Assessment of familiality, obesity, and other risk factors for early age of cancer diagnosis in adenocarcinomas of the esophagus and gastroesophageal junction.

OBJECTIVES: Adenocarcinomas of the esophagus and adenocarcinomas of the gastroesophageal junction are postulated to be complex genetic diseases. Combined influences of environmental factors and genetic susceptibility likely influence the age at which these cancers develop. The aim of this study was to determine whether familiality and other recognized risk factors are associated with the development of these cancers at an earlier age. METHODS: A structured validated questionnaire was utilized to collect self-reported data on gastro-esophageal reflux symptoms, risk factors for Barrett's esophagus (BE) and family history, including age of cancer diagnosis in affected relatives from probands with BE, adenocarcinoma of the esophagus, or adenocarcinoma of the gastroesophageal junction, at five tertiary care academic hospitals. Medical records of all relatives reported to be affected were requested from hospitals providing this cancer care to confirm family histories. Familiality of BE/cancer, obesity (defined as body mass index >30), gastroesophageal reflux symptoms, and other risk factors were assessed for association with a young age of cancer diagnosis. RESULTS: A total of 356, 216 non-familial and 140 familial, cancers were studied. The study population consisted of 292 (82%) men and 64 (18%) women. Mean age of cancer diagnosis was no different in a comparison of familial and non-familial cancers, 62.6 vs. 61.9 years, P=0.70. There were also no significant differences in symptoms of gastroesophageal reflux, body mass index, race, gender, and smoking history between familial and non-familial cancers. Mean age of cancer diagnosis was significantly younger in those who were obese 1 year before diagnosis as compared to those who were non-obese, mean age 58.99 vs. 63.6 years, P=0.008. Multivariable modeling of age at cancer diagnosis showed that obesity 1 year before diagnosis was associated with a younger age of cancer diagnosis (P=0.005) after adjustment for heartburn and regurgitation duration. CONCLUSIONS: Obesity is associated with the development of esophageal and gastroesophageal junctional adenocarcinomas at an earlier age. Familial cancers arise at the same age as non-familial cancers and have a similar risk factor profile.

Inflammatory bowel disease and coronary artery disease.

Chronic inflammation with the presence of excess serum acute-phase proteins, cytokines and cell adhesion molecules is increasingly being implicated in atherosclerosis. The association between inflammatory bowel disease (IBD) and coronary artery disease (CAD) is unstudied. This is a preliminary, thesis-generating cross-sectional study aimed at evaluating the presence of traditional atherosclerotic risk factors in patients with IBD and CAD compared with the control population. The medical records of 42 consecutive IBD patients with CAD from 1999 to 2005 (27 men) were reviewed for the Framingham risk factors. The Framingham risk score (FRS) is calculated based on age, sex, hypertension, diabetes and hyperlipidemia. FRS of patients with IBD and CAD was compared with the FRS of 137 age- and sex-matched (102 men) consecutive patients with CAD (controls). When the Framingham risk score adjusted for group and gender with age as a covariate, the adjusted total FRS score was higher in patients with CAD alone (10.0 [3.75]) as compared to those with; IBD and CAD: (8.1 [3.47]; p = 0.001). FRS is lower in cases (patients with IBD and CAD) when compared with the controls (CAD alone).

Outcomes for subsequent pregnancy in women who have undergone misoprostol mid-trimester termination of pregnancy.

In Australia, the most common method of mid-trimester termination of pregnancy (TOP) is by medical induction with the prostaglandin E 1 analog misoprostol. This study was undertaken to compare the pregnancy outcomes of women who had undergone a misoprostol mid-trimester TOP in their last pregnancy with those of a similar cohort of women without a history of misoprostol TOP. This study suggests a possibility that medical mid-trimester TOP with misoprostol increases the risk of preterm or very preterm delivery in a subsequent pregnancy but larger studies are needed to confirm or dismiss this.

A new formula for summarising the pregnancy history.

Pregnancy history formulae usually provide only summaries of numbers of pregnancies and births. Different pregnancy outcomes and their sequence are not captured. A new pregnancy history formula is proposed where one number provides information on parity, gravidity, sequence, gestation and outcome of pregnancies. For instance, 914 represents the history of a woman having had three pregnancies, where '9' represents a term first birth, '1', a miscarriage and '4', a preterm perinatal death in the third pregnancy. This formula could be used in medical records or perinatal databases.

Extensive gastrointestinal tract and thyroid involvement with Wegeners granulomatosis.

Wegeners granulomatosis (WG) is a pauci-immune systemic vasculitis involving small to medium sized blood vessels of the respiratory tract and renal vasculature. We report a 34-year-old lady with extensive gastrointestinal tract, pancreas and thyroid involvement. Literature review revealed only two prior reports of esophageal involvement, two reports of pancreatic involvement and few cases of thyroid involvement.

Clinicians' evaluations of fetal oximetry sensor placement in a multicentre randomised trial (the FOREMOST trial).

BACKGROUND: Fetal pulse oximetry (FPO) may improve the assessment of the fetal well-being in labour. Reports of health-care provider's evaluations of new technology are important in the overall evaluation of that technology. AIMS: To determine doctors' and midwives' perceptions of their experience placing FPO sensors. METHODS: We surveyed clinicians (midwives and doctors) following placement of a FPO sensor during the FOREMOST trial (multicentre randomised trial of fetal pulse oximetry). Clinicians rated ease of sensor placement (poor, fair, good and excellent). Potential influences on ease of sensor placement (staff category, prior experience in Birth Suite, prior experience in placing sensors, epidural analgesia, cervical dilatation and fetal station) were examined by ordinal regression. RESULTS: There were 281 surveys returned for the 294 sensor placement attempts (response rate 96%). Sensors were placed by midwives (29%), research midwives (48%), registrars (22%) and obstetricians (1%). The majority of clinicians had 1 or more years' Birth Suite experience, had placed six or more sensors previously, and rated ease of sensor placement as good. Advancing fetal station (P < 0.001) and the presence of epidural analgesia prior to sensor placement (P = 0.029) predicted improved ease of sensor placement. Having a clinician placing a sensor for the first time predicted a lower rating for ease of sensor placement (P = 0.001), compared to having placed one or more sensors previously. CONCLUSIONS: Clinicians with varying levels of Birth Suite experience successfully placed fetal oxygen saturation sensors, with the majority rating ease of sensor placement as good.

Women's evaluations of their experience in a multicenter randomized controlled trial of intrapartum fetal pulse oximetry (The FOREMOST Trial).

BACKGROUND: Fetal pulse oximetry improves the assessment of fetal well-being during labor. The objective of this study was to evaluate women's satisfaction with their experience with this additional technology. METHODS: We surveyed women participating in the FOREMOST trial, a randomized controlled trial comparing the addition of fetal pulse oximetry (FPO) to conventional cardiotocograph (CTG) monitoring (intervention group), versus CTG-only (control group), in the presence of nonreassuring fetal status during labor. Our survey evaluated 3 aspects of women's experience: labor, fetal monitoring, and participation in the research. The survey was administered within a few days of giving birth and repeated 3 months later. RESULTS: No differences were found between the intervention and control groups for women's evaluations of their labor, fetal monitoring, research, or overall experiences when surveyed on both occasions. Within each study group, a small but statistically significant decline occurred in women's scores for their experience of labor and overall experience from the initial survey close to the time of giving birth, to 3 months later. The magnitude of differences in responses over time was similar for the both groups. Women were more satisfied after a spontaneous or assisted vaginal birth than after cesarean section. Length of time the research midwife was present had a significant positive effect on women's ratings of their experience several days after giving birth (p = 0.006), but no effect at 3 months. CONCLUSIONS: The addition of fetal pulse oximetry for the assessment of fetal well-being during labor did not affect childbearing women's perceptions of fetal monitoring or their labor. Women evaluated their experience in the research process positively overall. Small changes occurred in women's perception of their satisfaction over time.

The effect of intrapartum fetal pulse oximetry, in the presence of a nonreassuring fetal heart rate pattern, on operative delivery rates: a multicenter, randomized, controlled trial (the FOREMOST trial).

OBJECTIVE: The objective of the study was to compare operative delivery rates for nonreassuring fetal status between 2 groups of laboring women: those having conventional cardiotocograph monitoring and those having cardiotocograph monitoring plus fetal pulse oximetry. STUDY DESIGN: The intrapartum fetal oximetry prospective, multicenter, randomized, controlled trial (the FOREMOST trial) was conducted in 4 Australian maternity hospitals. The primary outcome was operative birth rates for nonreassuring fetal status. RESULTS: There was a statistically significant 23% relative risk reduction in operative delivery for nonreassuring fetal status in the fetal pulse oximetry + cardiotocograph group (n = 75 of 305, 25%), compared with those in the cardiotocograph-only group (n = 95/295, 32%) (relative risk 0.77, 95% confidence interval 0.599, 0.999, P = .048). There were no significant between-group differences in overall operative births (fetal pulse oximetry + cardiotocograph group 73%, cardiotocograph-only group 71%, relative risk 1.04, 95% confidence interval 0.94, 1.15, P = .478) or neonatal outcomes. CONCLUSION: The use of fetal pulse oximetry to augment fetal well-being assessment during labor resulted in a statistically significant reduction in the operative intervention for nonreassuring fetal status, compared with the use of conventional cardiotocograph monitoring alone. This reduction was achieved with no significant difference in neonatal outcomes.

The role of reviews of perinatal deaths.

Systematic audit of stillbirths and neonatal deaths at an institutional and regional level is the first step in the descriptive epidemiology of perinatal mortality and a necessary means for identifying the causes of such deaths. Uniform classification systems within an organizational jurisdiction enable the identification of the major contributing categories, facilitate analysis, and enable consideration of possible interventions and strategies for prevention. This paper describes the application of the classification systems recently developed by the Perinatal Society of Australia and New Zealand (PSANZ), as part of a perinatal audit package, to a cohort of 3485 perinatal deaths in Victoria over a 5-year period, 2000-2004. There are many other perinatal mortality audit systems in place in other jurisdictions, designed to produce the same result, i.e. a better understanding of the causes of perinatal mortality and the possibilities for prevention.

Maternal deaths in Australia, 1997-1999.

Many maternal deaths in Australia are still preventable.

Calcium channel blockers for inhibiting preterm labour; a systematic review of the evidence and a protocol for administration of nifedipine.

OBJECTIVE: To assess the effects on maternal, fetal and neonatal outcomes of nifedipine (and other calcium channel blockers) administered as a tocolytic agent to women in preterm labour. METHODS: Standard methods of the Cochrane Collaboration and its Pregnancy and Childbirth Review Group were used. All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in preterm labour between 20 and 36 weeks' gestation, were considered. MAIN RESULTS: The systematic review includes 12 randomised controlled trials with a total of 1029 participating women. No trials were identified in which calcium channel blockers were compared with a placebo or no alternative tocolytic treatment. Calcium channel blockers appear to be more effective than betamimetic agents in prolonging pregnancy for 7 days or longer, are much less likely to cause maternal side-effects and are associated with reduced neonatal morbidity. CONCLUSION: Calcium channel blockers (especially nifedipine) can be considered safer and more effective tocolytic agents than betamimetics.

Reversible and Irreversible ElcB Mechanisms in the Hydrolysis of 2,2,2-Trifluoroethanesulfonyl Chloride: Carbanion Intermediates in Aqueous Acid(1).

Hydrolysis of 2,2,2-trifluoroethanesulfonyl chloride (1) is shown to take place by way of the sulfene (CF(3)CH=SO(2)), formed by (a) an irreversible E1cB process over the pH range 1.8-5 with water acting as the carbanion-forming base in the lower pH range and hydroxide anion at higher pH, and (b) a reversible E1cB reaction in dilute acid.

Alkyl 2,2,2-Trifluoroethanesulfonates (Tresylates): Elimination-Addition vs Bimolecular Nucleophilic Substitution in Reactions with Nucleophiles in Aqueous Media(1).

Alkyl 2,2,2-trifluoroethanesulfonate esters (tresylates), ROSO(2)CH(2)CF(3), react with aqueous base (pH >/= 9) to give the (alkoxysulfonyl)acetic acid, ROSO(2)CH(2)COOH; with the further addition of either a primary or secondary amine or of an alkanethiol, the product is the either the corresponding amide, ROSO(2)CH(2)C(O)NR(1)R(2), or a mixture in which the ketene dithioacetal, ROSO(2)CH=C(SR(1))(2), or the thioorthoester, ROSO(2)CH(2)C(SR(1))(3), may predominate. Kinetic and product studies are consistent with the following: (a) the reaction of tresylates with water is the normal sulfonic ester hydrolysis and (b) reaction with hydroxide is an (E1cB)(rev) process with loss of HF to yield the alkyl 2,2-difluoroethenesulfonate, ROSO(2)CH=CF(2), which rapidly yields the observed products. Benzyl 2,2,2-trifluoroethyl sulfone reacts analogously. The relationship between these observation with small molecules and those of earlier workers with tresyl agarose is discussed.