[Coenzyme Q10 (Q-ter) in treatment of functional voice disorders]. / Il Coenzima Q10 (Q-ter) nel trattamento dei disordini funzionali della voce.

Aim of this study was to evaluate the effectivness of Coenzyme Q-Ter and Vitamin A in functional voice disorders. Twenty two patients were treated with CoQ10-ter and vitamin A twice a day for ten days. A general otolaryngological/foniatric and logopedic examination were performed. Videolaringostroboscopy, GIRBAS, Voice Handicap Index questionnaire and Multi-Dimensional Voice analysis were carried out before and after treatment. In all patients an improvement was observed in almost all parameters considered after treatment. CoQ10-ter and Vitamin A risulted effective in treatment of patients with functional voice disorders (caused by vocal "malmenage" or "surmenage").

Association between an R338L mutation in the thyroid hormone receptor-beta gene and thyrotoxic features in two unrelated kindreds with resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is a rare syndrome characterized by reduced sensitivity to thyroid hormone due to thyroid hormone receptor-beta (TRbeta) gene mutations or deletion. RTH has been classified on the basis of clinical features into generalized (GRTH) and pituitary (PRTH) resistance. There is, however, overlap of clinical and biochemical findings in patients with the two forms of resistance, and similar TRbeta gene mutations have been identified in both. The 2 subtypes of RTH, therefore, are considered to be different manifestations of a single genetic entity. We report a mutation of the TRbeta gene, an arginine to leucine substitution at codon 338 (R338L), in 2 unrelated RTH kindreds of northern Italian ancestry. The same mutation was already reported in a single unrelated kindred affected by PRTH. Five individuals, 3 in the first and 2 in the second family, were clinically evaluated and followed for 3-11 years. During the long-term follow-up, the patients manifested symptoms and signs of hyperthyroidism including palpitations, fine tremors, heat intolerance, increased sweating, increased deep tendon reflexes, moist and warm skin, cardiac rhythm abnormalities, reduced body weight, and reduced bone mineral density. The clinical features of these kindreds are consistent with a predominant PRTH phenotype.

[Pancreatic beta-cell hyperplasia in adults. A clinical case]. / L'iperplasia delle beta-cellule pancreatiche nell'adulto. Caso clinico.

The author describe a rare case of pancreatic beta-cell hyperplasia. The patient was referred to us because of serious hypoglycemic crises. During hospitalization, endogenous hyperinsulinism was confirmed by hematochemical and instrumental tests. AngioCT of the pancreas evidenced a small lesion of the corpus, suspected of insulinoma. The patient underwent a corpus caudalis pancreatectomy: a small nodule with histologic neuroendocrine traits was ablated. A few days after the operation, new symptomatic hypoglycemia appeared. The hormonal tests confirmed a recurrence of endogenous hyperinsulinism. The patient underwent a new operation for pancreaticoduodenectomy: histological examination confirmed a pancreatic beta-cells hyperplasia. This condition has to be taken into account in the differential diagnosis of post prandial hypoglycemia. Besides, the observation of an insulinoma doesn't exclude the presence of a diffused disorder of islet cells as in the case above described.

[Intact whole bioactive parathormone: problems arising from comparing different methods]. / Paratormone intatto intero bioattivo: le problematiche emergenti dal confronto.

BACKGROUND: Parathyroid hormone (PTH) has important applications in the nephrological clinical practice. Because assays of Intact PTH (I-PTH) are liable to interferences by N-truncated fragments, a novel method for whole-(1-84) PTH has been proposed. This study is aimed at comparing the latter with some of the previous I-PTH assays. For each method the results are referred to pertinent markers of mineral metabolism. METHODS: We enrolled 171 subjects, including 56 healthy controls (C), 65 calcium stone- formers (CaSF), 40 haemodialysis patients (HD), 10 with primary hyperparathyroidism (PHP). On blood samples we measured: I-PTH by four methods (N-Tact, Advantage, Elecsys, Scantibodies), whole-(1-84) PTH, defined as CAP (Cyclase Activating PTH), total and ionised calcium, phosphate, vitamin D, osteocalcin and Crosslaps. The difference between I-PTH and CAP Scantibodies is defined as CIP (Cyclase Inhibiting PTH). RESULTS: Despite relating to each other (r>0.97) PTH values varied remarkably among methods. For all methods, the reference intervals differed from those provided by the producer. Assuming these new ranges, 10 CaSF had over-range values not always associated with abnormalities of mineral metabolism. One of the PHP patients was normal for I-PTH with 2/4 methods. In HD the differences among methods were even greater, there were inverse (p<0.05) and direct (p<0.001) relationships with ionised calcium and osteocalcin-crosslaps, respectively. The CAP/CIP ratio was lower in low bone turnover patients, but the two subgroups widely overlapped. CONCLUSIONS: This study indicates that the reliability of I-PTH assays is still unsatisfactory, and none of the four methods emerged as the best. Assay for CAP only improves diagnostic efficiency, whereas the CAP/CIP ratio does not exhibit powerful discriminating capacity. Our suggestion is that each Centre should establish its own reference ranges. PTH assay should always be coupled with measurements of other markers of mineral metabolism as well as renal function.

[A multicenter study of child poisonings. Preliminary epidemiological results]. / Studio multicentrico degli avvelenamenti nel bambino (S.M.A.B.). Risultati epidemiologici preliminari.

The project of a multicentre study of poisoning in children planned by 4 Italian pediatric departments to get epidemiologic and clinic information is presented. The study is carried out retrospectively on admissions during 1975-90 and prospectively during 1991-92. Poisonings are classified as not-confirmed, asymptomatic because of early treatment or symptomatic. In the latter group three degrees of severity are assessed. Diagnostic-therapeutic protocols will be elaborated and quality of the hospital care evaluated according to peer review methodology. Preliminary data on changing pattern of poisoning over the time and on main toxic agents involved in younger children are also reported. The first topic has been studied taking into account 1831 patients aged 0-13 years, admitted during 1977-79 and 1987-89. A decrease of exposures to drugs and an increase of poisonings under the age of 3 years have been observed in more recent period. On the other hand household products resulted to be the main poisoning agents in 1044 children under the age of 5 years during 1984-86. Lack of infant supervision by parents and possible influence of compulsory child resistant containers only for drugs are stressed. The findings suggest the need of health education campaigns in general population as well of safety devices for some domestic harmful products.

Viscoelastic characterisation of pig liver in unconfined compression.

Understanding and modelling liver biomechanics represents a significant challenge due to the complex nature of this organ. Unfortunately, there is no consensus on liver viscoelastic properties, and results are strongly dependent on sample type and status, adopted testing method, and testing conditions. Standard force-triggered tests (e.g. step response or dynamic mechanical tests) necessitate an initial contact between sample and testing apparatus, which may result in significant pre-stress to very soft and highly hydrated samples. In a previous study we proposed the epsilon dot method (ε̇M): a testing and analysis framework to address the drawbacks of standard mechanical tests. Focusing on ex-vivo unconfined bulk compressive tests, here we use both the ε̇M and dynamic mechanical analysis (DMA) to derive liver viscoelastic parameters in the region of small strains or the linear viscoelastic region (LVR). As liver samples were visibly deteriorated at the end of frequency sweep tests, a modified approach was adopted to reduce DMA testing times. This approach, termed step-reconstructed DMA (SRDMA), is based on dynamic measurements around specific frequencies and then reconstruction of liver behaviour in the entire frequency range of interest. The instantaneous elastic modulus obtained from SRDMA tests (2.65 ± 0.30 kPa) was significantly higher than that obtained with the ε̇M (2.04 ± 0.01 kPa). We show that the overestimation of stiffness is due to data acquisition in a local rather than an absolute LVR, highlighting the importance of using a rapid and zero pre-stress approach to characterise very soft and highly hydrated biological tissues.

Spot urinary iodine concentration as a measure of dietary iodine, evaluated in over 3800 young male subjects undergoing medical check-up preliminary to military enrolment in Piemonte and Aosta Valley (Italy).

The aim of the study was to assess iodine status in over 3800 young male subjects aged 18, living in 6 different provinces of Piemonte and in Aosta Valley, Italy. A cross-sectional study on 3837 young male subjects undergoing medical evaluation preliminary to military enrolment was performed. Spot urine samples were obtained in the morning hours and urinary iodine was measured by a colorimetric method. As outcome measure iodine status, based on spot urinary iodine median concentration, categorised as sufficient (>99 microg/l), mild deficiency (50-99 microg/l), moderate deficiency (20-49 microg/l) and severe deficiency (<20 microg/l), was obtained. Median urinary iodine concentration was 101.8 microg/l in our sample. Moderate-to-severe iodine deficiency was found in <10% of all subjects. Mild iodine deficiency was found in <40% of the subjects, with greater variability within the provinces considered. For each geographical area significant differences can be observed in more than 50% of the comparisons of the confidence intervals related to the frequencies of samples with spot urinary iodine concentration below 100 microg/l. The high frequency of mild iodine deficiency found in our sample suggests that dietary sources of iodine in Piemonte, Italy, have improved since the last evaluation 25 yr ago (2) but may still be insufficient. Further population studies are required.

[Analysis of right electrocardiographic leads in 195 normal subjects]. / Analisi delle derivazioni elettrocardiografiche destre in 195 soggetti normali.

AIM: The aim of the present study was to analyse age-related differences in the morphology of QRS complex and ST-T segment of right-sided chest ECG leads (V3R-V6R) in normal subjects. METHODS: One hundred ninety-five subjects evaluated for competitive sport training were divided into 2 groups according to age: group A (18-35 years) 77 subjects; group B (36-65 years) 118 subjects. All subjects underwent a complete clinical examination, conventional 12-lead ECG with right-sided chest leads, spirometric tests, a maximal stress-test (Bruce protocol), and a cardiac ultrasound study. None had signs or symptoms of cardiopulmonary disease nor of thoracic abnormalities, and all had normal standard ECGs. RESULTS: An rS morphology in V3R-V4R was observed in 92%-84% and 92%-81% of subjects in groups A and B, respectively (p = NS). The QS morphology in V6R was observed in 15% of subjects in group A and in 11% in group B (p = NS). Negative T-waves in V6R were more often observed in group A than B (94% vs 85%, p < 0.03). Isoelectric T-waves in V3R were found in 10% of subjects in group A and 21% in group B (p < 0.04). The amplitude of R-wave was always higher in group A (p < 0.01). An upsloping ST-T segment (0.5-1 mm) was observed only in V3R-V4R, with a prevalence of 23% in group A and 13% in group B in V3R (p < 0.05). CONCLUSIONS: No significant differences were observed between the 2 groups as to QRS complex of the right-sided ECG leads. A QS morphology may be observed even in normal subjects. The polarity of T-wave is quite variable, but in V6R it is most often negative among young people. Elevation of ST-T segment may be observed only in V3R and V4R, and more often in young subjects in the former lead.

Multiple myeloma: 'early' plasma cell phenotype identifies patients with aggressive biological and clinical characteristics.

The immunological phenotype of bone marrow myeloma cells and peripheral blood lymphocytes was evaluated in 38 untreated myeloma patients. A striking increase of monotypic cells expressing the same light chain as the M component was observed in bone marrow from 18/38 (47%) patients. A two-colour analysis clarified that the majority of myeloma cells co-expressed plasma cell and B lymphocyte markers (cyIg, CD38, CD56 and sIg), and were regarded as early-plasma cells (early-PC). In the remaining patients, myeloma cells expressed plasma cell markers only (late-PC). Phenotype corresponded to a distinct morphological pattern: early-PC showed a lympho-plasmocytoid feature with significantly lower diameters than late-PC (12.1 v 14.8 microns, P < 0.007). Moreover, the plasma cell labelling index was significantly increased in early-PC patients (1.2 v 0.5%, P < 0.04). In peripheral blood from patients with early-PC, monotypic cells co-expressing sIg and CD38, CD56, but not CD19, were also detected. These data suggest a recirculation of early-PC. Myeloma cells maintained their phenotypic pattern during the course of the disease. This observation suggests that the degree of maturation is an intrinsic characteristic of the myeloma cell population in individual patients. The evaluation of prognostic factors, such as beta 2-microglobulin, C-reactive protein and neopterin, showed a statistically significant increase in the early-PC patients, suggesting a poor outcome. In conclusion, myeloma cell phenotype allows identification of a myeloma variant with aggressive biological and clinical characteristics.

Interferon plus glucocorticoids as intensified maintenance therapy prolongs tumor control in relapsed myeloma.

Interferon-alpha-2b (IFN) has been demonstrated to prolong remission duration and survival in responding multiple myeloma (MM) patients. The aim of this study was to intensity maintenance therapy adding glucocorticoids (GLU) to the standard IFN therapy. Twenty-eight relapsed MMs with stable disease or response after conventional chemotherapy received IFN+GLU. The treatment included 3 megaunits of IFN 3 times a week continuously until relapse, plus 4 days pulsed high-dose dexamethasone (40 mg/day for 4 days every 28 days for 6 consecutive months every 12 months) in patients < 70 years, or oral prednisone (PDN, 50 mg 3 times a week) in patients > 70 years, both until relapse. Conventional chemotherapy induced a response in 12/28 MMs. For all patients the actuarial median progression-free survival from relapse was 24 months and the survival from relapse 42 months with no difference between responding and nonresponding patients. The first duration of tumor control, i.e. the interval from diagnosis to first relapse, was shorter than the period between first and second relapse in 11/28 patients (40%). Toxicity was mild and oral PDN significantly increased the subjective tolerability of IFN. These findings indicate that IFN+GLU after induction chemotherapy may prolong the duration of tumor control in relapsed MM.

Multiple myeloma: intensified maintenance therapy with recombinant interferon-alpha-2b plus glucocorticoids.

Interferon-alpha-2b has been demonstrated to prolong remission duration and survival in responding multiple myeloma patients. The aim of this study was to evaluate intensification of this maintenance therapy through the addition of glucocorticoids. Eighteen myeloma patients at diagnosis received six-12 courses of conventional chemotherapy and then interferon + glucocorticoids. This treatment included 3 megaunits of interferon three times a week, plus 4 days of pulsed high-dose dexamethasone (40 mg/d for 4 d every 28 d for 6 months/year) in patients < 70 yr old, or oral prednisone (50 mg three times a wk) in patients > 70 yr old. Conventional chemotherapy induced an objective response in 13/18 patients and a further reduction of the M component (> 50%) was achieved during interferon + glucocorticoids treatment in 7/13. 4/18 patients relapsed with a median follow-up of 22 months (range 13-40). These findings indicate that interferon + glucocorticoids, after inductional chemotherapy, further reduces tumor burden and may prolong remission.

Transplacental passage of autoantibodies to triiodothyronine.

Autoantibodies to T3 (T3Ab) were detected by immunoprecipitation in a 18-year-old female patient affected by Graves' disease. The presence of these antibodies was constantly confirmed during a 7-year follow-up period, independently of therapy and functional thyroid status. Antithyroid microsomal antibodies (McAb) and TSH binding-inhibiting antibodies (TBII) were also present. The title of AbT3, McAb and TBII fluctuated, at times, independently of one another. The patient became pregnant; during pregnancy T3Ab concentration fell and went up again 4 months after delivery. A normal baby was born. T3Ab were present in the cord blood and declined during the following 2-8 months. The T3Ab of both mother and child belonged to the IgG class. The concentrations and the binding affinities of T3Ab in mother and child were identical. The presence of T3Ab in the child did not affect his thyroid function.

Thrombosis-free survival and life expectancy in 187 consecutive patients with essential thrombocythemia.

A total of 187 consecutive patients with essential thrombocythemia (ET) were diagnosed and followed by our Hematology Department in the period October 1980-November 1994. The overall follow-up was 773 patient-years. Thrombosis-free survival and overall survival were calculated for the whole cohort; the same parameters were then calculated after arbitrary division of the cohort into two groups, according to the median age at diagnosis (55 years). Fifty percent of the patients had at least one thrombotic episode within 9 years after diagnosis. The thrombosis-free survival curves calculated for patients younger or older than 55 years at diagnosis were comparable. About 85% of the patients were alive 10 years after diagnosis. The survival curves for patients younger and older than 55 years at diagnosis were not significantly different in the observation period, and the observed mortality (seven patients) among patients younger than 55 years at diagnosis was significantly higher than expected (1.68 cases). The relative risk of death was four times greater (SMR = 4.17, 95% C.I. 1.6-8.6, p<0.01) than for healthy, age-matched people living in the same area. Age at diagnosis, smoking, sex, hypercholesterolemia, peak number of platelets, hypertension, and diabetes were not significant prognostic cardiovascular risk factors in our cohort. In conclusion, our data show that ET has to be considered a serious disease that significantly decreases both quality of life (expected life without thrombosis) and life expectancy for younger patients.

Multiple myeloma: increased circulating lymphocytes carrying plasma cell-associated antigens as an indicator of poor survival.

In multiple myeloma (MM) an increase in circulating lymphocytes expressing plasma cell-associated antigens (PCAA) has been described. Its prognostic significance was evaluated in this study. The immunologic phenotype of peripheral blood lymphocytes was analyzed with a panel of monoclonal antibodies specific for B, T, natural killer lymphocytes, and PCAA (CD38, PCA1) in 52 MM patients at diagnosis, remission, and during relapse, 18 monoclonal gammopathy of undetermined significance (MGUS), and 25 normal controls. No significant phenotypic alteration was observed in MGUS. In MM, the number of B lymphocytes was in the normal range at diagnosis and during the subsequent phases. A CD4/CD8 ratio decrease, during relapse, was due to both a CD4+ reduction and to an expansion of a subset of CD8+ activated suppressor lymphocytes. CD38+ and PCA1+ lymphocytes at diagnosis were significantly higher than in MGUS, and a further increase was observed during relapse, suggesting a correlation between PCAA expression and disease activity. The prognostic significance of increased PCAA was confirmed by a survival analysis of 32 patients evaluated at diagnosis using a CD38 cutoff of 0.45 x 10(9)/L positive lymphocytes. Median survival for patients with high values was only 14 months, whereas it was not reached at 32 months by those with low values (P less than .0007).

Consolidation treatment with dexamethasone and alpha-2B recombinant interferon further reduces the M-component level in multiple myeloma patients responding to conventional induction chemotherapy.

Three patients with symptomatic multiple myeloma who had achieved an objective response after conventional induction chemotherapy were treated with alpha-2b-interferon plus intermittent high-dose dexamethasone as consolidation therapy. This treatment included three mega units of alpha-2b-interferon three times a week, plus 4 days pulsed high-dose dexamethasone every 28 days for 6 months. Toxicity was limited to a mild flu-like syndrome. A further and significant M-component reduction (50%), obtained after conventional chemotherapy, suggests the value of intermittent high-dose dexamethasone plus interferon as consolidation therapy.

Bone turnover in hyperthyroidism before and after thyrostatic management.

Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity, and patients frequently have low bone mineral density and high bone turnover. The aim of this study was to examine the bone formation and resorption markers trend in 12 female patients, before and after normalization of thyroid activity. The following measurements were made at baseline and 1 and 6 months after hormone normalization induced by methimazole treatment: total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), collagen type C-terminal propeptide (PICP), osteocalcin (BGP), telopeptide (ICTP), urinary-hydroxyproline/urinary creatinine (uOHP/uCreat), urinary calcium/urinary creatinine (uCa/uCreat) and deoxypyridinoline crosslinks (D-Pyr). Compared with controls, all of these parameters were significantly increased (ALP p = 0.014; BALP p = 0.0001; PICP p = 0.013; BGP p = 0.009; ICTP p = 0.0001; uOHP/uCreat p = 0.002; uCa/uCreat p = 0.044; crosslinks p = 0.0001). After treatment the values of ALP, BALP and PICP in hyperthyroid patients showed an initial slight increase and then a significant downwards trend (ALP p = 0.008, BAP p = 0.001, PICP p = 0.026). Furthermore, resorption markers showed a significant decrease (uOHP/ uCreat p < 0.005 and D-Pyr p < 0.008). As regards lumbar BMD patients, measurements were significantly reduced in comparison with the control group (p = 0.005). Six months after serum thyroid hormones level normalization, we observed a significant increase (p=0.014 vs baseline). Both neoformation and resorption markers are useful to assess pathological bone turnover and bone involvement in hyperthyroidism. They could also be employed to monitor the effect of antithyroid treatment on bone and to indicate if bone antiresorption therapy should be considered.

Insulin binding to monocytes and in vivo peripheral insulin sensitivity are normal in Graves' disease.

Insulin resistance in hyperthyroidism seems to depend on increased glucose production rather than on decreased glucose utilization. A decreased insulin binding on different target cells has been reported in patients in whom an in vivo evaluation of peripheral insulin sensitivity was lacking. In 20 patients with Graves' disease (6 males, 14 females), aged 40.0 +/- 2.0 yr, BMI 23.7 +/- 0.7, and in 20 well-matched controls we performed the following tests: 75 g o.G.T.T., euglycemic-hyperinsulinemic clamp at 50 microU/ml combined with D-[3-3H] glucose infusion in tracer amounts, in vitro insulin binding on circulating monocytes. Fasting plasma glucose values were similar in the two groups, whereas plasma insulin values were significantly higher in hyperthyroids (21.4 +/- 2.5 vs 10.6 +/- 0.6 microU/ml, p less than 0.01). The values of peripheral glucose utilization (5.61 +/- 0.24 vs 6.01 +/- 0.22 mg/kg-min) and of total specific insulin binding (4.07 +/- 0.20 vs 4.39 +/- 0.23% bound to 10(7) cells/ml) were not significantly different in the two groups. These results indicate that in vitro and in vivo data, when recorded in the same patients, are concordant to confirm a normal peripheral tissue sensitivity to insulin in Graves' disease.

Multiple myeloma: beta-2-microglobulin is not a useful follow-up parameter.

Serum beta-2-microglobulin (beta 2M) has been suggested as the most powerful prognostic factor in multiple myeloma (MM). This paper investigates its ability to detect remission and relapse in individual patients. A correlation analysis was carried out between beta 2M and M component determinations, at diagnosis and monthly during follow-up in 21 consecutive MM patients with normal renal function. A statistically significant correlation was observed in 52.4% only. The lack of correlation in the remaining cases was due to low beta 2M production at diagnosis, or independent fluctuation of these 2 parameters. Serum beta 2M proved a much less reliable parameter for the detection of tumour variations than simpler M-component determination.

Impact of glycaemic control, hypertension and insulin treatment on general and cause-specific mortality: an Italian population-based cohort of type II (non-insulin-dependent) diabetes mellitus.

The aims of this study were to assess the impact of diabetes and associated variables (fasting plasma glucose, blood pressure, antidiabetic treatment, body mass index) on general and cause-specific mortality in an Italian population-based cohort with Type II (non-insulin-dependent) diabetes mellitus, comprising mainly elderly patients. The patients (n = 1967) who had Type II diabetes were identified in 1988 with an 80% estimated completeness of ascertainment. In 1995, a mortality follow-up (98% completeness) of the cohort was done amounting to a total of 11153 person-years. Observed and expected number of deaths were 577 and 428.7, respectively, giving a standardized mortality ratio (SMR) of 1.35 (95% CI 1.24-1.46). The most common underlying causes of death were malignant neoplasm, ischaemic heart disease and cerebrovascular diseases, which accounted for 18%, 17.8% and 17.5% of deaths, respectively. Cardiovascular disease as a whole (international classification of disease ICD-9 390-459) accounted for 260 of 577 deaths (SMR 1.21, 95% CI 1.07-1.36). In internal analysis, the most important predictors of general mortality were insulin-treatment (relative risk [RR] 1.72, 95% CI 1.19-2.49) and a fasting plasma glucose greater than 8.89 mmol/l ([RR] 1.29, 95 % CI 1.04-1.60), whereas the most important predictors of cardiovascular diseases were insulin-treatment and hypertension. In conclusion, this population-based study showed: 1) slight mortality excess of 35% in Type II diabetes being associated with 2) a 30% increased mortality in subjects with baseline fasting glucose greater than 8.89 mmol/l and 3) a 40% increased risk of death from cardiovascular diseases in hypertensive patients.