The HLA-DR13 haplotype is associated with "benign" multiple sclerosis in northeast Italy.
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Adult↗
Biomedical subjects
P Perini
Publications and source records attributed to P Perini.
The range of multiple sclerosis associated with neurofibromatosis type 1.
Multiple sclerosis associated with neurofibromatosis type 1 (NF1) is a very rare event. Seven patients with multiple sclerosis and NF1 are described in the literature, and all were reported to have the primary progressive form of multiple sclerosis. Three new patients with NF1 that developed multiple sclerosis are described and it is shown that the range of multiple sclerosis associated with NF1 includes the relapsing forms of the disease. The risk of having both NF1 and multiple sclerosis in north east Italy is higher than would be expected based on the prevalence rates of the two diseases.
Adult↗
Interferon-beta (INF-beta) antibodies in interferon-beta1a- and interferon-beta1b-treated multiple sclerosis patients. Prevalence, kinetics, cross-reactivity, and factors enhancing interferon-beta immunogenicity in vivo.
We analysed the role of dosage, route and frequency of administration of clinical grade interferon-beta (IFN-beta) preparations in inducing anti-IFN-beta antibodies (IFN-beta-Abs) in 5 groups of relapsing-remitting multiple sclerosis (RRMS) patients who were respectively treated as follows: 1) weekly intramuscular (i.m.) injections of 30 mg of recombinant IFN-beta1a (Avonex), 2) subcutis (s.c.) injections of 250 mg IFN-beta1b (Betaferon) every other day, 3) weekly i.m. injections of 250 mg IFN-beta1b (Betaferon), 4) s.c. injections of 22 mg of IFN-beta1a (Rebif) three times a week, and 5) i.m. injections of 22 mg of IFN-beta1a (Rebif) twice a week. IFN-beta-Abs were determined by ELISA. IFN-beta1b was more immunogenic than IFN-beta1a not only when administered s.c. every other day, but also when administered i.m. at a lower weekly dose; i.m. injection, however, significantly delayed the appearance, and induced lower serum levels of IFN-beta-Abs. In patients treated with s.c. IFN-beta1b, Ab levels peaked 3 to 9 months after therapy initiation, and then slowly, but progressively, declined to pre-therapy levels that in some patients were reached after three years. Patients treated with i.m. or s.c. IFN-beta1a only rarely developed IFN-beta-Abs, and then at very low titers. Overall, the i.m. weekly administration of IFN-beta1a was the less immunogenic treatment. In IFN-beta1b-treated patients, a wash-out period of two/three months was sufficient to bring the IFN-beta-Ab levels below the cut-off. Our findings suggest that the immunogenicity of IFN-beta1a is low, regardless of the route of administration and the dosage, while that of IFN-beta1b is high, and is significantly, but not completely reduced by i.m. administration. As IFN-beta-Abs are cross-reactive, a wash-out period is suggested when the preparation is changed from IFN-beta1b to IFN-beta1a in order to maintain the clinical benefits of the therapy.
Antibodies↗
Effect of IFNbeta and anti-IFNbeta antibodies on NK cells in multiple sclerosis patients.
We analysed longitudinally the numbers of CD3-CD16+ (natural killer cells, NK) and CD3-CD57+ cells (a subset of NK) in 15 IFNbeta1b- and 12 IFNbeta1a-treated relapsing-remitting multiple sclerosis (RRMS) patients. IFNbeta1b (Betaferon)-treated RRMS patients showed a rapid and marked reduction in the number of both NK subsets which started 1 month after therapy initiation, and reached highest significance after 3 months (P=0.000); however, figures reverted to pre-treatment values following the appearance of anti-IFNbeta antibodies. In IFNbeta1a (Avonex)-treated RRMS patients, the decrease in both CD3-CD16+ and CD3-CD57+ cell number was slower but more persistent; anti-IFNbeta antibodies were only rarely detected in these patients, and at lower titers than in IFNbeta1b-treated ones. Our findings suggest that NK cells might be one of the major immunological targets of IFNbeta-based treatments.
Adult↗
Interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor type I and II, and soluble E-selectin serum levels in multiple sclerosis patients receiving weekly intramuscular injections of interferon-beta1a.
BACKGROUND: interferon beta (IFN-beta) reduces relapse rate and disease progression in patients with the relapsing-remitting form of multiple sclerosis (RRMS). IFN-beta may act by upregulating the expression of anti-inflammatory components of the immune system. OBJECTIVES: To determine whether weekly intramuscular (i.m.) injection of IFN-beta1a had a short- or long-term effect on the expression of naturally occurring soluble factors that play an immunosuppressive role within the cytokine network. MATERIALS AND METHODS: serum levels of interleukin-1 receptor antagonist (IL-1Ra), soluble tumor necrosis factor alpha receptor type I and type II (sTNF-alphaRI and sTNF-alphaRII), and soluble E-selectin (sE-Sel) were followed over time in ten patients with RRMS who were treated with weekly i.m. injections of 30 mg (= 6 MU) of IFN-beta1a. Patient sera were sampled before, and 24, 48, 72, 96, and 168 hours after the first IFN-beta1a injection (short-term), and then at 1, 3, 6, 9 and 12 months after therapy initiation (long-term); highly sensitive, commercially available ELISA tests were used. RESULTS: serum levels of IL-1Ra, sTNF-alphaRI and sTNF-alphaRII, but not sE-Sel were significantly increased in both short- and long-term follow-up. Interestingly, IL-1Ra, sTNF-alphaRI and sTNF-alphaRII behaviors were completely different, suggesting that these naturally occurring immunoregulatory factors were differentially affected by IFN-beta1a. CONCLUSION: our study demonstrates that weekly i.m. injection of 30 mg of IFN-beta1a induces the expression of soluble mediators that may suppress the activities of pro-inflammatory cytokines such as IL-1 and TNF-alpha.
Adjuvants, Immunologic↗
Time-course analysis of CD25 and HLA-DR expression on lymphocytes in interferon-beta 1b-treated multiple sclerosis patients.
To identify immunological markers that could be used to monitor relapsing-remitting multiple sclerosis (RRMS) course/activity during interferon beta 1b (IFN beta 1b) therapy, we longitudinally studied HLA-DR and CD25 expression by T lymphocytes in 15 IFN beta 1b-treated RRMS patients. Peripheral blood T cell subsets were analysed before therapy (T0), and after 1 (T1), 2 (T2), 3 (T3), 6 (T4) and 12 (T5) months after therapy initiation. HLA-DR expression and the CD3+HLA-DR+ T cell number showed a peculiar trend in almost all (14/15) the patients: a significant decrease at T1 and T2 followed by a return to pre-treatment levels from T3 to T5. At T1 and T2, eight patients showed an up-regulation of CD25 on CD4, as well as an increase in the CD4+CD25+ cell number. However, a marked, significant reduction of this T cell subset was observed in all the patients at T3, followed by the progressive return to pre-treatment values from T4 to T5. All the patients developed anti-IFN beta 1b 'binding' antibodies within the first three months of therapy. Our findings demonstrate that: (1) the expression of HLA-DR and CD25 on T cells, as well as the number of circulating CD3+HLA-DR+ and CD4+CD25+ cells, are only transiently reduced in vivo in IFN beta 1b-treated RRMS patients, (2) the expression of HLA-DR and CD25 on T lymphocytes cannot be used to monitor MS course/activity during IFN beta 1b therapy, (3) the long-lasting beneficial effect of IFN beta 1b on RRMS reported in the literature cannot be explained by the down-regulation of MHC class II antigens and/or interleukin-2 receptor expression induced by this cytokine.
Adjuvants, Immunologic↗
Long-term treatment with the dual antithromboxane agent picotamide decreases microalbuminuria in normotensive type 2 diabetic patients.
Picotamide both inhibits thromboxane synthetase and acts as a thromboxane antagonist at the receptor level. We investigated the long-term effect of picotamide on urinary albumin excretion (UAE) at rest and induced by exercise in 30 type 2 diabetic patients who were normotensive and had microalbuminuria while at rest. The subjects of our study had a mean age of 52.5 +/- 1.6 years, BMI of 28.5 +/- 0.7 kg/m2, diabetes duration of 9.1 +/- 1.8 years, and HbA1c of 7.0 +/- 0.8%. The study was a randomized double-blind placebo-controlled trial. The patients were randomly allocated to receive for 1 year either picotamide, 300 mg, 3 tablets/day, or placebo, 3 tablets/day. The patients were asked to visit our outpatient clinic after 1, 3, 6, 9, and 12 months of treatment. At all times, blood pressure, microalbuminuria at rest, blood glucose, serum creatinine, serum picotamide, and creatinine clearance were measured; at baseline and after 6 and 12 months, all patients underwent submaximal physical exercise. After 6 months of picotamide, baseline and exercise-induced microalbuminuria were significantly decreased (up to one-third) as compared with the baseline and placebo level, with no further drops at month 12 of picotamide treatment. On placebo treatment, UAE at rest and after exercise was slightly increased compared with baseline values. The effects of picotamide occurred without significant side effects or changes in either blood pressure levels or glycometabolic control. Our study is the first long-term intervention trial in type 2 diabetes showing that an antithromboxane agent is able to decrease microalbuminuria, which in this disease is a dual marker of macro- and microangiopathy. Our findings suggest an important role for thromboxane in the pathophysiology of microalbuminuria in diabetes; moreover, we hypothesize that antithromboxane agents may have a place in the treatment/prevention of both macro- and microvascular complications in type 2 diabetic patients.
Administration, Oral↗
Growth hormone treatment in aging: state of the art and perspectives.
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Aging↗
Glutamate decarboxylase autoimmunity and growth hormone secretion in type I diabetes mellitus.
Insulin-dependent (type I) diabetic patients are known to have an exaggerated growth hormone (GH) response to GH-releasing hormone (GHRH), which is hypothesized to be due to a decrease in somatostatin tone. The aim of the study was to ascertain the influence of the presence and activity of the autoimmune process involving a key enzyme (glutamic acid decarboxylase [GAD]) in the synthetic pathway of a neurotransmitter regulating somatostatin secretion, ie, gamma-aminobutyric acid (GABA), on the GH response to GHRH alone or combined with an acetylcholinesterase inhibitor, pyridostigmine (PD), in patients with type I diabetes mellitus. Twenty non-obese type I diabetic patients and 17 normal subjects underwent an intravenous (IV) injection of 100 micrograms GHRH(1-29)NH2. Twelve of 20 diabetic subjects and all of the control subjects also underwent a second experimental procedure, administration of 120 mg oral PD 60 minutes before IV injection of 100 micrograms GHRH. Diabetic subjects with serum GAD antibody (GADA) levels more than 3 U (n = 10) showed significantly higher serum GH levels after GHRH injection as compared both with diabetic patients with GADA less than 3 U (n = 10) and with normal controls, whether expressed as absolute or peak values. GH peaks after GHRH were significantly (rs = .46, P < .05) correlated with the level of GADA in the whole population of type I diabetic subjects studied. PD significantly enhanced the GH response to GHRH, in terms of both absolute and peak values, in patients without GADA (n = 6) and in normal subjects. On the contrary, PD failed to enhance the GH response to GHRH in diabetic patients with GADA (n = 6). Our findings suggest that autoimmunity may play a key role in determining the exaggerated GH response to GHRH in type I diabetes mellitus. The mechanism underlying this effect is hypothesized to be the production of antibodies to GAD, a key enzyme in the synthesis of GABA, and in turn a reduced GABAergic stimulatory tone on somatostatin production at the hypothalamic level.
Adult↗
Genetic epidemiology of congenital muscular dystrophy in a sample from north-east Italy.
Congenital muscular dystrophy (CMD) is a heterogeneous disease with autosomic recessive transmission. In an epidemiological study in four provinces of Veneto (region of 2 586 830 inhabitants in north-east Italy), the recorded incidence rate for the period 1979-1993 was 4.65 x 10(-5); the prevalence rate in the year 1993 was 6.8x10(-6). The incidence and the prevalence rates that we have obtained during the course of our investigation represent the first estimates for CMD in Europe and show that this myopathy is among the most frequent neuromuscular diseases with autosomic recessive transmission.
Child↗
Response of phenylalanine and leucine kinetics to branched chain-enriched amino acids and insulin in patients with cirrhosis.
BACKGROUND & AIMS: We tested the effects of branched chain-enriched, aromatic-deficient amino acids with insulin to correct the altered protein turnover as well as phenylalanine (Phe) and leucine (Leu) rate of appearance in compensated cirrhotics and controls. METHODS: Phe and Leu tracers were infused both before and following intravenous amino acid administration with insulin and euglycemic clamp. RESULTS: In cirrhosis, fasting whole-body protein synthesis and protein degradation were normal; Phe rate of appearance was greater (P<0.05), whereas Leu rate of appearance/Phe rate of appearance ratio was approximately 35% less than in controls (P<0.001). Following the infusion, protein synthesis did not increase (+1% +/ 5% [NS] vs. +21% +/- 5% [P<0.05] in controls); protein degradation was more suppressed, whereas protein balance increased normally. Total Phe rate of appearance (0.91 +/- 0.13 micromol x kg-1 x min-1) and Leu/Phe disposal ratio (3.53 +/- 0.36) were nearly normalized (fasting controls, 0.68 +/- 0.07 micromol x kg-1 x min-1 and 2.87 +/- 0.14 micromol x kg-1 x min-1, respectively; P>0.05). However, Leu/Phe endogenous rate of appearance ration remained approximately 50% less (1.56 +/- 0.31 vs. 2.87 +/- 0.14; P<0.004) than in controls. CONCLUSIONS: Following this combined infusion in cirrhosis, net protein deposition increased normally despite a blunted response of protein synthesis. Phe and Leu to Phe peripheral disposal were near normalized; however, the exaggerated endogenous Phe production was not corrected entirely.
Amino Acids, Branched-Chain↗
Hypothalamic control of growth hormone (GH) secretion in type I diabetic men: effect of the combined administration of GH-releasing hormone and hexarelin, a novel GHRP-6 analog.
Insulin dependent (type I) diabetic patients show abnormal growth hormone (GH) secretion. Hexarelin is an analog of GHRP-6 which releases GH in part via somatostatin inhibition. The aim of our study was to evaluate the effects of hexarelin and GHRH, administered either alone or in combination, on GH secretion in 10 type I diabetic and 7 normal men. All the subjects were administered: 1) human GHRH (1-29) NH2 100 micrograms i.v. bolus at 0 min; 2) hexarelin 100 micrograms i.v. bolus at 0 min; 3) hexarelin 100 micrograms + hGHRH 100 micrograms i.v. bolus at 0 min. In type I diabetic patients significantly greater GH responses to GHRH and hexarelin have been observed with normal subjects. Hexarelin caused a significantly (p < 0.05) greater GH response as compared to GHRH in both diabetic and control subjects. After the administration of hexarelin+GHRH, a significant increase in both GH absolute and peak levels as compared to hexarelin or GHRH alone was found in all the subjects. However, the GH responses to the combined stimuli were not significantly different in diabetics as compared to normals; moreover, the interaction of GHRH and hexarelin was synergistic in controls and additive in diabetics. We hypothesize that a reduction in the hypothalamic somatostatin inhibitory tone combined with increased pituitary GH production may be responsible for the pattern of the GH responses to hexarelin and GHRH observed in our type I diabetic patients.
Adult↗
Relationship between energy expenditure and visceral fat accumulation in obese women submitted to adjustable silicone gastric banding (ASGB).
OBJECTIVE: To analyze the relationship between visceral fat accumulation and resting energy expenditure in obese women and to evaluate the effects of a severe weight loss both on energy expenditure and on fat distribution. DESIGN: Twelve premenopausal women, aged 19-50 years, undergoing adjustable silicone gastric banding (ASGB) for morbid obesity participated at the study. The patients were evaluated twice. The baseline evaluation was performed immediately before surgery. After surgery, a diet specifically developed for patients submitted to gastric restriction (2.5 MJ/day) was given to the patients. The second evaluation was performed 6 months after surgery. MEASUREMENTS: Resting metabolic rate (RMR) was determined by indirect calorimetry. Total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by abdominal computed tomography. Fat mass (FM) and fat free mass (FFM) were derived by bioelectrical impedance analysis. RESULTS: At baseline, RMR was positively related to VFA (r = 0.60, P < 0.05). ASGB induced a highly significant weight loss of 24.4 +/- 9.0 kg. This weight reduction was mainly due to a loss of FM (68.5 +/- 10.8 vs 48.5 +/- 9.2 kg, P < 0.001), whereas FFM was only slightly reduced (52.6 +/- 4.0 vs 47.9 +/- 4.6 kg, P < 0.05). The BMI reduction was positively related to the baseline BMI and FM values (r = 0.61, P < 0.05 and r = 0.55, P < 0.05, respectively). There was no significant correlation between the BMI reduction and the baseline variables of fat distribution, nor between the BMI reduction and the basal RMR. Weight loss was accompanied by modifications of fat distribution. In particular, the reduction of VFA after surgery was strictly related to the VFA values at baseline (r = 0.91, P < 0.001). Weight loss induced a significant reduction of RMR (7.96 +/- 1.77 vs 6.57 +/- 6.90 MJ/day; P < 0.01). The reduction of the RMR observed with weight loss was significantly related to the FFM loss (r = 0.63, P < 0.05), whereas no correlations were found between the changes of RMR and the FM loss. Regarding to fat distribution, the reduction of the RMR was significantly related to the visceral fat loss (r = 0.57, P < 0.05), but not to the modifications of total or subcutaneous fat area. The independent contribution of the modifications of FFM, FM, and visceral fat to the changes of RMR was analyzed by multiple regression analysis. In this model, both FFM and visceral fat changes resulted independently related to the RMR. CONCLUSIONS: (1) visceral fat accumulation was a significant predictor of RMR in the very obese woman; (2) visceral obese women lost more visceral fat than subcutaneous ones; (3) the reduction of the RMR observed during weight loss could partly be explained by a reduction of visceral fat mass.
Adipose Tissue↗
Accuracy of bioelectrical impedance analysis in estimation of extracellular space in healthy subjects and in fluid retention states.
Bioelectrical impedance analysis (BIA) is a noninvasive method recently introduced for body fluid evaluation in healthy subjects. The purpose of this paper is to verify the reliability of bioelectrical measurements in extracellular water (ECW) prediction in healthy subjects and in fluid retention states. We studied 40 subjects (19 males and 21 females) aged 21-81 years; 22 were healthy subjects, 12 were affected by chronic heart failure, and 6 by chronic renal failure. In all subjects resistance (R) and reactance (Xc) at 1 and 50 kHz corrected for height were compared with ECW measured by the bromide dilution method. Our results suggested a different behavior of the current in fluid-retention states with respect to healthy subjects. ECW was best predicted by resistance at 1 kHz corrected for height, group (considered as dummy variable), weight and gender (R2 = 0.89, p < 0.001, SEE = 1.7 liters). The bioelectrical impedance analysis at 50 kHz explained the 89% of ECW variability when resistance and reactance corrected for height are considered with gender group and weight (R2 = 0.89, p < 0.001, SEE = 1.7 liters). In conclusion, the bioelectrical method at 1 kHz can be considered sufficiently accurate in ECW prediction in healthy subjects and in fluid retention states. Also, the bioelectrical impedance analysis at 50 kHz is useful for predicting ECW, but his role must be further investigated.
Adult↗
Long-term persistence of IgM antibodies to HCV in chronic hepatitis C.
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Chronic Disease↗
Body composition study in the elderly: comparison between tritium dilution method and dual photon absorptiometry.
BACKGROUND: The methods commonly employed in body composition study in elderly persons derive fat-free mass (FFM) by measures of total body water (TBW); these methods assume FFM hydration constant (TBW/FFM = 0.732). The aim of our study was to verify the accuracy of the TBW method in FFM estimation and to study the variability of fat-free mass hydration (TBW/FFM) in healthy elderly subjects. METHODS: We assessed FFM in 27 healthy old subjects (76 +/- 7 yrs) by dual photon absorptiometry (DPA) and by TBW measured by 3H2O. Furthermore, to verify the accuracy in FFM estimation by our methods, we measured resting metabolic rate (RMR) by indirect calorimetry. RESULTS: FFM hydration was 71.9 +/- 4.9 (range 63.6-80.4%), a range larger than that reported by direct chemical analysis in adults. The FFM hydration measured in our subjects was not different from the 73.2 value currently used in healthy adults. FFM values derived by TBW (assuming TBW/FFM = 0.732) were not significantly different from FFM measured by DPA. We correlated FFM with resting metabolic rate and found a similar correlation between RMR and FFM-DPA (r = .89, p < .001) and FFM-TBW (r = .85, p < .001). CONCLUSIONS: Both methods employed in our study have proved to be accurate in estimating FFM in elderly persons; particularly, the value of 0.732 assigned to FFM hydration to derive fat-free mass in adults can be employed also in body composition study of the elderly.
Absorptiometry, Photon↗
Hepatitis C viraemia rebound after "successful" interferon therapy in patients with chronic non-A, non-B hepatitis.
A quantitative polymerase chain reaction (PCR) assay for hepatitis C viral RNA (HCV-RNA) was used to monitor viraemia levels in six patients at multiple time points before, during, and after interferon therapy for chronic non-A, non-B hepatitis (NANBH). Prior to therapy, serum HCV-RNA was detected in all patients at approximately 10(4)-10(5) HCV genomes/ml. HCV viraemia became undetectable within 1 month of commencing interferon in three of the five patients whose alanine aminotransferase (ALT) levels decreased to normal on therapy. In the remaining two responder patients, viraemia levels declined more slowly, becoming undetectable after a period of several months. Recurrence of viraemia during therapy was observed in two cases. The one patient whose serum ALT levels remained elevated throughout therapy showed no decline in viraemia. On stopping interferon after a 6 months course, HCV genome titres climbed rapidly in all patients, reaching higher levels than had been observed prior to therapy. Biochemical relapse occurred within 7 months of ending interferon treatment in all but one of the patients who demonstrated this viraemia "rebound" phenomenon.
Adult↗
Mediterranean-soy diet: hypocholesterolemic effects in FH E3/E2 heterozygous and type III patients.
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Adult↗