The Top 100 Cited Articles in the Microsurgical Treatment for Lymphedema.

BACKGROUND: Evidence-based medicine uses the current best evidence for decisions about patient care. Lymphedema is a chronic debilitating medical condition caused by a dysfunctional lymphatic system. This study analyzes the most cited articles, including the levels of evidence, for the surgical treatment of lymphedema. METHODS: The Web of Science Sci-Expanded Index was utilized to search for surgical treatment of lymphedema. Articles were examined by three independent reviewers and the top 100 articles were determined. The corresponding author, citation count, publication year, topic, study design, level of evidence, journal, country, and institution were analyzed. RESULTS: Since 1970, the top 100 articles have been cited 7,300 times. The average citation count was 68 and standard deviation was 55. The majority was case series (71), followed by retrospective cohort (8), prospective cohort (7), retrospective case-control (5), and randomized controlled trials (2). Based on the "Level of Evidence Pyramid," 71 articles were level IV, 13 articles were level III, and 9 articles were level II. On the Grading of Recommendations Assessment, Development, and Evaluation Scale, there were 71 articles with "very low," 20 articles with "low," and 2 articles with "moderate" quality of evidence. CONCLUSION: The top 100 cited articles were mostly case series and lacked high levels of evidence. Most studies are retrospective case series with short-term outcomes. However, low level evidence for new surgical procedures is to be expected. Current trends suggest the treatment and understanding of lymphedema will continue to improve.

Beat note stabilization in dual-polarization DFB fiber lasers by an optical phase-locked loop.

A fully fibered microwave-optical source at 1.5 µm is studied experimentally. It is shown that the beat note between two orthogonally polarized modes of a distributed-feedback fiber laser can be efficiently stabilized using an optical phase-locked loop. The pump-power-induced birefringence serves as the actuator. Beat notes at 1 GHz and 10 GHz are successfully stabilized to a reference synthesizer, passing from the 3 kHz free-running linewidth to a stabilized sub-Hz linewidth, with a phase noise as low as -75 dBc/Hz at 100 Hz offset from the carrier. Such dual-frequency stabilized lasers could provide compact integrated components for RF and microwave photonics applications.

Are emotionally driven and addictive-like eating behaviors the missing links between psychological distress and greater body weight?

There is now a large body of evidence suggesting a significant association between emotional discomfort management, disordered eating behaviors and weight status. In the field of overweight and obesity, emotionally driven eating habits that resemble addictive behaviors are considered as a risk factor. This study aimed to investigate in a large sample of French university students 1) the associations between self-reported levels of psychological distress (PD), emotional eating (EE), food addiction (FA) and Body Mass Index (BMI); and 2) the potential mediation effect of eating behaviors (EE and FA) between PD and BMI. The responses of 1051 students (76.3% females) to self-reports assessing PD (Perceived Stress Scale, Hospital Anxiety and Depression Scale), EE (Intuitive Eating Scale-2) and FA (modified Yale Food Addiction Scale) were analysed. Associations between variables (Spearman correlation) and group comparisons by sex and BMI categories (Student's t tests/ANOVA) were tested, followed by Structural Equation Modeling (SEM) by sex. Among females and males, EE and FA scores were positively inter-related and correlated with PD scores and BMI. Moreover, among females and males, SEM showed that both EE and FA acts as mediators between PD and BMI. Hence, among educated young adults, using food consumption for down-regulating negative mood places the individual at risk for overweight and obesity. This study further emphasizes the necessity to take into account emotionally driven and addictive-like eating behaviors in interventions for promoting healthy eating and weight management.

[Behavioral activation programs: A tool for treating depression efficiently]. / L'activation comportementale : un outil simple et efficace dans le traitement de la dépression.

INTRODUCTION: Major depressive disorder (MDD) is a debilitating disorder, and its treatment often requires complex and costly psychological therapies. Behavioral activation (BA) is a simple, effective and affordable psychotherapy recommended in the treatment of MDD. OBJECTIVES: (i) Explain the theoretical basis of BA and its application in clinical practice. (ii) Review the randomized controlled trials examining BA as a treatment for MDD through a systematic search of the existing literature. METHODS: Medline and ClinicalTrials databases were searched with the following keywords: ("behavioral activation" OR "behavioural activation") AND ("therapy" OR "psychotherapy"). (i) Articles describing BA's theoretical foundations and principles of therapy were selected. (ii) Randomized controlled trials studying BA as a treatment for depression were selected according to the PRISMA criteria. RESULTS: (i) BA is a behavioral therapy that helps patients to increase their behaviors towards rewarding and/or pleasant activities, and to decrease avoidant behaviors maintaining negative affects by negative reinforcement. BA also tends to increase behaviors towards life-goals used as positive reinforcement contingencies. BA is a brief and cost effective therapy, which can be evaluated by specific psychometric scales. (ii) BA has a strong therapeutic effect in MDD as evaluated by several randomized controlled trials of good quality. CONCLUSION: BA is a simple, affordable and effective treatment for MDD. Data is insufficient to provide proof for the interest of using commitment to life-goals as reinforcement contingencies. Behavioral inhibition is encountered amongst several psychiatric disorders and more studies should be conducted to discuss its use for other diseases such as schizophrenia or anxiety disorders.

Socioeconomic status and social anxiety: attentional control as a key missing variable?

BACKGROUND AND OBJECTIVES: The aim was to examine the role of attentional control as a psychological factor involved in socioeconomic status-related mental health differences, and specifically in social anxiety. Based on the literature on socioeconomic status differences in cognitive abilities and attentional control theory, we hypothesized that attentional control would account for the relation between socioeconomic status and social anxiety. We tested this hypothesis in an integrative model also including trait anxiety and subjective socioeconomic status. DESIGN: Cross-sectional. METHOD: Online, 439 French adults were recruited via social media. They completed self-reported measures of attentional control, objective socioeconomic status, subjective socioeconomic status, social anxiety, and trait anxiety. RESULTS: Using Structural Equation Modelling, findings showed a positive association between objective (but not subjective) socioeconomic status and attentional control, which in turn was related to social anxiety. Exploratory analyses showed that only income, as objective socioeconomic status indicator, was associated with attentional control. CONCLUSIONS: The current study is the first to support that low socioeconomic status individuals report less attentional control and more social anxiety symptoms. This suggests that attentional control is a psychological factor involved in social anxiety inequalities.

[Episodic ataxia type 2: a clinical, genetic and radiological study of 10 patients]. / Ataxia episódica tipo 2: estudio clínico, genético y radiológico de 10 pacientes.

OBJECTIVES: To describe a series of patients with episodic ataxia type 2 (EA2), attending to epidemiological, clinical, radiological, and therapeutic variables. MATERIAL AND METHODS: Retrospective revision of patients with molecular diagnosis of EA2 (CACNA1A mutations), between 1988 and 2022. Information achieved from the database of our Movement Disorders clinic. A descriptive statistical analysis was made. RESULTS: Ten patients from five families were analyzed (six women). Median age at diagnosis was 37.5 years-old, with a median diagnostic delay of 20 years. 70% reported familial history of CACNA1A associated symptoms, although 50% presented migraine, epilepsy, dystonia, or neuropsychiatric alterations. Two heterozygous consanguineous patients had homozygotic descendance with infant mortality due to early-onset epileptic encephalopathy type 42. Five pathogenic/probably pathogenic CACNA1A variants were detected. 80% of patients had episodic triggers, being stress the most common. Episodes had a weekly frequency before treatment initiation. Six patients developed chronic ataxia (one patient demand gait support). 50% of patients with neuroimaging presented cerebellar atrophy. Acetazolamide were initiated in 80%, and 75% of them showed improvement of episodic symptoms. Nephrolithiasis was the most frequent side effect. CONCLUSIONS: EA2 has a great intrafamilial and interfamilial phenotypic variability. The most frequent phenotype were weekly episodes of unsteadiness, several hours of length, stress as the main trigger, chronic ataxia and gaze-evoked nystagmus. Acetazolamide is effective, although complications are usual. Neurologist must be alert as diagnostic delay is constant.

TITLE: Ataxia episódica tipo 2: estudio clínico, genético y radiológico de 10 pacientes.Objetivo. Describir una serie de pacientes con ataxia episódica tipo 2 (AE2) según variables epidemiológicas, clínicas, radiológicas y terapéuticas. Material y métodos. Revisión retrospectiva de pacientes con diagnóstico molecular de AE2 (mutación en CACNA1A) entre 1988 y 2022, información recogida de la base de datos de la Unidad de Trastornos del Movimiento de nuestro centro. Se realizó un análisis estadístico descriptivo. Resultados. Se analizó a 10 pacientes procedentes de cinco familias. La mediana de edad en el momento del diagnóstico fue 37,5 años, con un retraso diagnóstico de 20 años. El 50% asociaba epilepsia, migraña, distonía o alteraciones neuropsiquiátricas. El 70% tenía una historia familiar de síntomas asociados a CACNA1A. Dos pacientes heterocigotos consanguíneos tuvieron descendencia homocigota con mortalidad infantil por encefalopatía epiléptica de inicio precoz de tipo 42. Se detectaron cinco variantes diferentes de CACNA1A. El 80% mostró factores desencadenantes, y el estrés fue el más común. La frecuencia episódica más habitual fue semanal. Seis pacientes desarrollaron ataxia interepisódica, aunque sólo uno precisó apoyo en la marcha. El 50% de los pacientes con neuroimagen presentó atrofia cerebelosa. El 80% inició acetazolamida durante el seguimiento, con respuesta a dosis altas en el 75%. La nefrolitiasis fue el efecto adverso más frecuente. La 4-aminopiridina fue una alternativa eficaz. Conclusiones. La AE2 presenta una alta variabilidad fenotípica inter- e intrafamiliar. El fenotipo más frecuente fueron episodios de inestabilidad, de horas de duración, semanales, con estrés como desencadenante, ataxia persistente y nistagmo evocado por la mirada. La acetazolamida, aunque es eficaz, no está exenta de complicaciones. El retraso diagnóstico es muy frecuente.

Primary and secondary non-traumatic intra-cerebral haemorrhage: MRI findings.

Intracranial haemorrhage (ICH) accounts for 10-30% of strokes, being the form with the worst prognosis. The causes of cerebral haemorrhage can be both primary, mainly hypertensive and amyloid angiopathy, and secondary, such as tumours or vascular lesions. Identifying the aetiology of bleeding is essential since it determines the treatment to be performed and the patient's prognosis. The main objective of this review is to review the main magnetic resonance imaging (MRI) findings of the primary and secondary causes of ICH, focusing on those radiological signs that help guide bleeding due to primary angiopathy or secondary to an underlying lesion. The indications for MRI in the event of non-traumatic intracranial haemorrhage will also be reviewed.

[E-consult®, an e-health application to improve breast cancer surgery patient's information]. / E-consult®, application d'e-santé pour mieux informer les patientes en consultation de chirurgie pour cancer du sein.

INTRODUCTION: The use of new information and communication technologies is one way of better informing the patient. E-health includes telemedicine but also patient information and self-monitoring, or continuous remote monitoring with connected objects and mobile apps. It is in this context that we have developed and designed a digital application, e-consult®, which we use at the François Baclesse center, dedicated to improving information for patients. The objective of this study was to assess the performance of the e-consult® application in current practice, in order to know if the information delivered to patients was better retained with the application. METHODS: We conducted a prospective, single-center study at the Cancer Center François Baclesse. One group was received in consultation with the use of e-consult®, the other without. Following the consultation, the patient was given a questionnaire concerning her illness and a satisfaction questionnaire concerning the application. RESULTS: The average score obtained on the questionnaire in the group having benefited from a consultation with e-consult® (7.12/10) was significantly higher than that obtained in the group having benefited from a consultation without e-consult® (6.4/10) (P=0.0276). CONCLUSION: Our study showed that patients understood better the information transmitted in consultation with the use of e-consult®. In our opinion, this is the only study evaluating an application in consultation. However, our study has several weaknesses, including the lack of randomization, a small number of patient, and unvalidated questionaries. Despite these promising results, more studies with better internal validity are needed. Future research may also study the impact of the application on the doctor-patient relationship.

[Artificial intelligence, radiomics and pathomics to predict response and survival of patients treated with radiations]. / Intelligence artificielle en radiothérapie : radiomique, pathomique, et prédiction de la survie et de la réponse aux traitements.

Artificial intelligence approaches in medicine are more and more used and are extremely promising due to the growing number of data produced and the variety of data they allow to exploit. Thus, the computational analysis of medical images in particular, radiological (radiomics), or anatomopathological (pathomics), has shown many very interesting results for the prediction of the prognosis and the response of cancer patients. Radiotherapy is a discipline that particularly benefits from these new approaches based on computer science and imaging. This review will present the main principles of an artificial intelligence approach and in particular machine learning, the principles of a radiomic and pathomic approach and the potential of their use for the prediction of the prognosis of patients treated with radiotherapy.

[Pathophysiology of post-operative cognitive dysfunction: current hypotheses]. / Physiopathologie de la dysfonction cognitive postopératoire du sujet âgé: hypothèses actuelles.

Post-operative cognitive dysfunction (POCD) has been reported after a variety of surgical procedures. POCD is associated with a decline in performance of activities of daily living of elderly patients and can cause substantial damage to family and/or to social support systems. The incidence of POCD in the first week after surgery is 23% in patients between 60 and 69 years of age and 29% in patients older than 70. Cognitive dysfunction was still present in 14% of patients over 70 at three month after surgery. The risk of POCD increases with age, and the type of surgery is also important since there is very low incidence of POCD after minor surgery. For many years, it has been known that general anaesthesia is associated with persistent changes in gene expression in the brain for at least 72 hours. These observed modifications suggest an interesting hypothesis to explain the side effects of anaesthetic agents on cognitive dysfunction, particularly in the elderly. The inflammatory response to surgery is consistent with the hypothesis that inflammation contributes to cognitive decline in the elderly. Most of the drugs administered during anaesthesia interact with the cerebral cholinergic system, which seems to be impaired with ageing. One can hypothesize that this cholinergic dysfunction is a potent factor in the pathogenesis of POCD. These findings have implications for the information provided before obtaining consent from elderly patients prior to surgery; a careful evaluation of mental status is mandatory for all elderly patients undergoing general anaesthesia. Perioperative physicians should be familiar with the prevention, diagnosis, and management of postoperative cognitive dysfunction.

Ataxia episódica tipo 2: estudio clínico, genético y radiológico de 10 pacientes / Episodic ataxia type 2: a clinical, genetic and radiological study of 10 patients

Objetivo: Describir una serie de pacientes con ataxia episódica tipo 2 (AE2) según variables epidemiológicas, clínicas, radiológicas y terapéuticas. Material y métodos. Revisión retrospectiva de pacientes con diagnóstico molecular de AE2 (mutación en CACNA1A) entre 1988 y 2022, información recogida de la base de datos de la Unidad de Trastornos del Movimiento de nuestro centro. Se realizó un análisis estadístico descriptivo. Resultados: Se analizó a 10 pacientes procedentes de cinco familias. La mediana de edad en el momento del diagnóstico fue 37,5 años, con un retraso diagnóstico de 20 años. El 50% asociaba epilepsia, migraña, distonía o alteraciones neuropsiquiátricas. El 70% tenía una historia familiar de síntomas asociados a CACNA1A. Dos pacientes heterocigotos consanguíneos tuvieron descendencia homocigota con mortalidad infantil por encefalopatía epiléptica de inicio precoz de tipo 42. Se detectaron cinco variantes diferentes de CACNA1A. El 80% mostró factores desencadenantes, y el estrés fue el más común. La frecuencia episódica más habitual fue semanal. Seis pacientes desarrollaron ataxia interepisódica, aunque sólo uno precisó apoyo en la marcha. El 50% de los pacientes con neuroimagen presentó atrofia cerebelosa. El 80% inició acetazolamida durante el seguimiento, con respuesta a dosis altas en el 75%. La nefrolitiasis fue el efecto adverso más frecuente. La 4-aminopiridina fue una alternativa eficaz. Conclusiones: La AE2 presenta una alta variabilidad fenotípica inter- e intrafamiliar. El fenotipo más frecuente fueron episodios de inestabilidad, de horas de duración, semanales, con estrés como desencadenante, ataxia persistente y nistagmo evocado por la mirada. La acetazolamida, aunque es eficaz, no está exenta de complicaciones. El retraso diagnóstico es muy frecuente.(AU)

Objectives: To describe a series of patients with episodic ataxia type 2 (EA2), attending to epidemiological, clinical, radiological, and therapeutic variables. Material and methods: Retrospective revision of patients with molecular diagnosis of EA2 (CACNA1A mutations), between 1988 and 2022. Information achieved from the database of our Movement Disorders clinic. A descriptive statistical analysis was made. Results: Ten patients from five families were analyzed (six women). Median age at diagnosis was 37.5 years-old, with a median diagnostic delay of 20 years. 70% reported familial history of CACNA1A associated symptoms, although 50% presented migraine, epilepsy, dystonia, or neuropsychiatric alterations. Two heterozygous consanguineous patients had homozygotic descendance with infant mortality due to early-onset epileptic encephalopathy type 42. Five pathogenic/probably pathogenic CACNA1A variants were detected. 80% of patients had episodic triggers, being stress the most common. Episodes had a weekly frequency before treatment initiation. Six patients developed chronic ataxia (one patient demand gait support). 50% of patients with neuroimaging presented cerebellar atrophy. Acetazolamide were initiated in 80%, and 75% of them showed improvement of episodic symptoms. Nephrolithiasis was the most frequent side effect. Conclusions: EA2 has a great intrafamilial and interfamilial phenotypic variability. The most frequent phenotype were weekly episodes of unsteadiness, several hours of length, stress as the main trigger, chronic ataxia and gaze-evoked nystagmus. Acetazolamide is effective, although complications are usual. Neurologist must be alert as diagnostic delay is constant.(AU)

[Implication of dexamethasone adjunctive therapy after the onset of cerebral vasculitis in Streptococcus pneumoniae meningitis]. / Implication du traitement adjuvant par dexaméthasone dans la survenue d'une artérite septique cérébrale au cours d'une méningite à Streptococcus pneumoniae.

Few adverse effects have been reported with adjunctive dexamethasone treatment in pneumococcal meningitis. Nevertheless, we report a case of cerebral vasculitis. A 49-year-old man was admitted for fever and altered mental status. Lumbar puncture revealed a high inflammatory response and Streptococcus pneumoniae was identified by culture. Antibacterial therapy and adjunctive dexamethasone treatment were initiated as recommended. The immediate outcome was favorable but due to the onset of focal cerebral abnormalities, a CT scan was performed on the ninth day showing cerebral vasculitis. The patient died on the thirteenth day despite antibacterial therapy and resuscitation. In our case, a secondary neurological worsening appeared when adjunctive dexamethasone treatment was stopped suggesting a rebound effect. Observation of similar cases may lead to modifying adjunctive dexamethasone treatment protocol in bacterial meningitis.

Estudio tras intervención formativa del taller de: prevención, tratamiento y adherencia en la enfermedad osteoporótica desde la farmacia comunitaria / Study after training intervention of the workshop: prevention, treatment and adherence in osteoporotic disease from the community pharmacy

JUSTIFICACIÓN: debido a los cambios demográficos derivados del envejecimiento de la población y el aumento de pacientes con enfermedades crónicas en el mundo, la osteoporosis se ha convertido en una enfermedad prevalente y un problema de salud pública, con importantes repercusiones debido a la morbilidad y morbimortalidad que conlleva, y a los gastos directos e indirectos que genera. Si no se interviene desde la prevención, tratamiento precoz y adherencia al mismo en la práctica clínica, el número de pacientes que sufrirán osteoporosis y sus consecuencias irá en aumento. OBJETIVOS: formar al farmacéutico comunitario en educación sanitaria para la población de más de 50 años susceptible de sufrir enfermedad osteoporótica. Establecer un conjunto de recomendaciones basadas en la evidencia científica acerca de la atención farmacéutica en la enfermedad osteoporótica. MATERIAL Y MÉTODOS: estudio cuasiexperimental con intervención formativa y evaluación antes/después. Procedimiento. Se imparte el taller de forma presencial en quince ciudades con una duración de 45 minutos, eligiendo el farmacéutico horario de mañana o de tarde. Éste consta de una parte teórica y un caso práctico dividido en tres fases de seguimiento. Los asistentes responden a cinco preguntas de impacto antes y después de asistir al taller y se comparan las respuestas.RESULTADOS/ DISCUSIÓN: un 15% más de los asistentes conoce tras el taller que el problema fundamental de la enfermedad osteoporótica es la fractura por fragilidad. La mayoría de asistentes ya sabían antes del taller que se trata de una enfermedad más frecuente en mujeres (92,3%) y que el tratamiento farmacológico más habitual son los bifosfonatos (87,6%). Además, tras asistir al taller, el 14% de los asistentes mejoraron el conocimiento de los factores de riesgo más importantes y el 16% aprendió que la técnica validada para la fragilidad ósea es la densitometría central. (AU)

Risk factors for substances use and misuse among young people in France: What can we learn from the Substance Use Risk Profile Scale?

BACKGROUND: The prevention of addictions in young people is a challenge for Mental and Public Health policies, and requires specific risk-screening tools. Specific personality traits, as assessed using the Substance Use Risk Profile Scale (SURPS), could play a key role in the onset and escalation of substance use. This study aimed to examine (1) measurement invariance across age and gender (2) the effects of age and gender on associations between SURPS scores and the most frequently-consumed substances. METHODS: Analyses were based on the responses from 5069 participants (aged 14-20 years) from the 2011 ESPAD-France dataset. Substance-use outcomes were experimentation and current frequency of alcohol, tobacco and cannabis use, and drunkenness. RESULTS: Our approach, consisting in analysing measurement and structural invariance and interaction terms, established the stability of (i) SURPS profiles, and (ii) relationships between these scores and substance experimentation and use over a developmental period ranging from mid-adolescence to early adulthood. Measurement invariance across genders was also confirmed despite the absence of scalar invariance for 2 items. Significant interactions between gender and SURPS factors were established, highlighting differential vulnerability, especially concerning Hopelessness and experimentation of alcohol and drunkenness, or Impulsivity and tobacco experimentation. Finally, Anxiety Sensitivity could be protective against substance use, especially for cannabis in girls. CONCLUSIONS: Our results suggest the relevance of the SURPS to assess vulnerability towards drug use, and underline the need to consider gender differences in addiction risks.

Novel mutations in the duplicated region of PKD1 gene.

Autosomal dominant polycystic kidney disease (ADPKD) exhibits a genetically heterogeneous transmission involving at least three different genes. PKD1 gene linked mutations are responsible for the disease in about 85% of ADPKD cases. The search for mutations is a very important step in understanding the molecular mechanisms underlying ADPKD. We undertook this study using denaturing gradient gel electrophoresis (DGGE), after a stage of long range PCR, to scan for mutations in the duplicated region of the PKD1 gene in French ADPKD families. This allowed us to identify eight novel mutations and several polymorphisms: among the mutations, three are nonsense mutations, two are deletions in the coding sequence leading to frameshift mutations, one is a splice mutation and two are highly probable missense mutations. In this paper, we also provide a review of the mutations reported so far which are widespread throughout the gene. Although no clear hot spot for mutation is apparent, we will focus on some clustering observed.

A prospective study of helical computed tomography angiography versus angiography for the detection of renal artery stenoses in hypertensive patients.

OBJECTIVE: To compare helical computed tomography angiography with arterial digital subtraction angiography in the diagnosis of renal artery stenoses. METHODS: Fifty hypertensives (24 men; mean age 53 years) were prospectively studied with computed tomography (Somaton Plus S, Siemens) and digital angiography (double-blind evaluation). Computed tomography was performed both in the sequential (the length of the abdomen) and in the helical (6 cm around renal arteries) modes during injection of 120 cm3 contrast medium. RESULTS: Digital angiography visualized 16 significant (< 50% on quantitative angiography) stenoses (16/131 renal arteries, including 32 accessory), in 14 (28%) patients. On helical computed tomography, 16 stenoses were detected, in 49 patients (16/122 renal arteries, seven accessory arteries were not identified because they were located out side the scan area); two patients had false-positive helical computed tomography results. The computed tomography sensitivity, specificity, positive and negative predictive values were 87.5% (14/16), 98.2% (111/114), 87.5% and 98.2%, respectively. In the sequential mode, two cases of bilateral adrenal hyperplasia, two aortic aneurysms and one renal neoplasm were detected. None of these patients had renal artery stenosis. CONCLUSIONS: Helical computed tomography is a suitable new non-invasive diagnostic modality for the detection of renal artery stenosis or adrenal pathology. With continued development and evaluation computed tomography could prove useful as a screening tool or as a replacement for digital angiography in patients with possible secondary hypertension.

Coronary sinus blood flow at rest and during isometric exercise in patients with aortic valve disease. Mechanism of angina pectoris in presence of normal coronary arteries.

In 46 patients with aortic valve disease, coronary sinus blood flow was measured using a continuous thermodilution method both at rest and during isometric handgrip exercise. All patients had normal coronary angiograms. The patients were separated into three groups: Group I, 12 patients with aortic stenosis (systolic gradient 72 +/- 12 mm Hg); Group II, 15 patients with both aortic stenosis and regurgitation; Group III, 19 patients with aortic regurgitation. At rest, the coronary sinus blood flow was two to three times normal. However, when corrected for left ventricular mass (ml/100 g), flow was within normal limits. The ratio diastolic pressure-time index/systolic pressure-time index (DPTI/SPTI) was decreased in all three groups at rest. During isometric exercise, coronary sinus blood flow increased significantly: by 60 percent in Group I, by 88 percent in Group II and by 118 percent in Group III. There was a significant reduction of the DPTI/SPTI ratio. Of the 18 patients with angina on effort during the test, 7 were in Group I, 6 in Group II and 5 in Group III. There were no differences in the coronary sinus blood flow between the patients with angina and those who were pain-free, either at rest or during exercise. Angina pectoris does not appear to be caused by a failure of coronary blood flow to increase. There was no discrepancy between myocardial demand, as measured by the pressure-time index and coronary blood flow. However, the DPTI/SPTI ratio was significantly lower during exercise in the patients with angina than in those who were pain-free. Underperfusion of the subendocardial muscle seems to be a causative factor in the patients with angina.

[Pharmacologic importance of the combination atenolol/nifedipine in hypertensive patients]. / Intérêts pharmacologiques de l'association aténolol/nifédipine chez les patients hypertendus.

When used as first-line treatment, any monotherapy selected from one of the main classes of agents for the management of slight to moderate arterial hypertension cannot be expected to have a success rate exceeding 60%. However, this level of efficacy approaches 80% if two classes of antihypertensive drugs with complementary modes of action are combined--a notable example being the combination of a beta-blocker, atenolol 50 mg, and a calcium antagonist, sustained-release nifedipine 20 mg. This fixed combination provides efficacy and tolerability in the treatment of arterial hypertension. Atenolol has beta-adrenolytic properties similar to those of propranolol, the most commonly named comparator drug. Atenolol is a selective beta 1-adrenergic antagonist with negative chronotropic, bathmotropic, dromotropic and inotropic actions. Because of its selectivity, it induces only moderate vasoconstriction. Its cardioselective nature diminishes the risk of bronchospasm, an event commonly induced by this type of drug. Atenolol reduces renin secretion from the renin-angiotensin system and consequently decreases the production of angiotensin II and plasma aldosterone. The renal effects of atenolol are an increase in both diuresis and natriuresis, with a reduction in the renal plasma flow. beta-Adrenergic antagonists in general modify carbohydrate metabolism and may mask the precursor signs of hypoglycaemia. They have a negligible effect upon lipid metabolism and practically no effect on total or high density lipoprotein cholesterol levels. Nifedipine belongs to the class of dihydropyridines. It acts by blocking the influx of calcium ions through the slow channels. Although a potent vasodilating agent, nifedipine does not induce tachycardia or water-sodium retention. The negative inotropic effect observed in vitro has not been reported in humans; the coronary dilatation produced by nifedipine is indisputable, both in unstable angina and exertional or exercise-induced angina. However, its cardioprotective effect remains questionable outside the context of recent-onset atheromatous plaques. Nifedipine increases renal blood flow and is practically devoid of diabetes-inducing factors. The fixed combination of atenolol 50 mg and sustained release nifedipine 20 mg offers a particularly interesting complementary action, the beta-blocker reducing the dihydropyridine-induced activation of the sympathetic nervous system and the latter reducing the vasoconstriction induced by the beta-blocker. Compared with each agent used alone, the pharmacokinetic profiles of atenolol and nifedipine remain unmodified by their administration in the fixed combination.

Electronic pill-boxes in the evaluation of antihypertensive treatment compliance: comparison of once daily versus twice daily regimen.

The objective was to compare the compliance of hypertensive patients treated with captopril twice daily or trandolapril once daily. After a 2-week placebo period, hypertensive patients (diastolic BP 95-115 mm Hg) were randomly allocated to trandolapril 2 mg once daily or to captopril 25 mg twice daily for 6 months. Trandolapril and captopril were packed in electronic pill-boxes equipped with a microprocessor that recorded date and time of each opening (MEMS). Patients' compliance was assessed both by standard pill-count and by electronic monitoring. Blood pressure was measured using a validated semi-automatic device at the end of the placebo period and of the treatment period. One hundred sixty-two patients entered the study. Compliance data were evaluable for 133 patients (62 in the captopril group and 71 in the trandolapril group). Treatment groups were comparable at baseline except for age (P = .046). Using electronic pill-box, overall compliance was 98.9% in the trandolapril group and 97.5% in the captopril group (P = .002). The percentage of missed doses was 2.6% in the trandolapril group and 3.3% in the captopril group (P = .06). The percentage of delayed doses was 1.8% in the trandolapril group and 11.7% in the captopril group (P = .0001). The percentage of correct dosing periods, ie, a period with only one correct recorded opening, was 94.0% in the trandolapril group and 78.1% in the captopril group (P = .0001). Results were unchanged when adjusted for age. At the end of the study, 41% of patients in the trandolapril group and 27% in the captopril group (NS) had their blood pressure normalized (systolic BP <140 and diastolic BP <90 mm Hg). In this 6-month study, the electronic pill-box allowed refined analysis of compliance of hypertensive patients. Patients' compliance with once daily trandolapril was higher than with twice daily captopril. The between-group difference is mainly explained by an increase in delayed doses in the twice daily group.

Compliance and antihypertensive efficacy of amlodipine compared with nifedipine slow-release.

Poor compliance is a principal cause of treatment failure in hypertensive patients. Once-daily dosing improves compliance, but 24-h antihypertensive activity should be provided. The compliance, efficacy, and safety of amlodipine and nifedipine slow-release (SR) were compared in patients with mild-to-moderate essential hypertension recruited among 24 centers in France. After a 2-week washout period, 103 patients were randomized to 12 weeks of 5 to 10 amlodipine mg once daily (n = 55) or 20 mg nifedipine SR twice daily (n = 48). Compliance was calculated by electronic drug monitoring. Efficacy was measured by ambulatory and casual BP recordings. Patients receiving amlodipine demonstrated better compliance than patients receiving nifedipine SR with respect to compliance index (the total number of doses taken divided by the total number of doses prescribed, expressed as a percentage; 98.3% v 87%; P < .0001), days on which the correct number of doses were taken (92.5% v 74.8%; P < .0001), and prescribed doses taken on schedule (88.7% v 71.6%; P < .0001). Absolute and relative therapeutic coverage were higher in patients receiving amlodipine than nifedipine SR (P < .0001). Mean SBP and DBP decreased equally in both groups, although amlodipine offered better BP control compared with nifedipine SR at specific times of day. Fewer patients had high nocturnal SBP with amlodipine (39.3%) than nifedipine SR (71.4%; P = .042). Adverse events and treatment withdrawals occurred less frequently in amlodipine-treated patients than in nifedipine SR-treated patients. Amlodipine (5 to 10 mg) once daily provides improved compliance, better 24-h BP control, and fewer adverse events than 20 mg nifedipine SR twice daily in patients with mild-to-moderate hypertension.