Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.

PURPOSE: Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy. EXPERIMENTAL DESIGN: A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels. RESULTS: The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption. CONCLUSIONS: We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.     

The effect of continuous intraabdominal nebulization of lidocaine during gynecological laparoscopic procedures- a pilot study

Although laparoscopic surgery is known to cause less postoperative pain when compared to laparotomy, some patients still suffer from excessive pain, especially during the first stages of recovery. The purpose of our study was to assess the effect of intraperitoneal nebulization of lidocaine during gynecological laparoscopic procedures on perioperative pain. The study was a prospective, randomized, double-blinded, placebo-controlled trial (Canadian task force classification I) that included 23 patients who underwent outpatient gynecological laparoscopic procedures. Patients were randomly assigned either to a study group that received 5 mg/kg of lidocaine intraperitonealy during surgery (n=15) or to a control group that received sterile water in the same manner (n=8). The fluid was infuslated along with the CO₂ through a Insuflow® device. All patients received the same anesthetic technique. Intraoperative pain as assessed by changes in the vital signs was treated with fentanyl. Postoperative pain was evaluated according to postoperative opioid requirements and by the Visual Analogue Scale (VAS) at 15 min, 1 h and 24 h postoperatively. The VAS score was found to be lower for the study group 1 h after surgery (p=0.023). There was no difference in the VAS scores at 15 min (p=0.9) and 24 h (p=0.11) after surgery. A correlation analysis showed no association between the amount of lidocaine insufflated and the severity of the postoperative pain. There was no difference in terms of fentanyl administration during surgery or opiod consumption following surgery between the groups. We concluded that continuous intraperitoneal insuflation of lidocaine using an Insuflow® device may significantly reduce pain in the initial stage of postoperative recovery.     

Indomethacin and corticosteroids: an additive constrictive effect on the fetal ductus arteriosus

The objective of this paper is to study the possible additive effect of corticosteroids to the known effect of indomethacin on potency of the human ductus arteriosus. Systolic and diastolic blood flow of the fetal ductus arteriosus was measured by echo Doppler at 26-32 weeks of gestation. Four groups of patients were studied according to the treatment they have received: group A (exposure to indomethacin and betamethasone); group B (indomethacin alone); group C (betamethasone); and group D (controls). Children in whom ductal constriction was noted in utero were followed by repeat cardiac echo Doppler examinations at the age of 1 to 2 years. In group A (indomethacin and betamethasone) fetal ductal constriction was significantly higher (p = 0.02) and occurred in 11 out of 15 fetuses (73.3%), compared with 5 out of 14 (37.2%) of the fetuses in group B (indomethacin alone). In group C (betamethasone) and D fetuses (no treatment), no significant ductal constriction was observed. Pathological tricuspid regurgitation and right ventricular dilation were found more frequently in fetuses from group A. No long-term sequella was noted in the infants in whom ductal constriction had been noted in utero. Corticosteroids and indomethacin have a synergistic effect on the frequency and severity of fetal ductus arteriosus constriction. In short-term treatment this effect is transient, and has no deleterious effects on fetal and neonatal cardiac function.     

Relationship between changes in neck circumference and cardiovascular risk factors

OBJECTIVE: Neck circumference (NC) is a simple screening measure for identifying overweight and obese patients. The main aim of the present study was to determine the relationship between changes in NC and changes in cardiovascular risk factors by evaluating some components of the metabolic syndrome. METHODS: The present longitudinal cohort study included 364 subjects (155 men and 209 women) with no known major medical conditions and who were not receiving any medication. Main indicators included NC, waist circumference, waist-to-hip ratio, body mass index, and fasting lipoprotein, glucose and uric acid levels. RESULTS: Pearson's correlation coefficients indicated a significant association between changes in NC and changes in body mass index (men, r=0.67; women, r=0.69; each, P<0.0001), waist circumference (men, r=0.69; women, r=0.56; each, P<0.0001), waist-to-hip ratio (men, r=0.27; women, r=0.33; each, P<0.0001), and total cholesterol (men, r=0.68; women, r=0.64; each, P<0.0001), low density lipoprotein cholesterol (men, r=0.58; women, r=0.59; each, P<0.0001), triglyceride (men, r=0.48; women, r=0.44; each, P<0.0001), glucose (men, r=0.51; women, r=0.44; each, P<0.0001) and uric acid (men, r=0.42; women, r=0.47; each, P<0.0001) levels. The relative changes in NC contributed to independent significant changes in total cholesterol (8% for men and 1% for women), low density lipoprotein cholesterol (1% for men and 1% for women) and triglycerides (23% for men); it did not significantly contribute to changes in high density lipoprotein cholesterol, glucose or uric acid levels. CONCLUSION: Changes in NC are positively correlated with changes in some factors of the metabolic syndrome and, therefore, are correlated with changes in the risk of cardiovascular disease.     

Mutational analysis of <Emphasis Type="BoldItalic">hMsh6</Emphasis> in Israeli HNPCC and HNPCC-like Families

Germline mutations in DNA mismatch repair (DNA-MMR) genes, mainly hMlh1 and hMsh2, underlie Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Germline hMSH6 gene mutations have been reported in a small subset of HNPCC families. In the present study, ethnically diverse individuals with HNPCC and HNPCC-like features were genotyped for hMsh6 germline mutations using exon-specific PCR, DGGE, and DNA sequencing. The study encompassed 92 individuals representing 88 unrelated families who were previously analyzed for Msh2 and Mlh1 mutations: Jewish Ashkenazim (n = 44), non-Ashkenazim (n = 27), Israeli Moslem-Arab (n = 15), Druze (n=3), and Cypriot non-Jews (n = 3). Of the study population, 71 had colon cancer (CRC), mean age at diagnosis was 50.9±13.2 years (range16–73 years), 5 had endometrial cancer (two with concurrent CRC), (mean 43.6±3.26 years, range 38–45 years), and unaffected individuals (n = 18) were first degree relatives within HNPCC families and were genotyped at a mean age of 48.3±11.7 years (range 30–69 years). Of the 92 individuals analyzed, none showed a truncating hMsh6 mutation, and 6 (6.6%) harbored one of three germline missense mutations: a previously reported one (V878A), and two novel mutations (V509A, S227I). The pathogenic significance of these three missense mutations is yet unclear. In addition, 5 polymorphisms were detected, 2 of which were novel. We conclude that the rate of pathogenic hMsh6 mutations in HNPCC families of Jewish and Mediterranean origin is low, and that mutations in other genes probably account for the phenotype in these families.     

Tobacco smoking, GSTP1 polymorphism, and bladder carcinoma

BACKGROUND: Although cigarette smoking is considered a major risk factor for bladder carcinoma, little is known about the interaction between metabolic genes such as glutathione-S-transferase P1 and tobacco smoking in this process. GSTP1 may play a role in detoxification of tobacco-related carcinogens. METHODS: In this case-control study of 145 cases with bladder carcinoma (male:female = 7.5:1) and 170 noncancer controls (male:female = 3.7:1), the relation between genetic polymorphisms of GSTP1 and susceptibility to bladder carcinoma was investigated and the gene-environment interaction between tobacco smoking and GSTP1 polymorphism was evaluated. Epidemiological data were collected for all cases and controls by a standard questionnaire. Polymorphisms of GSTP1 were measured by polymerase chain reaction-restriction fragment length polymorphism. The logistic regression model in SAS was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Cigarette smoking was confirmed as a risk factor of bladder carcinoma with an OR of 3.1 (95% CI: 1.7-5.9) after controlling for potential confounding factors. The OR for pack-years of smoking as a continuous variable was 2.4 (95% CI: 2.0-2.8). The ORs were 7.6 (95% CI: 1.18-49.51) for isoleucine/valine (Ile/Val) and 6.5 (95% CI: 1.01-41.56) for Ile/Ile when the homozygous Val/Val was considered as comparison group after adjusting for age, gender, race, and education. The adjusted OR for interaction between smoking and the GSTP1 (any Ile genotype) was 11.42 (95% CI: 0.53-248.15). CONCLUSIONS: The results indicate that the Ile 105 allele is associated with an increased risk of bladder carcinoma and suggest that individuals who smoke and possess the Ile allele might be at increased risk for bladder carcinoma.