Validation of a rapid enzyme immunoassay for the quantitation of retinol-binding protein to assess vitamin A status within populations.

OBJECTIVE: To compare the prevalence of vitamin A deficiency (VAD) among Cambodian preschool children as determined by the retinol-binding protein-enzyme immunoassay (RBP-EIA) and direct measurement of serum retinol by high-performance liquid chromatography (HPLC). SETTING AND SUBJECTS: Sera from 359 children were randomly selected from archived specimens collected in a national VAD prevalence survey in Cambodia. METHODS: Sera were first analyzed for retinol content by HPLC and then subjected to analysis using RBP-EIA to determine serum RBP concentrations. National Institute of Standards and Technology and control sera were used to ensure quality and accuracy for each set of analyses. To classify VAD, the same cutoff point of <0.70 micromol/l was employed for each indicator. RESULTS: Overall, the prevalence of VAD based on serum retinol was 22.3% (95% confidence interval (CI): 18.0, 26.6), whereas the RBP-EIA indicated a VAD prevalence of 20.9% (95% CI: 16.7, 25.1). A simple linear regression model indicated an R2 of 0.79, and a receiver operating curve analysis revealed an area under the curve of 0.92. CONCLUSIONS: We found no significant difference between the results of RBP-EIA compared to retinol analyzed by HPLC in estimating the prevalence of VAD. Use of the test could enable public health authorities to assess the extent of VAD and track progress in control programs in resource-poor settings.

Risk factors for nightblindness among women of childbearing age in Cambodia.

OBJECTIVE: To characterize risk factors for nightblindness among nonpregnant women of childbearing age, a group recently recognized to be at high risk of vitamin A deficiency in some developing countries. DESIGN: Case-control study. SETTING: The study included >15 000 households in National Micronutrient Survey of Cambodia conducted in 2000. SUBJECTS: The prevalence of nightblindness among 13 358 nonpregnant women was 2.0%. A total of 328 nonpregnant women with nightblindness were matched by province with 1009 nonpregnant women without nightblindness. METHODS: Univariate and multivariate logistic regression models were used to estimate odds ratios (ORs) as estimates of the relative risk of factors associated with nightblindness. RESULTS: In a final model, materials in the wall of the house (OR 1.4, 95% confidence interval (CI) 0.9-2.0), land ownership < or =0.5 hectares (OR 1.4, 95% CI 1.0-1.9), nightblindness in last pregnancy (OR 44.5, 95% CI 29.2-67.8), parity >3 (OR 1.5, 95% CI 1.0-2.1), diarrhea within the last 2 weeks (OR 1.9, 95% CI 1.3-2.8), maternal body mass index <18.5 (OR 1.8, 95% CI 1.2-2.7), and lack of consumption of vitamin A-rich animal foods in the last 24 h (1-60 retinol equivalents (RE) OR 1.1, 95% CI 0.7-1.6; > or =60 RE, OR 0.7, 95% CI 0.4-1.0) were associated with nightblindness among nonpregnant women. CONCLUSIONS: Women of childbearing age in Cambodia with low socioeconomic status, low consumption of vitamin A-rich animal foods, a history of nightblindness during the previous pregnancy, parity >3, malnutrition, and diarrhea have a higher risk of nightblindness. SPONSORSHIP: United States Agency for International Development (442-G-00-95-00515-00).

[Detection and surveillance of left atrial thrombosis by transesophageal echocardiography]. / Détection et surveillance des caillots de l'oreillette gauche par échographie transoesophagienne.

Out of 1,141 successive transoesophageal echocardiographic studies performed prospectively between 01/05/1993 and 31/12/1995, 26 cases of left atrial thrombosis were observed (2.2%); 5 were in the left atrium (20%), 19 in the left atrial appendage (73%) and the thrombi were in both atrium and left atrial appendage in 2 cases (7%). The 26 patients included 15 women and 11 men, with an average age of 69 +/- 16 years (range 25-89 years); 22 patients (84%) had permanent atrial fibrillation and 4 were in sinus rhythm. Only 5 of the patients were on oral anticoagulant therapy. All had underlying cardiac disease: 11 mitral valve diseases; 10 dilated cardiomyopathies; 2 hypertrophic cardiomyopathies; 3 other cardiac diseases. The indication for transoesophageal echocardiography was systemic embolism in 13 cases (50%); before D.C. cardioversion in 10 cases (38%) and before percutaneous mitral valvuloplasty in 3 cases. The thrombus was adherent in 18 cases (69%) and mobile in 8 cases (31%). Spontaneous contrast was observed in 23 cases (88%). Intravenous heparin was given as soon as the diagnosis was made. In 4 patients, thrombectomy was indicated in view of the threatening nature of the thrombus and/or the necessity for associated valve replacement. In 22 patients, heparin was relayed by oral anticoagulants on the 10th day of treatment. Control transoesophageal echocardiography was not performed because of the patient's refusal or poor general condition. The other 15 patients were reexamined 1 to 5 times between the 4th day and 12th month: a regression was observed in 13 cases (86%) which was complete in 11 and partial in 2 cases. No cases of embolism occurred during follow-up but six patients died: 1 of the operated cases and 5 of the patients treated medically (3 cardiac failures and 2 cerebral haemorrhages). The authors conclude that left atrial thrombosis is rare in the absence of classical embolic cardiac disease. With the exception of the surgical indication of a life-threatening thrombus and/or associated surgical mitral valve disease, anticoagulant therapy results in complete or partial regression of the thrombus visualised by transoesophageal echocardiography which is essential for follow-up. The prognosis depends on the severity of the underlying heart disease.

[Heart rate variability and vagal syncope in the young adult]. / Variabilité sinusale et syncope vagale chez l'adulte jeune.

Heart rate variability is a sign of sympathetic activity. The authors compared two study populations of young males aged 19 to 30 years: population T comprised 15 healthy volunteers who had two negative tilt tests, one under basal conditions and the other after a bolus of isoproterenol; population S comprised 12 patients without cardiac or other disease, who were followed up for malaise and in whom the basal tilt test was positive, confirming the vagal origin of syncope. Temporal and spectral (total power, low frequency 0.04-0.15 Hz, hight frequency 0.16-0.40 Hz) data was obtained concerning heart rate variability from 24 hour Holter monitoring. The main difference between the two study populations was in the temporal data over 24 hours especially with respect to the heart rate (T = 73.5 +/- 6.9; S = 65.4 +/- 6.2/min; p = 0.004) and the percentage of successive R-R intervals varying by more than 50 ms (PNN 50) (T = 20.2 +/- 8.3%; S = 30.7 +/- 10.2%; p = 0.024). At night, the lowest SDANN/5 (standard deviation of RR intervals over periods of 5 minutes) were observed in group S (67.2 +/- 16.7 ms vs 87.3 +/- 24.4 ms; p = 0.026). No statistically significant differences between the two groups was observed in the spectral data. The temporal data of heart rate variability on Holter ECG monitoring over 24 hours could therefore have a good predictive value of the vagal origin of syncope in young adults.

Tilt table testing of young adult patients: improved speed and sensitivity using an isoproterenol bolus and a continuous 60 degrees tilt.

The tilt table is a diagnostic device used to induce vagal syncope and determine etiology. Sensitivity enhancing techniques, such as the administration of isoproterenol, can be applied to children and young adults to compensate for the otherwise low sensitivity (20%-30%) observed in that population. This study describes an improved test that offers a simplified approach while decreasing the amount of time involved by up to 50%, without compromising sensitivity. This 45-minute procedure relies on sensitization with isoproterenol administered as a 2- to 80 micrograms bolus instead of a continuous infusion. The isoproterenol is injected at the 30th minute of a 45-minute 60 degrees tilt test without returning the patient to the supine position. In this study, the isoproterenol bolus tilt test was found to be "positive" in 24 of 30 patients reporting unexplained syncope: 10 cases before the 30th minute (11.2 +/- 8.4 min) and 14 cases after administration of 5.1 +/- 1.9 micrograms of isoproterenol.

Clinical electrophysiologic effects of a single high oral dose of amiodarone.

Several recent reports have described the antiarrhythmic effects of a single high oral dose of amiodarone but clinical electrophysiologic effects have not been reported. The present study was performed to assess electrophysiologic effects in 12 patients. After baseline electrophysiologic studies (EPS) patients were administered a single oral dose of 30 mg/kg of amiodarone. EPS was repeated 7.5 +/- 0.5 hours later. Plasma levels of amiodarone and its metabolite desethylamiodarone were determined at the time of the second EPS, Holter monitoring was performed for 24 hours after amiodarone administration. Amiodarone significantly increased the following parameters: corrected QT interval (+4.5%), functional refractory period of the right atrium (+7%); AH interval (+12.3%), effective refractory period of the atrioventricular node (+18.5%), and cycle length of Wenckebach block (+8.4%). These effects were not correlated with plasma levels of amiodarone and desethylamiodarone. Holter monitoring detected no significant bradycardia or arrhythmia. These findings indicate that the effects of a single high oral dose of amiodarone are the same as those known to be induced by acute intravenous administration.

Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients.

Most studies on the natural course of coronary artery spasm in patients with normal or nearly normal coronary arteries are based on medium-term follow-up in small populations. The present series includes 277 successive patients with a median follow-up of 89 months (range: 1 to 198 months). There were 206 men and 71 women whose mean age was 53.6 +/- 9.3 years. They were all assessed with coronary arteriography which revealed no stenoses greater than 50%. Spasm was confirmed during the coronary arteriography in 157 patients (56.7%), by a positive provocation test following the arteriography in 113 patients (40.8%), and by an electrocardiogram which showed Prinzmetal's variant angina in seven patients (2.5%). The majority of patients, 264 (95.3%) were treated with calcium channel blockers. At the end of this study: 35 patients (12.6%) were lost to follow-up; 20 patients (7.2% died) including 10 (3.6%) from cardiac causes; 18 patients (6.5%) experienced myocardial infarction in 11 of whom repeat coronary arteriography consistently demonstrated one or more significant stenoses (greater than 70%); 109 patients (39%) had persistent angina, in 52 of whom the severity (more than one episode per month) warranted repeat coronary arteriography which detected significant stenosis in 19 cases; 95 patients (34.3%) were asymptomatic. Multivariate statistical analyses showed that only predictors of major coronary events (death, myocardial infarction or angina requiring repeat coronary arteriography) were systemic hypertension or the finding of minor parietal irregularities on the initial coronary arteriogram. Conclusion. Despite treatment with calcium channel blockers, persistent or recurrent episodes of angina are frequently observed whereas complications such as myocardial infarction or death are rare.

[Pulmonary arteriovenous fistula. A rare cause of dyspnea and cyanosis in an adult]. / Communication artério-veineuse pulmonaire. Une cause rare de dyspnée et de cyanose chez l'adulte.

The authors report the case of a pulmonary arteriovenous fistula presenting with dyspnoea and cyanosis in a young adult. The malformation was situated on the proximal pulmonary vessels and was cured by surgical correction. The diagnostic value of the clinical signs and complementary investigations of this rare conditions, often detected during adulthood, is discussed. The functional tolerance of the condition is often variable. Oxygen desaturation of arterial blood indicates a right-to-left shunt. Pulmonary angiography enables visualisation of the lesions and guides surgical management. The prevalence of complications of this condition is not well known, but the potential severity is an argument for therapeutic intervention. Embolisation techniques are developing but there is a risk of a systemic embolism. Surgery is the reference for the treatment of proximal fistulae, its curative effect being immediate and definitive.

[Spasm of normal or irregular coronary arteries. Long-term outcome of 277 patients]. / Spasme sur artères coronaires normales ou irrégulières. Devenir à long terme de 277 patients.

The outcome of patients presenting with spasm of normal or subnormal coronary arteries is only known in small series of patients at medium-term. The authors reviewed the outcome of 277 successive patients over an average period of 86 +/- 43 months (12 to 174 months). There were 206 men and 71 women with a mean age of 54 +/- 9 years. Coronary angiography was performed in all cases and did not show any stenosis greater than 50%. Spasm was documented during coronary angiography in 157 cases (57%) by a positive Methergin test after coronary angiography in 113 cases (41%) and by an ECG recording of Prinzmetal angina in 7 cases (2.5%). Nearly all patients (264: 95%) were treated by calcium antagonists. At the end of follow-up, there were: 35 lost to follow-up (12.6%), 20 deaths (7.2%) of which 10 were cardiac (3.6%), 18 myocardial infarctions (6.5%): 11 had repeat coronary angiography which showed one or more new significant (> 70%) coronary lesions in all cases; 109 patients had persistence of chest pain (39%). The severity of symptoms in 52 cases (over one attack of chest pain per month) led to repeat coronary angiography which showed significant coronary disease in 19 cases; 95 patients (34%) were asymptomatic. A multivariate statistical analysis showed hypertension or subnormal appearances on the initial coronary angiography to be significant predictive factors for new coronary events (death, myocardial infarction or angina requiring repeat coronary angiography). The authors conclude that coronary spasm of angiographically normal or subnormal arteries is only well controlled at long-term in 39% of patients not lost to follow-up and is responsible for death or myocardial infarction in 11.6% of cases (nearly 1.5% per year).

[Detection of circulating endothelial cells: a new diagnostic test of angina at rest]. / Détection des cellules endothéliales circulantes: un nouveau test diagnostique de l'angor de repos.

The diagnosis of spontaneous angina depends on the recording of per-critical electrocardiographic changes. There is no simple biological test to make its retrospective diagnosis. The attack is usually triggered by instability of an atheromatous plaque which fissures and liberates endothelial cells in the blod stream. The detection of these cells cold therefore be a biological sign of this condition. The technique of detection of circulating endothelial cells by immuno-magnetic method was used in 3 groups of patients admitted to hospital within 24 hours: group I comprised 11 patients with acute myocardial infarction, group II comprised 23 patients who had suffered from spontaneous angina with ST segment depression during the attack and significant coronary arterial stenosis, group III comprised 6 patients with chest pain for which coronary angiography is normal and provocative test of spasm is negative. Circulating endothelial cells were detected in all patients of group I (100%), in 18 of the 23 patients of group II (78%) and only in one of group III (18%). These results confer on this biological test for spontaneous angina a specificity and predictive positive value of 83 and 95% and a sensitivity and negative predictive value of 78 and 50%. Therefore the detection of circulating endothelial cells could be used as a simple and reliable test for retrospective diagnosis of spontaneous angina. The mediocre sensitivity and negative predictive value may be explained by a mechanism other than fissuration of atheromatous plaque in some cases of spontaneous angina.

[Treatments of acute myocardial infarction other than recanalization ]. / Traitements de l'infarctus aigu du myocarde autres que la reperméabilisation.

During the past 15 years, the in-hospital mortality of patients with acute myocardial infarction has considerably declined. The 2 main reasons for this decrease in mortality have been the introduction of intensive coronary care units, and reperfusion of myocardial infarction, either by coronary thrombolysis or percutaneous transluminal coronary angioplasty. However benefits of other therapies should not be overlooked. General care measures should include: close supervision, bed rest, liquid diet, analgesics, reduction of anxiety, oxygen therapy, intravenous heparin and aspirin, monitoring of blood pressure and heart rate. beta-blockers and angiotensin-converting enzyme inhibitors, combined or not with thrombolytic therapy, are also available to reduce the rate of mortality and morbidity. The benefits to be expected from these 2 medications combined have not yet been demonstrated, so that it appears reasonable in common practice to choose either drug according to the patient's functional state.

[Comparison of the antispastic effect of Bi-Tildiem 120 mg and Tildiem 60mg]. / Comparaison de l'effet anti-spastique du Bi-Tildiem 120 mg et du Tildiem 60 mg.

Diltiazem (Tildiem 60 mg) is a calcium channel blocker with demonstrated efficacy and safety in the treatment of stable angina pectoris and spastic angina. The sustained release formulation of diltiazem, allowing two daily doses (Bi-Tildiem 120 mg), is already marketed in France for the treatment of stable angina. It was therefore interesting to evaluate the efficacy and safety of this form, administered in two daily doses, in coronary spasm, versus the classical formulation, Tildiem 60 mg, given at the same daily dose, i.e. 240 mg, in three divided doses per day. We conducted a single-centre, randomized, double-blind, cross-over clinical study in twelve patients, eleven men and one woman, between the ages of 42 and 70 years, presenting with angina and normal coronary arteries and spasm documented by a positive methylergonovine (Methergin) test. They were divided into two groups of six patients receiving either Tildiem followed by Bi-Tildiem, or Bi-Tildiem followed by Tildiem. The characteristics of the two groups were comparable at the time of the selection visit. The methylergonovine test, used to assess the efficacy of the two treatments, was improved by Tildiem and Bi-Tildiem compared to the placebo test (p = 0.001 and 0.002), without any significant difference between Tildiem and Bi-Tildiem: an improvement was obtained in 11/12 and 10/12 patients, respectively. No deterioration of the test was observed with Tildiem or Bi-Tildiem compared to placebo. The coronary symptoms and blood diltiazem levels were similar with Tildiem and Bi-Tildiem. The results confirmed the safety of Bi-Tildiem. A single adverse effect was attributed to treatment: an episode of mild insomnia. No serious adverse effect were observed and none of the patients discontinued the study. The efficacy and safety of Tildiem and Bi-Tildiem are comparable in the treatment of spastic angina.

[Vagal syncope in young adults: specificity of the tilt-table test]. / Syncope vagale de l'adulte jeune: spécificité du test d'inclinaison.

OBJECTIVE: The head-up tilt test has been used for more than 10 years to reproduce vagal lipothymia. The criteria for a positive test and specificity are however still lacking. METHOD: Thirty male volunteers, age 18 to 35 years, with no past history of lipothymia nor any signs of hypervagotonicity at physical examination, on fasting blood samples or on exercise tests with sudden interruption and Holter recording were selected for the study. Two head-up tilt tests at 60 degrees for 45 minutes were conducted, one with no presensitivisation and the other with a bolus of isoproterenol (2, 4, 6 and 8 micrograms) starting 30 minutes after the beginning of the test. Blood pressure was measured throughout the test. RESULTS: The systolic blood pressure curves showed drops of more than 30 mmHg accompanied by spontaneously resolving clinical signs in 6 of the 30 subjects during the non-sensitized tests and in 14 out of 30 during the sensitized tests. A symptomatic drop in systolic blood pressure of more than 30 mmHg compared to the moment before the malaise accompanied by clinical signs which did not resolve within 1 minute and required returning to the supine position occurred in one volunteer during a non-sensibilized test. This same type of reaction was observed in 4 volunteers during sensitized tests, three times after an isoproterenol bolus. CONCLUSION: Taking this later manifestation as the criteria for a positive head-up tilt test, the specificity of the non-sensitized and isoproterenol-sensitized tests in the young adult are 96.7 and 86.7% respectively. These findings must be considered with caution since there is no proof that these young men with no past history of hypervagotonicity but a positive head-up tilt test may be one day confronted with a situation generating a vagal reaction.

[Ambulatory venous thromboembolitic disease. Clinical, etiological and evolutive data]. / Maladie veineuse thrombo-embolique ambulatoire. Données cliniques, étiologiques et évolutives.

OBJECTIVES: Venous stasis in bedridden patients is recognized as one of the risk factors for venous thromboembolism but the phenomena is known to occur in ambulatory subjects and another cause must be involved. We investigated a series of consecutive ambulatory patients with venous thromboembolism in order to distinguish the particular clinical manifestations and possible aetiologies. METHODS: We compared a retrospective series of 120 consecutive patients with deep vein thromboembolism of the lower limbs and 127 patients with the same disease who had been bedridden at onset. In addition to the physical examination, the aetiological work-up included echography (n = 14), abdominal computed tomography (n = 38) and/or haemostasis studies (n = 61). Mean follow up was 23 +/- 13 months (range 1-45 months). RESULTS: Family history of deep venous thromboembolism was found in 17 patients and recurrence was observed in 50 patients. Phlebitis was on the right in 52 cases, on the left in 47 and bilateral in 17. Proximal locations were more frequent (74%) and pulmonary embolism occurred in one-half of the patients (n = 58). A cause was identified in 61 cases (50.8%): cancer (n = 24, 17 known, 7 previously unknown), dyscrasia (n = 17, protein S or C deficiency (5), increased plasminogen activator inhibitor I (8), circulating anticoagulants (3), hypofibrinogen (1), idiopathic varicose veins (n = 7), pregnancy (n = 5), oral contraceptives (n = 4) and other causes (n = 4). No cause was identified in 59 patients. Pulmonary embolism led to death in 4 cases. Seven patients were lost to follow-up and anticoagulation therapy was taken by 79 (72%) then interrupted in the others 3 to 6 months later. Eighteen patients died, 14 due to the underlying disease, 2 from new cancers and 12 after recurrent thromboembolism. CONCLUSION: Ambulatory venous embolism is as frequent as embolism in bedridden patients and the cause can be observed in 50% of the cases.

[False pseudoaneurysm of the left ventricle after myocardial infarction. Recognition by transesophageal echocardiography]. / Pseudo-faux anévrysme du ventricule gauche après infarctus du myocarde. Reconnaissance par l'échocardiographie transoesophagienne.

Left ventricular pseudo-false aneurysm is caused by a discrete rupture of the myocardial wall which remains circumscribed within the wall itself, realising a cavity joined to the left ventricle by a narrow neck. It is an extremely rare complication of myocardial infarction. Two cases diagnosed in vivo by left ventriculography are reported. Their diagnosis and precise locations were confirmed by transoesophageal echocardiography. In the first case, the pseudo-false aneurysm was situated in the interventricular septum and, in the second, in the antero-lateral wall. The natural history of asymptomatic pseudo-false aneurysms is unknown. The advanced age of the patients and the possibility of regular follow-up by transoesophageal echocardiography were the main reasons for surgical abstention in these particular cases.

[Comparison of continuous and intermittent treatment with glyceryl trinitrate by the transdermal route in stable effort angina]. / Comparaison du traitement continu et discontinu de trinitrine par voie transdermique dans l'angor d'effort stable.

The anti-angina efficacy of the continuous (C) transdermal application of nitroglycerin may lessen or disappear over the course of time. Pharmacological tolerance, which is probably responsible, might be prevented by intermittent (I) application. However few studies have compared the C and I methods. The effects of transdermal patches containing 10 mg, applied for 24 hours/day and for 15 hours/day for one week were evaluated in twelve patients. Exercise tests were performed before and 4 hours after the initial application and after one week of each type of treatment prescribed in random order with a 7 day wash-out between each treatment phase. Plasma nitroglycerin concentrations were measured at the same time. Total work and ischemia and angina thresholds after 4 hours application all increased significantly in comparison with baseline values. All these values persisted after one week of I treatment. With C treatment they decreased though remained significantly above baseline values with the exception of angina thresholds. I treatment appeared significantly better than C treatment regarding ischemia threshold (3,974.7 kpm v. 3,037.5-p < 0.01). Plasma nitroglycerin levels were the same during each treatment phase. These results suggest that the anti-ischemic efficacy of transdermal patches persists after one week of treatment, though with superiority of intermittent treatment. Continuous treatment tends to induce pharmacodynamic tolerance since there was no difference in plasma nitroglycerin levels.

[Contribution of myocardial biopsy and immunohistochemistry to the prognostic evaluation of cardiac amyloidosis]. / Apport de la biopsie myocardique et de l'étude immunohistochimique à l'évaluation pronostique des amyloses cardiaques.

The authors report four cases of cardiac amyloidosis, the diagnosis of which was confirmed by endomyocardial biopsy. They underline the value of immuno-histological studies with labelling of the biopsy fragments with anti-transthyretin and anti-light chain immunoglobulin antibodies. This approach provides a more precise typing of amyloidosis and a more accurate evaluation of the prognosis.

[Flecainide exercise induced left bundle branch with chest pain]. / Bloc de branche gauche douloureux d'effort induit par flécaïnide.

Ischaemia has been the suggested mechanism of simultaneous left bundle branch block and chest pain on effort with normal coronary angiography. This hypothesis is very controversial and was not the mechanism in the two new cases of this syndrome. The two patients in whom effort pain and left bundle branch block were observed had been treated for paroxysmal supraventricular tachycardia with flecaine. Withdrawal of the anti-arrhtymic resulted in the disappearance of this syndrome. In these cases, the ischaemic mechanism could be excluded without ambiguity. The flecaine was the only cause of rate-related LBBB by slowing conduction in the left bundle branch with no effects on coronary reserve. It would seem that LBBB alone was the cause of chest pain. The absence of coronary artery disease was confirmed in the first patient and the diagnosis was highly improbable in the second.