Adenovirus-mediated gene therapy is hampered by severe virus-related toxicity, especially to the liver. The aim of the present study was to test the ability of a vascular exclusion technique to achieve transgene expression within selected liver segments, thus minimizing both viral and transgene product toxicity to the liver. An E1-E3-deleted replication-deficient adenovirus expressing a green fluorescent protein (GFP) reporter gene was injected into the portal vein of BDIX rats, with simultaneous clamping of the portal vein tributaries to liver segments II, III, IV, V, and VIII. GFP expression and inflammatory infiltrate were measured in the different segments of the liver and compared with those of the livers of animals receiving the viral vector in the portal vein without clamping. The GFP expression was significantly higher in the selectively perfused segments of the liver as compared with the non-perfused segments (p < 0.0001) and with the livers of animals that received the vector in the portal vein without clamping (p < 0.0001). Accordingly, the inflammatory infiltrate was more intense in the selectively perfused liver segments as compared with all other groups (p < 0.0001). Fluorescence was absent in lungs and kidneys and minimal in spleen. The clinical usefulness of adenovirus-mediated gene transfer to the liver largely depends on the reduction of its liver toxicity. Clamping of selected portal vein branches during injection allows for delivery of genes of interest to targeted liver segments. Transgene expression confined to selected liver segments may be useful in the treatment of focal liver diseases, including metastases.

Adenoviridae↗

PubMedDate not supplied

Hepatic de novo lipogenesis after liver transplantation.

BACKGROUND: The liver can synthesize fatty acids from carbohydrate (de novo lipogenesis [DNL]). We hypothesized that stimulation of this process may be involved in the development of obesity and dyslipidemia, 2 conditions frequently encountered after liver transplantation. METHODS: Hepatic fractional DNL and glucose metabolism were measured in 2 groups of 5 patients (age 36.8 +/- [SD] 14.9 years, BMI 26.3+/-5.3 kg/M2) 1 to 5 years after liver transplantation and 8 healthy subjects (age 28.1+/-5.3 years, BMI 27.2+/-4.5 kg/M2). Subjects were studied while receiving an isoenergetic nutrition (based on 1.1 x their basal energy expenditure) as hourly oral liquid formula during 10 hours. Their hepatic DNL was measured by infusing 1-13C acetate and measuring tracer incorporation in VLDL-palmitate. Their glucose metabolism was assessed by means of 6,6-2H2 glucose and indirect calorimetry. RESULTS: Two liver transplant recipients and 4 healthy subjects were obese, as defined by a BMI > 27 kg/M2. Fractional hepatic DNL was not different in the 2 groups of subjects: liver transplant recipients 3.1+/-1.7% vs 3.2+/-2.1% in healthy subjects. In both groups, DNL increased in proportion to BMI. When both groups were analyzed together, BMI was positively correlated with DNL (DNL = 0.28 x BMI - 4.28, r2 = .445, p < .05). Whole body glucose turnover was 15.0+/-4.4 micromol/kg per minute in liver transplant recipients and 15.8+/-4.1 micromol/kg per minute in healthy subjects (NS). Net carbohydrate oxidation tended to be lower in liver transplant recipients (8.1+/-2.6 micromol/kg per minute) than in healthy subjects (10.4+/-2.4 micromol/kg per minute; NS). Net nonoxidative glucose disposal (4.0+/-2.7 in liver transplant recipients vs 1.9+/-1.8 in healthy subjects, NS) and energy expenditure (0.065+/-0.01 vs 0.065+/-0.01 kJ/kg per minute) were similar in both groups. CONCLUSIONS: These results indicate that fractional hepatic DNL is not altered by liver transplantation during near continuous nutrition. The disposal of orally administered carbohydrate is also essentially unchanged. This strongly argues against a role of hepatic DNL in the pathogenesis of obesity and dyslipidemia after liver transplantation.

Adult↗

PubMedDate not supplied

A single dose, combined vaccine against typhoid fever and hepatitis A: consistency, immunogenicity and reactogenicity.

BACKGROUND: Vaccines against hepatitis A and typhoid fever are well established and have an excellent safety and immunogenicity profile. Yet these diseases, which share the same geographic distribution, remain an important cause of morbidity in travelers to endemic countries. Combined vaccination provides dual protection and improves compliance and coverage for travelers. METHODS: This multicenter study evaluated the consistency of three lots of combined hepatitis A and typhoid fever vaccine. A total of 462 healthy subjects, aged 15-50 years, were enrolled and randomly allocated to 3 groups. The single dose of vaccine contains 25 microg typhoid Vi polysaccharide and at least 1,440 ELISA units of inactivated hepatitis A in a 1 mL dose. RESULTS: Bioequivalence of all production lots was shown in terms of safety and immunogenicity. Pain at injection site was the most frequent reported local symptom, and headache was the most frequent reported general symptom. As early as 14 days after immunization >95% of the subjects were positive for anti-Vi antibodies and >86% were positive for anti-HAV antibodies. The GMTs and seropositivity rates were maintained during the 6 month follow-up. CONCLUSION: The first combined vaccine against typhoid fever and hepatitis A was safe and elicited a very good immune response, with the majority of subjects seropositive at 1 month for both antigens. This combined vaccine offered more convenience and rapid seroconversion to travelers.

Adolescent↗

PubMedDate not supplied

[Parenteral hyperalimentation in digestive surgery with a 25 g per liter solution of amino acids].

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Adolescent↗

PubMedDate not supplied

[Alveolar hydatid disease of the liver. An experience based on 20 cases. I. Epidemiological, clinical, biological and radiological studies (author's transl)].

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Adult↗

PubMedDate not supplied

Combined radioimmunotherapy and radiotherapy of liver metastases from colorectal cancer: a feasibility study.

BACKGROUND: A combination of radioimmunotherapy (RIT) and radiotherapy (RT) should allow one to increase the dose of radiation targeting a particular tumour without the concomitant increase of toxic side effects. This might be obtained if the dose limiting side effect of each individual radiation therapy concerned different organs. METHODS: Six patients with limited liver metastatic disease from colorectal cancer were treated with 6.9 GBq (range 4.7 to 8.4 GBq) 131I-labelled anti-CEA MAb F(ab')2 fragments combined with 20 Gy RT to the liver. Both treatments were given in close association, according to timing schedules evaluated in animals that gave the best results. RESULTS: Reversible bone marrow and liver toxicity was observed in 6 and 5 patients, respectively. Three patients who first received 20 Gy RT to the liver, showed a significant platelet drop upon completion of RT. Repeat computerized tomography (CT) after 2 months showed a minor response in 1 patient and stable disease in 3 patients. CONCLUSION: The study shows potential ways of combining RIT and RT, suggesting that this combination is feasible for the treatment of liver metastases.

Adult↗

PubMedDate not supplied

[Baker and Itagliata's Quality of Life Scale in a group of 139 schizophrenic patients: factorial analysis and evaluation of global validity].

The Satisfaction with Life Domains Scale SLDS published by Baker and Intagliata in 1982 and translated in French by Chambon and al. is one of the most used rating scales in the field of Subjective Quality of Life (SQL) for patients suffering from schizophrenia. It comprises 16 scales in 7 points and Likert format exploring the following fields: home/apartment/place of residence, neighbourhood, food, clothes, health, people they live with, friends, love life, relationships with their family, how they get on with other people, job/work day programming, spare time, what they do in the community for fun, services and facilities in their area, economic situation, general quality of life. In this study we present results on SLDS about 139 schizophrenic patients (108 males, 31 females) recruited in two centers Lyon (n = 41) and Saint-Etienne (n = 98). The SLDS was a part of more comprehensive studies including evaluation of needs for care, social support, delivery and costs of services. Diagnosis were confirmed using either the SCAN and CATEGO program (n = 108) or the list of the ICD-10 criteria (n = 31) applied at time of inclusion or on the basis of a representative episode of the illness. Patients were classified in two groups, the S group (S, n = 53) for those patients presenting clinical features at time of inclusion excepted residual forms (F 20.5) and the non S group (N-S, n = 86) for those patients free of symptoms at the time of assessment. Non parametric statistics (U test and Kendall test) were used for comparisons between groups. The field by field comparison of the scores shows the poorest level of SQL for love life (m = 4.2; sd = 1.8) and economic status (m = 4.4; sd = 1.8). Comparisons between S and non-S groups show an average range systematically higher for the non-S group and significant differences for the following fields: food, friends, how they get on with other people. The same comparisons between males and females show no significant differences excepted for the following fields: love life, economic situation. Principal components analysis with Varimax rotation were performed and a 4 factors solution was considered as the best one. Before rotation the first factor accounts for 31% of the variance and comprises all the items with loading higher than 0.4 allowing us to consider the possibility of a global score. This global score is normally distributed (m = 95.1 sd = 17.3) and shows a significant difference between S and non S-groups (S m = 92.2 sd = 20.1; non S m = 99.6 sd = 15.4 p = .02) but not between centers and between males and females. After rotation the first factor comprises relationships with family, how they get on with other people, job/work/day programming, spare time, what they do for fun and life in general. The hypothesis of unidimensionality of QV has to be tested using the RASCH model.

Adult↗

PubMedDate not supplied

Extrarenal sorbitol clearance after liver transplantation.

Extrarenal sorbitol clearance was measured in liver transplant patients after a steady-state perfusion. Four measurements were performed in 3 patients with various liver diseases (beginning or patent acute rejection, cytomegalovirus hepatitis, hepatic metastasis). The mean (+/- SD) extrarenal sorbitol clearance was 14.8 +/- 0.1 ml/min.kg. In 5 patients with minimal or no liver abnormalities, the mean from 5 measurements of extrarenal sorbitol clearance was 18.9 +/- 5.0 ml/min.kg. Extrarenal sorbitol clearance values in this later group were higher than the values previously reported in healthy subjects.

Adult↗