Gender difference in gastro-esophageal reflux diseases

The incidence of esophageal adenocarcinoma(EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease(GERD) to Barrett's esophagus(BE,a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have des cribed that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.     

Management of acute pancreatitis in Japan: analysis of nationwide epidemiological survey

Acute pancreatitis(AP) is an acute inflammatory disease of the exocrine pancreas. In Japan, nationwide epidemiological surveys have been conducted every 4 to 5 years by the Research Committee of Intractable Pancreatic Diseases, under the support of the Ministry of Health, Labour, and Welfare of Japan. We reviewed the results of the nationwide surveys focusing on the severity assessment and changes in the therapeutic strategy for walled-off necrosis. The severity assessment system currently used in Japan consists of 9 prognostic factors and the imaging grade on contrastenhanced computed tomography. By univariate analysis, all of the 9 prognostic factors were associated with AP-related death. A multivariate analysis identified 4 out of the 9 prognostic factors(base excess or shock, renal failure, systemic inflammatory response syndrome criteria, and age) that were associated with AP-related death. Receiver-operating characteristics curve analysis showed that the area under the curve was 0.82 for these 4 prognostic factors and 0.84 for the 9 prognostic factors, suggesting the comparable utility of these 4 factors in the severity assessment. We also examined the temporal changes in treatment strategy for walled-off necrosis in Japan according to the 2003, 2007, and 2011 surveys. Step-up approaches and lessinvasive endoscopic therapies were uncommon in 2003 and 2007, but became popular in 2011. Mortality has been decreasing in patients who require intervention for walled-off necrosis. In conclusion, the nationwide survey revealed the comparable utility of 4 prognostic factors in the severity assessment and the increased use of less-invasive, step-up approaches with improved clinical outcomes in the management of walled-off necrosis.     

17 beta-Hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract.

The 17 beta-hydroxysteroid dehydrogenases (17 beta HSDs) play an important role in the regulation of intracellular levels of biologically active sex steroid hormones in various human tissues. To date, eight distinctive 17 beta HSD enzymes have been cloned and characterized in humans. Among these isoenzymes, 17 beta HSD type 2 (17 beta HSD2) catalyses the conversion of testosterone into androstenedione and/or oestradiol into oestrone in various tissues, and it has thus been suggested to be involved in the biological inactivation of these sex steroids. The human gastrointestinal tract and liver are considered as the principle sites of inactivation and metabolism of various forms of orally administered sex steroids. We therefore examined 17 beta HSD2 expression and activity in human adult non-pathological gastrointestinal tract in order to clarify further the biological significance of this enzyme. A total of 80 specimens (40 from males and 40 from females) of normal oesophageal, stomach, duodenal, ileal, colonic and rectal tissues were examined for immunohistochemistry. Altogether, 17 tissue specimens were used for enzyme assay, and eight for RNA analysis. 17 beta HSD2 activity was detected in the stomach, duodenum, ileum, colon and rectum. 17 beta HSD2 mRNA was most abundant in the small intestine. 17 beta HSD2 immunoreactivity was localized almost exclusively to the absorptive epithelium, which may be involved in the inactivation of excessive endogenous and exogenous active sex steroids. Results from the present study thus suggest that the human gastrointestinal tract is an important sex steroid metabolizing organ in humans.     

Arterial fraction of cerebral blood volume in humans measured by positron emission tomography

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary, and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003 ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous plus capillary fraction of CBV was 63-70% which is a important factor for the measurement of CMRO2 with MRI.     

Identification of the layered morphology of the esophageal wall by optical coherence tomography

AIM： To assess each layer of the optical coherence tomography （OCT） image of the esophageal wall with reference to the histological structure, METHODS： Resected specimens of fresh pig esophagus was used as a model for the esophageal wall. We injected cyanoacrylate adhesive into the specimens to create a marker, and scanned them using a miniature OCT probe. The localization of these markers was assessed in the OCT images. Then we compared the OCT-imaged morphology with the corresponding histological section, guided by the cyanoacrylate adhesive markers. We prepared a second set of experiments using nylon sutures as markers. RESULTS： The OCT image of the esophageal specimen has a clear five-layered morphology. First, it consisted of a relatively less reflective layer; second, a more reflective layer; third, a less reflective layer; fourth, a more reflective layer; and fifth, a less reflective layer. Comparing the OCT images with marked histological sections showed that the first layer corresponded to stratified squamous epithelium; the second to lamina propria; the third to muscularis mucosa; fourth, submucosa; and fifth, muscularis propria with deeper structures of the esophageal wa CONCLUSION： We demonstrated that the OCT image of the normal esophageal wall showed a five- layered morphology, which corresponds to histological esophageal wall components.     

Ulcerative colitis is associated with a promoter polymorphism of lipopolysaccharide receptor gene,CD14

BACKGROUND: Inflammatory bowel disease (IBD) is a multifactorial disease with a significant genetic background. Evidence is accumulating that molecules such as CD14, which interact with luminal bacterial constituents, are involved in the pathogenesis. It has recently been shown that the T allele of the 5'-flanking region of the CD14 gene at position -159 is related to high expression of CD14. In further exploring the genetic background of IBD, we investigated this novel polymorphism of CD14 gene in patients with ulcerative colitis or Crohn disease. METHODS: DNA was obtained from 101 patients with ulcerative colitis, 82 with Crohn disease and 123 healthy controls. All were typed for the promoter polymorphism of the CD14 gene at position -159 by restriction fragment length polymorphism analysis. Serum samples were obtained from 105 healthy controls and serum sCD14 levels were measured. RESULTS: T allele frequencies were 57.4%, 48.2% and 44.7% in ulcerative colitis, Crohn disease and healthy controls, respectively. The T allele and T/T genotype frequencies were significantly higher in ulcerative colitis patients than in healthy controls (P = 0.0074, OR = 1.67, 95% CI = 1.15-2.42, P = 0.022, OR= 1.96 95% CI: 1.10-3.48, respectively). The sCD14 level was significantly higher in TT genotype populations than CC (P = 0.0205). CONCLUSIONS: The promoter polymorphism of the CD14 gene at -159T plays a significant role in regulating the CD14 expression and is positively associated with ulcerative colitis, and this polymorphism may confer a genetic predisposition to ulcerative colitis. The results also support the concept that bacterial constituents may be involved in the pathogenesis of ulcerative colitis.     

Aspect clinique et profil évolutif de la carence en thiamine en milieu carcéral en Guinée : étude de trente-huit observations

Cardiovascular and neurological manifestations associated with thiamine deficiency in Guinean prisons are common but not reported.We performed a prospective study of 38 cases related to vitamin B1 deficiency over a period of 4 years. In this population, the literature of traditional data gathered: frequency peak after thirty (92.6%) and clear representation male (sex ratio M/F: 18/1). The clinical symptomatology remains essentially dominated by sensorimotor polyneuropathy and pure sensory (52.2%), overall heart failure (31.5%) and to a lesser degree by Gayet Wernicke’s encephalopathy (7.8%) and shoshin beriberi with severe evolution (5.2%). The study of nutritional status by body mass index (BMI) of the World Health Organization, by the criteria of Detsky and biological markers including albumin, shows that these patients are severely malnourished.     

Discrepant99mTc-ECD images of CBF in patients with subacute cerebral infarction: A comparison of CBF,CMRO2 and99mTc-HMPAO imaging

Three patients with subacute ischemic cerebral infarction examined by SPECT with^99mTc-ECD and PET within the same day showed signs of luxury perfusion in the subacute phase, which is between 9 to 20 days after the onset. A^99mTc-HMPAO SPECT study was also performed within 2 days of the ECD-SPECT study. ECD-SPECT images of three patients displayed a focal decreased uptake in the infarcted lesions, while in infarcted foci, there was almost equivalent or increased CBF compared to normal and unaffected areas, decreased CMRO₂, and high HMPAO uptake. The ECD-SPECT results were similar to those of CMRO₂ rather than CBF, though the HMPAO-SPECT image was similar to that of CBF. In one patient, HMPAO images revealed hyperfixation of the tracer. In the chronic phase and in the acute phase before 5 days after the onset, there were no discrepancies among the ECD-SPECT, CBF, HMPAO-SPECT, and CMRO₂ images. These observations indicated that^99mTc-ECD is a good indicator of damaged brain tissues in subacute ischemic infarction. They also suggested that^99mTc-ECD is a potential agent with which to evaluate cerebral tissue viability in some pathological states of cerebrovascular disease. The characteristics may be suitable for confirming the effects of thrombolytic therapy in acute ischemia, because these conditions often show signs of luxury perfusion when the therapy is successful.