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H Orrego

Publications and source records attributed to H Orrego.

100 records · Page 6Linked to original sources
PubMedDate not supplied

Assessment of prognostic factors in alcoholic liver disease: toward a global quantitative expression of severity.

The prognostic significance of a battery of clinical, laboratory, and histological indicators was assessed in relation to mortality risk in a 1-year study of 253 patients with alcoholic liver disease, of whom 51 died within such time. The relative risk associated with each abnormality was calculated. A number of abnormalities was found to be statistically associated with a higher risk of death. Among the clinical abnormalities, these were: collateral circulation, edema, ascites, encephalopathy, spider nevi, anorexia, and weakness. Among the laboratory tests, these were: albumin, bilirubin, hemoglobin, abnormal prothrombin time, and alkaline phosphatase. Two hundred and sixteen of these patients had liver biopsies in which the quantifiable abnormalities were scored. Among the histological findings, the alterations significantly related to mortality were necrosis, Mallory, and inflammation, while the presence of cirrhosis per se did not influence the mortality risk. The relative risk factors for mortality associated with the histological alterations were lower than those derived from clinical or laboratory measurements. The advantage of using only clinical and laboratory items to derive a global, quantitative expression of severity is discussed. The relative mortality risks provided a means of calculating a "unit of severity" for each clinical and laboratory abnormality. A combined clinical and laboratory index (CCLI) results when these mortality-risk units are added. Such a combined index had a quasi-linear relationship with the risk of mortality for the complete population. This method compared well with severity scores derived from computerized, linear step-wise discriminant function (SDF) analysis and from a logistic regression (LR) analysis. The factors chosen to have independent prognostic significance by the SDF analysis were: encephalopathy, albumin, prothrombin time, and hemoglobin, while only encephalopathy, albumin, and hemoglobin were chosen by the LR analysis. Within a range of values, LR can provide a good discrimination in relation to mortality, similar to that observed for the CCLI in its complete range. However, there are some advantages to the CCLI method vs. the LR or SDF analyses. The CCLI is less susceptible to being unduly influenced by a nonspecific effect of treatment on the items chosen than the SDF and LR analyses, as the CCLI contains a large number of factors. Obtaining a single-severity score such as the CCLI is of value in: (a) assessing the effectiveness of treatment modalities; (b) analyzing the success of randomization; (c) separating cohorts of different severity, and (d) comparing new liver tests, histological abnormalities, or specific biological events with the severity of alcoholic liver disease.

Age Factors↗
PubMedDate not supplied

Sinusoidal caliber in alcoholic and nonalcoholic liver disease: diagnostic and pathogenic implications.

Portal hypertension in alcoholic liver disease has been attributed to an increased resistance to blood flow either of sinusoidal or of postsinusoidal origin. The former should be accompanied by sinusoidal compression while the latter is expected to result in an increased or a normal sinusoidal diameter. Patients with alcoholic liver disease showed a marked reduction (p less than 0.001) in relative sinusoidal area (995 +/- 135 micron 2; n = 19) when compared to nonalcoholic patients with normal liver histology (5,100 +/- 389 micron 2; n = 6), or to patients with nonalcoholic liver disease (6,242 +/- 467 micron 2; n = 19). Hepatocyte surface area was significantly increased in patients with alcoholic liver disease when compared to hepatocytes from normal biopsies (563 +/- 32 micron 2 vs. 301 +/- 26 micron 2; p less than 0.001). Patients with nonalcoholic liver disease had hepatocyte surface areas within the normal range (327 +/- 14 micron 2). There was a significant inverse correlation between hepatocyte size and sinusoidal area (r = -0.63; p less than 10(-6); n = 44), indicating that larger hepatocytes were associated with sinusoidal compression. In the alcoholic patients, portal pressure correlated inversely (r = -0.77; p less than 0.01) with sinusoidal area only after the sinusoidal area was markedly reduced to areas below 20% of normal. Such a threshold was not reached in patients with nonalcoholic liver disease, in whom no correlation between sinusoidal area and portal pressure was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Ethanol-induced increase in portal hepatic blood flow: interference by anesthetic agents.

While a number of studies show that acute oral administration of ethanol results in increases in liver blood flow, a large body of evidence has also been presented in which such an effect is not observed. To shed light on this discrepancy, we have studied in rats, a number of variables that might modulate or inhibit the effect of ethanol. These included the use of three anesthetic agents studied at two different times after anesthetic administration and the effect of animal age, gender, batches and seasonal variation. Portal blood flows were determined by the radiolabeled microsphere method in 12 separate experiments in awake rats. Ethanol given at doses ranging from 0.5 to 4.0 gm per kg consistently increased portal vein blood flow by approximately 50% (42.2 +/- 3.5 to 63.4 +/- 6.5 ml per min per kg). The interexperiment variation was 2.4 to 3.0%, showing remarkable consistency, typical of an all-or-none effect at the doses employed. On the other hand, the ethanol-induced increase in portal blood flow was completely suppressed by ketamine (75 mg per kg), thiopental (50 mg per kg) and fentanyl (15 micrograms per kg) when given 15 min prior to blood flow determinations. This suppression was dependent on the dose and duration of anesthesia. These anesthetic agents had no effect on basal hepatic arterial or portal blood flows. Ethanol or the anesthetics were without effects on hepatic artery blood flow. Neither gender, weight (150 to 350 gm) nor animal batch had effect on the response to ethanol. Similarly, there was no effect of seasonal variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Antibodies against acetaldehyde-modified protein epitopes in human alcoholics.

Acetaldehyde, the primary metabolite of ethanol, binds covalently to proteins forming condensation products which have been recently shown to be immunogenic. To assess whether an antibody response against acetaldehyde-modified protein epitopes is associated with alcoholic liver disease, the serum immunoreactivity against proteins modified in vitro by acetaldehyde and against the corresponding unmodified proteins was measured by an enzyme-linked immunosorbent assay in 58 alcoholics with varying degrees of liver damage. Alcoholics showed significantly higher titers against protein-acetaldehyde conjugates than against the unmodified protein, independent of the nature of the carrier protein. The highest titers occurred in alcoholic hepatitis patients. Sera of patients with chronic hepatitis of nonalcoholic origin and of healthy controls also reacted with acetaldehyde conjugates, but their titers were significantly lower than those in alcoholic hepatitis patients. Our data support the idea that binding of acetaldehyde to proteins in humans generates antigenic determinants which trigger a corresponding immune response against such epitopes and suggest that this humoral immune response may be implicated in autoantibody formation and liver damage associated with excessive alcohol consumption.

Acetaldehyde↗
PubMedDate not supplied

Disposition of intravenous propylthiouracil.

Propylthiouracil was administered to 10 healty, male volunteers by a short intravenous infusion. Plasma and urinary drug concentrations were determined by a specific high-performance liquid chromatography assay, and protein binding was determined by equilibrium dialysis. After infusion, the plasma concentrations declined biexponentially, and the following median parameters (and ranges) were determined: clearance 273.5 ml/min (159.5-377.8 ml/min); free drug clearance, 1537.7 ml/min (985.9-1927.3 ml/min); apparent volume of distribution, 28.0 liters (22.7-44.4 liters); apparent elimination half-life, 1.28 hr (0.88-2.05 hr); k21, 3.12 hr-1 (1.06-5.36 hr-1): alpha 7.34 hr-1 (1.94-25.03 hr-1): Vc 9.40 liters (5.16-18.58 liters). In urine, only 1.28 per cent (0.03-2.01 per cent) of the administered dose was recovered over 24 hours as unchanged drug. The ratio (1.2 per cent) of urinary clearance (3.2 ml/min) to plasma clearance is far less (P less than 0.001) than the free fraction in plasma (median 18.2 percent, range 16.2-20.2 per cent) and this suggests that there is significant renal tubular reabsorption of propylthiouracil. In healthy subjects, both intraindividual and interindividual variation of protein binding is modest, and free drug clearance can be predicted from total drug clearance (y =- 257.6 + 4.56x, r = 0.95, P less than 0.001).

Adult↗
PubMedDate not supplied

Effect of alpha- and beta-blockers on ethanol metabolism.

The acute administration of propranolol or phentolamine resulted in a small (16-19%) but significant reduction in the rate of ethanol disappearance in vivo in the naive Wistar rat. A reduction of essentially similar magnitude was also observed in ethanol-treated rats and pair-fed (sucrose) control animals, following the administration of these blockers.

Alcohol Drinking↗
PubMedDate not supplied

Reliability of assessment of alcohol intake based on personal interviews in a liver clinic.

In 37 patients with alcoholic liver disease urinary alcohol was measured daily for up to 6 months. Every week the patients were asked about their drinking during the past week. Those who convinced the physicians of their abstinence were recorded as not drinking. Patients with alcohol in their urines convincingly denied alcohol intake 52% of the times that they were questioned. 25% of them denied drinking every time. Only 17% of all patients admitted it at all times. Patients who always admitted to drinking had an average urinary alcohol value of 1420 +/- 66 mg/l, compared to 81 +/- 5 mg/l in those who denied drinking every time. Those who admitted drinking intermittently had significantly higher urinary alcohol values (1001 +/- 57 mg/l) when admitting than when denying (538 +/- mg/l). The personal interview should not be used to separate populations of abstainers and non-abstainers in the follow-up of alcoholic patients. On the other hand, deniers appear to consume less alcohol than those who admit their drinking.

Alcohol Drinking↗
PubMedDate not supplied

Relationship between gamma-glutamyl transpeptidase and mean urinary alcohol levels in alcoholics while drinking and after alcohol withdrawal.

In 42 patients with alcoholic liver disease in whom daily urinary ethanol concentrations were measured for 3 months, after an abstinence of at least 1 month, serum gamma-glutamyl transpeptidase (GGT) activity was found to correlate (r = 0.69; p less than 0.0001) with mean urinary alcohol levels. The half-life of serum GGT decay in 32 patients who remained abstinent for an 8-week period was calculated to be 26 days. This prolonged half-life can result in high serum GGT levels in patients abstinent for prolonged periods, in whom serum GGT baselines before abstinence were very high. Individual variations in serum GGT levels should be interpreted in relation to continued alcohol consumption, keeping in mind the long half-life for this enzyme in these patients.

Ethanol↗