Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation.

BACKGROUND: The cytokine interleukin-4 (IL-4) is secreted mainly by activated T lymphocytes and characterizes the T-helper 2 (Th2) sub-type. In transplantation Th2 cells are believed to induce graft tolerance. Previous studies revealed that patients with a relatively high frequency of IL-4 producing helper T lymphocytes (HTL) before heart transplantation (HTX) had no or less rejection episodes compared with patients with a low frequency of IL-4 producing HTL. Three single nucleotide polymorphisms (SNPs) have been identified in the promoter region of the IL-4 gene, which influence promoter strength. We investigated whether there was a correlation between SNP genotypes in the IL-4 promoter and heart failure, and rejection after HTX. METHODS: Seventy HTX patients, 61 donors, and 36 controls were genotyped for the 3 SNPs by sequencing. RESULTS: Of the SNPs at -285 and -81, only the C and A alleles, respectively, were found in this study. Both alleles were found for the -590 SNP. No relation between patient genotype of the SNP at -590 and heart failure and rejection was found. However, incidence of rejection was significantly lower in patients that received a donor heart with the T-positive genotype compared with patients that received a heart from a T-negative donor. Patients who had the T-negative genotype and received a heart from a T-positive donor, suffered significantly less from rejection than T-negative patients that received a T-negative donor heart. This was not significant in the T-positive patient group. CONCLUSIONS: This indicates that IL-4 production within the donor heart and by cells from the donor is important for reducing incidence of episodes of rejection.     

聚合酶链反应产物特异性的阳性证实

以聚合酶链反应(PCR)法在mRNA水平检测T淋巴细胞受体α链可变区基因表达为例,介绍用~(32)P标记的人工合成寡核苷酸探针对PCR产物特异性作阳性证实的方法。该法以干琼脂糖凝胶作为支持物、相对较为简便和省财。用Ca探针以干凝胶作支持物的杂交结果,证实29个Vα基因的PCR扩增中物均为特异性的,放射自显影的带型与位置和溴乙锭染色所示完全吻合。     

Optimal use of coronary care units: A review

Patients at a low probability of acute cardiac pathology constitute a considerable proportion in many coronary care units (CCUs), such that physicians should consider more effective alternatives than CCU admission “to rule out myocardial infarction.” In this article, strategies to increase the efficiency of managing patients with acute chest pain are reviewed. Algorithms aiming to improve the diagnostic accuracy of the general practitioner have been developed but require an electrocardiogram recorded at the home of the patient. Another method of triage encompasses the identification in the emergency room of the hospital of patients at a low probability of acute cardiac pathology by using predictive models that include laboratory assessments. A third strategy includes alternatives to CCUs for patients at a low risk of acute cardiac pathology, such as the creation of a simple observation unit. Finally, some investigators have sought to identify patients with good prognosis for early transfer from the CCU to lower levels of care. It is concluded that a combination of these approaches will be most efficient, and that the most appropriate choice will be determined by local circumstances.     

The HIV prevalence among pregnant women in the Amsterdam region (1988–1991)

The objective of the study was to monitor the HIV prevalence in the years 1988–1991 among pregnant women in the Amsterdam region, visitors to an abortion clinic and 3 outpatient infertility clinics. All women attending these clinics were asked to participate in the study on a voluntary basis and were tested with informed consent. The women were questioned about risk-bearing behaviour of themselves and their sexual partner(s). In the period 1988–1991, of the 23,827 eligible pregnant women, 22,165 women participated (93.0%). Twenty-seven women were found to be positive for HIV antibodies (0.12%, 95% CI: 0.08%–0.17%), of whom twenty belonged to a known HIV risk group or had a partner who belonged to one of these groups and 7 women had no known HIV risk. Seventeen of the 27 women had a foreign nationality. The annual HIV prevalence among pregnant women was: 1988: 0.28%; 1989: 0.10%; 1990: 0.10%; 1991: 0.11%. In the years 1990 and 1991, of the 1,128 eligible women visiting the abortion clinic 953 (84.5%) were tested. Eleven women were HIV-seropositive (1.15%, 95% CI: 0.6%–2.0%), of whom 9 were from an AIDS endemic region, 1 woman had a partner from this region and 1 woman had no known HIV risk. Four African women had HIV-2 antibodies. At the 3 outpatient infertility clinics 1 woman was found to be HIV-positive (0.13%; 95% CI: 0.02–0.9). She had no other risk than a partner from an AIDS endemic area. In the Amsterdam region there was a steady and low HIV prevalence (0.1%) among pregnant women through the years 1988–1991. The prevalence in the abortion clinic was ten times higher. The program was able to detect possible high risk groups within the population. Migration and travelling can play an important role in the spread of HIV in the general heterosexual population.     

Genetic polymorphisms and heart failure.

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.     

Measuring quality of life in patients with myocardial infarction or stroke: a feasibility study of four questionnaires in The Netherlands.

OBJECTIVE--To test in patients with a history of myocardial infarction or stroke the feasibility of four quality of life measurements--the Nottingham health profile (NHP), the heart patients psychological questionnaire (HPPQ), the sickness impact profile (SIP), and the hospital anxiety and depression scale (HAD). DESIGN--Subjects were tested and retested after an interval of 14 days: questionnaires were self assessed. SUBJECTS--Participants were randomly selected from the Rotterdam stroke data bank (stroke patients; n = 16, mean (SD) age 66.0 (11.0) years and from the population based Rotterdam study (myocardial infarction; n = 20, mean (SD) age 72.7 (7.9) years, controls; n = 17, mean (SD) age 72.8 (7.3) years. MEASUREMENTS AND MAIN RESULTS--Mean (SD) administration times for the NHP, HPPQ, SIP, and HAD were 7.9 (3.5), 10.5 (4.3), 21.0 (9.8), and 5.5 (2.8) minutes respectively. On average, the test-retest reliability was good, with Spearman correlations ranging from 0.31 to 0.95. In spite of the limited size of the study, all instruments were able to show differences between the study groups. For instance, median SIP total scores for myocardial infarction and stroke patients were 12.4 (interquartile range 7.0-19.1) and 11.4 (5.9-15.4) respectively, compared with 7.7 (3.7-11.3) in the control group (p values of 0.04 and 0.14 respectively). CONCLUSIONS--This study suggests that use of the four instruments tested may be feasible and reliable for assessing aspects of quality of life in patients with a history of a myocardial infarction or stroke.     

5-HT1B Receptor Polymorphism and Clinical Response to Sumatriptan

The 5-HT₁ receptor agonist, sumatriptan, is highly effective in the treatment of migraine. Some patients, however, do not respond or experience recurrence of the headache. In addition, some patients report chest symptoms after sumatriptan. We investigated whether these different responses could be attributed to genetic diversity of the 5-HT_1B receptor, which most likely mediates the therapeutic action and the coronary side effects of sumatriptan. Allele frequencies of two polymorphisms in the 5-HT_1B receptor gene ( G861C and T-261G ) were investigated in migraine patients with consistently good response to sumatriptan (n=14), with no response (n=12), with recurrence of the headache (n=12), with chest symptoms (n=13), and in patients without chest symptoms (n=27). Allele frequencies (G:0.74; C:0.26 at nt 861 and T:0.39; G:0.61 at nt -261) did not differ between patient groups, indicating that genetic diversity of the 5-HT_1B receptor does not seem to be involved in the different clinical responses to sumatriptan.