[Nephrotic syndrome revealed by pulmonary embolism: about four cases]. / Embolie pulmonaire révélant un syndrome néphrotique : à propos de quatre cas.

Nephrotic syndrom is an association of proteinuria>3g/d or 50mg/kg/d, an hypoalbuminemia<30g/L and a hypoproteinemia<60g/L. Primary etiologies are minimal glomerular injury, focal segmental glomerulosclerosis and non membranous glomerulonephritis. Secondary etiologies are diabetes, high blood pressure and amyloidosis. We present four cases about nephrotic syndrome after thromboembolic disease. In every case, patients show a pulmonary embolism symptomatic of a nephrotic syndrom, whose diagnostic could be delayed up to six months after first pulmonary symptoms. This raised the problem of renal biopsy in these patients who need anticoagulation. In minimal change nephrosis, without hematuria, high blood pressure or renal dysfonction, a corticosteroid therapy test could be done assuming that is corticosensitive minimal glomerular injury. In every case, anticoagulation course must be completed and maintained in case of patent nephrotic syndrom with an albuminemia under 20g/L. In case of pulmonary embolism or deep vein thrombosis, idiopathic-looking, a nephrotic syndrome must be sought-after. The two diagnosis ways are the proteinuria on the urine dipstick and the hypoproteinemia on usual biology. The main mechanism is the coagulation factor leak, side effect of the nephrotic syndrom, notably because of the antithrombin III.

[Platypnea-orthodeoxia syndrome: case report]. / Le syndrome de platydéoxie-orthopnée : à propos d'un cas.

We report the case of an 80-year-old woman with symptomatic postural hypoxaemia caused by a right-to-left shunt through a patent foramen ovale. The hypoxaemia was enhanced by the supine position and disappeared in upright position. Potential mechanisms underlying postural variations of the shunt seemed to be similar to those describe in platypnea-orthodeoxia syndrome. Patient became asymptomatic after shunt resolution.

Gestational age-related reference values for amniotic fluid organic acids.

BACKGROUND: Normative data for amniotic fluid (AF) levels of organic acids at different gestational ages are lacking. They can provide a useful framework to investigate the accuracy of prenatal diagnosis for organic acidemias. METHODS: We report on the concentration of 21 organic acids in AF obtained by gas chromatography/mass spectrometry between the 12th and 34th weeks of gestation from 92 pregnancies that were not at risk for organic acidurias. RESULTS: We infer normal reference values that can be compared with 134 pregnancies at risk for several metabolic conditions, that is, propionic acidemia, methylmalonic acidemia (methylmalonyl-CoA mutase deficiency or defects in cobalamin metabolism), 4-hydroxybutyric acidemia, glutaric acidemia and pyroglutamic acidemia. CONCLUSION: Most of the metabolites tested did not show conspicuous variations across gestational ages in normal fetuses, with ranges that were consistently similar to available reference values from pooled samples in previous reports. With rare exceptions, knowledge of pathological versus normal values for relevant metabolites leads to clear-cut differentiation of affected versus unaffected fetuses. Nevertheless, it is strongly recommended that mutational analysis and/or additional biochemical approaches complement organic acid analysis for an adequate diagnostic workup.

Measurement of cystine in granulocytes using liquid chromatography-tandem mass spectrometry.

BACKGROUND: Cystinosis is a rare autosomal recessive disorder characterized by an accumulation of intralysosomal cystine due to a defect in cystine transport across the lysosomal membrane. This disorder can be treated specifically using high doses of cysteamine. Accurate measurement of intracellular cystine content is necessary for the diagnosis and monitoring of treatment with cysteamine. Here we describe a new method to measure intracellular cystine. It relies on a liquid chromatography-tandem mass spectrometry assay. We compare this novel method with the cystine-binding protein assay. METHOD: Cells were isolated and lysed in the presence of N-ethylmaleimide to avoid interference from cysteine. After deproteinization, addition of stable isotope d6 cystine and butylation, cystine was measured using an API 3000 MSMS. RESULTS: The cystine assay was linear to at least 50 micromol/L. Within-run and between-run coefficients of variation were 2.9% and 5.7% respectively. CONCLUSION: It is possible to measure very low concentrations of intracellular cystine with liquid chromatography-tandem mass spectrometry. The results obtained with this novel method correlate very well with those obtained using the cystine-binding protein assay.

[Screening for high risk cardiac diseases in athletes]. / Le dépistage des cardiopathies a risque chez le sportif.

The prevention of cardiovascular complications occurring during sporting activity requires detection of well-known pathologies which are often clinically latent but which may present with sudden death. The problem of detection and the recommendations and French laws concerning this subject are summarised in this article.

Management of heart failure in the elderly: recommendations from the French Society of Cardiology (SFC) and the French Society of Gerontology and Geriatrics (SFGG).

Heart failure, a frequent disease in the elderly, has a pejorative prognosis. Clinical diagnosis is complicated by atypical or difficult-to-interpret symptoms and by the concomitant presence of other diseases, particularly cognitive impairment, neurological disorders and diseases of the musculoskeletal system. Among the additional investigations, echocardiography remains underused. Impairment of diastolic left ventricular function is frequent. The usual laboratory tests must include calculation of the creatinine clearance, which is indispensable for dosage adjustment of certain drugs (ACE inhibitors, digoxin, spironolactone). The value of plasma natriuretic peptide assays as diagnostic tools has not been determined in elderly or very elderly populations and the plasma B-type natriuretic peptide increases with age. Comprehensive geriatric assessment is essential in order to screen for concomitant diseases and determine the patient's degree of dependence. The general objectives of treatment remain applicable to the elderly subject: improvement in the quality of life, reduction of mortality and the number and duration of hospitalisations, and slowing disease progression. In the frail elderly subject, symptom alleviation is to be the primary objective. In the absence of specific studies on elderly or very elderly subjects, most of the recommendations have been extrapolated from the data based on the evidence generated in younger populations. The dietary rules are to be more flexible than those used for younger subjects, particularly in order to prevent the risk of denutrition induced by strict salt-free diets. Special precautions for the use of heart failure drugs are due to comorbidities and the pharmacokinetic and pharmacodynamic changes related to aging. Drugs dosage increase is to be cautious and carefully monitored for adverse reactions. The therapeutic programmes in which multidisciplinary teams are involved reduce the number and duration of hospitalisations and the costs generated by the disease.

Prenatal diagnosis of some metabolic diseases using early amniotic fluid samples: report of a 15 years, experience.

BACKGROUND: In the present study, we report the results of 132 prenatal diagnoses performed on chorionic villi and cell-free amniotic fluid obtained simultaneously at 12-13 weeks of gestation. In addition, we report the result of 59 prenatal diagnoses performed at 12-13th week using amniotic fluid only. METHODS AND RESULTS: A total of one fetal loss (1/191) was observed when a sample of amniotic fluid was obtained at around 12-13 weeks, whereas three losses (3/82) were observed after midtrimester amniocentesis. We attribute this finding to the fact that only a very small volume of amniotic fluid was sampled using a very small needle. CONCLUSION: From these data it appears that when a couple is facing a high risk of recurrence of some metabolic diseases, the study of chorionic villus and amniotic fluid sampled simultaneously offers a safe and reliable method of early prenatal diagnosis.

[Preliminary validation of the French translation of anxiety sensibility index-revised (ASI-R)]. / Index de la sensibilité à l'anxiété révisé (anxiety sensibility index revised): validation préliminaire de la version française.

Anxiety sensitivity represents a stimulus-outcome expectancy that reflects individual differences in the propensity to experience fear in response to one's arousal-related bodily sensations. It refers to the fear of anxiety-related symptoms that are based on beliefs that such sensations have negative somatic, social or psychological consequences. Anxiety sensitivity occupies an important place in theory and research on panic and related interoceptive fear disorders. Findings from this body of research indicate that this construct may act as a specific vulnerability variable in the development of panic attacks and anxiety symptoms. However, anxiety sensitivity theory also has been applied to understanding mood disorders and chronic pain disorders. Thus, as a psychological construct, anxiety sensitivity holds specific relevance to understanding panic disorders and general relevance for expanding knowledge about negative emotional functioning in other pathologies. All the research on anxiety sensitivity has been completed with the 16-item Anxiety Sensitivity Index (ASI). The review of the literature using this instrument suggested that anxiety sensitivity has three lower-order factors that all load on a single higher-order factor. The lower-order factors represent Physical-Concerns, Mental Incapacitation Concerns, and Social Concerns, and the higher-order factor represents the global anxiety sensitivity construct (21). Taylor and Cox (22) suggested that this questionnaire was not designed on an a priori basis to measure the identified lower-order factors. The low number of items for the Social and Mental Incapacitation dimensions of the 16-item ASI often leads to relatively lower levels of reliability compared to the third dimension. To address this issue, Taylor and Cox (22) developed an expanded measure of the anxiety sensitivity construct. The 36-item Revised Anxiety Sensitivity Index (ASI-R) maintains the same format as the 16-item ASI, but expands the number of content domains assessed. The ASI-R was designed to assess 6 lower-order domains identified in previous factor analytic research using the 16-item ASI (21), including fear of cardiovascular symptoms, fear of respiratory symptoms, fear of gastrointestinal symptoms, fear of publicity observable reactions, fear of dissociative and neurological symptoms, and fear of cognitive dyscontrol. The principal components factor analysis using the ASI-R among psychiatric outpatients indicated that there were 4 lower-order factors tapping the constructs of (1) fear of respiratory symptoms, (2) fear of publicly observable anxiety reactions, (3) fear of cardiovascular symptoms, and (4) fear of cognitive dyscontrol (22). A recent study (27) provided an initial psychometric evaluation of the ASI-R in a large, diverse sample of people (n = 2,786) from 6 different countries: Canada, United States, Mexico, Spain, The Netherlands and France. The data suggested that the two-factor solution is most replicable than other solutions (2 to 6 factors). The underlying structure of the anxiety sensitivity construct was generally similar across countries, tapping fear about the negative consequences of anxiety-related physical and social-cognitive sensations. Lower-order factors were moderately to strongly correlated with one another and showed good internal consistency. This manuscript presents the French translation of the ASI-R and a preliminary validation study. This research was realized conjointly with the transcultural study previously mentioned (27). Seven hundred and one French university students (non-clinical participants) completed the questionnaire at the beginning of a class. Subjects were undergraduate students from 2 universities (psychology and classics). Table I provides age, sex and marital status. There were no differences between the two groups on sex. The two groups were not comparable on age and marital status. The psychology group was older than the other was. The psychology students were also more married. The total group (n = 701) comprises 79 men and 622 women, with a mean age of 21.29 (4.85). Table II provides the normative means and standard deviations for both groups of students. There was no difference between the two groups on the total of the questionnaire (no significant interaction between group and age). In regard to the physical concerns subscale and the social-cognitive concerns subscale, there was also no significant interaction between group and age. Assessment of the internal consistency of the ASI-R yielded an overall Cronbach alpha of 0.91 for the entire questionnaire, with an alpha of 0.88 for the fear of anxiety-related physical sensations subscale and 0.83 for the fear of anxiety-related social-cognitive sensations subscale. A series of ANOVAs between male and female groups revealed significant gender differences. As shown in table IV, women had significantly higher total score than did men. They also had significantly higher physical factor and social-cognitive factor scores than did men. This finding is consistent with research that indicates that women generally report more intense fears and men less intense fears, and that they differ in levels of overall anxiety sensitivity specifically (29). This preliminary report was the first attempt to examine the construct of anxiety sensitivity using the ASI-R in a French university students. It can serve as a reference point for future research.

Improving the prenatal diagnosis of citrullinemia using citrulline/ornithine+arginine ratio in amniotic fluid.

Prenatal diagnosis of citrullinemia is performed using a direct argininosuccinate synthetase (ASS) assay on chorionic villi (CV) and citrulline concentration measurement in early amniotic fluid (AF). Here we report the results of 40 prenatal diagnoses performed using this method, discuss the difficulties encountered in interpreting the results, and propose the use of the citrulline/ornithine+arginine ratio (which is more discriminatory than citrulline concentration alone) when performing prenatal diagnosis of citrullinemia.

[Study of blood pressure, hemodynamic, ventilatory and metabolic responses to isometric exercise performed during dynamic exercise in health subjects]. / Etude des réponses tensionnelles, hémodynamiques, ventilatoires et métaboliques à l'exercice isométrique réalisé au cours d'un exercice dynamique chez le sujet sain.

The object of this study was to study the blood pressure, haemodynamic, ventilatory and metabolic changes on isometric exercise during a dynamic effort in healthy subjects. Twelve healthy subjects underwent isometric exercise by manual prehension at 40% maximal capacity under these conditions: isolated (A), five minutes after the onset of rectangular dynamic exercise on a cycle at 60% of ventilatory threshold (B) and at the fourth minute of the recovery phase of dynamic exercise (C). The blood pressure, heart rate, stroke volume and cardiac index measured by Doppler echocardiography, systemic arterial resistances, respiratory flow and respiratory rate, were measured before and after each isometric exercise. The results showed blood pressure and heart rate to increase in a similar manner during isometric exercise under all conditions. The cardiac index increased by 29.5% +/- 8.3% (p < 0.01) under condition A and by 38.1% +/- 10% (p < 0.01) under conditions C but did not change significantly under conditions B. On the other hand, the systemic arterial resistances increased by 15.5% +/- 6.5% (p < 0.05) under conditions B, decreased by 8.8% +/- 3.9% (p < 0.05) under conditions C but did not change significantly under conditions A. The respiratory flow increased under all three conditions although the respiratory rate was only increased under conditions B. The authors conclude that, in healthy subjects, the increase in blood pressure during isometric and dynamic exercise is the result of an increase in systemic resistances whereas, during isometric exercise, it is flow-dependant.

[Epidemiology and prognosis of cardiac insufficiency]. / Epidémiologie et pronostic de l'insuffisance cardiaque.

Cardiac insufficiency, the outcome in the majority of cardiac diseases, is common and serious. The frequency is rising, and the fatality, even if it has diminished thanks to various treatments, remains elevated. The epidemiology of cardiac insufficiency is relatively little known in France, despite its considerable economic impact on the health system, while this constraint is ever increasing. Some significant French statistics: the number of cardiac insufficiency cases is about 500,000, there are 120,000 new cases each year. The incidence rises from 4@1000 of males and 3@1000 of females aged between 55 and 64 years to 50@1000 of males and 85@1000 of females aged 85 to 94 years. The average age for occurrence of cardiac insufficiency is 73.5 years; two thirds of patients are over 70 years. There are about 3.5 million consultations and 150,000 hospitalizations for cardiac insufficiency every year. The average length of stay is 11 days. There are more than 32,000 deaths annually from cardiac insufficiency. The costs linked to cardiac insufficiency represent more than 1% of total medical costs. Cardiac insufficiency is a major problem for public health, and it is more and more so. This must prompt us to treat our patients better, and to undertake more preventive measures.

Sustained attention in patients with obsessive-compulsive disorder: a controlled study.

Studies on attentional processes in obsessive-compulsive disorder (OCD) have been inconsistent. The present study focused on the question of sustained attention in OCD, using the 'Degraded Stimulus Continuous Performance Test' (DS-CPT) sensitivity index over time. This study included 20 OCD patients and 25 control subjects, comparable in sex, age and educational level. All subjects had a neuropsychiatric structured diagnostic interview, as well as a psychometric battery. The DS-CPT evaluated sustained attention. The sensitivity decrement during DS-CPT was significant in both controls and OCD subjects. Contrary to our expectations, OCD patients did not show a greater decrease in sensitivity over time, compared to controls: thus, OCD patients presented a no more important attention decrease than controls. Controls and OCD subjects became more conservative in their response criteria throughout the DS-CPT test. Comparing OCD with and without pharmacological treatment did not reveal any difference in CPT outcome. Moreover, we observed, in OCD, a positive significant correlation between the Y-BOCS compulsion score and the CPT sensitivity index. A significant negative correlation of the Y-BOCS compulsive score with the CPT false alarm score was also found. In conclusion, OCD patients did not present any disturbance in sustained attention during a task requiring an increased processing load.

Genotype/phenotype correlation in carnitine palmitoyl transferase II deficiency: lessons from a compound heterozygous patient.

Carnitine palmitoyl transferase II deficiency, an inherited disorder of long-chain fatty acid oxidation, may result in either a mild form (muscle disease in adults) or a severe form (hepatocardiomuscular syndrome in infants). The difference in severity between these two forms is related to a difference in levels of residual carnitine palmitoyl transferase II activity and long-chain fatty acid oxidation and in genotypes. Few data are, however, available regarding compound heterozygotes for a 'mild' and a 'severe' carnitine palmitoyl transferase II mutation. We report on such a patient carrying both the 'mild' S113L substitution and the 'severe' Y628S mutation. The patient's clinical picture (cardiac arrest at 6 years) was markedly more serious than usually observed in S113L homozygotes, and suggested that 'mild'/'severe' compound heterozygosity makes patients at risk from life-threatening events. Palmitate oxidation and carnitine palmitoyl transferase II activity were lower in lymphocytes from the S113L/Y628S patient than in those from a S113L homozygote. Thus, assessment of carnitine palmitoyl transferase II mutations, long-chain fatty acid oxidation, and carnitine palmitoyl transferase II activity, may help in predicting the potential severity of the muscular form of carnitine palmitoyl transferase II deficiency.

Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization.

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg x kg(-1) plus 0.04 mg x kg(-1)x min(-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 microg x kg(-1) plus 2 microg x kg(-1) x min(-1)), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 +/- 0.4 to 13.8 +/- 0.8 mA, p < 0.001) and lengthens VCT (28 +/- 3 to 44 +/- 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 +/- 0.6 and 8.4 +/- 0.7 mA, n.s.) or VCT (between 30 +/- 2 and 34 +/- 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.

Sustained reduction of hyperhomocysteinaemia with folic acid supplementation in predialysis patients.

BACKGROUND: Moderate hyperhomocysteinaemia, as occurs in chronic renal failure patients, is an established independent risk factor for atherosclerotic arterial occlusive accidents, the incidence of which is abnormally high in such patients. Folic acid supplementation has been shown to reduce plasma homocysteine level in end-stage renal disease patients treated with haemodialysis or peritoneal dialysis, but its long-term effects in predialysis patients had not been assessed. METHODS: We prospectively treated a total of 78 predialysis patients with folic acid for at least 1 year (range 12-74 months) together with oral pyridoxine and vitamin B12 supplements. Of the patients, 67 received 5 mg folic acid three times per week, whereas the other 11 patients who were treated with recombinant erythropoietin received 5 mg/day. Plasma fasting total homocysteine concentration was determined at baseline, after 3 months and at the end of follow-up. RESULTS: Mean (+/-SD) plasma total homocysteine level decreased from 21.2+/-6.4 micromol/l at baseline to 14.2+/-4.6 at 3 months and remained at 12.8+/-3.7 micromol/l at the end of follow-up (average duration 2.8 years), whereas plasma creatinine rose from 268+/-129 to 399+/-234 micromol/l. Mean plasma folate concentration rose from 19+/-12 to 47+/-13 nmol/l and mean plasma vitamin B12 rose from 237+/-119 to 347+/-191 pmol/l from baseline to end of follow-up. CONCLUSIONS: Moderate folic acid supplementation (2.15 mg/day) allows a substantial (40% as a mean) and sustained (up to 6 years) reduction of plasma total homocysteine level in predialysis uraemic patients without any detectable side effect. Folic acid supplementation may thus contribute to lower the risk of accelerated atherosclerosis in such patients.

[Evaluation of a specific French scale of activity in chronic heart failure. A national multicenter study. Group for Cardiac Insufficiency and Cardiomyopathy of the French Society of Cardiology]. / Evaluation d'une échelle d'activité spécifique française de l'insuffisance cardiaque chronique. Etude multicentrique nationale. Groupe insuffisance cardiaque et cardiomyopathie de la Société française de cardiologie.

Many systems have been proposed to evaluate the functional incapacity caused by chronic cardiac failure. The classification of the New York Heart Association (NYHA) is the best known. It is subjective, poorly reproducible and has a poor predictive value on effort. The authors propose a Specific French Scale of Activity with the object of a more accurate functional evaluation of cardiac failure, easier to use by the doctor and more specific to French patients and their life styles. A French multicentre study was set up in hospital departments by the French Society of Cardiology working group on Cardiomyopathy and Cardiac Failure to assess this new classification with respect to the NYHA classification and peak VO2 (Weber's classification). Eight centres participated in the study. A total of 124 patients with chronic cardiac failure and a mean age of 61 years (102 men) were included. Cardiac failure was due to ischaemic heart disease in 72 cases, hypertension in 10 cases, dilated cardiomyopathy in 40 cases and aortic regurgitation in 2 cases. Eighty-two patients underwent a double evaluation using the French Scale: 40 patients by 2 physicians and 42 patients by a physician and a nurse. Good reproducibility was found between the assessment by the 2 physicians in 35 cases (87%) and between the physician and nurse in 30 cases (71%). When compared with peak VO2, the classification was concordant in 47% of cases using the NYHA and in 61% of cases using the French Scale, with variation of one class in 40% of cases with the NYHA and 35% of cases with the French Scale. These results show good reproducibility and correspondence of classification with the exercise test which was better using the French Scale than the NYHA classification.

Does the polymorphism 677C-T of the 5,10-methylenetetrahydrofolate reductase gene contribute to homocysteine-related vascular disease?

Whether the 677C-T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene acts as a risk factor for homocysteine-related vascular disease remains a matter of debate. Testing for the 677C-T nucleotide substitution and assay of plasma homocysteine were carried out simultaneously in 69 controls and 113 vascular disease patients from the Paris area. The variant gene frequency as well as the variant homozygous genotype frequency were very similar in controls and patients. Conversely, plasma homocysteine levels were substantially higher in patients than in controls. A slight interaction between the 677C-T MTHFR polymorphism and homocysteinaemia was observed in the patient group only, while a negative correlation between fasting homocysteine and plasma folate levels was found in all individuals homozygous for the 677C-T MTHFR genotype, irrespective of vascular disease. These data suggest that the 677C-T MTHFR polymorphism is not a major determinant of the vascular disease but contributes to increased plasma homocysteine concentration in conjunction with low plasma folate levels.