Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine

The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.     

Josamycin concentrations in human dental granuloma after a single oral administration of josamycin

1. Josamycin concentrations in human serum and dental granuloma after a single oral administration of josamycin (600 mg) were assayed by an agar diffusion (paper disc) method. 2. The mean peak josamycin concentrations in serum and dental granuloma occurred at an identical time, approximately 90 min, and were 0.88 micrograms/ml and 1.61 micrograms/g, respectively. 3. The mean concentration ratio of dental granuloma to serum at the peak time was 2.24. 4. Josamycin concentration in dental granuloma at the peak time exceeded MIC80 for clinically isolated strains of Streptococcus group A, Peptostreptococcus spp., and Bacteroides spp.     

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia.

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor (bFGF), a new strategy for the treatment of chronic vascular occlusive disease, was examined in a rabbit model of hind limb ischemia. The left femoral artery was completely excised to induce an ischemic state in the hind limb of male rabbits. Simultaneously, a skin section was resected from the wound, and host fibroblasts were cultured. The cultured fibroblasts were infected with adenovirus vector containing modified human bFGF cDNA with the secretory signal sequence (AxCAMAssbFGF) or LacZ cDNA (AxCALacZ). At 21 days after femoral artery excision, the gene-transduced fibroblasts were administered through the left internal iliac artery. The fibroblasts significantly accumulated in the ischemic hind limb, and the AxCAMAssbFGF-treated cells secreted bFGF for less than 14 days without elevation of systemic bFGF level. At 28 days after cell administration, calf blood pressure ratio, angiographic score, capillary density of muscle tissue and blood flow of the left internal iliac artery were determined, and animals with AxCAMAssbFGF-treated cells showed significantly greater development of collateral vessels, as compared with those with AxCALacZ-treated cells. These findings suggest that adenovirus-mediated ex vivo gene transfer of bFGF was effective for improvement of chronic limb ischemia.     

IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis

PURPOSE: Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted. EXPERIMENTAL DESIGN: Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery. The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute Common Toxicity Criteria grade of > or =2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes. RESULTS: SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis. CONCLUSION: Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy.     

State of Adenomatous Polyposis Coli Gene and ras Oncogenes in Japanese Prostate Cancer

Genetic alterations of ras oncogenes (K-, H- and N- ras ) and adenomatous polyposis coli (APC) gene in tissues of prostate cancer from Japanese patients were examined using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis and direct sequencing. Tissues from 8 cases of untreated stage B prostate cancer surgically removed and from 10 cases of endocrine therapy-resistant metastatic disease obtained at autopsy were used in the present study. In four out of 18 cases (22%), ras point mutations were found, two in either codon 12 or 61 of K-ras and two in either 13 or 61 of H- ras . These point mutations were detected in one of the stage B cases (13%) and in three of the autopsy cases (30%). All these cases were poorly differentiated adenocarcinoma. In autopsy cases showing ras mutation in cancerous prostate, the same alteration was observed in metastatic tissues. No APC gene mutation was detected in any sample, although polymorphism was found in some cases. These results indicate that ras oncogene mutations are related to the progression of prostate cancer, whereas APC gene alteration is not involved in tumorigenesis and development of this cancer.     

Treatment of Status Asthmaticus—Hormone Changes before and after Aminophylline i.v. Drip Therapy

The treatment of status asthmaticus is one of the most important factors in controlling the patient with asthma attacks. We have studied hormone changes in status asthmaticus and considered what is the best treatment in the asthma attack condition in children. Antidiuretic hormone (ADH), renin activity, and aldosterone activity are elevated in severe asthma attack conditions, and these high levels are correlated with high levels in Wood's clinical score. It is theoretical that patients with dehydration and respiratory failure show such elevation in hormones, and it is well known that under such conditions β₂-stimulant enhances renin production. From our study, it is concluded that β₂2 -stimulant subcutaneous injection must be considered in status asthmaticus. In children, amminophylline i.v. drip therapy may be one of the best treatments in status asthmaticus.     

Plasma and right auricle concentrations of atrial natriuretic polypeptide in children with cardiac diseases

To investigate the atrial natriuretic polypeptide (ANP) levels in congenital heart diseases, we measured plasma immunoreactive ANP (ir-ANP) in 29 patients with left-to-righ shunt, and right auricle ir-ANP in 25 patients who underwent operation. The levels of ir-ANP in the pulmonary artery correlated with that in the femoral vein (r=0.95, P<0.001), mean pulmonary arterial pressure (r=0.74, P<0.001) and right atrial pressure (r=0.53, P<0.01). The right auricle ir-ANP level was high in patients with heart failure combined with pressure or volume overload of the right atrium, as observed in tricuspid atresia, complete endocardial cushion defect, and total anomalous pulmonary venous drainage. These results suggest that the production of ANP in the atrium increases as a compensatory or secondary response to persistent release of ANP into the circulation in cardiac diseases.Abbreviations ANP atrial natriuretic polypeptide - ir-ANP immunoreactive ANP - -hANP alpha human ANP - VSD ventricular septal defect - ASD atrial septal defect - PDA patent ductus arteriosus - TOF tetralogy of Fallot - DORV double outlet right ventricle - TAPVD total anomalous pulmonary venous drainage - cECD complete endocardial cushion defect - TA tricuspid atresia - MRAP mean right atrial pressure - MPAP mean pulmonary arterial pressure - Qp/Qs pulmonary-to-systemic blood flow ratio     

Clinical and Postmortem Findings of Two Cases With Karyotype: 48, XXX, +18

Clinical and postmortem findings of two cases with karyotype: 48, XXX, +18 are presented. In both patients the usual characteristics of trisomy 18 were found. Case 1 was complicated with congenital esophageal atresia, hypoplastic left auricle with external auditory canal atresia, left congenital dislocation of hip, and left club foot. The patient died on the 9th day after birth. Autopsy revealed mitral atresia, aortic stenosis, ventricular septal defect, patent ductus arteriosus, coarctation of aorta, bicuspid aortic and pulmonary valves, patent foramen ovale, and congenital esophageal atresia (type C). Case 2 died on the 8th day after birth. Postmortem examination revealed ventricular septal defect, but there was no other noteworthy malformation. Dermatoglyphic findings were more prominent on the right hand than the left. The severity of malformations may be biased to either the right or the left side.     

Recurrent low output syndrome after the weaning from mechanical circulatory support for postcardiotomy cardiogenic shock

We reviewed the cases of recurrent low output syndrome (LOS) after the weaning from mechanical circulatory support for postcardiotomy cardiogenic shock. Twelve patients were divide into 2 groups according to whether low output syndrome recurred or not, consisting of a recurrent low output syndrome (+) group [re-LOS (+) group, n = 6] and a recurrent low output syndrome (-) group [re-LOS (-) group, n = 6]. Between 2 groups, there was no statistical difference in preoperative left ventricular ejection fraction (LVEF), aortic closs-clamping time and cardiac index at the weaning from mechanical circulatory support. Only the LVEF at the weaning in the re-LOS (+) group was significantly less than that in the re-LOS (-) group (0.39 +/- 0.08 vs 0.62 +/- 0.19, p < 0.05). All patients in the re-LOS (-) group survived to discharge, while in the re-LOS (+) group, although 3 patients were re-supported by intra-aortic balloon pumping, 4 of 6 patients died of multiple organ failure and 2 survivors were in New York Heart Association class III. The results suggest that the key to survive to discharge after the weaning from mechanical circulatory support is whether the cardiac contraction could recover or not.