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Biomedical subjects

P Roger

Publications and source records attributed to P Roger.

179 records · Page 10Linked to original sources

Addition of benfluorex to biguanide improves glycemic control in obese non-insulin-dependent diabetes: a double-blind study versus placebo.

The oral antidiabetic benfluorex lowers insulin resistance in liver and muscle without stimulating insulin secretion; it is more effective than a biguanide in lowering insulin and triglyceride levels and does not elevate lactate. This double-blind multicenter community study compared the addition of benfluorex versus placebo to diet plus metformin in 127 uncontrolled obese type II diabetics. After a 2-month run-in on diet plus metformin, overall mean glucose was 7.7 mmol/L or greater (fasting) and/or 11 mmol/L or greater (2 h after 75-g oral glucose), with 20% or greater excess body weight [body-mass index (women/men): > or = 26.9/> or = 27.2 kg/m2). Patients were then randomized to adjuvant benflouorex (n = 63; 150 mg t.i.d.) or placebo (n = 64) for 90 days, with centralized biochemical monitoring. On benfluorex, glucose decreased from day 0 to day 90 (fasting: 8.99+/-2.76 to 7.81+/-2.32 mmol/L, p = 0.002; 2 h post-load: 16.56+/-4.49 to 15.09+/-5.09 mmol/L, p = 0.029) versus increases on placebo (intergroup p = 0.003 and p = 0.001, respectively). HbA decreased on benfluorex (7.47+/-1.44 to 7.12+/-1.13%; p = 0.013) versus no change on placebo. Basal and stimulated insulin and C peptide did not change in either group. Body weight remained similar in both groups. Tolerability was good in both groups, with no increase in hypoglycemia on benfluorex. Adjuvant behfluorex improves glycemic control in obese type II diabetics uncontrolled by diet plus metformin. The combination is safe, well-tolerated and suitable for introduction into routine practice.

Adult↗

Development of a functional human bronchial model of mucin secretion.

In an attempt to study the functional aspects of respiratory mucin secretion and the effects of mediators of inflammation on the release of M1/MUC5AC mucins in airways diseases, an ex vivo human bronchial model of mucin secretion was developed. Anti-M1 mucin monoclonal antibodies raised against the peptidic core of ovarian cyst M1 mucins were used. PAS and Alcian blue stainings of sections of bronchial rings revealed the presence of mucins in epithelial goblet cells as well as in glandular mucous cells. Immunohistochemical labelling of these sections with anti-M1 monoclonal antibodies revealed a preferential localization of M1/MUC5AC mucins in epithelial goblet cells. Functional studies were performed on this bronchial model using various secretagogues (methacholine, leukotrienes D4 and anti-human immunoglobulin E antibodies). No statistical difference of M1/MUC5AC mucin secretion was observed after a one-hour stimulation of bronchial rings with these agents. The development of an ex vivo functional human bronchial model of mucin secretion and the use of specific anti-M1 antibodies are essential tools in studying the regulation of the M1/MUC5AC mucin release from human airways.

Antibodies, Monoclonal↗

Policy and science of FMD control: the stakeholders' contribution to decision making. A call for integrated animal disease management.

Effective control of foot-and-mouth disease (FMD)--prevention, surveillance and response--requires integrated animal disease management as a cooperative effort between stakeholders, scientists and decision makers, at all levels: local, national, regional and international. This paper suggests a process and outlines specific critical issues that need to be addressed in order to best use the science and technology that is available now and to develop new technologies that will lead to significant improvements. The overall objective is not to allow the disease or the disease control measures to damage, violate or destroy public health, the environment, or the economy, or to allow politics to drive disease control policies at the expense of the ethical relationship between man and animals. Critical issues of prevention, surveillance and response policies are examined, and specific recommendations are made to reduce the risk or effect of natural and deliberate introductions. For prevention: a) rapid portable diagnostics and provision of vaccines to control and eradicate the reservoirs of disease. b) alerts, leading to increased controls at borders, animal movement restrictions and biosecurity on farms. For surveillance: a) reporting of unusual symptoms, rapid diagnostics and identification of patterns. b) enhanced role of geographic information systems (GIS) linked to an IT system. c) collection, storage and sharing of disease information. For response policies: a) the role and implementation of stamping out and of vaccination. b) simulation exercises with stakeholder participation. For all aspects of FMD control, consideration should be given to: a) the composition, responsibilities and role of the balanced, permanently operational Expert Group in EU member states as specified in the EU FMD Directive. b) establishment of a balanced, permanently operational European Expert Group. c) establishment of both a European and an International FMD Task Force. Stakeholders need access to accurate, up-to-date, unbiased information about the science of disease control, how the technologies work and can be used, and an assurance that the technologies best fit for the required purpose will be used. Researchers need to work together to avoid duplications and gaps in their research and to recognise the benefit of new, and sometimes innovative, technologies. They also need feedback from stakeholders on the acceptability and best use of the technologies. A process to achieve these goals through an EU funded collaborative research project will be described.

Animals↗

[Synthetic A.C.T.H. test. (Results obtained on aldosterone and cortisol blood level) (author's transl)].

During the beta 1-24 corticotropin stimulation test, it appears the increase of Aldosterone Blood level is more important (170,91% +/- 35,89 (S. E.)) and more significant (alpha less than 0,001) than for cortisol (+/- 54,47% +/- 9,45 (S. E.) - alpha less than 0,10). The authors suggest aldosterone assays have to be done in order to obtain a better estimation on adrenal response to synthetic A.C.T.H.

Addison Disease↗

Evaluation of a new nitrosoureido water-soluble sugar, ecomustine or CY 233 (NSC 609224), on human xenografts.

Because of its wide spectrum of activity against murine models regardless of the route of administration, CY 233 (NSC 609624) was investigated in human tumours xenografted in nude mice, namely one amelanotic melanoma, MeXF 274, and three colon adenocarcinomas, i.e. CXF 233, CXF 243 and CXF 609. CY 233 was highly active against the MeXF 274 melanoma and produced a complete response on day 14 at 20 mg/kg given i.v. on days 0 and 7. After three intermittent i.v. injections of 10 mg/kg, it produced a partial response of long duration against the colon adenocarcinoma CXF 243. The interesting fact that resistant lines responded to CY 233 warrants further investigation of other schedules of treatment and of the sensitivity profile of CY 233 in a wider panel of tumour xenografts.

Adenocarcinoma↗

Antitumour activity of a new water-soluble nitrosoureido sugar: CY233 (NSC 609224).

L1210 leukemia was used to evaluate the antitumour activity in vivo of CY233 (NSC 609224) a new water-soluble nitrosoureido derivative of deoxysugar currently being studied in preclinical trials. The antitumour activity of CY233 is dose-dependent with the same large therapeutic index whatever the route of administration (I.P., I.V., per os). Thus starting from a single dose of 10 mg/kg (less than 25% of the LD50), 80% to 100% of mice survive at 120 days, whether the drug is being administered I.V., I.P. or P.O. These results clearly emphasize the very original and promising potentiality of CY233 among the series of alkylating agents, and more precisely nitrosoureas.

Animals↗

[Gonadal dysgenesis in a mother and her daughter (author's transl)].

The authors present two cases of gonadal dysgenesis in a mother and her daughter. Caryotypes were 46, XX/45, X for the mother (RHG-banding) and 46, X, i (Xq)/45, X for the daughter. Some researches in family did not show any abnormalities to explain this very exceptionnel event in a mother and one of her 3 daughters.

Adolescent↗

[The utilization of small repeated doses of iodine 131 in the treatment of Graves' disease. Results (author's transl)].

In graves' disease small amounts of radioactive iodine administered repeatedly on a monthly basis depending on the progress of the disease is a method whose effectiveness we have studied on 192 cases over a period of 3 to 7 years. Relapses (4 %), failures (11 %) permanent hypothyroidism (24 % after 7 years) and the duration of the active stage have been collated with different clinical or biological parameters in order better to define the main factors that determine the course and prognosis. The size of the goitre and the presence of antithyroglobulin antibodies are among the most significant.

Antibodies↗

[Cushing's syndrome: diagnostic exploration].

The diagnosis of Cushing's syndrome is one of the most perplexing and controversial problems in endocrinology. However, significant advances in the diagnosis procedures have been made in the past decade. The diagnostic studies involved in the evaluation of patients with suspected Cushing's syndrome fall into two categories: confirming the presence of true hypercortisolism and establishing the precise aetiology. Diagnosis of Cushing's syndrome: ambulatory screening relies on the overnight 1 mg dexamethasone test. Negative tests are confirmed by measuring cortisol in two 24-hour urine samples. If cortisol excretion is slightly above normal, a 48-hour low-dose dexamethasone suppression test or an intravenous infusion dexamethasone suppression test are required. Diagnosis of the aetiology of Cushing's syndrome: the first step is to establish if the hypercortisolism is ACTH-dependent or not. This step is solved by measuring plasma ACTH and cortisol in the late afternoon. Computed tomography scanning of the adrenal glands is required in ACTH-independent Cushing's syndrome. A unilateral tumour will be demonstrated in most of cases. If bilateral lesions are found, dynamic testing using cortisol releasing factor and/or metyrapone must be performed to confirm the ACTH-independency of the syndrome. In ACTH-dependent Cushing's syndrome, the major difficulty is to distinguish between a pituitary source and an ectopic source of ACTH secretion. Magnetic resonance imaging of the pituitary with gadolinium enhancement must be preferred to computed tomography scanning but its sensitivity is not better than 70-80% and false positives can occur. When no macroscopic pituitary lesion can be detected, bilateral inferior petrosal sinus sampling coupled to CRH injection for ACTH measurement will indicate the source of ACTH secretion. If this test indicates the patient has Cushing's disease, pituitary trans-sphenoidal surgery can be performed. If the test indicates the patient has ectopic ACTH-secretion, a cervico-thoraco-abdominal scanning is necessary to identify the tumour. In the case of occult tumour the hypercortisolism must be controlled by pharmacological agents and the imaging investigations must be repeated at appropriate intervals.

Adrenocortical Hyperfunction↗