Pneumonectomy in cystic fibrosis.

A 17-year-old boy and a 12-year-old girl with cystic fibrosis (forced expiratory volume in 1 sec, 36% and 14% of predicted values, respectively) developed severe right-sided lung infections with abscess formations and complete atelectases unresponsive to medical therapy. In both patients, unilateral emergency pneumonectomy resulted in rapid clinical improvement. Despite her severe underlying lung disease, the girl experienced a remarkable increase in quality of life; 2 years after surgery, she died from respiratory failure. The male patient has now survived for 4 years, and lung transplantation still remains a therapeutic option for him. We believe that pneumonectomy is a valuable rescue therapy for patients with cystic fibrosis and intractable unilateral lung infections who are at high risk of dying while waiting for lung transplantation.

Comparison of captopril and ibopamine in mild to moderate heart failure.

OBJECTIVE: To determine the effects of ibopamine 100 mg three times daily compared with captopril 25 mg three times daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, parallel group comparison of the addition of ibopamine versus captopril during a period of 24 weeks. SETTING: 26 outpatient cardiology clinics in seven European countries. PATIENTS: 266 patients, with mild to moderate chronic heart failure (New York Heart Association (NYHA) functional class II, 81% and III, 19%) and evidence of an enlarged left ventricle. Patients received concomitant treatment with diuretics and/or digitalis. MAIN OUTCOME MEASURE: Exercise duration after 24 weeks of treatment, compared with baseline. RESULTS: Mean (SD) ejection fraction was 29 (8)% and the baseline exercise duration in the captopril and ibopamine groups 665 (160) and 675 (174) seconds, respectively. At the end of the study, exercise duration had improved in both groups, by 29 seconds in the ibopamine group (P < 0.01), and by 24 seconds in the captopril group (P < 0.05). There was no difference between groups (P = 0.69, 95% confidence interval -22 to 33). NYHA class, signs and symptoms score, and dyspnoea and fatigue index improved equally in both groups. The total number of adverse events was the same in both treatment groups, but gastrointestinal complaints occurred more often in the ibopamine group. The number of patients with premature withdrawals was no different. CONCLUSIONS: No difference was detected between the effect of captopril and ibopamine on exercise time in patients with mild to moderate heart failure during a treatment period of 24 weeks.

Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system.

A method has been developed for culturing cardiac myocytes in a collagen matrix to produce a coherently contracting 3-dimensional model heart tissue that allows direct measurement of isometric contractile force. Embryonic chick cardiomyocytes were mixed with collagen solution and allowed to gel between two Velcro-coated glass tubes. During culture, the cardiomyocytes formed spontaneously beating cardiac myocyte-populated matrices (CMPMs) anchored at opposite ends to the Velcro-covered tubes through which they could be attached to a force measuring system. Immunohistochemistry and electron microscopy revealed a highly organized tissue-like structure of alpha-actin and alpha-tropomyosin-positive cardiac myocytes exhibiting typical cross-striation, sarcomeric myofilaments, intercalated discs, desmosomes, and tight junctions. Force measurements of paced or unpaced CMPMs were performed in organ baths after 6-11 days of cultivation and were stable for up to 24 h. Force increased with frequency between 0.8 and 2.0 Hz (positive "staircase"), increasing rest length (Starling mechanism), and increasing extracellular calcium. The utility of this system as a test bed for genetic manipulation was demonstrated by infecting the CMPMs with a recombinant beta-galactosidase-carrying adenovirus. Transduction efficiency increased from about 5% (MOI 0.1) to about 50% (MOI 100). CMPMs display more physiological characteristics of intact heart tissue than monolayer cultures. This approach, simpler and faster than generation of transgenic animals, should allow functional consequences of genetic or pharmacological manipulation of cardiomyocytes in vitro to be studied under highly controlled conditions.

Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT).

OBJECTIVES: This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo. BACKGROUND: Ibopamine and digoxin are drugs that exert hemodynamic and neurohumoral effects. Because there is accumulating evidence that progression of disease in chronic heart failure is related not only to hemodynamic but also to neurohumoral factors, both drugs might be expected to have a favorable long-term effect. METHODS: We studied 161 patients with mild to moderate chronic heart failure (80% in New York Heart Association functional class II and 20% in class III), who were treated with ibopamine (n = 53), digoxin (n = 55) or placebo (n = 53) for 6 months. Background therapy consisted of furosemide (0 to 80 mg); all other drugs for heart failure were excluded. Clinical assessments were made at baseline and after 1, 3 and 6 months. RESULTS: Of the 161 patients, 128 (80%) completed the study. Compared with placebo, digoxin but not ibopamine significantly increased exercise time after 6 months (p = 0.008 by intention to treat analysis). Ibopamine was only effective in patients with relatively preserved left ventricular function, as it significantly increased exercise time in this subgroup (for patients with a left ventricular ejection fraction > 0.30; p = 0.018 vs. placebo). No patient receiving digoxin withdrew from the study because of progression of heart failure, compared with six patients receiving ibopamine and two receiving placebo. At 6 months, plasma norepinephrine was decreased with digoxin and ibopamine therapy (-106 and -13 pg/ml, respectively) but increased with placebo administration (+62 pg/ml) (both p < 0.05 vs. placebo). Plasma aldosterone was unaffected, but renin was decreased by both agents after 6 months (p < 0.05 vs. placebo). Total mortality and ambulatory arrhythmias were not significantly affected by the two drugs. CONCLUSIONS: Ibopamine and digoxin both inhibit neurohumoral activation in patients with mild to moderate chronic heart failure. However, the clinical effects of these drugs are different and appear to be related to the degree of left ventricular dysfunction.

[Cardiopulmonary capacity in patients with mucoviscidosis. Comparison of ergospirometry findings with clinical and radiological scores]. / Kardiopulmonale Leistungsfähigkeit von Patienten mit Mukoviszidose. Vergleich ergospirometrischer Befunde mit klinischen und radiologischen Scores.

AIM OF STUDY: Shwachman-Kulczycki- and Chrispin-Norman-Scores are widely used scoring systems for CF-patients. Maximum bicycle exercise testing was performed in 15 patients (medium age 13.4 years) to investigate whether clinical and radiographic scores or pulmonary function testing could predict cardiorespiratory fitness. METHODS: A progressive exercise test was used to determine maximum working capacity (Wmax). Prior to exercise testing, lung function and blood gases were investigated. Chest radiographs were scored by an independent radiologist (G.B.) applying the Chrispin-Norman-Score. The Shwachman-Kulczycki-Score was determined by two observers (F.F., H.S.). RESULTS: Chrispin-Norman-Score, Schwachman-Kulczycki-Score, results of lung function testing and blood gas values were significantly correlated to each other. However no significant correlation was found to the degree of exercise limitation. CONCLUSION: Clinical, radiographic scores and lung function testing cannot predict exercise tolerance. Exercise testing is mandatory to evaluate cardio-respiratory fitness in CF-patients.

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.

[Taurine supplementation in cystic fibrosis (CF): effect on vitamin E absorption kinetics]. / Taurin-Supplementierung bei Cystischer Fibrose (CF): Einfluss auf die Absorptionskinetik von Vitamin E.

Oral vitamin E (Vit.E) bioavailability is reduced in CF patients especially in case of malnourishment. Both exocrine pancreatic insufficiency and an altered bile acid composition showing an elevated glycine taurine ratio of conjugated bile acids which is due to excessive loss of bile acids in the stools may contribute to this observation. Because taurine supplementation reduces the glycine/taurine ratio of bile acids in duodenal juice of CF-patients it was the objective of this study to evaluate the effect of taurine supplementation on Vit.E absorption kinetics. Oral Vit.E tolerance tests (50 mg/kg) were performed before and after 3 months of taurine supplementation (30 mg/kg/day) in 11 CF patients (ages 7 to 22 years) under fasting conditions. Bodyweight and or weight for height of all patients were below the 25th percentile. Doses of all medications except antibiotics were kept unchanged during the study. Any additional Vit.E supplementation was stopped 14 days prior to each test. Serum Vit.E levels were measured over a 24 hour period. Determination of serum Vit.E concentrations was performed with a HPLC fluorescence technique. The glycine/taurine ratio in serum served as compliance parameter and dropped in all but one patients. Baseline Vit.E concentrations and serum Vit.E/total lipids ratios in serum considered as parameters of the Vit.E status increased significantly. Both the maximal Vit.E concentrations in serum and the areas under the oral absorption curves showed a significant increase with taurine supplementation. This study shows that the Vit.E status of malnourished CF patients can be improved with taurine supplementation due to improved Vit.E absorption kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

[Glucose homeostasis in mucoviscidosis]. / Untersuchung zur Glukosehomöostase bei Mukoviszidose.

In patients with cystic fibrosis (CF) of the pancreas an endocrine imbalance especially of insulin secretion due to progressive structural abnormalities of the pancreas must be expected. 30-75 percent of CF-patient exhibit impaired oral glucose tolerance tests (oGTT). Deterioration of the glucose homeostasis leads to a secondary diabetes mellitus that mimics a type II diabetes in the early stage, in the later course of disease it resembles a type I diabetes with absolute insulinopenia. In this study glucose homeostasis was investigated after an oral glucose load with 1.75 g glucose/kg bodyweight. Glucose, C-peptide and insulin were measured during 180 minutes. 32 nondiabetic CF-patients were studied. 16 patients revealed an impaired oral glucose tolerance according to the criteria of the National Diabetes Data Group. 6 patients showed a normal glucose tolerance and 10 patients with normal fasting and 120 minute glucose concentrations were hyperglycemic at midtest determinations. Impaired oGTTs were observed in malnourished CF-patients in a higher rate than in normal weight patients. A delayed and exceeded C-peptide and insulin response to the oral glucose load was determined with deteriorating glucose tolerance. Glucose values did not drop to fasting values at the 180 minute determination in cases of impaired oral glucose tolerance.

Atrioventricular conduction disturbance as an early feature of Reiter's syndrome.

Atrioventricular (A-V) conduction disturbances in Reiter's syndrome are usually described in longstanding disease. This report deals with two male patients with Reiter's syndrome who developed an A-V block early in the course of the disease. One of these patients developed a second degree A-V block, Wenckebach type, which has not been described before at an early stage of this syndrome.

Effect of procainamide, propranolol and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia.

The effect of short-term intravenous administration of procainamide (12 patients), propranolol (4 patients) and verapamil (4 patients) was studied in 12 patients with chronic recurrent sustained ventricular tachycardia. In all patients tachycardia could reproducibly be initiated and terminated with programmed electrical stimulation of the heart. Procainamide (1) lengthened the effective refractory period of the right ventricle, (2) affected the tachycardia zone, (3) reduced ventricular rate during tachycardia, and (4) lengthened the interval between the tachycardia-initiating premature ventricular beat and the first QRS complex of tachycardia. No effect on the refractory period of the right ventricle or the mechanism of tachycardia was seen after administration of propranolol or verapamil. Apart from their therapeutic implications these data suggest that it may be possible to use drugs to study mechanisms of ventricular tachycardia in the human heart.

Effect of verapamil studied by programmed electrical stimulation of the heart in patients with paroxysmal re-entrant supraventricular tachycardia.

Atrioventricular (AV) conduction, ventriculoatrial (VA) conduction, and the mechanism of tachycardia, were studied by programmed electrical stimulation before and after the administration of verapamil, in 10 patients with paroxysmal re-entrant supraventricular tachycardia. In 7 patients the tachycardia circuit was confined to the AV node. In 3 patients an accessory pathway conducting only in the ventriculoatrial direction was used during tachycardia. When administered intravenously during tachycardia, verapamil terminated the arrhythmia in 9 patients. Verapamil lengthened the effective and the functional refractory period of the AV node and the AV nodal transmission time in all patients in whom this could be studied. As a result of these changes, it was not possible to initiate tachycardia in 3 patients. The width of the zone of atrial premature beats able to initiate tachycardia (the tachycardia zone) narrowed in 5 patients, and increased in 2 patients. In 6 of these 7 patients the tachycardia zone shifted to longer premature beat intervals. Verapamil resulted in slowing of the heart rate during tachycardia. Apart from slowing in heart rate during tachycardia and termination of tachycardia after intravenous verapamil, the 3 patients with an accessory pathway showed no beneficial effect of verapamil on the mechanism of initiation of tachycardia. Five patients were restudied after 2 to 3 weeks of oral administration of verapamil. Though less, effects were similar to those obtained after intravenous administration.

Familial prevalence of asymmetric septal hypertrophy.

Echocardiography was used to detect the familial prevalence of asymmetric septal hypertrophy in relatives of patients with proven idiopathic hypertrophic subaortic stenosis. Idiopathic hypertrophic subaortic stenosis is only one clinical expression of a cardiomyopathic disease spectrum, including asymptomatic patients having asymmetric septal hypertrophy as a characteristic anatomic marker which can be detected by echo. The validity of previous proposed criteria to detect this marker was checked in our population. Therefore we examined normal subjects, patients with fixed left ventricular outflow obstruction (valvular aortic stenosis), and those with idiopathic hypertrophic subaortic stenosis who served as index cases. A septal thickness exceeding that of the free left ventricular posterior wall by 30% separates patients with a cardiomyopathy from those without this disease. 27 of 73 examined relatives of 14 index cases were found to have asymmetric septal hypertrophy. In those instances where information was available from the parents of the index cases, one parent was found to be affected. When the examined group is considered from a parent-child relationship (including the index case when appropriate), it included 78 children of affected single parents of which 20 males and 19 females had asymmetric septal hypertrophy. The history, clinical examination and electrocardiogram were not useful to detect the disease. The results suggest an autosomal dominant mode of inheritance of asymmetric septal hypertrophy with a high penetrance.

Effect of amiodarone in the Wolff-Parkinson-White syndrome.

The effect of amiodarone in the Wolff-Parkinson-White syndrome was studied with programmed electrical stimulation of the heart in 15 patients. All 15 patients had circus movement tachycardias; 7 also had atrial fibrillation. Programmed electrical stimulation was performed before and after 14 days of oral administration of amiodarone. The effective refractory period of the accessory pathway lengthened in an atrioventricular direction in all patients and in a ventriculoatrial direction in eight patients. The effective refractory period of the atrium and ventricle lengthened in 14 and 12 patients, respectively. After administration of amiodarone, circus movement tachycardia could no longer be initiated in five patients. The zone of tachycardia narrowed in four patients, did not change in two and increased in seven. The effect of amiodarone on initiation of circus movement tachycardia could be related to differences in effect of the drug and in the mechanism of tachycardia in individual patients. In all patients in whom tachycardias could still be initiated after treatment with amiodarone the heart rate during tachycardia was slower than before treatment. This slowing was caused by a decrease in conduction velocity of the circulatory wave in different parts of the tachycardia circuit. The effect of amiodarone in prolonging the refractory period of the accessory pathway makes this drug especially useful in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation.