Biomedical subjects

V Trischitta

Publications and source records attributed to V Trischitta.

At least 37 records · Page 2Linked to original sources

PubMed2001

A cluster of three single nucleotide polymorphisms in the 3'-untranslated region of human glycoprotein PC-1 gene stabilizes PC-1 mRNA and is associated with increased PC-1 protein content and insulin resistance-related abnormalities.

Glycoprotein PC-1 inhibits insulin signaling and, when overexpressed, plays a role in human insulin resistance. Mechanisms of PC-1 overexpression are unknown. We have identified a haplotype in the 3'-untranslated region of the PC-1 gene that may modulate PC-1 expression and confer an increased risk for insulin resistance. Individuals from Sicily, Italy, carrying the "P" haplotype (i.e., a cluster of three single nucleotide polymorphisms: G2897A, G2906C, and C2948T) were at higher risk (P < 0.01) for insulin resistance and had higher (P < 0.05) levels of plasma glucose and insulin during an oral glucose tolerance test and higher levels of cholesterol, HDL cholesterol, and systolic blood pressure. They also had higher (P < 0.05-0.01) PC-1 protein content in both skeletal muscle and cultured skin fibroblasts. In CHO cells transfected with either P or wild-type cDNA, specific PC-1 mRNA half-life was increased for those transfected with P (t/2 = 3.73 +/- 1.0 vs. 1.57 +/- 0.2 h; P < 0.01). In a population of different ethnicity (Gargano, East Coast Italy), patients with type 2 diabetes (the most likely clinical outcome of insulin resistance) had a higher P haplotype frequency than healthy control subjects (7.8 vs. 1.5%, P < 0.01), thus replicating the association between the P allele and the insulin resistance-related abnormalities observed among Sicilians. In conclusion, we have identified a possible molecular mechanism for PC-1 overexpression that confers an increased risk for insulin resistance-related abnormalities.

3' Untranslated Regions↗

PubMed2000

Mapping a dominant form of multinodular goiter to chromosome Xp22.

Multinodular goiter (MNG) is a common disorder characterized by a nodular enlargement of the thyroid gland and occurring with a female&rcolon;male ratio of 5&rcolon;1. This article reports the analysis of an Italian three-generation pedigree MNG, including 10 affected females and 2 affected males. After linkage to candidate regions previously implicated in various forms of goiter was excluded, a novel MNG locus was searched. Because no male-to-male transmission was present in the study pedigree, an X-linked autosomal dominant pattern of inheritance was hypothesized. Therefore, 18 markers spaced at 10-cM intervals on the X chromosome were examined. A significant LOD score was observed in the Xp22 region, where marker DXS1226 generated a maximum LOD score of 4.73 at a recombination fraction of 0. Analysis of six flanking microsatellites confirmed these data, and haplotype inspection delimited a 9.6-cM interval lying between DXS1052 and DXS8039.

Chromosome Mapping↗

PubMed2000

Role of insulin-like growth factor (IGF)-1 in the modulation of renal haemodynamics in Type I diabetic patients.

AIMS/HYPOTHESIS: We investigated in normotensive Type I (insulin-dependent) diabetic patients with normoalbuminuria the role of growth hormone-induced IGF-1 in the modulation of renal haemodynamics. METHODS: We measured glomerular filtration (GFR) and renal plasma flow (RPF) at baseline and at 24 h after injection of different doses of growth hormone (0.1, 0.2, 0.4 U x kg(-1) x body weight(-1) in six patients with normal GFR under a euglycaemic clamp. We also examined a 24 h profile of plasma growth hormone and IGF-1 during usual insulin therapy in two other groups each with seven patients with a lower (from 93 to 114 ml x min(-1) x (1.73 m2)(-1) and higher (from 121 to 146 ml min(-1) x (1.73 m2)(-1) GFR. RESULTS: Plasma growth hormone concentrations peaked 2 h after its injection and plasma concentrations of IGF-1 peaked about 24 h after the growth hormone injection. There was a significant increase in GFR and RPF 24 h after the highest dose of the growth hormone injection (corresponding to the highest IGF-1 concentration), from baseline values of 115 +/- 24 and 536 +/- 141 ml x min(-1) x (1.73 m2)(-1) to 160 +/- 33 and 657 +/- 137 ml x min(-1) x (1.73 m2)(-1), respectively (p < 0.01 for GFR and p < 0.05 for RPF). No differences were observed in the 24 h profile of growth hormone and IGF-1 plasma concentrations between the two groups; growth hormone and IGF-1 concentrations were lower than those obtained after the injection of 0.4 U x kg(-1) x body weight(-1) of growth hormone. CONCLUSION/INTERPRETATION: These results show that pharmacological growth hormone-induced IGF-1 concentrations are required to modify renal haemodynamics in Type I diabetic patients and suggest that, under the "physiological" conditions of diabetes, IGF-1 has no role as a mediator of glomerular hyperfiltration.

Adult↗

PubMed2000

Radioiodine and percutaneous ethanol injection in the treatment of large toxic thyroid nodule: a long-term study.

Surgery is generally recommended for large thyroid toxic nodules (TTNs). When surgery is not applicable, both radioactive iodine (RAI) and percutaneous ethanol injection (PEI) are alternative treatments. In this retrospective study, the long-term efficacy of nonsurgical treatments was evaluated in 43 patients with TTN, selected on the basis of presence of hyperthyroidism and a fairly large nodule (3- and 4-cm in diameter) completely inhibiting controlateral lobe captation during scintigraphy. Twenty-one patients were treated by RAI (administered dose 670+/-160 MBq; range 555-925) and twenty-two were treated by PEI (6+/-1 sessions; range 5-9). FT4, FT3, thyrotropin (TSH), and nodule volume were assessed before and at fixed intervals after treatment. Median follow-up was 36 months (range, 12-84). Compared to baseline values, with both therapies, serum FT4, FT3, and nodule volume were decreased (p < 0.01) and serum TSH was increased (p < 0.01), after 3 months and during the entire follow-up. Nodule volume reduction percentage was 66.8+/-22.0 and 78.4+/-18.0, in the RAI- and PEI-treated groups, respectively. At the end of follow-up, 34 patients were euthyroid (16 RAI- and 18 PEI-treated). Four RAI-treated patients (19%) showed slightly high TSH levels (4.2-5.3 mU/L), whereas three PEI-treated patients (13.6%) still had suppressed TSH levels, although being clinically asymptomatic. One RAI-treated patient (4.8%) showed overt hypothyroidism during the follow-up period and was then treated with L-thyroxin. One patient (4.6%), who was initially cured by PEI, became newly hyperthyroid during the follow-up period. Both treatments were well-tolerated. In conclusion, both of these nonsurgical treatments are effective and may be chosen also for relatively large TTNs. Specifically, RAI seems to be more effective for treating hyperthyroidism but has minimal sequelae of subclinical or clinical hypothyroidism, while, after PEI treatment the possibility of stable subclinical hyperthyroidism or hyperthyroidism relapse should be taken into account.

Adult↗

PubMed2000

Insulin/insulin-like growth factor I hybrid receptors overexpression is not an early defect in insulin-resistant subjects.

Hybrid receptors (HRs), insulin receptor (IR)/insulin-like growth factor I receptor (IGF-I-R) heterodimers have been reported increased in skeletal muscle of obese and type 2 diabetic patients and to contribute to the patient insulin resistance. To investigate whether or not the increased expression of hybrid receptors is an early defect (probably genetic) of insulin resistance, we measured by specific enzyme-linked immunosorbent assays both IR, IGF-I-R, and HR content in skeletal muscle of healthy nonobese, nondiabetic subjects either insulin sensitive or insulin resistant, and also in patients with moderate obesity. IR content was significantly reduced in insulin-resistant subjects both nonobese and obese, compared with insulin-sensitive subjects (2.32+/-0.26, 2.36+/-0.18, and 3.45+/-0.42 ng/mg protein, respectively, P = 0.002). In contrast, IGF-I-R content was similar in the three groups. Muscle HR content was not different in insulin-sensitive vs. insulin-resistant subjects (both nonobese and obese) (4.90+/-0.46, 4.69+/-0.29, and 4.91+/-0.25 ng/mg protein, respectively, P = not significant). These studies indicate that, in insulin-resistant subjects without diabetes or severe obesity, muscle IR content but not IGF-I-R or HR content is reduced. They do not suggest, therefore, a primary (genetic) role of increased HR as a cause of IR decrease and insulin resistance.

Adult↗

PubMed2000

A PC-1 amino acid variant (K121Q) is associated with faster progression of renal disease in patients with type 1 diabetes and albuminuria.

Insulin resistance characterizes type 1 diabetes in patients with albuminuria. A PC-1 glycoprotein amino acid variant, K121Q, is associated with insulin resistance. We examined the impact of the PC-1 K121Q variant on the rate of decline of the glomerular filtration rate (GFR) by creatinine clearance derived from the Cockroft-Gault formula in 77 type 1 diabetic patients with albuminuria who were followed for an average of 6.5 years (range 2.5-15). Patients carrying the Q allele (n = 22; 20 with KQ and 2 with QQ genotypes) had a faster GFR decline than those patients with the KK genotype (n = 55) (median 7.2 vs. 3.7 ml x min(-1) x year(-1); range 0.16 to 16.6 vs. -3.8 to 16.0 ml x min(-1) x year(-1); P < 0.001). Significantly more patients carrying the Q allele belonged to the highest tertile of GFR decline (odds ratio = 5.7, 95% CI 4.1-7.2, P = 0.02). Levels of blood pressure, HbA1c, and albuminuria were comparable in the two genotype groups. Albuminuria (P = 0.001), mean blood pressure (P = 0.046), and PC-1 genotype (P = 0.036) independently correlated with GFR decline. Because all patients were receiving antihypertensive treatment, the faster GFR decline in the patients carrying the Q allele could be the result of reduced sensitivity to the renoprotective effect of antihypertensive therapy. PC-1 genotyping identifies type 1 diabetic patients with a faster progression of diabetic nephropathy.

Adult↗

PubMed2000

Association between the human glycoprotein PC-1 gene and elevated glucose and insulin levels in a paired-sibling analysis.

We studied whether there is an association between the single nucleotide polymorphism c.533A>C (K121Q) in the glycoprotein PC-1 gene and features of the metabolic syndrome in case-control and intrafamily association studies in 922 subjects from Finland and Sweden. No difference was observed in the Q allele frequency between control subjects and type 2 diabetic subjects (12.9 vs. 15.1%). The QK genotype was associated with higher fasting plasma glucose (FPG) concentrations than the KK genotype in type 2 diabetic patients (P <0.001) and their relatives (P <0.05). A permutation test of siblings discordant for the QK and KK genotypes also showed that the nondiabetic siblings with the QK genotype had higher FPG (6.1 +/- 2.0 vs. 5.4 +/- 0.6 mmo/l, P <0.001) and fasting insulin (7.0 +/- 3.6 vs. 4.8 +/- 2.6 mU/l, P <0.05) concentrations than the carriers of the KK genotype. In addition, diabetic siblings with the QK genotype had higher systolic blood pressure (147.0 +/- 18.0 vs. 140.0 +/- 18.7 mmHg, P <0.05) and higher fasting (9.9 +/- 3.0 vs. 8.8 +/- 2.8 mmol/l, P <0.05) and 2-h plasma glucose (17.3 +/- 8.5 vs. 12.9 +/- 4.2 mmol/l, P < 0.05) concentrations than the diabetic carriers of the KK genotype. The present study shows that, although the Q allele of the human glycoprotein PC-1 gene is associated with surrogate measures of insulin resistance, it may not be enough to increase the susceptibility to type 2 diabetes.

Adult↗

PubMed2000

The K121Q variant of the human PC-1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians.

The human plasma-cell membrane differentiation antigen-1 (PC-1) has been shown to inhibit insulin receptor tyrosine kinase activity. Recently, a K121Q polymorphism in the human PC-1 gene was found in a Sicilian population and was shown to be strongly associated with insulin resistance. The objectives of the present investigation were to examine in the Danish Caucasian population whether the K121Q variant was associated with type 2 diabetes or, in glucose-tolerant subjects, with impaired whole-body insulin sensitivity. We genotyped 404 Danish type 2 diabetic patients and found that the allele frequency of the variant was 0.14 (95% CI 0.12-0.16), whereas the allele frequency was 0.16 (95% CI 0.13-0.19) among 237 matched glucose-tolerant control subjects (P = 0.6). In the control subjects, there were no significant differences among wild-type, heterozygous, or homozygous subjects in regard to 1) serum insulin and plasma glucose levels at fasting, 60 min, or 120 min during an oral glucose tolerance test (OGTT) or 2) the estimates of insulin resistance obtained from the homeostasis model assessment (HOMA). Furthermore, we investigated the impact of the variant in 2 other Danish population samples that comprised 356 young healthy subjects and 226 glucose-tolerant offspring of type 2 diabetic probands, respectively. In all of the study populations, the polymorphism was not associated with an altered insulin sensitivity index as estimated from an intravenous glucose tolerance test in combination with an intravenous injection of tolbutamide. In addition, among the 226 offspring, the variations in serum insulin and serum C-peptide responses measured during an OGTT were not related to the PC-1 genotype. In conclusion, the K121Q polymorphism of the human PC-1 gene is not associated with type 2 diabetes or insulin resistance among Danish Caucasians.

Adult↗

PubMed1999

Role of PC-1 in the etiology of insulin resistance.

Defects in insulin receptor tyrosine kinase activity have been demonstrated in tissues from insulin resistant subjects, but mutations in the insulin receptor gene are rare. Therefore, other molecules that are capable of modulating the insulin receptor most likely play a major role in insulin resistance. In cultured fibroblasts from an insulin resistant patient with Type 2 diabetes, we first identified membrane glycoprotein PC-1 as an inhibitor of the insulin receptor tyrosine kinase activity. PC-1 is overexpressed in fibroblasts from other insulin resistant subjects, both with and without Type 2 diabetes. PC-1 is a large class II exoprotein whose function is unknown. Studies in muscle and fat of insulin resistant subjects two primary tissues for insulin activation, reveal that elevated levels of PC-1 are inversely correlated with decreased insulin action both in vivo and in vitro. Transfection and expression of PC-1 in cultured cells demonstrate that overexpression of PC-1 produces impairments in insulin receptor tyrosine kinase activity, and the subsequent cellular responses to insulin. These studies indicate, therefore, that PC-1 is a major factor in the etiology of insulin resistance, and is a potential new therapeutic target for anti-diabetic therapy.

Animals↗

PubMed1999

The intravenous insulin tolerance test is an accurate method for screening a general population for insulin resistance and related abnormalities.

To verify whether the short intravenous insulin tolerance test (ITT) (a safe, reproducible, inexpensive, rapid and easy to perform measurement of insulin sensitivity) is a suitable test for insulin resistance screening in a general population, we measured in 60 non diabetic subjects, either non-obese (no.=40) or obese (BMI>28, no.=20) the K of glucose disappearance from plasma after ITT (K(ITT)), plasma glucose (PG) and insulin (IRI) both fasting (FPG, FIRI) and at 120 min of OGTT (PG- 120, IRI- 120), and also triglycerides (Tg), cholesterol (Chol) and blood pressure (BP). Subjects were subdivided into quartiles according to K(ITT) values. Average FPG, PG-120, FIRI, IRI-120, Tg and Chol values were progressively increased, and average HDL/Chol was progressively decreased from quartile 1 (the most insulin sensitive) to 4 (the most insulin resistant) (p<0.05, by 1-way ANOVA test). Also BP was increased in the insulin resistant patients, but statistical significance was not reached. Three or more of the studied parameters (FPG and/or PG-120, FIRI and/or IRI-120, Tg, HDL/Chol, mean BP) were altered (below the worst 25 degree percentile) in 64% of subjects from quartile 4; none of the subjects in quartile 1 was affected by such a cluster of alterations. K(ITT) values < or =4.8 identified the cluster of insulin resistance related alterations with an accuracy of 82% (sensitivity=83.3%, specificity=80.5%). In healthy subjects with a wide range of BMI the ITT is a reliable procedure for screening for the cluster of metabolic alterations related to insulin resistance.

Adolescent↗

PubMed1999

Screening of thyrotropin receptor mutations by fine-needle aspiration biopsy in autonomous functioning thyroid nodules in multinodular goiters.

Multinodular goiter (MNG) is characterized by nodules of different size and function. Areas of increased function may emerge, appearing as single, or more frequently, multiple autonomously functioning thyroid nodules (AFTN). The molecular mechanism for the autonomous growth and function of these nodules has been related to mutations in the thyrotropin receptor (TSHR) that constitutively activate the adenylyl cyclase. We searched for mutations in a limited area of the TSHR gene, covering the major mutational hotspot, in 38 AFTNs found in 37 patients with MNGs. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction enzyme analysis of fine-needle aspiration biopsy (FNAB) samples to rapidly identify 4 of the more frequently occurring TSHR mutations: D619G, F631C, T632I and D633E. Mutations were identified in 5 nodules (1 D619G mutation and 4 T632I mutations). Subsequently, the entire transmembrane portion of the TSHR gene was sequenced in a random sample of 12 AFTN samples that were free of mutations by RT-PCR and restriction enzyme analysis. By direct sequencing we identified a new mutation, F666L, in the seventh transmembrane domain in a sample from 1 nodule. Analysis of FMA samples of AFTN is an effective approach to identify TSHR gene mutations because individual mutations may be associated with different growth and function in vitro, our approach might, allow correlation of a given mutation with the clinical behavior in vivo.

Adult↗

PubMed1999

Percutaneous ethanol injection may be a definitive treatment for symptomatic thyroid cystic nodules not treatable by surgery: five-year follow-up study.

We present a prospective study on the long-term efficacy of percutaneous ethanol injection (PEI) treatment for thyroid cystic nodules. Among patients referred for symptomatic thyroid cystic nodules who had relapsed after two aspirations or whose nodules could not be aspirated due to the thickness of the cystic fluid, PEI was given when surgery was either refused or contraindicated. Forty-three patients were treated; the mean basal volume of the cysts was 38.4 mL. The purpose of the study was to evaluate long-term efficacy of PEI treatment on: (1) amelioration of symptoms and signs of local compression and (2) nodule volume reduction. In three subjects (7%), PEI failed to induce a significant (>50%) nodule reduction, so that surgical treatment was performed. In 40 patients (93%), an impressive nodule shrinkage was observed, reaching a plateau after 24 months (volume reduction = 91.9%+/-11.4%). A new PEI session was needed in two patients in whom a recurrence was noted within the first 6 months. After 6 months, no significant (> or =1 mL volume) nodule regrowth was observed up to 60 months. Both symptoms and tracheal displacement rapidly (within 1 month) and significantly (p<0.01) improved. After PEI, mild pain was the only side effect observed. No suspicious cytology was observed in any residual nodule greater than 1 mL 6 and 24 months after the last PEI session. Our data suggest that PEI is a first-line safe, effective, probably definitive, treatment for cystic thyroid nodules for which surgery is either refused or contraindicated.

Adult↗

PubMed1999

A soluble PC-1 circulates in human plasma: relationship with insulin resistance and associated abnormalities.

An increased tissue content of PC-1, an inhibitor of insulin receptor signaling, may play a role in insulin resistance. Large scale prospective studies to test this hypothesis are difficult to carry out because of the need for tissue biopsies. The aim of this study was to investigate whether PC-1 is measurable in human plasma and whether its concentration is related to insulin sensitivity. A soluble PC-1, with mol wt and enzymatic activity similar to those of tissue PC-1, was measurable in human plasma by a specific enzyme-linked immunosorbent assay and was inversely correlated to skeletal muscle PC-1 content (r = -0.5; P < 0.01). The plasma PC-1 concentration was decreased (P < 0.05) in insulin-resistant (22.7 +/- 3.0 ng/mL; n = 25) compared to insulin-sensitive (36.7 +/- 4.5; n = 25) nondiabetic subjects and was correlated negatively with the waist/hip ratio (r = -0.48; P < 0.001) and mean blood pressure (r = -0.3; P < 0.05) and positively with high density lipoprotein/total cholesterol (r = 0.38; P < 0.01) and both the M value and the plasma free fatty acid level decrement at clamp studies (r = 0.28; n = 50; P = 0.05 and r = 0.43; n = 22; P < 0.05, respectively). A plasma PC-1 concentration of 19 ng/mL or less identified a cluster of insulin resistance-related alterations with 75% accuracy. In conclusion, PC-1 circulates in human plasma, and its concentration is related to insulin sensitivity. This may help to plan studies aimed at understanding the role of PC-1 in insulin resistance.

Adult↗

PubMed1999

Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism.

The strategy of treatment for patients with adrenal incidentalomas (AI) may depend upon the presence of hormonal hypersecretion. Although alterations of bone turnover have been recently reported, data on bone mineral density (BMD) are not available in AI patients. We evaluated bone turnover and BMD in 32 female AI patients and 64 matched controls. Spinal and femoral BMD were similar in patients and controls. Serum bone GLA protein (6.8+/-3.5 vs. 8.8+/-3.2 ng/mL; P<0.005) and PTH (48.8+/-15.1 vs. 37.2+/-10.9 pg/mL; P<0.0001) were different in patients and controls. Patients were then subdivided into 2 groups: with (n = 8; group A) or without (n = 24; group B) subclinical hypercortisolism. PTH was higher (P<0.05) in group A than in group B and in both groups than in controls (57.1+/-13.6, 46.0+/-14.8, and 37.2+/-10.9 pg/mL, respectively), and bone GLA protein was lower in group A than in group B and controls (3.8+/-2.3, 7.5+/-3.1, and 8.8+/-3.2 ng/mL, respectively; P<0.05). Serum type I cross-linked C telopeptide and fasting urinary deoxypyridinoline/ creatinine were not different in the three groups. BMD at each site was lower (P<0.05) in group A than in group B and controls. Bone mass and metabolism are altered in AI patients with subclinical hypercortisolism and should be taken into account, therefore, when addressing the treatment of choice for these patients.

Adrenal Gland Neoplasms↗

PubMed1999

A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance.

The genes responsible for insulin resistance are poorly defined. Plasma cell differentiation antigen (PC-1) glycoprotein inhibits insulin receptor signaling and is associated with insulin resistance. We describe here a novel polymorphism in exon 4 of the PC-1 gene (K121Q) and demonstrate that it is strongly associated with insulin resistance in 121 healthy nonobese (BMI <30 kg/m2) nondiabetic (by oral glucose tolerance test [OGTT]) Caucasians from Sicily. Compared with 80 KK subjects, Q allele carriers (n = 41, 39 KQ and 2 QQ) showed higher glucose and insulin levels during OGTT (P < 0.001 by two-way analysis of variance) and insulin resistance by euglycemic clamp (M value = 5.25 +/- 1.38 [n = 24] vs. 6.30 +/- 1.39 mg x kg(-1) x min(-1) [n = 49], P = 0.005). Q carriers had higher risk of being hyperinsulinemic and insulin resistant (odds ratio [CI]: 2.99 [1.28-7.0], P < 0.001). Insulin receptor autophosphorylation was reduced (P < 0.01) in cultured skin fibroblasts from KQ versus KK subjects. Skeletal muscle PC-1 content was not different in 11 KQ versus 32 KK subjects (33 +/- 16.1 vs. 17.5 +/- 15 ng/mg protein, P = 0.3). These results suggest a cause-effect relationship between the Q carrying genotype and the insulin resistance phenotype, and raise the possibility that PC-1 genotyping could identify individuals who are at risk of developing insulin resistance, a condition that predisposes to type 2 diabetes and coronary artery disease.

Adult↗

PubMed1998

Efficacy of combined treatments in NIDDM patients with secondary failure to sulphonylureas. Is it predictable?

The treatment of NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50 NIDDM patients with secondary failure to glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime NPH insulin or a t.i.d. oral metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined therapies clearly improved glycaemic control. HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time NPH insulin was more effective on FPG reduction than metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast, metformin addition was more effective on PPPG reduction than bedtime NPH insulin addition (-30+/-2% vs 20+/-3%, p<0.01). Serum cholesterol was marginally but significantly decreased after metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after NPH insulin. Body weight increase was significantly greater after insulin addition than after metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of metformin rather than NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG, HbA1 c, post-glucagon C-peptide levels, insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime NPH insulin or t.i.d. metformin is similarly effective in improving glycaemic control. Metformin is better accepted by patients and provides a modest advantage in terms of body weight and cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments.

Adult↗

PubMed1998

Analysis of RET proto-oncogene abnormalities in patients with MEN 2A, MEN 2B, familial or sporadic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) may occur either as a sporadic or familial (FMTC) disease. Multiple endocrine neoplasia (MEN) type 2, inherited as an autosomal dominant disease, is characterized by coexistence of MTC with other endocrine neoplasia. Activating mutations of the RET proto-oncogene, involving the somatic or the germinal cell lineage, are found in both inherited and acquired forms. In this study, RET mutations were screened in 47 individuals either affected by MTC or belonging to families with hereditary MTC. Exons 10, 11, 13, 14, 15 and 16 of the RET gene were amplified by polymerase chain reaction and examined by DNA sequence and/or restriction enzyme analysis to detect mutations in purified amplicons. Six MEN 2A families with a germline mutation at codon 634, one FMTC family carrying a mutation at codon 618 and two MEN 2B families with a mutation at codon 918 were identified. In affected members of a MEN 2A family no known RET mutations were observed. Besides, we identified a germline mutation in a patient with apparently sporadic MTC and in two out of three sons, indicating the presence of a sporadic misclassified familial disease. In all of the families examined we were able to distinguish the affected vs unaffected (not at risk) members. A somatic mutation of codon 918 was detected in three out of ten patients with apparently sporadic MTC.

Adult↗

PubMed1998

Treatment of large cold benign thyroid nodules not eligible for surgery with percutaneous ethanol injection.

We studied the effect of percutaneous ethanol injection (PEI) in the treatment of cold, cytologically benign, large (>10 mL) thyroid nodules (CBNs) in 41 patients. The end-point of our study was to evaluate the efficacy of PEI on: 1) local symptomatology, assessed by an arbitrary symptom score; and 2) nodule volume and tracheal displacement (at ultrasonography). Follow-up ranged from 12-36 (21 +/- 9) months. Symptom score was significantly reduced (P < 0.01) after 6 months and at the end of the follow-up (2.1 +/- 0.3 vs. 0.2 +/- 0.5 and vs. 0.2 +/- 0.4). A significant (P < 0.01) nodule volume reduction was observed, without differences between solid or mixed CBNs; the reduction was 50% or more in 92.7% of patients. Neither clinical parameters nor pretreatment nodule ultrasonographic features were related to nodule reduction. Disappearance or significant reduction (>0.5 cm) of tracheal displacement was obtained in 61% and in 39% of patients, respectively. One patient experienced prethyroid region edema, pain, and mild fewer, which reversed within 1 week; and one patient had dysphonia, caused by vocal cord palsy, which reversed spontaneously within 1 month. At the end of the follow-up, nodules with just necrotic material at cytology showed a greater (P < 0.05) volume reduction than nodules with residual benign thyroid cells. Our data suggest that PEI is a safe and effective treatment of large CBNs, although sometimes serious side effects do occur.

Adolescent↗