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Biomedical subjects

M Colombo

Publications and source records attributed to M Colombo.

At least 163 records · Page 9Linked to original sources
PubMed1994

A multicenter randomized controlled trial of recombinant interferon-alpha 2b in patients with acute transfusion-associated hepatitis C.

To assess whether interferon-alpha might prevent non-A, non-B hepatitis from becoming chronic, 45 consecutive patients with transfusion-associated hepatitis were enrolled in a randomized clinical trial. Thirty-eight patients had hepatitis C virus infection, and 7 had non-A, non-B, non-C hepatitis. Twenty-six patients (22 with HCV) were given 3 MU of recombinant interferon-alpha 2b three times a week for 12 wk, whereas 19 (16 with HCV) were not. Biochemical and virological parameters were monitored at regular intervals during an 18-mo follow-up. At the end of the 3-mo therapy, 16 (73%) patients with hepatitis C had normal serum ALT activity, compared with 7 (44%) who were not treated (NS). Fifty-three percent of the treated patients and none of the untreated patients had normal ALT levels and no HCV RNA (p = 0.0087). At the end of the 18-mo follow-up, 13 (59%) treated patients had normal ALT levels, compared with 6 (37%) untreated controls (NS). Thirty-nine percent had normal ALT and no HCV RNA, compared with none of the controls (p = 0.035). Four patients (22%) had had sustained complete responses to interferon, defined as normal ALT levels and no HCV RNA at the end of the 3-mo treatment period and the 18-mo follow-up period. All seven patients with non-A, non-B, non-C hepatitis, treated and untreated, recovered uneventfully from hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Virology of the hepatitis A epidemic in Italy.

We studied the virologic aspects of a hepatitis A epidemic that occurred among hemophilia patients in Italy between 1989 and 1992. Twelve lots of factor VIII concentrate manufactured by the solvent-detergent chromatographic technique and suspected of contamination by the hepatitis A virus (HAV) were analyzed by a two-step, nested polymerase chain reaction (PCR) procedure. PCR was applied to 1-ml samples of factor VIII concentrate and 100-microliters serial serum samples available from 2 patients. Particular care was taken to rule out the possibility of false-positive results during analysis. Results demonstrated PCR amplification of the 3'-region of the VP3 gene in 5 of the 12 implicated lots of factor VIII and in the serial serum samples of both patients. PCR amplification also revealed that the gene sequences detected in patients' sera were identical to the sequences detected in the product they had received. In all, 3 VP3 sequences (found to be 96-99% identical) were amplified. Further characterization of the HAV found in the factor VIII concentrate and the patients' sera was attempted by PCR amplification of the VP1/2A region. Successful amplification of this region was achieved in the serum of only 1 patient and in the concentrate he received. This fourth amplified sequence was identical in both serum and factor VIII concentrate. Attempts to transmit hepatitis A from the contaminated lots to 3 chimpanzees resulted in no signs of infection after 10 months of observation. Based on the Italian experience, persons with severe hemophilia who receive large-pool concentrate are at potential risk for HAV infection and should be vaccinated against HAV or use an alternative to solvent-detergent-prepared concentrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Insulin sensitivity and body fat distribution in normotensive offspring of hypertensive parents.

Lean, healthy normotensive sons of essential hypertensive parents (OHyp) have lower insulin sensitivity (SI) than sons of normotensive parents (ONorm). We have tried to find out whether this disturbance in insulin metabolism is related to altered body fat distribution, fuel metabolism, or both. 21 OHyp and 21 ONorm of similar age and body-mass index were investigated after fasting overnight. Body composition was assessed by dual-energy X-ray absorptiometry and fuel metabolism by indirect calorimetry and urinary nitrogen excretion. Plasma insulin and glucose concentrations were measured during the frequent sampling intravenous glucose tolerance test, and SI was calculated by the minimum model method. Systolic blood pressure and heart rate were slightly but not significantly higher in OHyp than ONorm but the groups did not differ in fasting plasma insulin or glucose concentrations, carbohydrate or lipid oxidation, lean and fat mass, bone mineral content, or distribution of body fat. By contrast, SI was significantly lower in OHyp than ONorm (8.2 [0.7] vs 13.4 [1.5] 10(-4) L mU-1 min-1, p < 0.01). Within the whole study population upper-body fat mass was positively correlated with fasting plasma insulin (r = 0.33, p < 0.03) and lipid oxidation was positively correlated with SI (r = 0.35, p < 0.04) and negatively correlated with subscapular/triceps skinfold thickness (r = -0.43, p < 0.01). Thus, impairment of SI precedes both the development of overt hypertension and gain or redistribution of body fat. Therefore, the concept that SI is low as a result of altered fat distribution has to be reconsidered, at least in young male offspring of hypertensive parents.

Adipose Tissue↗
PubMed1993

The natural history of asymptomatic hepatitis B surface antigen carriers.

OBJECTIVE: To assess the long-term outcome in hepatitis B surface antigen (HBsAg) carriers who have normal liver function tests, focusing on survival and the development of severe liver disease and hepatocellular carcinoma. DESIGN: Cohort study with a mean follow-up of 130 months. SETTING: Liver clinic of a referral center. PATIENTS: Ninety-two HBsAg-positive blood donors with normal liver function tests. MEASUREMENTS: Histologic evaluation of liver specimens at baseline; clinical, biochemical, and serologic follow-up; and repeat liver biopsy if clinically indicated or after 10 years of follow-up. RESULTS: At baseline, 69 subjects had normal histologic findings or only minor abnormalities, 18 had chronic persistent hepatitis, and 5 had mild chronic active hepatitis. Serum enzyme levels remained normal in 58 of 68 patients who had regular follow-up. Three patients had biochemical changes consistent with hepatitis B virus (HBV) infection; in one of these patients, a later histologic evaluation showed progression to chronic active hepatitis. One patient developed alcoholic cirrhosis. Six other patients had mild or transient transaminase elevations, with no evidence of HBV replication, hepatitis D virus infection, hepatitis C virus (HCV) infection, or histologic deterioration. Liver histologic findings also remained unchanged in 21 patients who showed no biochemical changes during 10 years of follow-up and consented to have repeated liver biopsy. Ten patients showed loss of HBsAg; 2 of these patients acquired antibody to hepatitis B surface antigen (anti-HBs). All patients who did not have regular follow-up, except 1, were interviewed by telephone during 1990: All denied having liver disease. No patients developed hepatocellular carcinoma. CONCLUSIONS: Italian HBsAg carriers with initially normal liver function tests have an excellent prognosis: Delta superinfection is infrequent and the risk for developing hepatocellular carcinoma is low.

Adult↗
PubMed1993

Control of protein traffic between distinct plasma membrane domains. Requirement for a novel 108,000 protein in the fusion of transcytotic vesicles with the apical plasma membrane.

We have developed a cell-free system that reconstitutes the last step in transcytosis, i.e. the fusion of transcytotic transport vesicles with the apical plasma membrane (PM). Subcellular fractions containing transcytotic vesicles (the donor) or apical PM (the acceptor) were prepared from rat liver by sucrose density centrifugation. Fusion between the donor and acceptor fractions was measured by the conversion of the 120,000 transmembrane form of the polymeric IgA receptor (pIgA-R), an endogenous protein of transcytotic vesicles, to a processed fragment by a protease endogenous to the apical PM. Fusion occurred only at 37 degrees C and was critically dependent on the presence of ATP and cytosol. Fusion was inhibited by treating the in vitro fusion reaction with N-ethylmaleimide or by adding antibodies against N-ethylmaleimide-sensitive factor (NSF). We have previously identified a specific transcytotic vesicle-associated protein (TAP) and here show that TAP exists in both cytosolic and membrane-associated pools. Because of its exclusive interaction with transcytotic vesicles, we tested the involvement of TAP in distinct fusion processes. Removal of TAP inhibited fusion in an in vitro transcytotic fusion reaction but had no inhibitory effect in an in vitro endosome-endosome fusion system or in an in vitro intra-Golgi transport reaction. We propose that TAP represents part of the molecular machinery specifically involved in targeting and/or fusion of transcytotic vesicles with the apical PM.

Adenosine Triphosphate↗
PubMed1993

Detection of preclinical hepatocellular carcinoma in patients with cirrhosis.

The association between hepatocellular carcinoma (HCC) and cirrhosis provides a formidable means for prospectively studying patients who are at risk of HCC. Early diagnosis of HCC is possible not only due to knowledge of the risk factors for this tumor, but also because HCC has a very long phase of intrahepatic growth and tends to grow as a solitary mass. Early diagnosis is also possible because sensitive and relatively inexpensive diagnostic tools are available. Several prospective studies of Oriental and Western patients with cirrhosis now in progress have led to the identification of many patients with small tumors. However, in the face of this evidence that screening high-risk patients may increase the yield of subclinical small tumors, no firm conclusion has yet been reached on whether early diagnosis of HCC may also increase the number of operable patients and reduce the mortality rate for this tumor.

Carcinoma, Hepatocellular↗
PubMed1993

The effects of inferior temporal and dorsolateral frontal lesions on serial-order behavior and visual imagery in monkeys.

Four monkeys were trained preoperatively on a serial-order task to respond to a set of five visual stimuli in a fixed sequence independent of their location. They were then given a test of visual imagery in which only two of the five stimuli appeared at a time, and the animals were required to respond to them in the order in which they appeared in the original sequence. The monkeys then received bilateral lesions of either inferior temporal cortex or dorsolateral frontal cortex. Dorsolateral frontal lesions had no effect on either serial-order behavior or visual imagery. In contrast, inferior temporal lesions severely impaired serial-order behavior. Once the serial-order task was relearned, however, the inferior temporal animals were completely normal on the test of visual imagery.

Animals↗
PubMed1993

Multicentre randomised controlled trial of recombinant interferon alfa-2b in patients with acute non-A, non-B/type C hepatitis after transfusion.

To assess whether the risk of chronic disease in patients with acute non-A, non-B/type C (NANB/C) hepatitis after transfusion could be reduced by treatment with interferon, patients were randomised to receive 3 million units interferon (IFN) alfa-2b three times a week for three months or no therapy. At the end of treatment, IFN had significantly reduced the number of patients with abnormal alanine aminotransferase activities compared with untreated patients but this difference was not maintained during a 15 month follow up. Treatment with IFN alfa-2b was considered safe and was well tolerated.

Acute Disease↗
PubMed1993

[Early severe malnutrition and psychomotor development. Effects of a rehabilitation program].

This study evaluates the psychomotor development of 228 undernourished infants submitted to an integral rehabilitation program in Nutritional Recovery Centers. At admission these children present a moderate retardation of their developmental quotient: mean 0.59 +/- 0.17, improving significantly to mean 0.79 +/- 0.4 (p < 0.001) after an average period of 178.2 +/- 63.9 days of intervention. As regards areas of development, rehabilitation only demonstrates a significant change in coordination and language, not so in the social and motor areas. Those children presenting the most severe developmental delays are also those who obtain the greater benefits from this integral rehabilitation program.

Developmental Disabilities↗
PubMed1993

Pharmacological characterization of FCE 27262, a combined thromboxane synthase inhibitor and PGH2/TXA2 receptor antagonist.

The literature supports the hypothesis that the association of a thromboxane (TX)A2 synthase inhibitor and a PGH2/TXA2 receptor antagonist has a superior antithrombotic effect when compared to both aspirin and single agent alone; a compound endowed with the dual mechanism of action might therefore be of therapeutic value for the management of thrombotic disorders. FCE 27262, an imidazol-1-yl-ethylideneaminooxypentanoic acid, displaces in vitro the binding of [3H]SQ 29,548 to washed human platelets (IC50 = 6.0 +/- 0.6 x 10(-8) M) and antagonizes human platelet aggregation induced by U 46619 in PRP with an IC50 (95% confidence limits) of 4.5(3.3-5.1) x 10(-7) M. It also selectively antagonizes the isolated vessel contraction induced by U 46619. In the rat aorta the Kb (95% confidence limits) was 1.6(0.6-4.3) x 10(-7) M. Additionally it inhibits in vitro TXB2 production in rat and human whole blood, the IC50 being, respectively, 5.9(3.3-9.6) x 10(-8) M and 3.8(2.9-5.0) x 10(-8) M. When administered orally to fed rats it also inhibits ex vivo TXB2 production in whole blood during clotting, the ID50 being 0.62(0.4-0.8) mg/kg. Both in vitro and ex vivo the effect of FCE 27262 on TXA2 synthase was selective, the production of PGE2, the product of a different isomerase from the common precursors, PG-endoperoxides, being concomitantly enhanced. In a canine model of electrically-induced coronary thrombosis, FCE 27262 (1 mg/kg i.v.) inhibits ex vivo TXB2 synthesis (> 95%), antagonizes U 46619-induced platelet aggregation and prolongs occlusion time (controls: 72 +/- 8 min, FCE 27262: 215 +/- 38 min; p < 0.01). In the same model both aspirin (5 mg/kg i.v.) and a pure PGH2/TXA2 receptor antagonist (L 670596), at a dose giving a similar degree of TXA2 synthase inhibition and receptor blockade, respectively, are significantly less effective. Thus, FCE 27262 combines thromboxane synthase inhibition and PGH2/TXA2 receptor antagonism in one molecule, resulting in enhanced antithrombotic activity. FCE 27262 thus may be an appropriate pharmacological tool to test the therapeutic potential of the dual mechanism of action.

Animals↗
PubMed1993

Direct characterization of caffeoyl esters with antihyaluronidase activity in crude extracts from Echinacea angustifolia roots by fast atom bombardment tandem mass spectrometry.

Fast atom bombardment (FAB-MS) and fast atom bombardment tandem mass spectrometry (FAB-MS/MS) techniques (negative ions) have been successfully applied for identification of the constituents responsible for the antihyaluronidase activity of Echinacea angustifolia roots, whose extracts are widely employed for the adjuvant therapy of chronic inflammatory diseases. Crude extracts from different solvents were tested for antihyaluronidase activity, and those with the greatest inhibitory action (the ethylacetate, butylacetate and chloroform fractions, IC50 0.44, 0.50 e 0.62 mg/ml) were directly analyzed by MS. Full scan mass spectra produced intense molecular anions: collisional activation of these resulted in tandem mass spectra rich in significant product ions. Four main caffeoyl conjugates were detected and identified by tandem mass spectrometry (daughter and parent ion mode): 2,3-O-dicaffeoyltartaric acid (chicoric acid) and 5-O-dicaffeoylquinic acid (cynarine) and 2-O-caffeoyltartaric acid (caffaric acid) in the ethylacetate fraction. Among these caffeoyl conjugates, chicoric and caftaric acids had the greatest antihyaluronidase activity: IC50 = 0.42 and 0.61 mM, while the IC50 of cynarine and chlorogenic acid were 1.85 and 2.25 mM.

Acetates↗
PubMed1993

Breakfast omission and cognitive performance of normal, wasted and stunted schoolchildren.

This study focuses on the effects of breakfast omission on cognitive performance. We studied 279 children from low socioeconomic level background ranging in age from 8 years 7 months to 10 years 11 months, categorized nutritionally as: normal, wasted or stunted. Evaluation comprised three cognitive tasks designed to be applied with a microcomputer. Assessment took place in their natural setting, after a mean of 14 h of overnight fasting, some having received a standard breakfast at random while the remaining children continued a fasting situation. We found no consistent association between study condition and performance in short-term visual memory, problem solving and attention tasks in any of the three nutritional groups. Stunted children showed significantly lower scores in the attention test irrespective of having received breakfast or not. These results suggest that given a motivating short-term task and maintaining routine conditions, missing breakfast does not affect the accuracy of the cognitive performance of children. Nutritionally affected children did not show a particular vulnerability to the fasting condition, but did show a specific cognitive deficit.

Attention↗
PubMed1993

A multicentre randomized clinical trial of recombinant alpha-2a interferon therapy in patients with chronic hepatitis B.

Fifty six previously untreated patients who had been positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for more than 1 year with detectable serum levels of hepatitis B virus DNA (HBV-DNA) and a liver biopsy performed in the 6 months before enrollment, were randomized to receive recombinant alpha-2a interferon at doses of 3MU intramuscolarly thrice weekly for 6 months or no treatment. Treated and untreated patients had similar clinical characteristics in terms of ALT elevation, HBV-DNA levels, and degree of liver damage. Twenty one had chronic persistent or lobular hepatitis; 28 had chronic active hepatitis and 7 had cirrhosis. The percentages of patients who lost HBeAg at month 6, 12 and 18 were 22%, 32% and 38% in the treated group, and 16%, 20% and 37% in the controls (differences = ns). At the same time intervals, HBV-DNA detected by dot spot hybridization, cleared off in 39%, 39% and 41% of treated patients as compared to 16%, 36% and 37% of controls (difference = p < 0.05 for HBV-DNA clearance at month 6). At the end of follow-up, 12 treated patients (41%, including 8 antiHBe seroconverters) and 10 untreated controls (42%, including 6 anti-HBe seroconverters) had normal aminotransferase levels. Conclusions show that in patients with chronic hepatitis B, clearance of HBV-DNA but not of HBeAg was hastened by a 6-month treatment with low doses of recombinant alpha-2a interferon.

Adolescent↗