Efficacy and safety of combination therapy with interferon-alpha2b and ribavirin for chronic hepatitis C in HIV-infected patients.

OBJECTIVES: To evaluate the efficacy and safety of a combination therapy of interferon-alpha2b (IFN) and ribavirin for the treatment of chronic hepatitis C in HIV-seropositive patients. DESIGN: Open prospective trial. METHODS: Twenty patients co-infected with hepatitis C virus (HCV) and HIV, with a mean CD4 cell count of 350 +/- 153 x 10(6)/l were treated with IFN (3 MU three times per week) in combination with ribavirin (500 mg or 600 mg twice a day) for 6 months. Tolerance and efficacy were monitored at weeks 12 (month 3) and 24 (month 6). The primary endpoint was a complete virological response, as defined by the lack of detectable HCV RNA in serum. RESULTS: Baseline values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 121 +/- 72 IU/l and 75 +/- 67 IU/l, respectively. The total Knodell score was 10.4 +/- 2.4, with nine patients showing histological evidence of active cirrhosis (45%). All patients exhibited circulating HCV RNA. The treatment was well tolerated, with no impact on the course of HIV infection. After 6 months of combination therapy with IFN and ribavirin, 10 patients (50%) exhibited no further detectable HCV RNA viraemia, seven of whom achieved undetectable viraemia at month 3. Levels of ALT and AST decreased after 6 months of treatment from a mean of 121 +/- 72 to 51 +/- 40 IU/l and from a mean of 129 +/- 58 IU/l to 68 +/- 61 IU/l, respectively (P < 0.0002 and P < 0.0001). CONCLUSION: Our results indicate that combination therapy with IFN and ribavirin is effective in 50% of cases in clearing serum HCV RNA and may thus provide effective means of therapy in HIV-HCV-coinfected patients as initial treatment or in patients who have previously failed IFN monotherapy.

Clinical pharmacokinetics of lansoprazole.

Lansoprazole, a benzimidazole derivative with antisecretory and antiulcer activities, inhibits the acid pump activity at the final stage of the enzyme process and therefore reduces the acid secretion of parietal cells. Lansoprazole is converted to active metabolites in the acid environment of these cells. It is rapidly absorbed from a gastric acid-resistant formulation and is approximately 97% bound in human plasma. Single dose pharmacokinetics of lansoprazole appear to be linear over the range from 15 to 60mg. Food and time of dose influence absorption after single doses, but do not modify the antisecretory effect of multiple doses. Lansoprazole is extensively metabolised following oral administration into sulphone and 5-hydroxylated metabolites by the cytochrome P450 enzymes CYP3A4 and CYP2C18. Two other metabolites have been identified in plasma: sulphide and hydroxylated sulphone. Mean plasma elimination half-life (t1/2) is between 1.3 and 2.1 hours in healthy volunteers. 15 to 23% of the total dose is found in urine as free and conjugated hydroxylated metabolites, while unchanged lansoprazole is not detected. The pharmacokinetic profile of the drug is not modified by multiple administration. In healthy elderly volunteers, area under the plasma concentration-time curve (AUC) and t1/2 are significantly greater after single administration occurs to the same extent as in young volunteers. Renal failure has no influence on the pharmacokinetics of lansoprazole, but severe hepatic failure causes a significant decrease in clearance and an increase in the AUC and t1/2 of lansoprazole. This is accompanied by modifications in the AUC of metabolites, but severe hepatic failure has minimal effect on accumulation of the drug after multiple administration. The pharmacokinetics of lansoprazole in patients with acid-related disorders do not differ from those in healthy volunteers. Studies of interactions of lansoprazole with warfarin, prednisone, theophylline, phenazone (antipyrine), diazepam, phenytoin and oral contraceptives suggest minimal risk of any clinically significant interaction.

[Radiological and endoscopic study of the esophagus in 33 cases of generalized scleroderma]. / Studio radiologico ed endoscopico dell'esofago in 33 casi di sclerodermia generalizzata

The radiological and endoscopic picture of the oesophagus was investigated in 33 patients with generalised sclerodermia. Signs of involvement were noted in 26 subjects, whereas symptoms of such involvement had been observed in 13 only. Screening for oesophageal sclerodermia sites requires accurate assessment of oesophageal kinetics. Fibroscopic examination gives equally reliable evidence of involvement in the form of two distinctive signs: absence of peristaltic contractions in the lower half of the oesophagus and persistence of a "pool of water" in the organ for over 30 secs following injection of a few cc of water in the lying patient. Endoscopy frequently reveals concomitant peptic oesophagitis (10 cases). This is invisible radiologically. Endoscopy also permits accurate appraisal of the lesions associated with peptic stenosis. Fibroscopic examination of the oesophagus, in fact, could well be made a feature of the evaluation of all patients with actual or suspected generalised sclerodermia, on account of its aid to diagnosis and the early notice it gives of oesophageal complications.

[Human pentastomiasis: clinical, radiological and x-ray computed tomographic study of a case]. / Pentastomose humaine: étude clinique, radiologique et tomodensitométrique d'un cas.

A case of abdominal pentastomiasis in a 38-year-old Congolese man is reported. This parasitic disease has been described in Central Africa and South East Asia. The patient presented with unexplained permanent abdominal pain. The peritoneal and hepatic localisations of the parasite were recognized on plain abdominal film and documented by ultrasonography and CT scan studies. At laparoscopy multiples adherences were found, in spite of the fact that no previous abdominal surgery had been performed. These findings suggest a possible correlation between the clinical manifestations and the anatomic lesions in this disease which is usually considered to be asymptomatic.

[Collagenous colitis: a new case of exudative enteropathy]. / La colite collagène: une nouvelle cause d'entéropathie exsudative.

Collagenous colitis with intestinal protein loss was discovered in a sixty-six year-old female who presented with recurrent and prolonged diarrhea associated with hypoprotidemia, hypoalbuminemia, and increased clearance of alpha-1-antitrypsin. Histologic lesions of collagenous colitis were found during each episode of diarrhea. Biological and histological examinations were normal during the remission phases. Intestinal protein loss appeared to be due to collagenous colitis because of the parallel course of the clinical, biological and histological signs, and because no other cause had been discovered. The possibility of protein exudation, probably secondary to the extent of the epithelial detachment, could be an additional argument for the inflammatory etiology of collagenous colitis.

[Esophagitis in progressive systemic scleroderma. Prevalence and risk factors in forty-six patients]. / L'oesophagite au cours de la sclérodermie systémique. Prévalence et facteurs de survenue chez 46 patients.

Forty-six patients with progressive systemic sclerosis (37 women and 9 men) were successively evaluated by endoscopy, manometry, and esophageal pH monitoring. Fourteen patients (30.4 percent) had erosive esophagitis. Twenty-four patients were symptomatic; nineteen patients complained of dysplagia. Erosive esophagitis was significantly more frequent in symptomatic patients than in asymptomatic patients (50.0 percent vs 9 percent, P less than 0.01) and especially in patients complaining of dysphagia (57.9 percent vs 11.1 percent, P less than 0.01). Erosive esophagitis was not correlated with symptoms of gastroesophageal reflux. Abnormal esophageal motility was found in 34 patients (73.9 percent). Occurrence of erosive esophagitis was not linked with esophageal dysmotility. In patients with erosive esophagitis lower esophageal sphincter pressures were significantly lower than those in patients without erosive esophagitis. Twenty-four hr-pH monitoring showed pathological gastroesophageal reflux in 20 patients (43.5 percent). Erosive esophagitis was more frequent in patients with pathological gastroesophageal reflux than in patients with normal gastroesophageal reflux (50.0 percent vs 15.4 percent, P less than 0.02) especially in patients with pathological supine nighttime gastroesophageal reflux (61.5 percent vs 18.2 percent, P less than 0.01). Our data suggest that symptoms, dysphagia, diminished lower esophageal sphincter pressures, and pathologic nighttime gastroesophageal reflux are reliable predictors of the presence of erosive esophagitis in patients with progressive systemic sclerosis.

[Anguilluliasis hyperinfection in a patient receiving corticosteroids: hepatic and biliary involvement]. / Hyperinfestation à anguillules chez un patient sous corticothérapie: révélation hépato-biliaire.

A case of strongyloidiasis hyperinfection is reported in a 59 year-old man who presented cortico-dependent bronchial asthma. Several points of this case are uncommon: the long latency period (40 years), simultaneous aggravation of asthma requiring increasing doses of corticosteroids, and above all, liver and biliary tract involvement. Disseminated strongyloidiasis is widely believed to be precipitated by impairment of cell-mediated immunity. It is therefore unlikely that infestation of the liver and the biliary tract can interfere with hepatic function.

[Changes in levels of blood coagulation inhibitors in cirrhosis. Prospective study in 33 patients]. / Modifications des taux des inhibiteurs plasmatiques de la coagulation au cours de la cirrhose. Etude prospective chez 33 malades.

The variations of the main plasma inhibitors of coagulation were prospectively studied in 33 cirrhotic patients, of which 9 presented with hepatocellular carcinoma, 5 of those associated with portal vein thrombosis. The mean prothrombin index was 49 +/- 16 percent. All plasma values of inhibitors were diminished, but to varied degrees: the mean values were: protein C (PC): 33 +/- 15 percent, antithrombin III (AT III): 50 +/- 23 percent, total protein S (PST): 67 +/- 20 percent. The more severe the cirrhosis, the more decreased were the values of antithrombin II and protein C. According to Child classes A, B, and C, antithrombin III plasma values were 64 +/- 20, 50 +/- 21 and 26 +/- 11 percent and protein C values were 43 +/- 16, 32 +/- 8 and 19 +/- 9 percent, respectively. We were able to define expected plasma values of the plasma inhibitors as a function of coagulation factors during cirrhosis; AT III (percent) = 1.16 x factor II (percent) - 7.85; PC (percent) = 0.49 x AT III (percent) + 8.96; PC (percent) = 0.55 x factor II (percent) + 5.55; PST (percent) = 0.76 x factor II (percent) + 28.74. However those equations cannot be extrapolated to patients presenting with cirrhosis complicated with portal thrombosis.

["Dysphagia lusoria". Physiopathological discussion apropos of a clinical case]. / "Dysphagia lusoria". Discussion physio-pathologique à propos d'un cas clinique.

We report the observation of a patient suffering from dysphagia lusoria, a dysphagia caused by an anomalous form of the right subclavian artery. The diagnosis was confirmed by aortic arch angiography and cine-oesophagogram. Oesophageal manometric study revealed segmental hypoperistalsis and anti-peristalsis. Dysphagia disappeared with cisapride. This observation suggests that dysphagia lusoria is caused by oesophageal motility disorders and not by vascular compression.

[Prospective comparison of ultrasound endoscopy and computed tomography in the assessment of locoregional invasiveness of malignant ampullar and pancreatic tumors verified surgically]. / Comparaison prospective de l'échoendoscopie et de la tomodensitométrie dans le bilan d'extension loco-régionale de tumeurs malignes ampullaires et pancréatiques vérifiées chirurgicalement.

OBJECTIVE: To compare, in a prospective study, results of endoscopic ultrasonography and computed tomography in staging of pancreatic and ampullary carcinoma tumours, assessed surgically. METHOD: From January 1990 to May 1993, 37 patients with pancreatic tumours had per-operative endoscopic ultrasonography and computed tomography. All patients underwent surgery and surgical and histological staging were performed. RESULTS: All the tumours were visualized by endoscopic ultrasonography, and 92% were correctly localized; 63% of the tumours were visualized by computed tomography. In lymph node involvement diagnosis (23 patients), endoscopic ultrasonography. In major portal vessel involvement diagnosis (14 patients), endoscopic ultrasonography sensitivity and specificity were respectively 71.4% and 95.65%, and 21.4% and 100% for computed tomography. In a vessel-by-vessel analysis, endoscopic ultrasonography was superior to computed tomography for veinous involvement diagnosis (sensitivity: 68.4% vs 26.3%), and the results were similar for arterial involvement diagnosis (sensitivity: 55.5% vs 66.6%). CONCLUSION: Endoscopic ultrasonography is more accurate than computed tomography in detection of metastatic lymph nodes and portal involvement, and their results are similar in detection of arterial involvement.

[A new hereditary cause of portal vein thrombosis: the abnormal resistance to activated protein C by the Arg 506-->Gln mutation of the gene of factor V]. / Une nouvelle cause héréditaire de thrombose portale: la résistance anormale à la protéine C activée par mutation Arg506-->Gln du gène du facteur V.

We report 2 cases of portal vein thrombosis associated with a single point mutation in the factor V gene that replaces arginine in residue 506 with glutamine. This mutation induces abnormal resistance to anticoagulant activity of activated protein C and increases the risk of deep vein thrombosis. Both patients had a personal and familial history of deep vein thrombosis. Intraabdominal neoplasia or infection, myeloproliferative disorder, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria and coagulation inhibitor deficiency (antithrombin, proteins C and S) were excluded by exhaustive investigation. However, an abnormal resistance to activated protein C was found, and DNA analysis showed the factor V Arg506 to Gln mutation in both cases. Anticoagulant treatment was begun. A study of family history made in one case, showed the same genetic disease in one of the relatives. Resistance to activated protein C with factor V gene mutation should be investigated in patients with portal vein thrombosis. A study of family history, and anticoagulant treatment are justified for symptomatic patients.

[Spontaneous pneumoperitoneum in scleroderma]. / Pneumopéritoine spontané au cours de la sclérodermie.

A spontaneous and asymptomatic pneumoperitoneum was observed in two women presenting with pseudoileus resulting from severe gastrointestinal involvement in progressive systemic sclerosis. In the first case, pneumoperitoneum was associated with pneumatosis cystoides intestinalis and remained unchanged during 3 years. As obstruction resisted to medical management, surgery was performed; however at laparotomy neither perforation nor obstruction of the bowel could be found; the patient died during the postoperative course. In the second case, pneumoperitoneum disappeared after medical management of low-grade intestinal ileus but the patient died 6 months later because of cardiac failure. Autopsy revealed major distention of the bowel but failed to show any signs of perforation. These findings show that, in progressive systemic sclerosis, pneumoperitoneum can occur in the absence of digestive perforation and that surgery is not required. However this complication seems to carry a very poor prognosis.

[Comparison of lansoprazole (30 mg) and omeprazole (20 mg) in the treatment of duodenal ulcer. A multicenter double-blind comparative trial]. / Comparaison du lansoprazole (30 mg) et de l'oméprazole (20 mg) dans le traitement de l'ulcère duodénal. Essai thérapeutique multicentrique comparatif en double aveugle.

The efficacy of lansoprazole (30 mg/d) and omeprazole (20 mg/d) has been assessed in active duodenal ulcer disease in 144 patients included in a multicentric, randomized, double-blind trial. After two weeks, the healing rates were 74% and 58% in the lansoprazole and omeprazole groups, respectively (P = 0.049). After 4 weeks, the healing rates were 94% in each group (NS). The delay to pain relief was 2 days for lansoprazole and 3 days for omeprazole (NS). Minor side effects occurred in 12% of the lansoprazole treated patients and in 13% of the omeprazole treated patients. No severe adverse events were reported. A slight increase in serum gastrin level was observed, similar in both groups (+35 UI/L and +19 UI/L for lansoprazole and omeprazole respectively). This study confirms previous results concerning the efficacy of both treatments in duodenal ulcer disease. The statistical difference observed for healing rates after 2 weeks could correspond to a faster efficacy for lansoprazole (30 mg) than for omeprazole (20 mg).

[Epidemiologic relations between arteriopathy of the lower extremities and chronic gastroduodenal ulcer]. / Relations épidémiologiques entre artériopathie des membres inférieurs et ulcère gastro-duodénal chronique.

The authors report the results of a study of 3 565 consecutive patients over 30 years of age, of French nationality living in the Paris region, hospitalised over a 5 year period in a Department of internal medicine and vascular pathology. The incidence of gastroduodenal ulcer was compared in each sex in 10 year age groups in 764 patients with arterial disease and 2 801 patients without arterial disease. The incidence of ulcers was higher in patients with occlusive arterial disease in men in the 50 to 59 year age group (20,4 p. 100 compared to 9 p. 100, p less than 0,01), and in the 60 to 69 year age group (20,3 p. 100 compared to 9,8 p. 100, p less than 0,001), and after 70 years of age in females (12,8 p. 100 compared to 4 p. 100, p less than 0,01). The overall incidence in all patients with arterial disease (16,7 p. 100 of all 591 males, and 12,1 p. 100 of all females) was higher than in a corresponding control group (9,7 p. 100, p less than 0,0001, and 4,8 p. 100, p less than 0,001 respectively). These results only concern chronic ulcers. There was no difference in the incidence of acute ulcers.

[Maintenance therapy of ulcer disease. Comparative multicenter study of sucralfate, cimetidine and a placebo]. / Traitement d'entretien de la maladie ulcéreuse. Etude multicentrique comparative du sucralfate, de la cimétidine et d'un placebo.

Relapse rates were studied in one hundred patients in a multicentric, randomized trial during and after maintenance therapy comparing sucralfate, cimetidine and placebo. These patients were previously treated by cimetidine for peptic ulcer and were considered cured after endoscopic examination. Outpatients were randomly assigned to a 6 month maintenance treatment with either cimetidine (600 mg daily), sucralfate (300 mg daily) or a placebo. All patients underwent endoscopic evaluation after 3 and 6 months of therapy. A clinical évaluation was performed 6 months after all treatment had ceased. Clinical and endoscopic results proved the significant superiority of both sucralfate and cimetidine over the placebo. Remission rates with sucralfate were respectively 80,4 p. 100 after 6 months and 68,5 p. 100 after 12 months. These results were slightly superior to those observed with cimetidine (69,3 p. 100 and 61,3 p. 100). However, this difference is not statistically significant. Results for the placebo group were 47,9 p. 100 and 37,7 p. 100. Sucralfate is an effective medication in preventing the recurrence of peptic ulcer. Its pharmacological action, its few side effects and its effectiveness seem to make this medication very interesting in treating the ulcerous disease.

[Hemorrhagic gastroduodenal ulcer: contribution of new medical treatments]. / Ulcéres gastro-duodénaux hémorragiques. Apport des nouvelles thérapeutiques médicales.

The mortality due to upper gastrointestinal haemorrhage from ulcers has remained unchanged for several (estimated to be 6%), despite progress in surgery and intensive care, new drug treatments and, more recently, the development of endoscopic treatments. Drug treatments, although frequently used in practice always have a controversial haemostatic efficacy. Antacids have a haemostatic efficacy, but only at doses responsible for side effects. Antisecretory drugs appear to be systematically prescribed, if only to commence treatment of the peptic ulcer disease. However, their haemostatic efficacy has not been established except in the sub-group of gastric ulcers, especially in elderly subjects. According to a recent study, prostaglandins are as active as antacids. Since 1975, endoscopy is the support for haemostatic treatments, most of which are still under evaluation. Therapeutic injections, a simple and inexpensive technique, certainly represents one of the most promising methods. Different authors have proposed different solutions for injection (absolute alcohol, aetoxysclerol, adrenaline, thrombin...) with comparable haemostatic efficacy. Laser photocoagulation (Argon and Nd-YAG) is an expensive and impractical technique and a number of randomised studies indicate that the initial enthusiasm for this technique is not justified. Monopolar electrocoagulation does not constitute a real progress in contrast with bipolar electrocoagulation which significantly decreases the frequency of recurrent haemorrhages. Lastly, the efficacy of the heater probe remains to be evaluated in the light of promising studies, particularly those of Johnson in 1985. At the present time, these endoscopic haemostatic treatment should be reserved to high surgical risk patients (elderly or debilitated subjects).(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemorrhagic gastro-duodenal ulcers. In which cases should emergency surgery be performed?]. / Ulcères gastro-duodénaux hémorragiques. Lesquels faut-il opérer en urgence?

From January 1983 to December 1987, 127 patients with bleeding peptic ulcer were admitted to hospital. The mean age of the 85 males was 57 years and 72 years for 42 females. All but four of the patients were managed medically after emergency endoscopy. Twenty-seven patients required surgical operations (21.2%): seven for cataclysmic haemorrhage, eight for persistent haemorrhage, twelve for recurrent bleeding. An analysis of factors leading to the necessity of surgical haemostasis was undertaken by considering the clinical status, endoscopic findings and laboratory results. The size of the ulcer (greater than 2 cm) was the most significant parameter (less than 0.01). Five other criteria (rectal bleeding) shock, endoscopic signs of recent haemorrhage, gastric or duodenal posterior ulcer) were also significant (p less than 0.05). Considering the gravity of these patients (six deaths among twenty-seven), clinical trials in bleeding peptic ulcer disease should only include patients in the high risk group.

["Spontaneous" ischemic colitis: infectious or medicamentous colitis? 25 cases]. / Colite ischémique "spontanée": colite infectieuse ou médicamenteuse? 25 observations.

The diagnosis of non-gangrenous ischaemic colitis is difficult to assert when histological findings are not specific and when no precipitating cardiovascular event can be found. The constant absence of relapse after the initial episode suggests that an extraneous triggering event is involved. We have studied retrospectively 25 cases of spontaneous ischaemic colitis, looking for a non-haemodynamic triggering event. At the onset of colitis 9 patients had been taking non-steroidal anti-inflammatory drugs or antibiotics for 2 weeks or less. In 3 other patients colitis was associated with Escherichia coli O157:H7 infection. Striking clinical, endoscopic and histological similarities exist between ischaemic colitis on the one hand and colitis caused by absorption of non-steroidal anti-inflammatory drugs or ampicillin and the colitis reported in E. coli O157:H7 infection on the other hand. Non-steroidal anti-inflammatory drugs and E. coli O157:H7 intestinal infection, possibly facilitated by an antibiotic treatment with e.g. ampicillin, could be either non-haemodynamic triggering factors for ischaemic colitis, or responsible per se for a transient acute colitis with the same characteristics as ischaemic colitis.

[Acalculous cholangitis and cholecystitis in two AIDS patients]. / Cholangites et cholécystites alithiasiques chez deux malades atteints de SIDA.

Acalculous cholangitis and cholecystitis may occur in the course of AIDS. The symptoms are always the same: pain in the right upper quadrant, fever, nausea, vomiting, anorexia and diarrhoea, associated with biochemical signs of cholestasis, often without jaundice. Morphological explorations show thickening of the gallbladder wall and dilatation of the extrahepatic bile ducts, sometimes associated with stenosis of the major duodenal papilla and dilatation of the intrahepatic bile ducts.

[Colonoscopic surveillance of patients operated on in colorectal cancer. Retrospective evaluation of 269 tests in 125 patients]. / Surveillance coloscopique des patients opérés d'un cancer colorectal. Bilan rétrospectif de 269 examens chez 125 patients.

The ideal frequency of endoscopic surveillance of patients operated on for colorectal cancer is not known. We report our experience of colonoscopic follow up of 125 patients after excision of a colorectal cancer. The median interval between resection and the first check colonoscopy was 12 months. The median duration of follow-up was 28 months (range: 3 months to 10 years). 269 colonoscopies allowed diagnosis of 8 anastomotic recurrences within a median delay of 21 months after surgery (range: 3 months to 5 years). In 6 of these patients, the recurrence was clinically suspected. In 2 patients, it was asymptomatic and was discovered on systematic colonoscopy. Potentially curative surgery was only possible in 1 case. Follow up colonoscopies also allowed excision of 113 adenomatous polyps in 39 patients and the discovery of 4 new invasive cancers within a median delay of 7.4 years after excision of the first cancer. Due to the disappointing value of colonoscopy in the detection of anastomotic recurrences and the propensity of the remaining colon to develop new polyps, in the absence of a comparative trial, we arbitrarily adopted a follow up rhythm based on early post-operative colonoscopy (3 months post-surgery) and then yearly for the first 2 years. Further follow-up was similar to that adopted for patients with a past history of endoscopic polypectomy.