A semi‐quantitative approach to variation of the azygos vein course

The azygos vein (AV) is typically described (illustrated) as ascending vertically on the right of thoracic vertebrae. Most thoracic vein studies have focused on tributary patterns, but some have noted more leftward AV courses. This study statistically documents variation in AV course independent of tributary patterns. A more statistical approach to the probable position of AV at different vertical levels may aid clinicians in locating and assessing it in clinical contexts. The AV course was exposed in 84 cadavers by removing overlying viscera between the aortic hiatus and tracheal bifurcation. Subjectively, non‐pathological specimens were digitally photographed in anterior view. For each photo, a scaled grid was used to mark the horizontal position of the AV center at each of five vertical levels. The summated numerical distributions showed the following: ～5% of the AVs ascended on the right side (classical) position, ～30% did not cross the midline, ～70% included part or all of their course left of the midline, and ～14% reached the extreme left side. Based on this data, the modal AV course (1) begins at, or to the right of, the midline, (2) deviates leftward, (3) crosses the midline below mid‐level, (4) reaches a leftward maximum at about 3/5 of its course, (5) then deviates rightward (often only reaching the midline at the uppermost level). In several noticeable cases, the leftward maximum was associated with large connections to left‐side veins, suggesting a possible tension mechanism exerting traction on the AV over time. Clin. Anat. 27:1030–1037, 2014. © 2014 Wiley Periodicals, Inc.     

Cyclosporin-A increases synthesis of 1,25-dihydroxyvitamin D3 in the rat and mouse

We have previously observed elevated serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] levels in male rats treated with oral cyclosporin-A (CsA). This elevation was independent of changes in PTH, ionized calcium, or phosphate. This paper investigates the potential sources and mechanisms for this increase in both rats and mice. Kidney homogenates from rats treated for 14 days with (15 mg/kg) had a significant increase in 25-hydroxyvitamin D (25OHD)-24-hydroxylase (24-hydroxylase) activity (149 +/- 20 vs. 89 +/- 16 fmol/mg.min; P less than 0.05), but nonsignificant increases in 25OHD-1 alpha-hydroxylase (1 alpha-hydroxylase) activity compared to controls. Kidney homogenates from C57b16J mice after the administration of 30-50 mg/kg CsA for 3 days revealed a linear dose-related increase in renal 1 alpha-hydroxylase (r = 0.96; P less than 0.05), which became significant with doses of 30 mg/kg CsA or more (P less than 0.05). To investigate the source of this 1,25-(OH)2D production, serum 1,25-(OH)2D was measured before and 48 h after bilateral nephrectomy in rats receiving CsA for 16 days. The percent decrease in serum 1,25-(OH)2D values was not significantly different in CsA-treated and untreated rats (33.9 +/- 4.9% vs. 47.5 +/- 4.9%), indicating little or no contribution from nonrenal sources. Studies of MCRs and production rates (PRs) revealed that the elevated 1,25-(OH)2D values were due to enhanced production and not altered clearance (PR, 12.4 +/- 1.2 vs. 19.1 +/- 1.9 fmol/mg.min; P less than 0.01). CsA increases 1 alpha-hydroxylase activity and produces significant elevations in serum 1,25-(OH)2D levels in both rats and mice. This increase may have an impact on bone mineral metabolism and immune modulation in postorgan transplantation patients.     

Calcium supplementation lowers serum parathyroid hormone levels in elderly subjects

To determine the effect of calcium supplementation on parathyroid hormone levels (PTH) in a group of elderly subjects at risk for developing Type II (senile) osteoporosis, 40 healthy volunteers participated in a randomized double-blind crossover study. Calcium carbonate or placebo was administered for 4 weeks, followed by a 4-week administration of the alternative intervention. Fasting blood samples and 24-hour urine collections were obtained at baseline, and at the end of each intervention period. Calcium supplementation (1000 mg/day) decreased serum PTH levels from a mean of 50.1 +/- 3.0 pg/ml to 41.9 +/- 2.4 pg/ml (p less than .001). Additionally, urine calcium excretion significantly increased during calcium administration (from 3.64 mmol/mmol creatinine at baseline to 4.28 mmol/mmol creatinine), but creatinine clearances and serum calcium levels remained unchanged. Type II osteoporosis has been associated with age-related increases in PTH levels. We have demonstrated the ability of increased calcium intake to decrease these levels, which may have implications for the management of a subset of patients with involutional osteoporosis.     

Light Environment Influences Developmental Programming of the Metabolic and Visual Systems in Mice

PurposeLight is a salient cue that can influence neurodevelopment and the immune system. Light exposure out of sync with the endogenous clock causes circadian disruption and chronic disease. Environmental light exposure may contribute to developmental programming of metabolic and neurological systems but has been largely overlooked in Developmental Origins of Health and Disease (DOHaD) research. Here, we investigated whether developmental light exposure altered programming of visual and metabolic systems.MethodsPregnant mice and pups were exposed to control light (12:12 light:dark) or weekly light cycle inversions (circadian disruption [CD]) until weaning, after which male and female offspring were housed in control light and longitudinally measured to evaluate differences in growth (weight), glucose tolerance, visual function (optomotor response), and retinal function (electroretinogram), with and without high fat diet (HFD) challenge. Retinal microglia and macrophages were quantified by positive Iba1 and CD11b immunofluorescence.ResultsCD exposure caused impaired visual function and increased retinal immune cell expression in adult offspring. When challenged with HFD, CD offspring also exhibited altered retinal function and sex-specific impairments in glucose tolerance.ConclusionsOverall, these findings suggest that the light environment contributes to developmental programming of the metabolic and visual systems, potentially promoting a pro-inflammatory milieu in the retina and increasing the risk of visual disease later in life.     

Comprehensive Versus Targeted Genetic Testing in Children with Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomere that can be found in both children and adults and is associated with many causative mutations. In children who are not the index case of HCM in their families, current recommendations call only for targeted genetic testing for familial mutations. However, clinical experience suggests that de novo mutations are possible, as are mutations inherited from apparently an unaffected parent. A chart review was conducted of all patients who received HCM genetic testing at Johns Hopkins from 2004 to 2013. In total, 239 patient charts were analyzed for personal and familial genetic findings. Eighty-one patients with sarcomere gene mutations were identified, of which 66 had a clinical diagnosis of HCM. Importantly, eight patients had >1 pathogenic or likely pathogenic mutation, including six patients who were diagnosed with HCM as children (18 or younger). In this analysis, when a sarcomere mutation is identified in a family, the likelihood of a child with HCM having >1 mutation is 25 % (6/24), compared to 4.8 % (2/42) for adults. The large number of children with multiple mutations suggests that broad panel rather than targeted genetic testing should be considered in HCM presenting during childhood even if the child is not the index case.     

Trends in Simple Prostatectomy for Benign Prostatic Hyperplasia

The definitive treatment for symptomatic large volume (>80 mL) benign prostatic hyperplasia (BPH) is simple prostatectomy (SP). This can be performed by utilizing a retropubic, suprapubic, or a combined approach. The latter two approaches allow for the management of concomitant bladder diverticulum or stones through the same incision. Each approach affords unique technical strengths and weaknesses that must be considered in light of patient characteristics and concomitant pathology. SP allows for removal of the entire prostatic adenoma while obviating some of the neurovascular and continence issues that can arise from radical prostatectomy. Concerns with SP include its relatively high perioperative morbidity, notably bleeding. Therefore, there is increasing interest in less invasive options, including enucleation procedures and minimally invasive SP. This review presents an update regarding trends and outcomes of SP, as well as the effectiveness and popularity of alternative treatments.     

Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors

Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations.