Association of galactose-1-phosphate uridyltransferase activity and N314D genotype with the risk of ovarian cancer

Deficiency in the galactose-1-phosphate uridyltransferase (GALT) enzyme results in accumulation of galactose and its metabolites in the ovary (Am J Epidemiol 1989;130:904-10). Galactose may raise gonadotropin levels, resulting in proliferation of ovarian epithelium. In 1993-1999, the authors conducted a population-based case-control study of ovarian cancer in Hawaii and Los Angeles, California, to examine the hypothesis that reduced GALT activity is associated with an increased risk of ovarian cancer. A total of 239 ovarian cancer cases and 244 population controls were interviewed. A blood sample was collected to measure levels of GALT and to assay for the N314D (A940G) polymorphism of the GALT gene. Covariate-adjusted mean GALT activity was similar between cases (23.8 micro mol per hour/g hemoglobin (Hb)) and controls (23.7 micro mol per hour/g Hb) (p = 0.83). No evidence was found for a dose-response relation between the odds ratios for ovarian cancer and GALT activity or the ratio of lactose intake to GALT activity. The risk associated with the presence of at least one variant Asp314 allele was 0.77 (95% confidence interval: 0.42, 1.41). This study did not support the hypothesis that reduced galactose metabolism is a risk factor for ovarian cancer, although increased GALT activity attenuated the inverse association of oral contraceptive pill use with risk.     

Association of a common polymorphism in the human GH1 gene with colorectal neoplasia

BACKGROUND: Growth hormone (GH) may be associated with the development of colorectal tumors directly and/or indirectly via an increased plasma level of insulin-like growth factor-I (IGF-I), which has been associated with colorectal cancer risk. Because a T-to-A polymorphism in the human GH1 gene at position 1663 is putatively associated with lower levels of GH and IGF-I, we investigated the relationship of this polymorphism to the risk of colorectal neoplasia. METHODS: We analyzed data from two case-control studies conducted in Hawaii: a population-based study of 535 case patients with colorectal adenocarcinoma and 650 control subjects and a sigmoidoscopy screening-based study with 139 case patients with adenoma and 202 control subjects. All subjects were tested for the GH1 polymorphism. Logistic regression was used to adjust for known risk factors. Plasma IGF-I and IGF binding protein-3 (IGFBP-3) levels were measured in a subset of 293 subjects in the adenoma study (135 case patients and 158 control subjects). All statistical tests were two-sided. RESULTS: Adjusted odds ratios (ORs) for colorectal cancer associated with T/T, T/A, and A/A genotypes were 1.00, 0.75 (95% confidence interval [CI] = 0.58 to 0.99), and 0.62 (95% CI = 0.43 to 0.90), respectively (P(trend) =.006). Adjusted ORs for adenoma were 1.00, 0.76 (95% CI = 0.46 to 1.24), and 0.62 (95% CI = 0.31 to 1.22), respectively (P(trend) =.17). Data from both studies consistently showed that the A allele was associated with a lower risk of colorectal neoplasia than the T allele, although the association with adenoma was not statistically significant. These associations were consistently suggested in Caucasians and Native Hawaiians but not in Japanese. The ratio of plasma IGF-I/IGFBP-3 was lower in individuals with the A allele than in individuals with the T allele (P =.01). CONCLUSION: The human T1663A GH1 gene polymorphism, which may confer lower levels of GH and IGF-I, appears to be associated with a decreased risk of colorectal cancer.     

Case-control study of plasma folate, homocysteine, vitamin B(12), and cysteine as markers of cervical dysplasia

BACKGROUND: An association between B-complex vitamins and related compounds with the development of cervical neoplasia is biologically plausible, yet to the authors' knowledge epidemiologic investigations of these potential biomarkers are limited. METHODS: A case-control study was designed to examine the relation between plasma folate, homocysteine, vitamin B(12), and cysteine and early, premalignant changes in cervical epithelial cells among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. Fasting blood samples for plasma nutrient analysis, cervical smears for cytologic diagnosis, exfoliated cervical cells for human papillomavirus DNA testing by polymerase chain reaction, and a personal interview were obtained from 185 women with atypical squamous cells of undetermined significance (ASCUS) of the cervix, 147 women with squamous intraepithelial lesions (SIL), and 191 women with cytologically normal (Papanicolaou) smears. RESULTS: Age-adjusted and ethnicity-adjusted mean plasma concentrations of cysteine, but not other nutrients, were significantly lower among ASCUS cases (P = 0.006) and SIL cases (P = 0.01) than controls. A positive trend in the odds ratio for SIL but not ASCUS was found for increased plasma homocysteine concentrations, but this finding was not statistically significant. High plasma levels of cysteine were associated with a reduced risk of ASCUS (P value for trend = 0.006), with an odds ratio of 0.3 (95% confidence interval, 0.2-0.7) for the highest compared with the lowest quartile of cysteine concentration. A weak, negative relation between cysteine and the development of low grade SIL (LSIL) but not high grade SIL (HSIL) also was found. CONCLUSIONS: The results of the current study do not support the hypothesis that folate, homocysteine, or B(12) are markers of cervical dysplasia risk. A possible inverse association between plasma cysteine concentrations and the risk of cervical dysplasia needs further study.     

Wound Complications and Treatment of the Infected Implantable Cardioverter Defibrillator Generator

A bstract Since 1980, the automatic implantable cardioverter defibrillator (ICD) has evolved as effective therapy for prevention of sudden cardiac death following documented sustained ventricular tachycardia or fibrillation. During a 5-year period, 412 ICD devices were implanted at the University of Michigan Hospitals with a wound complication rate of 4.1%. In this group, there were 13 infections, 3 erosions of the generator pocket, and 1 wound hematoma. Of the 16 patients with infection or erosion, 12 patients were treated with a rectus abdominis muscle flap closure and 4 with ICD generator removal. In 83% (n = 12) of the muscle flap patients, the wound healed uneventfully. Preoperative chest CT scanning was found to be helpful in identifying probable infection of the epicardial leads. In these cases, all hardware had to be removed to achieve resolution of the infection. We concluded that rectus abdominis muscle flaps were helpful in salvaging infected or exposed ICD generators in the absence of infected epicardial leads.     

Pretreatment with ondansetron blunts plasma vasopressin increases associated with morphine administration in ferrets

Postoperative nausea and vomiting are significant problems. A method for measuring vomiting thresholds for anesthetics using plasma markers, such as arginine vasopressin (AVP), would be useful. We measured the change in AVP concentrations associated with morphine alone or in combination with ondansetron pretreatment. Data were collected from ferrets implanted with IV catheters. After recovery, the ferrets were administered IV morphine alone or with ondansetron pretreatment. Baseline blood samples were taken before morphine injection, and at 5, 10, 15, 30, 45, 60, and 90 min after morphine injection. Plasma AVP levels were measured using radioimmunoassay. Morphine alone was associated with a significant increase in plasma AVP concentrations from baseline at 45, 60, and 90 min (P < 0.05). Ondansetron alone did not change the plasma AVP concentration after 20 min (P > 0.46). There was no significant increase (P > 0.46) in AVP concentration in animals that were pretreated with ondansetron before administration of morphine. Two-way analysis of variance confirmed that ondansetron significantly decreased the increase in AVP by morphine at 60 and 90 min (P < 0.05). These data suggest that plasma AVP concentration may be an accurate marker for nausea, and may be useful to guide treatment for this condition. IMPLICATIONS: The antiemetic, ondansetron, has an effect not only on clinically perceived vomiting, but also on plasma vasopressin level.     

Association between the promoter polymorphism T/C at position -159 of the CD14 gene and anti-inflammatory therapy in patients with inflammatory bowel disease

Immune response to intestinal bacteria and genetic predisposition seem to play a crucial role in the pathogenesis of inflammatory bowel disease. A single nucleotide polymorphism in the promoter of the lipopolysaccharide-receptor CD14 gene (T/C at position -159) has recently been described. To evaluate the role of the CD14 gene in anti-inflammatory therapy, the functionally relevant T(-159)-->C promoter polymorphism has been genotyped in 72 patients with inflammatory bowel disease and associated with the cumulative steroid dose. Cumulative corticosteroid dose was significantly higher in ulcerative colitis patients with the TT genotype (2447.7 +/- 927.0 mg/yr) compared with the CT genotype (142.3 +/- 142.3 mg/yr, p=0.016) and the CC genotype (391.7 +/- 272.7 mg/yr, p=0.047). In contrast, in patients with Crohn's disease there was no significant difference of the cumulative corticosteroid doses between the various T(-159)-->C promoter CD14 genotypes. An altered immune response to lipopolysaccharides with influence on the anti-inflammatory therapy seems to play a role in the genetic predisposition to ulcerative colitis. Genetic stratification will lead to the development of individualized therapies in inflammatory bowel disease.     

Dietary patterns using the Food Guide Pyramid groups are associated with sociodemographic and lifestyle factors: the multiethnic cohort study

Dietary patterns have been used to identify typical combinations of foods that may be associated with disease risks. We defined dietary patterns among 195,298 participants of the Multiethnic Cohort Study in Hawaii and Los Angeles in 1993-1996. Intakes of Food Guide Pyramid groups were calculated from a quantitative FFQ for subjects of 5 ethnic groups (African Americans, Hawaiians, Japanese Americans, Latinos, and whites). Three distinct dietary patterns, "Fat and Meat," "Vegetables," and "Fruit and Milk," were identified by exploratory factor analysis with a varimax rotation and validated by confirmatory factor analysis. Similar factor loadings were found for each of 10 ethnic-gender groups in stratified analyses. The odds ratios (OR) for being above the median scores for each factor were calculated. Age, gender, and ethnicity had relatively strong associations with dietary patterns whereas education showed only weak associations. BMI > or = 30 was strongly positively associated with the Fat and Meat pattern (OR = 2.14, 95% CI: 2.08-2.20, vs. BMI < 25). Current smokers showed a positive association with the Fat and Meat pattern (OR = 1.67, CI: 1.62-1.72, vs. nonsmokers) and inverse associations with the Vegetables (OR = 0.66, CI: 0.64-0.68) and Fruit and Milk patterns (OR = 0.53, CI: 0.52-0.55). Physical activity was positively associated with the Vegetables and Fruit and Milk patterns but not with the Fat and Meat pattern. These findings support the hypothesis that dietary patterns are influenced by interrelated sociocultural, demographic, and other lifestyle factors and may be useful in investigations of diet-disease relations.     

Computed tomography of cystic lung diseases

A cystic lesion in the lung is defined as a well-demarcated epithel-lined cavity, that can be mostly filled with air, water, as well as solid material content. This definition includes a wide variety of diseases such as bronchogenic cyst, abscess formation, lymphangioleiomyomatosis, Langerhans cell histiocytosis, emphysema, bronchiectasis, and pneumatoceles. Despite the difficulties in differential diagnosis, there are some diagnostic criteria for CT-scanning helping the radiologist to differentiate between these cystic entities. Moreover, clinical informations are extremely important. The most important clinical parameters include age, sex, clinical history and symptoms. Thus, a better understanding of classic CT appearance of cystic lung disease will allow more definitive diagnosis and could, in some cases, avoid biopsy.