A cross-sectional study of basal platelet intracellular free calcium concentration in normotensive and hypertensive primigravid pregnancies

1. The intracellular free calcium concentration ([Ca2+]i) in washed human platelets was measured using the fluorescent indicator, fura-2, in a cross-sectional study of 36 normotensive, primigravid volunteers, 12 in each trimester of pregnancy and a further 12 at 6 weeks post partum. The results were compared with those obtained from 30 normal female volunteers not using oral contraception. 2. The mean basal [Ca2+]i in the platelets of the pregnant women in the first two trimesters (115.6 +/- 6.7 and 120.1 +/- 5.7 nmol/l, respectively) was not shown to differ significantly from that of normal non-pregnant volunteers (112.3 +/- 2.9 nmol/l). However, during the third trimester a significant increase in [Ca2+]i was noted (134.0 +/- 4.9 nmol/l; P less than 0.05), with a return to normal values in the post-partum period (108.2 +/- 6.1 nmol/l). 3. [Ca2+]i was also measured in the platelets of a group of 12 primigravid pregnant women in the third trimester whose pregnancies were complicated by gestational hypertension (pregnancy-induced hypertension and pre-eclampsia). A significant rise in basal [Ca2+]i was noted in the platelets of primigravidae whose pregnancies were complicated by pre-eclampsia (163.6 +/- 8.8 nmol/l) as compared with normotensive, third-trimester primigravidae (P less than 0.02). However, no correlation could be demonstrated between [Ca2+]i and systemic blood pressure.     

Clinical Impact of Tumour Involvement of the Anastomotic Doughnut in Oesophagogastric Cancer Surgery

INTRODUCTION

Published colorectal cancer surgery data suggest no role for the analysis of the anastomotic doughnuts following anterior resection. The usefulness of routine histological analysis of the upper gastrointestinal doughnut is not clear. Our study assessed the impact of cancer involvement of the doughnut on clinical practice. Factors associated with doughnut involvement and the effect on patients'' survival were also analysed.

PATIENTS AND METHODS

The clinicopathological details of 462 patients who underwent potentially curative oesophagogastrectomy for cancer with a stapled anastomosis between 1994 and 2006 in two specialist centres were retrospectively analysed. Univariate, multivariate and survival analyses were carried out.

RESULTS

Approximately 5% of doughnuts (22 of 462) were histologically involved with cancer. Microscopic involvement of the proximal resection margin, local lymph node metastasis and lymphatic invasion within the main resected specimen were independently associated with doughnut involvement (all P < 0.05). However, these three factors taken together failed to predict doughnut involvement. Doughnut involvement was an independent adverse prognostic factor for overall survival (P = 0.0013).

CONCLUSIONS

In contrast to findings in colorectal surgery, doughnut involvement with cancer appears to have useful prognostic information following oesophagogastrectomy. Routine histological analysis of upper gastrointestinal doughnuts is justified. Doughnut involvement could potentially strengthen the indications for adjuvant therapy in the future.     

Hospital treatment -is it affordable? A structured cost analysis of vaginal deliveries and planned caesarean sections

Introduction

The analysis of cost effectiveness in hospitals is as difficult as treating the patients properly. We are yet not able to answer the simple question of what costs are caused by a certain diagnosis and its treatment during an average hospital stay.

Methods

To answer some issues of the global problem of cost effectiveness during hospitalisation, we analysed the costs and the cost structure of a normal obstetrical hospital stay during an uncomplicated vaginal delivery and a planned caesarean section. Cost data was collected and summarized from the patients file, the hospital''s computer system gathering all cost centres, known material expenses and expenses of non obstetrical medical services.

Results

For vaginal deliveries/planned caesareans we can calculate with a surplus of about 83 €/1432 €. About 45% of the summarized costs are calculated on a reliable database.

Discussion

The introduction of the DRG based clearing system in Germany has aggravated the discussion on cost effectiveness. Our meticulous work-up of expenses excluded personal precautionary costs and personnel costs of documentation because no tools are described to depict such costs. If we would add these costs to the known expenses of our study, we strongly suspect that hospital treatment of vaginal deliveries or planned caesarean sections is not cost effective.     

Brown Adipose Tissue and Seasonal Variation in Humans

OBJECTIVE

Brown adipose tissue (BAT) is present in adult humans where it may be important in the prevention of obesity, although the main factors regulating its abundance are not well established. BAT demonstrates seasonal variation relating to ambient temperature and photoperiod in mammals. The objective of our study was therefore to determine whether seasonal variation in BAT activity in humans was more closely related to the prevailing photoperiod or temperature.

RESEARCH DESIGN AND METHODS

We studied 3,614 consecutive patients who underwent positron emission tomography followed by computed tomography scans. The presence and location of BAT depots were documented and correlated with monthly changes in photoperiod and ambient temperature.

RESULTS

BAT activity was demonstrated in 167 (4.6%) scans. BAT was demonstrated in 52/724 scans (7.2%) in winter compared with 27/1,067 (2.5%) in summer months (P < 0.00001, χ² test). Monthly changes in the occurrence of BAT were more closely related to differences in photoperiod (r² = 0.876) rather than ambient temperature (r² = 0.696). Individuals with serial scans also demonstrated strong seasonal variation in BAT activity (average standardized uptake value [SUV_max] 1.5 in July and 9.4 in January). BAT was also more common in female patients (female: n = 107, 7.2%; male: n = 60, 2.8%; P < 0.00001, χ² test).

CONCLUSIONS

Our study demonstrates a very strong seasonal variation in the presence of BAT. This effect is more closely associated with photoperiod than ambient temperature, suggesting a previously undescribed mechanism for mediating BAT function in humans that could now potentially be recruited for the prevention or reversal of obesity.Brown adipose tissue (BAT) was first discovered several hundreds of years ago (1). Extensive research has been conducted in animals to elucidate its function. BAT has been proven to be important in small mammals for nonshivering thermogenesis, particularly following hibernation (2). BAT often coexists with white adipose tissue (WAT) and is structurally very different (3). WAT is unilocular containing a large single vacuole, whereas BAT is multilocular containing large complex mitochondria with a rich vascular supply and is extensively innervated by the sympathetic nervous system. The functions of WAT and BAT differ. WAT acts as a chemical store and an insulator. BAT, however, enables rapid heat production directly from the metabolism of triglycerides, suitable for nonshivering thermogenesis. This function is important in mammals and also helps to counteract the cold stress of birth in newborn mammals including humans (4). BAT is activated by the cold, a function mediated by the sympathetic nervous system (2), and is capable of producing up to 300 times more heat per unit mass compared with all other tissues (5). Uncoupling protein (UCP)-1 is exclusively expressed in brown adipocytes and uncouples oxidative phosphorylation from respiration and the production of ATP, resulting in the production of large amounts of heat (2).BAT is thought to have a protective role against obesity because genetic knockout mice lacking BAT become obese (6). Strong recent evidence for the existence of active BAT in adults has come from positron emission tomography (PET)/computed tomography (CT) imaging, a technique enabling the visualization and anatomical localization of sites of glucose metabolism. Sites of high activity are seen within adipose tissue, particularly in adipose located in the supraclavicular regions but also in paraspinal and suprarenal regions. Three recent studies have demonstrated the presence of UCP-1 in areas corresponding to these areas of activity on PET/CT. Biopsy of the supraclavicular areas of activity confirmed the presence of BAT at this site, providing conclusive evidence for the presence of active BAT in adult humans (7,8,9). Although very likely to represent BAT, the other sites of presumed BAT activity have not been definitively confirmed on biopsy samples.The purpose of our study was to further examine the characteristics of BAT expression in a large cohort of adults undergoing PET/CT at our institution and to determine how this related to time of year. We specifically focused on the impact of photoperiod and ambient temperature because these are two key factors determining BAT function in small mammals (10,11).     

Association Between Helicobacter pylori Infection in Mothers and Birth Weight

Helicobacter pylori infection may cause intrauterine growth restriction (IUGR). However, it is unknown whether the growth of children from H. pylori-infected mothers is also affected or whether transmission of infection from mother to child occurs. This study aimed to determine if maternal H. pylori infection was associated with IUGR and low birth weight in a mouse model, and whether transmission of infection from mother to infant occurs. Female C57BL/6 mice were inoculated with H. pylori (n = 18) or water (control; n = 18) via gavage. Mice were mated at 6 weeks postinfection, with half of the mice sacrificed after 2 weeks of gestation. The remaining mice gave birth and a third of the litter was weighed and sacrificed at birth, during milk feeding (1.5 weeks), and during solid feeding (4 weeks). Stomachs of all mice and whole foetuses were cultured for the presence of H. pylori. There were no differences in litter size or foetus weight between control and H. pylori-infected mice. Pups from infected mothers had a lower weight during milk feeding (control, 5.91 ± 0.23 g; H. pylori, 4.59 ± 0.16 g; p < 0.05) and solid feeding (control, 12.73 ± 0.58 g; H. pylori, 10.01 ± 1.02 g; p < 0.05). H. pylori was not detected by culture in the pups at any age. H. pylori infection in mothers was associated with a decrease in infant weight during milk feeding and after weaning. Transmission of infection from mother to infant was not detected by culture, suggesting that decreased baby weight may be due to decreased milk supply or altered nutrition from the mother.     

Using DCE and ranking data to estimate cardinal values for health states for deriving a preference‐based single index from the sexual quality of life questionnaire

There is an increasing interest in using data derived from ordinal methods, particularly data derived from discrete choice experiments (DCEs), to estimate the cardinal values for health states to calculate quality adjusted life years (QALYs). Ordinal measurement strategies such as DCE may have considerable practical advantages over more conventional cardinal measurement techniques, e.g. time trade‐off (TTO), because they may not require such a high degree of abstract reasoning. However, there are a number of challenges to deriving the cardinal values for health states using ordinal data, including anchoring the values on the full health–dead scale used to calculate QALYs. This paper reports on a study that deals with these problems in the context of using two ordinal techniques, DCE and ranking, to derive the cardinal values for health states derived from a condition‐specific sexual health measure. The results were compared with values generated using a commonly used cardinal valuation technique, the TTO. This study raises some important issues about the use of ordinal data to produce cardinal health state valuations. Copyright © 2009 John Wiley & Sons, Ltd.     

Increased urinary nitric oxide oxidation products in children with active coeliac disease

BACKGROUND: Nitric oxide (NO) production catalyzed by iNOS (inducible NO synthase) is thought to take place mainly in macrophages after activation by inflammatory mediators. NO is subsequently oxidized to nitrite and nitrate, which are excreted in urine. The concentration of inflammatory mediators in small bowel biopsy specimens from patients with coeliac disease is increased. The latter could induce increased NO production by stimulation of intestinal macrophage iNOS, resulting in high levels of urinary NO oxidation products, nitrite and nitrate (NOx). AIM: In the present study we evaluated the urinary NOx/creatinine ratios in children with active coeliac disease (n = 22), coeliac disease patients on a gluten-free diet (n = 9), healthy (n = 11) and sick control children (n = 18). METHODS: The Griess reagent method was used for measuring urinary NOx. RESULTS: Median NOx/creatinine ratios of active coeliac disease patients, coeliac disease patients on a gluten-free diet, healthy and sick control patients were 1.21, 0.19, 0.10 and 0.13 mmol/mmol, respectively. All active coeliac disease patients showed increased NOx/ creatinine ratios. Urinary NOx/creatinine ratios of the active coeliac disease patients were significantly higher than those of healthy controls (p < 0.0001), sick controls (p < 0.0001) and coeliac disease patients on a gluten-free diet (p < 0.0001). CONCLUSION: The urinary NOx/creatinine ratio is increased in patients with active coeliac disease and reverts to normal on a gluten-free diet.     

Association between single nucleotide polymorphisms in the DNA repair gene LIG3 and acute adverse skin reactions following radiotherapy

Many genes have been associated with radiotherapy toxicity, but most have only been found in a single study. Using our cohort of 480 breast cancer patients, we provide replicated evidence that a polymorphism near the LIG3 gene is associated with acute skin toxicity following radiotherapy.