Three hundred and sixty diabetic patients (125 on insulin, 109 on sulfonylureas and 126 on diet alone) were selected to investigate the effect of the type of treatment and of the degree of metabolic control on serum lipoproteins. Prebeta-lipoprotein concentration was higher than normal in all treatment groups. Beta-lipoproteins were significantly higher in diabetic women than in controls. No difference in beta- and prebeta-lipoprotein concentration existed between the 3 treatment groups. Alpha-lipoproteins were significantly higher in insulin-treated than in diet-treated patients irrespective of the degree of metabolic control. The daily dose of insulin and, in patients on diet or sulfonylureas, serum IRI were positively correlated to alpha-lipoprotein concentration while this lipoprotein fraction was not significantly correlated to fasting blood sugar. Alpha-lipoprotein concentration, then, appears to be markedly influenced by exogenous and endogenous insulin, independently of the degree of metabolic control.

Adult↗

PubMedDate not supplied

Cholesterol distribution between HDL subfractions. A study of 498 subjects.

In 498 subjects (205 normolipidemics and 293 hyperlipidemics) of both sexes, the cholesterol content of high density lipoprotein (HDL) subfractions has been determined. The serum concentration of total HDL-cholesterol appears to be more strictly related to the cholesterol content of HDL2 than to that of HDL3. This latter one, however, gives a contribution to the variability of HDL-cholesterol so that the value of HDL-cholesterol cannot be assumed as a reliable estimate of the serum level of the more anti-atherogenic HDL2 subfraction. The cholesterol content of HDL and its subfractions is higher in women than in men and decreases with increasing serum VLDL-cholesterol level and body weight. Both HDL2- and HDL3-cholesterol appear to largely depend from the metabolism of triglyceride-rich lipoproteins in accordance with the data of experimental studies.

Adolescent↗

PubMedDate not supplied

Effects of serum storage on the determination of cholesterol.

Cholesterol determined by 4 different enzymatic commercial kits and by the dry chemistry Reflotron system was higher in serum stored at 4 degrees C and at -20 degrees C than in fresh serum. The effects of storage seem to be temperature-dependent. In fact, cholesterol values significantly increased only after 2h of freezing. The prolongation of freezing up to 2 weeks was not followed by further significant changes. In serum stored at 4 degrees C the increase in cholesterol was slower than in frozen serum. Both free and esterified cholesterol underwent an increase after storage. When cholesterol was determined by a chemical method (sulfuric acid-ferric chloride) after extraction with ethyl acetate and ethanol, no difference was observed in fresh and stored serum. Cholesterol, triglycerides and apoproteins A-I and B underwent parallel changes after storage both in whole serum and fractionated lipoproteins. Our findings strongly suggest that in serum stored at positive or negative temperature there is an alteration of the lipoprotein molecules which allows an easier availability of cholesterol for the enzyme-substrate reaction than in fresh serum. Current enzymatic methods underestimate (about 10%) cholesterol when the analysis is performed on fresh serum.

Apolipoproteins↗

PubMedDate not supplied

Relationship of serum triglyceride concentration to lipoprotein composition and concentration in normolipidemic and hyperlipidemic subjects.

In a series of 438 subjects (184 normolipidemics and 254 hyperlipidemics) the relationship among serum concentration of triglycerides, lipoprotein lipids and apoproteins A-I and B has been evaluated. The results show that as serum triglyceride level increases, VLDL rise and become enriched in triglycerides. The increase of VLDL is associated with a reduction of serum levels of LDL and HDL which appear to be rich in triglycerides and poor in cholesterol. The decrease in serum HDL level is mainly due to a reduction in serum concentration of the HDL2 subfraction. The triglyceride content of HDL2 and HDL3 rises with increasing serum triglycerides. The increase in serum triglyceride concentration seems then to be associated with a complex metabolic derangement which involves all the lipoprotein fractions.

Adolescent↗

PubMedDate not supplied

Serum lipoprotein subfractions before and during low-calorie diet in obese women.

Twenty-five obese women were put on low-calorie diet for one month. The mean weight loss was 2.7 kg and was accompanied by a 9% decrease of LDL-cholesterol. LDL-apolipoprotein B (in 13 subjects) showed a 16% fall and LDL-triglyceride levels did not change. The results suggest both a decrease of LDL concentration and a relative increase of triglyceride-rich particles in the density range of 1.006-1.063. HDL2-cholesterol showed a 17% decrease and HDL3-cholesterol a 16% increase. Total and lipoprotein triglycerides were not modified. The changes of lipoprotein pattern suggest a sluggish VLDL catabolism by lipoprotein lipase. In 10 women followed for 6 months the decrease of LDL-cholesterol seen after one month of diet was no more present at the 6th month, while the decrease of HDL2-cholesterol and the increase of HDL3-cholesterol were still evident. At the end of the 6th month a slight but significant decrease of total and VLDL-triglycerides also occurred.

Adolescent↗

PubMedDate not supplied

Bezafibrate inhibits HMG-CoA reductase activity in incubated blood mononuclear cells from normal subjects and patients with heterozygous familial hypercholesterolaemia.

In incubated blood mononuclear cells from normal subjects bezafibrate inhibited the incorporation of 14C-acetate into squalene, methylsterols and cholesterol. Similarly, the drug produced a sharp decrease of the incorporation of labelled 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) into non-saponifiable lipids, while the incorporation of 14C-mevalonate was unaffected by the presence of bezafibrate in the incubation mixture. This strongly suggests that bezafibrate inhibits HMG-CoA reductase activity. In cultured cells from patients with heterozygous familial hypercholesterolaemia the presence of bezafibrate in the incubation medium resulted in an inhibition of the incorporation of labelled acetate into non-saponifiable lipids. Bezafibrate then inhibits cholesterol biosynthesis in cells from normal and hypercholesterolaemic patients and this effect is likely, to contribute to the hypocholesterolaemic activity of the drug.

Acetates↗

PubMedDate not supplied

The role of clinical "experience" in diagnostic performance.

Twenty-one physicians examined records of 43 patients who had attended the hospital because of chest pain. Of these patients, 20 had had coronary heart disease (CHD), 15 had had nonspecific pain, and eight had had pulmonary embolism. The physicians indicated the probability of CHD in each case on the basis of 18 clinical findings, not including ECG, x-ray, or biochemical studies. The trial was repeated five years later, using the same records, by 16 of the same physicians. Diagnostic accuracy was evaluated by ROC curves, and the weight ascribed to each cue was inferred by multiple regression with estimated probability of CHD as the dependent variable. No significant change of areas under the ROC curves with increasing length of clinical experience was observed. Multiple regression was significant in 30 of 37 analyses. The distributions of most physicians' estimates of probabilities had similar shapes five years apart. It is concluded that "experience" does not have a clear role in diagnostic performance based on recorded data and that personal calibration and preferences in estimating probabilities often persist for years.

Adult↗

PubMedDate not supplied

Cholestasis is the main determinant of abnormal CA 19-9 levels in patients with liver cirrhosis.

BACKGROUND/AIMS: Altered CA19-9 levels are commonly found in patients with liver cirrhosis though a clear explanation for this finding has not yet been given. The aim of this study was to investigate whether CA19-9 levels might be related to alterations in biochemical parameters and/or to functional impairment in cirrhotic patients with and without hepatocellular carcinoma. METHODS: We studied 126 patients with liver cirrhosis, 60 of whom also had hepatocellular carcinoma. CA19-9 values were related to clinical, biochemical and functional parameters. In half of the patients CA19-9 levels were related to the monoethylglycinexylidide test, which is a dynamic liver function test. RESULTS: In more than half the cases CA19-9 values were above the upper limit. Liver function worsening as assessed by Child-Pugh's score and monoethylglycinexylidide test did not seem to influence the alteration of the marker. By contrast, in univariate analysis CA19-9 correlated with aminotransferases, gamma-glutamyltransferase and alkaline phosphatase. Multivariate analysis showed that besides alkaline phosphatase also the presence of hepatocellular carcinoma might influence the alteration of CA19-9, although the marker was of no use for the diagnosis of liver cancer in patients with altered though not diagnostic alpha-fetoprotein levels. CONCLUSIONS: In our study we confirmed the correlation of CA19-9 levels with cholestasis and cytolysis parameters. Moreover, we found no association between CA19-9 levels and impaired liver function as assessed by means of the Child-Pugh's score and the monoethylglycinexylidide test, which is cholestasis-independent and explores liver metabolic and clearance activities. The cholestatic picture that characterizes liver cirrhosis might enhance the expression and passage of the marker from the bile to the blood. The addition of CA19-9 assessment is not useful for the diagnosis of hepatocellular carcinoma in patients with non-diagnostic levels of alpha-fetoprotein. Caution should therefore be used when evaluating CA19-9 in cirrhotic patients with cholestasis, since false positive results may occur.

Adult↗

PubMedDate not supplied

Probability of non-response during interferon therapy in patients with chronic hepatitis C.

BACKGROUND/AIMS: About 50% of patients with chronic hepatitis C do not respond to interferon therapy and this failure is expensive. The aim of this study was to identify possible predictive factors of biochemical non-response during interferon therapy among biochemical, virological (HCV genotype), histological (Knodell's score) and pharmacokinetic (monoethylglycinexylidide formation test) pre-treatment parameters. METHODOLOGY: Our study included 60 patients with chronic hepatitis C undergoing a course of Interferon therapy. Patients whose serum ALT levels were normal at the 3rd month of therapy and remained so until the end of treatment were regarded as responders. RESULTS: In univariate analysis, only the gamma-glutamyltransferase (gamma-GT) and the gamma-GT/alanine aminotranferase ratio were significantly higher in non-responder patients. Multivariate logistic analysis showed that high gamma-GT levels, high histological activity index, low monoethylglycinexylidide formation rate and viral genotype 1 were the best combination for the identification of non-responder patients (16.7% error rate). By adding alanine aminotranferase modification at the 1st month of therapy the probability error was reduced to 5%. CONCLUSIONS: These results show that the combination of biochemical, histological, virological and pharmacokinetic pre-treatment variables, associated with alanine aminotranferase modification at the 1st month of therapy, can predict non-response to interferon and allow therapeutic modifications.

Adult↗

PubMedDate not supplied

13CO2 excretion in breath of normal subjects and cirrhotic patients after 13C-aminopyrine oral load. Comparison with MEGX test in functional differentiation between chronic hepatitis and liver cirrhosis.

BACKGROUND/AIMS: Liver function can be evaluated using 13C breath tests that explore liver Cytochrome P450 activity. Aminopyrine is one of the first compounds used in liver function testing. Lidocaine metabolism to monoethylglycinexylidide is also a valid tool to assess liver function. Although liver Cytochrome P450 metabolizes both compounds, lidocaine metabolism is flow-dependent while aminopyrine metabolism does not depend on liver blood flow. METHODOLOGY: The 1st part of the study evaluated the appearance and disappearance rate of 13CO2 in the breath of both normal subjects and in cirrhotic patients, so as to establish optimal sampling times and to evaluate the amount of time needed before performing a subsequent breath test. The 2nd part of the study compared the aminopyrine breath test with the monoethylglycinexylidide test in patients with chronic hepatitis or cirrhosis. RESULTS: Complete 13CO2 disappearance was recorded 24 hours after the test in normal subjects, while it took 3 days to disappear from the breath of cirrhotic patients. Breath sampling at 60, 120 and 180 min were equally valid in differentiating chronic hepatitis from cirrhosis. The aminopyrine breath test and monoethylglycinexylidide test showed a good yet not close correlation. CONCLUSIONS: This study showed that in cirrhotic patients a 13C breath test can be performed 3 days after the previous one. In chronic hepatitis and cirrhotic patients, the aminopyrine breath test and the monoethylglycinexylidide test evaluated similar, but not identical, hepatic subfunctions, suggesting that multiple 13C breath test using different substrates could explore liver function better.

Adult↗

PubMedDate not supplied

Does surveillance for hepatocellular carcinoma in HCV cirrhotic patients improve treatment outcome mainly due to better clinical status at diagnosis?

BACKGROUND/AIMS: Cirrhotic patients with hepatitis C virus infection are a group at higher risk for hepatocellular carcinoma. Conventional screening programs detect only few early hepatocellular carcinomas that are eligible for radical treatment. Our aim was to compare characteristics of patients, modality of treatment, and outcome in anti-HCV positive cirrhotics with hepatocellular carcinoma diagnosed during follow-up, or incidentally. METHODOLOGY: Sixty-one hepatocellular carcinomas were consecutively diagnosed in cirrhotic anti-HCV patients from 1993-1998 among which 34 during biannual ultrasonographic-biochemical follow-up and the others incidentally. Child-Pugh's score, alpha-fetoprotein levels, uni- or multifocality of the tumor, and treatment and survival of the patients were then analyzed on the basis of modality of diagnosis. RESULTS: Surgical treatment was feasible only in a minority of patients. Radical and palliative treatment was more frequent among patients with HCC diagnosed during follow-up. Child-Pugh's score was lower in these patients, moreover their survival rate was better. Analysis of survival of patients treated with the same procedure and grouped by modality of diagnosis did not demonstrate any differences. Regression analysis showed that patients with a lower Child-Pugh's score, one nodule, with a tumor diagnosed during follow-up and who were treated had a better survival rate. CONCLUSIONS: In our population surveillance did not detect a higher percentage of curable HCC. Nevertheless the results of palliative treatment and of curative treatment overlapped. Overall better outcome was observed in patients with preserved liver function whatever the treatment. Surveillance allowed us to diagnose HCC in patients with these characteristics thus leading to an improved survival rate.

Aged↗