Biomedical subjects

L M Blendis

Publications and source records attributed to L M Blendis.

At least 91 records · Page 5Linked to original sources

PubMed1987

Vascular reactivity in reversible experimental obstructive jaundice.

We studied the effect of jaundice on in vitro vascular reactivity to cumulative doses of norepinephrine (NE) by measuring the maximal response (Rmax) and the concentration of NE required to cause a 50% response (ED50) of isolated vascular smooth muscle. For this we prepared helically cut strips of thoracic aorta from bile duct ligated (BDL) rats at 1, 3, 6, 14, and 28 days postligation and compared them with those of nonoperated and sham-operated controls. From 1 to 6 days post-BDL, changes in liver blood chemistry and liver histology indicated cholestasis with necrosis. By 14 days, the tests for liver function and histology indicated a return to normal liver function and histology. In nonoperated controls, mean Rmax increased significantly from 883 +/- 67 mg of tension to 1220 +/- 68 mg of tension (P less than 0.0025) from 0 to 28 days, whereas ED50 remained unchanged. In sham-operated controls and BDL rats, an age-dependent increase in Rmax was also observed. However, in the sham groups, ED50 tended to decrease compared with nonoperated controls, indicating a surgically induced "sensitization" phenomenon of the vascular smooth muscle. In contrast, this was not seen in BDL rats since in these groups, the ED50 remained unchanged and significantly higher than in the sham groups, in both the jaundiced (1-6 days) and nonjaundiced (14-28 days) period. Furthermore, these changes occurred in the absence of any alteration in portal pressure. These changes may be important in understanding the mechanism of hypotension and shock in postoperative patients with obstructive jaundice even after the jaundice has been relieved.

Animals↗

PubMed1987

Role of atrial natriuretic peptide and urinary cGMP in the natriuretic and diuretic response to central hypervolemia in normal human subjects.

The response of plasma atrial natriuretic peptide (ANP) and urinary cGMP excretion to central hypervolemia induced by water immersion was assessed twice in five healthy male subjects, once while immersed in water to the neck for 3 h and again on a control day. Plasma ANP and urinary cGMP were measured by radioimmunoassay. Compared with the control day, overall change in plasma ANP on the immersion day was significant (p less than 0.05). In response to water immersion, plasma ANP increased from a base-line level of 13.2 +/- 3.1 (mean +/- SEM) to 24.2 +/- 5.5 pg/mL by 0.5 h of immersion and was sustained at that level throughout the immersion period. Plasma ANP returned to the base-line level at 1 h postimmersion. Urinary cGMP excretion increased significantly by 1 h of immersion and was sustained at that level throughout water immersion and 1 h postimmersion (p less than 0.05). During water immersion urine flow, urinary sodium and potassium excretion, free water clearance, and osmolar clearance increased while plasma renin activity, serum aldosterone, and blood pressure fell; all changes were significant (p less than 0.05). Creatinine clearance and hematocrit did not show any significant changes. These data suggest that an increase in plasma ANP may contribute to the natriuretic and diuretic response to central hypervolemia, and that the measurement of urinary cGMP may be a valuable marker of ANP biological responsiveness.

Adult↗

PubMed1987

Vascular reactivity in experimental portal hypertension.

Portal hypertension (PHT) is known to be associated with a hyperdynamic circulation, yet the pathogenesis of both remains unclear. Therefore, we have studied serially the relationship between portal pressure and in vitro peripheral vascular responsiveness in an animal model of presinusoidal PHT. In rats with partial portal vein stenosis (PPVS) or sham-operated (SO) controls, we studied contractile responses to cumulative doses of norepinephrine (NE) and to a single dose of 0.8 microM NE of 20-mm helically cut strips of thoracic aorta. At both 2 and 10 days postoperatively, the portal pressures (mean intrasplenic pressure) in PPVS, 14.3 +/- 1.5 mmHg and 14.1 +/- 1.3 mmHg were significantly elevated compared with SO controls, 7.6 +/- 0.6 mmHg (P less than 0.005) and 9.7 +/- 0.5 mmHg (P less than 0.01), respectively. Yet, there was no significant differences between the two groups in the Rmax and ED50 of the contractile response curves to cumulative doses of NE as well as in the fast (phase 1) and slow phase (phase 2) of the contraction to 0.8 microM NE. In contrast, at 21 days, portal pressure in the PPVS rats fell to 11.0 +/- 0.7 mmHg but remained significantly higher than that of the SO controls, 8.2 +/- 1.0 mmHg (P less than 0.05). This occurred in conjunction with a significant decrease in Rmax [698 +/- 87 mg (PPVS) vs. 1148 +/- 92 mg (SO); P less than 0.005] but no significant change in ED50, indicating a decreased sensitivity to NE due to an alteration in alpha-adrenoreceptor function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Transjugular intrahepatic portosystemic shunt: a nonoperative approach to life-threatening variceal bleeding.

Portosystemic venous shunts may be created nonoperatively with a Grüntzig balloon dilatation catheter using the transjugular route. The authors achieved technical success with this shunt in 15 of 20 patients with life-threatening gastrointestinal bleeding from variceal hemorrhage. All patients but one were considered at high risk for surgery because of end-stage liver disease; the exception was a patient in whom two previous operative portosystemic shunts had failed. An average decrease of 5.9 mm Hg in portal vein pressure was measured in 11 patients for whom sequential pressures could be obtained. Two patients survived longer than 12 months without subsequent operative procedures, and the shunt helped temporize in three other patients who later underwent operation. Nine patients with successful shunts died within 30 days of the procedure, comparing favourably with reported operative death rates of 40% to 80% in emergency shunt procedures. Follow-up portal venograms demonstrated shunt patency in six of nine patients, in one after 8 months. Tract patency was determined in four of seven patients on whom autopsy was performed, up to 6 months after the transjugular intrahepatic portosystemic shunt was created.

Adult↗

PubMed1987

Effect of modifying the rate of digestion of a food on the blood glucose, amino acid, and endocrine responses in patients with cirrhosis.

To see whether foods with slower rates of digestion may benefit the metabolic abnormalities seen in cirrhosis, the same food, processed in two different ways, was fed to seven patients with cirrhosis. The breakfast of lentils processed by prolonged heating, to produce more rapid in vitro digestion, resulted in a significantly higher incremental rise in large neutral amino acid levels at 60 min (p less than 0.02) and a tendency for a more rapid rise in total amino acid concentrations by comparison with conventionally cooked lentils with slower in vitro digestion rates. After more rapidly digested lentils, incremental levels of branched-chain amino acids were also higher at 60 min (67 +/- 9, p less than 0.001) despite a greater overall insulin response. Comparable incremental amino acid areas after both meals suggested that the total amount of amino acids absorbed was not influenced by processing. Greater blood glucose, insulin, and gastric inhibitory polypeptide responses were seen after the more processed meal with no significant differences in pancreatic glucagon, entroglucagon, or neurotensin levels. Processing a food to alter the rate of digestion may therefore be used to manipulate amino acid, glucose, and endocrine responses in cirrhosis.

Aged↗

PubMed1986

Effects of peritoneovenous shunting on body composition.

The effect of peritoneovenous shunting on body composition has been studied in 7 cirrhotic patients undergoing a successful shunt and 3 patients in whom the shunt was unsuccessful. In the 7 patients with functioning shunts, their weight had decreased by a mean of 9 kg (p less than 0.001) by 6 wk after initial diuresis, natriuresis, and kaliuresis, and was associated with a decrease in total body potassium (TBK) but not total body nitrogen (TBN). This resulted in a significant decrease in the TBK/TBN ratio from 2.12 +/- 0.74 to 1.66 +/- 0.20 (p less than 0.01). By a mean of 14 mo, in these 7 patients there was a significant increase in mean TBN (from 1.54 +/- 0.10 to 1.84 +/- 0.10, p less than 0.005) associated with an improvement in the mean nitrogen index (from 0.74 +/- 0.04 to 0.88 +/- 0.04, p less than 0.005). These changes were associated with a significant increase in nonalcoholic calories, a nonsignificant increase in protein consumption, and a positive nitrogen balance. After the initial kaliuresis, mean potassium balance remained constantly positive (+22.7 +/- 3.4 mmol/day), serum aldosterone levels normalized, and TBK increased. In contrast, 3 patients with failed peritoneovenous shunting continued to lose weight significantly despite the presence of ascites; TBN and nitrogen index also decreased. In conclusion, body composition studies appear to have confirmed the clinical observation that cirrhotic patients with massive ascites have depleted body protein which is gradually repleted only after successful shunting. In this situation TBK, long used as a measure of lean body mass, is less satisfactory than TBN and nitrogen index. This improvement in body protein appears to be explained by an increased dietary intake associated with improved nitrogen balance, but these changes are not found in patients in whom the shunt failed.

Adult↗

PubMed1986

Renal bilirubin excretion in canine models of jaundice.

Renal handling of bilirubin and its relationship to blood bilirubin level were investigated for up to 2 weeks in two models of jaundiced dogs, namely, chronic bile duct ligation (CBDL), which are mildly icteric, and choledococaval anastomosis (CDCA), which develop deep jaundice. The mean (+/- SD) urinary bilirubin excretion in CBDL plateaued at 30.3 +/- 9.3 mg/24 hr whereas in CDCA it continued to increase above the normal bilirubin production rate (56-84 mg/24 hr) up to 130-150 mg/24 hr. The renal clearance of bilirubin in both models was inversely proportional to serum bilirubin concentration. It was approximately twice as high in the CDCA model, which induced also a moderate diuresis. It is suggested that higher serum bilirubin levels in CDCA dogs is due to the increased production of bilirubin which is not compensated by the renal clearance of bilirubin.

Animals↗

PubMed1986

The LeVeen shunt: mechanisms of action, indications and contraindications to its use.

In summary, PVS has potentially a wide variety of indications. However, it is important to remember, as described in detail in this review, that this technically rather simple procedure may result in major complications. Thus, the clinician considering to employ PVS must be fully cognizant of its limitations so that it is wisely used and not abused.

Ascites↗

PubMed1986

Renal alpha-1-adrenoreceptors in rats with obstructive jaundice.

Alpha 1-Adrenoreceptor affinity constants (KD) and receptor numbers (Bmax) were determined in the kidneys of 3-day-old bile-duct-ligated (BDL) jaundiced rats using 3H-prazosin. The results were compared to 3-day-old pair-fed and nonpair-fed sham-operated rats as well as nonoperated rats as controls. Abdominal surgery (sham and BDL) resulted in a tendency towards a decrease in KD in all three groups of rats compared to nonoperated controls. The Bmax was also increased in the sham-operated groups compared to the nonoperated controls. In contrast, the tendency for a rise in the Bmax in the BDL group was significantly smaller than the rise seen in the two sham-operated groups. In summary, obstructive jaundice suppresses the normal renal alpha 1-adrenoreceptor response to abdominal surgery in the rat.

Animals↗

PubMed1986

The use of peritoneovenous shunting in unravelling the pathogenesis of ascites in cirrhosis.

In a series of studies, peritoneovenous shunting (PVS) has been used to dissect out some of the many factors involved in salt and water retention associated with hepatic ascites. Careful metabolic studies showed that, immediately following PVS, diuresis and natriuresis were associated with a marked rise in cardiac output, renal plasma flow and creatinine clearance, and a significant fall in the elevated serum aldosterone and plasma renin activity to within the normal range. Despite these changes, sodium excretion in these patients remained abnormal when challenged with a high salt diet. In contrast, an immediate increase in water excretion was not associated with a reduction in the elevated antidiuretic hormone (ADH) levels which do, however, decrease to some extent after 2 weeks. Thus, in the long term, these cirrhosis patients will have improved systemic and renal hemodynamics and function and normalization of the renin-aldosterone axis and ADH, yet will still have a "sodium-retaining lesion," the nature of which still needs to be elucidated.

Aldosterone↗

PubMed1985

Modification of pulmonary metabolism of noradrenaline in experimental obstructive jaundice.

The pulmonary metabolism of noradrenaline (NA) was measured in lungs removed from 3 day sham-operated rats and from rats whose bile ducts had been ligated 3 days earlier (BDL). The pulmonary metabolism of NA as measured by a single clearance of the radio-labelled 14C-amine was significantly increased in lungs excised from BDL rats as compared to that measured in the sham-operated rats. The change in metabolism was associated with an alteration in the pulmonary uptake of NA and not with the activities of the enzymes monoamine oxidase types A and B and catechol-O-methyl transferase. Moreover, it was not correlated with rises in the bilirubin or cholesterol concentrations in the serum of the BDL rats and occurred independent of any changes in pulmonary pressure. In a second series of experiments, the evolution of this abnormality over the period of one to six days postoperative was investigated. In the sham-operated rats, there was no significant change in the pulmonary metabolism of NA even by the sixth day. In contrast, there were time-dependent increases from one to six days in these metabolic processes in BDL rats with the highest values being at six days. In contrast, the serum concentrations of bilirubin and cholesterol and activities of the enzymes, alanine transaminase and alkaline phosphatase all rose to their maximum by the fourth day and thereafter declined. Although serum albumin levels fell significantly in BDL rats they were not significantly different from sham-controls. Thus, change in pulmonary metabolism of NA with obstructive jaundice increases with time from one to six days and it not related to the blood chemical changes of biliary obstruction or hepatic synthetic function.

Alanine Transaminase↗

PubMed1985

Serum bilirubin constituents in different experimental models of conjugated hyperbilirubinemia.

The object of the study was to explain the differences in bilirubin level in various experimental jaundice models. The Bil constituents in conjugated hyperbilirubinemic dog models were identified. Total Bil was measured using the Jendrassik and Grof method and direct spectrophotometry. Conjugated and unconjugated Bil were measured using the Weber-Schalm extraction method. Bilirubin covalently bound to albumin was measured indirectly from the total Bil and the non-CBBA fraction. The non-CBBA was estimated either as the sum of the CB and UCB concentrations determined by the W-S method or as the nonprecipitated fraction after deproteinization with ammonium sulfate-saturated ethanol when using DS. The TB, CB, UCB, and CBBA levels were compared in two hyperbilirubinemic dog models: chronic bile duct ligation (CBDL) and internal choledochocaval anastomosis (CDCA). The mean TB in internal CDCA (16.5 +/- 3.67 mg%) was significantly higher than in CBDL (3.4 +/- 1.75 mg%). Most of the serum Bil in these two models was conjugated, 13.4 +/- 2.24 and 3.2 +/- 1.7 mg%, respectively. No CBBA was found in the CBDL or in the partially obstructed internal-CDCA dogs. The TB in an external-CDCA model was essentially similar to the internal-CDCA model. The indirect Bil level in the external-CDCA model was six to seven times higher than the UCB level, and the CBBA level varied between 30 and 80% of the TB. Up to 50% CBBA was found also in patients with intra- or extrahepatic cholestasis. The findings indicate that, unlike the commonly assumed hypothesis, the serum TB level in the CDCA models, which was higher than in the CBCL one, is not due to high UCB levels. Rather, hyperbilirubinemia in the external-CDCA model is due to increased levels of CBBA or, perhaps, to variations in the amount and/or composition of CB entering the blood and cleared by the kidney.

Animals↗

PubMed1985

Obstructive jaundice blunts myocardial contractile response to isoprenaline in the dog: a clue to the susceptibility of jaundiced patients to shock?

Patients with obstructive jaundice are susceptible to postoperative shock. To clarify the mechanism of this phenomenon, we compared the contractile response to isoprenaline of isolated ventricular preparations from three groups of dogs: (a) dogs with chronic bile-duct ligation (CBDL), (b) dogs with choledochocaval anastomosis (CDCA) and (c) sham-operated dogs (SO). Isolated ventricular muscles from CBDL and CDCA dogs showed a depressed contractile response to isoprenaline as compared with SO dogs. Mechanical performance was spared in the CBDL and CDCA dogs. There were no differences in the contractile responses of SO and CBDL dogs, either to ouabain or to changes in the rates of stimulation (force-frequency relationships). These data demonstrate that, in the dog, obstructive jaundice and/or cholaemia are associated with blunted contractile response to beta-adrenoreceptor stimulation in the face of intact basic mechanical performance. Similar inotropic refractoriness to beta-adrenoreceptor stimulation could contribute to the susceptibility to postoperative shock in patients with obstructive jaundice.

Alanine Transaminase↗

PubMed1985

Reversible suppression of the vascular contractile response in rats with obstructive jaundice.

Both patients and experimental animals with obstructive jaundice manifest vascular instability, with animals showing a blunted vascular response to norepinephrine (NE). We sought an intrinsic abnormality of vascular smooth muscle by studying the contractile response of isolated, helically cut aortic strips and intact portal veins to cumulative doses of NE in rats with bile duct ligation (BDL) at different times compared with sham-operated (SO) rats as controls. At 3 days after surgery, the mean cumulative maximal contractile response (Rmax) of the aortic strip of BDL rats (94.3 +/- 9.0 mg/mg tissue) was significantly lower than that of SO controls (145.3 +/- 11.5 mg/mg tissue) (P less than 0.005), associated with a tendency toward decreased sensitivity (half-maximal dose [ED50]) (18.2 +/- 6.75 nmol/L vs. 6.7 +/- 0.6 nmol/L). By 6 days, there was no difference between the two groups. Similarly, by 3 days the mean Rmax for portal vein contraction in BDL rats (694 +/- 72 mg) was significantly lower than that for SO rats (1000 +/- 143 mg). In contrast, mean ED50 of the portal veins of BDL rats (327 +/- 65 nmol/L) was significantly less than that of SO rats (881 +/- 216 nmol/L), indicating greater sensitivity. At 1 and 6 days after surgery there was no significant difference between the two groups. These alterations in the vascular contractile response coincided with the maximum increases in serum bilirubin and liver enzyme levels. In conclusion, this study indicates that the circulatory abnormalities associated with obstructive jaundice are associated, at least in part, with suppression of the vascular contractile response caused by some abnormality of the vascular musculature.

Alanine Transaminase↗

PubMed1984

Slowly digested carbohydrate food improves impaired carbohydrate tolerance in patients with cirrhosis.

To test whether impaired carbohydrate tolerance in cirrhosis could be modified by dietary means ten cirrhotic patients, five of them taking insulin, took as breakfast either lentils or wholemeal bread and cottage cheese containing the same amount of carbohydrate and protein. Lentils resulted in significantly diminished blood glucose, insulin (in those not on insulin) and gastric inhibitory peptide responses. Enteroglucagon and neutrotensin levels were high with lentils, suggesting that absorption of lentil carbohydrate continued into the ileum with perhaps some malabsorption, so confirming the results of earlier studies in vitro. However, breath hydrogen studies on a separate group of eight healthy volunteers indicated that the difference in carbohydrate malabsorption between lentil, and wholemeal bread was insignificant. It is suggested that slowly digested carbohydrate foods, such as leguminous seeds, may minimize carbohydrate intolerance in patients with cirrhosis.

Blood Glucose↗

PubMed1984

The liver in systemic lupus erythematosus.

A 12-month prospective study was undertaken to determine prevalence and causes of clinical and subclinical liver disease in 260 SLE patients and 100 controls, and to look for concordance between 'unexplained' enzyme elevations and SLE activity. Hepatic status was assessed clinically and by tests of liver function with additional tests where indicated. In 76 per cent of patients there were no clinical or laboratory abnormalities. Liver enzyme elevations occurred in 23 per cent. In 15 per cent there were identifiable causes, and in 8 per cent the elevations were 'unexplained', compared with none in the controls. Four patients had persistent 'unexplained' mild transaminase elevations. Liver tissue available from 14 patients revealed no serious lesions. Data on 156 patients with more than four assessments were analysed. In 12 of 15 patients with 'unexplained' transaminase elevations, changes in SGPT levels were concordant with SLE activity. This study suggests that subclinical liver disease is a manifestation of SLE.

Adolescent↗

PubMed1984

Results and hemodynamic changes after interposition mesocaval shunt.

Forty-seven patients have been treated by interposition mesocaval shunting for portal hypertension and variceal bleeding between December 1973 and March 1980. The average age was 55 years. The underlying diseases were alcoholic cirrhosis in 26 patients (56%), macronodular cirrhosis in 11 patients (23%), and other causes in 10 patients (21%). Thirty-five operations (75%) were performed on an emergency basis for patients who continued to bleed after failure of conservative management. In these patients, the early mortality rate was 43%. Overall survival, rebleeding, and postshunt encephalopathy rates are correlated with the preoperative Child's classification. These figures are similar to those reported for end-to-side portocaval shunts. The improvement in postshunt encephalopathy rates as reported by Drapanas is not borne out by our results. Postshunt angiography was performed in 31 patients and shunt patency was confirmed in 28 (90%). In 26 patients, selective studies to determine portal flow patterns were carried out, and in only three patients was there any evidence of hepatopedal flow. In each of these patients, some kinking of the shunt was noted. Mesocaval shunting is a reasonable alternative to end-to-side portocaval shunts and is associated with similar rates of patency, rebleeding, mortality, and late postoperative encephalopathy. A well-constructed, patent mesocaval shunt totally diverts portal flow.

Adult↗

PubMed1983

The effect of liver cytosol on hepatic regeneration and tumor growth.

This report further evaluates the concept that the interaction of factors that originate within the liver can contribute, regulate or even initiate the actual development of hepatic regeneration after liver cell necrosis or partial hepatectomy. The effect of liver cytosol (100,000 g supernatant), both from intact adult rat liver (NLC) and from adult rat liver remnants that had been regenerating for 24 hours after 70% partial hepatectomy (PH) in posthepatectomy liver regeneration in the rat was studied. The specificity of the growth-controlling properties in liver cytosol was determined using tumor cells. The intraperitoneal administration of NLC after PH resulted in approximately 70-80% inhibition of the peak 3H-DNA specific activity seen in controls at 18 and 24 hours post-PH, with a significant increase in DNA synthesis at 31-40 hours post-PH. The intraperitoneal administration of RLC after PH, augmented the hepatic regenerative response normally produced. Autoradiographic determination of hepatic nuclear labeling confirmed the inhibitory and stimulatory properties of NLC and RLC respectively. Syngeneic NLC or RLC at six and 24 days after subcutaneous tumor inoculation resulted in significant inhibition of tumor growth for both a methylcholanthrene-induced bladder carcinoma (FBCa) and an HTC-hepatoma. The retardation of FBCa growth could be enhanced by administering NLC or RLC every three or seven days. Syngeneic and xenogeneic liver cytosol resulted in dose-dependent inhibition of P815 mastocytoma cell proliferation in vitro. It is apparent from these studies that both stimulatory and inhibitory factors can be extracted from liver tissue that not only influence liver cell regeneration, but also affect tumor growth. Further isolation and characterization of these factors may lead to an understanding of more fundamental problems such as the control of normal and malignant cell growth.

Animals↗