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Thoracoscopy is commonly used minimally invasive procedure in the field of interventional pulmonology. While medical thoracoscopy is the widely preferred modality, modifications to the technique and expansion in the scope of its utility have always challenged the conventional approach. We describe a modified technique of medical thoracoscopy in absence of pleural effusion also known as dry thoracoscopy under sedation and local anaesthesia.

Endobronchial ultrasound has revolutionized the field of bronchoscopy and has become one of the most important tools for the diagnosis of intrathoracic lymphadenopathy and para-bronchial structures. The reach of this technique has not been limited to these structures and pleural lesions have been at times accessible. To our knowledge, pleural fluid collections have not been accessed with endobronchial ultrasound (EBUS) through oesophageal approach and rationale behind using this approach. We report a case of 70 years old man who has been referred from physician for the EBUS in view of hilar mass with mediastinal lymphadenopathy with pleural effusion. The endobronchial ultrasound through oesophagus (EUS-B) was done for thoracocentesis and lymph node cytology evaluation and ultimately endobronchial biopsy of hilar mass was done as rapid on-site (ROSE) analysis of lymph node was suggestive of necrotic tissue. The cytology report of lymph node and pleural effusion was positive for malignant cells. The final diagnosis was metastatic poorly differentiating adeno-squamous carcinoma.

Introduction: Mepolizumab is an anti-IL5 humanized antibody approved for severe eosinophilic uncontrolled asthma. Long term safety has been assessed in registration studies, but few data are available on patients with echinococcus hepatic cyst (EHC) or other comorbidities i.e. lung cancer requiring chemotherapy (CT). Aim: analysis of one-year treatment outcomes in 30 patients on treatment with Mepolizumab, including one patient with known EHC and hepatic cyrrosis and one patient on treatment with cisplatin-gemcitabine for lung cancer (stage IV adenocarcinoma ). Methods: All patients were evaluated for blood eosinophylic count, oral corticosteroids (OCS) use and comorbidities in a single-center cohort case-note analysis. Results: Mepolizumab reduced OCS use (p Conclusions: Mepolizumab treatment improved asthma outcomes and was not related with hepatic impairment, relapse of EHC and did not affected chemotherapy at one year follow up.

Background and Aim. Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach. Methods. Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity. Results. 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients. Conclusions. This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low.

We have described a 67-year-old man, diagnosed to have adenocarcinoma of lung by transvascular approach with esophageal ultrasound using ultrasound bronchoscope (EUS-B). To the best of our knowledge this is the first case where EUS-B has been used for transvascular fine needle aspiration cytology to diagnose lung carcinoma. Keywords: EUS-B, TVNA, Transesophageus, EBUS

Eur J Clin Invest 2012; 42 (11): 1197–1204 Abstract Background The low-grade chronic inflammation present in obesity has been recognized as a risk factor for thrombosis, atherosclerosis and cardiovascular complications. In this context, production by adipose organ of a number of inflammatory adipokines could play a crucial role. It has been reported that obesity represents a risk factor for acquired thrombotic thrombocytopenic purpura (TTP), a disease caused by ADAMTS13 deficiency because of anti-ADAMTS13 antibodies, but the pathophysiological link between obesity and TTP is still unknown. We aimed to investigate mechanisms linking obesity to risk of TTP. Materials and methods Eighty obese patients consecutively admitted to Bariatric Unit of Padua between 2006 and 2009, and 39 lean subjects were characterized by anthropometric, metabolic and inflammatory parameters. ADAMTS13 autoantibodies, activity and antigen levels, and several cytokines including thrombospondin-1 were measured. Results 21·3% of obese patients were positive for noninhibitory ADAMTS13 autoantibodies, while all lean subjects were negative (P

Satellite cells (SCs) are undifferentiated skeletal muscle cells that allow muscular growth and regeneration. Since their first description, SCs were simply considered myogenic precursors, but now it is widely accepted that SCs are a heterogeneous stem cell population characterized by plasticity and self-renewal. In this report we focus on SCs capacity to undergo adipogenic differentiation both spontaneous and induced by adipogenic factors. Understanding SC behavior is especially important because their adipogenic potential could represent a pathophysiological explanation for the intramuscular fat depots and associated insulin resistance that characterize many metabolic diseases and age-related sarcopenia. Moreover, SC are a therapeutic promise for neuromuscular diseases in the context of tissue engineering, representing an interesting cell source for implantation.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease leading to worsening functional status and reduced survival for those patients who cannot undergo pulmonary endarterectomy (PEA). Pharmacotherapy with novel drugs for pulmonary hypertension may be useful in treating patients who are poor candidates for surgery, but there are still few clinical data on medical therapy for CTEPH. The aim of this prospective open-label, multicenter, study is to compare the efficacy of 1-year bosentan treatment to standard drugs in nonoperated patients with CTEPH.Thirty-four nonoperated patients with CTEPH were enrolled. Functional assessment included 6 minute walk test (6MWT), Borg index, WHO classification, arterial blood gases and echocardiography systolic pulmonary artery pressure (sPAP). Seventeen patients received bosentan (62.5 mg b.i.d. for 4 weeks and then 125 mg b.i.d.); 17 patients were treated with standard therapy alone.At admission sPAP was 76.18+/-5.96 mmHg in bosentan group and 71.48+/-3.71 mmHg in controls, p(a)O(2) 64.68+/-2.25 mmHg in bosentan group, and 59.52+/-2.05 mmHg in controls, 6MWT 297.53+/-34.25 mt in bosentan group, and 268.47+/-36.54 mt in controls. After 12 months there were significant differences between the groups in the 6MWT (+57.24+/-22.21 m vs -73.13+/-21.23 m, p0.001), dyspnoea index (Borg score 4.29+/-0.49 vs 7.06+/-0.32, p0.001) and oxygenation (p(a)O(2) 65.93+/-3.76 mmHg vs 48.48+/-1.31 mmHg, p0.001). The sPAP was stable after 12 months of bosentan (76.18+/-5.96 mmHg vs 71.00+/-5.41 mmHg, p=0.221) in contrast to controls (71.48+/-3.71 mmHg vs 80.44+/-4.70 mmHg, p=0.029).The data of this open-label study in nonoperated CTEPH patients suggest an improvement in functional outcomes adding Bosentan to diuretics and oral anticoagulants. No improvement was observed using only standard drugs after 1-year.

The aim of this study was to establish the duration and annual rate of menopause-related bone loss and to investigate the relationship between bone turnover and bone loss in early healthy postmenopausal women. The rate of change in bone mineral density (BMD) at the lumbar spine and in bone turnover was measured twice at the exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) and by the determination of plasma alkaline phosphatase levels (ALP) and fasting urinary hydroxyproline/creatinine ratio (OHPr/Cr), respectively, in 123 healthy premenopausal and postmenopausal women 45-60 years of age. The subjects were divided into nine groups according to their menstrual status and years since menopause (YSM). Annual bone loss at the lumbar spine of women who were menopausal for 1, 2, 3, 4, and 5 years was -2.62 +/- 0.37 (95% confidence interval -3.66, -1.58), -3.87 +/- 0.96 (-6.02, -1.73), -2.50 +/- 0. 37 (-3.29, -1.70), -2.86 +/- 0.73 (-4.44, -1.27), and -1.54 +/- 0.41 (-2.42, -0.66), respectively, and was significantly less than zero. But, the annual bone loss of women who were premenopausal or menopausal for 6, 7, and 8 years was -0.76 +/- 0.60 (-2.04, +0.53), -1.16 +/- 0.68 (-2.61, +0.29), 0.24 +/- 0.48 (-0.78, +1.26), and 0. 16 +/- 0.63 (-1.18, -1.49), respectively, and was not significantly different from zero. These results demonstrate that the early hormone-dependent bone loss commences in the first year after menopause and is arrested within 6 years after the onset of menopause. The overall bone loss for this phase is estimated to be approximately 15%. Annual change in ALP and OHPr/Cr seems to indicate that bone resorption prevails on bone formation in the first 2 YSM, whereas osteoblastic activity relatively prevails from YSM 3 to YSM 5, which explains the progressive repairing of the imbalance between bone resorption and formation.

This work was carried out in order to investigate possible relationships between bone turnover rate, as evaluated by bone biomarkers and skeletal mass, as evaluated by bone mineral density (BMD).Fifty-eight normal women and 30 female patients with osteoporotic fractures were enrolled. Three groups were defined: (1) fertile subjects (n = 24), mean age 33.7 +/- 8.1 years; (2) postmenopausal women (n = 32, including 11 patients with fractures) whose BMD values, in terms of T score, were less than -2.5 S.D. below the young adult mean obtained in our laboratory (mean age 61.7 +/- 7.9 years; and years since menopause (ysm), 12.6 +/- 8.3); (3) postmenopausal women (n = 32, including 19 patients with fractures) whose BMD values in terms of T score, were below -2.5 S.D. (mean age 62.9 +/- 8.6 years; and ysm 15.9 +/- 9.0). Groups II and III characterised, by inclusion criteria, by significant different mean BMD values, were similar as far as chronological and menopausal age were considered. Metabolic tests included a short urine collection to determine calcium, hydroxyproline, cross-linked N-telopeptides of type I collagen (NTx) and creatinine (Cr); half-way through this collection, a blood sample was taken for the measurement of total alkaline phosphatase activity (ALP) and tartrate-resistant acid phosphatase activity (TRAP). BMD at lumbar spine was evaluated.There were significant differences amongst the three groups in mean ALP (P0.001, by analysis of variance) TRAP (P0.006) and NTx/Cr (P0.001) values, but not as far as mean values of calcium/Cr or hydroxyproline/Cr ratios were concerned. Considering the group as a whole, there were significant inverse correlations between NTx/Cr, ALP, TRAP and BMD controlling for both age (r = -0.392, P0.001; r = -0.447, P0.001 and r = -0.327, P0.002, respectively) and ysm (r = -0.374, P0.001; r = -0.474, P0.001 and r = -0.333, P0.002).Our results indicate, that, even after controlling for both ageing and oestrogen status, there is an inverse relationship between bone mass (that at a given time represents the balance of all previous metabolic events) and a biochemical marker (which reflects bone turnover at the time of examination). These findings are in line with the belief that increased bone turnover should be regarded as a risk factor for osteoporosis. Furthermore, our results indicate that, unless there is no increase of hepatic isozyme, total ALP still maintains a possible role as a first analysis to evaluate bone turnover before requesting markers with greater specificity, sensitivity but also more expensive and whose analysis is sometimes time-consuming.

Obesity, systemic inflammation and changes in the heart functions are associated with increased cardiovascular risk. This study aimed to investigate coronary microvascular dysfunction as an early marker of atherosclerosis in obese patients without any evidence of cardiovascular disease.86 obese subjects (aged 44 ± 12 years, body mass index (BMI) 41 ± 8 kg m(-2)), without evidence of heart disease, and 48 lean controls were studied using transthoracic Doppler echocardiography for detecting coronary flow reserve (CFR). A value of CFR ≤ 2.5 was considered abnormal. We measured interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin in all patients. Patients with abnormal CFR underwent coronary multislice computed tomography (MSCT) in order to exclude an epicardial stenosis. CFR in obese subjects was lower than in lean subjects (3.2 ± 0.8 vs. 3.7 ± 0.7, p = 0.02) and was abnormal in 27 (31%) obese patients and in one (2%) control (p 0.0001). All subjects with abnormal CFR showed no coronary stenosis at MSCT. At multivariable analysis, IL-6 and TNF-α were the only determinants of CFR (p 0.02 and p 0.02, respectively). At multivariable logistic regression analysis, IL-6 and TNF-α were the only determinants of CFR ≤ 2.5 (p 0.03 and p 0.03, respectively).CFR is often reduced in obese subjects without clinical evidence of heart disease, suggesting a coronary microvascular impairment. This microvascular dysfunction seems to be related to a chronic inflammation mediated by adipocytokines. Our findings may explain the increased cardiovascular risk in obesity, independently of BMI.

Bone tissue is a source of growth factors; among them, insulin-like growth factor I (IGF-I) is probably an important local regulator of bone formation. This study has been carried out in order to assess the effects of natural menopause on plasma concentrations of IGF-I in the first 6 years after the cessation of gonadal function independent of age. We also examined the relationship between plasma IGF-1 levels and bone mineral density (BMD) measured at the lumbar spine (LS), at the ultradistal radius (UDR), and at the junction of the distal and middle thirds of the radius (MR). Sixty-seven healthy nonobese women, aged 45–55, were studied (premenopausal n = 21; postmenopausal n = 46, from 1 to 6 years since menopause). Plasma IGF-I levels were measured by RIA, after acid-ethanol extraction. BMD of the forearm was measured by dual-photon densitometer and BMD of the LS was assessed by quantitative digital radiography. Mean values of IGF-I plasma levels were significantly reduced in postmenopausal women compared to the premenopausal group. Menopausal duration did not influence IGF-I plasma levels in postmenopausal women. We also found a positive correlation between IGF-I levels and BMD measured at MR both in pre- and postmenopausal women, while a correlation with LS and UDR-BMD was found only in fertile subjects. The results show that IGF-I plasma levels decrease immediately after menopause, since significantly lower levels are reached in the first years. The correlations found between plasma IGF-I levels and BMD suggest a possible role of reduced IGF-I in bone loss at particular skeletal sites.

Summary The aim of this study was to evaluate the effects of ipriflavone treatment on bone remodeling in primary hyperparathyroidism. Nine patients, 6 females and 3 males (mean ± SD age 56 ± 12.5 years) were treated with 1200 mg/day of ipriflavone by oral administration divided in 3 daily doses. All patients were treated for 21 days; in 5 patients treatment was prolonged to 42 days. In all patients the main serum and urinary parameters of bone remodeling were evaluated. The results suggest that ipriflavone affects bone remodeling by inhibiting bone resorption without affecting bone formation. Ipriflavone is, therefore, indicated in the treatment of metabolic bone diseases characterized by a high bone turnover.

Background Laparoscopic sleeve gastrectomy (LSG) is considered an effective multipurpose operation for morbid obesity, although long-term results are still lacking. Also, the best procedure to be offered in the case of failed restrictive procedures is still debated. We here reported our results of LSG as a revisional procedure for inadequate weight loss and/or complications after adjustable gastric banding or gastroplasty. Methods Since April 2005, 57 patients (20 men and 37 women), with a mean age of 49.9 ± 11.9 years, underwent revisional LSG, 52 after laparoscopic adjustable gastric banding/adjustable gastric banding and 5 after vertical banded gastroplasty at our institution. The mean interval from the primary procedure to LSG was 7.54 ± 4.8 years. The LSG was created using a 34F bougie with an endostapler, after removing the laparoscopic adjustable gastric band or the anterior portion of the band in those who had undergone vertical banded gastroplasty. An upper gastrointestinal contrast study was performed within 3 days after surgery and, if the findings were negative, a soft diet was promptly started. Results A total of 41 patients had undergone concurrent band removal and LSG and 16 had undergone band removal followed by an interval LSG. Three cases required conversion to open surgery because of a large incisional hernia. The mean operative time was 120 minutes (range 90–180). One patient died of multiple organ failure from septic shock. Three patients (5.7%) developed a perigastric hematoma, 3 (5.7%) had leaks, and 1 had mid-gastric short stenosis. The median hospital stay was 5 days. The mean body mass index at revisional LSG was 45.7 ± 10.8 kg/m 2 and had decreased to 39 ± 8.5 kg/m 2 after 2 years, with a mean percentage of the estimated excess body mass index lost of 41.6% ± 24.4%. Two patients required a duodenal switch for insufficient weight loss. Conclusion LSG seems to be effective as revisional procedure for failed LAGB/vertical banded gastroplasty, although with greater complication rates than the primary procedures. Larger series and longer follow-up are needed to confirm these promising results.

To investigate the efficacy and tolerability of high-dose N-acetylcysteine (NAC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD).Randomised, double-blind, double-dummy, placebo-controlled study in 123 patients experiencing an acute exacerbation of COPD.NAC 1200 mg/day, 600 mg/day or placebo administered once daily for 10 days.The primary objective was to assess the proportion of patients with normalised C-reactive protein (CRP) levels. Also assessed were effects on interleukin (IL)-8 levels, lung function and symptoms.Both NAC 600 and 1200 mg/day were associated with a significantly higher proportion of patients achieving normalised CRP levels compared with placebo (52% and 90% vs 19% of patients; p/= 0.01); however, NAC 1200 mg/day was superior to NAC 600 mg/day (p = 0.002). Furthermore, treatment with NAC 1200 mg/day was more efficacious than NAC 600 mg/day in reducing IL-8 levels and difficulty of expectoration, while the two active regimens had similar beneficial effects on lung function and other clinical outcomes (cough intensity and frequency, and lung auscultation). Treatments were well tolerated with one adverse event reported in NAC 1200 mg/day recipients and two reported in placebo recipients.Treatment with NAC 1200 mg/day improved biological markers and clinical outcomes in patients with COPD exacerbations. It is speculated that the effect of NAC on inflammatory markers may be due to both mucolytic and antioxidant properties.

AIMS/HYPOTHESIS: Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. SUBJECTS AND METHODS: We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin. RESULTS: One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties. CONCLUSIONS/INTERPRETATION: These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.

The bradykinin B 2 receptor (B 2 R) gene is a candidate in the pathogenesis of insulin resistance, which often clusters with other abnormalities in metabolic syndrome. We investigated the distribution of the C-58T B 2 R gene polymorphism within a population of overweight/obese patients (BMI ≥ 25 kg/m 2 ) potentially characterised by different levels of insulin resistance. Patients with type 2 diabetes, dyslipidemia and hypertension were excluded in order to distinguish the effect of obesity on insulin sensitivity from that of confounding factors. Ninety-two unrelated adults (41 men and 51 women, aged 33.7 ′ 11.6 years) were recruited by random sampling from a general population evaluated for cardiovascular risk stratification. Measurements included BMI, waist circumference, body composition, blood pressure, serum leptin, and lipid profile. Insulin sensitivity was calculated according to the homeostasis model assessment (HOMA) method. C-58T genotypes - CC(n = 20), CT(n = 47) and TT (n = 25) - were determined by restriction fragment-length polymorphism PCR. Patients subdivided on the basis of C-58T polymorphism, showed no difference in any of the parameters examined, including HOMA index values, after adjustment for age, sex, BMI and waist circumference. The results indicate that the C-58T B 2 R gene polymorphism is not associated with different levels of insulin resistance within a population of obese patients.

OBJECTIVE: Glucocorticoids were found to inhibit adiponectin gene expression and secretion both in vitro and in animal models. We evaluated first the acute effect of i.v. glucocorticoids on adiponectin in normal subjects and secondly plasma adiponectin levels in a series of patients with Cushing's syndrome compared with controls. DESIGN AND METHODS: Hydrocortisone (25 mg) was administered i.v. to five healthy volunteers, with blood samples taken at -15, 0, 30, 60, 120 and 180 min. Twenty-one patients with Cushing's syndrome were divided in two groups: one with 11 obese and the other with 10 non-obese Cushing's patients. Each group was compared with controls that were matched for sex, age, body mass index, waist circumference, glucose, insulin, lipid levels and blood pressure. RESULTS: In normal subjects, hydrocortisone produced a decrease in adiponectin at 30 and 60 min, compared with placebo (P

OBJECTIVE: Little is known about the physiological role and the regulation of uncoupling proteins-2 and -3 (UCP-2 and -3) in adipose tissue. We investigated whether the expression of UCP-2 and -3 in adipose tissue was affected by weight loss due to a biliopancreatic diversion (BPD) and related to the daily energy expenditure (24-h EE). DESIGN: Ten morbidly obese subjects (mean body mass index +/- s.e.m.=49.80 +/- 2.51 kg/m(2)) were studied before and 18+/-2 Months after BPD. METHODS: We determined body composition using tritiated water and 24-h EE in a respiratory chamber. Adipose tissue UCP-2 and -3 mRNA, plasma insulin, glucose, free fatty acids (NEFA), free triiodothyronine (FT3), free thyroxine (FT4) and leptin were assayed before and after BPD. RESULTS: BPD treatment resulted in a marked weight loss (P

A hypercoagulable state and an increased incidence of thromboembolic complications are reported in Cushing's syndrome. The hypercoagulable state is related to an increase in plasma clotting factors, especially Factor VIII and von Willebrand factor complex, and to an impairment of fibrinolytic capacity. Retrospective analysis of postoperative thromboembolic events in a large group of patients with Cushing's syndrome, including 75 patients (group 1) evaluated in the period from 1972-1981 not receiving anticoagulants, and 232 patients (group 2), evaluated in the period from 1982-2000. Patients of group 1 underwent routine hemostatic function, i.e. prothrombin time and activated partial thromboplastine time. Patients of group 2 underwent a thorough investigation as to hemostatic parameters and received prophylactic treatment with heparin and/or warfarin. Patients with Cushing's syndrome showed various abnormalities of hemostatic parameters. A significant correlation between activated partial thromboplastine time and urinary free cortisol was observed. During follow-up, 15 patients (20%; mean follow-up, 9.4 +/- 6.4 yr) of group 1 and 14 (6.0%; mean follow-up, 6.6 +/- 4.2 yr) of group 2 showed thromboembolic complications. Of these patients, eight of group 1 and one of group 2 died. Survival analysis demonstrated a significantly higher morbidity and mortality due to thromboembolic events in group 1, not receiving anticoagulant prevention, than in group 2, treated with anticoagulants in the perioperative period until cure of the disease and normalization of clotting parameters. Cushing's syndrome is associated with a hypercoagulable state. An adequate anticoagulant prophylaxis can reverse this prothrombotic state and avoid postoperative thromboembolic events.

Objective: Obesity-related insulin resistance is closely associated with visceral fat accumulation. Several adipocyte-secreted molecules have been implicated in the development of type 2 diabetes, among them, the recently discovered adiponectin and resistin proteins. Some of these adipocytokines are also present in the immune system, thus suggesting an intriguing functional connection. Research Methods and Procedures: We determined adiponectin and resistin expressions in visceral (VAT) and subcutaneous adipose tissue of lean and obese Zucker (fa/fa) rats using reverse-transcription polymerase chain reaction. Moreover, we analyzed the variations after body-weight reduction in food-restricted obese rats. Results: Resistin and adiponectin expression was significantly lower in VAT of genetically obese in comparison with lean rats; no differences were observed when subcutaneous adipose tissues of the same animals were compared. Weight loss resulted in an increase of adiponectin expression in VAT, whereas a further significant decrease in resistin mRNA level was observed. Resistin is also present and equally expressed in splenocytes of lean and obese rats. Discussion: Adiponectin and resistin are down-regulated in VAT of obese rats. Adiponectin expression is restored to normal levels after body-weight reduction, supporting its link with obesity-related insulin resistance. On the contrary, the further decrease of resistin mRNA after weight loss does not support the hypothesis that resistin may play a causative role in insulin resistance in obese rats. Moreover, we demonstrated the presence of resistin in immunocompetent cells in both humans and rats, thus adding another factor to the list of molecules that adipose tissue shares with the immune system.

This study was carried out in order to evaluate clinical usefulness of cross-linked N-telopeptides (NTx) of type I collagen determination, in patients with primary hyperparathyroidism. Twenty-six consecutive patients (6 males and 20 females, aged 56.3 +/- 15.0, SD, yrs) with primary hyperparathyroidism were studied in basal conditions and, ten of them, after surgical cure of the disease. Cross-linked collagen peptides were measured by enzyme-linked immunosorbent assay and conventional markers of bone turnover according to standard procedures. Bone densitometry at the lumbar spine and proximal femur was performed using dual-energy X-ray absorptiometry. Bone mineral density, was also assessed at the junction of the distal and middle third of the radius and at the ultradistal radius of the non-dominant arm by a dual photon densitometer. Mean urinary NTx values (194.2 +/- 121.9 pmoles bone collagen equivalents/mumoles creatinine) were significantly higher (p < 0.001) in respect to those found in normal subjects. The mean increase of Z score values of both serum tartrate resistant acid phosphatase activity (1.4 +/- 1.8) and the fasting hydroxyproline/creatinine ratio (1.45 +/- 2.0) was significantly lower (p < 0.02) in respect to that of NTx Z score values (3.3 +/- 3.3); the latter values were not significantly different than mean Z score values of serum osteocalcin (4.0 +/- 3.9), serum alkaline phosphatase activity (2.6 +/- 2.6) and urinary calcium/creatinine ratio (3.2 +/- 3.3). We found a significant inverse correlation between NTx values and both lumbar spine (p < 0.01) and ultradistal radius bone mineral density (p < 0.05); a modest inverse correlation was also observed between serum tartrate resistant acid phosphatase activity and lumbar spine bone mineral density (p < 0.04). Following successful adenoma removal, the percentage decrease of both NTx and hydroxyproline was similar in patients with increased bone turnover rate; major discrepancies were observed in patients with normal values of NTx, the telopeptide reduction being greater than that of hydroxyproline. Finally, in a hypercalcemic patient with metastatic parathyroid cancer, telopeptide excretion was shown to be more sensitive in respect to urinary hydroxyproline when evaluating the effects of antiresorptive therapy. Our results seem to indicate that amongst the markers with good sensitivity, NTx is the only one that is inversely related with bone mineral density at two different skeletal sites. This assay should therefore have a place in both the initial screening and medical follow-up of patients with this glandular disorder; in fact, in both situations an increased urinary excretion of this marker should warn about the possibility of hidden bone loss.

We report the results of a longitudinal study aimed at better defining concomitant changes of both bone mineral density (BMD) and of four independent markers of bone turnover (serum osteocalcin, serum alkaline phosphatase activity, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratio) following natural menopause. The results obtained indicate that, within a relatively short period of time since cessation of gonadal function, conventional markers of bone turnover behave differently. In fact, while the mean values of hydroxyproline/creatinine ratio (felt to be a marker of bone resorption) rise immediately at the first control (19.7 +/- 11.7 months), the bone formation markers gradually increase and, as far as serum osteocalcin levels are concerned, this increment appears to be long-lasting. As a result of these changes, a negative skeletal balance follows, which is documented by the prolonged reduction of bone mineral density during the entire observation period. Mean +/- SD % measured yearly bone loss was -2.83 +/- 2.6. There was a highly significant correlation between initial and final BMD values (r = 0.908, p0.001; r2 = 82.5) and a weak inverse correlation (r = -0.298, p0.046) between initial serum alkaline phosphatase values and % yearly bone loss. In conclusion, measurement of the biological indices of bone remodelling following natural menopause indicate that the increase in osteogenesis is delayed compared to that of bone resorption; furthermore, in the immediate postmenopausal period, the actual bone mass should be considered the best predictor of future bone mass. The inverse correlation found between % yearly bone loss and serum alkaline phosphatase values seems to emphasize the importance of increased bone turnover as an independent predictor of bone loss.

Quantitative ultrasound measurements were done in a group of 26 patients (4 males and 22 females, aged 55.4 ±14.2 years) with primary hyperparathyroidism, and the results were compared with bone mineral density (BMD) carried out at various skeletal sites. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were measured with the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI). Mean ± SD values of SOS, BUA and stiffness in patients with primary hyperparathyroidism were 1522±38 m/seconds, 111±16 dB/MHz, and 80.4±19.8%, respectively. There were significant differences of mean T-score BUA values (-0.63±1.11) compared with corresponding T-score BMD values found at ultradistal (-1.85±1.73, P

The study investigated possible menopause-related changes in circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels and their relationship with insulin-like growth factor I (IGF-I) plasma levels. Forty-three healthy women, aged 45-55 years, were studied (22 premenopausal and 21 postmenopausal, matched for age and body mass index); in all subjects plasma IGF-I and IGFBP-3 levels were measured by radioimmunoassay. No difference was found between mean IGFBP-3 plasma levels in the two groups studied (premenopausal 3.42 +/- 0.49 v postmenopausal 3.46 +/- 0.58 mg/l), while mean IGF-I levels were significantly lower in postmenopausal as compared with premenopausal women (136.7 +/- 37.86 v 175.7 +/- 51.91 ng/ml, p0.02). Multiple regression analysis showed no significant effect of age, body mass index and years since menopause on IGFBP-3 levels; however, considering the IGF-I/IGFBP-3 ratio as a possible parameter of circulating free somatomedin C, an inverse correlation was found with years since menopause (n = 43, r = -0.499, p0.001). We conclude that lack of oestrogen induces different effects on circulating IGF-I and IGFBP-3, possibly reflecting a real decrease in IGF-I activity.

Minisola S, Romagnoli E, Scarnecchia L, Rosso R, Pacitti MT, Scarda A, Mazzuoli G. Serum carboxyterminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery. Eur I Endocrinol 1994;130:587–91. ISSN 0804-4643 This study was carried out in order to evaluate serum carboxy-terminal propeptide of human type I procollagen (PICP) in patients with primary hyperparathyroidism and to examine its changes following parathyroidectomy. Seventeen patients (four males and 13 famels, aged 53.8 ± 3.1 sem years) were studied in basal conditions; six patients also were investigated after successful parathyroid surgery. Mean serum PICP values of patients with primary hyperparathyroidism (194.5 ± 27 sem μg/l) were significantly higher (p < 0.001) with respect to those found in normal subjects. However, deviations from the norm (Z score values) were significantly less with respect to deviations of serum osteocalcin, alkaline phosphatase and urinary hydroxyproline/creatinine ratio. Following parathyroidectomy, it was possible to observe a discrepancy between markers of bone resorption and those of bone formation. The former tend to decrease, while the latter either do not show any significant change (serum alkaline phosphatase and serum osteocalcin) or increase (serum procollagen). The results of our investigation indicate that in basal conditions the assay of serum procollagen may be of clinical value but it would be better to use it in combination with other biomarkers of skeletal remodelling. The results obtained after parathyroidectomy are the opposite of those obtained following parathyroid hormone infusion and should be ascribed to the effect of acute hormone deficiency on collagen synthesis. The positive biochemical uncoupling following surgery might lend support to the rise of bone mineral density consistently reported in the first few months following parathyroidectomy. S Minisola, Istituto di II Clinical Medica, Policlinico Umberto I, Via del Policlinico 155, 00161 Rome, Italy

This study was carried out in order to determine interrelationships of age and sex on parameters within the parathyroid endocrine system in healthy men and women. One hundred and fifteen normal subjects (70 females and 45 males) subdivided into three groups aged 25-35, 45-55 and 65-75 years were studied. Female subjects aged between 45 and 55 were further subdivided into two age-matched groups in relation to gonadal functional status. Serum intact parathyroid hormone (PTH) concentrations were measured using a two-site immunoradiometric assay. We found that there was a significant decrease of serum ionized calcium with ageing only in men (r = -0.666, P < 0.001) and a significant increase of serum PTH with age in both men (r = 0.488, P < 0.001) and women (r = 0.279, P < 0.019). A significant inverse correlation was found between serum ionized calcium and PTH in male subjects (r = -0.661, P < 0.001) and in fertile females (r = -0.353, P < 0.037) but not in postmenopausal women or in the entire female population. Furthermore, we found a significant decline of serum phosphate (r = -0.484, P < 0.001) and TmP/GFR (r = -0.492, P < 0.001) with advancing age in men, but not in women. We believe that the decrease of serum ionized calcium, as a likely consequence of the physiological reduction of intestinal calcium absorption, is the pivotal factor responsible for the increased PTH levels we observed with advancing age. The phenomenon is clear in men and in premenopausal women, but is masked in the female sex at menopause by the effects of a shortage of oestrogen on the calcium-phosphorus metabolism. These may also be responsible for the differences observed between the two sexes as far as phosphate metabolism is concerned. In conclusion, this study has, for the first time, taken relationships between serum ionized calcium and PTH, over a wide age range, into consideration. The results obtained show a marked difference of serum ionized calcium values between sexes with ageing, while serum parathyroid hormone levels increase in both men and women. Important differences also exist, as far as phosphate metabolism is concerned, between males and females.

This investigation was carried out to evaluate the clinical utility and diagnostic value of serum intact PTH measurement using a recently introduced immunochemiluminometric assay (ICMA). Studies were carried out in 42 normal subjects, 24 patients with primary hyperparathyroidism, 21 patients on chronic maintenance hemodialysis, 8 patients with postsurgical hypoparathyroidism, 7 patients with cancer hypercalcemia and 6 patients with osteomalacia. A good correlation was found in normal subjects between serum ICMA PTH levels and both intact PTH measured by a two-site immunora-diometric assay (n=42, r=0.67, p

Calcium metabolism was studied in 37 patients with "idiopathic hypercalciuria" on a home diet and after 10 days of low calcium dietary intake (less than 400 mg/24h). After low calcium intake, urinary calcium excretion returned to within normal limits in 70% of the cases. In the group of patients which failed to respond to calcium restriction, TmPO4/GFR values were reduced and, furthermore, in 20% of them plasma iPTH and urinary cAMP levels were increased. These data seem to indicate that: the incidence of absorptive hypercalciuria is higher than hypercalciuria of renal origin; normocalcemic hyperparathyroidism due to primary calcium leak is present only in a limited number of cases, consequently, hypercalciuria secondary to renal phosphate leak is a rather frequent occurrence.

Plasma levels of calcium, phosphorus, immunoreactive calcitonin (iCT), immunoreactive parathyroid hormone (iPTH), and carcinoembryonic antigen (CEA) were measured in patients affected by tumors of various organs: 22 breast, 41 lung, 23 kidney, 16 gastrointestinal tract, and 8 other types. iCT plasma level was elevated in 53.6% of patients with bronchogenic cancer, in 31.8% with breast cancer, in 65.3% with renal cancer, in 31.2% with gastrointestinal cancer, and in 62.5% with other tumors. Blood calcium level was increased in 6 patients suffering from lung cancer; iCT plasma level was increased in all but one of these subjects. iPTH plasma level, measured in 35 patients, was elevated only in one case, in which normo-calcemia was present. Our results demonstrate that plasma iCT is increased in a high percentage of cancer patients and that it is probably a good tumor marker. The simultaneous measurement of CEA increases the diagnostic probability of the individual marker. The incidence of laboratory findings suggestive of primary or ectopic hyperparathyroidism was very low in our series of patients.

Calcitonin (CT) plasma levels and urinary hydroxyproline (OHPr) excretion were studied in twenty-eight patients (eleven males and seventeen females) with primary hyperparathyroidism in order to ascertain the effect of CT secretion on the severity of bone disease. The results show that in primary hyperparathyroidism plasma CT levels are increased in about 50% of patients independent of sex. Plasma CT levels were correlated with serum calcium values in males but not in females. Urinary OHPr excretion values appeared higher in those patients which showed lower CT plasma levels. In this latter group the incidence of undetectable CT plasma values was higher in females. The results suggest that in patients with primary hyperparathyroidism the persistent challenge of CT secreting parafollicular cells due to chronic hypercalcemia, may induce a decrease in their functional reserve, and that the bone involvement may have a greater incidence and more severe course in females, due at least in part, for their inability to increase CT secretion as much as males, due to an intrinsic sex-related lower CT secretory reserve.

This study has been carried out in order to investigate the effects of a standard oral calcium load in 18 hypercalciuric and 18 normocalciuric recurrent stone formers. Following oral loading there was not a significant difference in the two groups studied, as far as serum calcium increment was concerned; however, urinary calcium excretion was significantly greater in hypercalciuric stone formers. The results obtained, although they do not exclude the presence of intestinal calcium hyperabsorption, seem to demonstrate the existence of a diminution of renal tubular calcium reabsorption in patients with idiopathic hypercalciuria.

Summary— This study was carried out to evaluate the metabolic consequences of osteosclerotic skeletal metastases of prostatic origin in a homogeneous group of patients. We found significantly increased mean values of serum alkaline phosphatase activity and significantly reduced mean values of serum phosphate, 24-h urinary calcium, fasting calcium excretion and TmP/GFR in cancer patients with respect to age-matched controls. Mean serum immunoreactive parathyroid hormone (IPTH) levels were raised, with two patients showing increased values of the hormone above our normal limits. Our findings indicate that mild secondary hyperparathyroidism is a feature of these patients. However, it cannot be excluded that both the reduced serum phosphate and TmP/GFR values may be related, at least in some cases, to the effects of the tumour itself on tubular reabsorption of phosphate.

Early effects of parathyroid hormone (PTH) deficiency were studied in 12 patients with primary hyperparathyroidism due to single parathyroid adenoma by following the precise time course of changes in plasma calcium (Ca) and immunoreactive parathyroid hormone (iPTH) after parathyroid surgery and by prelabeling 2 patients with radiocalcium (Ca*). Surgical removal of the adenoma was immediately followed by a sudden increase in plasma Ca which preceded the usual fall. The increase in plasma Ca commenced simultaneously with the fall in iPTH and was accompanied by a parallel increase in specific activity (sp. act.) of plasma Ca*. Specific activity continued to rise for 2 h in both prelabeled patients, whereas blood calcium was already falling thereafter reaching a markedly low removal rate constant as long as plasma Ca decreased. When plasma Ca began to rise, sp. act. resumed a descending course. Our findings indicate that the initial hypercalemia depends on PTH withdrawal and results from a rapid flux into general extracellular fluid (ECF) of calcium coming from a compartment with higher sp. act., contained within the miscible pool, immediately followed by a reduction in calcium transfer from bone. These results suggest that acute PTH deficiency determines an outflow of calcium from bone cells and support the theory that PTH initiates its action by modifying their intracellular calcium content.

This study was carried out to investigate early effects of parathyroidectomy (PTx) on bone matrix collagen metabolism. Eleven patients suffering from primary hyperparathyroidism were studied by measuring urinary excretion of hydroxyproline (OHPr) and cAMP in samples collected before PTx and, on the day of surgery, at intervals of 1-3 h for the first 10 h and then at longer intervals. In six patients nondialyzable urinary OHPr and free plasma aminoacid levels were also assayed. We found that the average period required for OHPr/Cr ratio and plasma OHPr to reach normal values was longer than the mean time required for cAMP/Cr ratio to reach normal limits. In all patients the total amount of nondialyzable OHPr decreased in the first 24 h after PTx but thereafter a daily increase in the urinary excretion of nondialyzable component was seen, so that the fractional amount of nondialyzable OHPr in the fourth postoperative day (26.8 +/- 5.2 SE) was significantly higher than that of preoperative one (6.1 +/- 1.0; p less than 0.02). Our results confirm that PTx induces a reduction in the rate of bone collagen resorption and indicate that changes of OHPr/Cr ratio and free plasma OHPr values may be considered useful indices of successful parathyroid surgery, even though they lag behind those of cAMP. The different behavior of total and nondialyzable OHPr after surgery indicates that acute deficiency of parathyroid hormone induces a positive uncoupling of the two processes of bone remodeling, thus supporting the view that the acute direct effect of the hormone on bone formation is an inhibition of this process.

Summary Three patients with recurrent hyperparathyroidism (15, 8 and 3 years respectively, after the first operation) are described in order to establish the causes and define the clinical characteristics of the disease. The observation that in the present series recurrent hyperparathyroidism was associated either with an adenoma (two cases) or a carcinoma (one case), appears to stress the possibility of the pathological involvement of one gland even though recurrent hyperparathyroidism should be considered due to the chronic extrinsic stimulation of the parathyroid glands. The severity of the clinical and metabolic picture observed at the time of the first diagnosis and/or at the time of recurrence together with the simultaneous presence of bone and stone disease in the patients described is of particular interest. The cases reported underline the importance of carrying out careful metabolic investigations in patients with hyperparathyroidism not only before but also for a prolonged period of time after operation.