Assessment of long-term exposure to airborne dioxin and cadmium concentrations in the Lyon metropolitan area (France).

Identifying the long-term effects of airborne pollutants requires the computation of the spatial and temporal variability of their concentration in air to estimate the exposure of the population. To estimate exposure levels of individuals in a breast cancer case control study nested in a national prospective cohort, we determine here the differential impact of a variety of cadmium and dioxin sources on urban air over a large urban area and over a period of almost 20years. To that end, we couple an emission model, to estimate dioxin and cadmium atmospheric annual releases, with an urban dispersion model in order to compute pollutant concentration fields at a fine temporal (1h) and spatial (25m) resolution. The reliability of the modelling chain is compared to two types of measurement: i) localized industrial emissions and ii) dioxin and cadmium air monitoring data (from 2007 to 2008), collected at a fixed station, placed in the city centre, as well as at three mobile short-term dioxin monitoring stations, located in the suburbs (the latter providing dioxin data, only). Comparisons between measured and estimated emissions show non-negligible difference, with a correlations for dioxin (rs=0.42) and cadmium (rs=0.41). Despite this, mean values between estimated emissions and emission measurements are close to each other, in particular for cadmium. Weekly average modelled concentrations show an overall good agreement with weekly average measured concentrations in spring and summer but are generally lower than monitored data in winter due to peak concentrations from diffuse sources representing an important proportion of emissions in 2007/2008. The model provides better results for cadmium than for dioxin. Despite the relevant errors in the model predictions, the model meets the validation criteria, defined by Chang and Hanna for an urban dispersion model. Simulation scenarios of air pollutant concentrations, reconstructed over the last 20years, show the effects of the variability of the pollutant sources over time with decreasing levels of dioxin and cadmium concentrations in air. This is primarily due to the reduction in localized industrial releases, which results in a general trend of homogenization of the exposure of the population. The model further allows us to dissociate the contribution of different types of pollutant sources on the population exposure. The impact on local concentrations due to industrial emissions, which were originally responsible for the major impact on air quality, is shown to drop over the years by 99% and 92% for dioxin and cadmium, respectively. Today, the major contributions are due to diffuse miscellaneous sources in the case of dioxin and to traffic-related emissions for cadmium. Average modelled concentrations at the study subjects' residential locations range from 10.2 to 82.1fg-TEQ/m3 for dioxin and 0.10 to 1.6ng/m3 for cadmium and are comparable with data from the literature. The study results will be essential to increase the accuracy of the assessment of long-term airborne dioxin and cadmium exposure and improve the results of epidemiological studies.

TNM staging and classification (familial and nonfamilial) of breast cancer in Jordanian females.

PURPOSE: Staging of breast tumor has important implications for treatment and prognosis. This study aims at pinpointing the frequency of each stage among familial and nonfamilial breast cancers. MATERIALS AND METHODS: Ninety-nine Jordanian females diagnosed with familial and nonfamilial breast cancer between 2000 and 2002 were enrolled in this study All breast cancer cases were staged according to the TNM classification into in situ, early invasive, advanced invasive and metastatic. RESULTS: Forty-three cases were familial breast cancer and 56 were nonfamilial. One female breast cancer was diagnosed with ductal carcinoma in situ (DCIS) cancer. Fifty cases were diagnosed in early stages of invasive breast cancer, of which 31 cases were familial, 29 cases were classified as advanced invasive, where 21 cases were nonfamilial and 19 cases were metastatic stage of breast cancer, with 16 nonfamilial cases. Stage 2b was the most common stage of early invasive cases and represented 48% of the early stage of breast cancer. On the other hand, among cases diagnosed with advanced invasive breast cancer, stage 3a was the most common stage and represented 89.6% of the advanced stage. Interestingly, all cases of stage 3a belonged to TNM stages of T2N2M0 and T3N1M0. The tumor size in all cases of Jordanian females diagnosed with advanced invasive breast cancer exceeded 2 cm in size due to selection bias from symptomatic women in our study. CONCLUSION: The incidence of nonfamilial breast cancer was slightly higher than that of the familial type amongst studied the Jordanian females studied. The early invasive stage of breast cancer was more common in the familial while the advanced invasive and metastatic breast cancer cases were encountered more often in the nonfamilial type. Our study was based on a small sample and symptomatic women. Therefore, more research with larger population samples is needed to confirm this conclusion.

Relationship between plasma progesterone, estradiol and prolactin concentrations and breast cancer in pre and postmenopausal women.

UNLABELLED: Hormones such as estrogen, progesterone and prolactin are implicated in anumber of ways as possible causes of breast cancer. Throughout women life cycle, breast development and function depend on complex critical interplay of these hormones. The acknowledged gaps in our understanding concerning progesterone, estrogen and prolactin hormones involvement in human breast cancer has exposed the need to conduct this study for better understanding of the role played by these hormones in breast cancer during pre and post menopause status in order to influence prevention and treatment of breast cancer. Ninety women were enrolled, (80%) of them were breast cancer patients and the other (20%) were breast benign lesion patients. At attending King Hussein Medical Center, blood samples were collected and analyzed for plasma estradiol, prolactin and progesterone. Of the 72 breast cancer patients (66.6% and 33.4%), and of the 18 breast benign patients (27.8% and 72.2%) were in menopause and premenopausal, respectively. Of the breast cancer and benign patients groups, 55.6% of each had an association with either high plasma estradiol, prolactin or progesterone concentrations. Of the breast cancer patients that had association with high plasma hormonal concentrations, 47.5% had high plasma estradiol concentrations (155.0+/-36 pg/ml) and 89.5% of these were in menopause. Of the breast benign patients, 60% had high plasma prolactin concentrations (55.2+/-10.6 ng/ml). Menopausal breast cancer is associated with high plasma estradiol concentrations, while premenopausal breast benign were associated high plasma prolactin concentrations which indicate that high plasma estradiol in menopause is arisk factor for breast cancer development while high prolactin in premenopausal is arisk factor for breast benign. Therefore, breast cancer and benign are highly hormonal dependent. KEYWORDS: breast cancer, premenopausal and postmenopausal, plasma hormones.

Body composition, nutrient intake and physical activity patterns in young women during Ramadan.

INTRODUCTION: Muslims abstain from food and fluid between the hours of sunrise to sunset, and usually eat a large meal after sunset and a lighter meal before sunrise. The purpose of this study was to assess body composition, nutrient intake and physical activity patterns during Ramadan fasting. METHODS: This study was carried out during Ramadan in October 2004. A total of 57 female subjects were recruited from The Hashemite University in Jordan. Body weight, fat percentage, muscle mass, and percentage body water content were measured, and body mass index (BMI) was calculated. Estimated food records over a duration of three days were used to assess the intake of energy, carbohydrates, protein, fat, and sugars before and during Ramadan fasting. Physical activity patterns were determined from a three-day activity diary before and during Ramadan fasting; the amount of physical activity was expressed as the physical activity level. RESULTS: Body weight and BMI decreased significantly during Ramadan fasting. The mean energy and nutrients intake before Ramadan (energy; percent carbohydrates:protein:fat was 1,252; 56:12:33) and during Ramadan (1,171; 56:13:34) were not significantly different. The mean physical activity level was 1.54 before Ramadan and 1.51 during Ramadan, and this was also not significantly different. CONCLUSION: This study revealed that there was a significant weight loss during Ramadan. Estimates of energy, carbohydrates, protein, fat and sugar did not change, despite the reduction in the number of meals taken. The overall activity patterns remained similar.

Endocrine abnormalities in hemodialysis patients with iron overload: reversal with iron depletion.

The endocrine function was studied in 9 hemodialysis patients with iron overload (IO) before and after iron depletion. Diagnosis of IO was established by high serum ferritin (> 1100 micrograms/L), high hepatic CT density (> 70 Hounsfield units), and excessive iron stores in bone marrow aspirate (grade 6). At the start of the study, 8 patients had gonadal failure, 6 of whom had hypothalamopituitary disease, and 4 manifested thyroid abnormalities. At the end of the study, the hypothalamopituitary function and thyroid abnormalities improved in all patients except one who manifested hypothalamic disease. Primary gonadal failure persisted in the 8 patients. ACTH stimulation produced adequate increments in plasma cortisol at the start and end of the study. Pancreatic (beta cell) function was adequate at the end of the study as shown by normal oral glucose tolerance test and free insulin increments during the test. The CT scan and follow-up indicated significant iron mobilization from the liver, pancreas, and the adrenal glands. Hormonal studies were repeated in 4 of the 5 patients who manifested endocrine abnormalities and had received recombinant human erythropoietin (rHuEPO), 3 mo after discontinuation of the drug. Improvement in the endocrine function persisted in those patients. Our results indicated that dialysis patients exposed to iron overload are at risk for development of multiple endocrine defects. Fortunately, aggressive iron depletion can mobilize iron from these organs and reverse some of the defects.

Endocrine abnormalities in patients with amyloidosis.

This study was conducted to examine systematically the endocrine function in 10 patients diagnosed to have renal amyloidosis. Basal and dynamic endocrine tests (GnRh, TRH, and ACTH stimulation tests as well as modified glucose tolerance test) were performed in all patients. Eight patients had advanced renal disease (creatinine clearance < 10 mL/min). Hypofunction of the thyroid gland was present in 5 out of those 8 patients, and thyroid biopsy confirmed amyloid deposition. Of those 5 patients, pituitary and adrenal defects were present in 2. In conclusion, endocrine abnormalities were evident at a later stage of renal amyloidosis. Hypothyroidism was present in all patients who manifested endocrine defects and should be considered as an early sign of endocrine involvement with the disease.

Erythropoietin treatment in haemodialysis patients with iron overload.

Erythropoietic response to exogenously administered recombinant human erythropoietin (rHuEpo) was examined in 11 maintenance haemodialysis patients with iron overload (IO). All had required numerous blood transfusions earlier (> 12 units/year). Diagnosis of IO was established by high serum ferritin (SF) levels (> 1,100 micrograms/l), high hepatic CT density (> 70 Hounsfield units; HU) and excessive iron stores in bone marrow aspirate (grade 6). None of the patients had osteitis fibrosa cystica, aluminium intoxication, haemoglobinopathy or haemochromatosis alleles (HLA A3, B7 and B14). All patients responded to rHuEpo treatment (target haemoglobin level of 9-10 g/dl). None of the patients required iron supplementation or developed 'functional anaemia'. During 30 +/- 3 months of therapy, the initial maintenance dose of rHuEpo (103 +/- 12 units/kg/week) and median SF levels (2,250 micrograms/l) fell (50 +/- 8 units/kg/week and 1,060 micrograms/l, respectively) (p = 0.0003 and 0.0007). The initial and final rHuEpo doses correlated well with the respective SF levels (r = 0.89, p < 0.001). The maintenance dose of rHuEpo required for patients with IO at the start of the treatment period was significantly higher than that (50 +/- 5 units/kg/week) required by a control group of patients with adequate iron stores (SF = 100-600 micrograms/l) who were matched for age, sex and frequency of previous blood transfusions (p = 0.002). The findings suggested that excessive IO caused relative resistance to erythropoiesis on exogenous administration of rHuEpo and that iron supplementation was not warranted during rHuEpo therapy in those patients.

Hormonal and metabolic effects of neuroglucopenia.

We examined the role of central neuroglucopenia, induced by intracerebroventricular (i.c.v.) administration of 2-deoxyglucose (2-DG), on glucose and amino acid kinetics in conscious dogs. Group 1 received i.c.v. 2-DG at 2.5 mg.kg-1 x min-1 for 15 min. Group 2 received an equal intravenous (i.v.) amount of 2-DG. In the i.c.v. group, plasma glucose levels rose from 106 +/- 4 mg/dl to a peak of 204 +/- 12 mg/dl by 90 min. Blood lactate increased from 689 +/- 1 to 2,812 +/- 5 mumol/l and blood alanine not change from basal (256 +/- 41 mumol/l). The rate of hepatic glucose production, determined isotopically, was increased 2-fold over basal (P < 0.01). Significant increases (P < 0.001) over basal were also noted in plasma epinephrine, norepinephrine, insulin, glucagon and cortisol. Leucine rate of appearance (Ra) showed a 30% decrease from basal to 2.4 +/- 0.05 mumol.kg-1 x min-1 (P < 0.01). In group 2 plasma glucose levels were not altered but plasma cortisol and glucagon showed a modest transient increase above basal (P < 0.05). No significant changes were noted in amino acid kinetics. These findings suggest that periventricular neuroglucopenia, in the absence of peripheral glucose deprivation, is accompanied by hyperglycemia secondary to enhanced hepatic glucose production with decreased glucose utilization and by increased hepatic uptake of gluconeogenic precursors. These, however, were not accompanied by increased whole body proteolysis as was previously seen with generalized glucopenia resulting from insulin-induced hypoglycemia.

The role of the central nervous system in modulating glucose and protein metabolism during insulin-induced hypoglycemia.

We previously established that insulin-induced hypoglycemia is associated with enhanced proteolysis with the GI tract being the major contributor to this response. In the present study we examined whether brain hypoglycemia modulates the changes in amino acid and glucose kinetics during insulin-induced hypoglycemia. Studies were performed in 24 h faster conscious dogs chronically fitted with catheters in the femoral artery, portal vein, hepatic vein, femoral vein and in both carotid and vertebral arteries, and that were also fitted with permanent tracheostomies. Following a 30 min basal period insulin was infused i.v. at 300 mU/kg.h to achieve systemic hypoglycemia averaging 42 +/- 2 mg/dl. In group I (n = 6) both central and systemic (global) hypoglycemia was allowed to develop. The rate of net hepatic glucose output (NHGO) increased by 50% above basal. Plasma leucine increased from 120 +/- 12 mumol/l basally to 154 +/- 30 mumol/l during the last hour of hypoglycemia. The rate of leucine appearance into the plasma compartment (R(a)) increased from 154 +/- 30 to 200 +/- 36 mumol/kg.h and its rate of oxidation increased from 22 +/- 5 to 51 +/- 8 mumol/kg.h, while its non-oxidative rate of disposal (141 +/- 12 mumol/kg.h) did not change. Net leucine balance across the gut was neutral (6 +/- 5 mumol/kg.h) and switched to net output of 96 +/- 24 mumol/kg.h. In group II (n = 5) 10% dextrose in water was infused into both carotid and vertebral arteries to prevent profound CNS glucopenia. This was associated with a drop in NHGO.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of alpha and beta adrenergic blockade on glucose and lactate metabolism during acute stress.

In this study we examined the role of alpha and beta blockade on glucose and lactate metabolism during the acute stress of insulin-induced hypoglycemia. Three groups of conscious dogs with chronically fitted catheters in the femoral artery and in the femoral, portal, and hepatic veins were studied after an 18-hr fast. After a 1-hr basal period, hypoglycemia was induced with insulin infusion at 5 mU/kg.min for 3 hr. Group 1 received no other treatment. Groups 2 and 3 received, respectively, phentolamine (8 micrograms/kg.min) and propranolol (4 micrograms/kg.min) beginning 30 minutes before and throughout the experimental period. Despite similar hyperinsulinemia, plasma glucose dropped in Group 1 (from 115 +/- 10 to 40 +/- 3 mg/dl) and in Group 2 (from 110 +/- 4 to 60 +/- 3 mg/dl) but in Group 3 it was maintained at 45 +/- 4 mg/dl by exogenous glucose infusion at a rate of 2.2 +/- 0.4 mg/kg.min. Hepatic glucose production increased 50 +/- 13%, 127 +/- 30%, and 55 +/- 30% in Groups 1, 2, and 3, respectively, within 60 minutes and was 56 +/- 19%, 55 +/- 17%, and -0.04 +/- 12% during the last hour of the experiment. Glucose utilization did not change in Groups 1 and 2 but it increased in Group 3. Plasma lactate increased in Group 1 (from 850 +/- 190 to 1,980 +/- 450 mumol/L) and in Group 2 (985 +/- 180 to 4,785 +/- 500 mumol/L), while in Group 3 there was an early rise (to 695 +/- 120 mumol/L) within 30 minutes that gradually dropped to near basal.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of insulin-induced hypoglycemia on protein metabolism in vivo.

The effects of insulin-induced hypoglycemia (IIH) on leucine kinetics (mumol.kg-1.min-1) and interorgan flow of amino acids (AA) were examined in 2 groups of 18-h fasted conscious dogs. Insulin was infused at 5 mU.kg-1.min-1 for 3 h. IIH (40 +/- 5 mg/dl) resulted in a drop in plasma leucine (114 +/- 10 to 64 +/- 9 microM) and leucine rate of appearance (Ra) (3.1 +/- 0.1 to 2.4 +/- 0.2) within 1 h but gradually increased (P less than 0.05) to 145 +/- 30 microM and 3.8 +/- 0.5 by 3 h. Leucine oxidative rate of disposal (Rd) increased from 0.44 +/- 0.08 to 1.02 +/- 0.35 (P less than 0.01), and nonoxidative Rd dropped initially but was near basal levels by 3 h. When euglycemia was maintained, there was sustained drop in plasma leucine from 122 +/- 12 to 42 +/- 6 mumol/l, leucine Ra from 3.1 +/- 0.4 to 1.8 +/- 0.2, oxidative Rd from 0.36 +/- 0.03 to 0.22 +/- 0.04, and nonoxidative Rd from 2.75 +/- 0.4 to 1.6 +/- 0.2 (all P less than 0.01). IIH was associated with a significant net release of leucine (and other AA) across the gut (0.04 +/- 0.05 to 1.86 +/- 0.30 mumol.kg-1.min-1; P less than 0.05). In the group with euglycemia there was no significant change in the gut balance of leucine. We conclude that IIH is associated with a proteolytic response and that the gut is the major contributor to this response.

Amino acids augment insulin's suppression of whole body proteolysis.

Leucine (LEU) kinetics were assessed using a primed-continuous infusion of L-[1-14C]LEU in normal overnight-fasted male volunteers during a basal period and an experimental period where insulin (INS) was infused at either 0.6, 1.2, 2.5, 5.0, 10, or 20 mU.kg-1.min-1 with euglycemia maintained. Two protocols were used: 1) subjects were allowed to develop hypoaminoacidemia or 2) plasma essential amino acids (AA) were maintained near basal levels by frequently monitoring plasma LEU in conjunction with variable infusions of an AA solution (LEU infused = 0.41, 0.72, 0.93, 1.03, 1.31, and 1.35 mumol.kg-1.min-1 at escalating INS doses, respectively). Basal rates of LEU appearance (Ra), nonoxidative disappearance (NORd) and oxidative disappearance (OXRd) were similar in both protocols (means = 1.74, 1.40, and 0.36 mumol.kg-1.min-1, respectively). INS infusions without AA resulted in a progressive decrement in LEU Ra (14 to 45%), NORd (16-41%), and OXRd (3-56%) compared with basal values. The infusion of AA resulted in an additional reduction in endogenous Ra (P less than 0.01; approximately 100% suppression achieved at plasma INS greater than 1,000 microU/ml) and a blunting of NORd reduction (P less than 0.05) at each dose of INS. Observed differences in INS's suppression of LEU Ra between the two protocols suggests the existence of a component of whole body proteolysis that is highly dependent on circulating plasma AA. Therefore, hypoaminoacidemia associated with INS treatment would appear to blunt the responsiveness of INS's suppression of protein breakdown and in the presence of near basal plasma AA, proteolytic suppression by INS is enhanced.

Effects of naloxone on glucose homeostasis during insulin-induced hypoglycemia.

The present study was designed to examine the role played by beta-endorphin in the physiological response to the stress of insulin-induced hypoglycemia. Three groups (n = 5, each) of conscious overnight-fasted dogs, chronically fitted with catheters in the femoral artery and in the third ventricle were used for these studies. Each experiment consisted of an 80-min equilibration period (0-80 min), a 40-min basal period (80-120 min), and a 180-min (120-300 min) experimental period. One group received a 220-min intracerebroventricular (icv) infusion of naloxone (0.2 mg/h) beginning at t = 80 min. The second group received a 3-h intravenous infusion of insulin at 5.0 mU.kg-1.min-1 beginning at t = 120 min. The third group received naloxone at t = 80 min and insulin beginning at t = 120 min, and both were continued throughout the experimental period. The studies show that insulin-induced hypoglycemia was associated with a rise in plasma cortisol, beta-endorphin, epinephrine, norepinephrine, and glucagon. Pretreatment with naloxone diminished the rises in plasma beta-endorphin, epinephrine, and norepinephrine without affecting the responses of plasma glucagon and cortisol. Although the levels of hypoglycemia achieved in the two groups were identical, glucose rates of appearance into and disappearance from the plasma compartment were higher in the group pretreated with icv naloxone (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Pattern of obesity and insulin, glucagon, sex hormone binding globulin and lipids in obese Arab women.

A standard oral glucose tolerance test was performed in 86 healthy premenopausal obese Arab women (BMI greater than or equal to 30) Glucose, insulin and glucagon were measured at 0, 30, 60, 90 and 120 min. Sex hormone binding globulin (SHBG), plasma lipids and uric acid were also estimated. Waist-hip circumference ratio (WHR) had significant positive correlation with age, triglycerides (TG), uric acid, fasting and 120 min glucose, and 120 min insulin and significant negative correlation with SHBG. Body mass index (BMI) had significant correlation with uric acid, fasting and 120 min insulin, and significant negative correlation with high density lipoprotein cholesterol (HDL Chol). When separated in two subgroups, with WHR greater than 0.80 (41), and less than or equal to 0.80 (45 cases), plasma glucose was in the diabetic range in seven; and impaired glucose tolerance (IGT) in 11 women in the former subgroup. Only three with IGT but no diabetics, were in lower WHR subgroup. WHR in diabetics (0.93), and in IGT cases (0.90) was significantly higher than in other women (0.80). Fasting insulin was not different, but at 90 and 120 min, insulin was higher in the high WHR subgroup who had also higher fasting, 90 and 120 min glucose. Glucagon level, though slightly higher in the higher (WHR) subgroup, may indicate relative hyperglucagonaemia because of the associated significantly higher glucose. Compared with age matched non-obese controls, obese women in both subgroups had significantly higher insulin, uric acid and significantly lower HDL Chol and lower glucagon (insignificant). Obese women in the higher WHR subgroup (greater than 0.80) had also significantly higher systolic blood pressure, TG and lower SHBG.