17ß-estradiol levels and oxidative balance in a population of pre-, peri-, and post-menopausal women.

BACKGROUND: The high incidence of various diseases observed in post-menopausal women has been widely associated to the decline of 17ß-estradiol (E2) occurring in correspondence of menopausal transition. One of the mechanisms suggested to explain this link takes into account the ability of E2 to counteract oxidative stress (OS) which is believed to play an important role in several pathogenic processes. AIM: To investigate whether stages of women's life characterized by different levels of E2 influence OS. SUBJECTS AND METHODS: We conducted a cross sectional study of OS markers in 159 women subdivided in 65 pre-menopausal, 36 peri-menopausal, and 58 post-menopausal classified according to the Staging of Reproductive Aging Workshop (STRAW) criteria. E2, follicle-stimulating hormone, and markers of OS including hydroperoxides, thiols, uric acid, total and residual antioxidant power, were assessed. RESULTS: After adjustment for covariates, only total antioxidant power was significantly different according to menopausal status (p <0.01), with lower value in pre- with respect peri- and post-menopausal women. No significant correlations between E2 levels and OS markers were detected. CONCLUSIONS: Endogen E2, and, consequently, its decline during menopausal transition, is not a determinant factor for OS.

Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma.

PURPOSE: To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries. METHODS: Four centres reported scans from 50 patients with stage II-IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using 'normal' mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading). RESULTS: There was agreement that the response scan was 'positive' or 'negative' for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74-0.96) for conservative reading and 0.79 (95% CI 0.67-0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively. CONCLUSION: The criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting.

Body mass index is a major determinant of abdominal fat accumulation in pre-, peri- and post-menopausal women.

OBJECTIVE: To investigate the role of menopause, body mass index (BMI) and aging on body fat distribution in women. DESIGN: In this population-based cross-sectional study, 335 women (126 in pre-menopause, 75 in peri-menopause and 134 in post-menopause according to Stages of Reproductive Aging Workshop criteria) were evaluated for body mass composition and fat distribution by dual X-ray absorptiometry procedure. A sub-group of 79 women with similar age and BMI was extracted from the sample to examine the relative influence of BMI in body fat distribution. RESULTS: ANCOVA analysis of total sample showed an age-independent increase of total fat mass (p < 0.001) and percentage on total weight (p < 0.001), arms fat mass (p < 0.01), legs fat mass percentage on total fat (p < 0.05) and trunk fat mass (p < 0.001) and percentage (p < 0.05) in peri- and post- with respect to pre-menopausal women. In the sub-sample including age and BMI matched women the difference of regional fat parameters among menopausal status was no more statistically significant. CONCLUSION: BMI, and not age, is the main determinant of the increase of body fat mass (total and abdominal) observed during the menopausal transition.

Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation.

Elevation of homocysteine is associated with an increased risk for bone fractures. Whether the risk is due to homocysteine or to the reduced levels of cofactors necessary for its metabolisation, such as folates or vitamin B12, is not completely clear. In this study we wanted to determine whether in postmenopausal women, levels of folates, homocysteine or vitamin B12 are predictive of the rate of vertebral bone mineral density (BMD) change. The study was conducted at the centre for the menopause of our university hospital. Between September 2001 and March 2002, 161 healthy postmenopausal women volunteered for a cross-sectional evaluation of BMD and levels of serum folates, homocysteine and vitamin B12. Women were recalled for a second evaluation of vertebral BMD after about 5 years. Women having used anti-resorptive therapies for more than 1 year were excluded. The analysis was possible in 117 postmenopausal women. The annual rate of vertebral BMD change was independently related to levels of folates (coefficient of regression (CR): 2.040; 95%CI: 0.483, 3.596; p=0.011), and initial BMD values (CR: -0.060; 95%CI: -0.117, -0.003; p=0.040). No significant relation was found between the change of vertebral BMD and homocysteine or vitamin B12. BMD values at the first (r=0.225; p=0.016) and the second (r=0.206; p=0.027) evaluation were related to levels of folates, but not of homocysteine or of vitamin B12. These data suggest an important role for folates deficiency in the vertebral BMD decline of postmenopausal women.

Oxidative stress, body fat composition, and endocrine status in pre- and postmenopausal women.

OBJECTIVE: To evaluate the role of menopause on the regional composition and distribution of fat in women and eventual correlations with the oxidative state. DESIGN: In this observational clinical investigation, 90 women (classified for menopause status according to Stages of Reproductive Aging Workshop criteria) were evaluated for body mass composition and fat distribution by dual-energy x-ray absorptiometry and for oxidative status by determination of serum hydroperoxide levels and residual antioxidant activity. RESULTS: Total body fat mass increases significantly in postmenopause (P < 0.05) by 22% in comparison with premenopause, with specific increases in fat deposition at the level of trunk (abdominal and visceral) (P < 0.001) and arms (P < 0.001). Concomitantly, the antioxidant status increases significantly (P < 0.001) by 17%. When data were adjusted for age by analysis of covariance, statistical significance disappeared for the increase in fat mass, but it was retained for antioxidant status (P < 0.05). Both antioxidant status and hydroperoxide level increased with trunk fat mass, as shown by linear correlation analysis (r = 0.46, P < 0.001 and r = 0.26, P < 0.05, respectively). CONCLUSIONS: The results of our investigation demonstrate that fat content increases in the upper part of the body (trunk and arms) in postmenopause and that age is the main determinant of this increase. During the comparison of premenopausal and postmenopausal women, we also detected a significant increase in antioxidant status. Apparently this change is mainly related to menopausal endocrine and fat changes.

Effect of intense military training on body composition.

Individuals in a structural physical training program can show beneficial changes in body composition, such as body fat reduction and muscle mass increase. This study measured body composition changes by using 3 different techniques-skinfold thickness (SF) measurements, air displacement plethysmography (BOD-POD), and dual-energy x-ray absorptiometry (DXA)-during 9 months of intense training in healthy young men engaged in military training. Twenty-seven young men were recruited from a special faction of the Italian Navy. The program previewed three phases: ground combat, sea combat, and amphibious combat. Body composition was estimated at the beginning, in the middle, and at the end of the training. After the subjects performed the ground combat phase, body composition variables significantly decreased: body weight (P < 0.05), fat-free mass (FFM) (P < 0.001), and fat mass (FM) (P < 0.03). During the amphibious combat phase, body weight increased significantly (P < 0.01), mainly because of an increase in FFM (P < 0.001) and a smaller mean decrease in FM. There was a significant difference (P < 0.05) in circumferences and SF at various sites after starting the training course. Bland-Altman analysis did not show any systematic difference between FM and FFM measured with the 3 different techniques on any occasion. On any visit, FFM and FM correlation measured by BOD-POD (P = 0.90) and DXA was significantly greater than measured by SF. A significant difference was found in body mass index (BMI) measured during the study. BOD-POD and SF, compared with DXA, provide valid and reliable measurement of changes in body composition in healthy young men engaged in military training. In conclusion, the findings suggest that for young men of normal weight, changes in body weight alone and in BMI are not a good measure to assess the effectiveness of intense physical training programs, because lean mass gain can masquerade fat weight loss.

Multidisciplinary approach to the treatment of metabolic and morphologic alterations of HIV-related lipodystrophy.

BACKGROUND: Treatment for metabolic and morphologic alterations in HIV-related lipodystrophy include medical therapy, physical exercise, and surgical interventions. METHOD: We assessed the efficacy and safety of a comprehensive multidisciplinary approach for treating morphological and metabolic alterations of the lipodystrophy syndrome in consecutive patients attending the Metabolic Clinic (MC) of the University of Modena and Reggio Emilia who had at least 2 evaluations over a 48-week period. 245 patients were evaluated: 143 (62.4%) were men, 74 (36.1%) presented with lipoatrophy, 10 (4.9%) with fat accumulation, 93 (45%) with mixed forms, 24 (11.3%) had hypercholesterolemia (LDL >160 mg/dL), 87 (38%) had hypertriglyceridemia (TG >150 mg/dL), 13 (5.7%) had diabetes (glucose >126 mg/dL), and 78 (44%) had insulin resistance (HOMA-IR >4). RESULTS: At follow-up, a significant improvement was observed in both objective and subjective variables. Anthropometric improvement was observed in waist to hip ratio, waist circumference, and right and left cheek dermal thickness measurements. A nonsignificant improvement was observed in fat and lean regional mass by DEXA; CT showed improvement in visceral and subcutaneous adipose tissue. Glucose, HOMA-IR, total cholesterol, and APO B improved. Subjective variables improved in aesthetic satisfaction. CONCLUSION: We conclude that the medical and surgical interventions proposed in this multidisciplinary therapeutic approach are efficacious and safe in the management of lipodystrophy.

Screening for silent ischemia with coronary artery calcium and nuclear stress testing in nondiabetic patients prior to kidney transplant.

Whether coronary artery calcium (CAC) screening in pretransplant patients may help predict silent myocardial ischemia is unknown. Accordingly, we performed CAC imaging on 46 nondiabetic patients awaiting kidneytransplant. All patients underwent multidetector computed tomography imaging for CAC quantification, and a vasodilator myocardial perfusion stress (MPS) test was performed only in patients with a total CAC score>300 or>100 in a single coronary artery. The mean patient's age was 46+/-14 years and the median dialysis vintage was 33 months (interquartile range 19-53). The median CAC score was 82 (interquartile range 0-700) and correlated with patients' age (p=0.006) and dialysis vintage (p=0.02). Nineteen patients qualified for MPS, but 5 refused the test. Of the remaining 14 patients, 7 patients had normal scans and 7 showed a minimal perfusion defect in the inferoposterior segment of the left ventricle. At the time of writing, 12 patients have undergone successful kidney transplantation without untoward complications. CAC screening does not appear to be associated with silent ischemia in pretransplant patients. Though CAC is extensive in dialysis patients, calcium may be associated with nonobstructive atherosclerotic lesions or calcification of the media layer of the vessel wall.

Nuclear medicine imaging of inflammatory/infective disorders of the abdomen.

Different nuclear medicine modalities are currently used to study inflammatory and infective disorders of the abdomen. They are usually complementary to radiology and endoscopy, but they play a pivotal role in particular clinical situations. Several radiopharmaceuticals (e.g., 111In or 99mTc labelled white blood cells, monoclonal antibodies, human polyclonal immunoglobulins, 75Ga citrate) are commercially available, but they can not be used indifferently to study abdominal inflammatory disorders. The lack of comparative studies showing the accuracy of each radiopharmaceutical for the study of inflammatory/infective abdominal diseases does not allow the best nuclear medicine technique(s) to be chosen in an evidence-based manner. To this end we performed a meta-analysis of peer reviewed articles published between 1984 and 2004 describing the use of nuclear medicine imaging for the study of inflammatory bowel disorders, appendicitis and vascular graft infections. A guideline for the optimal radiopharmaceutical(s) to be used in each clinical condition and for different aims is provided.

Low-density lipoprotein (LDL) receptor/transferrin fusion protein: in vivo production and functional evaluation as a potential therapeutic tool for lowering plasma LDL cholesterol.

A soluble form of human low-density lipoprotein receptor (LDL-R) fused in frame with rabbit transferrin (LDL-Rs(hu)/Tf(rab)) is assessed in vivo as a therapeutic tool for lowering plasma LDL cholesterol. The cDNA encoding LDL-Rs(hu)/Tf(rab) is expressed in mice, using a hydrodynamics-based gene transfer procedure. The transgene is transcribed in the liver of transduced animals and the corresponding protein is secreted into the bloodstream. Circulating LDL-Rs(hu)/Tf(rab) binds LDL specifically, thus indicating that it is correctly processed through the cellular compartments in vivo. More importantly, the expression of LDL-Rs(hu)/Tf(rab) allows the removal of injected human (125)I-labeled LDL ((123)I-LDL) from the bloodstream of transduced CD1 mice, which show faster LDL plasma clearance, anticipating by approximately 90 min the same clearance value observed in control animals. A similar effect is observed in transduced LDL-R(-/-) mice, in which the clearance of injected human LDL depends solely on the presence of circulating LDL-Rs(hu) /Tf(rab). In these animals the extent of plasma LDL clearance is directly related to the concentration of LDL-Rs(hu)/Tf(rab) in the blood. Finally, LDL-Rs(hu)/Tf(rab) does not alter the pattern of LDL organ distribution: in transduced animals, as well as in control animals, liver and bladder are the predominantly labeled organs after (123)I-LDL injection. However, LDL-Rs(hu)/Tf(rab) has a quantitative effect on LDL tissue deposition: in treated animals LDL-Rs(hu)/Tf(rab) determines an increase in radioactivity in the liver at early times after (123)I-LDL injection and a progressive labeling of the bladder, starting 20 min after injection.

Functional, structural, and distribution analysis of the chorionic gonadotropin receptor using murine monoclonal antibodies.

LH and human chorionic gonadotropin (hCG) control steroid production and gametogenesis. They also function as growth factors through interaction with a specific receptor that is a member of the seven-transmembrane receptor family coupled via G proteins to signal pathways involving cAMP and phospholipase C/inositol 3 phosphate. For this study, monoclonal antibodies (mAbs) were raised against the human LH receptor (LHR)/hCG receptor (hCGR), using Chinese hamster ovary LHR-transfected cells as the immunogen. Two reagents were then selected on the basis of their ability to recognize the full-length transmembrane receptor expressed both by Chinese hamster ovary LHR-transfected cells and by a limited number of tumor cell lines. One of these mAbs reacts with the LHR/hCGR in tissue sections of both frozen and paraffin-embedded specimens. This unique feature allowed us to map the cytological distribution of LHR/hCGR in human breast tissues at different stages of development in physiological and benign pathological conditions. The same mAb proved to be agonistic: receptor ligation elicits signals that modulate the growth of selected breast tumor cell lines. This observation suggests that the mAb recognizes an epitope that is included in the domain of the receptor involved in the interaction with the natural ligand.

Role of carcinoembryonic antigen, magnetic resonance imaging, and positron emission tomography-computed tomography in the evaluation of patients with suspected local recurrence of colorectal cancer.

The role of carcinoembryonic antigen (CEA), magnetic resonance imaging (MRI), and positron emission tomography (PET)-computed tomography (CT) in detection of local recurrence of colorectal cancer is evaluated in 71 patients, selected due to suspected relapse at CT follow-up. Recurrence was confirmed by histology in 18 cases and excluded in 25 cases. Sensitivity, specificity, positive and negative predictive values, and accuracy were as follows: 44.4%, 92.5%, 66.7%, 83.1%, and 80.3% for CEA; 88.9%, 73.6%, 53.3%, 95.1%, and 77.5% for MRI; and 94.4%, 73.6%, 54.8%, 97.5%, and 78.9% for PET-CT. A diagnostic protocol integrating CEA and dedicated imaging studies is to be advocated.

Use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography in patients with Hodgkin lymphoma in daily practice: a population-based study from Northern Italy.

We conducted a population-based study to assess how positron emission tomography (PET) is currently used in patients with Hodgkin lymphoma (HL). Four cancer registries from northern Italy were used to identify patients with HL diagnosed from 2006 to 2008. Computed tomography (CT) and PET scans were collected before treatment start (B), at the end (F), and during treatment (I). One hundred and thirty-six patients were identified as the study population. B-PET, I-PET, and F-PET were performed in 82%, 65%, and 85% of patients, respectively. Overall, I-PET was coded as positive in 16% of cases. F-PET was positive in 13% of cases. The I-PET result was a prognostic factor for failure-free survival (FFS) (hazard ratio [HR] 5.33); the F-PET result was the only prognostic factor for overall survival (OS) (HR 14.2). This population-based study confirms the prognostic role of I-PET for FFS also in daily practice; the results of F-PET can be used to predict OS.

The variation of prognostic significance of Maximum Standardized Uptake Value of [18F]-fluoro-2-deoxy-glucose positron emission tomography in different histological subtypes and pathological stages of surgically resected Non-Small Cell Lung Carcinoma.

Even if the prognostic role of SUVmax of 18-FDG-PET has been largely investigated, many issues regarding its relationship with pathologic staging and histological subtypes still remain controversial. This retrospective study investigated the prognostic significance of SUVmax in 119 completely resected, pathologically proven NSCLC. The SUVmax values resulted significantly related to histological subtypes (p<0.001), histological grading (p<0.001), and pathologic stage (p<0.001). The optimal cut-off value of SUVmax to predict prognosis in the whole series was 6.7 (p=0.029). 2-Year disease-specific survival (DSS) was 91% for SUVmax < or =6.7 and 55% for SUVmax >6.7 (p<0.001). SUVmax still remain a significant predictor of survival in Stage IB (2-year DSS of 100% for SUVmax < or =6.7; 51% for SUVmax >6.7, p=0.016). The optimal cut-off values of SUVmax to predict prognosis were 5 for adenocarcinoma (p=0.027) and 10.7 for other non-adenocarcinoma NSCLC subtypes (p=0.010). These histologic-specific cut-offs resulted significantly related to survival when stratified for stage: 2-year DSS for Stage IB adenocarcinoma were 100% for SUV< or =5 and 40% for SUVmax >5 (p=0.051); 2-year DSS for Stage IB non-adenocarcinoma were 83% for SUVmax < or =10.7 and 26% for SUVmax >10.7 (p=0.018). Adenocarcinomas showed significantly lower survival results respect to other NSCLC for intermediate SUVmax level (range 5.5-11.3) (p=0.021). High SUVmax resulted an independent negative prognostic factor at multivariate analysis (HR of 15.7, 95% CI of 2.50-98.44, p=0.003). In conclusion, SUVmax represents a significant prognostic factor in surgically resected NSCLC but a great variability between different histological subtypes, even when adjusted for stage, is present and could be considered when planning future trials on prognostic role of FDG uptake.

Geometry and bone mass in primary hyperparathyroidism assessed by peripheral Quantitative Computed Tomography (pQCT).

PURPOSE: Non-invasive measurement by peripheral quantitative computed tomography (pQCT) of bone geometry, biomechanics, and mineral content in patients (pts) with primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: Total, trabecular and cortical mineral density (totBMD, cortBMD, trab BMD), bone geometrical properties (total area, trabecular area, cortical area, cortical/total area) and cortical thickness as biomechanical parameters, were assessed by pQCT at distal radius in 38 (32 F; 6 M) consecutive patients with PHPT (mean age: 62 yrs; range: 30-77). In a subgroup of 12 patients, bone mineral density (BMD) was also measured by means of dual X-ray absorptiometry (DXA) at the lumbar spine (L2-L4). RESULTS: Serum biochemical characteristics were: iPTH (269+/-214 pg/ml; range: 107-1438, normal: 30-65), Calcium (11.4+/-1.1 mg/dl; range: 10.6-13.5, normal: 8.1-10.4) and Alkaline Phosphatase (398+/- 392 U/L; range:173-1174, normal: 98-279). Compa-red with 87 healthy age-matched subjects, total, trabecular and cortical bone densities were reduced in all patients (TotBMD: 216+/-92 mg/cm(3) vs ctr 342+/-94, -37%, p<0.05; TrabBMD: 93+/-51 mg/cm(3) vs ctr 140+/-54, -34%, p <0.01; CorBMD: 711+/-178 mg/cm(3) vs ctr 802+/-175, -11%, p<0.02), such as cortical thickness (0.143+/-0.02 cm vs ctr 0.157+/-0.03, -9%, p<0.02). Among geometrical parameters, only cortical/total area was significant different in the two groups (0,29 vs 0.31; p<0.04). A strong correlation was found between peripheral trabecular bone density assessed by pQCT and axial bone mineral density measured by DXA at L2-L4 (r=0.80; p<0.01). CONCLUSIONS: pQCT measurements in PHPT showed: 1) osteopoenia in all bone compartments partly related to age and menopause; 2) reduced cortical density and cortical thickness consistent with "cancellization" of the inner cortex and lower ability of bone to absorb loading forces. DXA measurements showed osteopoenia also at the lumbar spine, a site rich in trabecular bone. PQCT allowing selective assessment of true volumetric cortical and trabecular bone density such as bone geometry, is proposable in clinical practice, in order to evaluate presurgical bone "status" and to monitor the response to parathyroidectomy.