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Biomedical subjects

G Giustina

Publications and source records attributed to G Giustina.

At least 37 records · Page 2Linked to original sources
PubMed1995

Characterization of the paradoxical growth hormone inhibitory effect of galanin in acromegaly.

Galanin is a 29-amino acid straight-chain biologically active peptide which has been found to decrease circulating GH levels in some acromegalic patients, whereas is able to increase GH secretion in normal subjects. The aim of our study was to ascertain the incidence, entity and mechanism of the paradoxical GH inhibitory effect of galanin in acromegaly also looking at possible correlations between the GH responses to galanin and the main clinical and biochemical features of the patients. Finally, the effects of either successful or unsuccessful neurosurgical intervention on the GH inhibitory effect of galanin in acromegaly were investigated. A series of 23 consecutive patients with active acromegaly seen at the Endocrine Section of the Department of Internal Medicine of the University of Brescia (Italy) between 1991 and 1994 was examined. The acromegalic patients were subdivided in group 1 (i.e. patients who were 1) untreated, 2) evaluated before surgery, and 3) not cured after surgery and radiotherapy) and group 2 (i.e. surgically cured). All patients were submitted at least once to the following biochemical and radiological evaluations: 1) baseline serum insulin-like growth factor-I and PRL samples, 2) iv infusion of synthetic porcine galanin (500 micrograms in 100 mL saline) from -10 to 30 min, 3) iv bolus injection of TRH (200 micrograms) at time zero, 4) oral glucose tolerance test (75 g glucose, orally) at time zero, and 5) magnetic resonance of the pituitary sella. Adenomatous tissue obtained during neurosurgery in four patients was cultured in vitro, and the effect of the addition of galanin in the culture medium on GH secretion was tested. During galanin infusion in 19 of 21 group 1 patients, serum GH levels were lower with respect to baseline (range of GH decrease, -6.2 to -85.4% with respect to basal levels). During galanin infusion, no reductions in GH levels were observed in the acromegalic patients cured after neurosurgery (group 2); on the contrary, 6 of 7 patients displayed a normal stimulatory response to galanin (range of GH increase, +120-1533.3% of the basal level). A significant correlation between the percent decrease in GH levels after galanin treatment and the percent increase after TRH was found in group 1 patients (r = -0.783; P < 0.05). In three of the four adenomas examined, galanin determined a clear decrease in GH secretion (mean nadir, 63.3 +/- 12% of the baseline secretion rate). In conclusion, we demonstrated that the large majority of numerous patients with active acromegaly show a decrease in serum GH levels after galanin administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗
PubMed1995

Pravastatin-associated myopathy. Report of a case.

A case of acute inflammatory myopathy associated with the use of pravastatin, a new hydrophilic 3-hydroxy-3 methylglutaril coenzyme A reductase inhibitor, is reported. The patient, a 69-year-old man was affected by non-insulin-dependent diabetes mellitus and hypertension. He assumed pravastatin (20 mg/day) because of hypercholesterolemia. He was admitted with acute myopathy of the lower limbs which resolved in a few days after pravastatin discontinuation. A previously unknown hypothyroidism, probably due to chronic autoimmune thyroiditis, was evidenced. Muscle biopsy (left gastrocnemius) revealed a perimysial and endomysial inflammatory infiltrate with a prevalence of CD4+ lymphocytes. While lovastatin and simvastatin have been associated with toxic myopathy, pravastatin-associated myopathy could represent a distinct, inflammatory entity.

Acute Disease↗
PubMed1994

A randomized controlled trial of thymopentin therapy in patients with chronic hepatitis B.

Strategies of treatment of chronic hepatitis type B are currently based on the use of either antiviral or immunomodulatory agents. A randomized, controlled trial was performed to assess the safety and efficacy of 6-month thymopentin therapy in 30 patients with chronic hepatitis B. Inclusion criteria were biopsy-proven chronic hepatitis, elevated alanine aminotransferase and serum HBsAg and HBV-DNA positivity for at least 12 months. At the conclusion of the study (1 year), HBV-DNA was negative and alanine aminotransferase had normalized in 13% and 20% of treated cases and in 20% and 27% of controls. None of the ten treated and one of the nine control patients who were initially HBeAg positive subsequently cleared HBeAg. None became HBsAg negative. A histologic improvement was noted in 27% of the treated patients compared with 18% of controls. These results indicate that this regimen of thymopentin therapy is not effective in treating chronic hepatitis B.

Adult↗
PubMed1994

Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. The Investigators of the European Concerted Action on Viral Hepatitis (EUROHEP).

A multicenter longitudinal study was performed to assess the survival of hepatitis B surface antigen positive compensated cirrhosis, primarily in relation to hepatitis B virus replication and hepatitis delta virus infection, and to construct a prognostic index based on entry characteristics. This cohort study involved nine university medical centers in Europe. Three hundred and sixty-six Caucasian HBsAg positive patients with cirrhosis who had never had clinical manifestations of hepatic decompensation were enrolled and followed for a mean period of 72 months (6 to 202 months). Inclusion criteria were biopsy-proven cirrhosis, information on serum hepatitis B e antigen and antibody to hepatitis D virus at the time of diagnosis and absence of complications of cirrhosis. At entry 35% of the patients were HBeAg positive, 48% of the patients tested were HBV-DNA positive and 20% anti-HDV positive. Death occurred in 84 (23%) patients, mainly due to liver failure (45 cases) or hepatocellular carcinoma (23 cases). The cumulative probability of survival was 84% and 68% at 5 and 10 years, respectively. Cox's regression analysis identified six variables that independently correlated with survival: age, albumin, platelets, splenomegaly, bilirubin and HBeAg positivity at time of diagnosis. According to the contribution of each of these factors to the final model, a prognostic index was constructed that allows calculation of the estimated survival probability. No difference in survival of hepatitis D virus infected and uninfected patients was observed. Termination of hepatitis B virus replication and/or biochemical remission during follow up correlated with a highly significant better survival. These data show that in compensated cirrhosis B, hepatitis B virus replication, age and indirect indicators of poor hepatic reserve and established portal hypertension significantly worsen the clinical course of the disease, whereas hepatitis D virus infection does not influence the prognosis. The highly significant improvement in life expectancy following cessation of hepatitis B virus replication and biochemical remission favors antiviral therapy in those patients with a guarded prognosis, as estimated by a prognostic index.

Adult↗
PubMed1994

Human immunodeficiency virus infection and hepatitis C pathology.

To investigate the possible influence of human immunodeficiency virus (HIV) infection on hepatitis C virus-related liver disease, liver morphology was evaluated in 160 HBsAg-negative patients with chronic hepatitis C, including 68 HIV-positive and 92 HIV-negative cases. No differences were detected in the severity of necro-inflammatory hepatic lesions between HIV-negative and HIV-positive patients when the CD4+ lymphocytes count exceeded 400 cells/mm3. In contrast, HIV-positive patients with CD4+ lymphocytes below 400 cells/mm3 showed a significantly lower grade of portal inflammation and piecemeal necrosis. These results suggest that liver lesions in hepatitis C may largely depend on immunomediated mechanisms.

Adult↗
PubMed1993

Picotamide, a dual TXB synthetase inhibitor and TXB receptor antagonist, reduces exercise-induced albuminuria in microalbuminuric patients with NIDDM.

We investigated the short-term effect of the TXB inhibitor picotamide on albuminuria induced by exercise in 15 microalbuminuric (i.e., with UAE at rest between 20 and 200 micrograms/min) type II diabetic patients (12 men and 3 women, age 56 +/- 2, BMI 28 +/- 1 kg/m2) and in six normal age-matched control subjects. The diabetic subjects performed five submaximal exercise tests (90% of theoretical heart rate) on a cycle ergometer: the first two under basal conditions; the third and fifth after subjects had received picotamide (900 mg/day) or placebo (3 tablets/day) for 10 days; the fourth exercise always was performed after 10 days of wash-out. Control subjects performed two exercises: the first in baseline conditions and the second after 10 days of picotamide administration (900 mg/day). When diabetic patients were untreated, a significant (P < 0.05) increase in UAE with respect to baseline levels was observed immediately after and 1 h after the exercise test. After picotamide administration, UAE significantly decreased (P < 0.05) immediately after and 1 h after exercise, as compared with diabetic patients given a placebo. In normal subjects, exercise was followed by a slight increase in UAE, which was not significantly affected by picotamide administration. Our results show that short-term administration of picotamide is associated with a reduction in UAE after exercise in type II diabetes patients with microalbuminuria while at rest. Picotamide, a TXB synthetase and receptor inhibitor, may decrease exercise-induced albuminuria in diabetic patients through a reduction in circulating TXB levels and inhibition of TXB action, which in turn may act by lowering glomerular capillary hydraulic pressure.

Albuminuria↗
PubMed1992

A randomized controlled trial of lymphoblastoid interferon-alpha in patients with chronic hepatitis B lacking HBeAg.

Ongoing hepatitis B virus replication in the presence of antibody to HBeAg can be observed in patients with active liver disease. These forms of chronic hepatitis B have been described as having a poor prognosis. We have conducted a randomized controlled trial to assess the efficacy of lymphoblastoid interferon-alpha in 60 patients with antibody to HBeAg and hepatitis B virus DNA-positive chronic hepatitis. Patients received 5 million U/m2 interferon three times a week for 6 mo, or no treatment. Final evaluation 18 mo after randomization showed hepatitis B virus DNA negativity and ALT normalization in 53% of treated patients and in 17% of controls (p less than 0.01). The probability of sustained hepatitis B virus DNA loss was significantly higher in treated patients than in controls (p less than 0.005). Blinded histological assessment revealed improvement in 50% of treated patients compared with 33% of controls. Pretreatment hepatitis B virus DNA and aminotransferase levels and histological appearance were not predictive of response. The results of this trial indicated that marked reduction of viral replication in serum and remission of liver damage can be obtained with lymphoblastoid interferon in about 50% of patients with HBeAg antibody- and HBV DNA-positive chronic hepatitis. This rate of response is higher than that reported previously.

Adult↗
PubMed1992

Induction of autoantibodies during alpha interferon treatment in chronic hepatitis B.

Thirty-two patients with chronic hepatitis B treated with alpha interferon were tested for 12 different antibodies. Only a minority (18%) of cases developed antinuclear antibodies and none developed clinical signs of autoimmune disease. These data suggest that, at the dose regimen used, interferon therapy of chronic hepatitis B is not associated with triggering of autoimmunity.

Adult↗
PubMed1992

Effect of galanin on the growth hormone response to growth hormone-releasing hormone in acromegaly.

Galanin enhances growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in normal man. In acromegaly, circulating GH levels are increased and the GH response to GHRH may be exaggerated. Galanin has been recently shown to decrease circulating GH levels in acromegaly. The aim of our study was to investigate the effects of galanin on the GH response to GHRH in acromegalic subjects. Five acromegalic patients (three men and two women) and seven healthy adult subjects (five men and two women) were studied. GHRH-induced GH secretion was evaluated during a 40-minute intravenous (IV) infusion of saline (100 mL) or porcine galanin (12.5 micrograms/min in 100 mL saline). In normal subjects, delta GH levels after GHRH+porcine galanin administration (47 +/- 7.5 micrograms/L) were significantly higher in comparison to levels obtained with GHRH+saline (21.7 +/- 3.5 micrograms/L, P < .05). In acromegalic patients, GH responses to GHRH (delta GH, 18.8 +/- 8.6 micrograms/L) were not altered by galanin infusion (delta GH, 17.6 +/- 5 micrograms/L). Our results give the first evidence that the same dose of galanin that induces a significant enhancement of the GH response to GHRH in normal subjects has no effect on the GH response to GHRH in acromegalic patients. It can be hypothesized that galanin may interact at the pituitary level with its own receptors expressed by somatotropes independent of GHRH. Failure of galanin to enhance GH response to GHRH in acromegalic patients could be due to a change in function of the galanin receptor on GH-secreting adenomatous cells.

Acromegaly↗
PubMed1992

Galanin decreases circulating growth hormone levels in acromegaly.

Galanin is able to elicit GH secretion in normal man. In acromegaly, circulating GH levels are elevated, and GH secretory dynamics are usually abnormal. The aim of our study was to investigate the effects of galanin on GH secretion in acromegalic subjects. Six acromegalic patients (four males and two females) and seven healthy adult subjects (five males and two females) underwent in randomized order: 1) iv infusion of 100 mL saline from 0-45 min, and 2) iv infusion of synthetic porcine galanin (0.5 mg in 100 mL saline) from 0-45 min. In normal subjects, peak GH levels after porcine galanin administration (8.2 +/- 1.9 micrograms/L) were significantly higher than after saline infusion (1.3 +/- 0.1 micrograms/L; P less than 0.05). In acromegalic patients, GH values fell from baseline (32.5 +/- 12 micrograms/L) to a mean nadir of 24.5 +/- 12.7 micrograms/L after galanin infusion. The mean change in GH values from baseline after galanin treatment in these subjects significantly differed from that observed after saline infusion from 15-90 min. Serum PRL levels were not significantly affected by galanin in either normal or acromegalic patients. Our results give the first evidence that the same dose of galanin, acting as a GH secretagogue in normal man, is, on the contrary, able to significantly inhibit GH in acromegalic patients. The cause of this paradoxical GH fall after galanin treatment in acromegaly remains to be explained. It can be hypothesized that galanin may interact at the pituitary level with its own receptors expressed by GH-secreting adenomatous cells.

Acromegaly↗
PubMed1992

Therapy for chronic hepatitis B with lymphoblastoid interferon-alpha and levamisole.

About one third of patients with chronic hepatitis B show a sustained response when treated with interferon-alpha. Combining interferon-alpha with immunomodulators might be a way to increase response rate. The aim of this study was to compare the efficacy of lymphoblastoid interferon-alpha given alone with its efficacy when combined with levamisole in chronic hepatitis B. Forty-five patients with HBeAg-positive chronic hepatitis were randomly selected (with stratification for ALT levels) to receive a 6-mo course of combination therapy with lymphoblastoid interferon-alpha (5 million units/m2 three times per week) and levamisole (150 mg three times per week) or lymphoblastoid interferon at the same dose regimen and a matching placebo. Final evaluation 18 mo after randomization revealed a loss of both HBeAg and hepatitis B virus DNA with ALT normalization in 38% of patients treated with interferon-alpha alone and in 10% of patients receiving combination therapy. The higher response rate observed in patients treated with interferon-alpha alone was maintained after stratification for basal ALT levels (i.e., higher [45% vs. 10%] or lower [31% vs. 9%] than three times the upper normal value). The length of time to sustained HBeAg clearance was significantly (p < 0.05) shorter in patients receiving monotherapy than in patients receiving combination therapy. Blinded histological assessment revealed improvement in 44% of patients treated with interferon-alpha alone compared with improvement in 6% of patients receiving combination therapy. These results indicate that levamisole has no additive effects when combined with interferon-alpha in the treatment of HBeAg-positive chronic hepatitis.

Adult↗
PubMed1991

Autoantibodies during alpha-interferon therapy for chronic hepatitis B.

The development of autoantibodies and autoimmune reactions has been reported during and after interferon (IFN) therapy. Thirteen different antibodies from the sera of 32 patients with chronic hepatitis B treated with alpha-interferon (alpha-IFN) were tested. Seventeen HBeAg-positive patients received 4.5 megaunits (MU) of recombinant IFN thrice weekly for 4 months, and 15 anti-HBe and HBV-DNA positive patients were treated with 5 MU/m2 of lymphoblastoid IFN thrice weekly for 6 months. Five patients (15%) had antinuclear antibodies (ANA) and one patient (3%) had smooth muscle antibodies before treatment. ANA appeared during IFN treatment in five (18%) of 28 previously negative patients. With discontinuation of treatment, the titer of ANA fell to undetectable levels in all patients. In contrast, none of the patients developed antibodies to endocrine organs, such as thyroid microsomal, thyroglobulin, parietal cells, pancreatic islet cell, and adrenal cortex antibodies or autoantibodies specifically associated with autoimmune liver disease such as liver kidney microsomal antibodies and antimitochondrial antibodies. There was no correlation between autoantibody positivity before therapy or autoantibody occurrence during treatment and response to IFN therapy. None of the patients developed clinical signs of autoimmune disease. These results indicate that these regimens of recombinant and lymphoblastoid IFN therapy of chronic hepatitis B are associated with a low risk of clinically significant autoimmunity.

Adult↗
PubMed1991

Low-dose octreotide is able to cause a maximal inhibition of the glycemic responses to a mixed meal in obese type 2 diabetic patients treated with insulin.

Short-term studies have shown that octreotide, a long-acting somatostatin analog, blunts postprandial glycemic responses and reduces insulin requirement in insulin treated diabetic patients. The aim of our study was to investigate the effects of three single, different doses of octreotide on the glycemic response to a mixed meal in eight insulin treated type 2 diabetic patients after secondary failure with hypoglycemic agents. Previous treatments were substituted by regular insulin, 0.5 U/kg/day divided into three sc injections, for at least seven days. All patients received: (a) regular insulin (0.1 U/kg, sc) at 7.30 am; (b) octreotide 25 micrograms sc or (c) 50 micrograms sc or (d) 100 micrograms sc simultaneously with insulin but injected at different sites. From 8.00 to 8.15 the patients consumed a preconstituted fluid mixed meal of 250 ml. Following insulin alone a significant increase in blood glucose levels was observed after the meal. Abolished and not significantly different blood glucose responses to the meal after each of the three doses of octreotide were observed. Our findings suggest that with a low dose of octreotide (25 micrograms) it is possible to abolish the postprandial glycemic peak in type 2 diabetic patients treated with insulin.

Blood Glucose↗
PubMed1991

Hepatitis C virus infection in chronic hepatitis B virus carriers.

One hundred eighty-four patients with hepatitis B surface antigen-positive chronic hepatitis were evaluated for antibodies to hepatitis C virus (anti-HCV). Only 11 (8%) of 136 patients with hepatitis B virus (HBV) replication (HBV-DNA-positive in serum) while 7 (35%) of 20 positive for antibody to hepatitis B e antigen (anti-HBe) but HBV-DNA-negative were positive for anti-HCV. By contrast, anti-HCV was never found in 30 anti-HBe-positive "healthy" carriers. Anti-HCV was more frequent in hepatitis D virus (HDV)-positive than in HDV-negative cases (32% vs. 12%). During 1-11 years of follow-up, anti-HCV persisted in 90% of cases, who showed continuing alanine aminotransferase elevation. Liver histology deteriorated in 2 of 4 anti-HCV-positive, anti-HBe-positive, HBV-DNA-negative patients. These results demonstrate the existence of a subgroup of patients with anti-HBe-positive, HBV-DNA-negative, HDV-negative chronic hepatitis B, where HCV may play a leading role in causing liver disease.

Adult↗
PubMed1991

Natural history and prognostic factors for chronic hepatitis type B.

One hundred and five hepatitis B surface antigen (HBsAg) positive patients presenting with chronic persistent hepatitis (n = 46) or chronic active hepatitis without cirrhosis (n = 59) were followed longitudinally for one to 16 years (mean 5.5 years) and underwent follow up biopsy. During a mean histological follow up of 3.7 years, active cirrhosis developed in 21 (20%) patients one to 13 years after entry to the study with a calculated annual incidence of 5.9%. The probability of evolution to cirrhosis was significantly higher in patients with chronic active hepatitis and bridging hepatic necrosis than in those with moderate chronic active hepatitis or chronic persistent hepatitis (p less than 0.0001). Cox multiple regression analysis showed that the following three variables independently implied poor prognosis: older age, presence of bridging hepatic necrosis, and persistence of hepatitis B virus DNA in serum (p less than 0.0001). These findings indicate that patients with severe chronic active hepatitis and persistent hepatitis B virus replication are at very high risk of rapid progression to cirrhosis.

Adult↗
PubMed1991

Septic polyarthritis in chronic tophaceous gout.

This paper reports the case of a 48 year old patient with chronic tophaceous gout who was admitted to the hospital with a pneumococcal polyarthritis affecting the same joints previously involved by gout attacks. The authors emphasize that the possibility of a septic arthritis should always be considered in the gouty patient, and not only in the elderly, as stressed in the literature, but also in younger patients.

Ampicillin↗
PubMed1991

Albuminuria induced by exercise in hypertensive type I and type II diabetic patients: a randomised, double-blind study on the effects of acute administration of captopril and nifedipine.

Physical exercise can increase urinary albumin excretion rate (UAER) in diabetic patients without microalbuminuria at rest (stage II diabetic nephropathy) or with baseline microalbuminuria (stage III diabetic nephropathy). The aim of this study was to compare the acute effects of captopril, an ACE inhibitor, and nifedipine, a calcium channel blocker, on exercise-induced microalbuminuria in hypertensive insulin-dependent (Type I) and non-insulin-dependent (Type II) diabetic patients with early stage nephropathy. Non-obese diabetic patients, 13 Type I (7 with stage II and 6 with stage III nephropathy) and 14 Type II (6 with stage II and 8 with stage III nephropathy), with hypertension, WHO stages I-II, underwent five submaximal cycloergometric tests: the first two in basal conditions, the other three after 24 hour administration of captopril (25 mg twice daily), placebo (1 tab twice daily) or nifedipine AR (20 mg twice daily) according to a randomised, double-blind design. Acute administration of both captopril and nifedipine was able to reduce exercise-induced microalbuminuria in hypertensive Type I and Type II diabetic patients regardless of the stage of their nephropathy. Captopril reduced systolic blood pressure less than nifedipine, in both Type I and Type II diabetics, but was more effective than nifedipine in blunting exercise-induced microalbuminuria, especially in Type I diabetics.

Adolescent↗