We analyzed whether normal human hepatocytes, which normally do not display Class II major histocompatibility complex antigens, can be induced to express them in vitro, and whether this induction has an in vivo counterpart in chronic liver diseases. While both alpha- and gamma-interferon induced expression of Class I antigens, only gamma-interferon induced expression of Class II antigens on hepatocytes in vitro. Recombinant interleukin 2 had no effect on major histocompatibility complex antigen expression. Both Class I and Class II antigens could be detected by indirect immunofluorescence on hepatocytes from patients with various forms of chronic liver disease, regardless of etiology. These findings suggest that gamma-interferon produced by T lymphocytes that infiltrate the liver during the course of chronic hepatitis induces Class II major histocompatibility complex antigen expression and may endow the hepatocytes with the capacity to perform accessory (antigen-presenting) cell functions.

Antibodies, Monoclonal↗

PubMedDate not supplied

Association between prolonged bleeding time and gastrointestinal hemorrhage in 102 patients with liver cirrhosis: results of a retrospective study.

BACKGROUND: Gastrointestinal bleeding is a frequent complication of liver cirrhosis (LC) and represents an important warning sign of imminent death. Platelet dysfunction is an abnormality occurring prevalently in severe liver failure, and could well predispose to bleeding. METHODS: One hundred and two patients with liver cirrhosis diagnosed by needle liver biopsy were studied. According to the Child-Pugh classification, 23 were A class, 42 B class and 37 C class cases. Prothrombin activity, aPTT, fibrinogen, FDPs, XDP and platelet count were measured in each patient; bleeding time was measured in all but 17 of them. Forty (39%) had experienced gastrointestinal bleeding during the last 3 years (2 A class, 12 B class, 26 C class). RESULTS: Patients with a history of previous gastrointestinal bleeding showed lower values for prothrombin activity and fibrinogen, and higher percentage of elevated FDP and XDP levels; moreover, they presented lower platelet counts and more prolonged bleeding times than patients without gastrointestinal blood loss. CONCLUSIONS: While our findings confirm the relationship between hyperfibrinolysis and bleeding, the association between bleeding time prolongation and gastrointestinal blood loss suggests studying platelet function prospectively in LC in order to analyze its role, if any, in favoring hemorrhage activity.

Adult↗

PubMedDate not supplied

The kidney and essential hypertension.

In the first part of the text the main elements of renal physiology are mentioned as well as the role played by sodium-modulating hormones in the preservation of sodium and water homeostasis. A personal contribution concerns the release as well as the circadian rhythm of atrial natriuretic peptide (ANP) and of the digitalis-like substance (DLS). In the second part, the problem is dealt with from a pathophysiologic point of view, with reference made to the literature, and to our own data. In particular, the problem of essential hypertension with reduced levels of plasma renin activity (PRA) is thoroughly analyzed. As is well known, this kind of hypertension is characterized by normal plasma aldosterone levels associated with reduced kallikrein urinary excretion. The data we gathered not only confirmed these findings but also enabled us to point out other typical features of this particular kind of hypertension: normal values of vasopressin, elevation of ANP and DLS, hyperactivity of Na+/K+ cotransport. The introduction of a single variant in the sodium-modulating systems confirmed that the low PRA patient also behaves distinctively from a dynamic point of view. In fact, prostaglandin inhibition determines hypertension only in these patients, while both oral kallikrein administration and intravenous ANP administration were particularly effective because of a primitive deficit of the natriuretic paracrine systems paralleled by a compensatory increase of ANP. After identifying this group of hypertensive patients we intended to ascertain whether, even in the normal or high PRA patients, it was possible to identify a sub-group of subjects with altered sodium-modulation. The patients we examined were subdivided according to their hormonal and renal response to a saline load, and to angiotensin II, into "modulators" (with normal) and "nonmodulators" (with reduced sodium excretion capacity). An analysis of the hormonal characteristics of non-modulators identified an increased responsiveness of all sodium-modulation systems and not only of the renin-angiotensin-aldosterone system as pointed out by some other authors. The last part of the text is devoted to clinical and therapeutic problems. The behaviour of the daily blood pressure profile in patients with essential hypertension, and then the influence that sodium-modulating systems may have on pressure are discussed. The consequences of a progressive reduction in renal function on the circadian rhythm of arterial pressure are then assessed, and, at the same time, how renal impairment parallels the flattening of the daily pressure rate is observed.

Adult↗

PubMedDate not supplied

[Correlations between circulation levels of natriuretic atrial peptide and urinary excretion of kallikrein in young normotensive and hypertensive subjects].

The relationships between atrial natriuretic peptide (ANP) and the renal sodium-modulating systems have not yet been completely examined. In particular, the relationships between ANP and the kinins system are almost unknown. We thus examined an extremely selected cohort of normotensive (n = 29, mean age 21 +/- 2 years) and hypertensive subjects (n = 51m mean age 21 +/- 2.9 years), both without hypertensive heredity. After 7 days under normal sodium intake (120 mEq of Na+/day), blood samples were taken in the morning on awaking, for radioimmunoassay of plasma levels of aldosterone, ANP and renin activity. Blood was again drawn after one active hour in orthostatism. We also evaluated urinary kallikrein excretion from urine collected over the previous 24 hours. Our results showed higher plasma levels of ANP in young hypertensives than in normotensives (statistical significance p less than 0.0025). Urinary excretion of kallikrein was markedly reduced (p less than 0.001) in the hypertensive group (0.46 +/- 0.3 U/24 h) compared to youths with normal blood pressure (0.79 +/- 0.24 U/24 h), in which a relationship between plasma ANP and urinary kallikrein was not evident; young hypertensives, on the other hand, showed an inverse correlation (r = -0.72; p less than 0.001). Finally, our investigation, aside from establishing the presence of high circulating ANP levels even at the initial phases of hypertension, points out a new possible means of feedback among sodium-modulating systems. The opposite relationship between ANP and urinary kallikrein excretion in young hypertensives could be attributed to reduced activity of the renal kinins system and a compensatory attempt on the part of ANP.

Adult↗

PubMedDate not supplied

[Oral administration of extracted kallikrein to patients with essential arterial hypertension].

Reduced kallikrein excretion has been demonstrated in essential hypertension, suggesting an impairment of the renal kallikrein-kinin system. Therefore, we evaluated the efficacy and safety of oral kallikrein administration (glandular kallikrein derived form porcine pancreas) in 20 essential hypertensives (14 males and 6 females) aged between 34 and 62 years. Kallikrein was administered (150 U.I. three times daily) over a period of eight days, under normal sodium intake (120 mEq of Na+/day). After the kallikrein administration period, urinary kallikrein resulted increased (from 0.9 +/- 0.4 U/24h, normal value greater than 1.2 U/24h, to 1.6 +/- 1 U/24h; p less than 0.05). Blood pressure decreased (systolic: from 154.6 +/- 13.8 mmHg to 140.3 +/- 12.5 mmHg; p less than 0.01--diastolic: from 92.5 +/- 1.5 mmHg to 86 +/- 3.9 mmHg; p less than 0.025), while urinary excretion of sodium (from 96.7 +/- 16 mEq/24h to 119.1 +/- 32.2 mEq/24h; p less than 0.05) and potassium (from 36.7 +/- 11 mEq/24h to 43.5 +/- 12.8 mEq/24h; p less than 0.05) increased after kallikrein administration. We observed only a transient episode of gastric pain. In conclusion, kallikrein administration has a mild hypotensive effect in hypertensive patients, and is generally well tolerated. The antihypertensive action is probably due to the natriuretic effect of kallikrein.

Administration, Oral↗