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Biomedical subjects

F Dubois

Publications and source records attributed to F Dubois.

At least 109 records · Page 6Linked to original sources

Uptake by rat liver of bovine growth hormone free or bound to a monoclonal antibody.

In the work reported here, we have compared the elimination from the blood, the uptake by the liver and the intracellular distribution of bovine growth hormone, free(Gh) or bound to a monoclonal antibody (GhAb). Results show that: a) the elimination from the blood is more rapid for Gh than for GhAb; b) both molecules are quickly taken up by the liver; c) probably after travelling through endosomes, Gh and GhAb get to lysosomes where they are degraded. However, Gh mostly ends in hepatocyte lysosomes while GhAb is recovered to a large extent in sinusoidal cell lysosomes; and d) binding by isolated hepatocytes is markedly less efficient for GhAb than for Gh.

Animals↗

Serum alanine aminotransferase measurement as a guide to selective testing for hepatitis C during medical checkup.

The efficiency of elevated serum alanine aminotransferase values for selecting subjects to be tested for hepatitis B or C infections in a large French population undergoing a medical checkup was investigated. For 5 consecutive weeks, serum alanine aminotransferase values were controlled in 9044 subjects; 308 subjects (202 males) were selected with alanine aminotransferase levels 1.2-fold above the normal value (58 iu/l for men, 34 iu/l for women). For each selected case, an age- and sex-cross-matched control was included. Of the 308 subjects with elevated alanine aminotransferase values, one was HBsAg positive and 15 (seven males) were anti-HCV positive. All anti-HCV sera tested by enzyme immunoassay were also positive by three immunoblots and 11/15 (73%) were HCV-RNA positive by reverse transcription-polymerase chain reaction. Of the 308 control subjects, two were HBsAg positive and four (two males) were weakly anti-HCV positive by enzyme immunoassay. Only one weakly anti-HCV positive serum was reactive by one immunoblot and all were HCV-RNA negative. This study shows the usefulness of alanine aminotransferase screening to detect hepatitis C virus infection in the general French population. Many of the anti-HCV positive subjects detected in this study were not aware of their hepatitis C virus seropositivity (12/15) or that they were viremic (11/15). Use of this low-cost assay will considerably reduce the number of subjects to be tested for hepatitis C virus serological status and therefore the cost. It may make possible the investigation of large populations by setting up public health programs to detect and treat hepatitis C virus. Hepatitis C virus infected subjects detected in these programs could benefit from medical follow up, including antiviral therapy.

Adolescent↗

Influence of human immunodeficiency virus infection on hepatitis delta virus superinfection in chronic HBsAg carriers.

It is generally agreed that hepatitis B virus (HBV) replication is reduced by hepatitis delta virus infection (HDV) and augmented by human immunodeficiency virus (HIV) infection. However, the precise nature of the interactions between HBV, HDV and HIV is controversial. The aim of this study was to evaluate the impact of HIV infection on HBV and HDV replication, and on histological scores during delta virus superinfection in HDV-positive, chronic carriers of hepatitis B surface antigen (HBsAg). We studied 38 men and six women, 15 of whom were HIV-positive and all of whom had at least one marker of HDV infection. Serum hepatitis B e antigen (HBeAg), HBV DNA, HDV RNA, anti-delta antigen antibodies (anti-HD) IgM, anti-HD IgG and hepatitis delta antigen (HDAg) were tested for in the serum and liver, respectively; anti-hepatitis C virus (HCV) antibodies were detected using a second-generation recombinant immunoblot assay. Histological specimens were scored blindly according to Knodell's classification for periportal and intralobular necrosis, portal inflammation and fibrosis. HBV DNA was detected more frequently in the HIV-positive patients than in those who were HIV-negative (25 vs 0%; P = 0.01), while markers of HDV replication (serum anti-HD IgM, serum HDV RNA and liver HDAg) were as frequent in the HIV-positive patients (69%, 40% and 50%, respectively) as in those who were HIV-negative (75%, 52% and 30%, respectively; P > 0.05). By contrast, 31% of the HIV-positive patients were serum HDAg-positive compared to only 6% of the HIV-negative patients (P = 0.001). HDV antigenaemia and anti-HD antibodies usually fluctuated in the HIV-positive patients during follow-up. The mean Knodell score was similar in the HIV-positive (11.5 +/- 3.2) and HIV-negative (10.7 +/- 2) subgroups, as was the mean semi-quantitative index of hepatic necrosis, inflammation and fibrosis. Our results provide evidence that in HDV-positive patients: (1) HIV infection counters the inhibitory effect of HDV superinfection on HBV replication; (2) serum anti-HD IgM. HDV RNA and liver HDAg are not more frequent in HIV-positive than in HIV-negative patients, suggesting that HIV infection has no effect on HDV replication (although the significance of the increased frequency of HD antigenaemia remains unclear); (3) the histological severity of liver disease is not influenced by HIV status.

Adult↗

Functional results of single-lung transplantation for chronic obstructive lung disease.

The feasibility and immediate tolerance of single-lung transplantation were recently demonstrated in patients with severe obstructive lung disease. Since initial reports, hundreds of procedures have been performed worldwide in such patients, but views regarding the results are still controversial. Since few data concerning medium-term functional results are available, we report here our series of 20 patients with chronic obstructive pulmonary disease who received a single-lung transplant. A group of 16 patients who survived for 6 mo or more form the basis of this report. Current 1- and 2-yr actuarial survival are 75 and 70%, respectively, with 4 perioperative deaths and 2 deaths at 9 and 15 mo after transplantation. Before transplantation the patients were severely obstructive, with a FEV1 of 17 +/- 6% of predicted, a PaO2 of 51 +/- 10 mm Hg, a PaCO2 of 49 +/- 11 mm Hg, and a 6 min walk test of 99 +/- 84 m. A significant functional improvement was observed postoperatively, the patients' FEV1 at 3 mo reached 53 +/- 13%, PaO2 81 +/- 3 mm Hg, and PaCO2 39 +/- 3 mm Hg. The distance covered during 6 min was 587 +/- 147 m at 6 mo. Throughout postoperative follow-up, lung function remained stable in some patients but decreased in others after several mo, this decline related to the occurrence of bronchiolitis obliterans, except in two patients who had airway complications. Impairment in lung function led to retransplantation in four patients, with good clinical results in three patients, one patient dying postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

[Complications of celioscopic cholecystectomy in 2006 patients].

The development of laparoscopic cholecystectomy is only justified if it can ensure the good results obtained by laparotomy. The purpose of this work is to study all complications which occurred in a homogeneous group of patients. From May 1988 to January 1993, we operated on 2006 patients by laparoscopy (724 men and 1282 women) with a mean age of 50.6 years. Signs of stones in the common bile duct were noted in 4.1% and acute cholecystitis was detected in 12.5%. A conversion to normal laparotomy was necessary in 2.1% of patients. All complications were systematically investigated restrospectively in any patient hospitalised for more than five days. Residual stones in the common bile duct were not taken into consideration when they were not complications obviously related to the operation. We observed five intraoperative complications (4 hemorrhages, 1 ileum puncture) and 40 postoperative complications (25 non biliary and 15 biliary). The 25 non biliary complications consisted of: 1 death by pulmonary embolism, 9 hemorrhages, 4 cases of acute pancreatitis, 4 subphrenic abscesses, 2 colon punctures, 2 parietal complications, 1 ulcer perforation, 1 myocardial infarction and 1 phlebitis. The 15 biliary complications consisted of: 3 lateral punctures of the common bile duct, 9 fistulas of the cystic duct (4 with a residual stone in the common bile duct and 5 without), 2 punctures of an abnormal right hepatic duct, one of which was treated by "Roux en Y loop" intestinal diversion, and a late stenosis of the common bile duct.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Extracorporeal lithotripsy associated with laparoscopic cholecystectomy: results of 60 patients.

Gallbladder extracorporeal lithotripsy was performed on 60 patients before laparoscopic cholecystectomy. Of the 44 cases with solitary stones (range, 17-45 mm; mean +/- SEM, 26.9 +/- 0.1 mm), satisfactory fragmentation was obtained in 77.2%. Of the 16 cases with multiple stones (range, 11-25 mm; mean +/- SEM, 14.9 +/- 0.7 mm), satisfactory fragmentation was obtained in 18.75%. Minimal adverse effects were observed both clinically and macroscopically during surgery. Upon histologic investigation, only two small gallbladder lesions could be attributed to extracorporeal lithotripsy. No changes in blood chemistry tests were recorded. When carried out with high performance equipment, extracorporeal lithotripsy appears to be an interesting procedure that permits an appreciable reduction in the number of parietal wall incisions that need to be widened, therefore simplifying laparoscopic cholecystectomy when dealing with large stones.

Adult↗

Vagotomies--laparoscopic or thoracoscopic approach.

The complications and sequelae of truncal vagotomy have been overemphasized in the surgical literature. With the introduction of minimally invasive techniques, the indications for vagotomy have to be reconsidered. The procedure can be performed either by laparoscopy or by thoracoscopy. The techniques for these approaches are outlined. In an experience of twenty-one vagotomies no major complication occurred, and the immediate results are fair.

Duodenal Ulcer↗

Regional uptake of [123I]-16-iodo3-R,S-methyl hexadecanoic acid in patients with myocardial infarction. Comparison with thallium 201 uptake and wall motion.

Thirty patients with recent myocardial infarction were intravenously injected with the modified fatty acid [123I]16-iodo-3R,S-methyl hexadecanoic acid (MIHA) at peak exercise to quantify viable myocardium after infarction. The results were analysed visually and quantitatively and compared with those obtained after injection of thallium 201 at peak exercise with single-photon emission computed tomography (SPECT) imaging immediately and 4 hours later. Ventriculography was used to study regional wall motion in all patients. In the visual comparison of 201Tl- and MIHA-SPECT scintigrams, 98.8% of normal segments (N) and 96% of temporary thallium-defect segments (T) were N or T on MIHA-SPECT scintigrams (91.3% and 70.5%, respectively, in the quantitative analyses). In contrast, 47.2% of permanent thallium-defect segments (P) were N or T on the MIHA-SPECT scintigrams (20.6% in the quantitative analysis). Revascularization therapy could only be recommended on the basis of MIHA-SPECTs in 5 to 8 of the 30 patients. To confirm the superiority of MIHA over 201Tl to evaluate myocardial viability, one must compare their uptake with myocardial contractility after revascularization.

Exercise Test↗

[Cholecystectomy via laparoscopy in situs inversus totalis. A case report and review of the literature].

The authors report a case of symptomatic cholelithiasis in a patient with situs inversus totalis, in which the surgical treatment was performed by laparoscopy. They discuss the etiopathogenesis of this anomaly and malformations often associated, moreover related clinical and surgical problems. Finally, they describe operative technique stressing the real possibility to perform the operation by laparoscopy on condition that the surgeons have sufficiently experience of biliary and laparoscopic surgery.

Cholecystectomy, Laparoscopic↗

Chloroquine allows to distinguish between hepatocyte lysosomes and sinusoidal cell lysosomes.

We have examined the effect of chloroquine on rat liver lysosomal enzyme distributions after isopycnic centrifugation in a sucrose gradient. Chloroquine injection causes the large majority of cathepsin C, acid phosphatase and N acetyl glucosaminidase to migrate towards lower density regions; on the other hand only about 50% of arylsulfatase and acid deoxyribonuclease are subjected to such a density shift. To specifically mark hepatocyte lysosomes and sinusoidal cell lysosomes, rats were injected with galactosylated bovine serum albumin (A) or mannosylated bovine serum albumin (B) labelled with 125I tyramine cellobiose; A is selectively endocytosed by hepatocytes, B by sinusoidal cells. The radioactivity distribution is affected by chloroquine in the same way as cathepsin C, after injection of A though it is not influenced by chloroquine after the injection of B. These results show that chloroquine does not modify the density of liver sinusoidal cell lysosomes when it decreases the density of hepatocyte lysosomes. Such a difference could result from the fact that sinusoidal cell lysosomes do not accumulate chloroquine to the same extent as hepatocyte lysosomes. Chloroquine treatment could be useful to distinguish between hepatocyte lysosomes and sinusoidal cell lysosomes.

Animals↗

Pharmacodynamic model of the haemodynamic effects of pinacidil in normotensive volunteers.

The concentration-effect relationships of pinacidil, a peripheral vasodilator, have been measured in 12 healthy adults who received placebo or pinacidil 25 mg daily for 1 week in a cross-over experiment. Diastolic blood pressure (DBP) and heart rate (HR) were recorded and blood samples were taken on days 1 and 7. Plasma drug concentration-time data were fitted by a biexponential function with zero-order input. The pharmacokinetic model was incorporated into a combined pharmacokinetic-dynamic model (PK-PD) using the Hill equation, which has three parameters: n, the sigmoidicity parameter, Emax the maximum effect and EC50 the concentration which gives 50% of Emax. For delta DBP, the parameter medians were estimated as n = 5, EC50 = 44.6 ng.ml-1 and Emax = 13.5 mmHg. A hysteresis loop was found when delta HR was plotted against concentration, which could be fitted by a linear effect compartment model. Simulations showed that experimental delta DBP points on Day 7 could be predicted from a simulated curve computed by the model using parameters estimated on Day 1. Using the simulation, it was possible to suggest an optimal dosage regimen for pinacidil tablets.

Adult↗

Influence of fatty acid backdiffusion on compartmental analysis of external detection curves obtained with 123-iodohexadecenoic acid in isolated rat heart.

In isolated rat hearts, we investigated a possible backdiffusion of fatty acids and tried to determine whether it impaired our compartmental analysis of myocardial time-radioactivity curves obtained with an iodinated fatty acid, 16-iodo-9-hexadecenoic acid (IHA). Backdiffusion was not observed directly in the coronary effluents but was estimated by analysis of the external detection curves. Furthermore, when backdiffusion was not taken into account in the mathematical analysis, we obtained similar data on IHA intramyocardial metabolism.

Albumins↗

Characterization of RNA-binding domains of hepatitis delta antigen.

Hepatitis delta antigen (HDAg), the only protein encoded by the hepatitis delta virus (HDV), binds specifically genomic and antigenomic strands of the HDV RNA. In a previous study, three recombinant HDAg subdomains were synthesized, covering residues 11 to 78, 79 to 163 and 164 to 212, and only the middle domain was shown to be responsible for the binding to HDV RNA. To investigate HDAg sequences involved in HDV RNA binding, we synthesized five peptides, 15 to 29 residues in length, and tested their ability to bind HDV RNA using a simple non-radioactive ELISA with digoxigenin-labelled HDV genomic or antigenomic RNA probes. The specificity of interactions was demonstrated by comparison with control peptides and non-HDV RNA probes, and with an inhibition assay using recombinant HDAg. The HDAg-binding domain found within the middle region (79 to 163) of HDAg was more finely mapped: it is located between residues 79 and 107. In addition, another domain (residues 2 to 27) of HDAg was also found to bind specifically to HDV RNA. These two peptides share sequence similarities at residues 2 to 10 and 97 to 107 with other RNA-binding domains.

Amino Acid Sequence↗

Prevalence and significance of hepatitis C virus (HCV) viremia in HCV antibody-positive subjects from various populations.

Hepatitis C virus (HCV) infection is currently assessed by detection of antibodies to HCV with immunoassays. However, in the absence of an in vitro system to isolate the virus, or an immunoassay to identify HCV antigen in blood, an ongoing acute or chronic HCV infection can be diagnosed only by detection of HCV RNA by polymerase chain reaction. We used a reverse transcription-nested polymerase chain reaction to detect an HCV 5' noncoding viral RNA sequence in serum specimens collected from anti-HCV-positive individuals belonging to different risk groups and compared the results with those obtained with a prototype recombinant immunoblot assay (Chiron HCV SIA prototype recombinant immunoblot assay [RIBA]) containing four different viral peptides (c22, c33c, c100, and NS5). The prevalence of HCV viremia ranged from 25.9% in HCV antibody-positive blood donors to 92% in HCV antibody-positive hemophiliacs. Elevated alanine aminotransferase values in HCV antibody-positive patients were clearly associated with viremia. Ninety-six percent of HCV RNA-positive patients reacted to two viral antigens or more, compared with only 64% of HCV RNA-negative patients. Contrary to previous reports, HCV viremia was not associated with either the presence or the absence of a particular antibody specificity. The newly introduced NS5 peptide did not improve the sensitivity or specificity of the RIBA. Although 20% of the patients in our study whose sera reacted to all of the antigens were HCV RNA negative, the positive predictive value of a RIBA considered positive by the manufacturer (two or more bands), was rather high (78%) and may allow suspicion of viremia in EIA2 enzyme-linked immunosorbent assay-positive patients.

Alanine Transaminase↗

Immune response to synthetic peptides of hepatitis delta antigen.

Hepatitis delta antigen (HDAg) is the only viral protein known to be expressed during hepatitis delta virus (HDV) infection. Detection of antibody to HDAg (anti-HD) is the usual method for diagnosis of HDV infection since viremia lasts only a few weeks. In an effort to identify the major epitopes recognized by humans during natural infection, four oligopeptides including residues 2 to 17 (SP1), 155 to 172 (SP2), 168 to 182 (SP3), and 189 to 211 (SP4) of the HDAg molecule were synthesized and probed by enzyme-linked immunosorbent assay with a panel of 80 serum specimens from 45 patients suffering from either HDV-hepatitis B virus coinfections (n = 17) or HDV superinfections (n = 28). Sera from infected patients recognized these relatively short peptides. Peptide SP2 was the most antigenic; 71% of serum specimens reacted. Antibody to SP2 was also the commonest in sera taken early in the course of the disease. Peptide SP2 corresponds to one of the two regions which is highly conserved between different isolates. Among the 63 serum specimens which scored anti-HD positive by a commercial assay, all but 3 reacted to at least one of the peptides (95% agreement). Peptide assays appeared to be significantly more sensitive than the commercial assay with native HDAg early in the course of HDV infection since 14 of 17 (82%) serum specimens which scored anti-HD negative in the commercial assay reacted to one or more peptides. All serum specimens giving one or more positive results with the various peptides were confirmed as being HDV positive by an inhibition assay with free peptide in solution. The immune response to HDAg peptides vared greatly between individuals. No specific reactivity profile could be assigned to those with either HDV-hepatitis B virus coinfections or HDV superinfections. Overall, HDAg peptides appeared to be convenient reagents in addition to native antigen for the development of new and improved diagnostic tests for HDV infection.

Amino Acid Sequence↗

[Celioscopic treatment of acute obstructions of the small intestine. Immediate results in 25 patients].

Laparoscopic treatment of small intestinal obstruction is associated with immediate advantages and it may be expected that the recurrence rate will be decreased because of the reduction of wound scars. Between september 1989 and september 1991, 25 patients (16 men and 9 women), mean age 53.8 years, underwent initial laparoscopy for acute small intestinal obstruction. These patients had undergone a total of 43 (1.7 per patient) laparotomies an average of 13 years previously. One patient had never been operated on, 13 had one previous laparotomy, five had two, four had three, and two had four previous laparotomies. Laparoscopic treatment of intestinal obstruction was possible in nine cases including three cases of bands and six cases of adhesions. In sixteen cases, laparoscopy had to be completed by laparotomy, 13 immediately and 3 secondarily. The cause of immediate failure was the impossibility of finding and/or treating the cause in seven instances, four cases of intestinal wounds, on case of intestinal necrosis which required resection, and one case of missed right colonic carcinoma. The cause of secondary failure were incomplete release of adhesions, volvulus, and missed left colonic carcinoma in one case each. Mean hospital stay and postoperative ileus were significantly shorter in the "laparoscopy" group than in the laparoscopy + laparotomy group (p < 0.001). Two complications, with one death, were noted in the laparoscopy + laparotomy group. In conclusion, laparoscopic treatment of intestinal obstruction seems possible but in less than half of cases. Failures are related to the difficulty with which the abdomen may be explored. Laparoscopic treatment should not be pursued in case of problems.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗