Homoeopathic eye drops in the treatment of mild-to-moderate dry eye disease: Randomised, prospective, multicentre, single-masked study.

INTRODUCTION: To compare the efficacy and safety of a homeopathic eye drop medicinal product (Homeoptic®) with 0.9% sodium hydrochloride eye drops (Larmabak®) in patients with mild-to-moderate dry eye disease (DED). METHODS: Prospective, single-masked, observer-blinded, multicentre study on adult patients. Non-inferiority primary endpoint of the relative change between treatment groups in a composite Visual Analogue Scale (VAS) score covering five symptoms of DED, namely pain, itching, sensation of dry eye, impression of foreign body presence and burning, after 30 days of treatment. Details of all Adverse Events (AEs) were recorded and analysed. RESULTS: Ninety three patients were randomised to each treatment arm. At Day 30, the mean VAS symptom score was 26.0 ± 18.8 in the Homeoptic® group and 32.8 ± 21.2 Larmabak® group. Homeoptic® was demonstrated to be non-inferior to Larmabak®: the mean treatment difference of -7 being below the 10 mm upper limit of the 95% CI ([-12.9; -1.0]) pre-set as significant. The superiority of Homeoptic® over Larmabak® was then established with detection of a significant difference between the two treatment groups (p = 0.022). Significant differences between the treatment groups in favour of Homeoptic® were also detected in isolated VAS scores for the symptoms dry eye sensation (p = 0.009) and burning (p = 0.004). Results of ocular surface staining tests to estimate corneal and conjunctival damage as well as patient satisfaction were also significantly in favour of Homeoptic®. No new safety concerns were identified. CONCLUSION: Homeoptic® is more effective than Larmabak® at relieving the symptoms of DED and constitutes an effective treatment for mild-to-moderate DED.

Glucagon and insulin secretion and their biological activities in hypothermic rats.

To clarify the impact of hypothermia on the hormonal control of glucose metabolism, rats were rendered hypothermic (25 C) after catheterization of the portal vein. Glucose, insulin, glucagon, and catecholamine concentrations were serially monitored, and the regional blood flows were measured, allowing the estimation of hormone outputs. Hypothermia reduced the portal blood flow by 50% without changing arterial blood pressure, blood gases, or pH. Portal plasma insulin secretion dropped (0.05 +/- 0.01 vs. 0.23 +/- 0.04 mU/min), and glucagon secretion increased (0.81 +/- 0.18 vs. 0.38 +/- 0.10 ng/min). The B cell responses to glucose, arginine, and glucagon were abolished, while the A cell response to arginine was not significantly affected. Glucose intolerance was apparent after iv glucose or arginine loads. Haloperidol and to a lesser extent phentolamine suppressed the cold-induced glucagon rise. Phentolamine and to a lesser extent haloperidol alleviated the cold-induced suppression of insulin release. Propranolol, naloxone, and atropine were relatively inactive. The cold-induced glucose intolerance was not corrected by phentolamine treatment. A marked resistance to iv insulin was apparent in these rats, which is in contrast to a normal sensitivity to iv glucagon.

[Measurement of pacemaker effect: incidences on the choice of pacing mode? A prospective and statistical study of 396 patients]. / La mesure de l'effet pacemaker: incidences sur le choix du mode de stimulation? Etude prospective et statistique de 396 patients.

Single ventricular stimulation induces haemodynamic disturbances, the best known of which is the pacemaker syndrome. In order to assess the prevalence and severity of these abnormalities, invasive blood pressure monitoring was performed in 396 consecutive patients undergoing endocavitary electrophysiological investigations: a decrease in systolic blood pressure at a rate near to that of the spontaneous rhythm defines the pacemaker syndrome. It is maximal after 3 to 5 beats of equivalent intensity with or without retrograde conduction. The pacemaker syndrome is greater in hypertensive and coronary patients than in subjects with healthy hearts (-44.2 mmHg and -37.2 mmHg versus -33 mmHg, p < 0.001 and p < 0.04). It is less pronounced in cases of cardiac failure (-31.8 mmHg). The pacemaker syndrome increases in intensity with age (-44.3 mmHg after 80 years of age versus -23.1 mmHg in subjects under 50 years of age; p < 0.001). Two electrophysiological abnormalities are associated with an increased pacemaker syndrome even in apparently normal hearts: sustained induced supraventricular tachycardia (-34.2 mmHg versus -26 mmHg, p < 0.002), mixed carotid sinus syndromes (-38 mmHg) and pure vasodepressive syndromes (-48.5 mmHg, p < 0.001). The study of the pacemaker syndrome is useful for three reasons: the detection of another cardiac abnormality in cases of sustained induced supraventricular tachycardia, even in an apparently healthy heart; to assess the presence of a second haemodynamic abnormality independent of the vagal effect in cases of carotid sinus syndrome with vasodepression; finally, to identify the patients at high risk of a pacemaker syndrome.

[Characteristics and influence of different clinical forms on the development and prognosis of carotid sinus syndrome. Apropos of 215 cases]. / Caractéristiques et influence des différentes formes cliniques sur l'évolution et le pronostic des syndromes du sinus carotidien. A propos de 215 cas.

The carotid sinus syndrome is a well-known cause of syncope: the cardio-inhibitory forms are the easiest to diagnose and probably the easiest to treat. However, the vasodepressive forms are as common but their outcome is mainly unknown. Eight hundred and fifty-three patients underwent endocavitary electrophysiological studies with invasive blood pressure measurement for unexplained syncope between October 1984 and January 1990. A carotid sinus syndrome was diagnosed in 215 cases. Fifty-two patients (24.2%) had a cardio-inhibitory form (ventricular standstill > or = 3 s during carotid sinus massage), 40 (18.6%) had a pure vasodepressive form (isolated fall of systolic blood pressure > 50 mmHg during massage) and 123 patients (57.2%) had a mixed form. The average age was 74.1 +/- 9.7 years with no difference between the different forms. A number of parameters was different on the cardio-inhibitory and vasodepressive forms: the number of men (75.6 vas 24.4%; p < 0.05) and the number of syncopes (83.3 vs 60%; p < 0.02) were greater in the cardio-inhibitory form; the vasodepressive forms were more often associated with a history of transient ischaemic attacks (15 vs 0%), a poor cardiovascular status (hypertension: 47.5 vs 15.7%; p < 0.01), coronary artery disease (47.5 vs 25.5%; p < 0.05), cardiac failure (27.5 vs 11.7%; p < 0.05), induction of sustained supraventricular tachycardia (50 vs 23.5%; p < 0.05) and a greater pacemaker effect (53.6 vs 34.8 mmHg; p < 0.01); of the 191 patients (84.9% of the population) followed up for an average of 21.2 months, 168 received treatment: implantation of a cardiac pacemaker in 108 patients, reduction of antihypertensive and/or potentially bradycardia-inducing drugs in 30 patients, prescription of antiarrhythmic therapy, in 30 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Iatrogenic pathology in coronary intensive care units. Results of a prospective survey on 802 patients]. / La pathologie iatrogénique en unité de soins intensifs cardiologiques. Résultats d'une enquête prospective sur 802 patients.

Iatrogenic disease in the coronary care unit was detected and analysed using a grid over a 17.5 month period (16.09.82 to 25.02.84). The cases of 802 patients, mean age 65.8 years, predominantly male (56.6%) were examined. Minor or minimal pathology in which the causal relationship was conditional or doubtful according to Karch's criteria was excluded. Only those conditions, moderate, severe or even lethal, specific or not to this type of unit, requiring specialised hospital care and in which the causal relationship could be adequately established were retained. Iatrogenic pathology was common: 11.84% of admissions. This group of 95 patients did not differ significantly from a control group with respect to age [average 4 years older (NS)] or mortality. However, there was a clear cut female predominance (68%, p. less than 0.01) and a different distribution of the organic pathology (p less than 0.001). The iatrogenic disease developed before hospital admission in 40% of patients and during hospitalisation in 60% of patients. It increased the duration of the patient's stay by half (2.77 days). Nearly a quarter of these patients had two or more types of iatrogenic disease. The undesirable effects of drugs were mainly bradycardia (44 cases), tachycardia (11 cases), haemodynamic changes, vascular, renal, gastrointestinal, metabolic and endocrine complications. Twenty-one complications of medical procedures and 13 of surgical procedures were also noted. This study, the first to have been performed in a Coronary Care Unit to the author's knowledge, confirms the high incidence of iatrogenic pathology. This fact should be born in mind before taking any therapeutic decision or before performing invasive diagnostic investigations.

[Carotid sinus syndrome. Contribution of arterial pressure monitoring to intracavitary electrophysiological exploration]. / Le syndrome du sinus carotidien. Apport de la monitorisation de la pression artérielle à l'exploration électrophysiologique endocavitaire.

A prospective study based on intracavitary electrophysiological exploration coupled with invasive arterial pressure monitoring was conducted in 245 patients aged 70.2 +/- 13 years who had experienced syncopes and/or lipothymias of uncertain origin. The study showed that 63 patients (25.7 p. 100) had carotid sinus syndrome (CSS). The syndrome was of the vagal type (cardiac inhibition) in 27 p. 100 of the cases, of the depressor type (vasodepression) in 22 p. 100 of the cases and mixed in 51 p. 100 of the cases with the two types of pathological response: electrophysiological and haemodynamic. Compared with the remaining 182 patients, these 63 patients were more frequently male (63.5 p. 100, p less than 0.01), of the same age (71.7 years, NS) and more symptomatic, meaning that syncopes occurred in 80 p. 100 of the cases and that their number per patient was higher (2.92, p less than 0.01). A predisposing factor (usually a vagal predominance) was found in 26.9 p. 100 of the cases. In 30 p. 100 of the patients CSS was associated with a sinus node disease or with disorders of atrioventricular conduction. Another haemodynamic abnormality often associated with CSS was a more pronounced (-38.7 mmHg, p less than 0.01) and more frequent (68 p. 100, p less than 0.01) pacemaker effect. 62 p. 100 of patients with mixed CSS had an increase in systolic arterial pressure during vagogenic manoeuvres with DDD mode stimulation as compared with the VVI mode stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Symptomatic sinus dysfunction. A new use of electrophysiology]. / La dysfonction sinusale symptomatique. Une nouvelle utilisation de l'électrophysiologie.

The authors undertook a prospective electrophysiological study of 950 patients: 53 subjects considered to be "controls" since they were free of any history of syncope or faintness were identified, as well as 39 symptomatic subjects with a strong suspicion of sinus dysfunction, since no other detectable cause of fainting episodes was found by extracardiac investigation, 24 hour ECG nor electrophysiology. Following the creation of a computerised tool enabling not only the entry of indirect tests, processing, averaging of results, printing and memorization, but also assistance in interpretation, several electrophysiological parameters were used: heart rate and existence of sinus arrhythmia, Strauss tests with adjusted data or not, effective nodal refractory period, Guize, Narula and Mandel tests, and an atropine (0.03 mg/kg) test which was performed only in the symptomatic group. These tests were studied by single-variate and correlative analysis to define their normal ranges, their critical values and their dependence or independence. The performance of each test (i.e. its efficiency, and the specificity and sensitivity of each critical value) was measured. Tests found to be most useful (specificity and efficiency > 90%) were as follows: Mandel test = CSRT > or = 534 ms, Narula test = TECASA > or = 339 ms, heart rate < or = 55/min, type II, IIa and chaotic Strauss curve associated with a pathological Guize test. The combination of these tests in this algorithm resulted in an increase in sensitivity to 84%, at the price of a very moderate fall in specificity to 87%.(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of intravenous flecainide in electro-induced supraventricular arrhythmia. Apropos of 37 cases]. / Intérêt du flécaïnide en intraveineuse dans les troubles du rhythme supraventriculaires électro-déclenchés. A propos de 37 observations.

Thirty-seven patients presenting with electro-induced supraventricular arrhythmia sustained for more than 10 min or symptomatic received an intravenous injection of flecainide acetate (1.5 mg/kg; 10 mg/min). There were 24 cases of atrial fibrillation, 13 of atrial tachysystole with more than 180 beats per minute. Electrophysiological exploration was carried out for syncope (13 cases), lipothymia with palpitations (11 cases) or without palpitations (8 cases), or for a stroke of unknown origin. The induced arrhythmia was the only electrophysiological abnormality in 57% of cases. A return of sinus rhythm was obtained in 70% of cases during the injection (12 cases) or shortly after the end of the injection (14 patients). Safety was good, with the exception of the onset of two junctional rhythms and one case of non-syncopal monomorphic ventricular tachycardia. After an initial reduction, the PR, QRS, PA and HV intervals were significantly longer than baseline, whereas the AH space and the systolic blood pressure remained virtually unchanged. Thus the provision of IV flecainide acetate can only be beneficial in carrying out study protocols of abnormalities of the atrial substrate.

Use of the headache impact test (HIT-6) in general practice: relationship with quality of life and severity.

To assess the global impact of episodic headaches in patients consulting general practitioners (GPs) using the Headache Impact Test (HIT-6) questionnaire, and to compare this with measures of headache severity and quality of life. A total of 2802 patients consulting 349 GPs participated to this cross-sectional study. Data were collected on headache severity using the Migraine Severity (MIGSEV) scale, headache impact with the HIT-6 and quality of life with the Qualité de Vie et Migraine (QVM) questionnaire. Diagnosis was assigned retrospectively according to the International Headache Society criteria. The association between the HIT-6 scale and the other scales was determined from a Pearson's chi-square test, an analysis of variance and Spearman correlation coefficients. Patients (2537) provided exploitable data. Six percent of the sample had little impact, 14% moderate, 14% substantial and 66% severe impact. The HIT-6 scores were significantly different between diagnostic groups, being highest in the migraine group. The HIT-6 score were well correlated with headache severity and QVM score. The HIT-6 scale correlates, across different diagnostic groups of headache, with both headache severity and with quality of life.

A new technique for hepatic portal vein catheterization in freely moving rats.

To perform kinetic studies of pancreatic hormones in freely moving rats, we have designed a new technique for hepatic portal vein catheterization through the left branch of the portal vein. Rats were followed up for 14-38 days. Catheter patency allowed blood sampling in 86% of rats on postoperative day 8 and in 55% on day 12. Rat growth, liver functions, and regional blood flows (measured with radiolabeled microspheres) were normal. In freely moving rats fasted for 16 h, portal venous concentrations in the basal state were: glucose, 112 +/- 4 mg/dl; insulin, 67 +/- 10 microU/ml; and glucagon, 480 +/- 74 pg/ml. These values remained stable for a 1-h period. Intravenous glucose infusion induced a biphasic insulin release, significant from the 1st min of infusion on, and a significant decline in glucagon level. Intravenous arginine stimulated both A and B cells. The portoperipheral hormone concentration gradient, which was detected in the basal state, increased during arginine infusion, particularly in regard to insulin. Ingestion of a mixed meal induced an early glucagon release and a sustained rise in insulin and glucose concentrations.