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Biomedical subjects

P Schaffer

Publications and source records attributed to P Schaffer.

At least 19 recordsLinked to original sources
PubMed1999

Repolarizing currents in ventricular myocytes from young patients with tetralogy of Fallot.

OBJECTIVE: It was the aim of our study to describe repolarizing currents in ventricular myocytes isolated from children with tetralogy of Fallot. This is the first report on outward currents in ventricular myocytes from children. METHODS: Ventricular myocytes were isolated from tissue samples of the outflow tract of the right ventricle which were obtained during corrective surgery of tetralogy of Fallot. Action potentials and whole-cell currents were recorded with the patch clamp technique at a temperature of 36-37 degrees C. RESULTS: The mean resting potential was -71.7 +/- 1.92 mV, action potential amplitude was 110 +/- 2.96 mV and action potential duration at 90% repolarization was 794 +/- 99.5 ms (n = 12). In four out of 12 myocytes early afterdepolarizations (EADs) were observed. Upon hyperpolarization Ba(2+)-sensitive inward currents similar to the inward rectifier current (IKl) could be observed. The current density at -120 mV was -22.8 +/- 2.47 pA/pF (n = 14). A transient outward current (Itol) could be recorded in all myocytes studied, the current density varied from 0.3 to 8.6 pA/pF with a mean of 3.77 +/- 0.47 pA/pF at +40 mV (n = 38). Recovery of Itol from inactivation was fast (70% recovery within 100 ms), rate-dependent reduction amounted to 38.2% at 4 Hz. A delayed rectifier current was seen in only two out of 38 myocytes (rapid component IKr). CONCLUSIONS: The electrophysiological characteristics of right ventricular myocytes isolated from children with tetralogy of Fallot resemble in most cases subendocardial myocytes from adults. The most prominent difference is a fast recovery from inactivation as well as a small rate dependent reduction of Itol. The observed EADs may have clinical implications.

Action Potentials↗
PubMed1999

The sulphonylurea glibenclamide inhibits voltage dependent potassium currents in human atrial and ventricular myocytes.

1 It was the aim of our study to investigate the effects of the sulphonylurea glibenclamide on voltage dependent potassium currents in human atrial myocytes. 2 The drug blocked a fraction of the quasi steady state current (ramp response) which was activated positive to -20 mV, was sensitive to 4-aminopyridine (500 microM) and was different from the ATP dependent potassium current IK(ATP). 3 Glibenclamide dose dependently inhibited both, the peak as well as the late current elicited by step depolarization positive to -20 mV. The IC50 for reduction in charge area of total outward current was 76 microM. 4 The double-exponential inactivation time-course of the total outward current was accelerated in the presence of glibenclamide with a tau(fast) of 12.7+/-1.5 ms and a tau(slow) of 213+/-25 ms in control and 5.8+/-1.9 ms (P<0.001) and 101+/-20 ms (P<0.05) under glibenclamide (100 microM). 5 Our data suggest, that both repolarizing currents in human atrial myocytes, the transient outward current (Ito1) and the ultrarapid delayed rectifier current (IKur) were inhibited by glibenclamide. 6 In human ventricular myocytes glibenclamide inhibited Ito1 without affecting the late current. 7 Our data suggest that glibenclamide inhibits human voltage dependent cardiac potassium currents at concentrations above 10 microM.

Adenosine Triphosphate↗
PubMed1999

Cancer registry data based estimation of regional cancer incidence: application to breast and colorectal cancer in French administrative regions.

STUDY OBJECTIVE: In many countries, cancer registries cover only a small part of the national population. Cancer incidence for the rest of the country has therefore to be estimated. This can be done from mortality data using the relation between incidence and mortality observed in the cancer registry areas. Such an approach was used to study geographical variation and trend of colorectal and breast cancer incidence in France where 10% of the national population is covered by cancer registries. DESIGN: This study applies the incidence/mortality ratios of cancer registry areas to regional mortality data to obtain an estimation of cancer incidence at a given point in time. Age and period effects are included in the statistical models. MAIN RESULTS: The incidence estimations are given for 21 administrative regions and three time points (1985, 1990, 1995). The European standardised incidence rates for breast cancer ranged from 86.8 to 128.8. For colorectal cancer, these rates ranged from 48.2 to 79.6 for men, and from 32.5 to 48.8 for women. Breast cancer incidence has increased considerably between 1985 and 1995 with a higher increase in the north than in the south of France. The incidence of colorectal cancer has also increased, albeit to a lesser extent. CONCLUSION: The incidence estimation method proposed leads to regional incidence rates that are useful for planning health care services on a regional basis and may also be used to study regional differences in incidence. This method is useful when only partial incidence data are available.

Adult↗
PubMed1999

Type 2 diabetes mellitus: association study of five candidate genes in an Indian population of Guadeloupe, genetic contribution of FABP2 polymorphism.

We studied by PCR-RFLP 6 polymorphisms in these 5 candidate genes: Ala54Thr in the fatty acid binding protein 2 gene (FABP2), A to G substitution in the uncoupling protein type 1 gene (UCP1), Asp905Tyr in the protein phosphatase type 1 gene (PP1G), Trp64Arg in the human beta 3 adrenergic receptor gene (beta 3AR) and 2 RFLP sites of the vitamin D receptor (VDR) gene (VDRTaq1 and VDRApa1). This study was conducted among 89 cases and 100 controls matched according to age, gender and absence of first degree family link (11 triplets with 2 controls for 1 case and 78 pairs with 1 control for 1 case). Cases and controls were taken among a sample of 429 individuals selected for the study of the prevalence of diabetes in this ethnic group from Guadeloupe. By conditional logistic regression analysis, there was a significant relation (p = 0.02) between the Ala54Thr FABP2 polymorphism and Type 2 DM. Multivariate analysis discriminate the FABP2 polymorphism (p = 0.10), a triglyceridemia over 2 g/l (p < 10(-3)) and high blood pressure (p = 10(-2)) as variables associated with Type 2 DM in this population. These findings suggest that FABP2 does not represent a major gene for Type 2 DM in this migrant Indian population living in Guadeloupe, but seems to be related to the metabolic insulin resistance syndrome.

Adult↗
PubMed1999

[Estimation of the incidence of digestive tract cancers by region].

OBJECTIVES: Information about the incidence of cancer in the national territory is a necessity for decision makers in public health. The aim of this study was to estimate for the first time the incidence of digestive tract cancers in each region of France in 1992 as well as trends in incidence between 1985 and 1995. METHODS: The incidence/mortality ratio established by sex, by age group and by localization in the departments covered by a cancer registry was applied to the mortality of each region studied. The mortality data were fit by applying a log linear model. RESULTS: The highest incidence rates of esophageal cancer were found in the North, in Brittany, Normandy and Picardy. The lowest rates were found in the regions of Midi-Pyrénées, Languedoc-Roussillon, Provence-Alpes-Côte d'Azur, Aquitaine and Poitou-Charentes. The incidence of this cancer decreased slightly between 1985 and 1995. Brittany and Normandy were also high risk regions for gastric cancer, while Provence-Alpes-Côte d'Azur, Midi-Pyrénées and Poitou-Charente were low risk regions. The incidence of gastric cancer also decreased more markedly than that of esophageal cancer. Colorectal cancer was more frequent in Alsace, Lorraine and in the North, it was less common in Provence-Alpes-Côte d'Azur, Midi-Pyrénées and Franche-Comté. The incidence of this cancer increased little over the 10 years of the study. CONCLUSION: There are regional disparities in the incidence and trends of digestive cancer incidence. These are more marked for esophageal cancer and gastric cancer than for colorectal cancer. The data supplied are of use both in the planning of health care and in the study of the causes or the prevention of digestive cancers.

Adolescent↗
PubMed1999

[Reporting of resected colonic carcinomas. Assessment of practices in 8 French counties in 1995].

OBJECTIVES: The objective of this work was to study the reporting of resected colonic carcinomas and to compare them with Consensus Guidelines published in January 1998. METHODS: The study included 535 colonic carcinomas collected in 8 French registries in 1995, and chosen by drawing lots. For each report, the presence of the information requested by the Guidelines was looked for. Three synthetic variables were built: 2 scores and one qualitative at 2 classes. The influence of patients, tumour and health care system's characteristics was analysed on the 3 dependent variables. RESULTS: Some important variations were observed for information's percents in reporting. In monovariate analysis, scores were significantly influenced by cancer's sub-location, area of patient's residence, surgical center, type of laboratories and pathologist case volume. In multivariate analysis, significant heterogeneity in practices remained between geographical areas. Types of laboratories and pathologist case volume affected differently dependent variables. CONCLUSION: This study shows the necessity to assess the practices before consensus because of the impact of pathological forms in therapeutic decisions and variations observed.

Aged↗
PubMed1998

[Breast cancer: epidemiology, risk factors, screening].

Breast cancer is the most frequent cancer in women: more than 8 to 9% of women will develop a breast cancer during their life and the incidence rate is regularly increasing. Despite therapeutic improvements, breast cancer mortality still remains important and varying according to regions (five years survival: 62 to 80% for the last years). The risks factors analysis shows that a primary prevention of the major risks factors is not yet possible (genetic or endogenous hormonal risk). The chemoprevention is still is discussion and under investigation. For the moment, secondary prevention using screening is the only way to improve survival. The lead-time induced by the screening allows an earlier detection of breast cancers. The randomized trials have demonstrated a significant benefit on mortality and morbidity from breast cancer in women aged 50 to 69. So many countries started regional, pilot or national breast cancer screening programmes using mammography with a 2-year interval and specialized centers.

Adult↗
PubMed1998

Estimation of outward currents in isolated human atrial myocytes using inactivation time course analysis.

The aim was to investigate outward currents in single, isolated, human, atrial myocytes and to determine the relative contribution of individual current components to the total outward current. Currents were recorded using the whole-cell patch-clamp technique at 36-37 degreesC. Individual outward current components were estimated from recordings of total outward current using a mathematical procedure based on the inactivation time course of the respective currents. This method allows estimation of outward currents without the use of drugs or conditioning voltage-clamp protocols to suppress individual current components. A rapidly activating and partially inactivating total outward current was recorded when myocytes were voltage clamped at potentials positive to -20 mV (peak current density 24. 0+/-0.97 pA/pF at +40 mV; n=107 cells, 33 patients). This total outward current comprised three overlapping currents: a rapidly inactivating, transient, outward current (Ito1) a slowly and partially inactivating current (ultrarapid delayed rectifier, IKur) and a third current component which most probably reflects a non selective cation current (not characterized). The average current densities at +40 mV were 8.92+/-0.44 pA/pF for Ito1 and 15.1+/-0.72 pA/pF for IKur (n=107 cells). Recovery from inactivation was bi-exponential for both currents and was faster for Ito1. A slowly activating delayed rectifier current (IK) was not found. The current densities of peak Ito1 and IKur varied strongly between individual myocytes, even in those from the same patient. The ratio IKur/Ito1 was 0.5-6.9 with a mean of 1.98+/-0.11 (n=107 cells), suggesting that IKur is the main repolarizing current. The amplitudes of the total outward current, Ito1 and IKur, and the ratio of the latter two were independent of patient age (16-87 years).

Adolescent↗
PubMed1998

L-type calcium current in human ventricular myocytes at a physiological temperature from children with tetralogy of Fallot.

OBJECTIVE: The aim was to investigate the electrophysiological properties of the L-type calcium current (ICa,L) in ventricular myocytes at a physiological temperature (36-37 degrees C) isolated from children undergoing surgical repair of tetralogy of Fallot. METHODS: ICa,L was recorded with the patch-clamp technique in the single electrode whose-cell mode at a physiological calcium concentration (1.8 mmol/l) at 36-37 degrees C. RESULTS: Under these conditions, maximum current density averaged -5.80 +/- 0.45 pA/pF. ICa,L showed a bell-shaped current-voltage relationship: the current activated at -37.7 +/- 1.36 mV, peaked at +9.41 +/- 1.60 mV and reversed at +57.7 +/- 2.12 mV (n = 17). At +10 mV, time to peak of ICa,L was 5.23 +/- 0.46 ms. Membrane potentials for half-maximal steady-state activation and inactivation of ICa,L were -6.02 and -20.4 mV, respectively, the slope factors were 7.16 mV for steady-state activation and 6.49 mV for steady-state inactivation. ICa,L did not completely inactivate and showed a big window current between -45 and +40 mV. The inactivation of ICa,L showed a biexponential time course with a fast time constant ranging from 9.11 to 12.9 ms and a slow time constant ranging from 60.9 to 220 ms between -30 and +30 mV. Only the slow time constant showed a pronounced voltage dependency. The recovery from inactivation of ICa,L was biphasic with a fast time constant of 60.7 ms and a slow time constant of 619 ms. beta-Adrenergic stimulation with isoprenaline (1 mumol/l) increased the ICa,L density from -5.71 +/- 1.55 to -13.8 +/- 1.96 pA/pF (142%; P < 0.05) at +10 mV. CONCLUSIONS: The present study demonstrates that most of the electrophysiological properties of ICa,L in ventricular myocytes isolated from children with tetralogy of Fallot resemble those of adult ventricular cells. The existence of a big calcium window current could be involved in the occurrence of early afterdepolarizations which could lead to the high incidence of arrhythmias after surgical repair of tetralogy of Fallot.

Adrenergic beta-Agonists↗
PubMed1998

[Determinants for choice of medical management in the Bas-Rhin].

UNLABELLED: It has already been established that the social origin and the demographic factors have an influence, among other things, on medical practice. What about it in the Bas-Rhin? Our survey's objective consists of emphasising on what motivates the choice of the type of medicine. METHOD: Phone survey on a representative sample of 1010 persons aged between 25 and over 64, residing in the Bas-Rhin. RESULTS: Participation has been of 66.3%. Among participants, there are 49.1% of men and 50.9% of women. 9 among 10 participants state that they have a family doctor. More women claim they are more likely to see a homeopathic doctor and/or a professional of alternative medicine. 8 among 10 persons have their blood pressure checked. 50.9% of participants have a blood analysis made in order to determine their cholesterol level. Building on these medical practices, several groups have been created. 54.1% of participants belong to the same group, having in common the facts of having a family doctor, having their blood pressure checked, and never seeing a professional of alternative medicine. The female participants are properly followed up on the gynecological point of view. Only 29 among 500 women have never had a cervical smear done. The carrying out of a mammography raises with age. When fearing a potential cancer, the first step taken by 56.2% of participants consists of seeing a generalist doctor, whereas 65.9% would prefer going to the hospital to perform further tests. As far as treatment is concerned, 76.8% of them would rather go to a specialised department, even if it is located far from their home. Special attention is to be paid to the fidelity of the population of the Bas-Rhin toward their family doctor. He represents the main link of information between the patient and the prevention policies that have been implemented over the last years.

Adult↗
PubMed1998

[Evaluation of the delays in treatment of myocardial infarction. Results of a survey in Alsace].

In order to assess the conditions of access to emergency care of acute myocardial infarction in Alsace, the authors carried out a survey in all hospitals and medical clinics in the region. All subjects admitted for acute myocardial infarction in the region between 3rd December 1995 and 3rd April 1996 were included. The study population comprised 405 persons. The onset of symptoms usually occurred at the patient's home (85% of cases). The first call was made to the general practitioner in 65% of cases. The emergency ambulance transported 40% of patients. The median time to hospital admission was 5 h 15 (average 21 h); the delay was greater in patients over 65 years of age (6 h 42 versus 3 h 51, p < 0.01). This mainly resulted from a delay in calling the doctor by the patients. Thirty nine per cent of patients underwent a myocardial revascularisation procedure (thrombolysis: 27%, direct coronary angioplasty: 12%). Therefore, ten years after a similar study, this survey shows that the delay to hospital admission has not improved and is still too long for effective emergency therapy to be given. In a region where ischaemic heart disease accounts for 10% of all deaths, a multidisciplinary approach is required to elaborate a regional policy for optimising the management of acute myocardial infarction.

Age Factors↗
PubMed1998

[Influence of knowledge relative to cancer on prevention behavior in the population of Bas-Rhin].

The tendency today is to make the population more aware of health in order to encourage their use of prevention activities. The aim of our telephone survey which was performed on a representative sample of the population (1,010) in the Bas-Rhin department in France, was to study the relationship between the level of knowledge of cancer and the use of screening techniques to prevent it. Eighty-two percent of the males and 78% of the females surveyed, show a profound understanding of cancer in general, the associated risk factors and its prevention. The level of awareness of males did not influence a specific behaviour (p = 0.68) towards cancer prevention. It was shown that in smokers, the more they smoke, the more they underestimate the chances of cure from all categories of cancer (p = 0.01). They both overestimate the number of cigarettes needed daily before smoking becomes toxic (p < 0.01) and are less active physically than nonsmokers (p < 0.007). Heavy smokers live in larger communities (p < 0.02) and smokers are younger than non-smokers (p < 0.0001). In the female population, the level of awareness did indeed influence their behaviour towards cancer prevention (p < 0.04). The level of knowledge was higher in both those who consciously attend cancer screening clinics (cervical Papanicolaou smears and faecal tests) and those who are opposed to faecal tests. Younger females are significantly less aware than those who are older (p = 0.0001) and more than two-thirds of these would not consider a cervical Papanicolaou smear as a preventative diagnostic tool. Females who conscientiously attend cancer screening clinics and who are very much aware of cancer, are generally older in age (p < 0.05). The occurrence of mammography as a preventative measure is both high and dependent on age. In conclusion, the level of knowledge of cancer cannot explain alone human behaviour towards the prevention of this disease. Other determinants responsible for influencing human behaviour towards cancer prevention will be better understood once the social sciences, epidemiology and anthropology units work together and combine resources to achieve a common goal.

Adult↗
PubMed1998

[Can we and must we organize cervical cancer screening in France? Results of the pilot project "EVE" in the department of Bas-Rhin].

EVE is a pilot project for cervical cancer screening whose aim is to test the feasibility of organized screening in the French liberal health system with a consensus of medical participants. After three and a half years, 74.8% of women aged 25 to 64 had had at least one smear. Coverage varies with age, from 89% between 25 and 29 to 56% between 55 and 60. Only 8% of smears are taken by General Practitioners. There is a tendency to space out smears because only 14% of women had had a second smear within one year and 41.1% within 2 years. On the other hand more then 20% percent of women do not return after 3 years. Pathological smears represent 1.94% of all smears. For these, a questionnaire is sent to the physician in order to get information on follow-up. This enables cytologic/histologic correlation. The histologic exam reveals a pathological lesion in 95% of cytologies consistent with invasive cancer, 91% of those consistent with high grade lesions and 70% of those consistent with low grade lesions.

Adult↗
PubMed1997

Descriptive epidemiology of cerebral gliomas in France.

BACKGROUND: Descriptive epidemiology of cerebral gliomas has recently been the subject of several studies, indicating a possible increase in brain tumor rates, particularly in the elderly population. METHODS: Between 1983 and 1990, 1376 registered patients with diagnoses of malignant astrocytomas, low grade astrocytomas, oligodendrogliomas - mixed oligoastrocytomas, and tumors without histologic confirmation were reviewed in 6 French cancer registries. The incidence rates by histologic type, age, and gender were calculated. The variation of the incidence between 1983 and 1990 was also analyzed. RESULTS: The highest incidence was observed in the malignant astrocytoma group (2.38/100,000/year) followed by the low grade astrocytoma group (0.54/100,000/year) and the oligodendroglioma - mixed oligoastrocytoma group (0.25/100,000/year). A significant male predominance was observed in the malignant astrocytoma group (male/female [M/F] ratio of 1.59; P < 0.001) and in the group without histologic confirmation (M/F ratio of 2.6; P = 0.008). Between 1983 and 1990, an increasing trend of 5% per year was observed in the incidence of malignant astrocytomas in the population older than 65 years. CONCLUSIONS: These data confirm the observation made in other countries that the incidence of primary brain tumors (particularly malignant astrocytomas) is increasing in elderly patients.

Adolescent↗