptide, with one exception, had no effect on normal C- and A-type neurons but caused an inward current in both types of neurons after sciatic nerve cut. In normal rats, NT caused an outward current in C-type neurons and an inward current in A-type neurons. After sciatic nerve cut, NT only caused an inward current in both C- and A-type neurons. These results suggest that (i) normal DRG neurons express receptors on their soma for some but not all peptides studied, (ii) C- and A-type neurons can have different types of receptors, and (iii) peripheral nerve injury can change the receptor phenotype of both C- and A-type neurons and may have differential effects on these neuron types.     

Universal nevirapine upon presentation in labor to prevent mother-to-child HIV transmission in high prevalence settings

OBJECTIVE: To assess the uptake of and adherence to nevirapine to prevent mother-to-child HIV transmission among women of unknown HIV serostatus presenting in labor. We also assessed preliminary efficacy of the approach. DESIGN: Women of unknown HIV serostatus presenting in labor were offered single-dose nevirapine in a prospective cohort study. Two additional contemporaneous comparison populations were also studied. METHODS: We measured uptake by counting the number of women that accepted enrollment when offered. We measured adherence with cord blood nevirapine assay. We measured preliminary efficacy with HIV DNA polymerase chain reaction of infant blood spots at 4-6 weeks of life. RESULTS: Of 1591 women approached in labor, 634 (40%) took up the intervention and received nevirapine, of whom 185 (29%) were HIV infected. Of 179 cord blood specimens from HIV-exposed infants that could be evaluated, 178 (99.4%) had nevirapine detected. This was higher than the 73 of 98 (74%) adherence rate observed in a comparison cohort in which women self-administered nevirapine before presenting to the labor ward (P < 0.001). Of 145 available infant specimens, 17 (11.7%) showed evidence of infection at 4-6 weeks, compared with 12 of 60 (20%) infants born immediately prior to study commencement whose HIV-infected mothers did not receive nevirapine (P < 0.05). CONCLUSIONS: Nevirapine without HIV testing upon presentation in labor was accepted by two-fifths of women. Because therapy is directly observed, adherence is nearly perfect. Labor ward dosing to enhance nevirapine coverage should be considered as an adjunct to antenatal nevirapine administration for prevention of mother-to-child transmission of HIV.     

Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety

Introduction: Approximately 10 – 20% of prostate cancer cases ultimately progress to castration-resistant prostate cancer (CRPC), for which there is a poor prognosis and a therapeutic need. Radium-223 dichloride (radium-223 [Xofigo]) is a first-in-class α-emitting radiopharmaceutical shown to significantly prolong overall survival in patients with CRPC with symptomatic bone metastases and no visceral metastases. Current treatment guidelines recommended it in both pre- and post-docetaxel settings.

Areas covered: Radium-223 mechanism of action, pharmacokinetics and key efficacy and safety data are reviewed. The evaluation of adverse events reported in the Phase III ALSYMPCA trial is summarized for the overall population and patient subpopulations (prior docetaxel, concomitant external beam radiation therapy and baseline opioid use). An evaluation of how radium-223 is being incorporated into the CRPC treatment paradigm and the implications of its safety profile for future use are provided.

Expert opinion: The pronounced efficacy and safety profile of radium-223 positions it as a valuable new therapeutic tool in the CRPC armamentarium. Its novel mechanism of action underlies low rates of hematologic adverse events. Radium-223 treatment will become common in the majority of pre-docetaxel symptomatic CRPC cases, as it has proved to be highly efficient with few safety concerns earlier in the course of disease.