Cardiomyopathy in Friedreich's ataxia: a Doppler-echocardiographic study. Heart involvement is frequent in Friedreich's ataxia (FA), the most prevalent of the spino-cerebellar degenerative diseases, which is inherited with an autosomal recessive pattern. However, the pathophysiological link between cardiac and neurological disorders is not yet clearly established. We compared a group of 10 patients with FA to a control group (C) of 16 normal subjects, using Doppler-echocardiography. To see whether cardiac involvement was specific to FA, the data of patients with FA were also compared to those of patients with autosomal dominant olivo-ponto-cerebellar atrophia (OPCA), another spino-cerebellar degenerative disease. There was an increase in left ventricular mass index in FA (154 +/- 9 g.m-2 vs 99 +/- 7 g. m-2 in C, P < 0.001), systolic function was normal, the ejection fraction (EF) slope and E/A ratio were decreased (85 +/- 9 mm.s-1 vs 130 +/- 7 mm.s-1 in C, P < 0.001 and 1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.01, respectively), while the isovolumic relaxation period was increased (96 +/- 3 ms vs 92 +/- 2 ms in C, P < 0.01). Deceleration time and time-velocity integrals of A wave to total mitral flow were not modified. In OPCA only the E/A ratio was decreased (1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.05). These data show the presence of cardiomyopathy in FA with left ventricular hypertrophy and suggest the presence of diastolic function abnormalities. The cardiomyopathy seems specifically associated with FA and not to spino-cerebellar degenerative disease in general.


Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise. The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.


Lp(a) levels in patients undergoing aorto-coronary bypass surgery. The aims of this study were to evaluate plasma lipid, apoprotein and Lp(a) levels in patients with severe coronary atherosclerosis undergoing aorto-coronary bypass surgery (BP) and to relate these parameters to the involvement of one or more vessels. Seventy-seven male patients and 77 cardiovascular disease-free controls, matched for sex, age and body weight were studied. Higher triglyceride and apo B levels with lower HDL-cholesterol and apo A-I levels were found in BP patients in comparison with the controls. Lp(a) levels were slightly, but not significantly, increased. Moreover BP patients presented a significantly higher prevalence of HDL-cholesterol levels below 35 mg dl-1 (49.3% vs 22.1%) and Lp(a) levels above 70 mg dl-1 (10.4% vs 1.3%) than the controls. When patients were divided according to the number of coronary vessels involved (one, two or three), no significant difference was found, with a trend to increase in Lp(a) mean levels and in prevalence of Lp(a) levels above 30 and 70 mg dl-1 in more severely diseased patients. These results suggest that patients with severe coronary artery disease undergoing aorto-coronary bypass surgery show low HDL-cholesterol levels with high triglyceride levels. Moreover Lp(a) levels above 70 mg dl-1 are highly associated with severe coronary vessel stenosis.


Atrial automatic tachycardia in infancy and childhood. Twenty-one cases (13 male, eight female) of atrial automatic tachycardia (AAT) assessed by standard and Holter-ECG in otherwise healthy infants and children have been documented. AAT was incessant in 12 patients, repetitive in seven, and of undetermined type in the remaining two. The frontal P wave axis suggested an ectopic focus in the high right atrium or right atrial appendage in 13 patients, in the low right atrium in one patient, and in the left atrium in seven patients. Thirteen out of 14 patients with the incessant or undetermined type of AAT were symptomatic, in contrast to only two of seven patients with the repetitive type. All patients were treated with between one and eight (median three) antiarrhythmic drugs. The most effective drug was amiodarone, followed by the class I C antiarrhythmic drugs, propafenone and flecainide. At present, all patients are alive 4 months to 21 years (median 2.5 years) after diagnosis of AAT. Twelve patients are in sinus rhythm, five of them without any medication. Nine patients still have AAT, which, however, is repetitive or intermittent in all but one. In conclusion, AAT is an unusual, and in its incessant form often severely symptomatic arrhythmia, which is resistant to conventional antiarrhythmic medication. However, amiodarone and class I C antiarrhythmic drugs are frequently effective. Since medical treatment with these drugs is often successful, and AAT may resolve completely, a conservative approach is indicated in many cases.


Prolonged cardiac arrest and complete AV block during upright tilt test in young patients with syncope of unknown origin--prognostic and therapeutic implications. The purpose of this study was to define the history and prognosis of 12 patients (8 males, 4 females) with syncope of unknown origin (5 to 15 episodes), who developed prolonged asystole or complete AV block during the upright tilt test (UTT). The mean age (+/- SD) of the patients was 29 +/- 7.4 years, and all had normal neurological and cardiological findings on evaluation. These patients were selected from a larger group of 92 cases with positive UTT out of a total of 136 subjects who were referred for recurrence of syncope. Neither clinical nor autonomic nervous system evaluation distinguished these 12 patients from those with positive UTT. Following UTT, therapy was initiated and consisted of transdermal scopolamine in four, disopyramide in two, and beta-blockers in four patients. During follow-up (mean, 17 +/- 5.4 months), four patients had recurrences but none experienced episodes of life-threatening syncope. These patients do not show an enhanced risk of sudden death, and drug therapy seems to improve their clinical course. Only long-term follow-up would correctly identify a subgroup at higher risk.


Chlamydial endocarditis: a report on ten cases. Over the period 1983-1990, 10 cases of infective native-valve endocarditis as a result of Chlamydia were seen. All patients were men, with a mean age of 42 years, and none had a history of exposure to Chlamydia psittaci. Symptoms, such as weight loss and anorexia, with fever in eight cases, had persisted for at least 2 months before admission. Haemodynamic failure was present in seven patients, and neurological signs in four. The aortic valve was involved in seven cases, the mitral valve in one and both valves in two. Vegetations, often fingerlike, were observed by echocardiography in nine cases. All patients required valve replacement, and three died in the year following diagnosis. Blood cultures were consistently negative in all cases, and no antibiotics had been given before admission. Significant titres of complement fixing anti-chlamydial antibodies were present in six cases, and micro-immunofluorescence using the three chlamydial species showed cross-reacting antibodies in all nine cases studied, with transient IgM positivity in six cases. Histologically, the leaflets were fibrosed and infiltrated by large macrophages containing dark red granules after Machiavello staining. These granules were specifically stained by immunofluorescence using monoclonal antibody to Chlamydia common antigen, but not by that specific for C. pneumoniae. No organisms were seen after Gram staining, and no positive chlamydial immunofluorescence was seen on sections of valves from patients with staphylococcal or streptococcal endocarditis.


The significance of myocardial ischaemia and verapamil treatment on the prevalence of supraventricular tachyarrhythmias in patients recovering from acute myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction. Twenty-four hour Holter monitoring and symptom-limited exercise testing were carried out prior to discharge in 157 patients recovering from acute myocardial infarction. Supraventricular arrhythmias (SVT) during Holter monitoring were recorded in 15%, and ST segment depression during exercise in 27%. No association between exercise-provoked ischaemia and SVT was found in the late hospital phase of myocardial infarction. After the tests, patients were double-blindly randomized to treatment with verapamil 120 mg t.i.d. or placebo. One month after randomization 24 h Holter monitoring was repeated in 125 patients (verapamil = 63, placebo = 62). At one month a significantly increased incidence of SVT was found in the placebo group (25%) compared to the verapamil-treated patients (9%) (P = 0.04). The increased prevalence in the placebo group was mainly due to an increased incidence of SVT in patients with exercise-induced ischaemia (P = 0.03). This increment was blurred in the verapamil group. In conclusion, the prevalence of SVT increases during the first month after myocardial infarction. The increase is most pronounced in patients with residual myocardial ischaemia and seemed to be prevented by treatment with verapamil.


Oxidative metabolism and myocardial blood flow changes after transthoracic DC countershocks in dogs. Changes in oxidative metabolism and myocardial blood flow were investigated in adult greyhounds following transthoracic shocks from a DC cardiac defibrillator (400 Joules stored energy, damped sine wave, 0.5 min intervals). Myocardial lactate extraction became negative maximally at 1 min, following both two (mean -24% +/- SEM24) or five (-193% +/- 148) shocks and returned to baseline by 6-15 min. Transient reductions were also observed in myocardial extraction of pyruvate and free fatty acids but not glucose. Myocardial necrosis assessed at 4 h following the shocks was 0.05 g (+/- 0.03) after two shocks, 6.5 g (+/- 1.5) after five shocks and zero in controls. Mean peak noradrenaline levels in arterial (785 +/- 319 pg.ml-1) and coronary sinus (916 +/- 313 pg.ml-1) blood at 1 min after five shocks were higher than after 0 shocks (82 +/- 33 pg.ml-1 and 201 +/- 63 pg.ml-1 respectively), P < 0.05. Great cardiac venous blood flow was measured by a thermodilution technique, with continuous infusion of 0.9% saline, before, during and after five shocks. Mean blood flow fell from 47 +/- 13 ml.min-1 to a minimum of 36 +/- 7 ml.min-1 during shocks, and then rose to 83 +/- 17 ml.min-1 at 2 min after the fifth shock (P < 0.05). Following damaging countershocks, oxidative metabolism is depressed, in keeping with a primary disturbance of mitochondrial function. These metabolic changes are not secondary to ischaemia, since an increase in blood flow in the great cardiac vein (GCV) is observed. Vasodilatation of the coronary vascular bed must occur to account for this.


Infective right atrial thrombus: a rare complication of total parenteral nutrition in an adult. We describe a case of an infective right atrial thrombus, following total parenteral nutrition, in a 21-year-old woman undergoing a surgical procedure for long-standing chronic ulcerative colitis. She presented with high temperature and the illness did not respond to antibiotic therapy. A 2-dimensional echocardiogram showed a mobile right atrial mass that at surgery was identified as a thrombus. Thrombus cultures grew coagulase-negative Staphylococcus aureus.


High-density lipoprotein cholesterol and coronary, cardiovascular and all cause mortality among middle-aged Norwegian men and women. From 1977 to 1982 screening for cardiovascular disease was performed in three Norwegian counties. All those aged between 40 and 54 years were invited, of whom 23,690 men and 23,425 women (90%) attended. Smoking habits and previous cardiovascular disease were recorded; total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), triglycerides and blood pressure were measured. During subsequent follow-up (mean 6.8 years) 422 men and 54 women died from coronary heart disease, 514 and 114 from all cardiovascular diseases and 983 and 404 from all causes, men and women respectively. For men, mortality decreased with increasing HDL cholesterol, to a minimum of around 1.5 mmol.l-1 (58 mg.dl-1), whereafter mortality increased. This applies to coronary, cardiovascular and all causes of death, as well as to men with and without a history of disease. The association between mortality and HDL cholesterol in healthy men disappeared when total cholesterol was below 6.5 mmol.l-1 (251 mg.dl-1). The inverse association between mortality and HDL cholesterol in women was somewhat stronger than in men, both for coronary and cardiovascular diseases. The relative risks of coronary death, associated with an increase in HDL cholesterol of 0.5 mmol.l-1 (19 mg.dl-1), from the Cox proportional hazards regression, with other major cardiovascular risk factors as covariates, were 0.8 (95% confidence interval: 0.6, 1.0) and 0.8 (0.7, 1.0) for men with and without history of disease, respectively. Corresponding figures for women were 0.5 (0.3, 0.9) and 0.7 (0.4, 1.3).


The European ST-T database: standard for evaluating systems for the analysis of ST-T changes in ambulatory electrocardiography. The project for the development of the European ST-T annotated Database originated from a 'Concerted Action' on Ambulatory Monitoring, set up by the European Community in 1985. The goal was to prototype an ECG database for assessing the quality of ambulatory ECG monitoring (AECG) systems. After the 'concerted action', the development of the full database was coordinated by the Institute of Clinical Physiology of the National Research Council (CNR) in Pisa and the Thoraxcenter of Erasmus University in Rotterdam. Thirteen research groups from eight countries provided AECG tapes and annotated beat by beat the selected 2-channel records, each 2 h in duration. ST segment (ST) and T-wave (T) changes were identified and their onset, offset and peak beats annotated in addition to QRSs, beat types, rhythm and signal quality changes. In 1989, the European Society of Cardiology sponsored the remainder of the project. Recently the 90 records were completed and stored on CD-ROM. The records include 372 ST and 423 T changes. In cooperation with the Biomedical Engineering Centre of MIT (developers of the MIT-BIH arrhythmia database), the annotation scheme was revised to be consistent with both MIT-BIH and American Heart Association formats.


A possible mechanism for pacemaker-induced T-wave changes. The genesis and the significance of pacemaker-induced T-wave changes remain unclear. Changes in body surface potential mapping (BSM) were observed and compared with resting thallium-201 myocardial scintigraphy (T1-SC) findings before, during and after ventricular pacing (VP) in 10 patients with various bradyarrhythmias. All studies were performed with the patients taking no medication. In all patients, isoarea QRST maps showed a characteristic abnormal dipolar pattern with positive values distributed over the upper chest and negative values over the lower chest during VP at a physiological rate for 14 days or more. These abnormalities were preserved almost completely after pacing was terminated; and coincided with deep T-wave inversions in leads II, III, aVF and V4-6. In three patients, BSM performed before VP showed normal QRST isoarea maps with positive values distributed over the left lower chest. All patients in whom resting T1-SC was performed during chronic VP showed transient perfusion defects in the posteroinferior (seven cases) or inferolateral (one case) left ventricular wall. In three patients, T1-SC was performed before VP and showed a normal distribution. Both the pacing-induced perfusion defects and the T-wave abnormalities remained unchanged 2 h after ceasing VP, were attenuated 7 days later and disappeared within a month. These findings suggest that chronic ventricular pacing may produce myocardial ischaemia, and that it persists for a certain period after the cessation of pacing, resulting in post-pacing T-wave inversion.


Efficacy of beta-blocking agents in reducing the number of shocks in patients implanted with first-generation automatic defibrillators. The efficacy of beta-blockers was tested in 11 patients who avoided sudden death as a result of ventricular tachycardia or fibrillation due to coronary artery disease or non-ischaemic underlying heart disease, after implantation of an automatic defibrillator. Ten patients initially tolerated acebutolol despite prior class III or IV heart failure in six cases; nadolol replaced acebutolol in nine cases for long-term therapy. In these 10 patients, periods of treatment with and without beta-blocking agent were available, making possible a crossover comparison, during a follow-up lasting 31.6 +/- 17.8 months. One hundred and ten shocks were delivered: 14 were considered as probably inappropriate and ruled out, leaving the remaining 96 shocks to be analysed. The monthly rate of shocks was lower during beta-blocking treatment: 0.12 +/- 0.24 vs. 1.09 +/- 1.41 (P = 0.03). While taking beta-blockers, only four patients received shocks, compared to 10 (i.e. all cases) not administered beta-blockers (P less than 0.01). Despite the technical limitations of the study, since only a few spontaneous shocks could be documented on ECG recordings, the efficacy of beta-blockers in preventing occurrence of severe ventricular tachyarrhythmias seems likely, and deserves further investigations using new implanted devices with improved memory functions.


Prognosis of ventricular fibrillation in hospital. In a retrospective study of 520 patients with in-hospital ventricular fibrillation 421 (81%) had acute myocardial infarction (MI), 66 (13%) had ischaemic heart disease (IHD) without MI, 33 (6%) had no signs of IHD. The in-hospital mortality of these three groups was 51%, 52%, and 27%, respectively (P = 0.01). Logistic regression analysis demonstrated that heart failure and cardiogenic shock were significant risk factors for in-hospital death among patients with IHD. Among discharged patients 1 and 5 years survival was 78% and 51% for patients with MI, 63% and 25% for patients with IHD, 67% and 54% for patients without IHD. A proportional hazard model demonstrated old age, heart failure and cardiogenic shock as risk factors for long-term prognosis, while MI was associated with a reduced relative risk ratio = 0.58 of long-term mortality among patients with IHD. In conclusion, patients with known IHD suffering in-hospital VF without AMI have a very poor short- and long-term prognosis. These patients need extensive cardiac examination.


Improvement in the efficacy of exercise first-pass radionuclide angiocardiography in detecting coronary artery disease and the effect of patient age. The most widely used criterion of normality during exercise radionuclide angiocardiography (a five EF units increase in left ventricular ejection fraction from rest to exercise) has been established in young, healthy volunteers resulting in a relatively low specificity when applied to older, less fit patients or in women. In a group of 57 patients ranging in age from 22 to 79 years with a low likelihood of coronary artery disease, the age of the patient was the only independent variable predicting left ventricular ejection fraction change during exercise. The efficacy of a new age-based criterion for the diagnosis of coronary artery disease was then evaluated in 115 patients with chest pain undergoing both exercise first-pass radionuclide angiocardiography and coronary arteriography. Compared to the classic five EF unit criterion, the age-based criterion had a higher specificity (73.2% vs 34.1% P less than 0.001) without significant loss in sensitivity (85.1% vs 92.6%; P = NS).


Comparison of three methods of glomerular filtration rate measurement with and without captopril pretreatment in groups of patients with left ventricular dysfunction. Methods of glomerular filtration rate measurement by 51Cr EDTA elimination, inulin clearance and creatinine clearance were compared with and without captopril pretreatment in 10 chronic heart failure patients and in 20 patients after transmural myocardial infarction. Strong intermethod correlations were found in chronic heart failure patients (EDTA: inulin r = 0.87; EDTA: creatinine r = 0.84; inulin: creatinine r = 0.9; all P less than 0.00001). Despite this, substantial absolute differences were observed in results obtained by different techniques. In particular, creatinine clearance significantly overestimated both 51Cr EDTA (18.0 +/- 18.4 ml.min-1, mean difference +/- SD, P less than 0.001) and inulin clearance (26.8 +/- 17.0 ml.min-1, P less than 0.001). The slight reduction in 51Cr EDTA elimination on captopril versus placebo (-8.3 +/- 9.2 ml.min-1, P less than 0.05) was related to a similar treatment difference in inulin clearance (r = 0.67, p = 0.03), but changes observed by either method were unrelated to captopril-induced changes in creatinine clearance. Thus, creatinine clearance is an unsatisfactory means of assessing the effect of angiotensin converting enzyme inhibition on glomerular filtration rate in chronic heart failure. In the post-myocardial infarction group, correlations between methods were poorer (EDTA: inulin r = 0.79; EDTA: creatinine r = 0.76; inulin: creatinine r = 0.67). In this group no significant effect of captopril on glomerular filtration rate was detected by any technique. As compared to the chronic heart failure patients, the weaker relationship between techniques post-myocardial infarction may be related to interference by thrombolytic or aspirin treatment.


Initial experience with a multiplane transoesophageal echo-transducer: assessment of diagnostic potential. the prototype of a transoesophageal echocardiographic transducer with a rotatable cross-sectional scanning plane underwent initial evaluation. the 5 MHz, phased array, 64 element transducer is incorporated into a 16 by 11 by 40 mm echoscope tip. The instrument also has pulsed wave and colour flow Doppler capabilities. Exterior controls allow continuous mechanical rotation of the scanning plane from 0 degree, corresponding to the conventional transverse plane, through 180 degrees, thereby encompassing all possible planes. 103 patients underwent examination without complications; two additional patients were excluded because of difficulty in swallowing the probe. Advantages include precise alignment of aortic valve long- and short-axis views, long-axis views of the ascending aorta (mean visualized length: 6 cm), and full scanning of the entire circumference of the mitral valve and the left ventricle. Separation of paravalvular and transvalvular leakage in prosthetic valves is distinctly improved. multiplanar transoesophageal imaging is feasible and increases the diagnostic yield, especially in mitral and aortic pathology and in the assessment of left ventricular wall motion. Three-dimensional reconstruction is an attractive potential application.


Compensatory regional contraction following coronary artery occlusion depends on subendocardial hyperaemia and hyperkinesis. The effects of circumflex coronary artery occlusion on regional myocardial performance and blood flow in the left ventricular anterior wall was studied, using 16 thoracotomized pentobarbital-anaesthetized cats. Two pairs of ultrasonic crystals were placed in the midwall; one segment (longitudinal) parallel to the subendocardial fibres, the other (circumferential) being aligned to the fibres of the outer half-layer. A shunt line from the right subclavian artery to the main left coronary artery was unrestricted in eight cats (Group A) and clamped in another eight cats (Group B) until coronary perfusion pressure was clearly reduced with only a minor reduction in shunt flow, but without changes in global cardiac function. After circumflex coronary occlusion hyperkinesis was most pronounced in segments parallel to subendocardial fibres (longitudinal), also validated as a marked leftward shift in the end-systolic pressure-length relation of these segments. Such a shift may indicate decreased regional afterloading along the cardiac major axis. Hyperkinesis of longitudinal segments was attenuated in Group B where a fixed shunt stenosis hampered subendocardial and mid-myocardial hyperaemia. The lesser hyperkinesis of Group B was associated with decreased left ventricular systolic pressure and cardiac output. Thus, impaired compensatory contraction outside an acute ischaemic region was produced by a significant coronary stenosis which precluded the subendocardial hyperaemia and hyperkinesis of that region.


Muscle energy metabolism in severe chronic congestive heart failure--effect of treatment with enalapril. By using biopsies, skeletal muscle metabolism was investigated in 22 patients with severe chronic heart failure. All the patients were in New York Heart Association functional class IV and constituted a subgroup of the previously published CONSENSUS trial. After this initial investigation of muscle metabolism in patients with chronic heart failure, the influence of the angiotensin converting enzyme inhibitor, enalapril, on skeletal muscle metabolism was studied by randomizing the patients in a double-blind manner to receive either placebo (n = 11) or enalapril (n = 11) in addition to conventional treatment. At the time of inclusion, the muscle content of energy-rich compounds, i.e. glycogen and the high energy phosphates, adenosine triphosphate (ATP) and phosphocreatine, was reduced as compared with healthy subjects and muscle lactate content tended to be higher than normal. Following study treatment, no significant changes occurred, neither within nor between the two subgroups. Thus, patients with severe chronic congestive heart failure display metabolic derangement in muscle, which, in this study, was not corrected by treatment with enalapril.


Rate of fibrinogen breakdown related to coronary patency and bleeding complications in patients with thrombolysis in acute myocardial infarction--results from the PRIMI trial. Four hundred and one patients with acute myocardial infarction of less than 4 h duration were randomized to receive intravenous thrombolytic treatment with either 80 mg of full length unglycosylated single-chain-urokinase plasminogen activator (INN saruplase) or 1.5 million IU of streptokinase delivered over a 60 min period. Angiographic patency rates were higher at 60 min in saruplase treated patients (71.8% vs 48%; P less than 0.001), but did not differ significantly at 90 min (71.2% vs 63.9%; P = 0.15). Fibrinogen levels dropped markedly in both groups, the decrease being delayed and less pronounced with saruplase. Total fibrin and fibrinogen degradation products and D-dimer values rose earlier and to higher peak values in streptokinase treated patients. In both groups marked plasminogen and alpha 2-antiplasmin consumption was observed. Lower fibrinogen levels, and in particular the faster rate of fibrinogen breakdown, were associated with higher patency rates at 90 min (P less than 0.05). Patients with bleeding complications had lower 'lowest points' and a more rapid decrease in fibrinogen (P less than 0.05). These findings were not related to the drug used. Increased heparin levels at 6 to 12 h were correlated to bleeding complications in streptokinase treated patients. It is concluded that the rate of fibrinogen breakdown during and following thrombolytic treatment for acute myocardial infarction is related to early vessel patency and bleeding complications.


Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive heart failure. The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent both right and left catheterization. Haemodynamic parameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1 in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than 0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


The heart in Duchenne muscular dystrophy: a non-invasive longitudinal study. Sixteen boys with Duchenne muscular dystrophy (DMD) underwent serial investigations of echocardiographic left ventricular dimensions, systolic time intervals (STI), ECG and vectorcardiography (VCG). Spirometry with measurement of vital capacity and forced expiratory volume was also performed, as well as tests of muscle function. ECG was abnormal with high right precordial R-amplitudes even in the youngest patients. In contrast, VCG QRS area progressively diminished with age. STI and echocardiographic contractility indices decreased with increasing age. There was no clinically useful relationship between the various non-invasive variables on the one hand and results from skeletal muscle tests or lung function tests on the other, or between the different cardiac investigation methods. It is concluded that several non-invasive tests are needed during follow-up studies of Duchenne patients to evaluate the effects of treatment or assess prognosis.


Comparison of diastolic blood pressure changes with dobutamine and exercise test. A total of 80 patients (44 with stable angina and 36 during coronary angioplasty follow-up) underwent both exercise and dobutamine stress testing within one week. Dobutamine was infused in doses of 5 micrograms.kg-1.min-1, up to 70 every 5 min with blood pressure and electrocardiographic control. Treadmill exercise testing was performed with a maximal, symptom-limited Bruce protocol. Both systolic blood pressure and heart rate increased significantly with dobutamine and exercise, but the increase was higher with exercise (P = 0.00001). Mean blood pressure increased only with exercise, while diastolic blood pressure increased with exercise and decreased with dobutamine (P = 0.00001). A test was positive when either typical angina or an ST segment shift greater than or equal to 1 mm 80 ms after the J point was present. There were 28 positive tests with exercise and 38 with dobutamine, 22 of them coinciding. In 36 patients both tests were negative. The concordance between both tests was 73%. When each test was related to coronary angiography, dobutamine showed greater sensitivity and efficacy than exercise. a dobutamine stress test induces a positive response in more patients than does an exercise stress test, although the increase in systolic blood pressure and heart rate is greater with exercise. The decrease in diastolic blood pressure with dobutamine probably plays a role in the positive response.


A multicentre, randomized trial on the benefit/risk profile of amiodarone, flecainide and propafenone in patients with cardiac disease and complex ventricular arrhythmias. Antiarrhythmic Drug Evaluation Group (A.D.E.G.). The long-term benefit/risk profiles of amiodarone, flecainide and propafenone were compared in 141 patients with complex ventricular arrhythmias and cardiac disease, in a trial designed to mimic the clinical decision-making process. The patients were randomized to various sequences of the three drugs, at two dose levels and followed for 2 years. Drug or doses were changed to deal with insufficient reduction of arrhythmias at 24 h ECG or severe adverse drug reaction (ADR). At 2 years 18 patients had died (9/18 suddenly), 19 had withdrawn because of major clinical events or severe ADR, 13 had dropped out, seven had been non-responders throughout the entire sequence of drugs, whereas eight were non-responders only at the last visit. Thus, 76 patients (54%) were responders after 2 years. Of these, 57 were responders for 2 years with the first drug. Median exposure time to amiodarone, 518 days.patient-1, was higher than for flecainide and propafenone, 218 and 178, respectively, indicating better overall response to amiodarone (P less than 0.01). A total of 50 ADRs led to drug withdrawal, with cardiovascular ADR being less frequent (P less than 0.03) for amiodarone (2/11) than for flecainide (13/16) and propafenone (16/23). In conclusion, with sequences of amiodarone, flecainide and propafenone, an overall response rate of 79% could be obtained in the short-term (7-28 days) and 54% at 2 years. Amiodarone has a more favourable therapeutic profile than flecainide and propafenone in these patients, having less tendency to worsen heart failure.


Efficacy and safety of anticoagulant therapy started pre-operatively in preventing coronary vein graft occlusion. Oral anticoagulant therapy with warfarin commenced pre-operatively (n = 102) to prevent coronary artery vein graft occlusions was compared in terms of efficacy and safety with dipyridamole and aspirin (n = 130) in a randomized consecutive series of patients. Anticoagulant therapy was started at least 2 weeks before coronary artery bypass surgery (CABG) and antiplatelet therapy was started at least 3 days before CABG with dipyridamole followed by a combination of 250 mg aspirin once a day via a nasogastric tube 6 h after CABG. Overall, vein graft patency at 3 months after surgery did not differ significantly between the anticoagulant group (203/275, 74%) and dipyridamole-aspirin group (238/311, 77%), but the occlusion rate for grafts with endarterectomy was higher in the anticoagulant (46%) than in the dipyridamole and aspirin group (16%), (P less than 0.05). The rate of peri-operative complications including deaths, re-operation and myocardial infarction was higher in the anticoagulant than antiplatelet group (26.5% vs 13.8%, P less than 0.05). The occurrence of postoperative bleeding complications did not differ significantly between the groups. Thus, oral anticoagulant therapy commenced pre-operatively has no advantages over conventional antiplatelet therapy in patients who undergo CABG. Neither antithrombotic regimens proved to be satisfactory for preventing acute bypass vein graft occlusions in this patient population with advanced coronary artery disease.


A comparison of the day-long antianginal effectiveness of nitroglycerin patches with that of three-times-daily isosorbide dinitrate: a double-blind study using dose titration. Eight men with stable angina, a positive treadmill test, and demonstrated responsiveness to chronic oral isosorbide dinitrate (ISDN) were studied after they had been taking effective doses of ISDN t.i.d. for at least 2 weeks. Exercise tests were performed every 1-2 h until 19.00 hours over one day after the 08.00 hours application of nitroglycerin patches in a previously titrated dose; on another day after the administration of ISDN capsules q5h; and on a third day after placebo patches and capsules. The mean necessary effective patch dose was 125 cm2 (60-220 cm2). The mean exercise duration to angina rose from 271 to 480 s 1 h after nitroglycerin patches (P less than 0.001). Nitroglycerin patches were superior to the placebo throughout the day, but in a declining degree--by 94 s at 19.00 hours (P less than 0.05). ISDN q5h provided peaks of increased walking time to angina 1 h after each dose, but after 3 h exercise time was down to placebo levels. Furthermore, the peaks were of diminishing amplitude: 200 s at 09.00 hours, 150 s at 14.00 hours, but only 70 s at 19.00 hours. Thus, neither nitrate regimen provided continuous near-peak benefit throughout the 11 h period, although nitroglycerin patches had a significantly greater (P less than 0.05) overall effect during the day.


Effect of fentanyl on cardiac automaticity and conduction: direct or mediated action? The effects of fentanyl at a dose of 100 micrograms.kg-1 on cardiac automaticity, refractoriness and conduction have been studied in a model of heterotopic heart transplantation which combines a denervated heart (donor) and a non-denervated heart (recipient) in each of 20 dogs employed. Once the surgical procedure had been completed, cycle length, sinoatrial conduction time, antegrade and retrograde A-V node block points, cycle length at which 1:1 conduction ceases to exist and the antegrade effective refractory period of the A-V node and ventricles were measured. These parameters were determined in hearts both in the basal situation and 10 min after fentanyl injection. In the recipient organs, fentanyl produced statistically significant prolongation of cycle length, sinoatrial conduction time, antegrade block point and antegrade effective refractory periods of the A-V node and ventricles, with respect to the basal situation (P less than 0.01 for all these parameters); in 20% of cases, a complete A-V block was produced. In the donor hearts (denervated), prolongations of cycle length (P less than 0.01) and the antegrade block point (P less than 0.05), as compared with the basal situation, were recorded, but no other modifications were detected. To test whether these effects were due to the action of fentanyl, 10 animals were subsequently injected with naloxone, an agent which reverted the reported changes, although in the recipient organs, there persisted a slight prolongation of the cycle length with respect to basal measurements (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


A closed-chest myocardial occlusion-reperfusion model in the pig: techniques, morbidity and mortality. Extensive preparative surgery and lengthy experimentation may lead to high rate of complications and mortality in myocardial ischaemia studies. These problems are particularly common when pigs are used as the subject as they are prone to develop lethal ventricular arrhythmias. Here, a closed-chest model is presented, in which the trauma of major preparative surgery is avoided. One-hundred and twelve pentobarbital-anaesthetized, mechanically ventilated pigs were used. Coronary occlusion was produced by injection of a 2 mm diameter ball via a modified coronary angiography catheter. Reperfusion was induced by retraction of the ball via a thin filament attached to the ball. The amount of the myocardium at risk (MAR) was 8.23 +/- 2.41% (mean +/- SD) of the left plus right ventricular weight. It was possible to carry out scheduled 24 h experiments in 87 out of 93 animals (93.5%). Preparative mortality was 1.8% and 24 h mortality 6.5%. Ventricular fibrillation (VF) occurred during preparation in 3.6%, during coronary occlusion in 7.3% and during reperfusion in 5.0% of the animals. VF was significantly related to a large zone of MAR and insufficient premedication. Catheter- or ball-induced complications were found in 10.7%. Mortality and incidence of VF are considerably lower in this closed-chest model than in a previously reported open-chest pig preparation.


Increase in radionuclide left ventricular ejection fraction after cardioversion of chronic atrial fibrillation in idiopathic dilated cardiomyopathy. To assess the potential improvement in left ventricular ejection fraction after cardioversion of chronic atrial fibrillation to sinus rhythm in idiopathic dilated cardiomyopathy, we studied prospectively 17 patients, aged 58 +/- 6 years, by radionuclide angiocardiography at rest. Left ventricular ejection fraction was determined before treatment and at a mean delay of 4.7 months after cardioversion. Return to sinus rhythm was obtained in 12 patients, pharmacologically or by electrical cardioversion. Five patients remained in atrial fibrillation. No clinical, echocardiographic or haemodynamic finding could predict the success of cardioversion. In chronic atrial fibrillation, the ejection fraction did not change significantly: 30.0 +/- 9.1% (19 to 44%) at the first evaluation and 29.5 +/- 8.3% (22 to 41%) after 4.7 months. After successful cardioversion, left ventricular ejection fraction improved from 32.1 +/- 5.3% (24 to 41%) to 52.9 +/- 9.7% (37 to 71%) (P less than 0.001). The difference was 20.8 +/- 11.3% and left ventricular ejection fraction was normalized in 50% (6/12) of the patients. There was a significant reduction in the cardiothoracic ratio on chest X-rays and of the left ventricular end-diastolic diameter on echocardiography; fractional shortening increased (27.7 +/- 4.3% vs 20.3 +/- 2.7%, P less than 0.01). A third evaluation was realized after a mean delay of 11.7 months in the patients with successful cardioversion. Sinus rhythm was present in 83% (10/12) of the patients: seven patients were reevaluated by radionuclide angiography. The improvement in left ventricular function observed at the 4.7 months evaluation was still present. In two patients with recurrence of atrial fibrillation, there was a severe deterioration of left ventricular systolic function.(ABSTRACT TRUNCATED AT 250 WORDS)


Laser-assisted tricuspid valve balloon dilation for acquired tricuspid valve atresia. Acquired pulmonary valve atresia is a well-recognized but uncommon complication of surgical systemic-to-pulmonary artery shunts in patients with tetralogy of Fallot. Acquired atresia of the tricuspid valve, however, has not been reported previously. This complication developed in a 3-year-old girl, with pulmonary atresia and an intact ventricular septum, after a Blalock-Taussig shunt and right ventricular outflow tract reconstruction. Percutaneous transcatheter laser-assisted balloon dilation re-established antegrade flow across the tricuspid valve.


Pharmacotherapeutic effects of antihypertensive agents on myocardium and coronary arteries in hypertension. Hypertensive left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations in the coronary microcirculation. This leads to impairment of diastolic function in the left ventricle and coronary flow reserve despite normal epicardial arteries. Consequently, antihypertensive treatment should aim at (1) reversing myocyte hypertrophy, (2) restoring myocardial structure and (3) improving coronary flow reserve without lowering blood pressure. In recent years many clinical studies have shown that regression of hypertensive hypertrophy can be induced by long-term treatment with ACE inhibitors, calcium-channel blockers, beta-receptor blockers and antisympathonic drugs. However, vasodilators and diuretics, which stimulate adrenoceptor activity and increase angiotensin II levels, were found to be less effective in reversing left ventricular hypertrophy. The trophic influence of catecholamines and angiotensin II on the myocardium counteracts the effect of systolic wall stress reduction due to blood pressure lowering. As regards reversal of interstitial fibrosis, ACE inhibitors seem to be effective, because fibroblast growth was found to be stimulated by angiotensin II. Recently, clinical studies have confirmed previous experimental data that improvement in impaired coronary vasodilator reserve can be realized by long-term antihypertensive therapy. In adopting an antihypertensive treatment strategy prime consideration should be given to reversal of cardiac remodelling through restoration of myocardial structure and repair of the coronary microcirculation.


Impact of regression of left ventricular hypertrophy on cardiac function in hypertension. It is now established that regression of left ventricular hypertrophy (LVH) occurs following reduction of arterial pressure in patients with hypertension. A number of factors contribute towards this regression, including the fall in blood pressure itself, the drug therapy given, and the pre-existing degree of hypertrophy. LVH is in some senses a beneficial adaptive response in terms of systolic function, and therefore it is important to clarify whether or not regression of hypertrophy is damaging to cardiac function. Overall assessment of these effects has been more difficult because the antihypertensive drug therapy and the changes in blood pressure also contribute to left ventricular function. Current data indicate that systolic function is maintained both at rest and following exercise but not necessarily improved. In contrast, diastolic function in some but not all studies, has been shown to have been improved. Recent information has allayed fears that regression of LVH may cause a deterioration in function if blood pressure is allowed to return to its pretreatment levels. It would appear that in this situation function is maintained both at rest and during exercise. Finally, the assessment of cardiac function following regression of hypertrophy remains a surrogate end-point. The key information required remains the influence of regression of hypertrophy and its alteration in function on morbidity and mortality in patients with hypertension.


Morphometric investigation of human myocardium in arterial hypertension and valvular aortic stenosis. Both arterial hypertension and aortic stenosis lead to pressure overload of the left ventricle. As intramyocardial vasculature is confronted with pressure overload in hypertension but not in aortic stenosis, structural differences are to be expected in both forms of left ventricular hypertrophy. With the aid of morphometry, we investigated human myocardium from autopsied hearts from six patients with arterial hypertension and 10 controls, as well as myectomy specimens from cardiac surgery from 14 patients with aortic stenosis. Mean left ventricular myocytic diameter was significantly (P less than 0.05) increased compared with controls (12.4 +/- 1.5 microns) during hypertension (+27%) as well as aortic stenosis (+65%) (P less than 0.05). This was combined with a greater volume density of perimyocytic fibrosis (controls = 0.8 +/- 0.4 V upsilon %) during hypertension (+250%) and aortic stenosis (+587%) (P less than 0.05). Walls of intramyocardial arterioles (external diameter 20-40 and 40-80 microns) were thickened to 32% and 44% (P less than 0.05) during hypertension, but not during aortic stenosis. Compared with controls, perivascular fibrosis of these arterioles was increased by +215% and 61% (P less than 0.05), respectively, during hypertension, but not during aortic stenosis. Myocytic hypertrophy and increased perimyocytic fibrosis accompany intraventricular pressure overload (hypertension and aortic stenosis) in human hearts. Myocardial structure as a result of arterial hypertension, but not aortic stenosis, is also characterized by intramyocardial arteriole wall-thickening and increased perivascular fibrosis. Thus, distinct structural reaction patterns are noted in the cardiac hypertrophy associated with hypertension and aortic stenosis.


Biological basis of diastolic dysfunction of the hypertensive heart. To study the diastolic properties of the heart includes examining active relaxation, passive ventricular stiffness and atrial contraction. (i) The main determinant of active relaxation is the adenosine triphosphate (ATP) concentration. Relaxation needs to occur so that the ATP content of the cell can be decreased by activation of the myosin ATPase, which in turn depends upon an intracellular messenger, elevation of the calcium transient. In a model of cardiac hypertrophy active relaxation is always slower. This slowing accompanies a slowing of the calcium transient, a diminution in the activity of the Na+/Ca2+ exchanger, a change in the properties of Na+, K+ ATPase and a decreased concentration of Ca2+ ATPase in the sarcoplasmic reticulum. (ii) Chamber stiffness is likely to be increased only in relation to the degree of ventricular hypertrophy. The main, if not unique, determinant of ventricular diastolic tissue stiffness is the structure and concentration of the collagen. Consequently tissue stiffness is augmented in cardiac hypertrophy in which the ventricular collagen concentration is elevated. It is important that both clinically and experimentally cases of cardiac hypertrophy, even those resulting from pressure overload in which myocardial stiffness and cardiac collagen concentration remain unchanged, have been documented. A good example of this is the DOCA-salt model of arterial hypertension. (iii) Atrial contraction is normally more rapid than ventricular contraction, the biological basis for which is the difference in isomyosin content.(ABSTRACT TRUNCATED AT 250 WORDS)


Myocardial collagen matrix remodelling in arterial hypertension. The cardiac interstitium is composed of non-myocyte cells and a structural fibrillar protein network which plays a dominant role in governing the structure, architecture, and mechanical behaviour of the myocardium. Herein we review the fibrillar collagen network, its various components, and the functions they serve in the normal and structurally remodelled myocardium in arterial hypertension. The heterogeneity in myocardial structure, created by the altered behaviour of non-myocyte cells, particularly cardiac fibroblasts, which are responsible for collagen synthesis or degradation and thereby fibrous tissue accumulation, is a major determinant for the appearance of diastolic dysfunction and ultimately systolic myocardial failure. Regulatory mechanisms related to this fibrous tissue response are reviewed to draw attention to the hitherto neglected role of cardiac fibroblasts in mediating adverse structural remodelling of the myocardium and showing how this can be prevented through the use of pharmacological agents that interfere with the regulation of the myocardial collagen matrix. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodelling of the non-myocyte compartment. These include the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition and aldosterone receptor antagonism that were found to prevent myocardial fibrosis in the rat with renovascular hypertension. In the rat with genetic hypertension, established left ventricular hypertrophy and abnormal myocardial diastolic stiffness due to interstitial fibrosis, RAAS inhibition resulted in restoration of myocardial structure and function to normal.(ABSTRACT TRUNCATED AT 250 WORDS)


Right ventricular performance in arterial hypertension. To investigate right ventricular function, 24 patients with arterial hypertension and five normotensive controls underwent equilibrium radionuclide ventriculography with simultaneous right heart catheterization. In normal subjects, left ventricular ejection fraction was 57 +/- 2% at rest and 71 +/- 5% on effort, and right ventricular ejection fraction (RVEF) averaged 51 +/- 5% at rest and 65 +/- 2% during exercise. Pulmonary vessel resistance (PVR) was 56 +/- 37 dyn.s.cm-5 at rest and 46 +/- 10 dyn.s.cm-5 on effort. Hypertensive patients were divided into three groups according to their left ventricular function: group 1 (n = 10) had normal left ventricular ejection fraction (LVEF) at rest and on effort (57 +/- 9%; 65 +/- 6%), in this group, right ventricular systolic reserve was reduced (RVEF 52 +/- 7% at rest, ns; RVEF 57 +/- 7% on effort, P less than 0.01 compared to controls). Pulmonary vessel resistance during exercise averaged 78 +/- 24 dyn.s.cm-5, which was significantly higher compared to controls (P less than 0.01). In group 2, left ventricular contractions were normal at rest (60 +/- 6%, ns) but deteriorated during exercise to 56 +/- 8% (P less than 0.001, compared to controls). These patients also showed a lack of right ventricular augmentation at ejection fraction (54 +/- 8% at rest, ns; 56 +/- 8% under exercise, P less than 0.05). PVR was significantly enhanced during exercise (88 +/- 40 dyn.s.cm-5, P less than 0.05 compared to controls).(ABSTRACT TRUNCATED AT 250 WORDS)


The role of coronary perfusion pressure. Coronary flow is normally autoregulated so that within wide limits of changes in perfusion pressure (which approximate to diastolic BP) blood flow to the heart remains constant. Thus, as perfusion pressure falls, the coronary arterioles dilate to maintain flow; under basal conditions a five-fold increase in coronary flow can occur, i.e. a flow reserve of five. Coronary flow reserve is markedly impaired in the presence of severe coronary artery stenosis and/or LVH. In the presence of severe stenosis and LVH a fall in perfusion pressure (DBP), which would be normally well tolerated, results in a fall of coronary flow, ECG changes and ventricular dysfunction (fall in ejection fraction instead of the usual increase). The above mechanisms underlie the J-curve relationship between DBP and myocardial infarction (MI) in high risk hypertensives. In the absence of overt coronary artery disease (CAD) and LVH, the lower the DBP the better. However in the presence of CAD and LVH lowering the DBP (phase 5) to below the low-mid 80s results in an increased frequency of MI.


Coronary haemodynamics in hypertensive heart disease. Cardiac constituents affected in arterial hypertension comprise the myocardium, interstitium and coronary circulation. With regard to coronary circulation, arterial hypertension is an important risk factor in coronary artery disease, but even in the absence of coronary artery disease, hypertensive patients frequently have angina pectoris or reveal electrocardiographic abnormalities suggestive of myocardial ischaemia due to coronary insufficiency. Under clinical conditions, determination of coronary flow reserve (dipyridamole; Argon-method) allows for the evaluation of impairment of coronary regulatory reserve. In comparison to healthy normotensives, coronary haemodynamics in hypertensive patients with microvascular angina are characterized by a severely increased minimal coronary resistance and reduced maximal coronary blood flow to dipyridamole. Accordingly, coronary reserve is markedly reduced by about 40%, and metabolic, myocardial and vascular factors may be involved in this reduction. In the compensated stage of arterial hypertension, with concentric left ventricular hypertrophy, myocardial factors, such as myocyte hypertrophy, extravascular compressing forces and functional implications of impaired relaxation, as well as metabolic factors, contribute to impairment in coronary reserve to a minor extent. The reduction in coronary flow reserve is not proportional to the elevation in left ventricular muscle mass and thus the degree of left ventricular hypertrophy does not seem to determine the reduction in vasodilator reserve directly. Thus the reduction in coronary reserve seems to be primarily the consequence of an impaired vasodilating capacity of the coronary resistance vessels, as indicated by a severely increased minimum coronary resistance to dipyridamole, i.e. a severely reduced overall coronary conductance capacity.(ABSTRACT TRUNCATED AT 250 WORDS)


Heterogeneity of endothelial dysfunction in hypertension. The endothelium may play a role as a target and mediator of hypertension. Due to its anatomical position, it is very exposed to mechanical forces; as a source of vasoactive material it may participate in increasing peripheral vascular resistance and in promoting local ischaemia in the heart and brain. Morphological and functional changes in the endothelium occur in experimental and human hypertension. However, the severity of the defect and the mechanisms involved among vascular beds and models of hypertension are heterogeneous. Endothelium-dependent relaxations are impaired in the aorta, carotid artery and in cerebral and mesenteric arterioles in hypertension. In the coronary circulation the defect is less pronounced. The mechanisms involve a reduced formation of nitric oxide, an enhanced production of prostaglandin H2 and an impaired responsiveness of vascular smooth muscle to nitric oxide. The role of endothelin in hypertension is controversial; circulating levels appear unaltered except in the presence of renal failure or atherosclerosis. The local vascular production of endothelin, however, may still be increased. The potentiating effects of threshold concentrations of endothelin on the vasoconstrictor response to noradrenaline are enhanced in hypertension. Thus, subtle and distinct endothelial function defects occur in hypertension, but not all vascular beds are similarly affected and different mechanisms contribute. Endothelial dysfunction may contribute to increased peripheral resistance, tissue ischaemia and cardiovascular complications.


Metabolically-modulated growth and phenotype of the rat heart. Heart muscle reacts to work overload and various neuroendocrine stimuli by inducing myocyte growth. A novel type of hypertrophy can be induced in the rat heart by etomoxir, which reduces fatty acid oxidation. This hypoglycaemic drug inhibits the mitochondrial carnitine palmitoyltransferase 1, and thus reduces the long-chain fatty acid uptake of mitochondria; in a compensatory manner, the glycolytic flux is enhanced. In rats, etomoxir induced a harmonious growth of the left and right ventricles of normal and pressure-overloaded hearts. To characterize the protein phenotype, myosin expression and sarcoplasmic reticulum (SR) Ca2+ pump activity were determined. In contrast to pressure-overloaded hearts, etomoxir increased the proportion of myosin V1, Ca(2+)-stimulated SR ATPase activity and the rate of SR Ca2+ uptake. Since etomoxir did not increase blood pressure, heart rate or circulating thyroid hormones, it appears that established mechanisms of other models of cardiac hypertrophy were not involved. The etomoxir-induced changes thus seem closely linked to the shift in energy metabolism.


Transient myocardial ischaemia in hypertensives: missing link with left ventricular hypertrophy. Hypertensive patients often complain of angina pectoris in spite of a normal coronary angiogram. The aim of this study was to establish whether electrographical signs of transient myocardial ischaemia during 24-h ST Holter monitoring are associated with an increased left ventricular muscle mass. Thirty-five hypertensive patients were studied by 24-h Holter monitoring and M-mode and two-dimensional echocardiography. For control purposes nine normotensives were studied by the same protocol. Hypertensives with and without ST-segment depression did not differ in respect of blood pressure or left ventricular muscle mass (162.9 +/- 80 vs. 162.3 +/- 53 g m-2). Since both groups only showed a borderline left ventricular hypertrophy, the myocardial factor does not seem to be important for the occurrence of ST segment depression. Primary functional and structural alterations at the microcirculation level seem to be responsible for the occurrence of transient episodes of ST segment depression in the Holter electrocardiogram, indicating transient myocardial ischaemia.


Hypertension, left ventricular hypertrophy, ventricular arrhythmias and sudden death. LVH is a common sequela of arterial hypertension; it increases the risk of sudden death and other cardiovascular morbidity and mortality independent of arterial pressure and has been associated with ventricular arrhythmias. Electrophysiological studies suggest a connection between ventricular arrhythmias in patients with LVH and sudden death. LVH can be reduced by specific antihypertensive therapy, although not all drugs are equipotent in this regard. A reduction in LVH has been shown to diminish ventricular ectopy. Preliminary findings suggest that a reduction of LVH and associated arrhythmias may reduce its inherent cardiovascular risk.


Electrophysiological and therapeutic implications of cardiac arrhythmias in hypertension. Hypertension, especially if associated with left ventricular hypertrophy (LVH), is a risk factor in complex ventricular arrhythmia (VA) and sudden cardiac death (SCD). To determine the effectiveness of the clinical use of programmed ventricular stimulation (PVS) we studied 40 symptomatic hypertensive patients after excluding coronary heart disease (CHD), as characterized by dizziness and palpitation, syncope, aborted SCD and/or documented complex VA. PVS revealed a normal result, i.e. a maximum of six ventricular echobeats, in 70% (group A) and a pathological result, i.e. ventricular tachycardia (VT) or fibrillation (VF) in 30% (group B). Both groups differed significantly with respect to LV (left ventricular) muscle mass: 158 +/- 45 (A) vs. 222 +/- 112 (B) g.m-2, LVEF (left ventricular ejection fraction): 71 +/- 17% (A) vs. 47 +/- 18% (B) and LV end-systolic volume index: 34 +/- 25 (A) vs. 63 +/- 27 (B) ml.m-2. Coronary reserve was comparably reduced in both groups: 2.6 +/- 1.0 (A) vs. 2.3 +/- 0.6 (B). In 3/8 (37%) patients with aborted SCD and VT/VF the clinical VA (2/2 VT and 1/6 VF) could be induced, whereas in the remaining five patients nsVT or no complex VA was induced. The therapeutic regimen included no drugs in 30%, beta-blockers in 50%, serial drug testing in 12% and implantation of an automatic cardioverter defibrillator (AICD) in 8% of patients. Ventricular late potentials (LPs), detected by the signal averaging electrocardiogram, represent zones of delayed myocardial activation, which may become an origin of ventricular tachycardias. Three criteria constitute a positive LP: (1) QRS duration greater than 114 ms, (2) root mean square voltage of the last 40 ms less than 20 microV and (3) duration of low amplitude signal below 40 microV greater than 38 ms. To look for the prognostic value of LP in hypertension we investigated 43 hypertensive patients without evidence of CHD. All three criteria were positive in 4/43 patients (9%), three of them demonstrating inducible monomorphic VT during PVS. 17/30 patients (56%) with LVH had at least one positive criterion, whereas only one out of 13 patients without left ventricular hypertrophy (8%) had one positive criterion. Symptomatic patients presenting with syncope, aborted SCD or documented VT/VF differed significantly from patients without symptoms or complex arrhythmias in regard to all three criteria. In hypertensive heart disease clinical arrhythmias as well as the result of electrophysiological testing are closely related to left ventricular performance and hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)


Left ventricular hypertrophy as a risk factor in arterial hypertension. Data on the evolution and prognostic implications of left ventricular hypertrophy (LVH) determined by ECG, chest X-ray and echocardiogram in the Framingham Study are reviewed. Echocardiographic examination provides the most sensitive and specific measure of left ventricular hypertrophy, providing a quantitative evaluation of the anatomical condition. Chest X-ray evaluation is also more sensitive than the ECG, but less specific than the echocardiogram. When ECG-LVH is present, X-ray and echocardiographic LVH are often found; but, when negative, the ECG clearly does not exclude anatomical LVH. The incidence of each variety of LVH increases with age, weight and blood pressure. Although it may also appear following coronary heart disease (CHD), valvular deformity and congenital cardiac defects, the former are the major determinants of LVH in the general population. Each contributes independently to the occurrence of LVH. LVH has emerged as a powerful non-invasive indicator of increased vulnerability to the occurrence of major cardiovascular disease outcomes in hypertension. It appears that X-ray and echocardiographic LVH measure anatomical hypertrophy, whereas the ECG variety is also indicative of ischaemic myocardial involvement when repolarization abnormality is present. Hypertension clearly predisposes to both anatomical and ECG-LVH which cannot be taken as an incidental compensatory feature since at any blood pressure those with ECG-LVH, X-ray or echo LVH are distinctly more prone to cardiovascular sequelae. ECG-LVH carries a greater risk than anatomical (X-ray) LVH. ECG-LVH with repolarization abnormality is more dangerous than that with voltage alone. The latter appears to reflect chiefly the severity and duration of accompanying hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of hypertension, left ventricular hypertrophy and psychosocial risks in cardiovascular disease: prospective evidence from blue-collar men. Epidemiological studies have demonstrated that, compared with the population as a whole, there is increased cardiovascular morbidity and mortality among lower socio-economic groups. To explore determinants of the increased risk within this group, a prospective 6.5 year investigation of a cohort of 416 middle-aged (40.8 +/- 9.6 years) male blue-collar workers was undertaken. In addition to established somatic and behavioural risk factors, psychosocial influences that measured chronic occupational stress in terms of an imbalance between high effort and low reward were assessed. Multivariate logistic regression analysis shows that hypertension (odds ratio (o.r.) 3.85; 95% CI 1.59-9.34), left ventricular hypertrophy (o.r. 3.62; 95% CI 1.06-12.37), hyperlipidaemia (o.r. 2.55; 95% CI 1.08-6.00), status inconsistency (measuring low reward at work) (o.r. 2.86; 95% CI 1.04-7.80) and 'immersion' (measuring high intrinsic effort at work) (o.r. 3.57; 95% CI 1.22-10.47) independently contribute to the prediction of fatal or non-fatal cardiovascular events (acute myocardial infarction, stroke). Expected probabilities of cardiovascular events are clearly elevated if the combined effects of left ventricular hypertrophy and psychosocial risks are analysed. In conclusion, increased incidence of cardiovascular disease among lower socio-economic groups is explained by a co-manifestation of established risk factors including left ventricular hypertrophy (by ECG) and psychosocial factors measuring chronic stress at work.


The reorganization of the human and rabbit heart in response to haemodynamic overload. A myothermal/mechanical analysis on non-failing and failing human hearts and normal and pressure overloaded rabbit hearts is reported. Heat production is partitioned into tension-dependent and tension-independent components together with force measurements to provide information about calcium and cross-bridge cycling. In the non-failing human heart the cross-bridge force-time integral is 0.51 +/- 0.06 (ns). This value is increased to 0.97 +/- 0.09 (P less than 0.05 s) in failing hearts. In control as compared to pressure-overload rabbit hearts the cross-bridge force-time integral increases from 0.36 +/- 0.02 to 0.96 +/- 0.11 (P less than 0.05 s). The increase in force-time integral allows the heart muscle to develop force with greater economy (less high energy phosphate hydrolysis) but at the expense of velocity and power. The amount of calcium cycled following activation in non-failing human hearts is 32.2 +/- 8.17 nmoles.g-1.-beat-1. In the failing preparations calcium cycling is reduced to 16.7 +/- 1.72 nmoles.g-1.-beat-1. In pressure-overloaded hypertrophied, as compared with control rabbit hearts, the calcium cycled per beat is reduced from 43.0 +/- 7.3 to 17.6 +/- 3.4 nmoles.g-1. It is suggested that the alterations in cross-bridge cycling are more likely to be related to isoenzyme shifts in light chains or troponin T than to myosin isoforms. The calcium cycling changes are well correlated with changes in the sarcoplasmic reticular and sarcolemmal calcium transport proteins. The alterations in the contractile and excitation contractions coupling systems contribute to the functional changes observed in the failing human and pressure-overload rabbit hearts.


Reduced peripheral and coronary vasomotion in systemic hypertension. In 53 patients with a history of arterial hypertension and 16 normotensive control subjects, coronary blood flow reserve by means of the argon method, and peripheral vascular flow reserve by means of venous occlusion plethysmography, were studied. The coronary flow reserve, expressed as the ratio of coronary vascular resistance under resting conditions to the minimal coronary vascular resistance after the administration of dipyridamole, was 4.34 +/- 0.89 in the normotensive group and 2.18 +/- 0.60 in the hypertensive group. There was no significant difference in forearm peak flow after 3 min of arterial occlusion between normotensive and hypertensive patients, while the peripheral minimal vascular resistance was significantly higher in hypertensive patients (8.8 +/- 3.8 mmHg x ml.min-1 x 100 ml-1 tissue) as compared to normotensive subjects (6.37 +/- 2.37 mmHg x ml.min-1 x 100 ml-1 tissue). Parallel to the reduction in coronary reserve, the peripheral flow reserve, expressed as the ratio of peripheral resting vascular resistance to peripheral minimal vascular resistance after 3 min of arterial occlusion, was significantly lower (P less than 0.01) in hypertensive subjects (3.85 +/- 2.28) as compared to normotensive subjects (5.31 +/- 1.72). These data suggest that in hypertensives an impaired vasodilator reserve of both coronary and peripheral microcirculation exists.


In vitro and in vivo effects of diethylene triamine penta-acetic acid on the distribution of indium-111 monoclonal antibody metabolism. The effects of diethylene triamine penta-acetic acid (DTPA) on indium-111 monoclonal antibody (MoAb) metabolism were examined. Sequential analysis of 111In-MoAb incubated in serum at 37 degrees C by high performance liquid chromatography (HPLC) and electrophoresis revealed that the radioactivity gradually moved from the MoAb to a 70-90 kDa molecular weight fraction. DTPA inhibited the transchelation of 111In to this fraction. It also decreased 111In uptake by isolated rat hepatocytes but did not remove 111In incorporated in hepatocytes. The daily in vivo administration of DTPA (0.5-2.0 mg/mouse daily) to athymic mice after 111In-MoAb injection significantly reduced the 111In uptake in the liver and kidney. The tumour uptake was decreased somewhat but not significantly. The serum radioactivity in the 70-90 kDa fraction was also decreased. Scintigraphic examination demonstrated a decreased liver uptake in the DTPA-treated group of mice. Our results show that 111In released from the DTPA-MoAb conjugate in serum binds to molecules of 70-90 kDa and that DTPA decreases the 111In uptake in this fraction, which induces a decrease of 111In accumulation in normal tissues.


The effect of hydration on the dose to the urinary bladder wall during technetium-99m diethylene triamine penta-acetic acid renography. A spherical bladder dynamic model for the estimates of the radiation dose to the bladder walls from intravenously injected radionuclides was implemented to investigate in theory the effect of hydration on the reduction of the bladder dose in technetium-99m diethylene triamine penta-acetic acid (99mTc) DTPA renography. This model gives due consideration to the variation with time of the urine flow rate to the bladder, following a known fluid load. According to the model, the estimated dose depends on the renal function, the fluid load, the time elapsed from the fluid load to the i.v. DTPA injection, the micturition volume and the residual urine volume. Experimental data concerning the values of these parameters for normal individuals were obtained from the literature. Calculations cover the time period from i.v. injection up to the time of the ninth postinjection void. Results show that the patient's condition of hydration is critical for the radiation protection of the bladder. It is shown that optimum combinations of the values of the parameters involved in the calculations exist, which minimize the radiation dose. On the basis of these results, a general protocol is proposed, referring to the hydration conditions under which the renal dynamic study may be normally carried out, with a minimal absorbed dose to the bladder walls (less than 0.045 mGy/MBq).


Heterogeneous myocardial distribution of iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in patients with hypertrophic cardiomyopathy. IT has been proposed that iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) is an agent for myocardial fatty acid metabolism in animal models. The aim of the present study was to determine whether alterations in fatty acid uptake and/or utilization in patients with hypertrophic cardiomyopathy (HCM) could be detected by 123I-BMIPP. Myocardial imaging with 123I-BMIPP and thallium-201 (201Tl) was performed in 14 fasted patients. A dose of 111 MBq of 123I-BMIPP was administered intravenously at rest, and myocardial emission computed tomography was obtained 20 min and 3 h after injection. The 201Tl imaging was also performed within 1 week after the 123I-BMIPP study. The regional myocardial uptake and clearance of 123I-BMIPP and 201Tl were assessed quantitatively. The myocardial distribution of 123I-BMIPP was more heterogeneous than that of 201Tl in patients with HCM. The myocardial uptake of 123I-BMIPP was lower in the anteroseptal region of the left ventricle than in the posterolateral region (74% vs. 85%, P less than 0.001). The anteroseptal wall showed a faster clearance of 123I-BMIPP than the posterolateral wall (33% vs. 27%, P less than 0.01). Both a decreased uptake and rapid clearance of 123I-BMIPP were observed in the hypertrophied myocardium of the anteroseptal wall, where 201Tl uptake was normal or even increased. Myocardial segments with a markedly increased thickness showed a lower uptake and faster clearance of 123I-BMIPP than those with mild hypertrophy (uptake 73% vs. 82%, P less than 0.05; clearance 30% vs. 25%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


The clinical impact of thallium-201 reinjection scintigraphy for detection of myocardial viability. In a clinical study, the value of thallium-201 reinjection was studied in 139 patients with suspected or known coronary artery disease who showed one or more persistent defects after conventional stress-redistribution imaging. Fifty-nine (42%) patients had sustained a Q-wave myocardial infarction. Sixty-eight (49%) patients showed a reversible defect in at least one myocardial segment at redistribution, while 71 (51%) had persistent defects only. Following reinjection additional segmental filling-in was seen in 95 (68%) patients, including 50 of the 68 (74%) patients with reversible defects and 45 of the 71 (63%) with persistent defects only. On the immediately post-exercise images, 458 (47%) of 973 segments showed perfusion defects. At redistribution 105 (23%) of the 458 defects showed filling-in, whereas of the remaining 353 persistent defects 164 (46%) resolved additionally after reinjection. Thirteen (10%) of 133 Q-wave related defects showed filling-in at redistribution compared with 22 (27%) of 82 remote defects (P = 0.001). After reinjection additional filling-in of defects was seen in 47 (39%) of 120 Q-wave related defects compared with 35 (58%) or 60 remote defects (P = 0.015). Overall, 60 (45%) of 133 Q-wave related defects resolved compared with 57 (70%) of 82 remote defects (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)


Thallium-201 single photon emission tomography of myocardium: additional information in reinjection studies is dependent on collateral circulation. A second thallium-201 injection under resting conditions is able to improve the differentiation between myocardial scar and ischaemia when compared with simple redistribution imaging. The aim of this study was to evaluate the dependence of this improvement on the degree of stenosis and the presence of collaterals. Single photon emission tomography (SPET) studies under exercise, redistribution and reinjection conditions were performed on 84 patients with 181 stenotic vessels (70 left anterior descending, 47 left circumflex, 64 right coronary artery) and compared with angiography. An improvement of the 201Tl uptake in the reinjection image was observed in 53% of the myocardial areas served by a coronary artery with a stenosis of over 90%. This is compared with 13% of the areas served by a vessel with a stenosis between 50% and 90%. 90% of the collateralized areas showed a fill-in effect, but only 7 of the 118 without angiographically visible collateralization (6%). The dependence of the fill-in effect, collateralization and stenosis was highly significant (chi 2 test, p less than 0.0001). In our patient group, there was much greater benefit from the reinjection study in vessels with a greater than 90% narrowing. The fill-in effect was closely correlated to the presence of collaterals. In these cases, the fill-in may be an indication for hibernating myocardium.


Prediction of reversible perfusion defects by quantitative analysis of post-exercise electrocardiogram-gated acquisition of technetium-99m 2-methoxyisobutylisonitrile myocardial perfusion scintigraphy. The aim of this study was to assess the reliability of the quantitative analysis of regional wall thickening with electrocardiographic-gated technetium-99m 2-methoxyisobutylisonitrile (SESTAMIBI) in predicting the reversibility of stress-induced perfusion defects. The assumption was that a preserved resting wall thickening in a segment with stress-induced perfusion defect would predict normal resting perfusion. Twenty-five patients with suspected coronary artery disease underwent planar stress-rest SESTAMIBI scintigraphy. The wall thickening was quantitatively evaluated as percentage increase in counts from diastole to systole; a ratio defined as the wall thickening index (WTI) between patient and normal profile (mean - 2 SD) below 1 was considered abnormal. Improvement of the perfusion pattern at rest was observed in 76% (54/71) of segments with a stress-induced perfusion defect; 90% of these segments had a (WTI) greater than 0.8. Five segments (9%) showed fixed perfusion defects despite a WTI value greater than 0.8. In conclusion, quantitative analysis of regional wall thickening by electrocardiographic-gated SESTAMIBI identifies segments with reversible perfusion defects; this may overcome the need for studies at rest and may direct the detection of hypoperfused but viable myocardium.


Accuracy and repeatability of left ventricular systolic and diastolic function measurements using an ambulatory radionuclide monitor. The accuracy and repeatability of a new ambulatory radionuclide detector (VEST) for left ventricular systolic (ejection fraction) and diastolic (peak filling rate) measurements were assessed. Seventeen patients underwent equilibrium radionuclide angiography immediately before and immediately after a VEST study. The accuracy was evaluated at the beginning and at the end of the VEST studies. Limits of agreement for the ejection fraction were -1%:2% at the beginning of the VEST study and -4%:4% at the end. Limits of agreement for the peak filling rate were -0.6:0.6 at the beginning of the VEST study and -0.7:0.5 at the end. For both measurements the limits of agreement were well within the clinical range. Repeatability was evaluated in a second group of 11 patients who underwent VEST studies in 2 separate days. The coefficient of repeatability (twice the standard deviation of the differences between the 2 studies) was 13 for the ejection fraction and 0.4 for the peak filling rate. Thus, the VEST is an accurate and repeatable method to measure both the ejection fraction and peak filling rate.


The use of thallium-201 lung/heart ratios. This survey gives an overview of the methodology of thallium-201 lung/heart uptake ratios often used as an independent factor in the assessment of patients with coronary artery disease undergoing myocardial perfusion scintigraphy. Different techniques have been used in the past. The most sensitive method is one which calculates a lung/heart ratio from scintigraphy obtained immediately after cessation of exercise. If single photon emission tomography (SPET) is routinely performed the anterior projection of the data set obtained during tomographic acquisition should be used in preference to a separate planar anterior static images recorded before or after the SPET procedure. The lung/heart ratio is useful as a prognostic indicator of outcome as it accurately mimics the degree of left ventricular dysfunction. With the increasing popularity of pharmacological stress testing there is evidence that this ratio still offer valid information. Additional work in this field is nevertheless required to further confirm this observation. In routine clinical practice, the lung/heart ratio should help and enable physicians to prioritise patients for urgent intervention.


Scintigraphic quantitation of gastrointestinal motor activity and transport: oesophagus and stomach. For the recognition and characterisation of oesophageal motor disorders, manometry represents the most reliable tool but yields no information on bolus transport. The transport can be quantitated by radionuclide techniques. The patient is positioned supine beneath a gamma-camera and instructed to swallow a radiolabelled bolus in a single gulp. Using a marker over the cricoid and the activity in the stomach as landmarks, regions of interest are drawn representing the upper, middle and lower third of the oesophagus and the gastric fundus. Activity-time curves enable one to recognise the clearance patterns in these regions. In combination, manometric and radionuclide transit studies recognise a higher number of motor disorders than either procedure alone. Radionuclide methods also are the most reliable and sensitive to quantitate gastric emptying. Procedure, meal size and composition as well as patient position must be standardised and correction techniques applied. The emptying of solid and liquid meal constituents can be evaluated concomitantly. Solids start to empty only after a lag phase of varying extent. With semi-solid meals, which are emptied at the same rate as solid meals of identical composition in the postlag phase, the recording time can be considerably shorter. Besides gastric emptying, the amplitude, frequency and propagation velocity of antral contractions can be recorded using serial images of short frame time and specially devised analytic techniques.


Acute hydrops of the gallbladder in childhood. Acute hydrops of the gallbladder (AHGB) is a rare paediatric disease being diagnosed with increased frequency due to its association with other illnesses and the availability of ultrasonography. The symptoms and signs of AHGB include abdominal pain, vomiting, abdominal mass and/or tenderness. As these clinical features mimic the more common surgical conditions such as acute appendicitis, intussusception and volvulus, some cases are still diagnosed only at laparotomy. Diagnosis is established by ultrasonography of the abdomen demonstrating normal biliary ducts and a distended gallbladder without calculi or congenital malformation. The aetiology of acute hydrops of the gallbladder is unknown but may be multifactorial. Treatment varies from non-operative management to surgical intervention.


Short stature with normal growth hormone and elevated IGF-I. We report on a Japanese girl with short stature, malar hypoplasia, up-slanting palpebral fissures, blue sclerae and thin, stiff and slightly brownish hair. Short stature started in utero and her psychomotor development was normal. Menarche appeared at 13 years 8 months. Height at 14 years 5 months was 132 cm (-4.6 SD). Her growth hormone (GH) sleep pattern and responses to insulin, L-dopa, arginine, propranolol-glucagon and growth hormone-releasing hormone were normal. Plasma insulin-like growth factor I (IGF-I) was high (2170-4860 units/l) and increased from 4860 to 7080 units/l 20 h after biosynthetic GH injection. Gel infiltration patterns of the free and protein-bound IGF-I in plasma from the patient were not different from the controls; IGF-I fraction of the high and low molecular weight binding protein and the non-protein bound fraction were 75.5%, 15.8% and 8.7%, respectively. IGF-I from the patient showed normal bioactivities when determined by [35S]sulphate and [3H]thymidine uptake into cultured rat chondrocytes, and by [3H]thymidine and [3H]alpha-aminoisobutyric acid uptake into the patient's skin fibroblasts. IGF-I binding to cultured skin fibroblasts from the patient was comparable to that of controls. These results suggest that tissue specific defects of IGF-I receptors may be the cause of increased IGF-I levels in the patient.


Upper gastro-intestinal tract bleeding in cirrhotic children candidates for liver transplantation. Signs of portal hypertension, history of upper gastro-intestinal tract bleeding episodes and outcome of the latter were recorded in 76 cirrhotic children evaluated for liver transplantation. Fifty-three (70%) had varices and 22 (29%) had experienced upper gastro-intestinal tract bleeding. Of these 22, 19 bled from varices and 3 from ulcers. Non bleeding ulcers were also found in five patients bleeding from varices. Iterative sclerotherapy controlled acute variceal bleeding in all but one patient in whom emergency transplantation was performed. Six of the eight patients with ulcers were successfully treated by the H2 histamine receptor antagonist ranitidine. We conclude that iterative sclerotherapy is efficient to control acute variceal bleeding and prevents recurrent bleeding in children with end-stage liver diseases awaiting liver replacement. Bleeding asymptomatic ulcers are frequent and respond to H2 histamine receptor antagonists.


A right lower quadrant mass in cystic fibrosis: a diagnostic challenge. In a cystic fibrosis (CF) patient a right lower quadrant (RLQ) mass may be a difficult diagnostic problem. Most frequently it is due to a distal intestinal obstruction syndrome also called meconium ileus equivalent, but the possibility of intussusception and appendiceal abscess should also be considered. We describe three CF patients with an appendiceal abscess seen in a 4-year period. All three patients had a palpable RLQ mass. Chronicity and obliteration of the appendiceal lumen with abnormally viscid mucus may lead to concealed perforation and be responsible for the atypical presentation.


Paraparesis secondary to a spinal mass as the presenting feature of erythroleukaemia in a 10-month-old child. Severe neurological impairment as the first symptom of acute leukaemia is a rather uncommon finding. We report the case of a 10-month-old infant who presented with acute paralysis of the lower extremities due to cord compression by an epidural tumour composed of malignant erythrocyte precursor cells. Diagnosis of erythroleukaemia (EL) was made by needle biopsy of the spinal epidural mass and confirmed by bone marrow aspiration. Antileukaemic treatment in combination with radiotherapy to the epidural tumour led to haematological remission and neurological recovery with disappearance of the mass lesion as demonstrated by MRI. However, haematological relapse occurred with death of the patient 7 months after diagnosis. This is the first reported case of EL presenting with paraparesis due to an epidural tumour. The clinical symptoms, results of cytogenetic and immunological studies and the clinical course are described.


Intracranial chordoma in a neonate.

Intracranial chordoma in a neonate. We report the first case of a congenital intracranial chordoma. Hydrocephalus, sixth and seventh cranial nerve palsy, and torticollis were observed shortly after birth. The tumour was delineated by sonography, CT scans and MRI and the diagnosis confirmed after subtotal resection at the end of the newborn period.


Disease patterns in early onset pauciarticular juvenile chronic arthritis. A group of 76 children with early onset pauciarticular juvenile chronic arthritis (JCA) was studied in order to establish different disease patterns and to try and identify parameters associated with an unfavourable outcome. An intermittent pattern of disease was found in 60 children (79%). Of the remaining 16 patients continuous persistent pauciarticular disease activity was present in 7 (9.2%) and extended pauciarticular in 9 children (11.8%). An extended pauciarticular pattern was seen predominantly in children with continuous disease activity. It appeared to be impossible to predict the course of the disease on the basis of clinical parameters. The frequency of complications, such as local growth disturbances or psychosocial problems and of chronic anterior uveitis resulting in visual handicap correlated with continuous disease activity. The extended pauciarticular pattern, resulting in polyarthritis resembled seronegative polyarticular JCA, underlining previous reports that the joint pattern during the course of disease may be more important than joint pattern at onset of disease.


Serious pertussis overlooked in infants. Two infants with life-threatening pertussis are presented in whom the diagnosis was delayed. A review of pertinent literature suggests that the diagnosis of pertussis in infants is frequently missed and therefore the morbidity and mortality from this disease is underestimated.


Exophiala dermatitidis pneumonia in cystic fibrosis. The chest X-ray film of a girl with cystic fibrosis (CF) showed slowly increasing mottled densities during the 6th and 7th year of her life. Pulmonary symptoms and distress proceeded fast in spite of intensive treatment with antibiotics, corticosteroids, and physiotherapy. Three different fungal organisms were repeatedly cultured from the sputum: Candida albicans, Aspergillus fumigatus, and Exophiala dermatitidis. Antibodies against C. albicans were in the normal range. Candida antigen in blood and antibodies against A. fumigatus were absent. Antibodies against E. dermatitidis were detected by a recently developed indirect immunofluorescence assay. It seems most probable that E. dermatitidis was the causal agent for fungal pneumonia in this case. Under therapy with amphotericin B and flucytosine the clinical course and radiological appearance improved but definitive eradication of E. dermatitidis was only achieved after treatment with itraconazole. The isolation of this fungus from the sputum of a CF patient is reported for the first time. The significance of fungal infections in CF is discussed.


Elastase alpha 1 proteinase inhibitor complex, granulocyte count, ratio of immature to total granulocyte count, and C-reactive protein in neonatal septicaemia. In a prospective study elastase alpha 1-proteinase inhibitor (E alpha 1PI), polymorphonuclear (PMN) count, the immature to total neutrophil count ratio (I/T ratio), and C-reactive protein (CRP) were analysed in 74 patients (76 cases) with neonatal septicaemia at the time of initial clinical symptoms. At that early stage of the disease, 94% of the patients had abnormal values for E alpha 1PI, 71% for I/T ratio, 61% for PMN count, and only 54% for CRP. PMN count was a poor indicator of septicaemia. Neutropenia, present in 26% of all patients, was related to normal E alpha 1PI in only 4 patients. The combined use of E alpha 1 and I/T ratio was the most sensitive indicator. In all patients irrespective of causative bacteria or disease onset at least one of these parameters was elevated. In early-onset septicaemia (n = 31), normal CRP values occurred significantly more often (63%) than in late-onset sepsis (33%). Even in five of the seven fatal cases, initial CRP measurements were normal. The sensitivity of PMN count and I/T ratio did not differ significantly between early- and late-onset septicaemia. Laboratory changes observed in 18 newborns during the first 3 days of the septic episode show that the rate of pathological values for E alpha 1PI and I/T ratio was highest at the time of initial clinical symptoms and decreased on days 2 and 3. In contrast, CRP reached maximal values as late as day 2 (88% abnormal values), followed by a decrease on day 3. We conclude that the use of E alpha 1PI may improve the laboratory detection of neonatal septicaemia especially if used in combination with I/T ratio.


Randomized double blind trial of Ambroxol for the treatment of respiratory distress syndrome. In order to test the ability of Ambroxol to improve the clinical course of respiratory distress syndrome and to reduce the incidence of complications a multicentre, randomized, placebo-controlled double-blind trial was conducted. Entry was limited to infants with a birth weight below 1500 g. A total of 179 neonates were enrolled, but 31 were later excluded because they had other diseases. Of the remaining 148 babies, 74 received Ambroxol (birth weight 1190 +/- 216 g; gestational age 29.1 +/- 1.9 weeks) and 74 placebo (birth weight 1168 +/- 216 g; gestational age 28.9 +/- 1.9 weeks). In the Ambroxol group 23 (31%) and in the placebo group 27 (37%) infants died during the first 5 months of life. In 28 day-survivors Ambroxol was able to significantly improve the PaO2/FiO2 ratio, mean airway pressure, phospholipid profile of tracheal effluent and pulmonary mechanics of spontaneously breathing infants. In addition, the incidences of bronchopulmonary dysplasia (29% vs 54%), intraventricular haemorrhage (25% vs 44%) and postnatally acquired pneumonia (15% vs 36%) were significantly reduced in the Ambroxol group as compared to the control group. No adverse events attributed to the Ambroxol treatment were reported.


Effect of dexamethasone on blood pressure--relationship to postnatal age. The relationship of the change in blood pressure levels of very preterm infants treated with dexamethasone to postnatal age was investigated. Sixteen infants, median gestational age 26 weeks (range 23-33) (early treatment group), and 15 infants, median gestational age 26 weeks (range 24-32) (late treatment group) were recruited. Dexamethasone was administered at a median postnatal age of 17 days (range 3-26) and 50 days (range 29-112), respectively. The systolic blood pressure at the start of treatment and the maximum systolic blood pressure achieved during therapy were both significantly lower (P less than 0.01) in the early rather than the late treatment group. The change in blood pressure, however, that is, from the pre-treatment level to the maximum systolic blood pressure achieved during therapy, was similar in the two groups (median 38 mmHg, range 23-59 early treatment group and median 34 mmHg, range 16-66 late treatment group). We conclude that, even in the first 4 weeks of life, dexamethasone can cause a marked elevation of systolic blood pressure. As a consequence, regardless of the postnatal age at which dexamethasone is administered, blood pressure levels must be measured regularly.


The relationship of fluid restriction during the 1st month of life to the occurrence and severity of bronchopulmonary dysplasia in low birth weight infants: a 1-year radiological follow up. One hundred consecutive low birth weight (LBW) infants (less than 1751 g) were randomized into a study group having a restricted fluid intake until 4 weeks of age and a control group following the fluid regimen conventionally used in the hospital. Chest X-ray films were examined on admission, at the ages of 3 days, 7 days, 2 weeks and 4 weeks and at 2-monthly visits to the outpatient clinic up to 1 year of age or until the chest examinations were normal. The severity of hyaline membrane disease (HMD) and typical radiological abnormalities of bronchopulmonary dysplasia (BPD) were assessed. Twelve patients succumbed, one in the study group and 11 in the control group. The study group seemed experience less severe HMD than the controls. Fifty-four percent of the former and 32% of the latter were alive and had no radiological signs of BPD at 4 weeks of age (P less than 0.05). The difference between the groups in the cumulative number of normal chest X-ray examinations during the follow up was even more significant. The percentage of normal X-ray films at 1 year of age was 92% in the study group and 72% in the control group. These results suggest that fluid restriction for the first 4 weeks of life can lower the incidence of radiological abnormalities typical of BPD obtained during the 1st year of life in LBW infants. Pulmonary oedema seems to be a significant aetiological factor causing HMD to develop into chronic lung disease.