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Biomedical subjects

C Vons

Publications and source records attributed to C Vons.

At least 55 records · Page 3Linked to original sources
PubMed1996

Comparison of a modified Sugiura procedure with portal systemic shunt for prevention of recurrent variceal bleeding in cirrhosis.

BACKGROUND: There is no agreement on the management of patients with cirrhosis and recurrent variceal bleeding after failure of medical or endoscopic treatments or both. Portal systemic shunts are highly effective in preventing rebleeding but are associated with a high incidence of chronic encephalopathy. This study compared the results of a slightly modified Sugiura procedure (esophageal transection plus esophagogastric devascularization plus splenectomy) with those of nonselective portal systemic shunts in patients with previous variceal bleeding. METHODS: Fifty-four patients were included in this randomized controlled study between January 1984 and April 1989. The major end point was chronic encephalopathy. Secondary end points were recurrent variceal bleeding, survival, ascites, and hepatocellular carcinoma. RESULTS: Twenty-seven patients were assigned to each group. The rate of chronic encephalopathy was significantly (p = 0.002) lower after modified Sugiura procedure than after portal systemic shunt. Recurrent variceal bleeding was more frequent after modified Sugiura procedure than after portal systemic shunt, but the difference is not significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%, respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively, in the portal systemic shunt group (p = 0.044). CONCLUSIONS: These results suggest that the modified Sugiura procedure is better overall than the nonselective portal systemic shunt in the management of patients with cirrhosis and recurrent variceal bleeding. Although the rebleeding rate is higher after the modified Sugiura procedure, this does not seem to affect mortality in these patients.

Carcinoma, Hepatocellular↗
PubMed1996

Primary cultured normal human hepatocytes for hepatitis B virus receptor studies.

BACKGROUND/AIMS: We analyzed the hepatitis B virus envelope specificities (HBs, preS2 and preS1) involved in virus attachment to normal human hepatocytes, and we performed in vitro hepatitis B virus infection experiments without addition of dimethyl sulfoxide and polyethylene glycol, which may affect cell membrane integrity, in order to study further the early steps of the life cycle of the hepatitis B virus. METHODS: Primary normal human hepatocytes were prepared from surgical biopsies by the two-step collagenase perfusion technique, and cultured in a fetal calf serum-free medium supplemented with 10(-6) M dexamethasone. Cell-binding assays, ligand blotting and immunohistochemistry experiments were carried out using our anti-idiotypic (Ab2) antibodies (Ab2s/preS1, Ab2s/preS2 and Ab2s/HBs). RESULTS: Probing primary normal human hepatocytes, the 35-kDa major preS1-binding protein (preS1-BP35) we have previously identified in human hepatoma HepG2 cells was recognized in blotting, whereas both HBs- and preS1-specificities of the hepatitis B virus envelope interacted strongly with normal human hepatocyte cell membrane in cell-binding assays and immunohistochemistry experiments. Hepatitis B virus infectivity studies confirmed a great inter-experimental variability depending on donors and liver perfusion, and demonstrated a great intra-experimental variability depending on the serum-derived hepatitis B virus isolate used for the inoculation. In our culture conditions, only increased detection of the RC and CCC DNA forms of hepatitis B virus in cells and of hepatitis B virus surface antigens in medium was observed 4 to 8 days after exposure of cells to hepatitis B virus. CONCLUSION: These findings support a potential role for preS1-BP35 as a receptor protein for hepatitis B virus. In our hands, limitation(s) in the hepatitis B virus life cycle may occur at some step after virion binding, and likely result from complex regulation of reverse transcription of the RNA and translation of core protein by extrahepatic host factors or/and by the virus itself. However, the normal human hepatocyte model developed here is available for studying the initial steps in hepatitis B virus entry into cells.

Cell Membrane↗
PubMed1996

Long-term hemodynamic effects of portocaval shunt and Sugiura procedure in patients with cirrhosis.

Systemic and splanchnic hemodynamics were studied before and six months after a portal systemic shunt (n = 6) or a Sugiura procedure (n = 9) in 15 patients with cirrhosis and a past history of variceal bleeding. Hepatic blood flow was estimated by hepatic extraction and clearance of continuous indocyanine green infusion. Azygos blood flow was measured with a continuous thermodilution catheter. After portocaval shunt, the cardiac index increased significantly from 4.0 +/- .4 to 5.4 +/- 0.8 l/min m2 (p < 0.05), the hepatic venous pressure gradient and hepatic blood flow were significantly decreased from 21 +/- 3 to 13 +/- 5 mm Hg (p < 0.05) and from 1.20 +/- 0.35 to 0.37 +/- 0.16 l/min (p < 0.05) respectively. The decrease in azygos blood flow was not significant (0.51 +/- 0.31 vs 0.25 +/- 0.33 l/min; p = 0.1). After Sugiura procedure, there was no significant change in cardiac index, hepatic venous pressure gradient, hepatic blood flow or azygos blood flow. This is the first study to show the long-term maintenance of splanchnic and systemic hemodynamics in patients with cirrhosis after Sugiura procedure. The absence of long-term hemodynamic alterations could explain the absence of encephalopathy after this procedure.

Azygos Vein↗
PubMed1996

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics.

Methacholine is frequently used to determine bronchial hyperresponsiveness (BHR) and to generate dose-response curves. These curves are characterized by a threshold (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) = sensitivity), slope (reactivity) and maximal response (plateau). We investigated the efficacy of 12 weeks of treatment with 1,000 microg fluticasone propionate in a double-blind, placebo-controlled study in 33 atopic asthmatics. The outcome measures used were the influence on BHR and the different indices of the methacholine dose-response (MDR) curve. After 2 weeks run-in, baseline lung function data were obtained and a MDR curve was measured with doubling concentrations of the methacholine from 0.03 to 256 mg x mL(-1). MDR curves were repeated after 6 and 12 weeks. A recently developed, sigmoid cumulative Gaussian distribution function was fitted to the data. Although sensitivity was obtained by linear interpolation of two successive log2 concentrations, reactivity, plateau and the effective concentration at 50% of the plateau value (EC50) were obtained as best fit parameters. In the fluticasone group, significant changes occurred after 6 weeks with respect to means of PC20 (an increase of 3.4 doubling doses), plateau value fall in forced expiratory volume in one second (FEV1) (from 58% at randomization to 41% at 6 weeks) and baseline FEV1 (from 3.46 to 3.75 L) in contrast to the placebo group. Stabilization occurred after 12 weeks. Changes for reactivity were less marked, whereas changes in log, EC50 were not significantly different between the groups. We conclude that fluticasone is very effective in decreasing the maximal airway narrowing response and in increasing PC20. However, it is likely that part of this increase is related to the decrease of the plateau of maximal response.

Administration, Topical↗
PubMed1996

[Laparoscopic colectomy: technique and results].

Laparoscopic preparation before colectomy consists of freeing the colon laparoscopically followed by a small elective laparotomy for resection and anastomosis. From January 1993 to October 1994, we performed 86 consecutive planned colectomies including 16 (19%) which had laparoscopic preparation. In 3 of these cases (19%) the procedure was converted to laparotomy due to difficult dissection. The 13 patients with complete laparoscopically prepared colectomy were retained for this study. There were 9 men and 4 women, mean age 54 +/- 14 years (range 34-79). Indications for surgery were benign tumor (n = 4), metastatic cancer (n = 3), diverticulosis (n = 3), volvulus of the pelvic colon (n = 2), and endometriosis involving the sigmoid (n = 1). Operative procedures were: short segmentary colectomy (n = 6), sigmoidectomy (n = 5), right colectomy (n = 2). Surgery duration was 280 +/- 75 minutes (range 150-390). The post-operative period was uneventful in all patients. Bowel activity resumed on the second day after surgery in most patients. Mean hospitalization time was 7.4 +/- 1.4 days (range 5-10 days). Laparoscopically prepared colectomy is a reliable simple method providing good patient comfort post-operatively. This technique should find its place in surgery of the colon.

Adult↗
PubMed1996

[Towards gene therapy in familial hypercholesterolemia].

Familial hypercholesterolemia (FH) is an inherited disease caused by a defect in the gene encoding the Low Density Lipoprotein receptor (LDL-R). The ex vivo hepatic gene therapy which restore the expression of the normal protein in hepatocytes should correct the disease. Improved transduction efficiency and long lasting expression of the transduced gene remain the main goals of gene therapy research. We developed an efficient and reliable method for in vivo transduction of human, mouse and primate primary hepatocytes. A retroviral vector bearing the LDL-R cDNA driven by the liver-type pyruvate kinase promoter allows high and tissue specific expression of the gene in primary hepatocytes. A second vector with a housekeeping promoter corrects the LDL-R deficiency in fibroblasts from a FH patient. Ex vivo preclinical studies in non-human primates will provide new insight in transduced cells biology after reimplantation.

Animals↗
PubMed1995

Efficient retroviral-mediated gene transfer into primary culture of murine and human hepatocytes: expression of the LDL receptor.

The ex vivo approach to hepatic gene therapy involves several steps, which include the isolation and culture of hepatocytes, followed by their transduction with a retrovirus. Subsequently, autologous hepatocytes are transplanted. The number of hepatocytes that can be transduced by retroviruses bearing the therapeutic gene is one of the limiting steps that can impair the success of this strategy. We presently describe an experimental approach that leads to improved transduction efficiency in mouse and human hepatocytes in vitro. By using a recombinant retrovirus bearing the Escherichia coli beta-galactosidase gene, we show that addition of growth factors to the cells, namely human hepatocyte growth factor (HGF), allows marked increase in the transduction efficiency in mouse (up to 80%) and human (40%) hepatocytes. Familial hypercholesterolemia (FH) is due to mutation in the low-density lipoprotein (LDL) receptor gene and results in a deficiency in LDL receptors. Transduction of the human LDL receptor cDNA under the transcriptional control of the L-type pyruvate kinase promoter-activator into mouse hepatocytes led to an elevated tissue-specific expression of the human protein. These results suggest that the ex vivo approach remains a promising alternative for hepatic gene therapy.

Animals↗
PubMed1995

Pressure-volume analysis of the lung with an exponential and linear-exponential model in asthma and COPD. Dutch CNSLD Study Group.

The prevalence of abnormalities in lung elasticity in patients with asthma or chronic obstructive pulmonary disease (COPD) is still unclear. This might be due to uncertainties concerning the method of analysis of quasistatic deflation lung pressure-volume curves. Pressure-volume curves were obtained in 99 patients with moderately severe asthma or COPD. These patients were a subgroup from a Dutch multicentre trial; the entire group was selected on the basis of a moderately lowered % predicted forced expiratory volume in one second (FEV1), and a provocative concentration of histamine producing a 20% decrease in FEV1 (PC20) < 8 mg.mL-1 obtained with the 2 min tidal breathing technique. The curves were fitted with an exponential (E) model and an exponential model which took the linear appearance in the mid vital capacity range into account (linear-exponential (LE)). The linear-exponential model showed a markedly better fit ability, yielding additional parameters, such as the compliance at functional residual capacity (FRC) level as slope of the linear part (b), and the volume at which the linear part changed into the exponential part of the curve (transition volume (Vtr)). Vtr (mean value Vtr/total lung capacity (TLC) = 0.79 (SD 0.07)) showed a close positive linear correlation with obstruction and hyperinflation variables, which might be due to airway closure, already starting at elevated lung volumes. The exponential shape factor K was closely correlated with b and mean values (K = 1.32 (SD 0.05) kPa-1; b = 2.96 (SD 1.16) L,kPa-1) and the relationship with age was comparable with data reported in healthy individuals. The shape factor of the linear-exponential fit showed no correlation with any elasticity related variable. Neither the elastic recoil at 90% TLC, as obtained from the linear-exponential fit, nor its relationship with age were significantly different from healthy individuals. We conclude that, for a more accurate description of the lung pressure-volume curve, a linear-exponential fit is preferable to an exponential model. However, the physiological relevance of the shape parameter (KLE) is still unclear. These results indicate that patients with moderately severe asthma or COPD had, on average, no appreciable loss of elastic lung recoil as compared with healthy individuals.

Adolescent↗
PubMed1995

[Hormone-mediated calcium responses of rat and human hepatocytes. Study of multicellular systems by videomicroscopy].

OBJECTIVES AND METHODS: Activation of hepatocyte hormonal receptors leads to the mobilization of intracellular Ca2+ which is thought to be an elaborate system for encoding hormonal messages. We studied hormone-induced calcium signals in freshly isolated multicellular systems of normal rat and human hepatocytes. Calcium signals were recorded by videomicroscopy after stimulation with noradrenaline, angiotensin II, and vasopressin. RESULTS: Calcium signals were highly organized in multiplets: the different hepatocytes responded to Ca(2+)-mobilizing hormones in a sequentially ordered manner, with a first, a second (doublets) and a third (triplets) responding cells. This pattern was an intrinsic feature of the multicellular systems, and seemed to be a result of a gradual heterogeneity of the sensitivity of the different cells, to the hormones. The stimulation of the same multiplet with two different agonists and the removal of the hormone during cell responses provides some evidence for the major role of hormonal receptors in this heterogeneity. CONCLUSIONS: Hormone responses in multicellular systems of rat and human hepatocytes are highly elaborate. The density of hormonal receptors could be the major determinant of the sequential pattern of Ca2+ responses. Hormonal receptors may be gradually distributed among the different cells of the multiplets in vitro and along the porto-centrilobular axis in situ.

Angiotensin II↗
PubMed1992

Gastroduodenal ulcer perforation in the patient with cirrhosis.

This retrospective study was done to stress the particular features of perforation of the gastroduodenal ulcer in patients with cirrhosis. From 1979 to 1987, 135 patients were operated upon for perforation of the gastroduodenal ulcer: clinical, biologic and roentgenographic data of 22 patients with cirrhosis were compared with 112 patients without cirrhosis. In the 22 patients with cirrhosis, three gastrectomies and 19 simple closures with omental patch were performed. Clinical ascites was present in 16 of 22 patients with cirrhosis. Acute abdominal pain and leukocytosis were less frequent in patients with cirrhosis (p less than 0.05), whereas associated bleeding in the upper part of the gastrointestinal (GI) tract was more frequent (p less than 0.05). In patients with cirrhosis, abnormal plasma creatinine level and associated upper GI bleeding were more frequent in patients with ascites (p less than 0.05); on the other hand, acute abdominal pain and rebound tenderness were less frequent (p less than 0.05). The incidence of pneumoperitoneum was higher in patients with cirrhosis. Surgical treatment was significantly delayed in patients with cirrhosis and ascites. Ulcers were larger in patients with cirrhosis and ascites than without (p less than 0.001). Over-all morbidity and mortality rates in patients with cirrhosis were 77.3 and 50.0 per cent, respectively. Mortality and morbidity were significantly higher in patients with ascites than without (62.5 versus 16.6 and 100 versus zero per cent, respectively), in patients with prothrombin times of less than 50 per cent and with plasma creatinine levels more than 110 micromolars.

Adult↗
PubMed1991

Splanchnic and systemic hemodynamics in cirrhotic patients with refractory ascites. Effect of peritoneovenous shunting.

The splanchnic and systemic hemodynamics of 14 patients with refractory ascites were studied and were compared to those of 15 patients with ascites responding to medical treatment. Among the 14 patients, 10 were grade B and 4 C, according to the Pugh classification. Of the 15 patients, 5 were Pugh B and 10 C. In patients with refractory ascites, free hepatic venous pressure was significantly higher and hepatic venous pressure gradient was significantly lower than in patients with responsive ascites. Hepatic and azygos blood flows were not significantly different between the two groups. Cardiac output was lower in patients with refractory ascites (p less than 0.05) than in those with responsive ascites. In patients with refractory ascites, six months after peritoneovenous shunting, there was a significant reduction of wedged and free hepatic venous pressures and azygos blood flow. Cardiac output increased by 20 % (p less than 0.02). This study shows that hemodynamic alterations in patients with refractory ascites is the consequence of increased intraabdominal pressure due to chronic ascites. Six months after peritoneovenous shunting splanchnic and systemic hemodynamics became similar to those observed in patients without ascites.

Adult↗
PubMed1991

Regulation of fatty-acid metabolism by pancreatic hormones in cultured human hepatocytes.

The effects of pancreatic hormones and cyclic AMP on long-chain fatty-acid metabolism were investigated in human hepatocytes isolated from 12 liver biopsy specimens and cultured for 4 days in an insulin-free medium. Glucagon (10(-6) mol/L) increased endogenous ketone body production by 150%. This resulted from alterations in the partition of long-chain fatty acids from esterification toward oxidation. Glucagon or cyclic AMP enhanced (14C) oleate oxidation (basal = 45.8% +/- 5.0%; glucagon = 66.8% +/- 5.3%; cyclic AMP = 67.6% +/- 5.0% of metabolized oleate) at the expense of oleate esterification. Insulin (10(-7) mol/L) antagonized the glucagon-induced oleate oxidation. After 24 hr in basal culture conditions, the rate of lipogenesis decreased to the same low rate as in glucagon-treated cells. The presence of insulin did not restore a high rate of lipogenesis. These results are the first direct evidence of a control of ketone body production by glucagon in the human liver.

Adult↗
PubMed1991

Total duodenal diversion in patients with previous gastric surgery.

Total duodenal diversion (TDD) was performed in 19 patients with severe post-gastric surgery symptoms. Previous operations were truncal vagotomy associated with pyloroplasty or antrectomy (n = 6), proximal esophagogastrectomy (n = 8) or total gastrectomy (n = 5). Technical adjustments to the standard procedure (truncal vagotomy, antrectomy and gastrojejunal anastomosis using a 70 cm Roux-en-Y loop) were required. There were no postoperative deaths, no anastomotic leakage or anastomotic ulceration. The main symptoms were eliminated, and endoscopic gastritis and esophagitis healed in all patients. Heartburn and bilious vomiting ceased in all patients, but in five out of 14 patients with a residual stomach some symptoms persisted. TDD proved a safe and effective treatment of disabling symptoms following gastric surgery.

Adult↗
PubMed1991

Analysis of morbidity and mortality rates in right hepatectomy with the preoperative APACHE II score.

Morbidity and mortality rates in 70 patients who underwent major liver resection for liver tumors (primary and metastatic) were determined and correlated with the preoperative APACHE II score. Patients were divided into three groups according to their preoperative APACHE II score: low (0 to 3), mid (4 to 7), and high (8 and above). A higher score was closely correlated with increased postoperative morbidity and operative mortality rates. The group with low scores had a postoperative morbidity rate of 34% and a mortality rate of 0%, the group with mid scores had a postoperative morbidity rate of 54% and a mortality rate of 3%, and the group with high scores had a postoperative morbidity rate of 80% and a mortality rate of 20%. Age did not correlate with morbidity. It was therefore postulated that morbidity and mortality rates were related to the combination of points for abnormal physiologic variables and points for chronic health, or APACHE II score minus points for age. As the combination of these points increases the postoperative morbidity and operative mortality rates increase significantly (from 24% in the 0-point group to 69% in the greater than or equal to 3-point group). Also the two deaths occurred in the group with 3 or more points. The preoperative APACHE II score may be used by clinicians to evaluate before surgery the risk of postoperative morbidity and death in elective major liver surgery.

Adult↗
PubMed1990

Elective resection for diverticular disease of the sigmoid colon.

From 1966 to 1987, 177 consecutive patients were operated on electively for diverticular disease of the sigmoid colon. The indications for surgery were: colovesical fistula (n = 12), suspicion of residual abscess (n = 39), two or more previous attacks of acute inflammation (n = 52), chronic symptoms (n = 72) and suspicion of carcinoma (n = 2). An abscess was found at operation in 76 patients (43 per cent) and this was extracolic with local peritonitis in 52 patients (29 per cent). An unsuspected abscess was found in 25 of the 72 patients operated on for chronic symptoms. Colonic resection with primary anastomosis was performed in 95 per cent of the 177 patients and in 94 per cent of those 52 patients with an extracolic abscess. There were no postoperative deaths and no clinical anastomotic leakages. Long-term results were very good in 85 per cent of the 177 patients and in 82 per cent of the 72 patients operated on for chronic symptoms. The results of this series suggest that a one-stage procedure can be safely performed with some technical precautions in most patients operated on electively for diverticular disease, even if an extracolic abscess is found. The good long-term results in patients operated on for chronic symptoms suggest that such symptoms should be taken into account with respect to surgical indications.

Abscess↗
PubMed1990

Comparison of rat liver preservation with Eurocollins and a modified University of Wisconsin solution: transplantation and isolation of hepatocytes for culture.

The efficiency of Eurocollins or modified University of Wisconsin (UW) solution (MUW) in preserving rat livers was compared. After cold storage with one of the solutions, the livers were transplanted or perfused by collagenase for isolation of hepatocytes. Five of the 6 rats receiving a graft preserved with MUW versus none of the 6 rat receiving a graft preserved with Eurocollins solution survived 24 h or more. A significantly greater number of hepatocytes were isolated from livers preserved with MUW than from livers preserved with Eurocollins solution. This suggests a better reperfusion of MUW-preserved livers by collagenase resulting from less endothelial injury. LDH release by cultured hepatocytes, ketone body production and stimulation by glucagon were not significantly different between the two groups. These results confirm the superiority of MUW solution over Eurocollins in preserving liver grafts. They suggest that the advantage of MUW solution results from better protection of vascular endothelium rather than of hepatocytes.

Adenosine↗