Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series.

BACKGROUND: Development of inhibitors is the most serious complication in haemophilia A treatment. The assessment of risk for inhibitor formation in new or modified factor concentrates is traditionally performed in previously treated patients (PTPs). However, evidence on risk factors for and natural history of inhibitors has been generated mostly in previously untreated patients (PUPs). The purpose of this study was to examine cases of de novo inhibitors in PTPs reported in the scientific literature and to the EUropean HAemophilia Safety Surveillance (EUHASS) programme, and explore determinants and course of inhibitor development. METHODS: We used a case series study design and developed a case report form to collect patient level data; including detection, inhibitor course, treatment, factor VIII products used and events that may trigger inhibitor development (surgery, vaccination, immune disorders, malignancy, product switch). RESULTS: We identified 19 publications that reported 38 inhibitor cases and 45 cases from 31 EUHASS centres. Individual patient data were collected for 55/83 (66%) inhibitor cases out of 12 330 patients. The median (range) peak inhibitor titre was 4.4 (0.5-135.0), the proportion of transient inhibitors was 33% and only two cases of 12 undergoing immune tolerance induction failed this treatment. In the two months before inhibitor development, surgery was reported in nine (22%) cases, and high intensity treatment periods reported in seven (17%) cases. CONCLUSIONS: By studying the largest cohort of inhibitor development in PTPs assembled to date, we showed that inhibitor development in PTPs, is on average, a milder event than in PUPs.

The triad psoriasis-obesity-adipokine profile.

Psoriasis is a chronic inflammatory skin disease, often associated with overweight/obesity. The adipose tissue is a complex organ that secretes several adipokines, involved in the regulation of some metabolic processes, such as lipid metabolism, glucose homeostasis, angiogenesis, blood pressure and inflammation. In obesity, the distribution and function of adipose tissue, and the adipokine profile are altered. The unbalanced production of pro- and anti-inflammatory adipokines in obesity, contributes to the development of a chronic low-grade inflammation state, which seems to favour worsening of psoriasis lesion and a poorer response to treatment. In this review, we will debate published data concerning the current knowledge about the triad psoriasis-obesity-adipokine profile.

Circulating cell-free DNA levels in Portuguese patients with psoriasis vulgaris according to severity and therapy.

BACKGROUND: Inflammation has a key role in the pathogenesis of psoriasis. Circulating cell-free DNA (CFD) is a marker of tissue cell damage closely associated with inflammation. OBJECTIVES: We aimed to understand the relation of CFD levels with psoriasis severity, defined by the Psoriasis Area and Severity Index (PASI), with inflammation and with psoriasis therapy. METHODS: Forty-six patients with psoriasis vulgaris were evaluated before (T0) and after 12 weeks (T12) of treatment with narrowband ultraviolet light B (NB-UVB; n = 17), psoralen plus UVA (PUVA; n = 20) or topical therapy (n = 9). We evaluated interleukin (IL)-6 and circulating CFD levels. RESULTS: Compared with controls, at T0, patients presented significantly higher levels of circulating CFD. CFD presented a significant positive correlation with IL-6 and a trend towards a positive correlation with PASI. Multiple linear regression analysis identified IL-6 as an independent variable associated with CFD circulating levels. As shown by the PASI score, a trend towards higher values of CFD was observed in the severe psoriasis forms; moderate and severe psoriasis presented also significantly higher CFD values, compared with control. Both NB-UVB and PUVA treatments significantly decreased the levels of CFD. CONCLUSIONS: Patients with psoriasis, at the active stage of the disease, presented an increased inflammation associated with raised circulating CFD levels, which seem to be linked to psoriasis severity. Both NB-UVB and PUVA, anti-inflammatory therapies, were effective in decreasing CFD values. We propose that the evaluation of circulating CFD may provide a new biomarker to monitor psoriasis, its severity and its treatment.

Microfluidic-based skin-on-chip systems for safety assessment of nanomaterials.

The skin is the body's largest organ, continuously exposed to and affected by natural and anthropogenic nanomaterials (materials with external and internal dimensions in the nanoscale range). This broad spectrum of insults gives rise to irreversible health effects (from skin corrosion to cancer). Organ-on-chip systems can recapitulate skin physiology with high fidelity and potentially revolutionize the safety assessment of nanomaterials. Here, we review current advances in skin-on-chip models and their potential to elucidate biological mechanisms. Further, strategies are discussed to recapitulate skin physiology on-chip, improving control over nanomaterials exposure and transport across cells. Finally, we highlight future opportunities and challenges from design and fabrication to acceptance by regulatory bodies and industry.

Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors.

BACKGROUND AND PURPOSE: Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. MATERIALS AND METHODS: In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. RESULTS: Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. CONCLUSIONS: Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles.

Cardiac rupture during exercise stress echocardiography: a case report.

Stress echocardiography is widely used in the evaluation of coronary artery disease. Dobutamine stress echocardiography has been the preferred method, but many centers have adopted exercise stress echocardiography, which can visualize myocardial motion during physiologic stress testing. The complications of this method in the post-myocardial infarction period are the same as those identified in conventional exercise testing. We report a case of myocardial rupture in the postinfarction period during exercise stress echocardiography.

Idiopathic hypereosinophilic syndrome presenting as cholestatic liver disease.

We report the case of a 34-year-old white man with recurrent episodes of abdominal pain, cholestasis and eosinophilia. The diagnosis of idiopathic hypereosinophilic syndrome (IHS) was made after exclusion of all known causes of eosinophilia. Liver biopsy revealed an eosinophilic infiltrate with biliary damage. The patient recovered after prednisolone treatment. We review the literature on the association between IHS and liver disease.

[The mechanism producing nausea during ventriculography performed with ioxaglate: the implications of a randomized study]. / Mecanismo de producción de las náuseas durante la ventriculografía realizada con ioxaglato: implicaciones de un estudio randomizado.

INTRODUCTION: The mechanism of ioxaglate-induced nausea has not been fully elucidated. Recent studies have demonstrated that serotonin is one of the principal neurotransmitters of emesis in humans. On the other hand, the greater capacity of ioxaglate to stimulate vomiting has been ascribed to its great ability to inhibit cholinesterase. METHODS: To determine if oral metoclopramide (a serotonin receptor-blocker) is effective in the prophylaxis of ioxaglate-induced nausea during left ventriculography, 637 of 711 consecutive eligible patients were included in a prospective study. Patients were randomized to receive, 60-90 minutes before the procedure, either diazepam 10 mg p.o. (control group [n = 315]) or diazepam 10 mg p.o. plus metoclopramide 10 mg p.o. (metoclopramide group [n = 322]). RESULTS: The two randomized groups were similar in relation to baseline clinical and hemodynamic characteristics. Nausea was documented in 103 patients (16.1%) with similar incidence in the two groups (control group: 16.8%, metoclopramide group: 15.5%; p = NS). Nausea duration was also similar (56 +/- 63 s vs 52 +/- 63 s; p = NS). When patients with and without nausea were compared, the following variables showed a significant difference between the two groups: male gender (86% vs 76%; p < 0.05), age (53 +/- 10 yrs vs 56 +/- 9 yrs; p < 0.05) and body surface area (1.84 +/- 0.2 m2 vs 1.78 +/- 0.1 m2; p < 0.01). Stepwise multiple regression analysis identified low age (p = 0.02) and male gender (p = 0.06) as independent predictors of nausea. The incidence of nausea was 24% in males < or = 45 yrs vs 9% in females > 45 yrs (p < 0.05). CONCLUSIONS: Prophylaxis with oral metoclopramide did not reduce the incidence of ioxaglate-induced nausea during left ventriculography. This data do not support a role of serotonin in the production of nausea by ioxaglate. Low age an male gender are independent predictors of nausea apparition during left ventriculography. A cholinergic mechanism is probably involved in the capacity of ioxaglate to stimulate vomiting.

[Residual myocardial function in dilated myocardiopathy. Response to post-extrasystolic potentiation]. / Função miocárdica residual na miocardiopatia dilatada. Resposta à potencição pós-extra-sistólica.

OBJECTIVE: to evaluate the effectiveness of post-extrasystolic potentiation (PESP) to detect latent residual contraction function in patients (pts) with idiopathic dilated cardiomyopathy. DESIGN: retrospective study in pts referred for cardiac catheterization. SETTING: Haemodynamic Laboratory of Cardiology Service, Bellvitge Hospital. Barcelona, Spain. PATIENTS: the criteria for including pts with sinus rhythm were (SR): 1-The appearance of an extra beat R' on the ventriculogram; 2-The location of R' in relation to the preceding sinus beat R1 and the following beat R2 being such that R1-R' less than R'-R2. In patients with atrial fibrillation (AF), the criteria were: 1-An early beat Re had to be identified; 2-R1-Re interval had to be at most half of the Re-R2 interval; 3-The length of the cardiac cycle preceding R, has to be equal to the mean cycle length. All the patients with an increase of the ejection fraction (EF) from R, to R2 less than 12% were included in group A: 12 patients (3 females, 9 males, mean age 51 years, 5 SR, FE 27 +/- 10%). In group B were included patients with an increase of the ejection fraction greater than or equal to 12%; 14 patients (4 females, 10 males, mean age 50 years, 7 SR, FE = 31 +/- 7%). MEASUREMENTS: In each ventriculogram we assessed the performance of left ventricle on R1 and R2 beats by determining: 1-Left ventricular end diastolic (EDV), end systolic (ESV), stroke (SV) volumes; 2-Volumes index (EDVI), (ESVI) (SVI); 3 - Ejection fraction (EF) - Change in ventricular contractility from R1 to R2, delta EF. RESULTS: in the sinus rhythm group the values of R1 and R2 were respectively: EDV: (184 +/- 48 ml/m2; 191 +/- 17 ml/m2; NS); SVI (53 +/- 19 ml/m2; 80 +/- 22 ml/m2; p less than 0.01) FE (29 +/- 7%; 42 +/- 10%; p less than 0.01), delta EF 13 +/- 6%. The change of the ejection fraction from R1 to R2 in pts with SR and AF were respectively: 13 +/- 6% and 11.5 +/- 6.4%; NS. Group A: Deterioration of the functional class and two deaths occurred. Group B: Improvement in functional class in all cases but one. CONCLUSION: our data suggest that augmented ventricular filling and consequent Starling's effect is not a significant contribute for PESP in pts with dilated cardiomyopathy. The analysis of post extrasystolic beat in SR pts and the beat following an early beat with a long diastole in AF, is a valuable method of determining the residual left ventricular function in this group of pts.

[Direct coronary angioplasty versus thrombolysis in the acute phase of myocardial infarction--inpatient outcome]. / Angioplastia coronária directa versus trombólise na fase aguda do enfarte do miocárdio--evolução intra-hospitalar.

Both thrombolysis and percutaneous transluminal coronary angioplasty (PTCA) are effective methods for the treatment of acute myocardial infarction (AMI). In our centre we perform primary PTCA during the available schedule of the hemodynamics laboratory. In this article we compare the predischarge evolution of patients submitted to each therapeutic procedure. From January 1996 to June 1997, 298 patients were admitted with the diagnosis of AMI. Eighty-four patients (28%) were thrombolysed (TB group) and 30 patients (10%) underwent primary PTCA (PTCA group). There were no significant differences among the two groups concerning demographic characteristics: age (61 +/- 13--TB and 59 +/- 12 years--PTCA); sex (male 81%--TB; 83%--PTCA), risk factors and previous cardiac history. The mean time since the onset of symptoms until arrival at the hospital was 156 +/- 156 minutes for TB and 202 +/- 210 minutes for PTCA (p < 0.02). The delay since admission until the beginning of treatment was 100 +/- 88 minutes for TB and 119 +/- 142 minutes for PTCA. The primary success rate of PTCA was 94% and there were no complications during the procedure. During the hospital stay, 12 patients developed post-infarction angina in the TB group and two patients in the PTCA group; in 15 patients of the TB group a revascularization procedure was performed (surgery in 5 and PTCA in 10 patients); one patient suffered reinfarction in the TB group. Two patients of the TB group (2.4%) had intracranial hemorrhage; the in-hospital mortality was 9.5% in the TB group and 3.3% in the PTCA (p < 0.001). The mean in-hospital stay was 11 +/- 5.6 in the TB group and 7.8 +/- 2.5 days in the PTCA group (p = 0.055). In our experience, primary PTCA in AMI appeared to be a safe procedure with lower occurrence of coronary events and hemorrhagic complication, with an earlier hospital discharge when compared to thrombolysis.

[Myocardial ischemia caused by anomaly at the origin of the left coronary artery]. / Isquémia do miocárdio por anomalia na origem da artéria coronária esquerda.

The case of a 68 years old man admitted because of angina "de novo" and submitted to coronariography is reported. The rest ECG showed abnormalities of the ST-T suggesting myocardial ischemia. The coronariography showed: No significant atherosclerotic lesions. The left coronary artery had an anomalous origin; the left descending coronary artery originated from an independent ostium located at the right Valsalva sinus, the circumflex artery had its origin at the same ostium as the right coronary artery.

[Pulmonary stenosis in adults. Report of a clinical case]. / Estenose pulmonar no adulto. A propósito de um caso clínico.

The authors report a case of valvular pulmonary stenosis in a 60 years old patient, admitted to hospital with heart failure and angor pectoris. Four years previously a VVI pacemaker had been implanted for complete heart block. At the time of the admission he had two pacemakers leads in the right ventricle; one of them was retained and functionless since the changing of the generator which occurred 1 year before. The usual complications of endocardial pacemakers are discussed, as well as the natural course and surgery indications for valvular pulmonary stenosis in adults.

[Atrial fibrillation and coronary disease]. / Fibrilhação auricular e doença das coronárias.

OBJECTIVE: To study the incidence of atrial fibrillation in patients (pts) with angiographic coronary artery disease and its relation with clinical and angiographic parameters. DESIGN: Retrospective study. SETTING: Six hundreds consecutive pts, submitted to diagnostic coronary angiography, performed in Hemodynamic Laboratory of Santa Marta Hospital (from 88/04/03 to 90/05/04). MATERIAL AND METHODS: From six hundreds pts were excluded 43 because they had also valvular heart disease and/or minimal coronary artery lesions. Two groups were considered: Group I-pts with atrial fibrillation (n = 7) and Group II-pts in sinus rhythm (n = 549). We evaluated the following parameters: age, sex, clinical history, basal ECG, cardiac enlargement in chest X-ray, angiographic score of LVF, left ventricular diastolic pressure (LVDP), ventricular aneurysm, mitral regurgitation and number of vessels disease. RESULTS: We only found significant statistically differences between the two groups concerning the following parameters: a) age-mean age was superior in group I (Group I-64.2 +/- 8.2 versus 56.3 +/- 9.6), the number of pts older than 60 years in group I was 75% vs 33.8% in group II (p < 0.02); b) heart failure-the incidence was superior in group I, 37.5% vs 9% in group II (p < 0.03); c) cardiac enlargement in chest X-ray-75% pts of group I vs 22% of group II (p < 0.002); d) moderate to severe mitral regurgitation-25% of pts in group I vs 5% of pts of group II (p < 0.05). CONCLUSIONS: Atrial fibrillation is an unusual rhythm in pts with angiographic coronary artery disease. Its presence is related with age, clinical evidence of heart failure, cardiac enlargement and moderate to severe mitral regurgitation.

[Ebstein's anomaly. Clinical aspects and surgical therapy]. / Anomalia de Ebstein. Clínica e terapêutica cirúrgica.

OBJECTIVE: We reviewed the clinical findings and surgical results of Ebstein's anomaly in adult and adolescent age. DESIGN: Retrospective analysis on clinical data, surgery and follow up. SETTING: Patients (pts) studied in the Cardiology and Cardiothoracic Surgery Departments of the Santa Marta Hospital, Lisbon. PATIENTS: All pts in whom Ebstein's anomaly was diagnosed by cardiac catheterization or echocardiography or both, between 1875 and 1989 were included. RESULTS: There were 8 cases (4 female and 4 male). The age varied from 15 and 53 years. Cyanosis and dyspnoea were the presenting features in 7 pts. One of the youngest pts had asymptomatic murmurs. Late appearance of cyanosis had no relation with prognosis. Three pts had pulmonary tuberculosis. One woman had no deterioration in cardiac function during two pregnancies. Clinical findings were variable and ranged from absent murmur with third and fourth sounds to systolic murmurs of high intensity. The ECG was abnormal in all pts. A case with delta wave and normal PQ interval was noted. On the chest X-ray we found cardiomegaly in all pts. Echocardiograms were recorded in 6 pts. The delay of tricuspid valve closure on mitral closure was not always diagnostic. Uncomplicated catheter studies were done in 6 pts. Two pts had associated cardiac lesions: ventricular septal defect (VSD) with pulmonary hypertension and mild pulmonary valve stenosis. Right ventricular angiographies were diagnostic in all cases. During medical follow up from 1 year to 10 years (mean-4) one death occurred in one pt with VSD. In the remaining 4 cases no deterioration in cardiac function or cyanosis was noted. Three pts were operated. The indications for surgery were: severe heart failure and/or increasing cyanosis. Two pts had tricuspid valve replacement with biological prosthesis. One pts had Danielson's tricuspid annuloplasty. During surgical follow up from 2 to 15 years (mean-7) functional class improved and cyanosis disappeared in 2 pts and it decreased in the other. CONCLUSION: In our series of pts with Ebstein's anomaly clinical findings were variable. The indications for surgery were heart failure and cyanosis. The 3 pts operated are alive and have mild symptoms.

Incidence, characteristics and coronariographic significance of myocardial ischemia during daily life in patients with angina pectoris.

OBJECTIVES: To evaluate the incidence, characteristics and angiographic significance of myocardial ischemia detected on Holter monitoring in a group of patients with stable angina pectoris. SETTING: Department of Cardiology of a Central Terciary Hospital. METHODS: In 24 patients (pts) with stable angina pectoris and proven coronary artery disease (11 pts with left main or three vessel disease; 13 pts with one or two vessel disease), a 24 hour Holter monitoring was performed. Two groups of ischemic episodes were considered: Group I with 65 ischemic episodes detected in pts with left main or three vessel disease and group II constituted by 17 ischemic episodes detected in pts with one or two vessel disease. RESULTS: The incidence of myocardial ischemia was 91% in pts with left main or three vessel disease and 46% in pts with one or two vessel disease. Statistically significant differences were seen between group I and II concerning the mean heart rate variation from two minutes before onset of ST-segment depression to its onset (3.5 bpm vs 7.4 bpm; p less than 0.05) and from the onset of ST-segment depression to its maximal depression (6.5 bpm vs 15 bpm; p less than 0.000001). CONCLUSIONS: The presence of myocardial ischemia and some of its characteristics on Holter monitoring seem to have a relation with the severity of coronary artery disease in patients with stable angina pectoris.

[Arrhythmic profiles evaluated by Holter's technique in sick sinus syndrome]. / Perfis arrítmicos avaliados por método de Holter na doença do nódulo sinusal.

OBJECTIVES: The aim of this study was to evaluate in a group of patients with sick sinus syndrome: 1) Characteristics of arrhythmia on Holter monitoring. 2) Value of Holter monitoring to select patients for pacemaker implantation. SETTING: Department of Cardiology in a Central Hospital. METHODS: In 40 patients (27 men and 13 women, aged 37 to 83 years) Holter monitoring during a 24-hour period was performed. According to the arrhythmia profiles four groups of patients were considered: group A--with severe sinus bradycardia; group B--with sinus bradycardia associated to sinoatrial exit block or to sinus pauses; group C--characterized by the bradycardia-tachycardia syndrome and group D--defined by the finding of atrial fibrillation with a slow ventricular response. Symptoms and the presence of structural heart disease were evaluated. RESULTS: In this patients population, 24 patients had coronary artery disease and/or hypertensive heart disease. A severe sinus bradycardia was found in 14 patients (group A) and in other 11 patients it was accompanied by sinoatrial exist block of sinus pauses (group B); 12 patients had the bradycardia-tachycardia syndrome (group C) and periods of atrial fibrillation with a slow ventricular response were found in 3 other patients (Group D). Nonspecific clinical pattern was observed in this population. CONCLUSIONS: Holter monitoring was important to the diagnosis of sick sinus syndrome and for posterior definitive pacemaker implantation. Coronary artery disease and/or hypertensive heart disease were the main pathologies found in this study, being the severe sinus bradycardia and the bradycardia-tachycardia syndrome the principal manifestations of the sick sinus syndrome.

[Acute myocardial infarct: the prognostic significance of complex coronary lesions]. / Enfarte agudo do miocárdio: significado prognóstico das lesões coronárias complexas.

OBJECTIVE: The aim of our study was to analyze the possible influence of coronary lesion morphology on the prognosis of patients (pts) with Acute Myocardial Infarction (AMI) evaluated by coronary angiography before hospital discharge. DESIGN: Retrospective study. SETTING: Study performed at the Cardiology Department of a Central Hospital. MATERIAL AND METHODS: 141 consecutive pts admitted because of AMI were evaluated, with an age average of 53.4 +/- 9.6 years, who had hospital discharge. All pts were submitted to angiography between the 2nd and 3rd week after AMI. The ventriculography was evaluated to determine the ventricular function score, as defined by the CASS protocol. The coronarography was performed to access the number of diseased vessels and to analyze their lesion morphology. Complexity was defined by the presence of one of the following characteristics: irregularity, shoulder, ulcers, filling defects, contrast retention and ecstasy. TWO GROUPS OF PTS WERE CONSIDERED: Group I--n = 64 pts, with complex lesions, and Group II--n = 69 pts with non complex lesions. Seven pts were excluded from the study because they had no significant coronary disease. Mean time of the follow up was 21.4 +/- 8.5 months and was similar in the two groups. The cardiac events considered were angina after AMI; reinfarction; heart failure; new hospital admission, percutaneous transluminal coronary angioplasty; coronary artery bypass grafting and death. RESULTS: In relation to both groups no statistically significant difference was found concerning sex, age, left ventricular function score and number of diseased vessels. In group I a higher incidence was found for cardiac events (p 0.006) and for the occurrence of angina after AMI (p < 0.02). In this group the number of pts with cardiac events was also higher (p < 0.01). No difference was found in relation to each of the morphologic characteristics and a high risk profile could not be found. CONCLUSIONS: Besides left ventricular function and the number of diseased vessels, the analysis of coronary lesion morphology, evaluated 2 to 3 weeks after AMI, could be useful in risk stratification after AMI.

Effects of diltiazem on myocardial ischemia in patients with coronary artery disease.

OBJECTIVES: To evaluate the effect of diltiazem on the characteristics of ischemic episodes detected by Holter monitoring in a group of patients with proven coronary artery disease. SETTING: Department of Cardiology, Santa Marta Hospital, Lisbon. METHODS: Eleven selected out-patients, aged 48 to 79 years, with transient ST-segmental depression on Holter monitoring and proven coronary artery disease, were submitted to a double-blind crossover placebo controlled study, during hospitalization. The total ischemic burden of each patient and an analysis of ischemic episodes were evaluated before and during the drug/placebo phase trial. Three groups of ischemic episodes were considered: group I constituted by 66 episodes found on basal Holter recording; group II by 28 episodes detected during placebo trial and group III by 12 episodes detected during diltiazem trial. RESULTS: A reduction of the number of ischemic episodes was predominantly observed with the diltiazem administration. Statistically significant differences were observed between basal and placebo groups and especially between basal and diltiazem groups concerning the mean maximum ST-segment depression (2.17 vs 1.80; p = 0.030 and 2.17 vs 1.54; p = 0.0091). Significant differences were also obtained between the above mentioned groups concerning the heart rate variation from the onset of ST-segment depression to its maximum depression (13.5 vs 9.69; p = 0.023 and 13.5 vs 2.91; p = 0.01) and from two minutes before the onset of ST-segment depression to its maximum depression (21.2 vs 12.67; p = 0.012 and 21.2 vs 8.75 p = 0.016). CONCLUSIONS: Diltiazem seems to reduce the number of ischemic episodes in patients with coronary artery disease, during hospitalization. The study of its effects on the characteristics of ischemia requires further investigation with a greater number of patients. The limitations of the present study, described in the discussion, must be taken into account in future pharmacological investigations with Holter monitoring.