Fibrinogen and pentoxifylline.
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Biomedical subjects
Publications and source records attributed to S Lancrenon.
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A collaborative exploratory study was undertaken by 139 private angiologists in 427 out-patients with PVD stage II treated for 90 days with Pentoxifylline 1 200 mg per day. In 306 patients (71,6%) the fibrinogen level was decreased by 0,21 g/l in mean (p less than 0.01). This significant decrease is correlated to the global improvement (p less than 0.01) and is within the magnitude of difference that is associated between vascular death and comparative groups in recent epidemiologic studies. In 121 patients (28, 4%) of the non responders in whom the claudication was not improved or was even worsened, no change in the fibrinogen level was seen.
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In a group of 22 autistic children aged 5 to 16 years and a group of normal controls matched for age and sex, catecholamines metabolism was investigated in plasma, platelets, and urine. This investigation was part of a research project in which several biological parameters (including serotonin) were explored simultaneously in the same children. In the autistic group, epinephrine and norepinephrine were significantly elevated in plasma, while epinephrin, norepinephrine, and dopamine were significantly lower in isolated platelets. No significant difference was found between the two groups for the urinary excretion of epinephrine, norepinephrine, dopamine, DOPAC, and MHPG. Other differences between the two groups in the statistical correlations of several biochemical parameters also suggest abnormalities of bioamine metabolism in the platelets of autistic children.
A multicentre controlled trial was carried out to determine the optimal dosage of a 2/1 combination of captopril plus hydrochlorothiazide (HCTZ) in mild hypertension at three doses against placebo in a 6 week double-blind trial. The number of patients was 111:27 received placebo; 26 were treated with captopril 25 mg plus HCTZ 12.5 mg (25/12.5); 25 with captopril 50 mg plus HCTZ 25 mg (50/25); and 33 with captopril 100 mg plus HCTZ 50 mg (100/50). A significant fall in blood pressure was seen in all four groups, but was greater with the active treatments. The percentage of patients who were normalized [diastolic blood pressure (DBP) less than or equal to 90 mm Hg] or good responders (10% fall in DBP) increased as a function of the dose. At Day 21, the antihypertensive effect of 50/25 was similar to that of 100/50, but greater than that of captopril 25-HCTZ 12.5. At Day 42, the antihypertensive effects of the three doses were similar. Tolerance data showed a higher incidence of side-effects with 100/50 than with the other dosages. Thus, 50/25 appeared to be the optimal dosage for the control of mild hypertension.
Hexahydro-2,3,4,3',4',5'-benzophenone (exifone, Adlone), a novel compound proposed for treating cognitive dysfunction in geriatric patients, was tested in a battery of standard psychopharmacological tests in the mouse. The results indicated that the compound was non-toxic and induced no signs of overt stimulation or sedation after acute administration of oral doses up to 1024 mg/kg. The compound was devoid of anxiolytic, anticonvulsant or classical neuroleptic activity and did not antagonize the effects of reserpine or a high dose of apomorphine, two tests indicative of classical antidepressant activity. On the other hand, exifone clearly decreased the duration of immobility in the tail suspension test and antagonized the hypothermia induced by a low dose of apomorphine. The compound shortened the duration of barbital induced sleep without affecting the duration of sleep induced by pentobarbital. The effects observed suggest that exifone is not devoid of psychotropic activity and might possess some properties of an atypical antidepressant.
To compare the effect of diet, cirrhotic patients with ascites were randomised into two treatment groups: (1) a low sodium diet (21 mmol) per day or (2) an unrestricted sodium intake. Both groups received effective doses of diuretics (spironolactone or, if necessary, spironolactone and furosemide. One hundred and forty patients from 12 liver units were included according to well defined criteria (group 1: 76; group 2: 64). After an initial four to seven day period of bed rest and salt restriction (21 mmol sodium pd), randomisation was done in each centre. We saw no significant difference between the two groups with respect to clinical and biochemical data; mortality or withdrawal (definitive or temporary) because of biochemical disturbances (group 1: 34%, group 2: 22%); the time for complete disappearance of ascites was significantly shorter (p = 0.014) for the salt restricted patients actuarial survival (curves plotted up to the 120th day) was not statistically different (p = 0.18), but division into subgroups using various prognostic factors showed that survival was significantly better for salt restricted patients without previous gastrointestinal bleeding (p = 0.02); hospitalisation time and costs were identical in both groups. We conclude that the advantage of a normal salt diet was not shown in this study.
49 diabetics (D) (26 IDD and 23 NIDD) were compared to 32 controls (C). Absence of ischemic cardiopathy (IC) was confirmed by routine investigations and noninvasive cardiovascular techniques, including an exercise ECG using 12 leads and a thallium 201 scintigraphy. Our results show: a) a prolonged mean isovolumetric relaxation time (IVRT) as studied by the M mode echocardiography and phonomechanography: D = 0,10 sec +/- 0,04; C = 0,05 sec +/- 0,02; p less than 0,0001; b) a reduced mean EF slope: D = 97,48 +/- 37,08 mm / sec; C = 125,68 +/- 34,35; p less than 0,005; c) a high mean Weissler index (ratio of PEP to LVET): D = 40 +/- 0,08; C = 33 +/- 0,05; p less than 0,01. IVRT and EF slope abnormalities are related to increased myocardial stiffness and impaired LV compliance. In the absence of changes in preload and afterload, the high Weissler index reflects impaired contractility of the myocardium. These abnormalities are related neither to the duration of diabetes nor to the presence or severity of the complications. With the M mode echocardiography, mean diastolic and systolic thickness of the septum is greater in D with retinopathy than in C (p less than 0,005 and p less than 0,03 respectively); mean diastolic and systolic thickness of the posterior wall is greater in NIDD than in C (p less than 0,001 and p less than 0,025). We conclude that there is evidence of left ventricular functional abnormalities specific to diabetes and unrelated to IC and hypertension. Our findings support the hypothesis that they may be due to metabolic disorders and/or myocardial microangiopathy.
The 58 items version of the Hopkins Symptom Check List (Derogatis et al.) was scored on 85 depressed outpatients treated by general practitioners. The data were obtained before any anti-depressant treatment. A principal component factorial analysis with Varimax rotation was used. 41 of the 58 items of the check list were assigned to seven independent factors: interpersonal sensitivity, somatisation (pain), retardation, digestive disorders, autonomic symptoms, sleep and obsessive disorders, depressive mood. Our results are compared to those published by Derogatis.
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The efficacy and safety of diflunisal versus placebo in the treatment of pain were compared in a multicenter, double-blind study of 1,037 patients treated for seven days by general practitioners. A statistically significant (P less than 0.001) difference in favor of diflunisal was seen using four evaLuation criteria. The incidence of side effects was generally low with both treatments; nevertheless, the number of patients suffering at least one side effect was greater after diflunisal than after placebo (P less than 0.05). A comparison of the profile of responders to diflunisal and to placebo showed no particular pattern.
Important progress has been made in the knowledge of depressive states but there remains great confusion in clinical classification. It seemed interesting to investigate more precisely the semeiology of retardation which had been less studied than Depressed Mood, as it appears to be independent from aetiological factors; retardation could in fact correspond to a common behavioral pattern of all depressive states and the target of antidepressant drugs. A scale for the quantitative rating of retardation was elaborated and was tested in its first two forms which respectively 35 and 38 depressed patients. The principal component analysis of the results seems to indicate that the concept of retardation corresponds to a univocal factor accounting for almost 50% of variance, although it rests on a wide variety of motor, verbal and intellectual items. Is is now sought to study the correlation of this behavioral pattern with the efficacy of antidepressant drugs.
Myocardial protection by a combination of cardiac hypothermia and chemical cardioplegia (high concentration of K+ and Mg++, hyperosmolarity, acid pH), was studied during 20 valve replacements. Essentially assessed on the basis of repeated measurements of postoperative cardiac output, the results were compared with those obtained previously using local hypothermia only (20 patients) and hypothermic cardioplegia using Ringer Lactate (20 patients). Analysis of haemodynamic data, which thus involved 60 patients, indicated the superiority of physicochemical cardioplegia, and this for clamping periods of up to 2 hours, but also showed the desirability of changes in the protection protocol during the ischaemia phase and during reperfusion which might improve the results.
State-anxiety has been defined as a transitory emotional response involving unpleasant feelings of tension and apprehensive thoughts. Trait-anxiety, on the other hand, has been defined as a personality trait referring to individual differences in the likelihood that a person would experience state anxiety in a stressful situation. The aim of the present study was to assess trait and state-anxiety in a population of patients consulting physicians for anxious complaints. Thus, patients who stopped the benzodiazepine (BZD) treatment after three months and those who continued it for six months were compared. Included patients were evaluated at inclusion (D0), after three months (M3) and after six months (M6). The investigator filled the Covi anxiety scale, the Raskin depression scale and a CGI; patients were asked to fill the Spielberger state/trait-anxiety questionnaire. 1,112 patients have been included, 48% considered their anxiety as chronic, 50% said the evolution was progressive, 87% considered it resulting of a trigger factor, 69% received a benzodiazepine (BZD) treatment. At D0: Covi anxiety score was 5.3 +/- 2.3 points, STAI I (state-anxiety) score was 57.4 +/- 12.2 points and STAI II (trait-anxiety) score was 52.7 +/- 10.2 points. At M3, all scores decreased, and 85% were considered as ameliorated, but differences were significant (p = 0.0001) at M6. When comparing at D0 patients who stopped BZD treatment at M3 and those who continued it, some differences appeared. In fact subjects who stopped the treatment had lower score at the STAI II, presented significantly less flushes (p = 0.01), less tremor (p = 0.04) and less feverishness (p = 0.05). Their score at Covi tended to be lower (p = 0.11). The severity of the disease, evaluated with the CGI, was also lower for the patients who stopped the BZD treatment. The trait-anxiety appeared as a good predictor of the efficacy of the BZD treatment. In fact, the trait-anxiety refers to a tendency to be anxious and higher anxiety necessitates longer treatment. The treatment response was less important in the patients who continued the treatment at M3, indicating the presence of residual anxiety in these patients.
Depression in the elderly appears to be frequently poorly understood and underdiagnosed. The frequency of depressed illness in subjects over the age of 65 years is an important problem of health care. General practitioners are often in the first line of care. The objective of this trial was to compare the efficacy and safety of fluoxetine 20 mg/day to tianeptine 37.5 mg/day in elderly patients suffering from major depressive episode defined according to DSM III-R criteria, Newcastle Depression Scale < or = -20, without associated dementia Mini Mental Status (MMSE), treated by general practitioners in ten different french regions during 3 months. 237 patients were randomised, each patient had to be treated for 12 weeks and was reviewed 5 times during the trial. Patients had signed an informed consent. This trial was in favor of the superiority of fluoxetine compared to tianeptine. The main criterium, defined as the difference of the Montgomery and Asberg Depression Rating scale (MADRS) score between day 0 and day 84, was significantly different in favour of the fluoxetine group (intent to treat and per protocol analysis) (p = 0.019). The success rate at the end of the treatment (MADRS < or = 10) was significantly higher in the fluoxetine group (fluoxetine group: 48.4% vs tianeptine group: 28.1%) (p = 0.005). These results were confirmed by analysis of the other assessment criteria Geriatric Depression Scale (GDS) and Clinical Global Impression (CGI). During the study, the safety of the two treatments was comparable.
In the phase III of the french national study on OCD, 155 patients suffering from an OCD (full DSM III-R criteria, score on NIMH-OC > or = 7, not treated or undertreated) had entered a naturalistic follow-up of 12 months duration. Obsessions, compulsions, depression, anxiety, impulsivity and global functioning were assessed by using NIMH-OC, CPRS-OC2, MOCI, MADRS, HAD (-A, -D), BDS (Behavioral Dyscontrol Scale), CGI and GAS (DSM III-R). From the initial population (155 patients), 130 (84%) had been treated with drugs and were "completers" and assessed at M6 and M12; 18 (11.6%) were lost to follow-up and 7 (4.5%) had dropped out because of treatment refusal, side-effect or improvement. Only 19% of patients had received a behavior therapy. In spite of selection of patients with severe and chronic OCD associated to depression (mean MADRS score = 25), 85% of treated patients had been treated with one anti-OCD drug (105 with fluoxetine, 17 with clomipramine and 17 with other antidepressants), 4.5% needed a treatment substitution and 4.5% a bitherapy (combination of 2 anti-OCD drugs); 84% of patients were considered as "good compliant" with visit agenda and treatment. At the end of follow-up, global improvement was observed in 77% of patients treated. Clinical improvement was assessed by different response criteria (final NIMH-OC score, 30% decrease on NIMH-OC, 35% decrease on MOCI, final GAF score > or = 70) which showed 4 patterns of response to treatment: "positive response on M6 and M12" = 43-64%; "only M12" (slow response) = 13-24%; "only M6" (escape or relapse) = 4-6%; "negative response on M6 and M12" (resistant OCD) = 19-33%. During 12 month treatment, 31 patients (22.5%) had presented an adverse effect in which 7 cases (5.1%) with "serious adverse event" and 5 cases (3.6%) who required treatment drop-out. Predictive factors of clinical response to anti-OCD drugs were explored: 1) "lack of insight" was the best factor to characterise the resistant group; 2) high base-line of "impulsivity" predict better response at M6; 3) important to severe slowness was associated with a longer delay to response (between M6 and M12). The results of the phase III from the french multi-site study will be compared to the international data on long-term treatment of OCD.
This paper presents the definite data from a French multi-center study (EPIDEP). The aim of EPIDEP was to show the feasibility of validating the spectrum of soft bipolar disorders by practicing clinicians. In this report we focus on data concerning the frequency of BP-II disorder and the key characteristics of BP-II by systematic comparison versus Unipolar depression. EPIDEP involved training 48 french psychiatrists in 15 sites; it is based on a common protocol following the DSM IV criteria (Semi-Structured Interview for Hypomania and Major Depression), and Akiskal (Soft Bipolarity), as well as criteria modified from the work of Angst (Hypomania Checklist), the Ahearn-Carroll Bipolarity Scale, HAM-D and Rosenthal Atypical Depression Scale; Semi-Structured Interview for Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal). Comorbidity and family history (Research Diagnostic Criteria) were also obtained; EPIDEP was globally scheduled in two phases: Phase 1 devoted to recruiting major depressives, and phase 2 involved in more sophisticated assessment of soft bipolarity and administrating related measures. Results are presented on the total of 537 patients included at "visit 1" and 493 assessed for soft bipolarity at "visit 2". The BP-II global rate which was 21.7% at initial evaluation, nearly doubled (39.8%) by systematic evaluation of hypomania. Intergroup comparison versus unipolar depressives showed the following key characteristics of BP-II disorder: 1) distinct clinical presentation at index depressive episode despite uniformity in global intensity of depression (overrepresentation in BP-II of "suicidal thoughts", "guilt feelings", "depersonalisation-derealisation", "hypersomnia" "and weight gain"; and of "psychic anxiety" and "initial insomnia" in UP); 2) different course of illness with younger age of onset of first depression, higher rate of suicidal attempts, recurrency and hospitalisations; 3) more difficulties for recognition of the correct diagnosis; 4) more complex temperamental dysregulations (mixture of cyclothymic, hyperthymic and irritable traits which are highly represented in BP-II group); 5) higher rate in family history of mental disorders, especially bipolar disorders. Finally, EPIDEP data confirmed the diagnostic reliability of self-rating of hypomania and cyclothymia. With a systematic search of hypomania, almost 40% of major depressive episodes seen in psychiatric settings were classified as BP-II, of which only half were recognized by the clinicians at study inclusion. The BP-II validity as a distinct disorder from Unipolars was confirmed. Moreover, EPIDEP emphasized the reliability of self-rating in assessing soft-bipolarity (hypomania and cyclothymia). In total, EPIDEP data indicated that recognition of BP-II is feasible in diverse practice settings and proposed for clinicians some adapted clinical tools for assessing soft bipolarity.