A wireless-implantable microsystem for continuous blood glucose monitoring.

A remotely powered implantable microsystem for continuous blood glucose monitoring is presented. The microsystem consists of a microfabricated glucose biosensor flip-chip bonded to a transponder chip. The transponder chip is inductively powered by an external reader with a 13.56-MHz carrier. It then measures the output signal of the glucose biosensor and transmits the measured data back to the external reader using load-shift keying (LSK). The microsystem has a volume of 32 mm(3). The procedures for the microfabrication of the glucose sensor and the assembly of the microsystem are described along with the description of the circuit blocks of the transponder chip. The transponder chip has been fabricated with the TSMC 0.18-mum CMOS process and has a total area of 1.3 x 1.3 mm(2). The chip can measure the sensor output current ranging from 1 nA to 1 muA with less than 0.3% nonlinearity error, provided that the amplitude of the received RF signal is higher than 2.6 V; the circuit consumes a total current of about 110 muA.

A Low-Light CMOS Contact Imager With an Emission Filter for Biosensing Applications.

In this paper, a fully functional low light 128 X 128 contact image sensor for cell detection in biosensing applications is presented. The imager, fabricated in 0.18 mum CMOS technology, provides low-noise operation by employing both a modified version of the active reset (AR) technique and a modified version of the active column sensor (ACS) readout method. High-sensitivity, low noise performance of the presented sensor is well-suited for fluorescence imaging. For this purpose, an emission filter was fabricated and integrated with the sensor. The filter was fabricated using PDMS and Sudan II Blue dye mix, spin-coated and deposited in a class 1000 clean room. The designed filter is suitable for excitation at wavelengths below 340 nm and emission at 450 nm and above. The fabricated imager architecture and operation are described, noise analysis is presented and measurements from a test chip are shown. Experimental results using live neurons from the pond snail, Lymnaea stagnalis, and fluorescence polystyrene micro-beads prove the functionality of the fabricated system and indicate its biocompatiblity.

[Evolution of secondary prevention medication prescriptions after myocardial revascularisation: the ANCOR survey]. / Evolution de la prescription de prévention secondaire chez les coronariens après revascularisation: enquête ANCOR (analyse nationale de la prise en charge de la maladie coronaire avant et après revascularisation).

The ANCOR survey was designed to assess the evolution of the prescription of secondary prevention medications in patients undergoing myocardial revascularisation, from the preoperative period to 3-6 months post-procedure. A total of 1535 patients (mean age: 64 years, 79% men), 321 after coronary surgery and 1214 after percutaneous coronary intervention, were included. Of them 37% still described anginal symptoms (Canadian class 1 in 80% of them); 38% still had elevated blood pressure (> or = 140 mm HG systolic and/or > or = 90 mmHg diastolic) and 27% of previous smokers still smoked after the procedure. All classes of secondary prevention medications were more often prescribed after than before intervention, antiplatelet agents (63.5 to 89%), beta-blockers (53 to 73.5%), statins (51 to 3%), ACE inhibitors (27 to 39%) and nicorandil (14 to 21%). Factors associated with the prescription of the different classes of medications were both expected (such as hypertension for ACE inhibitors or statins in hyperlipidemic patients) or unsupported by scientific evidence (less beta-blockers in diabetic patients). Overall this survey shows that myocardial revascularisation constitutes a key point in the management of patients with coronary disease, and that cardiologists consider that treatment of the atherosclerotic process is as important as the treatment of focal coronary artery stenoses.

[Risk factors management in 5708 ambulatory patients suffering from peripheral vascular disease followed in urban practices]. / Contrôle des facteurs de risque dans une population de 5 708 artériopathes des membres inférieurs vus en médecine de ville.

STUDY OBJECTIVE: we examined the management of risk factors in patients suffering from obliterating peripheral arterial disease (OPAD), in urban medical practice. METHODS: PRISMA, ECLAT1 and APRES are surveys based on urban medicine in France. These 3 studies have allowed a compilation of data pertaining to the control of risk factors in patients suffering from one or more clinical manifestations of atherothrombosis, including cerebral vascular accident, coronary insufficiency or OPAD. The study population was divided among patients with isolated OPAD, versus OPAD associated with coronary artery disease (CAD), versus OPAD associated with cerebral vascular disease. RESULTS: a total of 5 708 patients with stable OPAD were included among the 3 studies. Risk factors were not managed in the majority of patients, including 62.6% of hypercholesterolemic patients, 71.1% of diabetics, and 77.4% of hypertensive patients. Overall, the control of risk factors was less satisfactory in patients with OPAD than in patients with CAD. Smoking (70.6% current or past smokers) remains a major risk factor in OPAD. The proportion of current smokers was significantly higher is the group with isolated OPAD than in the other 2 groups of patients (p < 0.0001). CONCLUSIONS: The control of risk factors in patients with OPAD is suboptimal, mainly because of failure to reach the therapeutic goals, rather than because of poor medical management. It is important that recent recommendations be implemented in medical practice. Awareness of the primary physicians will be key in the optimisation of treatment prescriptions and, above all, in the achievement of a higher level of clinical performance.

[Prevalence and management of patients with a prior history of atherothrombotic disease in primary care in France. Results of the ECLAT1 survey]. / Prévalence et prise en charge des patients avec antécédents athérothrombotiques dans le cadre des consultations de médecine générale en France. Résultats de l'enquête ECLAT1.

This cross-sectional study assessed the prevalence of subjects with a previous history of atherothrombotic disease (myocardial infarction, ischemic stroke and/or lower limb arterial disease) among patients treated in general medicine. A random sample of 3,009 French general practitioners was recruited. Patients who consulted one of these general practitioners on December 7th 2000 were included. Those with a previous history of atherothrombotic disease were identified and further data on their cardiovascular risk factors and drug use were collected. The prevalence of patients with a previous history of atherothrombotic disease was 2% [95% confidence interval: 1.9-2-1] in subjects younger than 65, 13.4% [12.7-14.2] between 65 and 74 and 17.0% [16.2-17.8] in subjects older than 74. Arterial hypertension was found in 62.2% of the patients with a previous history of atherothrombotic disease, overweight or obesity in 59.4%, hypercholesterolaemia in 55%, current or past smoking in 48.3%, and diabetes mellitus in 20.1%. The last blood pressure and LDL-cholesterol measurements were respectively higher than or equal to 140/90 mmHg and 3 mmol/l in 70.6% of the patients suffering from arterial hypertension (missing data in 2.2%) and in 48.2% of the patients suffering from hypercholesterolaemia (missing data in 31.4%). Atherothrombosis represents a significant part of the primary care activity in France. Despite a widespread antihypertensive and hypocholesterolaemic drug prescription, the control of cardiovascular risk factors is insufficient. The high prevalence of overweight may contribute to this poor control.

Protein S-100b serum levels in trauma-induced brain death.

OBJECTIVE: To analyze the time course of serum protein S-100b in patients with traumatic brain injury deteriorating to brain death and to investigate the predictive value of initial S-100b levels in relation to clinical and radiologic measures of injury severity with regard to brain death. METHODS: Forty-seven patients who sustained severe head injury were studied. Blood samples for measurement of S-100b were drawn on admission in the intensive care unit and every 24 hours thereafter for a maximum of 6 consecutive days or until brain death occurred. Variables related to outcome were recorded, including age, sex, Glasgow Coma Scale (GCS), and brain CT findings on admission. Outcome was defined as deterioration to brain death or not. RESULTS: Of the 47 patients studied, 17 deteriorated to brain death and 30 did not. On admission, patients who became brain dead had higher median serum S-100b levels compared with those who did not (2.32 microg/L vs 1.04 micro g/L, p = 0.0028). Logistic regression analysis showed that initial S-100b was an independent predictor of brain death (p = 0.041), in the presence of advanced age (p = 0.043) and low GCS score (p = 0.013). The odds ratio of 2.09 (95% CI, 1.03 to 4.25) indicates a more than doubling of the probability of deteriorating to brain death per 1- micro g/L increase in S-100b on admission. At clinical brain death, median S-100b was higher in patients with brain death compared with the peak S-100b value obtained over a 6-day period in those who did not become brain dead (6.58 microg/L vs 1.49 microg/L, p < 0.0001). CONCLUSIONS: Prediction of brain death after severe head injury can be improved by combining clinical and S-100b data; thus, serum S-100b determination deserves to be included in the neuromonitoring of patients with severe traumatic brain injury.

[FACT: French national registry of acute coronary syndromes. Specific study of French general hospital centers]. / FACT: registre national français des syndromes coronaires aigus. Etude particulière des centres hospitaliers généraux français.

UNLABELLED: The FACT registry is currently the French registry including the greatest number of patients with acute coronary syndromes. PURPOSE: The study presents epidemiologic data, modalities and delays for medical admission. METHOD: Three thousand nine hundred and two patients were included in FACT by 362 French centers of cardiology between 06/01/2003 and 03/02/2003. One thousand eight hundred and ten patients, who had been placed in the cardiology departments of French general hospitals, were isolated from this registry. The French general hospitals represented 50.8% of the 362 centers. In order to clarify the study, these patients were divided into three groups: group A: patients without ST segment elevation but with suggestive ECG modifications; group B: patients with ST segment elevation; group C: all other patients. The results were mainly studied for groups A and B and compared. These results were also compared to those of the FACT registry and of other registries. RESULTS: The results show that the average delay for admission is 2.9 h after a first delay between the pain and the help of 6.7 h. The first intervening party is a general practitioner (36.4%) then the SAMU (31.6%) and finally the emergency departments (18.7%). 16.6% of the patients from group B undergo pre-hospital thrombolysis. The recommendations of the European Society of Cardiology are widely applied except for the most recent of them since only 27.6% of the patients from group A having a TIMI score > or = 5 receive an anti-GIIB IIIA treatment. The reasons of the non-prescription of the recommended classes are mostly linked to contra-indication and intolerance. The strategy of coronary reopening mainly depends on the presence or the absence in the department of an available medical equipment for angioplasty. If there is one, the percentage of primary angioplasty reaches 54.2% and the percentage of thrombolysis 7.9%. On the opposite, there is 8.3% of angioplasty and 54.2% of thrombolysis for the unequipped centers. The global mortality reaches 5.8% but is inversely proportional to the level of equipment of the departments: 5.9% for the departments with angioplasty, 11% for the departments with coronarography but without angioplasty and 13.8% for the departments without any interventional equipment. Nevertheless, the age of the patients is different and this influences the results: we notice that the less equipped the department is, the older the patients are. CONCLUSION: The FACT registry and the data from the general hospitals give the opportunity to think about the possibilities to improve the delays of call to the first intervening party (more particularly to the SAMU) but it also allows us to think about how to better organize the geographical distribution giving access to a medical equipment for angioplasty. All these information will also help the cardiologists to gather around the recommendations by convincing them that the benefit/risk ratio is positive.

[Registry of cardiac insufficiency in cardiology]. / Registre de l'insuffisance cardiaque en cardiologie libérale.

The epidemiological data on cardiac insufficiency in cardiology are very scarce. Therefore, with its members the National College of French Cardiologists has conducted a survey in order to evaluate the clinical, biological and therapeutic characteristics of cardiac insufficiency patients, and thus the possible seasonal variations, and to compare them to the current recommendations and to the data from a previous survey with the same methodology performed in 1994. During each season of the year 622 cardiologists recruited the first 5 cardiac insufficiency patients who had been stable for at least three months. 8618 observations were analysed. The results showed 68% are male with an average age of 70 years, with an ischaemic aetiology in 47% of cases, hypertensive in 23%, and in NYHA stage II or III in 94% of cases. The left ventricular ejection fractions are < 30% in 22% of cases, between 30 and 50% in 62% of cases, and > or = 50% in 16% of cases (20% in those over 78 years). Medical treatment includes diuretics in 78% of cases, with 28% of patients on spironolactone, angiotensin converting enzyme inhibitors (ACE inhibitors) in 82% of cases, betablockers in 29% of cases; ACE inhibitors and betablockers are clearly prescribed more often than during the previous 1994 survey but at doses often lower than the recommendations. Lastly, there are no seasonal variations in prescriptions.

[Prognostic importance of ambulatory arterial pressure monitoring in France. Initial results of the OCTAVE II study. OCTAVE II Research Group]. / Intérêt pronostique de la mesure ambulatoire de pression artérielle en France. Premiers résultats de l'étude OCTAVE II. Groupe de Recherche OCTAVE II.

RATIONALE: Ambulatory blood pressure measurement (ABPM) is commonly used in clinical practice, whereas its added value to the management of hypertension is not definitely documented. OBJECTIVE: The OCTAVE II study was launched in 1991 to explore the prognostic value of ABPM, compared to that of the gold standard, the clinical blood pressure measurement. METHODS: Two hundred and six French cardiologists recruited 3569 participants over 18 years of age, provided they deemed ABPM was useful (mean age of 56 years, 52% of men, 65% already treated by antihypertensive drugs). The prognostic value of various blood pressure measurements, systolic or diastolic, clinical or ambulatory (diurnal, nocturnal or during 24 hours), has been assessed in multivariate models adjusted on the baseline characteristics associated with risk. The outcome was the occurrence of a major cardiovascular event, including stroke, myocardial infarction and cardiovascular death. RESULTS: After an average follow-up of five years, cardiovascular morbidity was known for 85% of the participants, and their vital status for 91%. On the whole population, the best prognostic indicators were systolic blood pressure compared with diastolic, ABPM compared with clinical blood pressure measurements, and nocturnal ABPM compared with diurnal ABPM. In the untreated participants at baseline, cardiovascular risk regularly increased among the four groups: normotensives, white-coat hypertensives, dippers, non-dippers. Between the extreme categories, the cardiovascular event rate was multiplied by 6.5. CONCLUSION: In this French population, ABPM and most of all its nocturnal component, was better correlated with cardiovascular prognosis. It remains to assess: 1) the general value of our findings, 2) the respective values of self blood pressure measurement versus ABPM, and 3) whether ABPM allows a better risk prevention.

Association between activation of the renin-angiotensin system and secondary erythrocytosis in patients with chronic obstructive pulmonary disease.

PURPOSE: An association between activation of the renin-angiotensin system and enhanced erythropoiesis has been observed in patients with several diseases, including congestive heart failure and hypertension. Our goal was to examine whether the renin-angiotensin system is associated with secondary erythrocytosis in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Plasma renin activity, plasma aldosterone concentration, serum erythropoietin level, and serum angiotensin converting enzyme (ACE) activity were measured in 12 patients with COPD and secondary erythrocytosis [mean (+/-SD) hematocrit of 53% +/- 3%] and in 12 matched controls with COPD who did not have erythrocytosis (hematocrit 45% +/- 5%). All patients had chronic hypoxemia (PaO2 <60 mm Hg). RESULTS: Both plasma renin and aldosterone levels were threefold greater in patients with secondary erythrocytosis compared to controls. No difference in erythropoietin levels was observed between patients with or without secondary erythrocytosis. Renin levels (r = 0.45; P = 0.02) but not erythropoietin levels (r = 0.15; P = 0.47) were correlated with hematocrit in the entire sample. Renin levels and PaO2 were the only variables independently and significantly associated with hematocrit values in a multiple linear regression model. CONCLUSION: Activation of the renin-angiotensin system is associated with the development of secondary erythrocytosis in chronically hypoxemic patients with COPD. The exact mechanism is not yet fully understood, but angiotensin II may be responsible for inappropriately sustained erythropoietin secretion or direct stimulation of erythroid progenitors.

VLSI neural system architecture for finite ring recursive reduction.

The use of neural-like networks to implement finite ring computations has been presented in a previous paper. This paper develops efficient VLSI neural system architecture for the finite ring recursive reduction (FRRR), including module reduction, MSB carry iteration and feedforward processing. These techniques deal with the basic principles involved in constructing a FRRR, and their implementations are efficiently matched to the VLSI medium. Compared with the other structure models for finite ring computation (e.g. modification of binary arithmetic logic and bit-steered ROM's), the FRRR structure has the lowest area complexity in silicon while maintaining a high throughput rate. Examples of several implementations are used to illustrate the effectiveness of the FRRR architecture.

[Presentation of OCTAVE II. A current epidemiologic study in France of the added prognostic value of ambulatory blood pressure monitoring]. / Présentation d'OCTAVE II. Une étude épidémiologique en cours en France sur la valeur pronostique ajoutée par la mesure ambulatoire de la pression artérielle.

The diagnosis of "white coat" hypertension, the measurement of indices of 24 hour variability of the blood pressure and increased accuracy of blood pressure estimation are some of the advantages of ambulatory blood pressure monitoring. They are part of the reason why the method has been adopted by ambulatory blood pressure monitoring is really useful in the treatment of hypertension is fragile: although the correlation with target organ complications seems better than with conventional blood pressure measurement, it remains to be shown that this information helps to predict and then improve the prognosis of hypertension. With respect to this first stage of demonstration of the added prognostic value attributable to ambulatory blood pressure monitoring, several studies have been undertaken, one of which is OCTAVE II. The goals were to analyse the predictive values of the indices obtained by ambulatory blood pressure monitoring in terms of cardiovascular morbidity and mortality after having described the correlations between these indices and the characteristics of individual patients. Two hundred and sixty six cardiologists, members of the French College of Cardiology, included 3,569 patients in whom an indication for ambulatory blood pressure monitoring had been retained, over a period of 10 months in 1991. These patients were 56.4 year old on average, with 52.6% men, hypertensive or not. The 5 year follow-up should end at the beginning of 1997.

Pharmacokinetic study of ethanol after oral administration: a new approach to enzymatic elimination.

A new approach to the enzymatic elimination of ethanol in vivo allows us by means of a one-compartment model to take into account all the phases of the ethanol concentration-time curve after oral administration. The Michaelis-Menten equation is an approximation of this model; indeed it constituted the only non-linear approach to the kinetic study of ethanol. To express the model in the form of an equation leads to a third-order system of bilinear differential equations which has no analytical solution. The identification of the model is based on the optimization of a conformity criterion between experimental values and those predicted by the model. Optimization is performed by means of an iterative algorithm minimizing non-linear functions. This method permits the estimation of initial concentrations of products involved in the enzymatic reaction (substrate, enzyme) and kinetic constants (characterizing absorption and enzymatic reaction). Kinetics in nonalcoholics, alcoholics, and former alcoholics were identified using this new model. A good fit between the experimental values and the simulated curve was obtained. The in vivo estimation of the kinetic constants of each elementary step of the enzymatic reaction represents an original approach likely to provide more knowledge of ethanol metabolism.

Non-linear kinetics of ethanol elimination in man: medico-legal applications of the terminal concentration-time data analysis.

Research regarding parameters suitable for reporting on the activity of enzymatic systems responsible for ethanol metabolism is of obvious interest in medico-legal practice. Blood ethanol concentration-time curves, following oral administration of ethanol, have been developed for ethylic and non-ethylic subjects. This study has confirmed the non-linear kinetics of ethanol elimination; however, existing non-linear models appear to be inadequate for usual medico-legal practice, because of their complexity. We observed three phases during the elimination of ethanol. The first order terminal phase is characterized by its half-life. This parameter seems adequate as a basis for determining the activity of enzyme systems responsible for the metabolism of ethanol.

Evolution of plasma acetate concentration during ethanol metabolism in man.

Following oral administration of ethanol to ethylic as well as non-ethylic volunteers, the entire time course of plasma acetate concentration has been observed. The curve shows a typical evolution in three phases: (1) a quick ascending phase (2) a steady state characterized by a mean concentration (-C) (3) a first-order decrease, characterized by its half-life (t1/2) These parameters show significant variations (increase of -C, decrease of t1/2) in the ethylic subjects, in comparison with the non-ethylic ones. The variation of the area under the acetate curve according to the dose of ethanol given, is linear. The comparison of such a development with the one, typically non-linear, of the area under ethanol curve previously analyzed for the same subjects, may guess the origin of the non-linearity of ethanol kinetics.

[Mitral valve prolapse and spasmophilia in the adult]. / Prolapsus valvulaire mitral et spasmophilie chez l'adulte.

75 cases of mitral valve prolapse (MVP) for which no cause was found underwent electromyography (EMG). In 64 cases (85.3%) EMG showed changes suggestive of spasmophilia. The symptoms observed were those already described in this condition. The specific clinical signs of spasmophilia were often elicited with a positive Chvostek sign in 20 out of 30 cases (73.3%). Radiological, echocardiographical and haemodynamic studies underlined the hyperkinetic state of the left ventricle. Biochemical investigations showed a high incidence of low erythrocytic magnesium levels. Chest pain suggestive of angina pectoris, mitral valve prolapse and spasmophilia are frequently associated. The role of the low erythrocyte magnesium on left ventricular hyperkinesis and the production of MVP is discussed.

[Coronary insufficiency in the female: possible effect of menopause]. / L'insuffisance coronarienne chez la femme: influence de la ménopause

A population of 239 women suffering from chronic coronary disease was divided into two groups according to whether or not they had sustained a myocardial infarction. For the 226 post-menopausal women, the type of menopause (natural or artificial) and their age at its onset were determined, together with the age of onset of the infarction or angina, and possible correlations with other risk factors in atherosclerosis. Whilst the average age at the time of artificial menopause was markedly less than that of natural menopause, the age of onset of coronary complications was comparable regardless of the type of menopause, this applying to both groups. Contrary to a classically accepted opinion, early menopause would not appear to favourise the premature development of atherosclerotic coronary problems, and, in addition, would not appear to affect other coronary "risk factors".