Low doses of calcium-heparin in liver cirrhosis.
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Biomedical subjects
Publications and source records attributed to C Cordova.
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Intravenous lidocaine was infused at 0.82 ml/min in a concentration of 1.2 mg/ml (2.3 mg/kg) for 120 min in awake chair-restrained baboons (Papio anubis), and measurements of esophageal peristalsis and LES pressure were compared before and after lidocaine or control infusions. Lidocaine produced a progressive and significant (P less than 0.05) decrease in amplitude in the peristaltic wave in the smooth muscle portion of the distal esophagus during the 120-min infusion. Lower esophageal sphincter pressure was similarly significantly lower than control after the infusion of lidocaine (P less than 0.05). Velocity and duration of the peristaltic wave were unchanged during the infusion. The decreased amplitude occurred during therapeutic and stable serum concentrations of lidocaine. It did not appear that the inhibitory effect of lidocaine was due to an induction of prostaglandin synthesis, because pretreatment of animals with indomethacin did not change the inhibitory effect of lidocaine, and serum metabolites of prostacyclin decreased during the infusion. Furthermore, the inhibitory effect of lidocaine was not topical. The response to the muscarinic agonist, bethanechol was similar in lidocaine-treated animals and control animals. The preservation of a bethanechol response after lidocaine inhibition of LES pressure and distal esophageal amplitude suggests that lidocaine acts proximal to the muscarinic receptor in the esophageal body and smooth muscle portion of the lower esophageal sphincter. This study suggests that lidocaine produces an inhibitory effect on the peristaltic wave and lower esophageal sphincter pressure that is similar to inhibitory effects described after anticholinergic agents and calcium channel blocking drugs, but intravenous lidocaine infusion requires a longer period of time to produce inhibition of muscle function.
Thrombin-induced platelet malondialdehyde (MDA) formation and plasma malondialdehyde-like material (MDA-LM) were evaluated in 12 healthy subjects before and after 1 and 7 days from aspirin (1 g) ingestion. 24 hr after aspirin administration, platelet MDA was almost abolished while MDA-LM showed a 23% decrease. Platelet MDA and plasma MDA-LM returned to baseline values 7 days after aspirin ingestion. These data suggest that platelet cyclooxygenase pathway affects only in part plasma MDA-LM. The evaluation of plasma MDA-LM before and after aspirin could be useful for evaluating in vivo platelet cyclooxygenase activation.
In contrast to convalescent hepatitis B patients, who exhibit the ability to elicit a specific immune response to HBsAg, patients with chronic hepatitis B virus (HBV) infection are markedly hyporesponsive to HBsAg and show a decrease in the normal ratio of OKT4-positive (helper/inducer) to OKT8-positive (suppressor/cytotoxic) lymphocytes. In this study the role of OKT4-positive and OKT8-positive cells on cellular immune response to HBsAg was evaluated in patients with chronic HBV infection and the ability of such patients to develop antigen-specific suppressor lymphocytes after in vitro sensitization to HBsAg. Elimination of OKT8-positive cells markedly improved the in vitro lymphocyte proliferative response to HBsAg without altering the reactivity of cells from the same donor to PPD or Candida. In contrast, the degree of responsiveness to HBsAg was not affected by the depletion of OKT4-positive cells. In vitro co-culture experiments, performed in the seven chronically HBV-infected patients who showed a proliferative response when their PBM were cultured with purified HBsAg or PPD, have demonstrated that lymphocytes from chronic HBV carriers, stimulated with HBsAg, inhibit the response of autologous PBM to HBsAg but not to the unrelated antigen PPD.
Platelet aggregation (PA) and plasma beta-thromboglobulin (beta TG) values were evaluated in 40 patients affected by chronic airway obstruction (CAO). PA and beta TG were significantly higher than those observed in normal subjects. Beta TG plasma levels were inversely correlated with PaO2, directly with PaCO2 and [H+]. Two h after a venesection of 300-400 ml, no change of beta TG and PA was seen in 10 healthy subjects, while a significant increase of beta TG and PA values was observed in 29 patients. The investigation suggests that in patients with CAO in vivo platelet activation is present.
The behaviour of plasma malondialdehyde-like material (MDA-LM) was evaluated in 13 healthy subjects by a single-blind study that consisted of placebo (30 days), vitamin E treatment (300 mg/day) (30 days) and placebo (30 days). The study demonstrated that MDA-LM did not change during placebo treatment while it significantly decreased after vitamin E administration.
Apolipoproteins A-I, A-II and B were evaluated in 18 chronic active hepatitis and 27 liver cirrhotic patients. The latter were also divided into compensated and decompensated subgroups. Significantly low values of apolipoproteins A-II and B were seen in chronic active hepatitis and liver cirrhotic patients, while apolipoprotein A-I was decreased in liver cirrhotic patients only. Chronic active hepatitis had higher apolipoprotein values than liver cirrhosis and in the latter one decompensated subgroup showed lower apolipoprotein levels than the compensated one. Apolipoproteins A-I, A-II and B correlated also well with prothrombin activity (Normotest) in liver cirrhotic patients, especially the apolipoprotein A-II values. This study suggests that serum values of apolipoproteins are affected by the type of liver damage and that their decrease could be partly due to impaired liver synthesis.
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Prekallikrein (Prekk), antithrombin III (ATIII), plasminogen and alpha 2-antiplasmin were evaluated in chronic active hepatitis and in liver cirrhotic patients and correlated with Normotest. Prekk, ATII and plasminogen were significantly decreased in chronic active hepatitis as well as in liver cirrhosis. Alpha 2-antiplasmin levels in chronic active hepatitis patients did not differ from controls; liver cirrhotic patients, on the contrary, showed significantly low values of alpha 2-antiplasmin, Prekk, ATIII and plasminogen were significantly correlated with Normotest in both groups, but when cirrhotic patients were divided into the compensated and decompensated state only Prekk was correlated with Normotest in the decompensated state. The investigation seems to suggest that Prekk could be a reliable index for protein liver failure.
Complexes between HBsAg and IgM have recently been described in the sera of HBsAg carriers. A solid phase RIA for HBsAg/IgM complexes has been described. Fifteen patients with acute viral hepatitis type B, and 52 HBsAg chronic carriers were studied. Testing of serial sera in acute hepatitis patients revealed that HBsAg/IgM complexes disappeared (preceding HBsAg negativization and usually at the same time as seroconversion from "e" to "anti-e") with 4 weeks in all but one patient who became a chronic HBsAg carrier. In addition, HBsAg/IgM complexes were found in 48% of HBsAg chronic carriers, in 69% of CPH patients, but in only 20% of healthy carriers (p less than 0.005). Although complexes were detectable in 93% HBeAg positive chronic carriers, they were also frequently found in anti-HBe positive patients, but never in e/anti-e negative patients (p less than 0.001). HBsAg/IgM complexes seem to be of important prognostic and diagnostic value in acute and chronic hepatitis B.
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In recent years, we have carried out several studies on brainstem mechanisms associated with pain modulation. Of particular interest has been the region of the nucleus tractus solitarius (NTS) at the level of the area postrema (AP) in the dorsomedial medulla. This region has been found to be rich in opiate receptors and to be involved in pain modulation. Having previously demonstrated the EEG and behavioral effects of systemic administration of morphine, we initiated the present study to determine whether microinjection of naloxone directly into the region of the NTS will modify any or all of the EEG effects induced by subsequent systemic administration of morphine. Our results have shown that microinjections of naloxone into the region of the NTS block the cortical EEG synchronizing effects of systemically administered morphine. These results indicate that morphine-induced cortical EEG synchronization is mediated through the region of the NTS. This region may, therefore, comprise part of an opiate sensitive system which can influence cortical EEG activity.
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In these studies, power spectral analysis techniques were utilized to quantify changes in the cortical and hippocampal EEG obtained from rats reared on either an 8% or 25% casein diet as they mature from 14 to 22 days of age. Analyses of the power spectral data obtained from the frontal cortex of rats reared on the 25% casein diet during this preweaning period (14-22 days) indicated increases in the power in the 0.5-3.5 c/sec frequency band primarily during slow-wave sleep. Prenatal protein malnutrition (8% casein diet) significantly reduced the low frequency power content in the cortical EEG obtained during slow-wave sleep at 18 and 22 days of age. Analyses of power spectral data obtained from the hippocampal EEG during REM sleep also revealed developmental and diet-related differences. The frequency at which the peak power occurs in the theta band (4-11 c/sec) was found to increase normally in a linear fashion from 14 to 22 days of age (from 4.4 to 5.5 c/sec) in rats reared on the 25% casein diet. In addition, power in the 4-7 c/sec band significantly increased during this preweaning period. Prenatal protein malnutrition significantly slowed the development of theta frequency and produced higher values of power in the component of theta rhythm. Finally, vigilance profiles showed that rats normally progress from 14 days of age when REM sleep dominates their vigilance profile, to 22 days of age when they spend significantly more time in slow-wave sleep. Prenatal protein malnutrition retards this normal developmental sequence by significantly reducing the REM sleep time at 14 and 18 days of age and increasing the time spend in aroused waking at both these ages. However, at the time of weaning, i.e., at 22 days of age, these differences in sleep-waking behavior were no longer observed to be significant.
The relationship between T cell subset, as defined by monoclonal antibodies, and suppressor cell function, using a short lived suppressor cell assay, was studied in 38 chronic hepatitis B virus (HBV) carriers and in 32 patients with HBsAg negative chronic active hepatitis (CAH). Patients with HBV chronic infection showed an absolute reduction in the OKT4 positive subset and a significantly decreased OKT4/OKT8 ratio, as compared with healthy controls. Patients with anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) positive CAH with or without antibodies to HBV antigens, namely anti-HBs and anti-HBc, demonstrated a significant reduction in cytotoxic/suppressor T cells and an increased helper/suppressor ratio. A negative correlation between suppressor index (SI) and OKT4/OKT8 ratio (P less than 0.01), and a positive correlation between SI and OKT8 positive cells absolute number (P less than 0.01) were also observed.
The significance of the HBeAg/anti-HBe system and other HBV markers in the evolution of HBsAg-positive liver cirrhosis to primary hepato-cellular carcinoma (PHC) was studied by following up 70 cirrhotic patients from February 1978 to February 1981. Eight out of 19 (42.1%) patients with HBsAg positive liver cirrhosis developed PHC. On the other hand, only 7.8% of the patients with HBsAg-negative liver cirrhosis developed PHC. In the HBsAg-positive group only the patients who had already seroconverted to anti-HBe (7 out of 11) or were negative for both HBeAg and anti-HBe (1 out of 3) at the time of first observation and showed a histological picture of inactive cirrhosis, developed PHC during the follow-up period. No HBeAg-positive cirrhosis showed such an evolution. The absence of HBeAg in the sera of patients who developed PHC suggests that active HBV replication becomes increasingly defective during the course of malignant transformation.
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