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BACKGROUND For more than 20 years, hip fracture 1-year mortality has remained around 20%. An elevation of the postoperative troponin peak within 72 hours (myocardial injury after noncardiac surgery [MINS]) is associated with a greater risk of short-term mortality in the general population. However, there seem to be conflicting results in the specific population who undergo hip fracture surgery, with some studies finding an association between troponin and mortality and some not. The objective of the present study was to investigate the association of MINS and the short- (before 28th day), intermediate- (before 180th day), and long-term (before 365th day) mortality after hip fracture surgery. METHODS We conducted a single-center retrospective cohort of patients undergoing hip fracture surgery from November 2013 to December 2015. MINS was defined as postoperative troponin peak within the 72 hours >5 ng/L. Four MINS subgroups were defined according to the value of troponin peak (ie, ≥5

Although lithium is widely used in current practice to treat bipolar disorder (BD) and treatment-resistant major depressive disorder (MDD) among older adults, little is known about its efficacy and tolerability in this population, which is generally excluded from randomized clinical trials. The objective of this study was to evaluate the efficacy and tolerability of long-term use of lithium among older adults with BD and MDD.Data from the Cohort of individuals with Schizophrenia and mood disorders Aged 55 years or more (CSA) were used. Two groups of patients with BD and MDD were compared: those who were currently receiving lithium versus those who were not. The effects of lithium on psychiatric (i.e., depressive symptoms severity, perceived clinical severity, rates of psychiatric admissions in the past-year), geriatric (overall and cognitive functioning) and physical outcomes (i.e., rates of non-psychiatric medical comorbidities and general hospital admissions in the past-year) were evaluated. All analyses were adjusted for age, sex, duration of disorder, diagnosis, smoking status, alcohol use, and use of antipsychotics, antiepileptics or antidepressants.Among the 281 older participants with BD or MDD, 15.7% were taking lithium for a mean duration of 12.5(SD = 11.6) years. Lithium use was associated with lower intensity of depressive symptoms, reduced perceived clinical global severity and lower benzodiazepine use (all p 0.05), without being linked to greater rates of medical comorbidities, except for hypothyroidism.Data were cross-sectional and data on lifetime history of psychotropic medications was not assessed.Our results suggest that long-term lithium use may be efficient and relatively well-tolerated in older adults with BD or treatment-resistant MDD.

OBJECTIVES: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk of ventilator-associated pneumonia in this specific population. DESIGN: Cohort exposed/nonexposed study among the REA-REZO surveillance network. SETTING: Multicentric; ICUs in France. PATIENTS: The coronavirus disease 2019 patients at admission were matched on the age, sex, center of inclusion, presence of antimicrobial therapy at admission, patient provenance, time from ICU admission to mechanical ventilation, and Simplified Acute Physiology Score II at admission to the patients included between 2016 and 2019 within the same surveillance network (1:1). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall incidence of ventilator-associated pneumonia, the cumulative incidence, and hazard rate of the first and the second ventilator-associated pneumonia were estimated. In addition, the ventilator-associated pneumonia microbiological ecology and specific resistant pattern in coronavirus disease 2019 exposed and nonexposed patients were compared. Medication data were not collected. A total of 1,879 patients were included in each group. The overall incidence of ventilator-associated pneumonia was higher among coronavirus disease 2019 exposed patients (25.5; 95% CI [23.7-27.45] vs 15.4; 95% CI [13.7-17.3] ventilator-associated pneumonia per 1,000 ventilation days). The cumulative incidence was higher for the first and the second ventilator-associated pneumonia among the coronavirus disease 2019 exposed patients (respective Gray test p < 0.0001 and 0.0167). The microbiological ecology and resistance were comparable between groups with a predominance of Enterobacterales and nonfermenting Gram-negative bacteria. The documented resistance pattern was similar between groups, except for a lower rate of methicillin-resistant Staphylococcus aureus in the coronavirus disease 2019 exposed patient (6% vs 23%; p = 0.013). CONCLUSIONS: There was a higher incidence of ventilator-associated pneumonia occurring among coronavirus disease 2019 patient compared with the general ICU population, with a similar microbiological ecology and resistance pattern.

The biguanide drug metformin is one of the most commonly used medications for the treatment of type 2 diabetes mellitus. Diabetics are at an increased risk for cancer. Previous studies have demonstrated improved outcomes in patients taking metformin suffering from prostate, colon, lung, thyroid, and esophageal cancers. Metformin's main antineoplastic mechanism of action is thought to be mediated through inhibition of mammalian target of rapamycin, inhibition of hypoxia-inducible factor 1 (HIF-1) alpha, and activation of p53. We investigated the overall survival of type 2 diabetic patients on metformin with pancreatic cancer and lymphoma using the Computerized Patient Record System at the Veterans Affairs Medical Center, Memphis TN.Lymphoma and pancreatic cancer patients with type 2 diabetes were sorted into an experimental (metformin) group and a control (nonmetformin) group. Patients were compared on baseline characteristics including race, body mass index, and age. Cancer outcomes including overall survival, metastasis, recurrences, and incidence of new malignancies were recorded. Hemoglobin A1C, creatinine and cancer treatment modalities were recorded and compared. Statistical analyses used included unpaired t tests and Chi-squared tests.There was significantly greater overall long-term survival in the metformin group compared to the nonmetformin group for lymphoma (5.89 vs 1.29 years, P0.001) and for pancreatic cancer (0.68 vs 0.22 years, P = 0.016). Cancer treatment modalities in both groups were comparable.Metformin is associated with a significant, positive effect of increased overall survival in type 2 diabetes patients with pancreatic cancer and lymphoma. These results are encouraging, and prospective studies should be done to further investigate metformin's effects in cancer.

Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of -0.47 and -0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia.

Background Septic shock is associated with altered peripheral perfusion. Core-to-skin temperature gradient depends on skin perfusion and microcirculatory function. We hypothesized that a high core-to-skin temperature gradient is correlated with mortality in septic shock. Methods We conducted a prospective observational study including 61 patients at the first 24 h of a septic shock in an intensive care unit. During the 24 first hours after norepinephrine administration, we collected clinical and circulatory characteristics, skin perfusion assessment (Capillary refill time (CRT), Mottling score) and we measured skin temperature with an infrared thermographic camera. We measured the Core-to-skin temperature gradient to evaluate if it is a predictor of day-8 mortality. Results Day-8 mortality was 16.3%. Core-to-index finger temperature gradient >7 °C was associated with day-8 mortality (OR = 18.0, [3.02–346.14], p = 0.002). This association was still significant after adjustment to the SOFA (Sequential Organ Failure Assessment) score. A model including a high SOFA score and a core-to index finger >7 °C was effective to predict day-8 mortality (c-statistic: 0.8735 [0.770–0.976]). Core-to-index finger temperature gradient was correlated with CRT, Mottling Score, and arterial lactate levels. Conclusions Core-to-index finger temperature gradient higher than 7 °C predicts day-8 mortality in septic shock and is correlated with other tissue perfusion markers.

Little is known about the respective effects of depression and cognitive impairment on quality of life among older adults with schizophrenia spectrum disorder.We used data from the Cohort of individuals with Schizophrenia Aged 55-years or more (CSA) study, a large multicenter sample of older adults with schizophrenia or schizoaffective disorder (N = 353). Quality of life (QoL), depression and cognitive impairment were assessed using the Quality of Life Scale (QLS), the Center of Epidemiologic Studies Depression scale and the Mini-Mental State Examination, respectively. We used structural equation modeling to examine the shared and specific effects of depression and cognitive impairment on QoL, while adjusting for sociodemographic characteristics, general medical conditions, psychotropic medications and the duration of the disorder.Depression and cognitive impairment were positively associated (r = 0.24, p 0.01) and both independently and negatively impacted on QoL (standardized β = -0.41 and β = -0.32, both p 0.01) and on each QLS quality-of-life domains, except for depression on instrumental role and cognitive impairment on interpersonal relations in the sensitivity analyses excluding respondents with any missing data. Effects of depression and cognitive impairment on QoL were not due to specific depressive symptoms or specific cognitive domains, but rather mediated through two broad dimensions representing the shared effects across all depressive symptoms and all cognitive deficits, respectively.Because of the cross-sectional design of this study, measures of association do not imply causal associations.Mechanisms underlying these two broad dimensions should be considered as important potential targets to improve quality of life of this vulnerable population.

Purpose Several remarks have been raised regarding the variables and cut-points used in the Sequential Organ Failure Assessment (SOFA) score. This study revisited the SOFA score and created a new simplified and accurate sa-SOFA score. Methods The study grouped four prospective cohorts (2005–2016) of patients with Systemic Inflammatory Response Syndrome. It collected 28-day mortality, sociodemographic characteristics, and the SOFA score with all variable values at Day 1. A logistic regression analysis was used to select the most relevant variables and a minimum p value approach with a 10-fold cross-validation were used to find the optimal partition of selected variables. The minimum number of cut-points (2, 3, or 4) was also tested by comparing the distributions of areas under receiver operating characteristic (AUROC) curves. Results Among the 1436 participants, 416 died within 28 days (28.9%). The sa-SOFA kept one variable per dimension and two cut-points per variable. The AUROC curves that investigated the abilities of the sa-SOFA and SOFA scores to predict 28-day mortality were 0.739 [0.712–0.768] and 0.687 [0.656–0.717], respectively (p-value of DeLong test Conclusion Keeping the conventional SOFA dimension variables, the new sa-SOFA proved to be simpler and more accurate in predicting 28-day mortality.

The severity of psychopathology has a strong negative impact on quality of life (QoL) among older adults with schizophrenia spectrum disorder. However, because these subjects generally experience multiple psychiatric symptoms, it remains unclear whether decreased QoL in this population is due to specific symptoms (e.g., hallucinations), specific dimensions of psychopathology (e.g., negative symptoms), a general psychopathology dimension representing the shared effect across all psychiatric symptoms, or a combination of these explanations. Data were derived from the Cohort of individuals with Schizophrenia Aged 55 years or more (CSA) study, a large (N = 353) multicenter sample of older adults with schizophrenia spectrum disorder recruited from French public-sector psychiatric departments. We used structural equation modeling to examine the shared and specific effects of psychiatric symptoms on QoL, while adjusting for sociodemographic characteristics, general medical conditions, global cognitive functioning and psychotropic medications. Psychiatric symptoms and QoL were assessed face-to-face by psychiatrists using the Brief Psychiatric Rating Scale (BPRS) and the Quality of Life Scale (QLS). Among older adults with schizophrenia spectrum disorder, effects of psychiatric symptoms on QoL were exerted mostly through a general psychopathology dimension (β = − 0.43, p

Aims. – Motor threshold (MT) is an important parameter for the practice of transcranial magnetic stimulation. Our goal was to compare three methods to estimate MT in a clinical setting. Methods. – Comparison of three MT estimation algorithms: 1) the Rossini-Rothwell method consists in lowering stimulus intensity until only five positive responses out of 10 trials are recorded, defining MT; 2) the Mills-Nithi method considers the MT as the mean of an upper threshold (10 positive out of 10 trials) and a lower threshold (0 out of 10 trials); 3) the supervised parametric method estimates the MT by fitting (mathematically and graphically) a sigmoid function on raw data obtained by stimulation at variable intensities. Six MT estimations (two per method) were recorded in a single session in 10 healthy subjects. Results. – The within-subject variation of MT (expressed as % of the mean MT ± standard deviation) during a single session was of 8.5 ± 7.2% for the Rossini-Rothwell method, 8.7 ± 5.7% for the Mills-Nithi method and 9.5 ± 4.0% for the supervised parametric method. No significant differences in variability of MT estimation were found between the methods, but the Rossini-Rothwell method was significantly shorter (half the number of stimuli compared to the two other methods). Conclusion. – In our setting, Rossini-Rothwell method was superior to the two other methods. The variability of MT estimation measured in our study is important, yet acceptable for clinical applications. However, this variability can be a source of considerable errors in excitability studies and should be a focus of future research.

Concentrations of telithromycin were measured in plasma, bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM) following multiple oral doses. Concentrations were determined using a microbiological assay. There were 20 subjects in the study, allocated to three nominal time periods: 2, 12 and 24 h. Mean concentrations in plasma, BM, ELF and AM for 2, 12 and 24 h were as follows: 2 h, 1.86 mg/L, 3.88 mg/kg, 14.89 mg/L and 69.32 mg/L; 12 h, 0.23 mg/L, 1.41 mg/kg, 3.27 mg/L and 318.1 mg/L; and 24 h, 0.08 mg/L, 0.78 mg/kg, 0.97 mg/L and 161.57 mg/L. These concentrations of telithromycin in BM and ELF exceeded for 24 h the mean MIC90s of the common respiratory pathogens Streptococcus pneumoniae (0.12 mg/L) and Moraxella catarrhalis (0.03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

BACKGROUNDBalloon coronary angioplasty has been reported to be ineffective in patients treated for end stage renal disease because of a high restenosis rate.OBJECTIVETo compare the clinical outcome following coronary angioplasty with provisional stenting in dialysis versus non-dialysis patients.DESIGNA case–control study.PATIENTSOf 1428 consecutive patients who underwent coronary angioplasty, 100 (7%) were being treated for end stage renal disease. These were compared with 100 control patients matched for age, sex, coronary lesions, presence of diabetes mellitus, and rate of coronary stenting (40%).MAIN OUTCOME MEASURESIn-hospital and one year clinical outcome.RESULTSThe rates of procedural success (90% v 93%), in-hospital mortality (1% v 0%), stent thrombosis (0%v 0%), and Q wave myocardial infarction (0% v 1%) were similar in dialysis and non-dialysis patients. One year clinical outcome after coronary angioplasty was similar in the two groups in terms of clinical restenosis (31% v 28%) and myocardial infarction (6% v 2%), but cardiac death was more common in dialysed patients (11% v2%, p CONCLUSIONSDialysis does not increase the risk of clinical restenosis after coronary angioplasty with provisional stenting. Coronary angioplasty is a safe and effective therapeutic procedure in selected dialysis patients with culprit lesions accessible to stenting. However, the one year survival is reduced in this high risk population.

W coronary stenting has been shown to reduce acute closure and 6-month restenosis in humans,1,2 few data on angioplasty and stenting are available in dialysis patients. The purpose of the current study was to determine the influence of dialysis: (1) on in-hospital outcome after balloon angioplasty with stent or without coronary stenting, and (2) on 1-year clinical outcome after coronary stenting or balloon angioplasty with ,30% residual stenosis. • • • The patient cohort included a consecutive series of 1,201 patients (1,363 narrowings) treated with balloon coronary angioplasty with or without coronary stenting between January 1995 and June 1998. Baseline clinical and angiographic characteristics, procedural results, and in-hospital complications had been entered prospectively into a computerized database. Patients were divided into 4 groups according to the use of stent during the procedure, and according to dialysis for at least 90 days before coronary angioplasty. There were 864 non-dialysis patients (72%) without coronary stenting, 250 non-dialysis patients (21%) with coronary stenting, 60 dialysis patients (5%) without coronary stenting, and in 27 dialysis patients (2%) with coronary stenting. The high percentage of patients with end-stage renal disease was due to an association with a renal disease program. The cause of renal failure was diabetes in 18%, hypertension in 23%, and other conditions in 59%. All patients were treated and studied after giving informed consent. All patients underwent left ventriculography and coronary angiography in multiple projections. Percutaneous transluminal coronary angioplasty was performed using standard techniques and adjunctive therapy, as previously described.3 All patients received aspirin 250 mg/day and a bolus of heparin (100 IU/kg) just before angioplasty. Indications for stenting included elective or provisional use following a bailout or a suboptimal result with residual stenosis exceeding 30% after balloon angioplasty. Procedural success was defined as diameter stenosis reduction of .20% with a residual stenosis ,50%, in the absence of major complications including death, myocardial infarction, and need for emergency surgery. Myocardial infarction was defined by increased serum creatine phosphokinase level .3 times the upper limit of normal, with $10% creatine phosphokinase-MB values relative to the total creatine phosphokinase. Vascular complications included hematoma requiring a blood transfusion or false aneurysm requiring surgical repair or prolonged compression. The poststent antithrombotic treatment included ticlopidine (500 mg/day), begun immediately after the procedure and continued for 4 weeks, and aspirin (100 mg/day for 4 weeks and then 250 mg/day). The qualitative angiographic analyses were performed independently by 2 experienced interventional cardiologists. Disagreements were resolved by consensus. Quantitative angiographic analyses were performed using digital computed-assisted calipers (DCI Philips, CAAS System, Eindhoven, Holland). The degree of stenosis before and after angioplasty was measured after intracoronary injection of sin-1 (linsidomine, 1 mg) in the view showing the most severe stenosis and expressed as the minimal luminal diameter and the linear percent luminal diameter reduction using the average diameter of the nearest normal segment as reference. Long-term follow-up data were obtained by serial telephone interviews. Late clinical events were corroborated by primary source documentation. Control angiography was restricted to patients with recurrence of limiting symptoms or severely documented ischemia, or both. Restenosis was diagnosed when a $50% diameter narrowing was found at the site of the previous dilation. Indications for a new revascularization procedure were divided between restenosis at a site of previous dilation and the appearance of a new significant coronary artery stenosis not present on the initial angiogram. Continuous variables are presented as means 6 1 SD. Categorical data are presented as percent frequencies. Univariate analyses were performed using the chi-square test for categorical data and analysis of variance for continuous variables. Multiple logistic regression and stepwise logistic regression analyses were performed in the standard manner. A multivariate, stepwise, logistic regression analysis that included clinical, angiographic, and hemodynamic baseline variables (Table I) was used to identify the best set of predictors for procedural failure and for the occurrence of in-hospital complications or major cardiac events during follow-up. A p value ,0.05 was considered significant. Dialysis patients were younger, more often hyperFrom the Service de Cardiologie, Hopital Necker, Service de Nephrologie, Hopital Saint Louis, and Service de Nephrologie, Hopital Necker, Paris, France. Dr. Le Feuvre’s address is: Cardiologie, Hopital Necker, 149 rue de Sevres, 75015 Paris, France. Manuscript received September 13, 1999; revised manuscript received and accepted December 9, 1999.

To explore the mechanisms of the "white coat" phenomenon, the effects of talking, reading, and silence were analyzed. Fifty essential hypertensive patients were randomly allocated to periods of stress talking and relaxing reading, alternating with three periods of silence. While talking, systolic/diastolic blood pressure increased sharply, from 142 +/- 0.7/97.7 +/- 0.5 mm Hg to 159 +/- 0.7/111 +/- 0.5 mm Hg (P < .0001). While reading, systolic/diastolic blood pressure decreased (P < .0001). Moreover, talking and reading had opposite residual effects. The silence and reading periods gave the best approximations of the daytime ambulatory period. The predictive value of clinical blood pressure can be improved if measured during a period without talking, thus decreasing the "white coat" phenomenon.

Objective: To investigate the effect of teriflunomide on the efficacy and safety of seasonal influenza vaccine. Methods: The 2011/2012 seasonal influenza vaccine (containing H1N1, H3N2, and B strains) was administered to patients with relapsing forms of multiple sclerosis (RMS) treated for ≥6 months with teriflunomide 7 mg (n = 41) or 14 mg (n = 41), or interferon-β-1 (IFN-β-1; n = 46). The primary endpoint was the proportion of patients with influenza strain–specific antibody titers ≥40, 28 days postvaccination. Results: More than 90% of patients achieved postvaccination antibody titers ≥40 for H1N1 and B in all groups. For H3N2, titers ≥40 were achieved in ≥90% of patients in the 7 mg and IFN-β-1 groups, and in 77% of the 14-mg group, respectively. A high proportion of patients already had detectable antibodies for each influenza strain at baseline. Geometric mean titer ratios (post/prevaccination) were ≥2.5 for all groups and strains, except for H1N1 in the 14-mg group (2.3). The proportion of patients with a prevaccination titer

Both white coat effect (the tendency of blood pressure to rise during a medical visit) and talking effect were analyzed in 42 patients with essential hypertension. Blood pressure was measured during the clinic visit and over the subsequent 24-hour ambulatory period, with the physician performing 49 +/- 4 measurements for each patient. Three silent periods and two talking periods (stress and relaxation) were randomly allocated in a crossover design and studied, using analysis of variance. During the initial 11-minute silent period, systolic/diastolic blood pressures increased by 6 mm Hg/5 mm Hg. During the subsequent talking periods, these variations were significantly greater: +22 mm Hg/+17 mm Hg. Measures of systolic/diastolic blood pressure were higher during stressful talking than during relaxed talking. The talking and its emotional contents seemed to explain 70% of the white coat phenomenon. To minimize the white coat phenomenon in the clinic, physicians, nurses, and clinicians are advised to measure blood pressure during an initial period of silence.

Only a moderate degree of concordance has been reported between stress-redistribution-reinjection thallium-201 single photon emission computed tomography (SPECT) and dobutamine echocardiography for the identification of myocardial viability after acute myocardial infarction. SPECT with rest-reinjection performed 4 hours after exercise testing and digitized two-dimensional (2-D) ultrasound reconstruction of the left ventricle at baseline and after low-dose dobutamine (5 to 10 microg/kg/min) infusion were compared in 50 patientsor = 8 days (12 +/- 7 days) after acute myocardial infarction. Five patients were excluded because of technically inadequate echocardiograms. Both SPECT and dobutamine echocardiography were assessed in a 16-segment model and interpreted in the remaining 45 patients. Digitized 2-D reconstruction of the left ventricle in each wall motion was scored from 1 (normal) to 4 (dyskinesia). Myocardial viability was identified on ultrasound wall-motion improvement of one or more grades from baseline to echocardiography performedor = 30 days (60 +/- 41 days) after systematic revascularization procedure of the infarct-related artery. Reversible defect under thallium-201 SPECT and wall-motion improvement under dobutamine echocardiography were concordant in 163 (69 percent) of the 235 baseline dyssynergic segments and in 30 (67 percent) patients. Myocardial viability was identified after angioplasty (n=37) or surgery (n=8) in 29 patients and 109 segments. Positive and negative predictive values per patient in the diagnosis of myocardial viability were 86 percent and 57 percent, respectively, for stress thallium-201 SPECT with reinjection, and 100 percent and 62 percent for dobutamine echocardiography. Positive and negative predictive values per segment were 80 percent and 69 percent for the isotopic method and 91 percent and 70 percent for dobutamine echocardiography. We conclude that dobutamine echocardiography and stress thallium-201 SPECT with reinjection have similar accuracies to identify myocardial viability after acute myocardial infarction, with excellent positive but relatively low negative predictive values.

The response to the maze test was studied in 31 subjects on no medication, including seven subjects with mild essential hypertension. Beat-by-beat finger blood pressure (BP) was measured with a Finapres device. Pulse interval from which heart rate (HR) was derived was obtained from the BP signal. A period of 5 min baseline was used to define resting levels of systolic BP and HR using 20-s averaged values for the calculation of the 95% confidence limit of the two variables. The average test duration was 10 min. During this period a series of video-displayed mazes had to be solved with easy mazes preceding difficult ones. No subject had been exposed to the test before. The maximal BP elevation associated with the test was 27 mmHg. The HR response averaged 11 beats/min. Significant elevations were observed for half the test duration. No significant relationship between these two responses was observed and some subjects exhibited isolated systolic BP or HR responses. When indices obtained during this active mental stress were compared to resting values, positive correlations were observed. When the resting standard deviation (SD) of systolic BP was higher the systolic response was greater. A similar relationship was observed for HR. In addition, when the systolic BP level at rest was higher, the systolic BP reactivity index was greater. However, systolic BP or HR at baseline were not predictive of the systolic BP or HR responses. This study demonstrates the applicability of a new test to assess cardiovascular reactivity. The main advantage of non-invasive continuous BP measurement with the Finapres is the ability to provide variability indices in addition to the peak responses.

Data concerning the clinical and therapeutic characteristics of patients with schizophrenia treated by antipsychotic in naturalistic conditions are useful. Two national pharmacoepidemiological studies were conducted in France, a retrospective survey RÉALITÉ and a prospective study RÉALITÉ LT, to examine the use of loxapine, first in acute and chronic psychotic states and second in long-term treatment prescribed for patients with schizophrenia.The aim of RÉALITÉ LT is to specify the clinical characteristics of schizophrenic patients treated by loxapine for at least 4 months and the description of the methods of use of this antipsychotic medication during a 6-month follow-up in "real life" conditions.RÉALITÉ LT is an epidemiologic, observational, longitudinal, prospective (during a half-year period), multicenter and national study of the prescription of loxapine in routine clinical practice. For this study, 645 patients with schizophrenia treated by loxapine were recruited, assessed by PANSS, CGI, GAF, MeDra-SOC-PT for side effects and Girerd questionnaire for compliance; statistical analysis used SAS 9.2.Six hundred and forty-five adult patients were included and assessed at inclusion, month 3 and 6. These patients were mostly male (69%), with an average age of 41, inactive (68%), lonely with no child (79%), under psychiatric care for more than 5 years (81%), less than one third were inpatients. The subtypes of schizophrenia were paranoid (59%), disorganised (21%), undifferentiated or residual (10%), the outcome of psychotic illness was episodic (50%) or continuous (33%). The daily mean dosage of loxapine was 168,4 mg/d, in antipsychotic loxapine monotherapy (27%) or in combination with other antipsychotics (63%); it was often associated with psychotropic medications (anxiolytic [72%], antidepressant [21%], normothymic [19%]). The stability of the dosage of loxapine during the 6 months follow-up (60%) was associated with strict loxapine monotherapy or antipsychotic monotherapy (loxapine associated with other psychotropic medication). Safety, side effects and compliance were compared with previous studies.These results are discussed, comparing the two pharmacoepidemiological studies RÉALITÉ and RÉALITÉ LT, loxapine is used in compliance with the two indications (smpc) and French guidelines (HAS, Haute Autorité de santé).

Forty-nine patients admitted for assessment of chest pain underwent coronary angiography, planar Thallium 201 myocardial scintigraphy after submaximal exercise (TE) and transoesophageal atrial pacing (TAP). Early hypofixation with redistribution after 4 h indicated ischaemia. The criterion for a myocardial infarction (MI) was a fixed perfusion defect. Coronary angiography was carried out in all patients. Sixteen patients (group 1) had no MI and over 50% narrowing of at least one main coronary vessel. Ischaemia was noted in 10 of the 16 patients during exercise, and in 14 of the 16 patients during atrial pacing. The sensitivity for the prediction of coronary stenosis was 62% for TE and 87% for TAP. Nineteen patients (group 2) had had a previous MI. Reversible ischaemia was noted in 10 of the 19 patients during exercise, and in 11 of the 19 patients during TAP. Four of 14 patients with normal coronary arteries (group 3) had a reversible ischaemia with TE, and three of these same patients developed a positive scan with TAP. The respective specificities were 71% and 78%. Comparison of segmental hypoperfusion after TE and TAP gave identical results in 72 of the 80 segments studied in group I (90%), and in 88 of the 95 segments studied in group 2 (92%). The localizing value of TAP was good in left anterior descending (12 out of 18) and right coronary disease (16 out of 19), but poor in left circumflex stenosis (3 out of 9) misclassified as right coronary disease in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to evaluate the prognosis and functional outcome of mitral regurgitation caused by ischemic papillary muscle dysfunction with respect to treatment, and to determine the role of coronary angioplasty in this context. Thirty patients with severe ischemic mitral regurgitation were followed up for 33 ± 3 months. Thirteen patients were treated medically (group I) and 17 patients underwent surgery or angioplasty (group II). The 3-year survival was 59.5% (45.6% in group I and 70.2% in group II). Angioplasty was only used in paroxysmal mitral regurgitation caused by papillary muscle ischemia. This technique resulted in spectacular immediate results in three patients with pulmonary edema caused by mitral regurgitation during myocardial ischemia. Surgical correction of mitral regurgitation should be considered without delay if angioplasty is not feasible or if the regurgitation is permanent or severe. Widening the indications of surgery or angioplasty should result in an improvement of the prognosis of these high-risk patients.

Usher's syndrome is a heterogeneous autosomal recessive disorder characterised by dual sensory impairment: profound congenital hearing impairment and progressive visual loss due to retinitis pigmentosa, sometimes associated with vestibular dysfunction. Some patients develop a psychotic illness, the etiology of which is still debated. Diagnosis may be difficult, and there are only a few reports in the psychiatric literature.The present case reports a 57-year-old man, double diagnosed with sensory impairment and psychosis. The severity of his psychosis required several hospitalisations in a psychiatric in-unit, even under third party decision or compulsory hospitalisation, for acute states with disruptive behaviour, aggressiveness against his mother, persecutory delusion and auditory hallucinations, self-talking, major anxiety, and depressive affects, without dissociation. Deafness had been diagnosed when he was six years old; he was able to attend school and learn to read and speak, using hearing aids, and was able to hold a job for three months. Severe psychotic symptoms appeared when he was 18 years old and contributed in confirming the diagnosis. Progressive loss of vision until blindness began later, between the age of 40 to 50. No specific abnormal results were revealed during the neuroradiological check-up. Treatment consisted in antipsychotics, notably depot, first in a mental health care in-unit and subsequently in an out-patient unit: although he denied psychotic symptoms, he became compliant with medication and could go on with treatment, associated with multidisciplinary interventions at home, in order to improve his quality of life.Usher's syndrome is the most frequent cause of combined deafness and blindness in adults (three and five individuals per 100,000), but difficulties in communication need to increase clinical awareness of this disorder, especially for psychiatrists. Three subtypes are recognized by the International Usher Syndrome Consortium: Type 1 is characterised by profound congenital deafness, retinal degeneration beginning in childhood, and progressive vestibular dysfunction; Type 2 is characterised by moderate to severe hearing impairment, later onset of retinal degeneration, and normal vestibular function; Type 3 is characterised by progressive hearing loss and variable age of onset of retinal degeneration. Although nearly 23% may have psychotic symptoms, the aetiology remains unclear: sensory deprivation associated with environmental stress, organic changes such as cerebral abnormalities, genetic link (two genetic loci for both Usher's syndrome and psychotic illness are very close). Treatment of psychiatric symptoms is based on antipsychotics, well tolerated by the patients, who improve change of behaviour and communication abilities. Genetic counselling may be useful for parents.Access to mental health services is particularly difficult for deaf and deaf-blind people, and difficulties in communication are a challenge for patients and for caregivers too. Antipsychotic medications are helpful for associated psychotic symptoms. Potential link between Usher syndrome and psychosis is still unclear and needs further studies.

To assess the effect of successful late coronary angioplasty of an occluded infarct-related artery on the prevalence of ventricular late potentials, signal-averaged electrocardiograms were recorded in 123 consecutive patients surviving a first acute myocardial infarction (58 with and 65 without mechanical reperfusion of the occluded coronary artery). Multivariate analysis showed that successful reperfusion by late angioplasty of the infarct artery contributes to a decrease in the prevalence of late potentials.

The pharmacokinetic profiles of single and repeated oral doses of telithromycin 800 mg/day were compared in patients with hepatic impairment and healthy subjects in two open-label, non-randomized, parallel-group, multicentre studies. The maximal plasma concentrations (Cmax) and the area under the plasma concentration-time (AUC) curves for telithromycin were similar in hepatically impaired patients and healthy subjects in the single- and repeated-dose studies. The extent of formation of RU 76363, the major circulating metabolite of telithromycin, was decreased following single and repeated doses in patients with hepatic impairment compared with healthy subjects. In the single-dose study, the Cmax of RU 76363 was 2-fold lower (P

The authors report on six cases of aortic dissection (AD). The work intended to bring out AD characteristics and attempt to define a profile of African patients who manifested this disease. The diagnosis of AD was determined on the basis of: clinical and radiological criteria (six cases); echocardiographic data (five cases); aortographic and surgical informations (two cases).There were three males and three females with an average age of 40.2 years, with a variation of +/- 10.6 years (from 17 to 49). The frequency of AD was estimated at 1.8/10,000 admissions considering all causes and 5.4/10,000 for cardiovascular disease. Strain was the only triggering factor--noted in two cases (Observations 2 and 3). All patients suffered from severe arterial hypertension (AHT) of which there was one case of renovascular AHT based on the Takayasu arteritis. All symptoms and physical findings were the same described in literature. Operations were successful on two patients. The four unoperated patients died (tamponade: two cases, undetermined cause: two cases).The authors conclude as to the similarity of the AD charts described in the literature. However they stress the almost exclusive role of AHT in African studies series as well as that, in rare cases, of Takayasu's disease. They recommend preventing AD through the sustained and effective treatment of AHT.

Combined coronary angioplasty and coronary angiography is performed in most catheter laboratories and has become a routine procedure. The aim of this study was to assess its clinical results and economic value. This was a retrospective monocenter study performed over an 11 year period (1990-2000) which included 2,727 patients requiring coronary angioplasty after coronary angiography. The angioplasty procedure was performed at the same time as angiography (combined, n = 1,809) or after angiography (deferred, n = 631). Patients admitted for acute coronary syndromes not stabilised by pharmacological interventions were excluded from the study. The comparison of these two modes of angioplasty was based on primary success rates, complications, duration of hospital stay and hospital costs. The combined procedure was used progressively more frequently over the study period, increasing from 54% to 88% in 2000. The hospital clinical results (Success and complication rates) were comparable in the two groups. The predictive factors of failure were the year of the angioplasty procedure and occlusive lesions on multivariate analysis. The combined procedure was associated with a shorter hospital stay than deferred angioplasty (8.2 +/- 6.1 days versus 15.0 +/- 8.0 days, p = 0.0001) and with lower costs. The authors conclude that combined coronary angiography-angioplasty is as effective and as safe as deferred angioplasty. It is associated with a shorter hospital stay and lower hospital costs.

The aim of the study was to establish a relationship between the clinical efficacy of risperidone (Risp), the biological levels of Risp and its metabolite, 9-hydroxyrisperidone (9-OH-Risp), and the turnover of blood biogenic amines during a long-term treatment (1 year). Risp is one of the newer atypical antipsychotic drugs with potent serotonin (5HT2), moderate D2 and real alpha 1-alpha 2 adrenoreceptor antagonistic effects. The study has been performed in an open setting and included 17 patients, but only 15 were followed-up from 3 to 12 months. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grading using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI), the Global Assessment of Functioning Scale (GAF), the Quality of Life Scale (QLS) and the Extrapyramidal Symptoms Rating Scale (ESRS) and the determinations of plasma and red blood cell (RBC) Risp and 9-OH-Risp, whole blood 5HT and tryptophan (Trp), plasma homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5HIAA) and dihydroxyphenylethyleneglycol (DHPG). The therapeutic drug monitoring needed oral Risp daily dose of 4.5 +/- 2.3 mg (range 2-8) and the stabilized concentrations (ng/ml) at endpoint in plasma and RBC were 10 +/- 8 (range 1-23) and 3.5 +/- 2 (range 1-8) for Risp and 29 +/- 19 (range 8-70) and 11.5 +/- 6.6 (range 2.6-22.5) for 9-OH-Risp, respectively. 9-OH-Risp appears to be the major active metabolite compound at higher concentrations than Risp. Positive linear correlations were found only between plasma and RBC 9-OH-Risp and the daily dose and the score of the GAF. Statistically significant clinical results showed that Risp is a potent antipsychotic agent efficacious both on positive and negative symptoms and on quality of life. Positive symptoms decreased after about the second month and the negative symptoms improved secondly. Patients (n = 8) who responded to Risp were characterized, on the long-term, by a statistically significant decrease of whole blood 5HT and increase of plasma DHPG.

The results of balloon coronary angioplasty are very disappointing in haemodialysis patients because of the high restenosis rate. On the other hand, the use of stents in this population had not previously been assessed. This retrospective study compared 63 coronary patients on haemodialysis with a référence group of 63 paired patients with respect to gender, age, and the necessity or not of stent implantation. There was a higher frequency of hypertension (79 vs 39%) and of hypertriglyceridaema (22 vs 8%) in the haemodialysis group than in the controls. However, there was no significant difference with respect to primary success rate of angioplasty (92 and 89% respectively), nor to the development of early cardiovascular complications (4% and 1.9% respectively). After a two-year follow-up, there was no significant difference in the restenosis rate in the haemodialysis patients (33%) compared with the controls (25%). Nevertheless, the mortality rate at 2 years was higher in the dialysis group (15%) compared with the reference group (3.5%, p = 0.03). However, this mortality rate was lower than that reported in the literature in haemodialysis patients after balloon angioplasty. Therefore, haemodialysis does not increase the risk of restenosis when an optimal angiographic results is obtained either by balloon angioplasty or by angioplasty with stenting. Coronary angioplasty is a safe and effective method of revascularisation in coronary haemodialysis patients when the lesions are accessible to stenting.

Noninvasive detection of restenosis in patients remaining asymptomatic after percutaneous transluminal coronary angioplasty (PTCA) remains a major clinical problem. The value of exercise electrocardiography (ECG) and exercise-redistribution thallium-201 single-photon emission computed tomography (SPECT) in detecting restenosis in such patients remains uncertain. Discordances between these tests and coronary angiography is a common situation. We studied 179 consecutive patients remaining asymptomatic after successful PTCA (208 vessels), who underwent 6 ± 2 months of exercise ECG, SPECT, and coronary angiography. We sought to assess the diagnostic value of the noninvasive tests compared with coronary angiography, and identify the determinants of discordances between the tests. Restenosis (diameter stenosis >50%) was detected in 39% of patients and in 37% of vessels. The overall sensitivity, specificity, and accuracy for exercise ECG and SPECT in detecting restenosis in individual vessels were, respectively, 53% versus 63% (p = 0.06), 59% versus 77% (p = 0.0001), and 57% versus 72% (p = 0.0001). On multivariate analysis, positive exercise ECG was associated with higher heart rate response (p = 0.02), incomplete revascularization (p = 0.004), and angiographic restenosis (p = 0.03), whereas positive SPECT was associated with incomplete revascularization (p = 0.02), infarct-related artery PTCA (p = 0.01), and angiographic restenosis (p = 0.0001). Accuracies of the 2 tests were not significantly different in patients with incomplete revascularization or PTCA of an infarct-related vessel. Overall, SPECT is more accurate than exercise ECG in detecting asymptomatic restenosis. Nevertheless, incomplete revascularization and PTCA of an infarct-related artery could cause reversible perfusion defects regardless of restenosis, reducing the diagnostic value of SPECT in such patients.

The 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O2-). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation. This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin. In vitro studies were used as an approach to investigate how simultaneous productions of NO and O2- from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O2- scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect. This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O2- release, independently of H2O2 formation.

Buprenorphine, which is used in France as a substitution drug for opioid addiction, is widely abused, and several fatal cases have been reported. In order to confirm a recent intoxication or to establish retrospectively chronic abuse, a simple and reliable gas chromatographic-mass spectrometric method was developed and validated for quantitation of buprenorphine and its active metabolite norbuprenorphine in urine and hair. Two milliliters of urine or 50 mg of pulverized hair was submitted to a pretreatment (enzymatic hydrolysis for urine and decontamination with dichloromethane followed by incubation in 0.1 M HCI for hair). Buprenorphine-d4 was chosen as the internal standard. Selective solid-phase extraction with Bond Elut Certify columns provided recoveries higher than 85% for urine and 43% for hair. By using a mixture of MSTFA/TMSIM/TMCS (100:2:5), buprenorphine and norbuprenorphine produced stable silylated derivatives. The detection was carried out with a quadrupole mass detector working in El selected ion monitoring mode. Ions at m/z 450 and 468 were chosen for the quantitation of buprenorphine and norbuprenorphine, respectively (m/z 454 was used for the internal standard). Limits of quantitation were 0.25 and 0.20 ng/mL, respectively, for buprenorphine and norbuprenorphine in urine and 0.005 ng/mg for the two compounds in hair. Calibration curves were linear from 0 to 50 ng/mL in urine and from 0 to 0.4 ng/mg in hair. Between-day and within-day precisions were less than 8.4% in hair and 6.1% in urine for both molecules in all cases. This method was applied to urine and hair samples collected from patients in a withdrawal treatment program and demonstrated its good applicability in routine analysis and its benefit for clinicians. This technique, which requires instruments already available to many toxicology laboratories, offers an attractive alternative to more sophisticated techniques.

1. The aim of the study was to determine if a more rational therapeutic approach could be devised for neuroleptic resistant psychotic patients treated for months and years with clozapine. Clozapine is an atypical antipsychotic medication, but its therapeutic benefit has been limited by a high incidence of agranulocytosis and seizures. 2. The study has been performed in an open setting and included 12 patients. Some of them developed a secondary depression and were treated with fluoxetine. 3. Pharmacokinetic analysis were conducted at the same time as clinical evaluations, grading using the BPRS, the PDS, and QLS, and determinations of plasma and red blood cell clozapine and desmethylclozapine, plasma and RBC fluoxetine and norfluoxetine, whole blood serotonin and tryptophan. 4. A positive linear correlation was found only between RBC concentration and the evolution of the QLS. 5. Clozapine is efficacious both on positive and negative symptoms but its mechanism of action remains unclear. Positive symptoms disappear more quickly, sometimes followed by a post psychotic depression. Negative symptoms improve more slowly but regularly. They seem to be correlated with serotoninergic mechanisms. For whole blood 5HT, an important increase was seen about 4 weeks after Cloza administration, and then a decrease. 6. Therapeutic drug monitoring (on the same sample drawn for haematological monitoring providing) could play a useful role in the management of patients treated by clozapine: compliance, lowest dose, possible toxicity, drug interaction, lack of efficacy, relapse predictivity.

Whole blood coagulation analysers are widely used during percutaneous coronary interventions. The precise degree of anticoagulation in patients is important in this setting. The aim of this investigation was to compare the results obtained with ACT (Hemochron) and HMT, the Heparin Management Test (TAS) in patients undergoing percutaneous coronary interventions. Patients (n = 100) were enrolled prospectively. Each patient received 10,000 units of heparin. At the end of the procedure, the mean ACT was 284+/-31 seconds and the mean HMT was 292+/-33 seconds. The correlation between the two methods was highly significant (r = 0.64, p0.001). The HMT correlates well with ACT values in patients undergoing percutaneous coronary interventions. Its use in the management of these patients should be considered.

Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty.In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10,250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37+/-0.66 mm, 51.9+/-21.0%) did not differ from the corresponding values in the control group (1.48+/-0.59 mm, 48.8+/-18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%).Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.

This study sought to determine whether pravastatin affects clinical or angiographic restenosis after coronary balloon angioplasty.Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty.In a multicenter, randomized, double-blind trial, 695 patients were randomized to receive pravastatin (40 mg/day) or placebo for 6 months after successful balloon angioplasty. All patients received aspirin (100 mg/day). The primary angiographic end point was minimal lumen diameter (MLD) at follow-up, assessed by quantitative coronary angiography. A sample size of 313 patients per group was required to demonstrate a difference of 0.13 mm in MLD between groups (allowing for a two-tailed alpha error of 0.05 and a beta error of 0.20). To allow for incomplete angiographic follow-up (estimated lost to follow-up rate of 10%), 690 randomized patients were required. Secondary end points were angiographic restenosis rate (restenosis assessed as a categoric variable,50% stenosis) and clinical events (death, myocardial infarction, target vessel revascularization).At baseline, clinical, demographic, angiographic and lipid variables did not differ significantly between groups. In patients treated with pravastatin, there was a significant reduction in total and low density lipoprotein cholesterol and triglyceride levels and a significant increase in high density lipoprotein cholesterol levels. At follow-up the MLD (mean +/- SD) was 1.47 +/- 0.62 mm in the placebo group and 1.54 +/- 0.66 mm in the pravastatin group (p = 0.21). Similarly, late loss and net gain did not differ significantly between groups. The restenosis rate (recurrence50% stenosis) was 43.8% in the placebo group and 39.2% in the pravastatin group (p = 0.26). Clinical restenosis did not differ significantly between groups.Although pravastatin has documented efficacy in reducing clinical events and angiographic disease progression in patients with coronary atherosclerosis, this study shows that it has no effect on angiographic outcome at the target site 6 months after coronary angioplasty.

The aim of this open study was to determine a more rational therapeutic approach for psychotic patients treated with clozapine for several months, using measurement of plasma and red blood cell levels (P, RBC) of clozapine (cloza) and N-desmethylclozapine (descloza), the major metabolite of clozapine, which has been reported to be less active but more toxic (agranulocytosis) than clozapine itself. The RBC concentration may be considered as more representative of the free fraction drug. The study concerned 7 patients suffering from chronic paranoid schizophrenia according to the DSM-IV criteria. All of them were treatment-refractory schizophrenic inpatients (4 men, 3 women, mean age +/- SD: 38.2 +/- 8.4 years; mean duration of illness +/- SD: 14.4 +/- 5.1 years). They had received at least two different neuroleptics, for 6 weeks, before entering the study. Treatment started in our hospitalization unit with clozapine 25 mg up to a maximum of 900 mg/d (mean stabilized daily dose +/- SD: 507 +/- 211 mg and mean daily dose per kg: 6.91 +/- 3.08 mg). Clinical evaluations (Quality of Life Scale: QLS), regular blood monitoring and biological samples were conducted at the same time, weekly for 18 weeks and then monthly (duration of the study: 4 to 38 months; mean +/- SD: 12.9 +/- 11.5 months). Plasma and RBC (after lysis) levels were determined by reversed phase HPLC and UV detection after extraction with hexane. All the patients improved very quickly after the first week of treatment and six were able to leave the hospitalization unit and start outpatient care such as daily hospitalization, returning home or in sheltered accommodation. With the following plasma (P) and RBC levels: mean cloza +/- SD: (P = 294 +/- 146 ng/ml; RBC = 110 +/- 82 ng/ml) and mean descloza +/- SD: (P = 173 +/- 106 ng/ml; RBC = 76 +/- 54 ng/ml); none of the seven patients developed agranulocytosis. The blood levels, ensuring better surveillance, have a predictive value for clinical improvement. A linear pharmacoclinical correlation was only found between RBC cloza concentrations and the evolution of the QLS scores. Clozapine fulfils the criteria for therapeutic drug monitoring, and determination of plasma, and more particularly RBC, cloza and descloza levels may help to find the lowest effective dose with the fewest side effects.

The aim of this study was to assess the effects of amlodipine on left ventricular function at rest and on effort, at least 30 days after myocardial infarction. The 30 patients included in the study had resting isotopic ejection fractions of 40 to 60%. At inclusion and after 15 days treatment with 10 mg of amlodipine, the patients underwent exercise stress testing with a standard Bruce protocol and resting and exercise isotopic left ventricular ejection fractions were measured. The association of betablockers was allowed but vasodilator therapy was prohibited. During the second exercise stress test, the duration of exercise increased (437 +/- 167 to 518 +/- 154 s; p0.002) and the work level rose from 140 +/- 56 to 169 +/- 60 Watts; p0.04. The number of electrically positive tests did not change significantly (33 vs 26.7%; NS). The resting ejection fraction did not increase after 15 days treatment with amlodipine (47.4 +/- 6.7 vs 48.3 +/- 8.9%; NS). Similar results were observed with respect to the exercise ejection fraction (51.4 +/- 10.4 vs 52.6 +/- 8.6%; NS). These patients may however be divided into two subgroups. In the first subgroup of 10 patients, the resting ejection fraction rose by more than 5% with amlodipine whereas the exercise ejection fraction remained unchanged (54.4 +/- 7.7% vs 54.5 +/- 7.5% with amlodipine). In the second subgroup of 20 patients, the resting ejection fraction decreased slightly with amlodipine (48 +/- 6.9% vs 45.3 +/- 8%; p = 0.04) but increased significantly on exercise (45.3 +/- 8% vs 51.7 +/- 9.1%; p0.0002). Therefore, amlodipine, a new generation calcium antagonist, does not induce any deleterious effect after myocardial infarction with mild left ventricular dysfunction.

Multivessel coronary angioplasty, defined as angioplasty of 2 or 3 main coronary vessels performed during the same procedure, was performed in 203 selected patients between 1981 and 1986. The results in men (n = 159, group I) were compared with those in women (n = 44, group II). The angiographic appearances were comparable in the two groups, but the women were older, more often hypertensive and diabetic, and more symptomatic than the men (82% vs 57% in grades 3 or 4 of the Canadian Cardiovascular Society (CCS) Classification; p0.009). Complete revascularisation with angioplasty of all stenoses50% was attempted during the same session. The primary success rate per lesion was comparable in the two groups (90% in men, 93% in women; NS), as was the number of segments successfully dilated per patient (2.2 +/- 0.7 in group I and 2.2 +/- 0.8 group II; NS). Angioplasty was complicated by myocardial infarction and/or emergency coronary bypass surgery in 11 men and 2 women (NS). Clinical follow-up was obtained for an average of 71 +/- 22 months in the men and 70 +/- 22 months in the women in 96% of cases. The global seven year survival rate without recurrent infarction or cardiovascular death was 81% in men and 83% in women (NS). The number of repeat revascularisation procedures was comparable in the two groups (46% in women and 43% in men; NS) as was the number and duration of hospital admissions during follow-up (8.4 +/- 12.3 days in the women and 6.7 +/- 8.4 days in the men; NS). The functional status at the end of follow-up was the same in the two groups with 84% of men and 81% of women being asymptomatic or grade 1 of the CCS classification. The authors conclude that the long-term results of multivessel angioplasty are good and comparable in men and women. This revascularisation procedure should be considered as an alternative to surgery in women and men.

It has been shown that the presence of ventricular late potentials is a predictive factor of ventricular tachycardia and sudden death after myocardial infarction. The value of thrombolysis in the reduction of the prevalence of ventricular late potentials is now well established. However, the effects of other modes of revascularisation is less well known and more controversial. The authors undertook a retrospective study of 139 consecutive patients undergoing coronary angiography after primary myocardial infarction. The presence of ventricular late potentials fulfilling two of the three usual criteria was sought after a revascularisation procedure. The overall prevalence of ventricular late potentials was 30.9%. This was not affected either by the site of infarction of by the single or multiple character of the coronary artery disease. In addition, the left ventricular ejection fraction was not significantly different in patients with positive ventricular late potentials compared with the others. On the other hand, revascularisation of the culprit lesion responsible for the infarction was strongly correlated with a lower incidence of ventricular late potentials (p10 (-5)). In particular, the different incidence of positive late potentials between the dilated (9.3%) and non-dilated group (49.2%) was statistically significant (p10 (-6)) without any correlation to the single or multiple character of the coronary disease. The authors discuss the different reports in the literature concerning the effects of angioplasty and coronary bypass surgery on the incidence of ventricular late potentials. Conclusion; the review of the literature shows that thrombolysis significantly reduces the incidence of late potentials after myocardial infarction and the present study suggests that angioplasty and coronary bypass surgery may also be effective.

The aims of this study were to determine the value of quantifying mitral valve disease by transoesophageal echocardiography before percutaneous mitral commissurotomy (PMC) and to analyse the incidence of embolic complications during PMC since the introduction of transoesophageal echocardiography. From March 1987 to December 1991, 317 patients with pure or dominant mitral stenosis were selected by Doppler echocardiography to undergo PMC at the Montreal Institute of Cardiology. The clinical features of the first 138 patients (Group I) were the same as those of the last 179 patients (Group 2) who also underwent routine transoesophageal echocardiography the day before the procedure. A thrombus in the left atrial appendage was observed in 8 patients in Group 2 (4.4%). No embolic complications have occurred since the protocol was changed to include routine transoesophageal echocardiography, whereas 4 embolic episodes, 3 of which were fatal, occurred in patients in group 1. The indication of PMC was turned down because of angiographically severe mitral regurgitation which was underestimated by transthoracic echocardiography in 2 patients in Group 1 (1.4%) and in 3 patients in group 2 (1.6%). The mobility, thickness and degree of calcification of the valves were attributed a score from 0-4 at transthoracic and transoesophageal echocardiography. No difference was observed in the scores of mobility (2.3 +/- 0.5 versus 2.3 +/- 0.05, NS) or valve thickness (2.1 +/- 0.4 versus 2.1 +/- 0.4, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Radionuclide ventriculography before, during, and after atrial transesophageal pacing was carried out in 15 patients with suspected coronary artery disease (CAD) and without myocardial infarction. All patients underwent coronary angiography. Ten patients (group 1) had a coronary lesion > 50% on at least one of the main coronary arteries. Five patients (group 2) had normal coronary arteries. Radionuclide left ventricular ejection fraction (LVEF) before pacing was 56 ±3% in group 1 and 59 ±3% in group 2 (NS). Radionuclide ventriculography during pacing was 45 ±4% in group 1 (P < 0.0001 vs basal in group 1) and 45 ±6% in group 2 (P < 0.01 vs basal in group 2, NS vs group 1 during pacing). Immediate postpacing ejection fraction did not differ in the two groups and was identical to the prepacing value. A quantitative regional wall motion analysis was performed in 105 segments. Regional radionuclide ventriculography was calculated in each segment as follows: end-diastolic counts — end-systolic counts/end-diastolic counts. The relative decrease in regional LVEF during pacing was more important in the 39 segments related to a narrowed vessel than in the 66 segments related to normal coronary artery (32 ± 13% vs 13 ±10%, P < 0.0001). A more than 20% relative decrease in at least one segment during pacing occurred in 10 patients in group 1 (sensitivity 100%) and in 2 patients in group 2 (specificity 60%). In conclusion, global radionuclide ventriculography during transesophageal atrial pacing decreases in patients with and without CAD. In contrast, regional wall motion abnormalities during pacing are more important in segments related to a narrowed coronary artery and can be proposed for patients unable to exercise as an alternative to pharmacologic stress test in the diagnosis of CAD.

The authors studied retrospectively a series of 39 patients with a documented second restenosis after coronary angioplasty between January 1987 and November 1992, 33 of whom (31 men, 2 women) underwent a third procedure. The artery dilated was the left anterior descending (n = 17 including 9 proximal stenoses), the right coronary (n = 10), the left circumflex or its branches (n = 5) and the left main stem (n = 1). The lesions were confirmed to one vessel in 25 cases (75%) and affected two vessels in 8 cases (25%). The third angioplasty procedure was performed on a single artery in all cases. The average left ventricular ejection fraction was 60% (43%-75%). The diameter of the dilated artery was over 3.25 mm in 24% of cases (8/33). The primary success rate was 100% without any complications. The average period between the first and second angioplasties was 16 +/- 10 weeks, and between the second and third angioplasties 19 +/- 12 weeks. Angioplastic controls of the 3rd angioplasty were performed in 25 cases (75%). A third restenosis (n = 7) was treated by surgical bypass (n = 1), repeat angioplasty (n = 4), endocoronary stenting (n = 1) or medically (n = 1), with a global follow-up of 22 months (2-56 months), 2 patients underwent coronary bypass grafting, 2 have residual angina (contralateral lesion which could not be dilated), 1 had an infarct in the territory of an undilated artery, and 28 (85%) were asymptomatic. The restenosis rate after the third angioplasty procedure was 28% (7/25).(ABSTRACT TRUNCATED AT 250 WORDS)

Fifty-five patients with suspected coronary artery disease underwent planar thallium-201 myocardial scintigraphy after atrial transoesophageal pacing. Coronary angiography was carried out in all patients. Eighteen patients had no myocardial infarction, but a greater than 50% narrowing of at least one main vessel: initial hypoperfusion with redistribution at 4 h occurred in 16 patients (sensitivity 89%). Twenty-one patients had had a previous myocardial infarction: a reversible thallium defect was observed in 12 patients and an irreversible defect in the nine remaining patients. Sixteen patients had normal coronary arteries: a reversible thallium defect was observed in three patients (specflcity 81%). After a mean follow-up of 22±13 months (range 6 to 40), 23 cardiac events occurred: cardiac death in one patient, unstable angina in three, and revascularization procedures for recurrent angina despite medical therapy in 19 (coronary artery bypass surgery in 7 and coronary angioplasty in 12). By univariate analysis, the predictors of future cardiac events were a history of previous myocardial infarction (odds ratio 55, P

Fifty nine of the 280 percutaneous mitral valvuloplasties (21%) performed between March 1987 and December 1991 at the Montreal Heart Institute were carried out for symptomatic mitral restenosis 15 +/- 6 years after surgical commissurotomy. The patients were selected according to echocardiographic criteria. The mitral valve disease was comparable to that of patients without previous surgical commissurotomy. Patients with good hemodynamic result had undergone surgical commissurotomy more recently and had less severe valvular damage than patients with an incomplete (n = 10) or poor result (n = 7). One patient died of a cerebral embolism during the procedure, two patients underwent emergency surgery for a mitral valve rupture and 4 patients had an atrial septal defect with Qp/Qs ratio greater than 1.5 by oximetry. The numbers of successes and complications were comparable to those observed in patients without previous surgical commissurotomy. The patients who had undergone previous surgical commissurotomy were followed up for 1 year. At 12 months, 4 remained in Class II of the NYHA classification, 44 (74%) were improved by at least 1 functional class and 10 (17%) had required a mitral valve replacement. Percutaneous mitral valvuloplasty is therefore a useful procedure in patients with moderate degrees of valvular disease who develop restenosis after surgical commissurotomy. A functional improvement can be expected in 3/4 of patients Complications related to the procedure are rare and acceptable compared with the risks of a second thoracotomy. Failure of percutaneous mitral valvuloplasty is generally due to the degree of valvular disease which contraindicated surgical commissurotomy and required mitral valve replacement.

The hemodynamic effects and safety of milrinone, a phosphodiesterase inhibitor, were studied in 57 patients in the acute phase of cardiac failure. The drug was given intravenously as an initial push dose of 50 micrograms/kg in 10 min followed by a 24 hour infusion at the dose of 0.5 micrograms/kg/min. Maximal response was obtained after 15 min and persisted throughout the infusion. Cardiac index rose by 40%, while pulmonary capillary pressure fell from 25 mmHg to 17 mmHg (-30%) by the fifth minute of treatment. Mean pulmonary artery pressure fell by 20% by the 15th minute. Systemic resistance decreased by 26% and pulmonary vascular resistance by 22%. All these variations were significant. Heart rate and systemic blood pressure remained stable. Study of three sub-groups: digoxin vs non-digoxin, sinus rhythm vs atrial fibrillation, and coronary patients vs non-coronary patients, revealed no significant difference. Safety of the drug was good, no extra-cardiac actions having required interruption of the infusion. Stoppage was made necessary by two instances of ventricular tachycardia. Improved hemodynamic effects and the good safety/acceptability of the drug indicate that milrinone is a treatment of choice in cardiac failure.

Forty three men and 3 women, with an average age of 59 years (13 to 78 years) underwent aorto-coronary bypass surgery despite severe left ventricular dysfunction (ejection fraction35%); 96% of the patients had previous infarction; 60% (N = 28) had unstable angina, 52% (N = 24) had had pulmonary oedema or an episode of congestive cardiac failure. The average ejection fraction was 29 +/- 4%, range 17 to 35%. Thirteen patients had ventricular aneurysms, 4 had grade 3 or 4 mitral regurgitation. The coronary lesions were usually multivessel left main coronary (6), triple vessel disease (27), double vessel disease (12), single vessel disease (1). The average number of bypass grafts per patient was 2.3. The average aorting clamping time was 63 minutes (range 26 to 133 minutes). There were 4 mitral valve replacements, 4 resections of ventricular aneurysms and 1 double procedure (aneurysmectomy and valve replacement). The operative mortality was 2.1% (1 death). During an average follow-up period of 27 months (range 3 to 90 months), there were: 2 recurrent infarctions, 13 episodes of cardiac failure and 8 cardiac deaths (cardiac failure: 5, sudden death: 2, recurrent infarction: 1). Two patients underwent cardiac transplantation. The regression of angina (90% of operated patients were asymptomatic) and the low operative risk, justify aortocoronary bypass surgery despite left ventricular dysfunction in patients with severe symptoms (unstable angina, chronic, invalidating angina). The medium-term results indicate a high risk of cardiac failure which is partially responsible for the secondary mortality rate of 17% at 2 years.

Between 1988 and 1990, 150 patients treated for an infarction by intravenous thrombolysis underwent coronary arteriography. Sixty seven were managed by revascularisation by angioplasty (n = 49) or bypass (n = 18) more than 48 hours after thrombolysis. In this delayed revascularisation group, the time before initial fibrinolysis was 114 +/- 55 minutes. The artery responsible for the infarction was patent in 88 per cent of cases at 12 +/- 9 days, with ejection fraction being 56 +/- 12 per cent. Indications for revascularisation were: recurrence of angina, Thallium stress test showing redistribution (n = 9), diffuse lesions (n = 11) or tight (greater than 75 per cent) proximal stenosis without vessel wall sequelae (n = 10). Comparison of the bypass and angioplasty groups showed a lower ejection fraction in the former than the latter (47% VS 58%, p less than 0.01), more frequent three-vessel disease (50% VS 6%, p less than 0.01) and more frequent revascularisation of the anterior interventricular (100% VS 37%, p less than 0.01). There were 2 deaths and 5 recurrences of infarction at one year. Follow-up arteriography was performed between at 2 and 6 months in 72% of the patients: 16 had restenosis after angioplasty and 4 occlusion of the graft after bypass. A second revascularisation procedure was necessary 15 times (14 angioplasties, 1 bypass). The outcome after bypass or angioplasty was favourable in 90% of cases in this group of patients exposed to a recurrence of infarction.