Glucocorticoid effect on repair processes in vascular connective tissue. Morphological examination and biochemical studies on collagen RNA and DNA in rabbit aorta.

Male rabbits were injured by a single mechanical dilatation of the aorta and then injected with prednisone 2 mg/kg saline for 14 days or starved. Morphological studies and biochemical measurements of the collagen metabolism, the content of alpha-amino nitrogen, RNA, DNA, water and fat, and the aorta to serum ratio of 125I-albumin were performed on the intima-media layer of the descending thoracic aorta. Prednisone inhibited the intimal thickening. In the media the infiltration by mononuclear cells, the proliferation and regeneration of the smooth muscle cells and the calcification were reduced. Prednisone caused a decrease in 0.45 M NaCl soluble collagen as well as in the dialysable and non-dialysable 14C-hydroxyproline fractions. The total amount of collagen, elastin and alpha-amino nitrogen was unchanged, whereas the 14C-proline incorporation in the non-dialysable protein fraction was inhibited to a greater extent than the 14C-hydroxyproline synthesis. The findings indicate that prednisone inhibits the biosynthesis of collagen, which is inhibited to a greater extent than the general protein synthesis. Prednisone increased the dialysable to non-dialysable 14C-hydroxyproline ratio consistent with a relative increase in the catabolism of newly synthesized collagen. The aortic content of RNA and DNA was reduced consistent with the inhibition of protein synthesis and cell proliferation. Finally prednisone decreased the aortic content of water when related to the wet weight and increased the aortic content of fat. The aorta to serum ratio of 125I-albumin was not influenced by prednisone. It is concluded that administration of glucocorticoid for 14 days exerts an inhibitory action on the histological reaction to injury as well as on the biosynthesis of collagen of the repair processes in vascular connective tissue. A comparison with the effects of prednisone on undamaged rabbit aorta (Manthorpe et al. 1974) demonstrates that the metabolism of collagen of vascular connective tissue during repair is more sensitive to the antianabolic effects of prednisone than collagen in the non-injured aorta. Starvation caused an increase of the aortic percentage of water but otherwise had no influence on the repair processes in the vascular connective tissue.     

Careography: Staff Experiences of Navigating Decisions in Neonatology in Denmark

In this article, we explore medical doctors’ moral experiences of being responsible for decisions on the lives and sometimes deaths of infants in a Danish Neonatal Intensive Care Unit (NICU). Drawing on fieldwork, we investigate how clinicians navigate the tension between exercising medical authority and enabling parental involvement in decisions. Introducing the term “careography”, we call attention to how the doctors steer this tension through care for the infant, parents, colleagues, and society in ways that help them overcome moral ambivalences. We suggest that “careography” holds analytical potential to bridge anthropological theories of power, experience, and care.     

Improving pancreas graft utilization through importation

Background

We analyze our outcomes utilizing imported allografts as a strategy to shorten wait list time for pancreas transplantation.

Methods

This is an observational retrospective cohort of 26 recipients who received either a locally procured (n = 16) or an imported pancreas graft (n = 10) at our center between January 2014 and May 2017. Wait list times of this cohort were compared to UNOS Region 9 (New York State and Western Vermont). Hospital financial data were also reviewed to analyze the cost‐effectiveness of this strategy.

Results

Imported pancreas grafts had significantly increased cold ischemia times (CIT) and peak lipase (PL) levels compared to locally procured grafts (CIT 827 vs 497 minutes; P = .001, PL 563 vs 157 u/L; P = .023, respectively). There were no differences in graft or patient survival. The median wait time was significantly lower for simultaneous kidney‐pancreas transplants at our center (518 days, n = 21) compared to Region 9 (1001 days, n = 65) P = .038. Despite financial concerns, the cost of transport for imported grafts was offset by lower standard acquisition costs.

Conclusions

Imported pancreas grafts may be a cost‐effective strategy to increase organ utilization and shorten wait times in regions with longer waiting times.     

Prevalence of Hypospadias in Danish Boys: A Longitudinal Study, 1977–2005

Background

Hypospadias is a relatively common congenital malformation. Data on temporal trends in prevalence of hypospadias are conflicting. It is unclear whether changes of maternal age distribution over time are associated with changes in hypospadias prevalence.

Objective

To study changes in prevalence of hypospadias in Denmark during a 29-yr period and to investigate whether maternal age was associated with the prevalence of hypospadias.

Design, setting, and participants

Through Denmark's National Patient Registry, covering all Danish hospitals, we identified all boys diagnosed with hypospadias in Denmark. From the Danish Medical Birth Registry, we obtained information on maternal age and on the annual total number of live-born boys from 1977 to 2005.

Measurements

Prevalence of hypospadias at birth.

Results and limitations

Among 921 745 boys born alive from 1977 to 2005, we identified 3490 boys with hypospadias. The prevalence increased from 0.24% in 1977 to 0.52% in 2005, corresponding with an annual increase in prevalence of 2.40% (95% confidence interval: 1.94–2.86). The prevalence of hypospadias did not differ according to maternal age. The mean annual prevalence was 0.38% in sons of mothers aged ≤25 yr, 0.37% in sons of mothers aged 26–30 yr, 0.39% in sons of mothers aged 31–35 yr, and 0.39% in sons of mothers >35 yr.

Conclusions

The hypospadias prevalence was increasing in Denmark from 1977 to 2005. Increased maternal age did not explain this trend.     

Efficacy of FODMAP Elimination and Subsequent Blinded Placebo-Controlled Provocations in a Randomised Controlled Study in Patients with Ulcerative Colitis in Remission and Symptoms of Irritable Bowel Syndrome: A Feasibility Study

Background: Patients with inflammatory bowel disease (IBD) and symptoms of irritable bowel syndrome (IBS) may be intolerant to fermentable carbohydrates (FODMAPs). The aim of this study was to test the feasibility of eliminating and subsequently reintroducing FODMAPs in patients with IBS symptoms as part of the IBD manifestation and to compare the severity of IBS symptoms and pain, bloating and quality of life (QoL). Methods: An eight-week randomised open-label FODMAP elimination with double-blinded, crossover provocations of FODMAP and placebo. Diet patients were on a low-FODMAP diet for eight weeks with blinded two-week provocations after two and six weeks. Questionnaires, blood and stool samples were collected. Results: Patient enrolment was challenging. Nineteen participants were included in the study. Eliminating low FODMAP for two weeks resulted in significant decreases in pain and bloating scores (p < 0.003), whereas there were no statistical differences in pain scores between diet patients and controls. Pain and bloating scores increased, returning to baseline levels after two weeks of double-blinded provocations with placebo, (p > 0.05). Conclusions: The results document the possibility of performing a randomised controlled study following the gold standard for testing food intolerance with blinding of the Low FODMAP diet. Recruitment of participants was challenging.     

Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring.

Prochloraz is a commonly used fungicide that has shown multiple mechanisms of action in vitro. It antagonizes the androgen and the estrogen receptors, agonizes the Ah receptor, and inhibits aromatase activity. In vivo prochloraz acts antiandrogenically in the Hershberger assay by reducing weights of reproductive organs, affecting androgen-regulated gene expressions, and increasing luteinizing hormone (LH) levels. The purpose of this study was to investigate reproductive toxic effects after exposure during gestation and lactation to prochloraz alone and a mixture of five pesticides (deltamethrin, methiocarb, prochloraz, simazine, and tribenuron-methyl). Prochloraz (30 mg/kg/day) or the mixture (20 mg/kg/day) was dosed to pregnant Wistar dams from gestational day (GD) 7 until postnatal day (PND) 16. Some dams were taken for cesarean section at GD 21, and others were allowed to give birth. Results showed that prochloraz and the mixture significantly reduced plasma and testicular testosterone levels in GD 21 male fetuses, whereas testicular progesterone was increased. Gestational length was increased by prochloraz. Chemical analysis of the rat breast milk showed that prochloraz was transferred to the milk. In males a significant increase of nipple retention was found, and the bulbourethral gland weight was decreased, whereas other reproductive organs were unaffected. In addition cytochrome P450 (CYP)1A activities in livers were induced by prochloraz, possibly as a result of Ah receptor activation. Behavioral studies showed that the activity level and sweet preference of adult males were significantly increased. Overall these results strongly indicate that prochloraz feminizes the male offspring after perinatal exposure, and that these effects are due, at least in part, to diminished fetal steroidogenesis.