Mortality from cancer and other causes in commercial airline crews: a joint analysis of cohorts from 10 countries.

BACKGROUND: Commercial airline crew is one of the occupational groups with the highest exposures to ionising radiation. Crew members are also exposed to other physical risk factors and subject to potential disruption of circadian rhythms. METHODS: This study analyses mortality in a pooled cohort of 93 771 crew members from 10 countries. The cohort was followed for a mean of 21.7 years (2.0 million person-years), during which 5508 deaths occurred. RESULTS: The overall mortality was strongly reduced in male cockpit (SMR 0.56) and female cabin crews (SMR 0.73). The mortality from radiation-related cancers was also reduced in male cockpit crew (SMR 0.73), but not in female or male cabin crews (SMR 1.01 and 1.00, respectively). The mortality from female breast cancer (SMR 1.06), leukaemia and brain cancer was similar to that of the general population. The mortality from malignant melanoma was elevated, and significantly so in male cockpit crew (SMR 1.57). The mortality from cardiovascular diseases was strongly reduced (SMR 0.46). On the other hand, the mortality from aircraft accidents was exceedingly high (SMR 33.9), as was that from AIDS in male cabin crew (SMR 14.0). CONCLUSIONS: This large study with highly complete follow-up shows a reduced overall mortality in male cockpit and female cabin crews, an increased mortality of aircraft accidents and an increased mortality in malignant skin melanoma in cockpit crew. Further analysis after longer follow-up is recommended.

Diet and cataract: a case-control study.

We conducted a case-control study to assess the association between diet and risk of cataract in Athens, Greece. Totals of 314 cases and 314 frequency-matched controls of both sexes, aged 45-85 years and attending the ophthalmology department of a major teaching hospital in Athens, Greece, were included in the study. All participants were interviewed using a semi-quantitative food-frequency questionnaire, covering the average frequency of consumption of about 120 food items. Analyses were conducted through multiple logistic regression. The analysis was carried out taking cataract as a general outcome (all types of cataract combined) and repeated by the specific type of cataract. We found significant inverse associations of cataract with dietary consumption of fish (OR = 0.69, p < 0.001), vegetables (OR = 0.47, p < 0.001), fruits (OR = 0.53, p < 0.001), and potatoes (OR = 0.76, p = 0.004), while consumption of meat was positively associated with cataract (OR = 1.46, p = 0.001). High intake of total fat (OR = 2.00, p < 0.001) and cholesterol (OR = 1.65, p < 0.001) increased the risk of cataract. There was a protective association between cataract risk and intake of carbohydrates (OR = 0.39, p < 0.001), carotene (OR = 0.56, p < 0.001), vitamins C and E (OR = 0.50, p < 0.001 and OR = 0.50, p < 0.001 respectively). We identified an association between the risk of cataract and several food groups and nutrients. Diets rich in fruits, vegetables, fish, pulses and starchy foods may protect against cataract. In addition, high intake of vitamins C and E and carotene with reduction of intake in total fat and cholesterol may be beneficial. Dietary advice along these lines may provide adequate public health guidelines for the delay of age-related cataract.

Reliability and validity of the KIDSCREEN-52 health-related quality of life questionnaire in a Greek adolescent population.

BACKGROUND: The KIDSCREEN-52 is a worldwide instrument for measuring health-related quality of life (HRQoL) in children and adolescents. The aim of this study is to assess reliability and validity of the Greek version of KIDSCREEN. METHODS: Questionnaires were collected from a representative nationwide sample of 1,194 adolescents aged from 11 to 17 years. Internal consistency reliability was determined by calculation of the Cronbach α coefficient. A confirmatory factor analysis (CFA) was conducted in order to test the construct validity of the questionnaire. Validity was further examined by investigating the correlation of KIDSCREEN with the Strengths and Difficulties Questionnaire (SDQ) and its association with socioeconomic and health-related factors. RESULTS: Internal consistency reliability was accepted with a Cronbach α above 0.73 for all KIDSCREEN dimensions. CFA showed that the ten-dimensional model fitted the data well (root mean square error of approximation (RMSEA) = 0.048, comparative fit index (CFI) = 0.971 and goodness of fit index (GFI) = 0.965). Correlation coefficients between KIDSCREEN and SDQ dimensions were significant. Adolescents of low socioeconomic status reported lower scores in the majority of KIDSCREEN dimensions. Also, adolescents with chronic health problem had poorer quality of life concerning physical well-being and other dimensions of KIDSCREEN. CONCLUSIONS: The Greek version of KIDSCREEN-52 was found to have satisfied psychometric properties and could be suitable for assessing HRQoL in Greek adolescents.

High prevalence of autonomous aldosterone secretion among patients with essential hypertension.

BACKGROUND: Previous studies based on standard endocrine testing have generally shown a low prevalence of primary aldosteronism, a form of autonomous aldosterone secretion (AAS), in hypertensive individuals. The purpose of this case-control study was to evaluate whether use of appropriately defined controls and combined testing reveal previously undetected AAS in hypertensives. MATERIALS AND METHODS: We investigated aldosterone secretion in 180 hypertensives with (n = 44) and without (n = 136) adrenal adenomas on computerized tomography (CT) and 72 matched nonhypertensive individuals with normal adrenal CT. Serum aldosterone and active renin were measured, and the aldosterone/active renin ratio was calculated before and after a modified fludrocortisone-suppression test (FST). In the latter, to eliminate any stimulatory effect of endogenous stress-induced adrenocorticotrophin hormone on aldosterone secretion, we administered 1 mg of dexamethasone on the last day of the classical FST fludrocortisone/dexamethasone suppression test (FDST). RESULTS: Using the 97·5 percentiles of serum aldosterone (74 pM L(-1)) and the aldosterone/renin ratio (32 pM L(-1) mU(-1) L(-1)) values obtained from the controls following the FDST, normal cut-off values indicative of adequate aldosterone suppression were established. Using the combination of these cut-offs, the estimated prevalence of AAS in patients with hypertension was 31%. Multiple linear regression analysis revealed a significant correlation between systolic and/or diastolic arterial blood pressure and the aldosterone value (P < 0·0001 and P < 0·01, respectively) and/or the aldosterone/renin ratio (P < 0·0001 and P < 0·01, respectively), which were obtained following the FDST. CONCLUSIONS: By applying new cut-offs obtained following modification of standard testing, AAS is quite prevalent in hypertensive individuals and correlates highly with arterial blood pressure. This may have relevance for both the aetiology of the hypertension and its optimal therapy.

Flavonoid intake and liver cancer: a case-control study in Greece.

In the context of a case-control study undertaken in Greece, we examined the role of six flavonoid classes in the etiology of hepatocellular carcinoma (HCC), by viral status, and of cholangiocarcinoma (CAC). Data and blood samples were collected between 1995 and 1998. Information about dietary intakes and covariates, including chronic infection with hepatitis B (HBV) and C (HCV) virus, were available for 250 HBV and/or HCV positive HCC cases, 83 HBV and HCV negative HCC cases, six CAC cases, and 360 hospital controls. In logistic regression models including gender, age, education, tobacco smoking, and total energy intake, there were no distinct patterns with respect to either HCC virus positive and HCC virus negative in relation to total flavonoids or any class of flavonoids, with the exception of flavones. Flavone intake, mostly derived from spinach and peppers, was inversely associated with both virus positive (P-trend, 0.049) and virus negative (P-trend, 0.084) HCC. There was also a suggestion of an inverse association of CAC with flavan-3-ols, anthocyanidins, and total flavonoids which, however, has to be taken with due caution on account of the small number of cases of this rare tumor. We conclude that flavones may be inversely associated with HCC risk, irrespective of its dominant etiology (viral or non viral).

Bone mass density and associated factors in cystic fibrosis patients of young age.

AIM: To investigate bone mineral status in young cystic fibrosis (CF) patients and determine risk factors related with the development of low bone mineral density (BMD). METHODS: We determined, in 81 patients with CF, 4 to 23-years-old, BMD as well as factors, which are thought to play a role in the development of reduced BMD. RESULTS: BMD Z-score was between -1 and -2.5 in 27 (33%) and lower than -2.5 in 9 (11%). Means of BMD Z-score were lower than the expected value of 0 in the three groups of children, adolescents and young adults (P = 0.004; P < 0.001; P = 0.048, respectively), but they did not differ among them (P = 0.114). Analysis showed that Shwachman-Kulczycki (SK) score, gender and levels of 25-hydroxy-vitamin D were significant predictors of BMD Z-score. Significant also was the interaction between gender and SK score. CONCLUSIONS: Our study supports that BMD may be reduced from a young age in CF patients though this needs to be confirmed using true volumetric measures of BMD. This defect is related to disease severity with males being more vulnerable. Inefficient levels of vitamin D are very common and contribute significantly to impaired bone health. The latter finding underlines the need for higher supplementation doses.

Management and postoperative outcome in primary lung cancer and heart disease co-morbidity: a systematic review and meta-analysis.

BACKGROUND: Co-morbidity of primary lung cancer (LC) and heart disease (HD), both requiring surgical therapy, characterizes a high risk group of patients necessitating prompt diagnosis and treatment. The aim of this study is the review of available evidence guiding the management of these patients. METHODS: Postoperative outcome of patients operated for primary LC (first meta-analysis) and for both primary LC and HD co-morbidity (second meta-analysis), were studied. Parameters examined in both meta-analyses were thirty-day postoperative mortality, postoperative complications, three- and five-year survival probabilities. The last 36 years were reviewed by using the PubMed data base. Thirty-seven studies were qualified for both meta-analyses. RESULTS: The pooled 30-day mortality percentages (%) were 4.16% [95% confidence interval (CI): 2.68-5.95] (first meta-analysis) and 5.26% (95% CI: 3.47-7.62) (second meta-analysis). Higher percentages of squamous histology and lobectomy, were significantly associated with increased (P=0.001) and decreased (P<0.001) thirty-day postoperative mortality, respectively (first meta-analysis). The pooled percentages for postoperative complications were 34.32% (95% CI: 24.59-44.75) (first meta-analysis) and 45.59% (95% CI: 35.62-55.74) (second meta-analysis). Higher percentages of squamous histology (P=0.001), lobectomy (P=0.002) and p-T1 or p-T2 (P=0.034) were associated with higher proportions of postoperative complications (second meta-analysis). The pooled three- and five- year survival probabilities were 68.25% (95% CI: 45.93-86.86) and 52.03% (95% CI: 34.71-69.11), respectively. Higher mean age (P=0.046) and percentage lobectomy (P=0.009) significantly reduced the five-year survival probability. CONCLUSIONS: Lobectomy and age were both accompanied by reduced five-year survival rate. Also, combined aorto-coronary bypass grafting (CABG) with lobectomy for squamous pT1 or pT2 LC displayed a higher risk of postoperative complications. Moreover, medical decision between combined or staged surgery is suggested to be individualized based on adequacy of coronary arterial perfusion, age, patient's preoperative performance status (taking into account possible co-morbidities per patient), tumor's staging and extent of lung resection.

Circulating angiogenic factors during periovulation and the luteal phase of normal menstrual cycles.

OBJECTIVE: To measure serial serum concentrations of the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG) in the periovulatory and secretory phase of normal menstrual cycles in healthy women and to determine their peaks, which might reflect the stage of their critical angiogenic action. DESIGN: Prospective study. SETTING: University departments of obstetrics and gynecology. PARTICIPANT(S): Thirty-three healthy Swedish women with regular menstrual cycles. INTERVENTION(S): Serial blood samples were collected from each woman. Luteinizing hormone surge was identified by testing morning urine. MAIN OUTCOME MEASURE(S): Circulating levels of VEGF, bFGF, and ANG. RESULT(S): Circulating peak concentrations were determined for VEGF on day 0 and 9 after ovulation, for bFGF on day 1 before ovulation and day 9 after ovulation, and for ANG on day 3 after ovulation. CONCLUSION(S): Circulating VEGF increased in a stage-dependent cyclic fashion. Basic FGF peaked during the late proliferative and mid secretory phase. Circulating ANG showed increased expression around the early secretory phase of the cycle.

The influence of indomethacin co-administration on ofloxacin levels in plasma and cerebrospinal fluid in rats.

The possible increase of ofloxacin levels in serum and cerebrospinal fluid (CSF) by concomitant indomethacin administration was investigated in 120 healthy adult rats. The animals were administered intramuscular doses of ofloxacin 30 mg/kg alone (Group A, n = 60) or with indomethacin 2 mg/kg (Group B, n = 60). Blood and CSF samples were obtained from both groups at 30, 45, 60 and 90 min post-administration. Concentrations of ofloxacin were estimated using a microbiological assay. Co-administration of indomethacin did not affect plasma levels of ofloxacin significantly; however, higher levels were found in all CSF samples after co-administration with indomethacin, particularly after 90 min with 0.59 microg/ml versus zero median values when only ofloxacin was administered (P = 0.05). No central nervous system adverse effects were observed clinically. No correlation between levels of ofloxacin in plasma and CSF could be established either in rats administered only ofloxacin or in rats administered both drugs. The presented pharmacokinetic findings revealed that co-administration of ofloxacin and indomethacin may result in protracted quinolone levels in the CSF. However, the absence of significant correlation between concentrations of ofloxacin in plasma and CSF upon co-administration of indomethacin, as well as of central nervous system adverse effects, make the probability of an epileptogenic interaction between them unlikely. These results merit further clinical evaluation.

Secular growth changes in the Hellenic population in the twentieth century.

Statural growth is dependent on hereditary and environmental factors, i.e disease, nutrition. The improvement of socioeconomic conditions that took place during the 20th century resulted in a secular trend towards greater height and earlier sexual maturation. Greek society has changed dramatically from a mainly agricultural society at the beginning of the 20th century to a mainly urban one in the second half of the century, and during this period Greece became a developed country. The various studies examining the height of children living in Athens during this period show a gradual increase in the height of children, the difference of the mean height between 2001 and 1928 being 11.8 cm and 7.3 cm for 17 year old boys and girls, respectively. The difference in mean height was present at all ages. The difference in final height was mainly due to prepubertal growth. Girls at the age of 10 and boys at 11 years were about 8 cm taller in 2001 than in 1928. A growth study carried out on conscripts in 1990 found no significant difference in the height of males coming from urban or rural areas of the country, whereas such a difference was detected in 1968, rural men being significantly shorter than urban ones in 1968. There are only a few studies on the sexual maturation of Greek children. The available data suggest a secular trend towards earlier puberty in females; however, this can not be substantiated for males. Menarcheal age in Greek girls showed a positive secular change that is in agreement with the observed trend for earlier pubertal maturation in girls. In conclusion, Greek children in the 20th century experienced a positive secular trend in stature which also includes final height. A secular trend for earlier sexual maturation can be shown only for girls.

Intratympanic and systemic steroids for sudden hearing loss.

OBJECTIVE: To investigate the therapeutic efficacy of intratympanic dexamethasone combined with systemic prednisolone in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Prospective, quasirandomized, multicenter clinical trial. SETTING: One university hospital and 2 affiliated hospitals. PATIENTS: A total of 92 eligible patients with ISSNHL were allocated into 2 groups. Patients in the control group were treated with systemic prednisolone alone. Patients of the combined treatment group received additionally 3 intratympanic dexamethasone injections within 5 days. MAIN OUTCOME MEASURES: The main outcome measures used were the differences between pretreatment and posttreatment pure-tone audiometry averages (PTAs) and speech discrimination scores (SDSs). Successful treatment was defined as a greater than 10 dB improvement in PTA and 15% in SDS. The final assessment of hearing was performed 3 months after completion of treatment. RESULTS: Significant hearing recovery was observed in 31 (67.39%) of 46 cases, and in 24 (52.17%) of 46 control patients. Patients receiving combination therapy had a median improvement in PTA of 23.12 dB and a median increase in SDS of 32%. In the control group, the median hearing gain was 16.87 dB and 18%, respectively. The differences between the 2 groups were not statistically significant (p = 0.10 and p = 0.13). However, after performing a post hoc analysis by excluding individuals with profound hearing loss (PTA, >90 dB), the combined treatment group showed significant improvement compared with the control group (p = 0.04). No serious complications or adverse reactions were reported. CONCLUSION: The addition of intratympanic steroids to the conventional systemic steroid therapy may provide a safe and potentially effective therapeutic option in patients with mild-to-severe ISSNHL.

Vascular endothelial growth factor inhibitors for treatment of corneal neovascularization: a meta-analysis.

PURPOSE: To evaluate the therapeutic effect of bevacizumab (Avastin) on corneal neovascularization (NV). METHODS: Systematic review and meta-analysis of the literature was performed. Seven eligible clinical human studies and 18 eligible experimental animal studies examining the effectiveness of bevacizumab treatment on corneal NV were included in the meta-analysis. Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened, and data were extracted from each eligible study. The random-effects model (of DerSimonian and Laird) was used to combine the results from the selected studies. Heterogeneity was explored using available data. Publication bias was also assessed. RESULTS: A significant reduction of corneal neovascularized area was seen in clinical human studies, with a pooled reduction of 36% [95% confidence interval (CI), 18%-54%] overall, of 32% (95% CI, 10%-54%) for subconjunctival anti-vascular endothelial growth factor injections, and 48% (95% CI, 32%-65%) for topical treatment. Pooled mean change in best-corrected visual acuity showed an improvement in best-corrected visual acuity by 0.04. The summary standardized mean difference in animal studies indicated a statistically significant reduction in the area of corneal NV when treated with bevacizumab compared with the control group by -1.71 (95% CI, -2.12 to -1.30). The subtotal pooled standardized mean differences were -1.83 (95% CI, -2.38 to -1.28) for subconjunctival anti-vascular endothelial growth factor injections and -1.50 (95% CI, -1.88 to -1.12) for topical treatment. CONCLUSION: Our results suggest that both topical and subconjunctival bevacizumab achieve significant reduction in the area of corneal NV. This meta-analysis provides an evidential basis for the new therapeutic concept of treating corneal NV with antiangiogenic therapy.

The epidemiology of cataract: a study in Greece.

PURPOSE: We conducted a case-control study to identify risk factors for cataract in the Mediterranean Greek population. Three hundred and fourteen cases and 314 frequency-matched controls of both genders, aged 45-85, attending the ophthalmology department of a major teaching hospital in Athens, Greece, were included in the study. METHODS: Cases were medically diagnosed and classified. Controls were healthy visitors without cataract. A detailed questionnaire, covering demographic, socioeconomic, somatometric, lifestyle and medical history variables, provided data on possible risk factors for cataract. Analyses were conducted through multiple logistic regression. MAIN OUTCOME MEASURES: Cataract overall and by type: nuclear, cortical and posterior subcapsular (PSC). RESULTS: Statistically significant increased risk for cataract overall was found for current (OR = 1.99, 95%CI: 1.23-3.23) and ex-smokers (OR = 1.64, 95%CI: 1.02-2.70), history of coronary heart disease (OR = 2.25, 95%CI: 1.43-3.55), family history of ophthalmologic diseases (OR = 1.51, 95%CI: 1.03-2.20) and higher sunlight exposure at the beach (OR = 2.26, 95%CI: 1.37-3.72) as well as at work (OR = 2.03, 95%CI: 1.32-3.12). Use of measures protecting against sunlight at the beach, i.e. hat (OR = 0.58, 95%CI: 0.39-0.85) and vision repair spectacles (OR = 0.44, 95% CI: 0.30-0.65), were associated with reduced risk. RESULTS for cataract overall were also evident for the nuclear type and in most circumstances for PSC type, but were only suggestive for the cortical type of cataract. CONCLUSION: We identified certain possible risk factors for age-related cataract. In a Mediterranean Greek population, we found that smoking, use of cortisone drops, cardiovascular heart disease and sunlight exposure increase the risk for cataract, while use of hat and vision repair spectacles act protectively.

Intratympanic steroid therapy for sudden hearing loss: a review of the literature.

OBJECTIVE: Administration of steroids systematically is considered to be the most commonly accepted treatment for idiopathic sudden sensorineural hearing loss (ISSNHL). In recent years there has been increasing scientific interest in treating ISSNHL by means of local steroid delivery. Usually, intratympanic steroids are used in three main protocols, as initial treatment, as adjunctive treatment given concomitantly with systemic steroids and as salvage treatment after failure of standard therapy. The purpose of this review is to examine the published literature regarding the therapeutic value of each method of treatment and to seek answers about the best delivery technique and the optimal administration schedule. DATA SOURCES: Literature review from 1996 to 2009, PubMed and Medline. STUDY SELECTION: We searched for trials concerning clinical evaluation of intratympanic steroids in ISSNHL patients, as a salvage treatment, as a first line therapy and in combination with the conventional therapy. Randomized and non-randomized case control studies and case series studies were the types of trials available for review. DATA EXTRACTION: All the articles described in the study selection were used for this review. DATA SYNTHESIS: Statistical techniques were not used. CONCLUSION: On the basis of the available literature, it seems that topical steroids can be a valuable solution for ISSNHL patients who either cannot tolerate systemic steroid therapy or are refractory to it. Concerning the combined therapy, due to the controversial results of the existing studies, it cannot be determined yet whether this treatment protocol could yield superior results as a first line therapy. The need for establishment of standard criteria of hearing recovery should be underlined.

Multiplex RT-PCR-based detections of CEA, CK20 and EGFR in colorectal cancer patients.

AIM: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting circulating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. METHODS: Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival. Median follow-up period was 19 mo (range 8-28 mo). RESULTS: Rates of CEA, CK20 and EGFR detection in CRC patients were 95.5%, 78.4% and 19.3%, respectively. CEA transcripts were detected in 3 healthy volunteer samples (7.5%), whereas all control samples were tested negative for CK20 and EGFR transcripts. The increasing number of positive detections for CEA, CK20 and EGFR transcripts in each blood sample was positively correlated with Astler-Coller disease stage (P < 0.001) and preoperative serum levels of CEA (P = 0.029) in CRC patients. Data analysis using Kaplan-Meier estimator documented significant differences in the overall survival of the different CRC patient groups as formed according to the increasing number of positivity for CEA, CK20 and EGFR transcripts. CONCLUSION: These data suggest that multiplex RT-PCR assay can provide useful information concerning disease stage and overall survival of CRC patients.

Logistic Regression and Linear Discriminant Analyses in Evaluating Factors Associated with Asthma Prevalence among 10- to 12-Years-Old Children: Divergence and Similarity of the Two Statistical Methods.

Logistic regression and discriminant analyses are both applied in order to predict the probability of a specific categorical outcome based upon several explanatory variables (predictors). The aim of this work is to evaluate the convergence of these two methods when they are applied in data from the health sciences. For this purpose, we modeled the association of several factors with the prevalence of asthma symptoms with both the two methods and compared the result. In conclusion, logistic and discriminant analyses resulted in similar models.

Occupational physical activity in relation with prostate cancer and benign prostatic hyperplasia.

Using data from two case-control studies undertaken in Athens, Greece from 1994 to 1997, we have examined the association of occupational physical activity with the risk of prostate cancer and benign prostatic hyperplasia (BPH). Cases consisted of 320 patients with histologically confirmed incident prostate cancer and 184 patients with surgically treated BPH. Controls were 246 patients hospitalized for minor conditions. Occupations before retirement were classified, independently and blindly as to case-control status, into high, medium, and low physical activity levels. After fine controlling for years of schooling, there was a suggestive inverse association of physical activity with prostate cancer (P for trend 0.12) and a significant one with BPH (P for trend 0.04). The odds ratio (95% confidence interval) for high versus low activity was 0.69 (0.40-1.22) for prostate cancer and 0.59 (0.31-1.11) for BPH. The association of physical activity with both conditions tended to be more pronounced among men 65 years old or younger. Given the high frequency of occurrence of the examined conditions in the male population and our limited knowledge about other modifiable risk factors, preventive measures may have to focus on increasing physical activity.

Angiopoietin-2 in the perinatal period and the role of intrauterine growth restriction.

BACKGROUND: Angiopoietin-2, an angiogenic factor, causing destabilization and postnatal remodeling of blood vessels, is upregulated by hypoxia. We hypothesized that circulating Angiopoietin-2 levels might differ in intrauterine growth restricted and appropriate for gestational age fetuses and neonates, as the former have restricted growth and development and suffer from in utero hypoxia. METHODS: This is a prospective, controlled study, including forty asymmetric, mainly due to hypertension or pre-eclampsia intrauterine growth restricted (0-9 customized centiles, corrected for gestational age, sex, maternal weight, height, ethnic group, and parity), and 20 appropriate for gestational age (42-82 customized centiles) full-term infants, as well as their mothers. Blood samples were drawn from mothers, from the doubly clamped umbilical cord (mixed arteriovenous blood, representing fetal state), and from neonates on days 1 (N1) and 4 (N4) of life (representing transition and stabilization to extrauterine life, respectively). Circulating angiopoietin-2 levels were measured by enzyme immunoassay and the statistical analysis involved t-test and Pearson correlation. RESULTS: Angiopoietin-2 levels were significantly higher in intrauterine growth restricted cases only in N4 (p = 0.04). No dependence on the mode of delivery and gender was documented. CONCLUSIONS: These findings may suggest that intrauterine hypoxia possibly does not upregulate circulating angiopoietin-2 levels in intrauterine growth restricted fetuses and day 1 neonates; however, increased angiopoietin-2 on N4, after stabilization to extrauterine life, might signify initiation of catch-up growth-related angiogenesis and stimulation of angiogenic factors, granted that angiopoietin-2 is critically involved in postnatal vascular remodeling.

A pooled analysis of bladder cancer case-control studies evaluating smoking in men and women.

OBJECTIVE: A recent study suggested that risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes. We pooled primary data from 14 case-control studies of bladder cancer from Europe and North America and evaluated differences in risk of smoking by gender. METHODS: The pooled analysis included 8316 cases (21% women) and 17,406 controls (28% women) aged 30-79 years. Odds ratios (ORs) and 95% confidence intervals (95% CI) for smoking were adjusted for age and study. Exposure-response was evaluated in a stratified analysis by gender and by generalized additive models. RESULTS: The odds ratios for current smokers compared to nonsmokers were 3.9 (95% CI 3.5-4.3) for males and 3.6 (3.1-4.1) for females. In 11 out of 14 studies, ORs were slightly higher in men. ORs for current smoking were similar for men (OR = 3.4) and women (OR = 3.7) in North America, while in Europe men (OR = 5.3) had higher ORs than women (OR = 3.9). ORs increased with duration and intensity in both genders and the exposure-response patterns were remarkably similar between genders. CONCLUSION: These results do not support the hypothesis that women have a higher relative risk of smoking-related bladder cancer than men.