Evaluation of various doses of testosterone on accessory reproductive organs and plasma testosterone in intact and gonadectomized rhesus monkeys (Macaca mulatta).

The effect of 10 days i.m. treatment of testosterone propionate (TP) on plasma testosterone and accessory reproductive organs were studied in adult (6 to 6 1/2 kg) male rhesus monkeys, housed under natural light conditions using six different dose levels. The study was scheduled in the month of September and October. To maintain the weight of accessory reproductive organs and testosterone levels in castrates, different dose levels of exogenous testosterone propionate were required: 3.2 mg/d for seminal vesicles, 4.8 mg/d for ventral prostate and 3.2 mg/d for plasma testosterone titer. The levels of so-called "physiological" doses of exogenous testosterone varied for various target organs under consideration. TP at a dose of 0.4 mg/d had a depressing effect on plasma testosterone in intact monkeys. For higher doses, plasma testosterone increased roughly similarly in both intact and castrated monkeys. It suggests that with otherwise "physiological" doses of testosterone propionate, there is an almost complete blockage of endogenous testosterone secretion.     

A case of longitudinally extensive transverse myelitis (LETM): neuromyelitis optica

Neuromyelitis optica (NMO), characterised by longitudinally extensive transverse myelitis (LETM), was previously thought to be a variant of multiple sclerosis. Transverse myelitis may be a manifestation of autoimmune connective tissue diseases and NMO is now recognised to be a humorally mediated autoimmune disease. We present a case of NMO associated with non-organ-specific autoantibodies and the absence of the characteristic NMO-IgG antibody. Our case provides an opportunity to review the diagnostic criteria of NMO and its distinction from other autoimmune and demyelinating conditions. We report successful treatment with plasmapheresis and rituximab in NMO-IgG-negative relapsing disease.     

Point mutations at the purine nucleoside phosphorylase locus impair thymocyte differentiation in the mouse

Three point mutations on the Np^b allele of the purine nucleoside phosphorylase locus in the mouse have been recovered by male germ cell mutagenesis. The mutants were backcrossed, 12–14 generations, and are designated in increasing order of severity of enzyme deficiency and phenotype: B6-NPE, Met-87 → Lys; B6-NPF, Ala-228 → Thr; and B6-NPG, Trp-16 → Arg. A marked decline in total cell numbers per thymus occurs between 2 and 3 months for the more severe B6-NPF and B6-NPG mutants (35% and 52%, respectively) and by 8 months for the less severe B6-NPE mutation. The thymocyte population is thereafter characterized by a 3- or 8-fold expanded precursor, CD4⁻CD8⁻ double-negative population and 15% or 55% reduced CD4⁺CD8⁺ double-positive cells for the B6-NPF and B6-NPG strains, respectively. Spleen lymphocyte Thy-1⁺ cells are reduced by 50% and spleen lymphocyte response to T cell mitogen and interleukin 2 is reduced by 80%. Increases of thymocyte dGTP pools of 5- and 2.5-fold for B6-NPF and B6-NPG mutants, respectively, are observed. The purine nucleoside phosphorylase-deficient mouse exhibits age-dependent progressive perturbations in thymocyte differentiation, reduced numbers of thymocytes, and reduced splenic T cell numbers and response. The progressive T cell deficit is similar to the human disorder.     

Pre-conceptual and prenatal supplementary folic acid and multivitamin intake,behavioral problems,and hyperkinetic disorders: A study based on the Danish National Birth Cohort (DNBC)

Objective: To evaluate whether early folic acid or multivitamin supplementation during pregnancy prevents diagnosis of hyperkinetic disorders (HKD), treatment for attention deficit hyperactivity disorder (ADHD), and ADHD-like behaviors reported by parents participating in the DNBC for children at age 7.

Methods: HKD diagnosis and ADHD medication use data were obtained from the Danish National Hospital, Central Psychiatric and Pharmaceutical registers. We estimated hazard ratios (HRs) for HKD diagnosis and ADHD medication use and risk ratios (RRs) for parent-reported ADHD behavior collected with the Strength and Difficulties Questionnaire (SDQ), comparing children whose mothers took folic acid or multivitamin supplements early in pregnancy defined as starting periconceptionally (4 weeks prior to their last menstrual period (LMP)) through 8 weeks after their LMP (4–8 weeks), to children whose mothers indicated no supplement use for the same entire period.

Results: We identified 384 children (1.1%) with a hospital diagnosis for HKD and 642 children (1.8%) treated with ADHD medication. We found no association between risk of HKD diagnosis or intake of ADHD medication and early maternal folic acid use. However, early multivitamin use was associated with an approximately 30% reduction in risk for HKD diagnosis (aHR: 0.70, 95% CI: 0.52–0.96) and 21% reduction in treatment with ADHD medication (aHR: 0.79, 95% CI: 0.62–0.98). We observed a reduced risk in parent-reported ADHD behaviors, but these results were attenuated after adjustment.

Conclusion: Our data suggest that multivitamin use in early pregnancy may reduce risk for HKD diagnosis and treatment for ADHD in the offspring.     

An Update on Retinopathy of Prematurity (ROP)

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the retina of premature infants. The clinical spectrum of ROP varies from spontaneous regression to bilateral retinal detachment and total blindness. Between these two extremes lies the form of ROP, which is amenable to treatment with laser photocoagulation, anti-vascular endothelial growth factor drugs or surgery. Increasing rates of preterm births coupled with better survival rates but lack of uniform quality of neonatal care and delays in diagnosis have led to increasing ROP blindness. Atypical forms of Aggressive Posterior ROP are seen in heavier birth weight babies in developing countries. Prevention of ROP by following stringent protocols for supplemental oxygen, prevention of sepsis, timely screening and laser treatment by a concerted and collaborative effort of neonatologists and ophthalmologists are required to fight the blindness from ROP.