Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281.

Purpose: Optimal treatments for metastatic carcinoid tumor remain undefined, and the role of chemotherapy for symptomatic patients with progressive disease is uncertain.

Patients And Methods: Two hundred forty-nine patients with advanced carcinoid tumors were randomized to either doxorubicin with fluorouracil (FU/DOX) or streptozocin with fluorouracil (FU/STZ). Patients crossed over to the dacarbazine (DTIC) treatment after disease progression following first-line treatment (either FU/DOX or FU/STZ), and 73 patients were assigned to one of these three treatments based on their previous treatment or on abnormal baseline cardiac or renal function.

A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282.

Purpose: The median survival time of patients with locally advanced adenocarcinoma of the pancreas is 8-10 months. Radiation therapy has been used to improve local control and palliate symptoms. This randomized study was undertaken to determine whether the addition of 5-fluorouracil (5-FU) and mitomycin-C (MMC) to radiation therapy improves outcome in this patient population.

Differential gonadotropin releasing hormone (GnRH) expression, autoregulation and effects in two models of rat luteinized ovarian cells.

GnRH has been suggested to participate in corpus luteum function. Here we studied the expression of GnRH mRNA and peptide in two models of rat luteinized tissues: ovarian cells from PMSG-hCG treated prepubertal rats (SPO) and from intrasplenic ovarian tumors (Luteoma). A GnRH autoregulatory effect was evaluated as well as its action on cell proliferation and apoptosis.

Association of short-term ambient air pollution concentrations and ventricular arrhythmias.

The authors evaluated the association between ventricular arrhythmias detected by implantable cardioverter defibrillators and ambient air pollution concentrations in the hours immediately before the arrhythmia. Patients given implantable cardioverter defibrillators at the New England Medical Center in Boston, Massachusetts, between mid-1995 and 1999 who lived within 40 km of a central monitoring site (n = 203) were followed until July 2002. The authors used a case-crossover design to study the association between ambient air pollution and up to 798 confirmed ventricular arrhythmias among 84 subjects.

Phenotype of microsatellite-stable colorectal carcinomas with CpG island methylation.

A distinctive pathway of colorectal carcinogenesis termed CpG island methylator phenotype is characterized by extensive DNA methylation in colorectal carcinoma (CRC) cells but not in nonneoplastic mucosa. Many CRCs with CpG island methylator phenotype have methylation of the hMLH1 mismatch repair gene and consequently have high levels of microsatellite instability (MSI-H). MSI-H confers distinctive clinical-pathologic features, but the phenotype of microsatellite-stable CRC with methylation has not been characterized in detail.

Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury.

Thiazolidinedione rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), are two peroxisome proliferator-activated receptor (PPAR)-gamma ligands. The aim of this study was to investigate the effect of rosiglitazone and 15d-PGJ2 on the lung injury caused by bleomycin administration. Mice subjected to intratracheal administration of bleomycin developed significant lung injury.

Possible human sacrifice at the origins of Rome: novel skeletal evidences.

Recent archaeological excavations at the Carcer/Tullianum, in the Roman Forum, allowed the unexpected recovery of human burials associated with the very early foundations of the monument, at the beginning of the iron age. The study of these burials resulted in interesting paleopathological discoveries, concerning the skeleton of a strongly-built male, radiocarbon-dated between 830 and 780 BC. The telltale posture of the skeleton and the presence of a massive perimortal blunt force trauma of the skull shed light on the mode and circumstances of the death of this subject, and are suggestive of ritual sacrifice.

Effect of androgens on sexual differentiation of pituitary gamma-aminobutyric acid receptor subunit GABA(B) expression.

Previous work demonstrated a sexually dimorphic ontogenic expression of gamma-aminobutyric acid receptors (GABA(B)R) in rat pituitary. As sex steroids determine sex-specific expression patterns, we now studied the effect of sex hormones on pituitary GABA(B)R expression. GABA(B)R subunits, measured by Western blot and by semi-quantitative RT-PCR and luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone measured by RIA were determined in two experimental designs: First experimental design: 8- and 15-day-old females (8F, 15F); 8F and 15F treated with 100 mug testosterone propionate (TP) on day 1 of life (8F100TP, 15F100TP), 8- and 15-day-old males (8M, 15M) and 8M and 15M castrated on day 1 (8MC, 15MC).

Glucose tolerance and risk of gestational diabetes mellitus in nulliparous women who smoke during pregnancy.

Gestational diabetes mellitus has been associated with adverse maternal and infant outcomes, including preeclampsia and fetal macrosomia. Although cigarette smoking has been associated with increased insulin resistance, its effect on gestational diabetes mellitus risk is uncertain. The authors evaluated the effects of smoking on glucose tolerance in a cohort of pregnant women who participated in the Calcium for Preeclampsia Prevention trial, a randomized study of nulliparous women conducted in five US medical centers from 1992 to 1995.

The influence of obesity and diabetes on the risk of cesarean delivery.

Objective: To determine the influence of pregravid obesity and diabetes on cesarean delivery (CD) risk.

Study Design: Women with singleton pregnancies of 23 weeks or more estimated gestational age who were undergoing a trial of labor January 1997 through June 2001 were categorized by pregravid body mass index (underweight [<19.8 kg/m 2 ], normal [19.

The influence of obesity and diabetes on the prevalence of macrosomia.

Objective: This study was undertaken to determine the relative contribution of abnormal pregravid maternal body habitus and diabetes on the prevalence of large-for-gestational-age infants.

Study Design: Maternal and neonatal records for singleton term (> or =37 weeks' estimated gestational age) deliveries January 1997 through June 2001 were reviewed. Subjects were characterized by pregravid body mass index (BMI), divided into underweight (BMI <19.

Evaluation of body composition of large-for-gestational-age infants of women with gestational diabetes mellitus compared with women with normal glucose tolerance levels.

Objective: The purpose of this study was to determine whether there is a difference in body composition and the factors that are associated with fat mass in the large-for-gestational-age infants of women with gestational diabetes mellitus compared with the large-for-gestational-age infants of women with normal glucose tolerance levels.

Study Design: Large for gestational age was defined as weight >90th percentile for gestational age, race, and sex on the basis of our population's normative data. Anthropometric measurements and/or total body electrical conductivity estimated body composition that included fat mass, percent body fat, and lean body mass were obtained.

Reversal of insulin resistance postpartum is linked to enhanced skeletal muscle insulin signaling.

The restoration of maternal insulin sensitivity postpartum represents an important physiological and metabolic adaptation in a woman's reproductive lifespan. The present study was conducted to examine the potential cellular mechanisms underlying the changes in insulin sensitivity from late pregnancy to postpartum in human skeletal muscle. Nine nonobese women (age, 32 +/- 2 yr; body mass index, 21.

Structure-affinity studies for a novel series of homochiral naphtho and tetrahydronaphtho analogues of alpha 1 antagonist WB-4101.

A number of enantiomeric pairs of naphthodioxane, tetrahydronaphthodioxane and naphthoxy analogues of WB-4101 (1) were designed and synthesized in order to improve the selectivity profile of the parent compound, hopefully in favour of the alpha(1a)-AR with respect to the other two alpha(1) subtypes and the 5-HT(1A) receptor. The new compounds 2-8 and, in addition, the two enantiomers of 1 were tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT(1A) receptor. Two of them, namely the naphtho- and tetrahydronaphthodioxane derivatives (S)-2 and (S)-3, showed lower, but significantly more specific alpha(1a) affinity than (S)-1, while the two enantiomers of the 2-methoxy-1-naphthoxy analogue 6 maintained most of the very high alpha(1a) affinity of (S)-1 and its alpha(1a) versus alpha(1b) selectivity slightly increasing the alpha(1a)/alpha(1d) and alpha(1a)/5HT(1A) affinity ratios.

Under-reporting of alcohol consumption in household surveys: a comparison of quantity-frequency, graduated-frequency and recent recall.

Aim: To compare alternative survey methods for estimating (a) levels of at risk alcohol consumption and (b) total volume of alcohol consumed per capita in comparison with estimates from sales data and to investigate reasons for under-reporting.

Setting: The homes of respondents who were eligible and willing to participate.

Participants: A total of 21,674 Australians aged 14 years and older.

Treatment with a novel poly(ADP-ribose) glycohydrolase inhibitor reduces development of septic shock-like syndrome induced by zymosan in mice.

Objective: Poly(ADP-ribose) is synthesized from nicotinamide adenine dinucleotide by poly(ADP-ribose) polymerase (PARP) and degraded by poly(ADP-ribose) glycohydrolase (PARG). The activation of the PARP/PARG pathway has been found in a variety of animal models of diseases, including septic shock-like syndrome. We have previously demonstrated that PARP inhibition by 3-ami-nobenzamide or GPI 6150 ameliorates multiple organ dysfunctions induced by zymosan.

Longitudinal changes in energy expenditure and body composition in obese women with normal and impaired glucose tolerance.

Our primary objective was to evaluate changes in energy expenditure and body composition in women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). A secondary objective was to examine the relationship between maternal leptin and nutrient metabolism. Fifteen obese women, eight with NGT and seven with GDM, were evaluated before conception (P), at 12-14 wk (E), and at 34-36 wk (L).

The minimally invasive sinus technique: theory and practice.

Minimally invasive sinus technique (MIST) is a targeted endoscopic intervention, introduced in 1994, with goals virtually identical to those originally reported for FESS but with distinct differences. The procedure, as outlined in the following section, is the only stepwise intranasal intervention with a defined beginning and end for all patients regardless of disease severity, thereby standardizing the procedure for surgeons and patients alike. This elegant, reproducible method avoids unnecessary disruption of normal mucosa while restoring mucociliary clearance through the primary birth ostia and reduces operative morbidity.

[Indications and results of the first 100 liver resections in Bolzano].

The aim of the study was to report on a survey of 100 liver resections performed over an 8-year period. Seventy-four patients underwent surgery for primary or secondary liver tumours, 15 for benign diseases, and 11 for traumas. The overall operative mortality rate was 3.

Exact analysis of dose response for multiple correlated binary outcomes.

The neurotoxicity of a substance is often tested using animal bioassays. In the functional observational battery, animals are exposed to a test agent and multiple outcomes are recorded to assess toxicity, using approximately 40 animals measured on up to 30 different items. This design gives rise to a challenging statistical problem: a large number of outcomes for a small sample of subjects.

Personal exposures to particles and their relationships with personal activities for chronic obstructive pulmonary disease patients living in Boston.

An exposure study of 18 subjects with chronic obstructive pulmonary disease (COPD) living in the Boston, MA, area was conducted. The objective was to examine determinants of personal exposures to particulate matter (PM) with aerodynamic diameters of less than 2.5 microm (PM2.

Minimally invasive sinus technique: what is it? Should we consider it?

Purpose Of Review: To understand the theory and application of the surgical model for endoscopic sinus surgery termed minimally invasive sinus technique (MIST). In simple terms: What is MIST? When should we use it? Does it work?

Recent Findings: Several recent publications have addressed the efficacy of MIST. Using reliable outcome instruments and a 23-month follow-up period, results following MIST were found to equal or surpass those following functional endoscopic sinus surgery (FESS).

Increased fetal adiposity: a very sensitive marker of abnormal in utero development.

Objective: Because offspring of women with gestational diabetes mellitus have an increased risk of obesity and diabetes mellitus as young adults, our purpose was to characterize body composition at birth in infants of women with gestational diabetes mellitus and normal glucose tolerance.

Study Design: One hundred ninety-five infants of women with gestational diabetes mellitus and 220 infants of women with normal glucose tolerance had anthropometric measurements and total body electrical conductivity body composition evaluations at birth. Parental demographic, anthropometric, medical and family history data, and diagnostic glucose values were used to develop a stepwise regression model that related to fetal growth and body composition.