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Biomedical subjects

F Thomas

Publications and source records attributed to F Thomas.

At least 91 records · Page 5Linked to original sources
PubMed1998

Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study.

OBJECTIVES: To assess the weight-reducing effects and tolerability of 5 mg, 10 mg and 15 mg daily doses of sibutramine, a novel serotonin and noradrenaline reuptake inhibitor (SNRI). DESIGN: Multicentre, double-blind, and placebo-controlled study. After a one week run-in period, patients were randomized to receive placebo or sibutramine over a 12-week period. Advice on diet and behaviour modification was provided. One follow-up was conducted four weeks after cessation of treatment. SUBJECTS: 235 obese outpatients, aged 18-65 y with a body mass index (BMI) within the range 27-40 kg/m2. MEASUREMENTS: Weight, height, waist and hip circumference, and medical history, assessment of hunger, satiety, appetite and craving for sweet, savoury and carbohydrate foods, and also for carbohydrate snacking, standard laboratory assessments, blood pressure, heart rate and ECG. RESULTS: The group mean (+/- s.e.m.) weight loss at end-point was 1.4 +/- 0.5 kg for placebo (n = 59), 2.4 +/- 0.5 kg for 5 mg sibutramine (n = 56), 5.1 +/- 0.5 kg for 10 mg sibutramine (n = 59) and 4.9 +/- 0.5 kg (n = 62) for 15 mg sibutramine. The difference observed between the placebo and the 10 mg and 15 mg groups was statistically significant from week 2 onwards (P < 0.01), but there was no significant difference between these sibutramine groups. The percentage of patients losing > 5% of initial bodyweight was significantly greater for 15 mg sibutramine (55%) and 10 mg sibutramine (49%) than for treatment with placebo (19%), (P < 0.001). During the double-blind period, 41 patients (17%) withdrew prematurely and 168 patients (71%) reported 453 adverse events. The incidence and type of adverse event and the rates of withdrawal, were not significantly different in the four groups. No significant differences between the groups were observed, in respect of changes in systolic and diastolic blood pressure, but a significant increase in heart rate (about 4 beats/min) was noted for patients who received 10 mg or 15 mg sibutramine, compared with the placebo (P < 0.001). CONCLUSION: These data demonstrate dose-related weight loss with sibutramine treatment for up to 12 weeks in obese patients. Doses of 10 mg and 15 mg once daily were shown to be similarly effective, well tolerated and significantly more effective than the placebo.

Adult↗
PubMed1998

[Cholesterolemia and total, cardiovascular and cancer mortality. Study of a cohort of 220,000 people].

The distribution of cholesterolemia and their relationship to total mortality, cardiovascular mortality, and cancer mortality were studied in a population of 125,513 men and 96,301 women, aged 16-90. Cholesterolemia in the population increases with age, up to age 50-60 for men and 60-70 for women. Beyond these ages, cholesterolemia decreases very significantly for men and moderately for women. Upon global examination of the entire population, the relationship between cholesterolemia and total mortality is observed as a U-shaped curve. The relationship with cancer mortality is slightly negative in men and appears as a U-shaped curve in women. The relationship with cardiovascular mortality in men is strongly positively correlated when adjusted for body mass index, blood pressure, tobacco consumption, gamma GT, and age. This relationship is not significant in women. There is a significant interaction in the relationship between cholesterolemia and mortality in men for weight, body mass index, vital capacity, maximum expiration volume per second, tobacco consumption, urea, serum albumin, hematocrit, hemoglobin, alkaline phosphatases, gamma GT, red cell volume, and sedimentation rate. Age is a fundamental variable to take into account. Thus, in men under 50 years of age at the time of inclusion, the relationship between cholesterolemia and total mortality shows a positive tendency, and the relationship with cardiovascular mortality is strongly positive. In men over 65 years of age, these relationships are negative. The same tendencies exist for cancer mortality. The reasons for these negative relationships may be related to the decreased cholesterol levels in subjects with malnutrition or diseases (essentially hepatic diseases); this is especially true in older subjects. These data push for additional in-depth analysis of these relationships and interactions, according to age categories and detailed causes of mortality. They also reinforce the idea that, in some patients, low cholesterolemia appears to be a marker for predisposition or the result, but not a cause, of cancer.

Adolescent↗
PubMed1998

Hosts manipulated by one parasite incur additional costs from infection by another parasite.

Manipulation of host phenotype by parasites often serves to increase the predation rate of definitive hosts on intermediate hosts. For intermediate hosts, the indirect consequences of manipulation may extend beyond the direct increase in predation, however. Metacercariae of the trematode Curtuteria australis encyst in the foot of New Zealand cockles, Austrovenus stutchburyi, and stunt its growth, rendering cockles incapable of burrowing into the sediments. Here, we show that cockles manipulated by C. australis are 5 times more likely to be infected by the castrating sporocysts of another trematode than normal, nonmanipulated cockles. Our results indicate that the consequences for C. australis-manipulated cockles are far more important than a simple increase in the risk of predation and that indirect repercussions of manipulation can be as severe as direct ones.

Animals↗
PubMed1998

Nonmanipulative parasites in manipulated hosts: 'hitch-hikers' or simply 'lucky passengers'?

Manipulation of intermediate host behavior to favor parasitic transmission has been demonstrated in a wide of range of parasitic taxa. Recent advances in parasitology have suggested that nonmanipulative parasite species can obtain a high probability of transmission simply by infecting hosts already manipulated ('hitch-hiker' parasites). In this study, from a field collection of Gammarus aequicauda (Amphipoda, second intermediate host), we analyzed the ecological association between the manipulative trematode Microphallus papillorobustus and the 2 nonmanipulative trematodes Microphallus hoffmanni and Levinseniella tridigitata. Although these 2 nonmanipulative parasites should be a priori advantaged when infecting manipulated gammarids, there was no significant ecological association between parasite species. We discuss the possible reasons why these 2 nonmanipulative parasites are only 'lucky passengers' rather than 'hitch-hikers.'

Animals↗
PubMed1997

Use of Doehlert matrices for study of poliovirus-1 adsorption.

Experiments designed according to Doehlert matrices were carried out to study poliovirus-1 adsorption to Na-montmorillonite in a complex aqueous environment. Salt concentration and valence, virus load, clay concentration, and organic matter concentration were included in the design as selected parameters for possible or known involvement in viral adsorption in environmental waters. Use of this experimental design not only allowed to detect and quantify direct influence of the tested parameters upon the viral response, but also to reveal the influence of interactions between these tested factors. Thus, beyond the reassessment of the higher efficiency of multivalent cations on virus adsorption, as opposed to monovalent ones, detection was enabled of a tannic acid/aluminium specific interaction that seemed to be responsible for the nonavailability of these elements for interaction with viruses. Such a statistical tool allows for a gain in experimental accuracy beyond technical improvements and is particularly suited for low-cost study of multifactorial phenomena.

Adsorption↗
PubMed1997

Evaluation of four candidate genes encoding proteins of the dopamine pathway in familial and sporadic Parkinson's disease: evidence for association of a DRD2 allele.

We assessed the role of four candidate genes encoding proteins involved in dopaminergic transmission, the dopamine transporter (DAT), the dopamine receptor D2 (DRD2), and the main catabolic enzymes of dopamine, monoamine oxidase A (MAOA) and B (MAOB), through allelic association studies in a population of familial and sporadic Parkinson's disease (PD). Using intronic polymorphisms of the four candidate genes, we studied the allelic distributions of the polymorphic markers in 18 affected members, one patient was chosen randomly from each PD family; 60 sporadic PD and 60 healthy unrelated control subjects were matched for sex and for country of origin. All subjects were white. To complete the study of the DRD2, we subsequently tested 40 additional sporadic PD and 40 control patients, who were recruited using a similar procedure. For DAT, MAOA, MAOB polymorphisms, similar allelic frequencies were present in familial, sporadic PD and control patients. In contrast, at the DRD2 locus, the overall allelic distribution was significantly different in the sporadic PD (p < 0.01) and in the familial PD groups (p < 0.05), each was compared with the controls. The odd ratios were significant (p < 0.01) in sporadic PD and in familial PD for allele 3 with respective values of 1.84 (95% CI, 1.23-2.74) and 2.83 (95% CI, 1.32-6.08). Individuals who were homozygous for allele 3 were 2.3 times more frequent in the sporadic PD than in controls. Results suggest that DRD2, but not DAT, MAOA and MAOB, might be a genetic determinant of PD in the population tested.

Alleles↗
PubMed1996

A homogeneous fluorescence polarization assay for detection of antibody to Brucella abortus.

A homogeneous fluorescence polarization (FP) assay (FPA) was developed for detection of antibody in bovine sera to Brucella abortus. The assay used O-polysaccharide prepared from B. abortus lipopolysaccharide in the molecular weight range of 20-30 kDa which was conjugated with fluorescein isothiocyanate and used as a tracer. Fluorescence polarization was measured with a FPM-1 fluorescence polarization analyzer. Sample (20 microliters) was added to 2.0 ml of diluent buffer at ambient temperature. A serum blank reading was taken and tracer (10 microliters) to yield approx. 1.5 nM fluorescein equivalents was added. The FP of the tracer was determined after a period of greater than 2 min. A positive reaction was indicated by a significant elevation of the FP reading over the negative control. In a blind study, 9480 bovine sera were tested in addition to sets of four controls which were included with each lot of 100 samples tested. The controls were a strong positive, a weak positive, a negative and a serum derived from a B. abortus strain 19 vaccinated cow. Test sera included 8669 sera from Canadian cattle which were negative by routine serological tests, 561 sera from cows from which B. abortus had been isolated either from tissues or milk and 250 sera from cattle previously vaccinated with B. abortus strain 19 at various times. One lot of O-polysaccharide tracer was used for all tests. The initial cut-off for negative samples in the fluorescence polarization assay was set at 107.2 mP. This resulted in a sensitivity estimate of 98.1 +/- 1.1% and the specificity was 99.8 +/- 0.09%. After decoding the samples and retesting false positive and negative reactions, the sensitivity estimate was 98.5 +/- 1.0% and the specificity was 100%. It became evident that the initial cut-off value was set too high and, using ROC analysis, a cut-off of 90 mP increased the sensitivity to 99.02% while the specificity decreased to 99.96%. Of the 250 sera from vaccinated cattle, 248 were negative giving a point specificity value of 99.2%.

Animals↗
PubMed1996

Determination of the three-dimensional structure of hordothionin-alpha by nuclear magnetic resonance.

The high-resolution three-dimensional solution structure of the plant toxin hordothionin-alpha obtained from korean barley was determined by using two-dimensional NMR techniques combined with distance geometry and restrained molecular dynamics. Experimentally derived restraints including 292 interproton distances from nuclear Overhauser effect measurements, 16 hydrogen bond restraints together with four disulphide bridge restraints were used as input to calculations of distance geometry and restrained molecular dynamics. Also included in the calculations were 36 phi and 17 chi 1 torsion angles obtained from 33JHN alpha and 3J alpha beta coupling constants in double quantum filtered COSY and primitive exclusive COSY experiments, respectively. The overall protein fold is similar to crambin and purothionin-alpha 1. Two alpha-helices running in opposite directions are found on the basis of 3JHN alpha and 3J alpha beta and deuterium exchange rates for backbone NH protons, and encompass residues 7-18 and 22-28. These two helices are connected by a turn and form a 'helix-turn-helix' motif. A short stretch of an anti-parallel beta-sheet exists between residues 1-4 and 31-34. the two protein termini of hordothionin-alpha are 'well-anchored'; the N-terminus of the protein is immobilized by this short beta-sheet whereas the C-terminus is 'pasted' to the carbonyl group of Cys-4 by a very stable hydrogen bond. The average root-mean-square differences for the backbone and heavy atoms after the restrained molecular dynamics calculations are 0.62 and 1.16 A respectively. These numbers represent a significant improvement over the corresponding values for the previous NMR structures of other thionins. The distance violation from the experimental interproton distances for the final structures is 0.14 for all atoms.

Amino Acid Sequence↗
PubMed1996

Parasites as host [corrected] evolutionary prints: insights into host evolution from parasitological data.

The close relationships which link parasitic organisms to their hosts have led to the use of parasites as biological tags. Most studies on this topic refer to parasites as host ecological tags. Recent development of molecular methods which give access to the genomic structures of populations have provided new information on the evolutionary biology of parasites. In this paper, we have attempted to review whether parasites can be considered as "host evolutionary prints", and focus our discussion on host biodiversity and biogeography.

Animals↗
PubMed1996

The influence of intensity of infection by a trematode parasite on the reproductive biology of Gammarus insensibilis (Amphipoda).

Following the behavioural alterations induced by the trematode Microphallus papillorobustus Rankin 1940 (Trematoda, Microphallidae) on its second intermediate host, the amphipod Gammmarus insensibilis, infected individuals are likely to mate among themselves. We investigated the influence of parasite intensity on the reproductive biology of infected hosts. In the mating system of amphipods, males compete severely for access to females and large males have greater ability to obtain large and more fecund females. We showed that the null hypothesis of random pair formation according to parasite intensity could not be rejected. In addition, infected males obtained females of the expected size according to their own sizes, whatever their parasite intensities. However, in both males and females, the parasite intensity increased the intermoult duration. Because size and reproductive success are strongly correlated in amphipods, we discuss the influence of this process on host fitness.

Animals↗
PubMed1996

The distribution and abundance of Lernaeocera lusci (Copepoda) on hake (Merluccius merluccius) and bib (Trisopterus luscus) (Teleostei).

Distribution patterns, mean intensity and prevalence of Lernaeocera lusci (Copepoda, Pennellidae) in its hosts Trisopterus luscus (Teleostei, Gadidae) and Merluccius merluccius (Teleostei Merlucciidae) were examined, together with parasitic abundance and aggregation in relation to the size of the host. The mean parasite abundance and variance to mean abundance ratio increased with host size, suggesting that the accumulation of this parasite had no noticeable impact on the structure of either host population. Merluccius merluccius being a newly colonized host in the Mediterranean, these results are discussed in relation to current ideas on the evolution of pathogenicity in heterospecific associations.

Animals↗
PubMed1996

Lanreotide inhibits human jejunal secretion induced by prostaglandin E1 in healthy volunteers.

1. Somatostatin inhibits hormonal secretions in the gastrointestinal tract. Somatostatin analogues are used in the treatment of VIPome-related watery diarrhoea. In addition, more than 10% of patients with AIDS suffer from diarrhoea likely due to the increased intestinal secretion of water and ions. However, the direct effect of somatostatin on the flux of water and ions in the intestine has not been, so far, analyzed in vivo. The aim of the present study was to evaluate the effect of lanreotide, a somatostatin analogue, on the movements of water and ions in the jejunum in man. 2. Accordingly, 10 healthy volunteers (age 18-35 years, mean 27) and two patients with AIDS (26 and 33 years) suffering from water diarrhoea (> 800 ml day-1) underwent intestinal perfusion using a four lumen tube with proximal occluding balloon. The segment tested was 25 cm long. The jejunum was infused by an isotonic control saline solution containing polyethylene glycol (PEG) as nonabsorbable marker. Basal jejunal secretions were measured in all subjects. Prostaglandin E1 (PGE1) was administered intraluminally to stimulate jejunal secretion in healthy volunteers. The effect of intravenous lanreotide on the jejunal PGE1-induced secretions of water and electrolytes was analysed in healthy subjects and on the basal secretions in AIDS patients. Each period was analyzed on the basis of three (10 min) successive intestinal juice collections after 20-30 min equilibration time. The antisecretory effect of lanreotide was evaluated in each subject as the difference between fluxes compared to the control period. 3. In healthy volunteers, PGE1 induced secretion of H2O, Na+, K+ and Cl- in the jejunum and lanreotide reduced significantly PGE1-induced response. In both AIDS patients basal fluxes of water and ions were reduced by lanreotide in a dose-dependent manner. 4. Somatostatin can reduce stimulated-jejunal secretion of ions and water in normal subjects and may improve water diarrhoea in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Effect of maternal diabetes on the pattern of selected insulin resistance syndrome parameters in normal glucose tolerant subjects of two Algonquin Indian communities in Quebec.

OBJECTIVE: To determine whether a maternal antecedent with diabetes has an effect on insulin resistance syndrome parameters. RESEARCH DESIGN AND METHODS: We studied 352 Algonquin Indians from Quebec aged at least 15 years who had no personal antecedents with diabetes. Data concerned clinical and biological parameters and the parental antecedents with diabetes. RESULTS: For subjects over > 30 years, fasting insulin and cholesterol levels were significantly higher in the group with a maternal history of diabetes than in the group with a paternal history. Significant differences were observed for serum triglyceride, BMI, and subscapular skinfold thickness when comparing subjects with a maternal history and those with no parental history of diabetes. Blood pressure and fasting glucose did not differ according to parental history. CONCLUSIONS: Subjects of maternal antecedents with diabetes have known risk factors for NIDDM. This study does not identify whether there is a genetic or maternal environmental reason for this association.

Adolescent↗
PubMed1996

The synthetic tetrapeptide AcSDKP protects cells that reconstitute long-term bone marrow stromal cultures from the effects of mafosfamide (Asta Z 7654).

The tetrapeptide AcSDKP (Seraspenide) has been described as an inhibitor of CFU-S entry into DNA synthesis; as a result, its administration can protect mice against lethal doses of cytosine arabinoside. We have studied the ability of AcSDKP to protect and promote the growth of early CD34+ human bone marrow (BM) stem cells in Dexter long-term cultures following exposure to a toxic concentration of mafosfamide. The protection assay was based on the preincubation of CD34+ BM cells with or without AcSDKP at 10(-10)M or 10(-8)M followed by exposure to a toxic dose of mafosfamide (100 micrograms/mL). The production of granulomonocytic progenitor cells (CFU-GM) was subsequently studied in long-term bone marrow cultures (LTBMC) of the samples exposed to mafosfamide and preincubated or not (control) with AcSDKP. After a lag of 2 to 3 weeks, the number of CFU-GM peaked at the 4th to 5th week in both the supernatant and the adherent layers. A greater production of granulomonocytic progenitor cells was observed in LTBMC from the samples preincubated with AcSDKP compared with control cells. Depending on the BM samples, enhanced production of CFU-GM in the AcSDKP-treated cell cultures was observed at either the 10(-10)M or 10(-8)M concentration. These results suggest that AcSDKP can protect in vitro human long-term culture-initiating cells (LTC-IC) from mafosfamide, resulting in an increased production of CFU-GM from this early stem cell compartment.

Amino Acid Sequence↗
PubMed1995

Pattern of failure in patients with inflammatory breast cancer treated by alternating radiotherapy and chemotherapy.

BACKGROUND: Patients with inflammatory breast cancer have a high risk of developing a local recurrence and/or distant metastases. Treatment with combined chemotherapy and locoregional radiotherapy contributes to a decrease in both risks. This study presents treatment results and evaluates the pattern of failure when an alternating chemoradiotherapy schedule is used. METHODS: One hundred twenty-five patients with nonmetastatic inflammatory breast cancer were treated with an alternating schedule of radiotherapy and chemotherapy. All women recruited were younger than 70 years of age and had a T4d, histologically proven infiltrating carcinoma with N0 to N2 axillary disease. The protocol consisted of three cycles of induction chemotherapy with doxorubicin, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil followed by three series of locoregional radiotherapy, delivering a total dose of 65-75 Gy to the breast tumor. Five additional cycles of chemotherapy with 5-fluorouracil/doxorubicin/cyclophosphamide were to be administered in between the first two and after the third radiotherapy course. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. RESULTS: Toxicity was moderate and this strategy proved feasible although most of the patients only received six instead of the eight planned cycles of chemotherapy. Eighty-two percent of the patients achieved a complete response at the end of the treatment. The cumulative 5-year local failure and distant metastasis rates were 27% and 53%, respectively. Assuming competing events, local failures, contralateral recurrences, and distant metastases were the first site of failure in 18%, 5%, and 38% of patients, respectively. The 5-year overall and disease free survival rates were 50% and 38%, respectively. The main prognostic factor was tumor size. CONCLUSIONS: Alternating high doses of radiotherapy and chemotherapy is a feasible treatment schedule and permits breast conservation. Disease free survival is comparable to that of recently published series. As the main causes of failure are distant metastases, higher dose chemotherapy should be evaluated, in an attempt to further improve overall survival.

Adenocarcinoma↗