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Alessandro Antonelli

Publications and source records attributed to Alessandro Antonelli.

At least 19 recordsLinked to original sources

New trends in the treatment of undifferentiated carcinomas of the thyroid.

INTRODUCTION: Malignant tumours of the thyroid are generally classified as either well-differentiated thyroid carcinoma, which is composed of papillary and follicular carcinoma, or undifferentiated/anaplastic thyroid carcinoma (ATC). ATC is not only the most lethal disease in the field of endocrine surgery but also one of the most aggressive tumours characterized by an almost invariable fatal outcome, which only very rarely exceeds a 1-year course. DISCUSSION: The impact of surgical resection in association with external beam radiation on ATC outcome has been extensively investigated also in studies based on multicentric database, and there is a general agreement on the significance of a complete resection of the tumour. It has been difficult up to now to collect data regarding chemotherapy adjuvant treatment. In spite of the lack of an extensive review about the results of this kind of treatment by itself or as part of a multimodal approach, it seems that among the several chemotherapy agents experienced, none proved to influence significantly ATC prognosis. Neither doxorubicin (the most commonly used) nor other drugs, such as cisplatin, bleomycin, fluorouracil or cyclophosphamide, showed any real efficacy in controlling the disease. CONCLUSION: The most recent development in this field seems to be represented by the possibility offered by PPARg agonists; even more promising might be the use of adenovirus-mediated p53 tumour suppressor gene therapy or BMP-7. All these new therapies need further confirmation coming from ongoing clinical trials such as those involving the use of vascular and growth factor-targeted agents.

Antibiotics, Antineoplastic↗

Induction of chromatid-type aberrations in peripheral lymphocytes of hospital workers exposed to very low doses of radiation.

Radiological personnel represent workers exposed to low cumulative doses of radiation. As their surveillance is generally based on physical dosimetry, there is little or inconclusive information on biological effects due to radiation exposure at these doses. We aimed to explore the extent of chromosomal damage in circulating lymphocytes of hospital workers (technicians, nurses and physicians) chronically exposed to a very low level of radiation using conventional and molecular cytogenetic analyses (chromosome painting with chromosomes #2, #3 and #10 as probe cocktail). Compared with controls, exposed workers displayed a significant increase in the frequency of aberrant lymphocytes (1.26+/-0.11/100 cells versus 1.63+/-0.17/100 cells). In particular, exposed technicians showed significantly higher mean values than nurses or physicians (3.68+/-1.17/100 cells versus 1.36+/-0.18/100 cells and 1.36+/-0.09/100 cells, respectively). Interestingly, we found that the chromosomal damage was prevalently expressed as chromatid-type aberrations. Chromosome painting indicated that the frequency of chromosome rearrangements (CR; translocations and dicentrics pooled together) was approximately comparable between radiological workers and the control group. Moreover, we did not detect any significant difference due to radiation exposure when CR rates were considered separately for each of the three chromosomes in the probe cocktail.

Chromatids↗

Analysis of chromosome damage in circulating lymphocytes of radiological workers affected by thyroid nodules.

The aim of our study was to assess whether or not thyroid nodularity in combination with occupational exposure to low levels of ionising radiation would be correlated with chromosome damage in peripheral lymphocytes. Conventional chromosome-aberration analysis was performed on a group of 92 hospital workers with or without thyroid nodules. On the basis of measurements of their exposure levels, the workers were classified into a low (mean total level=0.03 mSv), medium (mean total level=1.04 mSv) or high (mean total level=8.60 mSv) exposure category. Our results indicate that among workers with thyroid nodules, the high-exposed workers showed significantly higher levels of both total (2.35+/-0.34 per 100 cells) and chromosome-type aberrations (1.46+/-0.20 per 100 cells) than medium-exposed (0.98+/-0.42 and 0.68+/-0.25 per 100 cells, respectively) or low-exposed workers (1.11+/-0.29 and 0.58+/-0.17 per 100 cells, respectively). Workers without thyroid nodules had comparable frequencies of chromosome aberrations among the three exposure categories. To our knowledge, this is the first study revealing a slight, but significant increase of chromosome damage in peripheral lymphocytes from hospital workers who developed thyroid nodules under conditions of occupational exposure to radiation well below the threshold limit for the workplace. The existence of a possible association between chromosome aberrations and development of thyroid nodularity will be discussed.

Analysis of Variance↗

Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing.

No study has evaluated contemporaneously serum CXC and CC chemokines changes in normal ageing. Serum levels of CXCL10 (sCXCL10) (CXC) and CCL2 (sCCL2) (CC) prototype chemokines have been measured in 164 healthy subjects, from 10 to 79 years of age (82 males/82 females). By simple regression analysis, sCXCL10 and sCCL2 were significantly related with increasing age (r=0.32, p<0.001; r=0.31, p<0.0001, respectively), and with each other (r=0.30, p=0.0004). In a multiple linear regression model, only age and sCCL2 were significantly related to sCXCL10 levels (p<0.001); age and sCXCL10 were significantly related to sCCL2 levels (p<0.001). Subjects with high sCXCL10 levels (>150 pg/ml) were not significantly associated with those with high sCCL2 levels (>559 pg/ml). This study, performed in healthy subjects on an age gradient, demonstrates an increase of sCXCL10 and sCCL2 with advancing age; the differential increase of sCXCL10 or sCCL2 may reflect a general shift towards Th1 or Th2 cytokines pattern, respectively.

Adolescent↗

Clinical aspects and surgical treatment of urinary tract endometriosis: our experience with 31 cases.

OBJECTIVES: To present and discuss clinical and surgical management of urologic endometriosis. METHODS: Retrospective review of a database on surgical patients with endometriosis. RESULTS: Thirty-one patients (incidence, 2.6%; mean age, 33.1 yr) were affected by urologic endometriosis (bladder, 12; ureter, 15; both, 4). Bladder endometriosis was revealed by symptoms related to menses and showed a typical endoscopic picture, whereas ureteral involvement had a nonspecific or silent symptomatology. All patients affected by bladder endometriosis and undergoing transurethral resection (2 cases) developed a bladder recurrence; a ureteral recurrence was observed in two of six patients submitted to laparoscopic ureterolysis and in one of two patients submitted to ureterectomy with ureteroureterostomy. Conversely, no relapses were observed among the 14 patients who had partial cystectomy or the 9 who had ureterectomy and ureterocystoneostomy. Finally, two patients underwent nephrectomy due to end-stage renal atrophy. CONCLUSIONS: Cystoscopy is advisable in women with pelvic endometriosis with lower urinary tract symptoms; the upper urinary tract should be evaluated in all patients with pelvic endometriosis to exclude asymptomatic ureteral involvement. Partial cystectomy gives the best results when used to treat bladder endometriosis. Ureterolysis can be successful only in case of limited ureteral involvement with no urinary obstruction, whereas terminal ureterectomy and ureterocystoneostomy should be preferred in case of obstructive ureteral endometriosis.

Adult↗

Thyroid disorders in chronic hepatitis C virus infection.

The prevalence of thyroid disorders has been evaluated in patients with hepatitis C virus (HCV) infection by many studies. From a review of the published controlled studies, it is possible to observe that: (1) most investigated patients with chronic HCV hepatitis, while a minority evaluated hepatitis C virus antibody (HCVAb)- seropositive patients (the two conditions are not comparable with regards to thyroidal repercussions, in fact, HCVAb-seropositive patients do not necessarily display changes of the immune system present in chronically infected HCV patients); and (2) some authors selected as internal control hepatitis B virus (HBV)-infected patients, while others selected apparently healthy controls or HCVAb-negative subjects. Pooling all data about HCV-positive patients (with chronic hepatitis or HCVAb positivity) and using as control the sum of healthy controls, HBV-infected patients and sera negative for HCVAb, a significant increase of the prevalence has been observed both for thyroid autoimmune disorders (odds ratio [OR] = 1.6; 95% confidence interval = [C]) 1.4-1.9) as well as for hypothyroidism (OR = 2.9; 95% CI = 2.0-4.1). The results of the epidemiologic studies showing an association between HCV infection and thyroid cancer need to be confirmed. The abovementioned evidences seem sufficient to suggest careful thyroid monitoring during the follow-up of patients with HCV infection.

Autoimmune Diseases↗

Increase of interferon-gamma-inducible CXC chemokine CXCL10 serum levels in patients with active Graves' disease, and modulation by methimazole therapy.

BACKGROUND: CXCL10 plays an important role in the initial phases of Graves' disease (GD) and autoimmune thyroiditis (AT); however, until now, CXCL10 serum levels (sCXCL10) in patients with GD have never been evaluated in relation to thyroid function and treatment. OBJECTIVE: To evaluate sCXCL10 in GD. DESIGN: Cross-sectional. PATIENTS: One hundred and three GD, 164 AT, 20 nontoxic multinodular goitre (NTMNG), 16 toxic nodular goitre (TNG) patients and 70 healthy controls (age- and sex-matched). MEASUREMENTS: We measured sCXCL10 in patients and controls, to relate this parameter to the clinical phenotype. RESULTS: Mean sCXCL10 in GD and AT patients were comparable (122+/-81 and 133+/-102 pg/ml) and significantly higher (P<0.01) than in controls or NTMNG patients (73+/- 32 and 76+/- 25 pg/ml, respectively). Hyperthyroid GD had significantly higher sCXCL10 than euthyroid or hypothyroid GD (145+/- 92, 107+/- 56 and 105+/- 46 pg/ml, respectively; P=0.01). GD patients with untreated hyperthyroidism had higher sCXCL10 than hyperthyroid or euthyroid GD patients under methimazole (MMI) treatment (166+/-125, 124+/- 41 and 94+/- 35 pg/ml, respectively; P=0.006). Comparable sCXCL10 levels were observed in newly diagnosed untreated hyperthyroid GD patients with respect to untreated patients with relapse of hyperthyroidism after a previous MMI course (176+/-125, 155+/- 97 pg/ml, respectively). GD had similar sCXCL10 to AT and higher than TNG patients or controls (all age- and sex-matched) (144+/- 81, 149+/- 114, 101+/- 27 and 86+/- 44 pg/ml, respectively; P=0.02). CONCLUSIONS: sCXCL10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. The reduction in sCXCL10 in treated patients with GD may be related to the immunomodulatory effects of MMI.

Adult↗

Surgical treatment of adrenal metastasis from renal cell carcinoma: a single-centre experience of 45 patients.

OBJECTIVE: To report, in a retrospective study, the diagnostic problems and oncological results of surgery in patients with either synchronous or metachronous adrenal metastasis, which are uncommon in renal cancer, at 2-10% of patients. PATIENTS AND METHODS: Of 1179 patients treated for renal cancer between 1987 and 2003, 914 had renal surgery with concomitant ipsilateral adrenalectomy (routinely in 875 and for abnormal findings on computed tomography, CT, in 39) and 15 contralateral adrenalectomy (all after suspicious findings on CT). During the follow-up after renal surgery, another 14 patients had adrenalectomy for CT evidence of an abnormal adrenal gland, contralateral to the previous renal tumour in 12 and bilaterally in two. RESULTS: Of 914 ipsilateral adrenal glands removed during renal surgery, 854 (93.5%) were normal on pathological examination, 28 (3%) had a benign pathology, six (0.8%) were directly infiltrated by the tumour and 26 (2.7%) were metastatic. For both benign and metastatic ipsilateral adrenal pathology, CT had sensitivity, specificity and positive/negative predictive values of 47%, 99%, 73% and 96%, respectively. Of 29 contralateral glands removed because of suspicious CT findings (15 at diagnosis of renal cancer, 14 during the follow-up) there was no abnormality in one (3.4%), a benign pathology in seven (24%) and a metastasis in 21 (72%). Thus there were 32 synchronous (incidence 2.7%; ipsilateral to the renal tumour in 24, contralateral in six and bilateral in two), and 13 metachronous adrenal metastases (incidence 1.0%; contralateral in 11 and bilateral in two). The metachronous metastases were diagnosed at a mean (range) interval of 30.6 (8-73) months after renal surgery. No ipsilateral adrenal metastases were discovered at diagnosis or during the follow-up in the 382 patients with an organ-confined renal tumour of <4 cm in diameter. Twenty-seven patients with an isolated adrenal metastasis (synchronous in 14, metachronous in 13) had statistically significantly (P < 0.001) better survival than the 18 (all synchronous) with multiple sites of metastatic disease. In particular, there was long-term survival (mean 83 months) in 10 patients with an isolated adrenal metastasis. CONCLUSION: Sparing the ipsilateral adrenal is advisable only for organ-confined renal tumours of <4 cm in diameter; clinical local staging of renal cancer is the best predictor of the risk of adrenal metastasis. Conversely, CT had good diagnostic ability for the contralateral adrenal gland, especially during the follow-up. Some patients with isolated adrenal metastasis could be treated by metastasectomy, with long-term survival free of disease and confirming that, even if in a few and unselectable patients, removing all the neoplastic bulk can be curative. Nevertheless, the high rate of relapse underlines the need for an effective systemic therapy, and more so for widespread metastatic disease that currently cannot be cured.

Adrenal Gland Neoplasms↗

Prevalence of hypothyroidism and Graves disease in sarcoidosis.

BACKGROUND: The association of sarcoidosis (S) and thyroid autoimmunity has been reported by several studies in a wide range of variability. The aim of our study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with S vs gender-matched and age-matched control subjects. METHODS: Thyroid hormones and antithyroid antibodies, thyroid ultrasonography and fine-needle aspiration were performed in 111 patients with S who had been consecutively referred to the Respiratory Pathophysiology Section of the University of Pisa, and the results were compared to 333 gender-matched and age-matched control subjects from the same geographic area. RESULTS: The odds ratio for subclinical hypothyroidism for female patients with S vs control subjects was 2.7 (95% confidence interval [CI], 1.3 to 5.9); for anti-thyroid peroxidase antibody titer (AbTPO) positivity, 2.2 (95% CI, 1.2 to 3.9); and for thyroid autoimmunity, 1.9 (95% CI, 1.1 to 3.2). The mean values of thyroid-stimulating hormone and AbTPO were higher in female S patients than in control subjects (p < 0.01). A significantly higher prevalence of clinical hypothyroidism (four patients) and Graves disease (three patients) was observed in female S patients than in control subjects (none; p = 0.005 and 0.0026, respectively). Two cases of papillary thyroid cancer were detected in S patients. No significant difference between S patients and control subjects was detected for free triiodothyronine and thyroxine, antithyroglobulin autoantibodies, thyroid volume and nodularity, and subclinical hyperthyroidism. CONCLUSIONS: Thyroid function, AbTPO antibodies, and ultrasonography should be tested as part of the clinical profile in female S patients. Subjects who are at high risk (female subjects, those with positive AbTPOs, and those with hypoechoic and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.

Age Distribution↗

Increased serum CXCL10 in Graves' disease or autoimmune thyroiditis is not associated with hyper- or hypothyroidism per se, but is specifically sustained by the autoimmune, inflammatory process.

OBJECTIVE: Serum CXCL10 (an interferon-gamma-inducible chemokine) levels (sCXCL10) are increased in several autoimmune conditions, including Graves' disease (GD) and autoimmune thyroiditis (AT). Longitudinal assessment of sCXCL10 in autoimmune hypo- or hyperthyroidism has not yet been performed. DESIGN AND METHODS: We longitudinally assayed sCXCL10 in the following groups: thirty-three GD and 11 toxic nodular goiter (TNG) patients when hyperthyroid (Hyper) and when reaching euthyroidism (Eu) with methimazole therapy (MMI) sixty-six AT (33 hypothyroid (Hypo) and 33 Eu) patients, basally and after reaching EU (for Hypo) with levothyroxine (L-T4) therapy twenty-two patients with thyroid cancer (CA) under L-T4-suppressive treatment, of whom 11 were re-evaluated after L-T4 withdrawal for diagnostic WBS, and 11 after recombinant TSH (rhTSH) administration thirty-three healthy controls. RESULTS: At initial evaluation, Hyper GD and AT (Hypo significantly higher than Eu) showed significantly higher mean sCXCL10 than all other groups. MMI treatment led to a significant decrease in sCXCL10 only in GD (not in TNG), while restoration of Eu, in Hypo AT, by L-T4 was not accompanied by significant sCXCL10 change. CA showed sCXCL10 comparable to controls, and both Hypo after L-T4 withdrawal and rhTSH injection had no effect on sCXCL10. CONCLUSIONS: Treatment of Hyper leads to a significant decrease in sCXCL10 only in GD, and this probably depends upon the MMI immunomodulatory effect. L-T4 correction of Hypo is not accompanied by significant modification of sCXCL10 in AT. Increased sCXCL10 is not associated with Hyper or Hypo per se, but is specifically sustained by the autoimmune inflammatory event occurring in both GD and AT.

Adult↗

Surgical approach to urinary endometriosis: experience on 28 cases.

OBJECTIVES: Endometriosis (e.) involving the urinary tract must be regarded as a rare condition with specific surgical implications. Our experience on the treatment of 28 patients is presented. PATIENTS AND METHODS: Twenty-eight patients with a urological e. (bladder 11 patients, ureter 14, both bladder and ureter 3) were observed and treated between 1995 and 2005. Thirteen patients (46%) had been previously surgically treated for pelvic e. at a mean distance of 22 months before. All the patients with bladder e. presented with typical symptoms related to menses and the urinary location was isolated in 42.8%. Differently, the patients having ureteral involvement complained often a vague or silent symptomatology, but they always showed some extra-urinary pelvic locations. Among the cases with bladder e., 2 patients underwent TUR and hormonal therapy and 12 partial cystectomy. The patients with ureteral e. were submitted to ureterolysis in 5 cases, segmentary ureterectomy and uretero-ureteroanastomosis in 2 and terminal ureterectomy and ureterocystoneostomy in 8. Two more cases with ureteral e. were nephrectomized due to end-stage renal atrophy. RESULTS: At a mean distance of 58 months (9-110 months) from surgery, 22 patients have a unremarkable follow-up. On the other hand, an urological relapse was evidenced in 5 cases previously submitted to TUR (2 cases), ureterolysis (2 cases) or segmentary ureterectomy and termino-terminal ureteral anastomosis (1 case). The relapsing e. was treated by partial cystectomy or terminal ureterectomy with ureterocystoneostomy, with good results over time. CONCLUSION: Urinary tract is rarely involved by e., but this condition has peculiar clinical and surgical implications. Being TUR ineffective, the therapy of choice of bladder e. is partial cystectomy, possibly via a laparoscopic approach. Differently from bladder e., the preoperative diagnosis of ureteral e. is surely hard. So, a high index of suspect should be regarded in each young female patient with a ureteral stricture and a study of the upper urinary tract (US and/or urography) should be performed in all the patients with pelvic e. Ureterolysis can be successful only in a minority of the cases showing a very limited disease not determining any urinary flow obstructions. In all the other cases the procedure of choice is terminal ureterectomy and ureterocystoneostomy without employing the distal ureter.

Adult↗

Durable and complete remission of a metastatic bladder sarcomatoid carcinoma with chemotherapic and surgical treatments.

The sarcomatoid carcinoma of the urinary bladder is a rare variant of transitional carcinomas with an extremely aggressive clinical course and dismal prognosis regardless therapies. The diagnosis of a bladder sarcomatoid carcinoma involving perivesical tissues with limphnodal, hepatic and lung metastasis was done in a 34-years old male. The disease underwent complete remission after neoadjuvant chemotherapy with adriblastine and ifosfamide, radical surgery and adjuvant chemotherapy with the same drugs, as confirmed by CT, vesical biopsies during chemotherapy and by the findings detected on the surgical specimen. Follow-up is negative for relapses at 72 months. The sarcomatoid bladder carcinoma is a rare variant of transitional carcinoma (0.31%), usually diagnosed in the late decades of life, with a survival time of a few months for metastatic patients regardless of any adopted therapies. The case presented is remarkable due to the young age of the patient but, overall, for the complete and durable regression of the disease achieved applying a chemotherapic scheme commonly adopted to treat pure sarcomatous mesenchimal neoplasms. Due to the rarity of the disease and the consequent unfeasibility of randomized studies, in our opinion these results, even if obtained in a single case, suggest a viable therapeutic option.

Adult↗

High prevalence of thyroid autoimmunity and hypothyroidism in patients with psoriatic arthritis.

OBJECTIVE: To evaluate the prevalence of thyroid disorders in a group of patients with psoriatic arthritis (PsA). METHODS: A complete thyroid investigation was carried out in 80 patients with PsA, in gender- and age-matched subjects (1:5) drawn from the general population (controls), and in 112 patients with rheumatoid arthrtitis (RA) with similar iodine intake. RESULTS: Anti-thyroid peroxidase antibodies (AbTPO), a hypoechoic thyroid, and subclinical hypothyroidism were significantly more frequent in women with PsA than in control women, and their frequency was similar to that in patients with RA (positive AbTPO titer 28%, 12%, and 31%; hypoechoic thyroid 31%, 16%, and 36%; subclinical hypothyroidism 25%, 8%, and 12%, respectively). Among men, positive AbTPO titers and a hypoechoic thyroid were found more frequently in the patients with PsA and RA than in controls (positive AbTPO titer 14%, 5%, and 2%; hypoechoic thyroid 16%, 10%, and 3%, respectively). All patients with PsA with subclinical hypothyroidism had polyarticular involvement (p </= 0.05) and a longer disease duration (years 19 +/- 15 vs 11 +/- 8, p = 0.03) than patients with euthyroid PsA. The prevalence of subclinical hyperthyroidism, thyroid nodules, and thyroid enlargement was not significantly different among the 3 groups. CONCLUSION: Our results demonstrate a significantly higher prevalence of thyroid autoimmunity (positive AbTPO, hyoechoic thyroid) findings in men and women with PsA and of subclinical hypothyroidism in women with PsA than in the general population. Therefore, thyroid function tests, an AbTPO assay, and thyroid ultrasound should be performed as part of the clinical evaluation, particularly in women with PsA.

Adult↗

Effects on inflammatory and nutritional markers of haemodiafiltration with online regeneration of ultrafiltrate (HFR) vs online haemodiafiltration: a cross-over randomized multicentre trial.

BACKGROUND: HFR [double chamber haemodiafiltration (HDF) with reinfusion of regenerated ultrafiltrate] is a novel dialytic method which combines the processes of diffusion, convection and adsorbance. In this technique an adsorbent cartridge of resin and charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The aim of this multicentre randomized cross-over study was to compare HFR to online HDF in terms of inflammatory and nutritional parameters. METHODS: After a 1 month run-in period of standard bicarbonate dialysis (HD) with a synthetic membrane, 25 chronic dialytic patients were randomized (A-B or B-A) to be treated by HFR (A) with a two-chamber filter (SG 8 Plus - high permeability Polysulphone HF 0.7 m2 + SMC 1.95 sqm; Bellco, Mirandola, Italy) or by online sterile bicarbonate HDF. Each study period of 4 months was separated by 1 month of HD and the entire length of the study was 10 months. CRP levels were measured by a highly sensitive nephelometric assay (Dade, Behring) with a sensitivity of 0.1 microg/ml. Cytokine concentrations were determined by EIA [Interleukin (IL) 6, Biosource, USA and IL-10 Bender MED-Systems, Vienna]. The sensitivity thresholds were < 5 pg/ml for IL-6 and < 8 pg/ml for IL-10. Serum leptin was determined with a ELISA method (Biosource, USA). All parameters were determined monthly in patients starting a midweek dialytic session. RESULTS: Plasma CRP and IL-6 were significantly reduced during the 4 months of HFR and HDF: CRP from 8.0 +/- 3.2 to 5.6 +/- 3.4 mg/l with HFR (P < 0.05) and from 9.4 +/- 4.3 to 5.9 +/- 3.9 mg/l with HDF (P < 0.05). IL-6 decreased from 14.8 +/- 6.3 to 10.1 +/- 3.2 with HFR (P < 0.02) and from 12.1 +/- 4.2 to 9.6 +/- 3.7 with HDF (P = ns) with a percentage decrease after 4 months of 32% with HFR vs 21% with HDF. During the 1 month wash-out period with HD, CRP increased from 5.7 +/- 3.6 to 8.7 +/- 3.9 mg/l (P < 0.01) and IL-6 from 10 +/- 3.4 to 13.5 +/- 5.2 pg/ml (P < 0.01). A significant increase in IL-10 was detected either in HFR (from 4.8 +/- 2.1 to 6.89 +/- 1.7 pg/ml) and in HDF (from 3.3 +/- 1.7 to 8.95 +/- 4.3 pg/ml; P < 0.05) after 4 months. No significant variation in serum leptin levels were observed during the study. CRP and IL-6 were highly correlated (r = 0.54; P < 0.001) as was serum albumin and prealbumin (r = 0.39; P < 0.001). Serum albumin was negatively correlated with CRP (r = -0.26; P < 0.01) and IL-6 (r = -0.19; P < 0.05); serum prealbumin was correlated with IL-6 (r = 0.37; P < 0.001) and with CRP (r = 0.24; P < 0.01). CONCLUSIONS: Haemodiafiltration with online regeneration of ultrafiltrate and online HDF are highly biocompatible techniques and no significant difference between HFR and online HDF was observed in terms of reduction of inflammatory markers. Further studies with a longer follow-up are needed to evaluate the clinical relevance of the online endogenous reinfusion to counteract the chronic inflammatory state of the uraemic patient.

Aged↗

Interferon-gamma-inducible alpha-chemokine CXCL10 involvement in Graves' ophthalmopathy: modulation by peroxisome proliferator-activated receptor-gamma agonists.

CONTEXT: CXC alpha-chemokine CXCL10/inducing protein-10 play an important role in the initial phases of autoimmune thyroid disorders. Human thyrocytes in primary culture produce large amounts of CXCL10 when stimulated by interferon-gamma (IFNgamma) and TNFalpha. OBJECTIVE: Serum CXCL10 levels (sCXCL10) were measured in patients with active or inactive Graves' ophthalmopathy (GO). The effects of IFNgamma and TNFalpha stimulation and peroxisome proliferator-activated receptor-gamma (PPARgamma) activation on CXCL10 secretion in primary cultures of thyrocytes, orbital fibroblasts, and preadipocytes were tested. PATIENTS: Sixty consecutive patients with Graves' disease, 60 age- and sex-matched patients with GO, and 60 controls were studied. RESULTS: sCXCL10 was higher (P < 0.0001) in Graves' disease (120 +/- 83 pg/ml; n = 60) and GO (122 +/- 71; n = 60) patients than in age- and sex-matched euthyroid controls (72 +/- 32; n = 60). Among GO patients, sCXCL10 levels were significantly higher in those (n = 14) with active disease (171 +/- 197) than in those with inactive disease (114 +/- 45 pg/ml; P < 0.003). In primary cultures of thyrocytes, retrobulbar fibroblasts and retrobulbar preadipocytes from GO patients, CXCL10 production was absent under basal conditions; dose-dependent secretion of CXCL10 was not induced by TNFalpha alone, whereas stimulation with IFNgamma or TNFalpha plus IFNgamma induced CXCL10 release. Treatment of all cell types with the PPARgamma agonist, rosiglitazone, dose-dependently (0.1-10 microm) suppressed IFNgamma- plus TNFalpha-induced CXCL10 release. CONCLUSIONS: We conclude that in GO, thyrocytes and retrobulbar cell types participate in the self-perpetuation of inflammation by releasing chemokines under the influence of cytokines. PPARgamma activation plays an inhibitory role in this process.

Adult↗

Clinical, resting echo and dipyridamole stress echocardiography findings for the screening of renal transplant candidates.

BACKGROUND: Preoperative screening for coronary artery disease is recommended in high-risk renal transplant candidates. Aim of this study was to prospectively assess the value of a comprehensive risk stratification strategy including clinical, resting echo, and dipyridamole stress echo findings before renal transplantation. METHODS: The study group consisted of 71 renal transplant candidates (47 men; age 54+/-11 years) fulfilling one or more of the following high-risk clinical criteria: history of coronary artery disease, wall motion abnormalities at resting echo, dialysis dependency lasting >5 years, presence of 2 or more risk factors. Clinical history, resting echo, and dipyridamole stress echo (up to 0.84 mg over 10 min + atropine up to 1 mg) were obtained in all subjects. RESULTS: Mean number of risk factors was 2.5+/-1.0. Known coronary artery disease and diabetes were present, respectively, in 2 (3%) and 11 (15%) persons. No patient had left ventricular ejection fraction <45%. Left ventricular hypertrophy was found in 53 (74%) cases. Stress echo showed 100% safety and 97% overall feasibility. Inducible ischemia (new wall motion abnormalities) was detected in 3 (4%) subjects. During follow-up (36+/-12 months), 8 (11%) cardiac events occurred: 2 deaths, 2 myocardial infarctions, 3 coronary interventions, and 1 pulmonary edema. The perioperative period and subsequent follow-up (22+/-12 months) was uneventful among 32 patients who received renal transplantation. Four-year event-free survival was 92% in those without ischemia; it was 96% in the non-diabetic population. Diabetes (HR=4.78), age (HR=1.14), and left ventricular mass index (HR=1.02) were independent prognostic indicators among clinical and resting echo variables. The global chi-square of the statistical model was 18.8; it increased to 27.3 (+45%) after the addition of stress echo result. CONCLUSIONS: Renal transplant candidates can undergo effective stratification of risk by combining clinical, resting echo and dipyridamole stress echo findings.

Adult↗

3,5-diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats.

The effect of thyroid hormones on metabolism has long supported their potential as drugs to stimulate fat reduction, but the concomitant induction of a thyrotoxic state has greatly limited their use. Recent evidence suggests that 3,5-diiodo-L-thyronine (T2), a naturally occurring iodothyronine, stimulates metabolic rate via mechanisms involving the mitochondrial apparatus. We examined whether this effect would result in reduced energy storage. Here, we show that T2 administration to rats receiving a high-fat diet (HFD) reduces both adiposity and body weight gain without inducing thyrotoxicity. Rats receiving HFD + T2 showed (when compared with rats receiving HFD alone) a 13% lower body weight, a 42% higher liver fatty acid oxidation rate, appoximately 50% less fat mass, a complete disappearance of fat from the liver, and significant reductions in the serum triglyceride and cholesterol levels (-52% and -18%, respectively). Thyroid hormones and thyroid-stimulating hormone (TSH) serum levels were not influenced by T2 administration. The biochemical mechanism underlying the effects of T2 on liver metabolism involves the carnitine palmitoyl-transferase system and mitochondrial uncoupling. If the results hold true for humans, pharmacological administration of T2 might serve to counteract the problems associated with overweight, such as accumulation of lipids in liver and serum, without inducing thyrotoxicity. However, the results reported here do not exclude deleterious effects of T2 on a longer time scale as well as do not show that T2 acts in the same way in humans.

AMP-Activated Protein Kinases↗