BRAF mutation analysis in thyroid nodules with indeterminate cytology: our experience on surgical management of patients with thyroid nodules from an area of borderline iodine deficiency.

PURPOSE: Fine-needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains indeterminate for 12-18 % of nodules. BRAF V600E mutation has been reported to show a high specificity for malignant thyroid nodules and the use of this marker to refine indeterminate FNA cytology results may be a useful diagnostic adjunctive tool in the pre-operative evaluation of thyroid nodules. The aim of this study was to estimate the prevalence of BRAF exon 15 mutation (V600E) and its clinical value as a diagnostic tool in a series of thyroid nodules with indeterminate cytology from an area of borderline iodine deficiency. SUBJECTS AND METHODS: One hundred and fifty-three thyroid samples obtained by FNA of thyroid nodules from 151 patients were subjected to the analysis of BRAF V600E mutation by direct sequencing. In the study 54 nodules with indeterminate cytology, 56 benign and 43 malignant thyroid nodules were included. RESULTS: V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules and in only 1/54 indeterminate nodules that, after histology, turned out to be at a papillary thyroid carcinoma. CONCLUSIONS: The application of BRAF exon 15 analysis showed limitations when applied to discriminate thyroid nodules with indeterminate cytology if wild-type BRAF is found, and there is no role for avoiding diagnostic thyroid surgery.

High values of Th1 (CXCL10) and Th2 (CCL2) chemokines in patients with psoriatic arthtritis.

OBJECTIVE: To evaluate serum levels of CXCL10 and CCL2 in a large series of PsA patients, and to relate chemokines levels to the clinical phenotype of these patients. METHODS: Serum levels of CXCL10 and CCL2 were measured in 68 PsA patients, and in gender- and age-matched (1:1) controls drawn from the general population. RESULTS: PsA patients showed significantly (p<0.001) higher mean CXCL10 serum levels than controls (p<0.0001), (269+/-234 vs. 92+/-53 pg/ml; respectively). By defining a high CXCL10 level as a value at least 2 SD above the mean value of the control group (>198 pg/ml), 49% of patients with PsA and 5% of the control subjects had high CXCL10 (p<0.0001; chi-square). A significant inverse correlation was observed between CXCL10 serum levels and disease duration (r= 0.374, p=0.002).Patients with PsA showed significantly higher mean CCL2 serum levels than controls (p<0.001), (512+/-309 vs. 386+/-172, pg/ml; respectively). By defining a high CCL2 level as a value at least 2 SD above the mean value of the control group (>730 pg/ml), 19% of patients with PsA, 2% of the control subjects had high CCL2 (p<0.001; chi-square=22.02). CONCLUSION: In conclusion, high circulating levels of CXCL10 and CCL2 have been found in PsA patients, with a Th1 immune predominance in the early phase of the disease. A decline of CXCL10 levels has been observed in long lasting PsA, with a significant increase of the CCL2/CXCL10 ratio, suggesting a shift from Th1 to Th2 immune response in long duration PsA.

Thyroid involvement in patients with overt HCV-related mixed cryoglobulinaemia.

BACKGROUND: Mixed cryoglobulinaemia (MC), a systemic vasculitis associated with hepatitis C virus (HCV) infection in >90% of cases, is frequently complicated by multiple organ involvement. The prevalence of thyroid disorders in MC has not yet been studied. AIM: To investigate the prevalence and clinical features of thyroid involvement in patients with HCV-associated MC (HCV + MC). DESIGN: Case-control study. METHODS: HCV + MC patients (n = 93, 17 men and 76 women, mean +/- SD age 63 +/- 10 years, mean disease duration 14 +/- 7 years) consecutively referred to the Rheumatology Unit were matched by sex and age (+/- 2 years) to (i) 93 patients with chronic C hepatitis (CH) without MC and (ii) 93 healthy (HCV-negative) controls from the local population. Measurements included prevalence of hypo- or hyperthyroidism, thyroid autoantibodies, thyroid nodules and thyroid cancer. RESULTS: By McNemar's chi(2) test, the following thyroid abnormalities were significantly more frequent in HCV + MC patients than in HCV-negative controls: serum anti-thyroperoxidase autoantibody (AbTPO) (28% vs. 9%, p = 0.001); serum AbTPO and/or anti-thyroglobulin autoantibody (31% vs. 12%, p = 0.004); subclinical hypothyroidism (11% vs. 2%, p = 0.038); thyroid autoimmunity (35% vs. 16%, p = 0.006). Serum AbTPO were also significantly more frequent in HCV + MC patients than in CH controls (28% vs. 14%, p = 0.035). DISCUSSION: The prevalence of thyroid disorders is increased in patients with HCV-related mixed cryoglobulinaemia. We suggest careful monitoring of thyroid function in these patients.

Thyroid cancer in HCV-related mixed cryoglobulinemia patients.

OBJECTIVE: The prevalence of thyroid cancer in a series of unselected HCV-related mixed cryoglobulinemic patients was investigated in comparison with a control group. METHODS: Among 107 consecutive patients with mixed cryoglobulinemia (MC), 94 were eligible for the study. A control group was obtained from a sample of the general population (2,401 subjects), age > 50 years, who had undergone thyroid ultrasonography (582 subjects); 5 sex-matched controls were randomly assigned to each MC patients (470 individuals). The mean age was similar in the MC patients and controls (64.2 +/- 10.0 vs. 63.4 +/- 7.0). RESULTS: The prevalence of thyroid nodules was higher, although not significantly so, in control subjects than in MC patients (65.3 vs. 54.8%). Two patients with papillary thyroid cancer were found in the MC series, while no case was observed among controls (p = 0.001, chi-square P value; p = 0.02, Fisher's exact test). In both MC patients with papillary thyroid cancer lymphocytic infiltration was observed in the thyroid tissue. CONCLUSION: The possible association between HCV-related MC and thyroid cancer indicates that a careful monitoring of the thyroid would be opportune during the clinical follow-up of HCV-associated MC patients, especially in those with signs of thyroid autoimmune disorders.

Effects of ageing and increased haemolysis on the levels of dolichol in rat spleen.

Dolichol is a long-chain polyisoprenoid. No enzyme pathway for dolichol degradation was discovered. Dolichol accumulates in human and rodent tissues during ageing. Red blood cells contain a larger amount of dolichol and red blood cell life span is shorter in older rats. The effects of age and of the load of dolichol from red blood cell degradation on the ageing-associated accumulation of dolichol in spleen were studied in 2, 6, 12, 18 and 24 month-old male Sprague Dawley rats fed ad libitum (AL) or on an anti-ageing dietary regimen (EOD). Tissue dolichol was extracted and assayed by HPLC [J. Gerontol. 53A (1998) B87]. Levels of dolichol increased in spleen, liver, kidney and muscle in parallel fashion from the age of 2 to 12 months. Unexpectedly, spleen dolichol decreased in older rats whereas liver, kidney and muscle dolichol increased significantly. The effects of haemolysis on spleen dolichol were tested by the administration of phenylhydrazine. Results show that haemolysis does not increase, but rather decreases the levels of dolichol in erythroclastic organs. It is concluded that the levels of spleen dolichol may decrease in the absence of any known enzymatic degradative pathway if the spleen and its resident phagocytes are forced to cope with a higher number of red blood cells to be cleared. Free-radical mediated decomposition of dolichol by phagocytic cells during erythrophagocytosis might be involved in the process.

Enrofloxacin-theophylline interaction: influence of enrofloxacin on theophylline steady-state pharmacokinetics in the beagle dog.

Enrofloxacin, a quinolone antibiotic developed exclusively for use in animals, was investigated for its effects on the steady-state pharmacokinetics of theophylline in six healthy Beagle dogs. A sustained-release theophylline formulation was given alone (20 mg/kg per os twice daily at 12 h intervals) for 9 days and then co-administered with enrofloxacin (5 mg/kg i.v. once a day) for 5 days. Mean trough theophylline concentrations progressively and significantly increased during the five days of enrofloxacin co-administration. Theophylline clearance and concentration-time profile were significantly changed by enrofloxacin co-administration. No significant change was observed in enrofloxacin pharmacokinetics. The kinetic interaction between theophylline and enrofloxacin could be of clinical significance and may require plasma drug concentration monitoring and adjustment of theophylline dosage.

Long term therapy with a new liquid L-thyroxine preparation: bioequivalence with L-T4 tablets.

Seventy-four euthyroid patients with nodular goiter (55) or primary hypothyroidism (19) were selected for long term treatment with a new preparation containing L-T4 in solution (Tiroxen, Laboratori Baldacci, Pisa, Italy). Each patient underwent, before or after receiving the L-T4 in solution, long term treatment with L-T4 in tablet form at the same dose. The serum concentrations of TSH, TT4, TT3, FT4 and FT3 were measured basally and during therapy with each of the two L-T4 preparations (liquid and tablet). In the golter group, mean serum TSH concentration was 1.4 microUI/ml basally, while it was 0.47 microUI/ml following both L-T4 tablet therapy and L-T4 solution administration. Mean basal TSH value was significantly different from the two values on the therapy (p < 0.001 in each instance). Mean basal serum TT4 concentration was 8.2 +/- 0.25 microgram/dl basally while it was 9.9 +/- 0.28 microgram/dl (p < 0.001) on L-T4 tablet therapy and 9.7 +/- 0.26 (p < 0.001) on L-T4 solution administration. Mean basal serum concentration of TT3, FT4, FT3 was not significantly different from the value on the therapy, either with L-T4 tablet or with L-T4 solution. In the hypothyroid patients the high mean basal serum TSH concentration (23.6 microUI/ml) returned to normal similar values on L-T4 tablet therapy (0.96 microUI/ml; p < 0.01) and on L-T4 solution administration (1.24 microUI/ml; p < 0.01). The serum TSH concentration value during L-T4 therapy varied from unmeasurable level to 3.5 microUI/ml during the tablet administration and to 4.8 microUI/ml during the solution administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term results of surgically treated brainstem gliomas.

Long-term results of 16 surgically treated brainstem gliomas are reported. The results have been reviewed with reference to the clinical and pathological criteria defined by Hoffman and co-workers (1980) in the attempt to differentiate a distinct group of benign tumours. A good correlation has been obtained. The usefulness of surgical treatment of brainstem gliomas has been stressed in view of the survival time as well quality of survival.

Rapid colorimetry of zinc in seminal fluid.

This colorimetric method for determination of zinc in seminal liquid is based on the reaction between zinc and 4-(2-pyridylazo)resorcinol in a buffered solution at pH 9.5. It is very simple, fast (approximately equal to 10 min), and economical. It can be used to determine zinc in "whole" semen, seminal plasma, or isolated spermatozoa. We verified its accuracy for sample concentrations up to 0.4 g/L by comparison with a reference method based on atomic absorption spectroscopy of acidic wet-ashed samples. Calcium and magnesium do not interfere, even in concentrations exceeding the physiological values. Between-run precision at a normal concentration of 0.14 g/L is about +/- 7 mg/L; within-run precision at the same concentration is about +/- 2 mg/L.

Status epilepticus with cognitive symptomatology in a patient with partial complex epilepsy.

A 16-year-old patient who had a history of complex partial seizures, had frequent episodes of status epilepticus with diffuse slow-wave discharges. The clinical manifestations were apparently insignificant due to the fact that vigilance, orientation and behaviour were unimpaired. Neuropsychological investigations showed that the cognitive processes were selectively impaired during such episodes. The electroclinical pattern was interrupted by break-off of contact concomitant with high-frequency spike discharges. Cognitive impairment is believed to represent the specific feature peculiar to this type of status epilepticus.