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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

Therapeutic efficacy of the thymidine kinase/ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study.

Contradictory experimental results and human trials have questioned the clinical relevance of the HSVtk/ganciclovir system. To bypass the problem of transfection efficiency, we used a glioma cell line stably expressing the HSVtk gene, which was also fully characterized from gene to protein. We also designed a more clinically relevant experimental protocol, consisting of late GCV delivery on large tumor formations. In short-term studies, histological examination revealed a significant decrease in tumor volume in GCV-treated animals from day 1 or from day 10 after cell inoculation. We observed that late GCV delivery is as efficient as early delivery, probably because GCV can reach tumor cells more easily when neoangiogenesis occurs. In long-term experiments, the survival of treated rats bearing 15-day tumors was improved by 60% compared with C6 control animals. Surprisingly, a 30% survival rate was observed in C6TK control animals. Nuclear magnetic resonance imaging demonstrated, in all surviving animals, a complete regression of tumors without mass effect. These results clearly demonstrate that the HSVtk/GCV system remains a potent therapeutic strategy, even when tested in large tumors, in contrast with the microscopic tumor formations previously reported.

Animals↗

Determinants of left ventricular mass in a French male population.

The aim of this analysis was to study the determinants of left ventricular mass evaluated by echocardiography. A total of 843 healthy men aged 47-61 years, who had a standard health check-up at the Centre d'Investigations Preventives et Cliniques (IPC Center), were included in the study. None of the subjects were being treated for cardiovascular disease at the time of their visit and each had a standard clinical and biological examination. The answers to a lifestyle questionnaire, weight at 20 years and family history were recorded. All subjects had an echocardiogram to evaluate left ventricular mass. Left ventricular mass values were adjusted for height using the ratio of left ventricular mass to height. Current body mass index, systolic and diastolic blood pressure, brachial circumference, triglycerides and a family history of sudden death were positively associated with this ratio (p < 0.01). Physical activity and tobacco consumption were associated with left ventricular mass. Body mass index at 20 years, variation of body mass index since that age, systolic blood pressure and family history of sudden death explain 21% of the ratio of left ventricular mass/height (body mass index at 20 years: 11.8%; variation of body mass index: 5.1%; systolic blood pressure: 2.3%; and family history of sudden death: 0.4%). The other factors explain only 1.4% of this variance and were not significantly associated with the ratio of left ventricular mass to height. Body mass index at 20 years was the strongest determinant of left ventricular mass, suggesting that left ventricular mass at middle age is in large measure determined much earlier in life. A family history of sudden death before the age of 60 years is also an important determinant of left ventricular mass, independent of obesity. These factors must be taken into account in order to prevent an increase in left ventricular mass.

Age Factors↗

Associations between heart rate and other risk factors in a large French population.

OBJECTIVES: In a large general French population of 100,000 subjects, the relationship of resting heart rate with age, gender, demographic parameters, physical activity and classical risk factors was evaluated. POPULATION AND METHODS: A population composed of all the subjects who had a free health check-up at the IPC Centre between 1992 and 1995 (62,353 men and 35,371 women) was analysed. Heart rate was considered either as a continuous parameter or as a qualitative parameter. The study population was divided into four heart rate classes: < 65, 65-74, 75-84 and > or = 85 beats/min. RESULTS: Women had significantly higher heart rate values than men, and this gender difference was constant in the different age groups. In both genders, heart rate was positively associated with blood pressure, triglycerides, glycaemia and physical inactivity, and negatively with body height Heart rate was also correlated with total cholesterol but only in men. The only factor having opposite effects on heart rate in men and women was tobacco smoking (positive in men and negative in women). Among untreated hypertensive men, 21.3% had a heart rate > or = 85 beats/min compared with only 4.0% among normotensive men. In women, these percentages were 23.6 and 7.6%, respectively. Subjects with untreated mild hypertension or uncontrolled treated hypertension also showed increased rates of tachycardia compared to normotensives. CONCLUSIONS: The present analysis, performed in a large French population, shows that high heart rate is associated with several other risk factors, especially hypertension, suggesting that tachycardic subjects have a high risk profile.

Adult↗

Calf-thigh sequential pneumatic compression compared with plantar venous pneumatic compression to prevent deep-vein thrombosis after non-lower extremity trauma.

OBJECTIVE: To compare the effectiveness of calf-thigh sequential pneumatic compression devices with the effectiveness of plantar venous intermittent pneumatic compression devices in prevention of venous thrombosis after major trauma. SUBJECTS AND METHODS: We evaluated 181 consecutive patients after major trauma without lower extremity injuries that precluded the use of pneumatic compression devices. We randomly assigned 149 patients to either calf-thigh sequential pneumatic compression or plantar venous pneumatic compression. After blinding the observers to the method of prophylaxis against deep-vein thrombosis, we performed bilateral compression ultrasonography on or before day 8 after randomization. RESULTS: Among 149 randomized patients, 62 who received calf-thigh sequential pneumatic compression and 62 who received plantar venous intermittent pneumatic compression devices completed the trial. Thirteen patients randomized to plantar venous intermittent pneumatic compression (21.0%) and 4 patients randomized to calf-thigh sequential pneumatic compression (6.5%) had deep-vein thrombosis (p = 0.009). Seven of 13 patients with deep-vein thrombosis after prophylaxis with plantar venous intermittent pneumatic compression had bilateral deep-vein thromboses, whereas all 4 patients with deep-vein thrombosis after prophylaxis with calf-thigh sequential pneumatic compression had unilateral deep-vein thrombosis. CONCLUSION: Calf-thigh sequential pneumatic compression prevents deep-vein thrombosis more effectively than plantar venous intermittent pneumatic compression after major trauma without lower extremity injuries.

Adult↗

Influence of heart rate on mortality in a French population: role of age, gender, and blood pressure.

-The aim of the present study was to assess the effects of high heart rate on mortality in different subgroups in a French population according to age, gender, and blood pressure levels. We studied 19 386 subjects (12 123 men, 7263 women), aged 40 to 69 years, who had a routine health examination at the Centre d'Investigations Préventives et Cliniques (IPC) between 1974 and 1977. Heart rate (HR) measured by ECG was classified into 4 groups: HR1, <60; HR2, 60 to 80; HR3, 81 to 100; and HR4, >100 bpm. Mortality data were recorded for the period of 1974 through 1994. In both sexes, HR was a significant predictor of noncardiovascular mortality. In men, the relative risk (95% confidence interval) for cardiovascular death after adjustment for age and other risk factors in the HR2, HR3, and HR4 groups was 1.35 (1.01 to 1.80), 1.44 (1.04 to 2.00), and 2.18 (1.37 to 3.47), respectively, when compared with HR1. In women, HR did not influence cardiovascular mortality. The association of HR with cardiovascular mortality in men was (1) related to a strong association with coronary but not cerebrovascular mortality, (2) independent of age and hypertension, and (3) influenced by the level of pulse pressure; in patients with high pulse pressure (>65 mm Hg), accelerated HR was not associated with increased cardiovascular mortality. In conclusion, in a large French population, accelerated resting HR represents an independent predictor of noncardiovascular mortality in both genders, and of cardiovascular mortality in men, independent of age and the presence of hypertension. Further investigations are needed to explain the complex interactions between HR, pulse pressure, and cardiovascular complications.

Adult↗

Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population.

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.

Adult↗

Ambulatory and community-based services.

The shift in the site of service delivery from inpatient and institutional to ambulatory and community settings has been prompted by concerns over cost and the prospect for improving the quality of life. In response to these concerns, Medicare has implemented several demonstrations that emphasize ambulatory and community-based services. In this issue, articles are presented on four demonstrations, which focus on the extent to which coordinated care models reduce health care costs, and the cost effectiveness and beneficiary outcomes of disease-specific programs. Two articles are included on home health. One examines home health care in relation to the other Medicare post-acute benefits, and the other focuses on the use of home health care in the treatment of end stage renal disease (ESRD). Finally, two articles report on Section 1915c Medicaid home and community-based waiver programs.

Aged↗

Diagnosis of bovine brucellosis using a homogeneous fluorescence polarization assay.

To evaluate the fluorescence polarization assay (FPA) for the serological diagnosis of bovine brucellosis, 118 sera from cattle which were culture positive for Brucella abortus, 1751 sera from cattle from premises containing cattle infected with B. abortus, 1222 sera from cattle vaccinated with B. abortus strain 19 and 1199 sera from cattle with no evidence of brucellosis were tested in Argentina, Chile, Mexico and in the American states of Iowa, Missouri and Texas. Initial determination of serological positivity and negativity was based upon reactivity in currently used serological tests, consisting of a rapid screening test, the rose-bengal or the buffered plate antigen tests, followed by a second serological test, the complement fixation test. Sensitivity of the FPA (sera from culture positive animals) ranged from 87.5% to 100%. Serological positivity of cattle from infected premises ranged from 65.5% to 99.0% while the % negative cattle in herds without evidence of brucellosis was between 94.9 and 100%. Of B. abortus strain 19 vaccinated cattle which were positive in at least one in-use serological tests, 88.2% were negative in the FPA. In contrast, previous Canadian studies, sensitivity values were 99.0% and 100% and the specificity in both cases was 100%. This discrepancy was probably due to the use of less well characterized sera in the current study.

Animals↗

A comparison of sibutramine and dexfenfluramine in the treatment of obesity.

OBJECTIVE: Because long-term weight reduction is often unsuccessful with dietary restriction alone, pharmacological agents have been used to promote weight loss. We have compared the novel (multiple monoamine neurotransmitter reuptake inhibitor) antiobesity drug sibutramine (10 mg once daily) with the extensively studied serotonin-releasing antiobesity agent dexfenfluramine (15 mg twice daily). RESEARCH METHODS AND PROCEDURES: 226 healthy outpatients (aged 18 to 65 years; body mass index > or =27 kg/m2) were included in a 12-week, randomized, double-blind, parallel group study. The main outcome measures were changes in weight, body mass index, waist and hip circumference and ratio, and safety profiles. RESULTS: Mean (+/-SEM) absolute weight loss was 4.5 +/- 0.4 kg in the sibutramine group (n = 112) and 3.2 +/- 0.3 kg in the dexfenfluramine group (n = 112) (endpoint analysis); 4.7 +/- 0.4 kg in the sibutramine group (n = 101); and 3.6 +/- 0.3 kg in the dexfenfluramine group (n = 94) (completers analysis). Comparing the two treatments under the conventional null hypothesis of equality as a secondary analysis, weight loss at endpoint in patients receiving sibutramine was significantly greater than that achieved with dexfenfluramine (p<0.05). Both drugs had similar adverse events profiles: 174 patients (77%) experienced adverse events; 17 patients withdrew due to adverse events (sibutramine, n = 6; dexfenfluramine, n = 11). Pulse rate increased significantly in sibutramine-treated patients (3.6 bpm), but decreased in dexfenfluramine-treated patients (-0.9 bpm). DISCUSSION: Sibutramine (10 mg once daily) is at least as effective as dexfenfluramine (15 mg twice daily) in achieving weight loss in patients with obesity.

Adult↗

Exploitation of manipulators: 'hitch-hiking' as a parasite transmission strategy.

For many parasites with complex life cycles, manipulation of host behaviour is an adaptation to increase the probability of successful transmission. Since manipulation is likely to be costly, other parasites may exploit hosts already manipulated so as to ensure their transmission without investing in manipulation. Such a cheating strategy, called 'hitch-hiking', could be adaptive in a range of situations. We first propose and discuss criteria that should be met by any parasite to be considered a hitch-hiker. Then, to understand the evolution of the hitch-hiking strategy, we use simple mathematical models to analyse the influence of several variables on the potential benefits for a nonmanipulative parasite of actively seeking a ride to the definitive host with a manipulative parasite. The models suggest that the prevalence or abundance of manipulative parasites will be a key determinant of whether hitch-hiking can be an advantageous option for other parasites. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

[Laparoscopic appendectomy in the adult].

AIM OF THE STUDY: The benefits of laparoscopic appendectomy remain controversial. The aim of the study was to evaluate the advantages and disadvantages of this technique. MATERIAL AND METHODS: Four hundred and forty-eight patients operated on for suspected appendicitis during a 5-year period were analysed in a retrospective study. The preoperative diagnosis was corrected in 21.4% of the cases (8.1% for males and 28.7% for females) and the conversion rate was 9.7%. There were 17 patients with generalized peritonitis and 28 with localized peritonitis. During the past year, this surgical method was introduced in another hospital and a prospective study included 92 consecutive patients operated on for appendicitis. The operating time was 53 minutes and the conversion rate was 7.6%. There were five patients with generalized peritonitis and eight with localized peritonitis. RESULTS: There were no postoperative deaths. In the first period, the morbidity rate was 2.3% in the laparoscopic group without conversion. After pathological examination, there was a 14.2% rate of normal appendix. The mean hospital stay was 4.3 days. In the second period, there were only three minor complications and the mean hospital stay was 4.19 days. CONCLUSION: The choice of laparoscopic approach is associated with some advantages: corrections of the diagnosis (mainly in young women) and simplification of the postoperative course, provided that the surgeon has sufficient experience.

Adolescent↗

Manipulation of a mollusc by a trophically transmitted parasite: convergent evolution or phylogenetic inheritance?

We investigated the influence of infection by the trematode Curtuteria australis on the burrowing behaviour of its intermediate host, the bivalve Austrovenus stutchburyi. Laboratory experiments and field observations revealed that cockles, unable to bury completely or even partially under the sediment, have a reduced foot length compared with buried individuals. The ability to bury proved to be highly repeatable in field experiments: cockles found at the surface and transplanted to an experimental area did not bury themselves, and cockles found buried stayed buried when relocated. All metacercariae of C. australis were found strictly in the foot and for each of 3 samples collected in different sites, there was a negative and significant relationship between the relative length of the foot and the parasite load. A predation test conducted under natural conditions indicated that cockles with the stunted foot and the altered behaviour are significantly more susceptible to predation by aquatic birds than other cockles. Given that the definitive host of C. australis is an oystercatcher, we first discuss our results in the context of transmission strategy. Comparisons with other studies on more or less related trematode species parasitic in bivalves and evolving under similar constraints for their transmission, shed light on the origin of this adaptation in C. australis.

Animals↗

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↗

[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↗

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↗

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↗