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Biomedical subjects

M Zoli

Publications and source records attributed to M Zoli.

At least 145 records · Page 8Linked to original sources
PubMed1991

Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score.

Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity: P less than 0.025; aminopyrine breath test: P less than 0.001; ICG clearance: P less than 0.005) and common clinical and biochemical data (encephalopathy: P less than 0.001; ascites: P less than 0.001; serum bilirubin: P less than 0.005; serum albumin: P less than 0.001; prothrombin index: P less than 0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P = 0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification.

Aminopyrine↗
PubMed1991

Elimination of infused branched-chain amino-acids from plasma of patients with non-obese type 2 diabetes mellitus.

Increased plasma levels of branched-chain amino-acids (BCAA) have been demonstrated in poorly controlled diabetes mellitus, and related to absolute or relative insulin deficiency. To study the pathogenesis of this alteration, the elimination of BCAA from plasma was measured in 8 patients with non-obese type 2 diabetes mellitus and in 8 age-matched control subjects during steady-state BCAA concentrations induced by a primed-continuous infusion. Fasting BCAA levels were increased by 40-50% in patients with diabetes. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady-state concentration, were reduced by 20% in diabetics, despite 50% hyperinsulinemia (P < 0.01). Basal BCAA levels and BCAA clearance were negatively correlated (r(2) = 0.46 - 0.56). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were normal in diabetics, and there was no difference in the apparent volumes of distribution of BCAA. The increased basal concentration of BCAA in poorly controlled type 2 diabetics (693 [SD 114; n = 8] mumol/l vs 479 [88; n = 8] in controls (P < 0.005) is attributable to changes in plasma clearances, without any change in the efflux of BCAA into plasma. This may be due to insulin resistance.

Journal Article↗
PubMed1991

Thyroid gland size and function in patients with cirrhosis of the liver.

Thyroid dysfunction has long been reported in patients with liver disease, but limited information is available on thyroid gland size in cirrhosis. Most studies were carried out on small, selected series of patients, and no study has measured thyroid volume in relation to the etiology of liver disease. Thyroid volume was measured at ultrasound in 118 consecutive patients with cirrhosis of different etiology and 48 healthy subjects matched for age and sex. No subjects had evidence of overt thyroid disease. The mean volume was increased by 17% (from 16.0 [SD 5.2] ml in controls to 18.8 [7.6] in cirrhosis; P less than 0.025), and thyroid enlargement (antero-posterior diameter greater than 20 mm) was present in 38% of cases, in the presence of hormone values indicative of low-T3 syndrome. No significant differences in thyroid gland size were observed in relation to the extent of liver dysfunction or to the etiology of liver disease. The prevalence of thyroid nodules was similar in controls and in patients with cirrhosis. In only 8% of cases were laboratory values indicative of hypothyroidism, with low free triiodothyronine and raised thyroid-stimulating hormone levels; in these patients thyroid volume was decreased on average by 26%. This was mainly the case with patients with primary biliary and alcoholic cirrhosis. The largest mean thyroid volume was observed in patients with HBsAg + ve postnecrotic cirrhosis, whose thyroid volume was increased on average by 37%, and 53% of subjects had thyroid enlargement. This finding raises the question of a possible direct involvement of the thyroid in hepatitis B virus infection.

Female↗
PubMed1991

Effect of physical exercise on one-sample antipyrine clearance.

Moderate physical exercise for a few hours is not expected to reduce the hepatic elimination of drugs exhibiting capacity-limited metabolism (low-clearance drugs such as antipyrine). However, previous studies have shown that antipyrine half-life, measured by the multiple-sampling technique, is increased by exercise. A simplified one-sample procedure for antipyrine clearance determination is increasingly being used as a liver function test. The effects of exercise on this measurement have never been evaluated. We measured antipyrine clearance, using the one-sample, simplified procedure in a group of 50 young Italian army soldiers, while at rest and during a 6 hour march in the mountains (extra energy expenditure: 7.43 kjoule per min). Mean antipyrine clearance was on average 46.6 (SD 10.2) ml/min (range 30.5-65.4) while resting, and 46.2 (10.5) (range 25.5-64.8) while exercising (not different). No specific advice regarding physical exercise is needed whenever liver function is measured in outpatients by the one-sample, simplified antipyrine clearance test.

Adult↗
PubMed1991

A new model of focal brain ischemia based on the intracerebral injection of endothelin-1.

Endothelin-1 and its receptors are widely distributed in the brain of rodents and humans. In view of its potent and long-lasting vasoconstrictor activity, a role of endothelin-1 has been proposed in brain ischemia. In the present paper, the local injection of endothelin-1 was utilized to induce ischemia in rat striatum. An evaluation of the rostrocaudal extension of the lesion is reported. By using intracerebral microdialysis, a marked increase of lactate and dopamine, but not glutamate, was observed in this region upon endothelin-1 administration. Moreover, preliminary data reported show a protective effect of ganglioside treatment on endothelin-1 lesion of rat striatum. The characteristics of the present model of brain ischemia are discussed in comparison with well characterized models, such as the Pulsinelli's four vessel occlusion and the middle cerebral artery occlusion.

Animals↗
PubMed1991

Prognostic indicators in compensated cirrhosis.

In an attempt to identify variables predicting prognosis, 100 consecutive patients with compensated cirrhosis of the liver were followed for a mean of 4.9 (SD 0.7) yr. Fifty-one patients belonged to Child-Pugh class A, 49 to class B. At entry, five laboratory parameters were considered, together with sex, the grade of esophageal varices, and seven variables measured by ultrasonography (liver and spleen volume and the calibers of the splanchnic vessels). In a subgroup of 56 patients, the galactose elimination capacity also was determined. Forty-six patients were alive at the end of follow-up. Survival was analyzed according to Cox's model. Six parameters were able to predict survival (albumin, bilirubin, liver volume, prothrombin activity, cholesterol, varices). However, step-wise Cox regression analysis identified only four variables that independently correlated with survival: albumin, bilirubin, cholesterol, and liver volume. Galactose elimination failed to add any significance to routine liver function tests. This prospective study confirms the ability of routine liver function tests in predicting survival in compensated cirrhosis. The measurement of liver volume, easily obtained by ultrasonography, is also significant for prognosis, and may be introduced into clinical practice.

Actuarial Analysis↗
PubMed1991

Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: a simplified method.

The functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass. The clinical feasibility of the test has so far been limited by methodological problems. A simplified procedure was used to measure the urea-nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis. The method was based on only four consecutive 2-hr urine collections and five blood samples. Total body water was calculated from a nomogram based on age and anthropometric data, whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis (0.17 in control subjects and 0.26 in patients with cirrhosis). Finally, a solution of a single amino acid, alanine, was infused as substrate for urea synthesis. Urea-nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentration, and the slope of the regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from 37.5 +/- 7.0 L/hr to 18.4 +/- 6.7 L/hr; p less than 0.005. The hepatic nitrogen clearance was linearly related to the clinical status (Child-Pugh score), to routine liver function tests and to galactose elimination capacity (r = 0.869), a well-established, quantitative, liver function measure. The simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use. The test might prove useful to study the alterations of nitrogen metabolism in cirrhosis, with special reference to hepatic encephalopathy.

Adult↗
PubMed1990

Evidence for a role of neosynthetized putrescine in the increase of glial fibrillary acidic protein immunoreactivity induced by a mechanical lesion in the rat brain.

The effect of alpha-difluoromethylornithine (alpha-DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) the rate limiting enzyme of polyamine biosynthesis, was studied on the astroglial reaction in a model of mechanical brain injury. alpha-DFMO markedly decreased the astroglial activation induced by the microdialysis probe implantation in the striatum of the male rat, as studied by glial fibrillary acidic protein (GFAP) immunocytochemistry. This response was restored by putrescine (20 nmol/ml) administered via the microdialysis probe. These results suggest that the astroglial reaction and the polyamine biosynthesis activation induced by a localized mechanical lesion are causally linked phenomena.

Animals↗
PubMed1990

Repeated electroconvulsive shock increases glial fibrillary acidic protein, ornithine decarboxylase, somatostatin and cholecystokinin immunoreactivities in the hippocampal formation of the rat.

Rats were submitted to single or repeated (7 days, one session for each day) sessions of electroconvulsive shock. A computer-assisted morphometric and microdensitometric analysis of glial fibrillary acidic protein-, ornithine decarboxylase-, somatostatin- and cholecystokinin-like immunoreactivities was performed in the hippocampal formation and other brain areas. The results of the study showed a significant increase of the intensity of the immunostaining for glial fibrillary acidic protein, ornithine decarboxylase, somatostatin and cholecystokinin in the hippocampal formation and distinctively in the dentate gyrus following repeated, but not single, electroconvulsive shock. No significant change was found in the number of somatostatin- and cholecystokinin-like immunoreactive cell bodies in any hippocampal subregion and in the number of glial cells in the hilus of dentate gyrus in rats treated with single or repeated electroconvulsive shock. It is a distinct possibility that the observed increase in the content of the neuropeptides in the hippocampal formation reflects a compensatory response of the brain to seizure-inducing stimuli and that such an increase may play a role in the therapeutic effect of electroconvulsive shock.

Animals↗
PubMed1990

Morphometrical and microdensitometrical studies on peptide- and tyrosine hydroxylase-like immunoreactivities in the forebrain of rats prenatally exposed to methylazoxymethanol acetate.

Methylazoxymethanol acetate (MAM Ac) injected into pregnant rats at a dose of 25 mg/kg at gestational day 15 causes microcephaly due to an atrophy of various telencephalic areas, mainly neocortex, hippocampus and basal ganglia. Previous studies demonstrated alterations in various neurochemical markers of classical transmitter systems in these regions. The present paper deals with changes in peptide and tyrosine hydroxylase (TH)-containing neurons in MAM Ac-induced microcephaly using immunocytochemistry coupled with computer-assisted morphometry and microdensitometry. No change in the number of vasoactive intestinal polypeptide (VIP)-immunoreactive neurons in the neocortex and neuropeptide Y (NPY)-immunoreactive neurons in the nucleus caudatus-putamen was found whereas cholecystokinin (CCK)-and NPY-immunoreactive neurons in the neocortex and CCK- and VIP-immunoreactive neurons in the hippocampus were decreased. The reduction of the latter peptide containing neuronal populations led to a maintained density of cells in MAM Ac-exposed rats, due to the parallel reduction of the overall mass of these regions. TH immunoreactivity was found to be unchanged in the basal ganglia, and increased in the cerebral cortex in agreement with previous reports on noradrenaline cortical system after MAM Ac exposure. The present results show a heterogenous vulnerability of different peptide immunoreactive neuronal populations to MAM Ac exposure. The sparing of VIP- and NPY-immunoreactive neurons may be due to their late development in the neocortex and striatum, respectively. The hypothesis is introduced that cortical VIP interneurons can develop independent of marked alterations in the intrinsic circuitry of the cortical region.

Animals↗
PubMed1990

Ultrasonographic follow-up of liver cirrhosis.

Ultrasonography and upper gastrointestinal endoscopy were prospectively used to study 100 consecutive patients with liver cirrhosis. After a period of 20 months to 55 months, 21 patients had died, 23 were lost at follow-up, and 56 patients were reevaluated. In the patients who died during follow-up, the entry liver volume, measured by means of the hepatic volumetric index, was lower as compared to the 56 cirrhotics who survived. During the study period, liver volume significantly decreased to values similar to those observed, at entry, in patients who died. Moreover, esophageal varices increased in size, and the splanchnic veins enlarged. Abdominal ultrasonography provides data regarding the natural history of liver cirrhosis, which might be used, in addition to tests of liver function and endoscopy, as prognostic factors in cirrhotic patients.

Adult↗
PubMed1990

Effects of transient forebrain ischemia on peptidergic neurons and astroglial cells: evidence for recovery of peptide immunoreactivities in neocortex and striatum but not hippocampal formation.

The effects of transient (30') forebrain ischemia (4 vessel occlusion model) on peptidergic neurons and astroglial cells in various diencephalic and telencephalic areas have been analyzed. The study was performed at various time intervals of reperfusion, i.e. 4 h, 1, 7 and 40 days. Neuropeptide Y (NPY), somatostatin (SRIF), cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP) and arginine-vasopressin (AVP) immunoreactive (IR) neuronal systems and glial fibrillary acidic protein (GFAP)-IR glial cells have been visualized by means of the indirect immunoperoxidase procedure using the avidin-biotin technique. The analysis was performed by means of computer assisted microdensitometry and manual cell counting. At the hippocampal level a huge reduction of neuropeptide (CCK, SRIF, VIP) IR cell bodies was observed, still present 40 days after reperfusion. On the contrary, in the frontoparietal cortex the number of the neuropeptide (CCK, SRIF, VIP, NPY) IR neurons showed a decrease at 4 h, 1 and 7 days after reperfusion followed by a complete recovery at 40 days. A rapid reduction followed by an almost complete recovery (7 days after reperfusion) was also observed at striatal level where SRIF- and NPY-IR neurons were detected. A marked decrease of NPY-IR terminals was observed in the paraventricular and periventricular hypothalamic nuclei and in the paraventricular thalamic nucleus. AVP-IR was markedly reduced in the magnocellular part of the paraventricular nucleus throughout the analyzed period (7 days after reperfusion). GFAP-IR was increased in the hippocampal formation and neostriatum while a not consistent increase was observed at neocortical level. These data point to a differential recovery of peptide-IR and to a different astroglial response in the various brain areas after transient forebrain ischemia. Region-specific factors rather than factors related to neuronal chemical coding seems to play a major role in determining the vulnerability of neuronal populations to transient ischemia.

Animals↗
PubMed1990

Cellular and synaptic alterations in the aging brain.

The morphological and functional impairments observed in the aging brain are discussed in the framework of theoretical concepts, such as the existence of different modalities of intercellular communication and of specific trophic features in the central nervous system. The relevance of changes at the cellular level (disappearance of neuronal cell bodies and proliferation of astroglial cells) and at the synaptic level (alterations in neurotransmitter and receptor levels) is discussed. Two, non-mutually exclusive hypotheses are advanced to explain the frequent absence of correlation between neuropathological findings and functional deficits in aged patients. According to the first, the physiological reshaping of brain circuits during aging may lead to "wrong" readjustments of neural networks (e.g. due to less effective endogenous and exogenous orienting signals) causing minor morphological alterations but marked functional deficits. The second hypothesis maintains that the absence of correlation between neuropathological and functional deficits is due to the impairment of restricted neuronal populations ("pacemaker and command neurons") which play a special role in the hierarchical organization of neuronal networks. These neurons (inter alia, peptidergic neurons) may also be involved in volume transmission (diffusion of electrical and chemical signals in the extracellular fluid to reach distant targets). Moreover, the relevance of glial cells, not only as regulators of the extracellular medium but also on the basis of their trophic links with neurons, is considered. Finally, the interplay between trophic factors and therapeutical experience for the maintenance and/or recovery of an impaired function in elderly patients is discussed.

Aging↗
PubMed1990

Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. The Italian Multicenter Study Group.

In a double blind randomized study, branched-chain amino acids and placebo (casein) were compared as a treatment for chronic hepatic encephalopathy in cirrhosis. After a 15-day run-in period with controlled diet (45-65 g protein), the patients were administered, in addition to their diet, branched-chain amino acids (0.24 g/kg, 30 patients) or an equinitrogenous amount of casein (34 patients). One patient on branched-chain amino acids and two on casein were lost to the study. After 3 months, the index of portal-systemic encephalopathy significantly improved in patients on active treatment (from 40 [S.D. 14]% to 21 [17]), but was not in subjects receiving casein (from 37 [13]% to 36 [12]). Two or more parameters of the index improved in 24 patients treated with amino acids (80%; confidence limits, 61-92%), and only in 12 receiving casein (35%; confidence limits, 20-54%; p less than 0.001). Patients who did not improve were given an alternative treatment for 3 more months. Casein-treated patients given branched-chain amino acids rapidly improved. The changes in neuropsychologic function were associated with an improvement in semiquantitative nitrogen balance, which became consistently positive in amino acid-treated subjects; there was also a mild improvement in nutritional parameters and in liver function tests. The supplementation of oral branched-chain amino acids to the diet is superior to casein as a treatment for providing adequate nitrogen supply and improving the mental state of cirrhotic patients with chronic encephalopathy.

Adult↗
PubMed1990

Synthesis of urea after a protein-rich meal in normal man in relation to ageing.

An age-related decline in the functional capacity of the liver has been repeatedly demonstrated by means of dynamic tests. We measured the urea-N synthesis rate in response to a protein-rich meal in 24 healthy subjects divided into three age-groups (less than or equal to 55 years, 56-70 years; greater than or equal to 71 years). No differences were observed in the basal state. The peak urea synthesis and the mean urea synthesis in the 5 hours after the meal were blunted with increasing age, and a negative correlation was present between mean or peak urea synthesis and age (r = -0.572 and r = -0.541, respectively). No differences in basal and post-meal total alpha-amino-nitrogen or individual plasma amino acids were observed. Hormone responses were similar. Galactose elimination capacity was also reduced with increasing age, and correlated with mean and peak urea synthesis after a protein mean (r = 0.640 and r = 0.591, respectively). These data suggest that the capacity of the liver to produce urea in response to a protein-rich meal is reduced in the elderly in relation to a decreased functional liver cell mass.

Age Factors↗