Biomedical subjects

Gherardo Mazziotti

Publications and source records attributed to Gherardo Mazziotti.

24 records · Page 2Linked to original sources

PubMed2003

Type-1 response in peripheral CD4+ and CD8+ T cells from patients with Hashimoto's thyroiditis.

OBJECTIVE: In this study we performed single-cell analysis of the intracellular cytokine expression in peripheral CD4+ and CD8+ lymphocytes from patients with Hashimoto's thyroiditis (HT) to investigate the type-1 response separately for the two lymphocyte sub-populations. DESIGN AND METHODS: Twenty-nine patients affected by HT and 20 healthy subjects, matched for sex and age, were enrolled. After the analysis of the lymphocyte sub-populations, the intracellular content of interferon-gamma (IFN-gamma) in phorbolmyristate acetate (PMA)-stimulated CD4+ and CD8+ lymphocytes was assayed. Moreover, the CD4+ lymphocytes were also evaluated for the intracellular expression of IL-4. RESULTS: No significant differences in CD3+, CD4+ and CD8+ lymphocytes were found between HT patients and control subjects. However, the HT patients showed higher numbers of CD4+ IFN-gamma+, CD4+ IL-4+ and CD8+ IFN-gamma+ (t-test, P< or =0.001) cells than the control subjects. Analysing the intracellular expression of IFN-gamma and IL-4 in relation to thyroid function, we found that the euthyroid patients (18 cases) showed more expression of IL-4 in CD4+ lymphocytes than the control subjects, without any significant modification of IFN-gamma expression in CD4+ and CD8+ lymphocytes. However, the hypothyroid patients (11 cases) showed an increase of IFN-gamma expression in both CD4+ and CD8+ lymphocytes with respect to the control subjects and the euthyroid patients. Moreover, the expression of IL-4 in CD4+ cells from hypothyroid patients was significantly lower than that seen in the euthyroid cases and comparable to that found in the control subjects. CONCLUSIONS: Our study has demonstrated that the peripheral CD4+ and CD8+ T lymphocytes from the HT patients show a type-1 activation strictly correlated to the occurrence of hypothyroidism. Further studies will be needed to clarify the exact role of peripheral lymphocytes in HT and whether they could provide a reliable marker of thyroid immune involvement.

Adolescent↗

PubMed2002

Serum insulin-like growth factor I evaluation as a useful tool for predicting the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a prospective study.

BACKGROUND: Although experimental studies have demonstrated an important role of insulin-like growth factor I (IGF-I) in hepatocarcinogenesis, the clinical data about IGF-I in patients with hepatocellular carcinoma (HCC) are scarce and controversial. To the authors' knowledge, this is the first prospective study investigating the longitudinal correlation between modifications in serum IGF-I levels and the development of HCC in a cohort of patients with hepatitis C virus (HCV)-related cirrhosis. METHODS: One hundred fourteen consecutive patients with HCV-related Child Grade A cirrhosis were followed prospectively at the Second University of Naples for 56.4 +/- 12.0 months with ultrasound examinations of the liver and serum alpha-fetoprotein determination every 6 months. At each clinical evaluation, the severity of disease was graded according to the established Child-Pugh scoring system. Serum IGF-I levels were measured prospectively at the study entry and at least every 12 months throughout follow-up. RESULTS: Twenty patients (19.2%) developed HCC during follow-up. Eleven of these patients had persistent Child Grade A cirrhosis for the whole study, whereas the other 9 patients developed HCC after their cirrhosis progressed from Child Grade A to Grade B. In patients who remained free of HCC for the whole study, serum IGF-I concentrations did not modify significantly during follow-up. Conversely, in patients who developed HCC, IGF-I levels decreased significantly during follow-up (from 72.6 +/- 29.9 microg/L to 33.8 +/- 14.5 microg/L; P = 0.001). In these patients, the significant decrease occurred both in patients with persistent Child Grade A cirrhosis and in patients with cirrhosis that progressed from Child Grade A to Grade B. The reduction in IGF-I level preceded the diagnosis of HCC by 9.3 +/- 3.1 months. CONCLUSIONS: This prospective study demonstrates that, in patients with HCV-related cirrhosis, 1) the development of HCC is accompanied by a significant reduction of serum IGF-I levels independent of the grade of impairment of liver function; and 2) modification of the IGF-I level precedes the morphologic appearance of HCC, permitting a precocious diagnosis of the tumor.

Adult↗

PubMed2002

Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly.

BACKGROUND AND OBJECTIVE: The therapeutic efficacy of lanreotide SR and octreotide LAR has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR in previously untreated patients with acromegaly. We aimed to investigate the long-term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy. PATIENTS AND METHODS: Twenty-three newly diagnosed patients with acromegaly (14 women, nine men) with active disease began the study; of these, three were lost for follow-up, leaving a total of 20 patients to complete the study. Patients were assigned randomly to lanreotide SR (12 patients) and octreotide LAR (eight patients), and the randomization stratified patients to assure a balance between the groups with respect to baseline tumour dimension, age and sex. Tumour volume was evaluated by magnetic resonance imaging of the sella, and calculated with the rotating ellipsoid formula. A morphological and biochemical evaluation was performed at baseline, 12 and 24 months after beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour volume of at least 10% was considered significant. RESULTS: Biochemical control increased progressively throughout the study in patients with microadenomas more than in patients with macroadenomas (70% vs. 10%; P < 0.05) and without a difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/- 18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/- 17.0% vs. 16.1 +/- 8.0%, respectively; P < 0.05). No statistical difference in the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy, no further overall shrinkage was observed, compared to the 12-month evaluation (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%, respectively). CONCLUSIONS: This study showed that the new long-acting somatostatin analogues, lanreotide SR and octreotide LAR, cause significant shrinkage of pituitary GH-secreting adenomas in previously untreated patients with acromegaly. This effect was more marked in macroadenomas than microadenomas, and did not correlate with control of GH hypersecretion.

Acromegaly↗

PubMed2002

Iodized salt improves the effectiveness of L-thyroxine therapy after surgery for nontoxic goitre: a prospective and randomized study.

OBJECTIVE: To investigate whether the addition of iodized salt to daily diet in thyroidectomized patients for nontoxic goitre could influence the effectiveness of nonsuppressive L-thyroxine (L-T4) therapy on thyroid remnant size, during 12 months' follow-up after thyroid surgery. DESIGN AND PATIENTS: A consecutive series of selected 139 patients (26 males, 113 females; median age 45 years, range 30-69 years) living in a moderate iodine-deficient area, and undergoing thyroid surgery for nontoxic multinodular goitre, was enrolled. Patients were assigned randomly to two different therapeutic regimens: 70 patients received L-T4 therapy alone (Gr. L-T4), while the remaining 69 patients took iodized salt on a daily basis in addition to L-T4 treatment (Gr. L-T4 + I). In both groups, the initial L-T4 dose was 1.5 microg/kg/day, which, in our experience, has been shown to be intermediate between suppressive and replacement doses. To avoid the risks of mild thyrotoxicosis and to limit the excessive TSH stimulation of the thyroid remnant, the L-T4 dose was adjusted in those patients with serum TSH levels outside the lowest two-thirds of the normal range (0.3-2.5 mU/l). An ultrasound evaluation of thyroid remnant size was performed after thyroid surgery and 12 months later. RESULTS: After surgery, the median thyroid remnant volume was 3.5 ml (range 0.4-13.9 ml) in Gr. L-T4 and 4.6 ml (range 0.5-12.7 ml) in Gr. L-T4 + I (P = 0.06). After 1 year of follow-up, the patients treated with L-T4 + I obtained a remnant volume reduction (-39.7%, range -87.0% to +91.2%) significantly (P = 0.006) greater than that observed in patients assuming L-T4 alone (-10.2%, range -89.4% to +85.0%). However, the percentage of patients showing an increase in remnant size in the months following surgery was higher in Gr. L-T4 than in Gr. L-T4 + I (22/60 vs. 9/66; P = 0.01). In Gr. L-T4 patients the thyroid remnant volume variation throughout 12 months of treatment was correlated significantly with the size of the thyroid remnant found at the first ultrasound evaluation (R(2) = 0.3; P < 0.001). No such correlation was found in Gr. L-T4 + I patients, for whom the therapy maintains a similar effectiveness in patients with either a large or a small postsurgery thyroid remnant. In patients treated with L-T4 alone, the remnant volume variation was correlated significantly with the median serum TSH values attained in the course of treatment (R2 = 0.4; P < 0.001). The highest reduction in remnant volume was observed only by lowering the serum TSH concentrations. In patients treated with L-T4 plus iodine, instead, the thyroid remnant volume reduction occurred independently of the plasma TSH levels attained in the course of treatment. CONCLUSIONS: Our short-term prospective and randomized study leads us to conclude that, in patients living in a moderate iodine-deficient area and undergoing thyroid surgery for nontoxic goitre: (1) the iodine prophylaxis improves the effects of postsurgery nonsuppressive L-T4 therapy on thyroid remnant size. (2) In patients treated with L-T4 alone the therapeutic effectiveness decreases in the presence of a large postsurgery thyroid remnant. With the addition of iodine, the L-T4 maintains a similar efficacy in patients with either a large or a small remnant. (3) During treatment with L-T4 alone the highest therapeutic effectiveness is attained by lowering the plasma TSH concentration. With the addition of iodized salt to the daily diet the effects of L-T4 on remnant size are relevant independently of the TSH levels.

Adult↗

PubMed2002

The addition of ribavirin to interferon-alpha therapy in patients with hepatitis C virus-related chronic hepatitis does not modify the thyroid autoantibody pattern but increases the risk of developing hypothyroidism.

OBJECTIVE: The aim of this study was to investigate whether the addition of ribavirin (RIBA) to interferon-alpha (IFN-alpha) therapy increases the risk of developing thyroid autoimmunity and/or dysfunction. DESIGN AND METHODS: The study group (group A) included 72 patients undergoing treatment with IFN-alpha (3-6 million units three times weekly) plus RIBA (1.0-1.2 g/day) for chronic hepatitis C (CHC), as first line therapy (30 cases) or as a second therapeutic attempt after a previous ineffective IFN-alpha treatment (42 cases). The control group (group B) encompassed 75 age- and sex-matched patients affected by CHC, undergoing treatment with IFN-alpha alone as first line therapy (35 cases) or as a second therapeutic attempt (40 cases). Thyroid autoimmunity and function were retrospectively evaluated on frozen aliquots, drawn before, after 6 months, and at the end of the antiviral treatment. In patients receiving two antiviral treatments (42 cases in group A and 40 cases in group B) thyroid parameters were also assayed on serum samples drawn before and at the end of the first IFN-alpha therapy. RESULTS: Thyroid autoimmunity rate (17/72 for group A and 17/75 for group B) as well as anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) serum levels were comparable between the two groups. Similarly, in patients undergoing two consecutive antiviral treatments (42 cases in group A and 40 cases in group B) the percentage of positivity for thyroid autoantibodies did not change significantly from the first to the second therapeutic schedules in both groups, with no significant increase of median TgAb and TPOAb levels. By the same token, all but one patient negative for thyroid autoantibodies at the end of the first treatment remained so also during the subsequent treatment. In group A patients, the rate of hypothyroidism (11/72) was significantly higher than that observed in group B (3/75). Similarly, in patients undergoing two consecutive antiviral treatments the percentage of hypothyroidism increased significantly from the first to the second therapeutic schedule in group A (from 4.8% to 19.0%; P<0.05) but not in group B (from 4.7% to 7.1%; not significant). In group A, the occurrence of hypothyroidism during treatment with IFN-alpha+RIBA was significantly correlated with a long-term remission of CHC. CONCLUSIONS: Our study shows that: (i) the addition of ribavirin to IFN-alpha therapy for CHC does not modify the thyroid autoantibody pattern but it is associated with a higher risk of hypothyroidism; (ii) the patients without thyroid autoantibodies at the end of a previous treatment with IFN-alpha alone are protected from the development of thyroid autoimmunity and/or dysfunction in a second course of antiviral treatment with IFN-alpha+RIBA; (iii) the development of hypothyroidism in patients with thyroid autoantibodies undergoing treatment with IFN-alpha+RIBA is significantly associated with the long-term remission of CHC.

Adult↗

PubMedDate not supplied

Glucocorticoid-induced osteoporosis: an update.

Glucocorticoid-induced osteoporosis occurs in two phases: a rapid, early phase in which bone mineral density is reduced, possibly as a result of excessive bone resorption, and a slower, progressive phase in which bone mineral density declines because of impaired bone formation. Although the indirect effects of glucocorticoids on bone are evident, their direct effects on osteoblasts, osteoclasts and osteocytes are primarily operative in the pathogenesis of glucocorticoid-induced osteoporosis. The management of patients exposed to glucocorticoids includes general health measures, sufficient calcium and vitamin D, and reducing the therapeutic regimen to the minimal effective dose. The gold standard in the pharmacological treatment of glucocorticoid-induced osteoporosis in postmenopausal women involves the use of bisphosphonates, which should be started soon after beginning chronic glucocorticoid therapy. Anabolic and alternative therapeutic strategies are currently under investigation in glucocorticoid-induced osteoporosis.

Bone Density↗