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Biomedical subjects

G Sanna

Publications and source records attributed to G Sanna.

At least 37 records · Page 2Linked to original sources

Increased pulmonary epithelial permeability in systemic sclerosis is associated with enhanced cutaneous nerve growth factor expression.

Background: Nerve growth factor (NGF), a neurotrophic factor that indirectly induces fibroblast proliferation and collagen production, has been found to be increased in the affected dermis of patients with systemic sclerosis (SSc). To investigate the possibility of a relationship between cutaneous NGF production and pulmonary damage in SSc, we studied seven non-smoking scleroderma patients. Methods: Abnormalities in lung structure were assessed by radiological lung examination, and pulmonary epithelial permeability (PEP) was determined by ventilation lung scintigraphy. All patients underwent skin punch biopsy with NGF immunohistological staining. Results: A statistically significant correlation was found between the PEP values and the cutaneous NGF staining scores, which were markedly increased in all of the patients examined, irrespective of the age, disease duration, or radiologically defined lung abnormalities. Conclusion: These results support the hypothesis that functional and anatomical changes in SSc target organs may be determined by a local tissue hyperproduction of NGF.

Journal Article↗

Evaluation of a commercial serological kit for detection of salivary immunoglobulin G to Helicobacter pylori: a multicentre study.

OBJECTIVE: To evaluate the usefulness of a commercial serological enzyme immunoassay (EIA) for detecting salivary immunoglobulin (Ig) G to Helicobacter pylori. DESIGN: Prospective, multicentre study. SETTING: The study was conducted at 11 gastroenterology hospital centres throughout Italy. PARTICIPANTS AND INTERVENTIONS: Two hundred and thirteen dyspeptic patients underwent gastroscopy with antral biopsies. At each centre, two of the following three tests for H. pylori diagnosis were performed: urease quick test, histology, and 13C-urea breath test. Samples of unstimulated saliva and venous blood were collected from each patient. Salivary and serum H. pylori IgG were determined with the EIA Helori-test IgG (Eurospital, Trieste, Italy). MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and accuracy of the salivary and serum EIAs. RESULTS: By using a receiver operating characteristic curve, salivary EIA yielded 81% (95% confidence interval 73-87%) sensitivity, 73% (62-83%) specificity, 84% (76-90%) positive predictive value, 69% (58-79%) negative predictive value, and 78% (72-84%) accuracy. At the cut-off suggested by the manufacturer, serum EIA had 90% (84-95%) sensitivity, 78% (67-86%) specificity, 88% (81-93%) positive predictive value, 82% (71-90%) negative predictive value, and 86% (81-91%) accuracy. CONCLUSION: In this large multicentre study, detection of salivary H. pylori IgG with a commercial serological EIA was a fairly accurate diagnostic method. Data confirm that saliva testing does not compare favourably with serology in the assessment of H. pylori status.

Adolescent↗

Effect of vitamin C on forearm blood flow and glucose metabolism in essential hypertension.

In 9 patients with essential hypertension, we tested whether a high-dose (12 mg. min(-1)) vitamin C infusion into the brachial artery, by improving endothelium-dependent vasodilatation, would also attenuate the insulin resistance of deep forearm tissues. We measured the effect of vitamin C on acetylcholine (Ach)-induced vasodilatation and on forearm glucose uptake during systemic hyperinsulinemia; in all studies, the contralateral forearm served as the control. Intrabrachial Ach infusion produced a stable increase in forearm blood flow, from 2.6+/-0.3 to 10.6+/-2.1 mL. min(-1). dL(-1); when vitamin C was added, a further rise in forearm blood flow (to 13.4 mL. min(-1). dL(-1); P<0.03 vs Ach alone) was observed. In response to insulin, blood flow in both the infused and control forearms did not significantly change from baseline values (+10+/-16% and +2+/-11%, respectively). In contrast, when vitamin C was added, blood flow in the infused forearm increased significantly (to 3.7+/-0.7 mL. min(-1). dL(-1); P<0.02 vs 2.8+/-0.6 mL. min(-1). dL(-1) in the control forearm). Insulin stimulated whole-body glucose disposal to 20+/-2 micromol. min(-1). kg(-1), compatible with the presence of marked insulin resistance. Forearm glucose uptake was similarly stimulated after 80 minutes of insulin infusion (to 2.11+/-0.42 and 2.06+/-0.43 micromol. min(-1). dL(-1), infused and control, respectively). When intrabrachial vitamin C was added, no difference in glucose uptake was observed between the 2 forearms (infused, 2.37+/-0.44 micromol. min(-1). dL(-1)and control, 2.36+/-0. 53 micromol. min(-1). dL(-1)). Forearm O(2) uptake at baseline was also similar in the 2 forearms (infused, 9.7+/-0.7 micromol. min(-1). dL(-1) and control, 9.6+/-1.1 micromol. min(-1). dL(-1)) and was not changed by either insulin or vitamin C. We conclude that in the deep forearm tissues of patients with essential hypertension and insulin resistance, an acute improvement in endothelial function, obtained with pharmacological doses of vitamin C, restores insulin-mediated vasodilatation but does not improve insulin-mediated glucose uptake. Thus, the endothelial dysfunction of essential hypertension is unlikely to be responsible for their metabolic insulin resistance.

Ascorbic Acid↗

Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations.

The aim of this study was to evaluate morphological and functional abnormalities by cerebral imaging in a series of systemic lupus erythematosus (SLE) patients with and without overt central nervous system (CNS) manifestations, and to detect possible relationships with clinical parameters and a large panel of autoantibodies, including those reactive against neurotypic and gliotypic antigens. 68 patients with SLE were investigated in a cross-sectional study which included clinical evaluation of symptoms, cerebral magnetic resonance imaging (MRI) and brain single photon emission tomography (SPECT) analysis, electroencephalography (EEG), and serological tests for antibodies directed against nuclear, cytoplasmic neuronal and glial cell-related antigens. The results of this study showed: (1) a significant positive association of (a) anti-glial fibrillary acidic protein (GFAP) serum antibodies with neuropsychiatric (NP) manifestations and (b) anti-serin proteinase 3 (anti-PR3/c-ANCA) serum antibodies with pathological cerebral SPECT; (2) the presence of significantly higher values of (a) SLICC organ damage index in patients with abnormal MRI and (b) SLAM activity index in patients with abnormal SPECT; and (3) the association of (a) abnormal MRI with nonactive NP manifestations and (b) combined abnormality of brain SPECT and MRI with the occurrence of overall overt NP manifestations and with those of the organic/major type. Neuropsychiatric manifestations, namely those of the organic/major type, appeared to be significantly associated to the presence of a serum antibody against GFAP, a gliotypic antigen. There was also evidence of an association between SPECT abnormality and the presence of anti-PR3 (c-ANCA). Furthermore, brain imaging by MRI and SPECT applied to SLE patients appears to express CNS involvement significantly related to specific categories of NP manifestations. The abnormalities detected by the two tests seem to be preferentially associated with different activity phases of the NP disorder or of the lupus disease.

Adolescent↗

Bleomycin-induced scleroderma: report of a case with a chronic course rather than the typical acute/subacute self-limiting form.

We report a case of bleomycin-induced scleroderma in a 35-year-old woman treated with chemotherapy for Hodgkin's disease. Approximately 6 months after the first chemotherapy cycle, the patient developed skin sclerosis in both arms. The lesion showed no signs of spontaneous clinical amelioration and treatment with steroids was unsuccessful. A partial remission of the skin sclerosis was instead obtained by the administration of D-penicillamine. A family history revealed other cases of autoimmune diseases and HLA typing showed the presence of antigens associated with scleroderma. The association between bleomycin therapy and scleroderma is discussed.

Adult↗

HLA-DRB1*01 and DRB1*04 alleles in Sardinian rheumatoid arthritis patients.

In Sardinia, like in other Caucasoid populations, rheumatoid arthritis (RA) is significantly associated with HLA-DR4 and DR1 antigens. To discover which DR4 and DR1 alleles were associated with the disease we selected 22 Sardinian patients affected by RA. Fifty DR4+ and 28 DR1+ healthy individuals coming from the same geographical area were used as controls. In the Sardinian patients only two DRB1*04 alleles were observed: DRB1*0405 in 11 and DRB1*0403 in three patients. The DRB1*0102 allele was observed in two patients and DRB1*0101 in six patients. Hereditary predisposition to RA in Sardinia therefore seems to be almost exclusively associated with the DRB1*0405 and DRB1*0101 alleles which share the 67LLEQRRAA74-85VG86 epitope in the peptide binding groove.

Alleles↗

Effects of acute alpha 2-blockade on insulin action and secretion in humans.

We tested whether acute alpha 2-blockade affects insulin secretion, glucose and fat metabolism, thermogenesis, and hemodynamics in humans. During a 5-h epinephrine infusion (50 ng.min-1.kg-1) in five volunteers, deriglidole, a selective alpha 2-receptor inhibitor, led to a more sustained rise in plasma insulin and C-peptide levels (+59 +/- 14 vs. +28 +/- 6, and +273 +/- 18 vs. +53 +/- 14 pM, P < 0.01 vs. placebo) despite a smaller rise in plasma glucose (+0.90 +/- 0.4 vs. +1.5 +/- 0.3 mM, P < 0.01). Another 10 subjects were studied in the postabsorptive state and during a 4-h hyperglycemic (+4 mM) clamp, coupled with the ingestion of 75 g of glucose at 2 h. In the postabsorptive state, hepatic glucose production, resting energy expenditure, and plasma insulin, free fatty acid (FFA), and potassium concentrations were not affected by acute alpha 2-blockade. Hyperglycemia elicited a biphasic rise in plasma insulin (to a peak of 140 +/- 24 pM), C-peptide levels (1,520 +/- 344 pM), and insulin secretion (to 410 +/- 22 pmol/min); superimposed glucose ingestion elicited a further twofold rise in insulin and C-peptide levels, and insulin secretion. However, alpha 2-blockade failed to change these secretory responses. Fasting blood beta-hydroxybutyrate and glycerol and plasma FFA and potassium concentrations all declined with hyperglycemia; time course and extent of these changes were not affected by alpha 2-blockade. Resting energy expenditure (+25 vs. +16%, P < 0.01) and external cardiac work (+28% vs. +19%, P < 0.01) showed larger increments after alpha 2-blockade. We conclude that acute alpha 2-blockade in humans 1) prevents epinephrine-induced inhibition of insulin secretion, 2) does not potentiate basal or intravenous- or oral glucose-induced insulin release, 3) enhances thermogenesis, and 4) increases cardiac work.

Adrenergic alpha-2 Receptor Antagonists↗

Vasodilation with sodium nitroprusside does not improve insulin action in essential hypertension.

The vasodilation induced by systemic insulin infusion is mediated by nitric oxide and is impaired both in obese subjects and patients with essential hypertension. Whether this vascular defect explains the metabolic resistance to insulin action is uncertain. In 8 overweight male patients with essential hypertension, we used the double forearm (ie, infused versus control) technique, combined with the euglycemic hyperinsulinemic clamp, to test whether sustained vasodilation (induced by intra-arterial sodium nitroprusside infusion) improves insulin-mediated glucose uptake. During the clamp, whole-body glucose disposal rose to 24.4+/-2.9 micromol x min(-1) x kg(-1). Forearm blood flow in the control forearm was stable (3.1+/-0.4 versus 2.9+/-0.3 mL x min[-1] x dL[-1]), while in the infused forearm it increased from 3.4+/-0.5 to 10.6+/-1.3 mL x min(-1) x dL(-1) in response to sodium nitroprusside. During insulin administration, tissue glucose extraction rose from 2+/-1% to 21+/-4% (P<.001) in the control forearm and from 2+/-1% to 8+/-3% in the infused forearm (P<.02 versus baseline for both); the calculated net glucose uptake reached similar plateaus in the two forearms (3.5+/-0.7 versus 3.7+/-0.6 micromol x min(-1) x kg(-1), control versus infused, P=.6). We conclude that in overweight male patients with essential hypertension, increasing forearm perfusion with sodium nitroprusside does not attenuate the insulin resistance of forearm tissues.

Adult↗

Epidemiology of myasthenia gravis in northwestern Sardinia.

A previous epidemiological study on myasthenia gravis (MG) in Sardinia indicated a prevalence rate of 4.5 per 100,000 population and an incidence of 0.25 per 100,000 population in the period 1958-1986. This study, however, investigated the entire Sardinian population (about 1,500,000) and the reported rates are likely to be underestimated. Because the use of a very large population has been found to cause major bias in case finding, the present study was designed to overcome this bias by determining the prevalence and incidence of MG in a well-defined area of Northwestern Sardinia, with a population of about 270,000 (1991 census). Potential MG cases were ascertained using all possible medical sources. The diagnosis of MG was based on the clinical, neurophysiological and conventional pharmacological findings (Tensilon test, response to anticholinesterases). On prevalence day (December 31, 1994) 29 MG patients were living in the study area (17 women and 12 men). Since the total population on prevalence day was 268,926 (137,284 women and 131,642 men), the calculated prevalence was 11.1 per 100,000 population (12.4 women and 9.9 men). The present study shows that the risk of MG in Sardinia is higher than previously suggested. The risk, however, is not significantly different from that found in other comparable Italian and European areas. It contrasts with what has been found for other autoimmune diseases such as multiple sclerosis and insulin-dependent diabetes mellitus in Sardinians, both showing frequencies up to 3-5 times higher than in the rest of Italy.

Adolescent↗

HCV transmission in family members of subjects with HCV related chronic liver disease.

To investigate the risk of sexual and intrafamilial transmission of HCV, 220 family members of 76 patients (index cases) with chronic type C viral liver disease were tested for serological markers of HCV. Of the family members, 129 were offspring, 64 sexual partners, 15 parents and 12 siblings of the index cases. Anti-HCV was tested in all the household contacts; HCV-RNA was tested in antibody positive samples. The serologic markers of HCV were tested in a control group of 168 family members of 81 patients with chronic hepatitis unrelated to HCV. The overall prevalence of anti-HCV was 8.2% compared to 0.6% in the control group (p < 0.001). Sexual partners were anti-HCV positive more frequently than the other contacts (20% vs 2.2%; p < 0.001), without any difference in males or females. No correlation was observed between the occurrence of HCV infection in contacts and age, severity of liver disease or risk factor for the acquisition of HCV in the index cases. Seven of the 18 (39%) anti-HCV positive family contacts had bio-chemical evidence of chronic liver disease, histologically confirmed in the 6 patients who underwent a liver biopsy. Liver chemistry was normal in all the HCV-negative contacts. Ten of the 18 anti-HCV positive contacts (55%) were HCV-RNA positive, Genotypes were the same (1b) in 4 of the 7 viremic couples of subjects: in 3 of the 6 couples of sexual partners and in the only mother/son couple. These data suggest the occurrence of intraspousal transmission of HCV, while intrafamiliar acquisition of HCV in non-sexual contacts seems to be rare.

Adolescent↗

Insulin decreases circulating vitamin E levels in humans.

Both hyperinsulinemia and free oxygen radicals have been implicated in the pathogenesis of atherosclerosis, but the relationship between insulin levels or insulin action and the oxidant/antioxidant balance has not been explored. We measured the effect of physiologic hyperinsulinemia on plasma concentrations of vitamin E, a major free radical scavenger molecule. Isoglycemic clamps (at an insulin infusion rate of 6 pmol . min-1 . kg-1) were performed in four groups of subjects: (1) 12 non-insulin-dependent diabetic (NIDDM) patients, (2) eight patients with essential hypertension, (3) 11 nondiabetic obese individuals, and (4) 12 healthy subjects. In 10 healthy volunteers, a time-control experiment was performed by replacing the insulin infusion with normal saline. Vitamin E and plasma lipid levels were determined at baseline and after 2 hours of insulin/saline infusion. Insulin sensitivity was reduced in diabetic, obese, and hypertensive groups in comparison to healthy controls, but fasting plasma vitamin E concentrations were similar in all groups. A consistent decrement in plasma vitamin E concentrations (averaging 12% of baseline, P < .0001) was observed in all subjects receiving insulin regardless of the level of insulin sensitivity, whereas no significant changes in plasma vitamin E were seen in subjects receiving saline infusion (P < .001 v insulin infusion groups). The insulin-induced decrement persisted in all study groups when plasma vitamin E concentrations were corrected for total serum cholesterol levels (-8.9% +/- 1.2% v -0.4 +/- 2.3% of saline controls, P = .0004) or serum low-density lipoprotein (LDL(-10.0% +/- 1.2% v -0.4% +/- 2.2%, P = .0002). We conclude that insulin infusion acutely depletes vitamin E in circulating lipids regardless of insulin resistance. This effect may represent a physiologic means of transferring vitamin E into cell membranes; alternatively, it might reflect a pro-oxidant action of insulin in vivo.

Adult↗

[Effects of filtering techniques on time-domain analysis of signal-averaged ECG after acute myocardial infarction: a multicenter study, GISS-3 arrhythmia sub-project].

AIM OF THE STUDY: To evaluate the influence of different filtering techniques on the measurement of ventricular late potentials (VLP) the Sottoprogetto Aritmie of GISSI-3 collected signal-averaged ECG (SAECG) from 647 patients. METHODS: Data were recorded after myocardial infarction (10 +/- 4 days) in 20 Italian Coronary Units. Three main filtering algorithms were used in the different commercial devices: Bidirectional Filter (ART, Aerotel, Fidelity Medical) (BF: 340 Patients), Spectral Filter (Marquette) (SF: 258 Patients) and Del Mar Filter (Del Mar Avionics) (DF: 49 Patients). QRS duration (QRSD), low amplitude signal duration (LAS40) and root mean-square-voltage (RMS40), were measured with various filters set at 40-250 Hz high and low pass frequencies. RESULTS: After correction for clinical variables the measurements of VLP in the three different groups were different. QRSD value obtained by BF (100.6 +/- 13 ms) was shorter than that obtained by SF (109.1 +/- 12 ms). No differences were found in LAS40 and RMS40 values between SF and BF, while DF gave longer LAS40 and lower RMS40 than SF and BF. Residual noise was lower in BF (0.3 +/- 0.1 muV). than in SF and DF (0.5 +/- 0.1 muV). Applying standard criteria DF gave a higher prevalence of VLP (48.9%) than BF (23.8%) and SF (19%) groups. CONCLUSIONS: This study demonstrates that the use of different filters produces discordant result on VLP measurements. For correct application of SAECG analysis in risk stratification after myocardial infarction, normal and abnormal values must be specifically established for the different filter techniques.

Adult↗

Effect of insulin on uric acid excretion in humans.

Although hyperuricemia is a frequent finding in insulin-resistant states, insulin's effect on renal uric acid (UA) handling is not known. In 20 healthy volunteers, diastolic blood pressure, body weight, and fasting plasma insulin were positively (and age was negatively) related to fasting plasma UA concentrations, together accounting for 53% of their variability. During an insulin clamp, urine flow was lower than during fasting conditions (1.01 +/- 0.12 vs. 1.56 +/- 0.32 ml/min, P = 0.04), whereas creatinine clearance was unchanged (129 +/- 7 and 131 +/- 9 ml/min, P = not significant). Hyperinsulinemia did not alter serum UA concentrations (303 +/- 13 vs. 304 +/- 12 microM) but caused a significant decrease in urinary UA excretion [whether expressed as absolute excretion rate (1.66 +/- 0.21 vs. 2.12 +/- 0.23 mumol/min, P = 0.03), clearance rate (5.6 +/- 0.8 vs. 7.3 +/- 0.8 ml/min, P = 0.03), or fractional excretion (4.48 +/- 0.80 ml/min vs. 6.06 +/- 0.64%, P < 0.03)]. Hyperinsulinemia was also associated with a 30% (P < 0.001) fall in urine Na excretion. Fractional UA excretion was related to Na fractional excretion under basal conditions (r = 0.59, P < 0.01) and during the insulin period (r = 0.53, P < 0.02). Furthermore, the insulin-induced changes in fractional UA and Na excretion correlated with one another (r = 0.66, P < 0.001). Physiological hyperinsulinemia acutely reduces urinary UA and Na excretion in a coupled fashion.

Adult↗

Tracheo-bronchial mucociliary clearance in patients with primary and secondary Sjögren's syndrome.

We determined the tracheo-bronchial mucociliary clearance (MCC) in order to evaluate a possible impairment of this function in patients affected by Sjögren's syndrome (SS) with or without overt clinical symptoms of xerotrachea. The MCC was expressed as flow rate (mm/min) and studied in 22 non-smoking SS patients (10 pSS and 12 sSS) and in 8 control subjects by specifically adapted ventilation lung scintigraphy (VLS). The MCC in the control group was 5.9 +/- 1.1 mm/min. No values were produced for MCC in 16 SS patients (8 pSS and 8 sSS) in the time interval considered and were reduced in the remaining 6 SS patients (3.3 +/- 1.2 mm/min). In all nine cases with clinical evidence of xerotrachea no values for MCC were obtained. A significant correlation was found between the MCC values and the rate of stimulated salivary excretion determined by dynamic scialoscintigraphy in the same patients (p < 0.001). These preliminary data show that the majority of SS patients studied presented with MCC impairment, always found when clinical symptoms of xerotrachea were present.

Adult↗