Repetitive use of levosimendan for treatment of chronic advanced heart failure: clinical evidence, practical considerations, and perspectives: an expert panel consensus.

BACKGROUND: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. METHODS AND RESULTS: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. CONCLUSIONS: The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.

Total beta-adrenoceptor deficiency results in cardiac hypotrophy and negative inotropy.

The present study investigated cardiac function in hearts of mice with total deficiency of the beta1-, beta2- and beta3-adrenoceptors (TKO) in comparison to wildtype mice (WT). We investigated cardiac morphology and echocardiographic function, measured protein expression of Ca2+-regulatory proteins, SERCA 2a activity, myofibrillar function, and performed running wheel tests. Heart weight and heart-to-body weight ratio were significantly smaller in TKO as compared to WT. This was accompanied by a decrease in the size of the cardiomyocytes in TKO. Heart rate and ejection fraction were significantly diminished in TKO as compared to WT. Protein expressions of SERCA 2a, ryanodine receptor and Na+/Ca2)-exchanger were similar in TKO and WT mice, but phospholamban protein expression was increased. PKA-dependent phosphorylation of phospholamban at serine 16 was absent and CaMKII-dependent phosphorylation at threonine 17 was decreased in TKO. All alterations were paralleled by a decrease in SERCA 2a-activity. A similar maximal calcium-dependent tension but an increased myofibrillar calcium-sensitivity was measured in TKO as compared to WT. We did not observe relevant functional impairments of TKO in running wheel tests. In the absence of beta-agonistic stimulation, SERCA 2a activity is mainly regulated by alterations of phospholamban expression and phosphorylation. The decreased SERCA 2a activity following beta-adrenoceptor deficiency may be partly compensated by an increased myofibrillar calcium-sensitivity.

Reduced troponin I phosphorylation and increased Ca(2+)-dependent ATP-consumption in triton X-skinned fiber preparations from Galphaq overexpressor mice.

Overexpression of the Galphaq-protein has been shown to result in hypertrophic and dilated cardiomyopathy. This study investigated Ca(2+ )sensitivity of tension and myosin-ATPase activity in skinned fiber preparations of male and female wildtype (WT; n = 12) and transgenic mice with a cardiac specific overexpression of the Galphaq-protein (Galphaq-OE; n = 11). In addition, the phosphorylation status of troponin I was measured. Ca(2+) sensitivity of tension was increased in Galphaq-OE with a significant reduction in the half-maximum Ca(2+) concentration (EC(50)) compared to WT. Similarly, Ca(2+) sensitivity of myosin ATPase activity was increased in Galphaq-OE when comparing Galphaq-OE to WT. Maximum Ca(2+)-dependent tension and ATPase activity were both enhanced in Galphaq-OE compared to WT littermates. Phosphorylation of troponin I was significantly reduced in Galphaq-OE compared to WT. In the above experiments, no gender specific differences were observed in either Gaq-OE or in WT. We conclude that, in mice, increased expression of the Galphaq-protein induces alterations of myofibrillar function and energy consumption, which are also characteristics of human heart failure. This may result from a decreased phosphorylation of troponin I in Galphaq-OE.

Differential increase of CD34, KDR/CD34, CD133/CD34 and CD117/CD34 positive cells in peripheral blood of patients with acute myocardial infarction.

OBJECTIVE: Circulating progenitor cells (CPC) may contribute to cardiac regeneration and neovascularization after acute myocardial infarction (AMI). For potential therapeutic use, understanding the endogenous mechanisms after ischemia is inevitable. We investigated the absolute number, but also the subset composition of CD34+ CPC after AMI. METHODS: CD34+, KDR+/CD34+, CD133+/CD34+ and CD117+/CD34+CPC were analyzed by FACS in peripheral blood of 10 patients with acute MI (59+/-5 yrs, m/f=8/2) at day of AMI (day 0) and days 1-5. For comparison patients with stable coronary artery disease (CAD, n=12, 66+/-2 yrs, m/f=10/2) and young healthy volunteers (n=7, 26+/-2 yrs, m/f=3/4) were studied. RESULTS: CD34 and KDR/CD34, CD133/CD34, CD117/CD34 were increased day 3 and 4 after AMI. KDR+ fraction within CD34+ population remained unchanged (58.3+/-7.8% vs 55.3+/-10.6%), whereas CD133+ (64.9+/-3.1% vs 43.5+/-5.9%, P=0.006) and CD117+ fractions (71.7+/-5.6% vs 50.1+/-5.5%, P=0.02) were elevated. In CAD, all CPC and fractions were similar as AMI day 0. Healthy volunteers had more CD34+ than CAD and AMI day 0. Double positive CPC were also higher, but fractions were unchanged vs CAD with more KDR/CD34 in trend (72.8+/-10.6% vs 50.5+/-5.6%, P=0.058). After AMI both absolute numbers of CD34+ and their subset composition change, suggesting selective mobilization of CPC. Increased CPC after AMI never reach numbers of young healthy volunteers.

Nebivolol induces eNOS activation and NO-liberation in murine corpus cavernosum.

Erectile function is critically dependent upon the activation of the endothelial nitric oxide synthase (eNOS) in the smooth muscle cells of penile corpus cavernosum tissue. Nebivolol is a beta(1)-selective beta-adrenoceptor blocker (beta-ARB) with additional vasodilating properties, which have been attributed to eNOS-activation. Our study investigated whether nebivolol is able to increase eNOS activity in erectile tissue. Murine penile tissue was incubated in an organ bath under control conditions and in the presence of nebivolol or metoprolol. Immunofluorescence staining was performed using specific antibodies against eNOS-activation or eNOS-serine 1177 phosphorylation. Corpus cavernosum smooth muscle tissue was identified using a smooth muscle actin antibody. In addition, slices of murine erectile tissue were incubated with diaminofluorescein (DAF), a specific fluorescence marker for NO-liberation. Under control conditions and after application of metoprolol, we observed a small eNOS-activation and serine 1177-phosphorylation in murine corpus cavernosum tissue. A significant increase in eNOS-activation and serine 1177-phosphorylation of eNOS was observed only in the presence of nebivolol (10 muM). These alterations of the eNOS protein induced after application of nebivolol were associated with a time-dependent increase in DAF fluorescence in murine erectile tissue. We conclude that beta-adrenoceptor blockers differentially influence erectile tissue. Since cardiovascular diseases are often associated with the development of erectile dysfunction, the nebivolol-induced eNOS-activation in corpus cavernosum may be beneficial when treating patients suffering from cardiovascular disease.

Chronic treatment with carvedilol improves Ca(2+)-dependent ATP consumption in triton X-skinned fiber preparations of human myocardium.

Evidence is given that beta-blocker treatment differentially influences gene expression and up-regulation of beta(1)-adrenoceptors in human myocardium. Here, we investigate whether long-term treatment with carvedilol or metoprolol may functionally alter myofibrillar function in end-stage human heart failure. Investigations were performed in Triton X (1%, 4 degrees C, 20 h)-skinned fiber preparations of explanted hearts from patients undergoing heart transplantation due to idiopathic dilative cardiomyopathy. Five patients were not on beta-adrenoceptor blocker treatment (DCM_NBB), and 5 patients received either carvedilol (DCM_CAR) or metoprolol (DCM_MET). Nonfailing (NF) donor hearts (n = 5), which could not be transplanted due to technical reasons, were investigated for comparison. Ca(2+)-dependent tension (DT) development and actomyosin-ATPase activity (MYO) were measured and tension-dependent ATP consumption was calculated by the ratio of DT and MYO ("tension cost"). In addition, we measured the phosphorylation of troponin I (TNI) by back phosphorylation. Maximal DT and TNI phosphorylation were reduced, with myofibrillar Ca(2+) sensitivity of DT and MYO as well as tension cost being increased in DCM_NBB compared with NF. Metoprolol treatment restored TNI phosphorylation, decreased Ca(2+) sensitivity of tension development and of myosin-ATPase activity, but did not alter the tension-dependent ATP consumption. Carvedilol treatment improved maximal DT and significantly decreased tension-dependent ATP consumption without altering myofibrillar Ca(2+) sensitivity. TNI dephosphorylation was increased in patients treated with carvedilol. In conclusion, chronic beta-adrenoceptor blockade functionally alters myofibrillar function. The more economic cross-bridge cycling in patients under carvedilol treatment may provide an explanation for the efficacy of carvedilol in the treatment of chronic heart failure patients.

Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men.

1. Hypertensive men treated with beta-blockers frequently complain of erectile dysfunction. The present study investigated the effects of two beta(1)-adrenoceptor-selective antagonists, namely nebivolol and metoprolol, on erectile function in hypertensive men. 2. Male out-patients (age range 40-55 years) with newly diagnosed or existing stage 1 essential hypertension (mean seated systolic blood pressure 140-159 mmHg; diastolic blood pressure 90-99 mmHg) were enrolled in the study. All patients lived in a stable, heterosexual partnership and had no history of sexual dysfunction. After a 2-week placebo run-in period, patients were randomized double-blind to either Treatment group A (comprising nebivolol 5 mg once daily for 12 weeks, followed by placebo for 2 weeks and then metoprolol succinate 95 mg once daily for 12 weeks) or Treatment group B (comprising metoprolol succinate 95 mg for 12 weeks, placebo for 2 weeks and then nebivolol 5 mg for 12 weeks). An international index of erectile function (IIEF) questionnaire and a diary documented patients' sexual function and activity. 3. Nebivolol and metoprolol lowered blood pressure to a similar extent. Metoprolol, but not nebivolol, significantly decreased the IIEF erectile function subscore by 0.92 in the first 8 weeks after onset of beta-blocker treatment. In contrast with metoprolol, nebivolol improved secondary sexual activity scores and other IIEF subscores. 4. Despite similar antihypertensive efficacy of the cardioselective beta(1)-adrenoceptor antagonists nebivolol and metoprolol, nebivolol may offer additional benefits by avoiding erectile dysfunction in male hypertensive patients on long-term beta-adrenoceptor antagonist therapy.

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system.

AIMS/HYPOTHESIS: The angiotensin II (type 1) (AT1) receptor mediates many biological effects of the renin-angiotensin system (RAS), leading to remodelling of cardiac tissue. The present study was designed to analyse changes in the function and expression of the AT1 receptor as principal effector of the RAS in myocardium from type 2 diabetic patients compared with non-diabetic myocardium as control. In addition, we determined the effect of treatment with ACE inhibitors or AT1 receptor blockers on expression levels of the receptor in diabetic patients. METHODS: Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium. We investigated functional coupling of the receptors by measuring contractility in isolated trabeculae stimulated with increasing concentrations of angiotensin II. RESULTS: Diabetic myocardium showed a significant increase in protein expression (170 +/- 16% of control) and median mRNA expression (186% of control) of the AT1 receptor. The additional receptors were functionally coupled, resulting in a stronger inotropic response upon stimulation with angiotensin II (89 +/- 5.5% vs 29 +/- 1.6% in controls), whereas receptor affinity was similar in both groups. However, myocardium from diabetic patients treated with ACE inhibitors or AT1 receptor blockers showed no increase in AT1 receptor expression. CONCLUSIONS/INTERPRETATION: AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS. These findings could at least in part explain the strong therapeutic benefit of RAS inhibition in diabetic patients.

Beta3-adrenergic stimulation in the human heart: signal transduction, functional implications and therapeutic perspectives.

Next to beta1- and beta2-adrenoceptors, a third beta-adrenoceptor population is expressed in the human heart, the beta3-adrenoceptor. In mammalian ventricular myocytes, beta3-adrenergic stimulation leads to a decrease in contractility via a release of nitric oxide (NO). Recently, different molecular mechanisms of beta3-adrenergic activation of endothelial nitric oxide synthase (eNOS) have been uncovered in cardiac myocytes. In the non-failing and especially the failing heart, beta3-adrenergic stimulation may offer protection against excessive catecholaminergic beta1-adrenoceptor stimulation. In this context, the beta3-adrenoceptor is discussed as a novel target for the pharmacological therapy of heart failure.

Overexpression of sorcin enhances cardiac contractility in vivo and in vitro.

Sorcin (SOR), an EF-hand Ca(2+)-binding protein, interacts with the sarcolemmal proteins Annexin VII and L-type Ca(2+)-channel and with the sarcoplasmic reticulum (SR) Ca(2+)-release channel (ryanodine-receptor, RYR), and has been implicated to influence the intracellular Ca(2+)-homeostasis. The present study aimed at investigating the effects of increased SOR expression on force development and relaxation in virus transfected rat hearts and isolated cardiomyocytes. We generated an adenovirus encoding the SOR coding DNA with a separate cassette for green fluorescent protein (GFP) both driven by the CMV-promoter to induce SOR-overexpression (Ad.SOR.GFP). As control served an adenovirus carrying an empty cassette with a separate cassette for GFP also driven by CMV-promoters (Ad.GFP). Cardiomyocytes of healthy male rats were isolated, transfected and cultured for 48 h with Ad.SOR.GFP as well as Ad.GFP as control. In addition, Ad.SOR.GFP was injected into coronary arteries via a catheter-based technique and rat hearts were transfected in vivo for 12 days. Echocardiography was performed to assess cardiac function at 7 and 12 days before the animals were sacrificed. A 1.7-fold increase of the SOR protein amount in cultured myocytes treated with Ad.SOR.GFP compared to Ad.GFP-transfected cells indicated a successful overexpression of SOR. Cell-contracting experiments using infected cardiomyocytes (transfection: 48 h; frequency: 0.5 Hz) exhibited a significantly higher peak force of contraction (FOC) in the SOR-overexpression group (n = 64) vs. control (n = 21) (6.8% +/- 0.2% vs. 4.3% +/- 0.1%). Beta-adrenergic stimulation with forskolin resulted in similar increases in FOC. Echocardiography of in vivo transfected rat hearts exhibited enhanced fractional shortening (65.9 +/- 5.5% vs. 79.3 +/- 2.5%) and decreased end-systolic diameters indicating enhanced cardiac contractility. Gross morphology was similar in both groups after 14 days of transfection. These results strengthen the notion that overexpression of SOR improves cardiac contractility independent of beta-adrenergic stimulation and may prove beneficial in the treatment of decreased cardiac output such as heart failure.

The effect of preoperative antiplatelet therapy in coronary artery surgery: blood transfusion requirements for patients on cardiopulmonary bypass.

INTRODUCTION: Bleeding after heart operations remains a common complication and contributes to morbidity and death. Recent studies have suggested that antiplatelet therapy (APT) may not increase homologous blood requirements in coronary bypass surgery. The purpose of this study was to examine the influence of APT therapy on haemorrhage and transfusion requirements in patients undergoing coronary artery bypass (CABG) on cardiopulmonary bypass (CPB). MATERIALS AND METHODS: Records from 290 consecutive patients who underwent CABG with CPB were retrospectively reviewed, including 145 patients who received APT within 5 days prior to surgery and 145 control patients (CON). Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge. RESULTS: Both groups were well matched with respect to demographic and intra-operative data. There was significantly (p < 0.0005) more mediastinal tube drainage at 24 h in the APT group (1123 mL +/- 537 mL) compared to CON patients (874 mL +/- 351 mL). In addition, the APT group received significantly more units of blood (APT: 2.6 +/- 2.5 vs CON: 1.6 +/- 1.8; p < 0.0005), platelet units (APT: 1.2 +/- 1.8 vs CON: 0.2 +/- 0.8; p < 0.0005), and fresh frozen plasma units (APT: 2.0 +/- 2.2 vs CON: 1.3 +/- 2.0; p = 0.01). CONCLUSION: This study suggests consideration should be given to delaying elective CABG for patients who have received APT treatment until APT is discontinued for at least 5 days.

Calcineurin independent development of myocardial hypertrophy in transgenic rats overexpressing the mouse renin gene, TGR(mREN2)27.

Myocardial hypertrophy is an independent risk factor for development of heart failure. The intracellular calcium homeostasis is altered in myocardial hypertrophy, and recent studies in animal models have confirmed an interaction between the Ca2+/calmodulin-dependent calcineurin signaling cascade and development of cardiac hypertrophy. There is evidence for the involvement of various pathways in development of hypertrophy. A transgenic rat model overexpressing the mouse renin gene, TGR(mREN2)27 has been shown to progress profound cardiac hypertrophy, possibly due to a monogenetic disorder. However, the exact mode of action is not known. To study a possible involvement of calcineurin and its downstream pathway in development of cardiac hypertrophy in this transgenic rat model we measured the protein expression of marker proteins of the calcineurin cascade (calcineurin, NFAT-3, GATA-4) and calcineurin phosphatase activity and GATA-4 DNA binding in TGR ( n=10) compared to age-matched Sprague-Dawley rats ( n=10). In our study there was no significant difference in calcineurin activity between the transgenic hearts and the hearts of Sprague-Dawley rats. Furthermore, we found neither an increase in protein expression of calcineurin B nor a rise in nuclear translocated NFAT-3 DU. Interestingly, the protein expression of GATA-4 and its DNA binding activity were significantly higher in hypertrophied myocardium than in control hearts. In transgenic rats overexpressing the mouse renin gene and thereby developing pronounced cardiac hypertrophy [TGR(mREN2)27] we thus found no activation of calcineurin or its downstream pathway. However, the expression of the transcriptional factor GATA-4 and its DNA binding activity were significantly increased in hearts of transgenic rats. Thus GATA-4 seems to be a marker of hypertrophy independently of calcineurin activation, possibly activated by various pathways.

Interference by cellular phones with permanent implanted pacemakers: an update.

AIMS: The aim of this study was to test pacemakers with feedthru filters for interference with a digital cellular telephone. METHODS: The study comprised 100 patients having their first pacemaker implantation between January 2001 and May 2003. A GSM-standard cellular phone was tested in the standby, dialing and operating mode against 23 single-chamber and 77 dual-chamber pacemakers. Continuous surface electrocardiograms, intracardiac electrograms, and marker channels were recorded when calls were made by a land phone to the cellular phone. RESULTS: In 2 patients we observed pacing inhibition with the cellular phone positioned directly above the pacemaker pocket. The unipolar and bipolar ventricular sensitivity setting was 0.25 mV in one dual-chamber pacemaker, and when we changed the sensitivity to 0.50 mV and higher no interference could be detected. The second inhibition occurred in a single-chamber pacemaker with unipolar and bipolar ventricular sensitivity setting of 0.5 mV, where a sensitivity change to 1.0 mV eliminated the interference. CONCLUSION: Anticipating a correct setting of ventricular sensitivity, currently available pacemakers equipped with feedthru filters do not show any interference with cellular phones. Since interference was only observed with sensitivity settings below 0.50 mV, we recommend that permanent programming of ventricular sensitivity should be set at 2.0 mV and higher.

[Beta-adrenoceptor antagonists in the treatment of chronic heart failure]. / Beta-Adrenozeptorblocker in der Therapie der chronischen Herzinsuffizienz.

Beta-Adrenoceptor antagonists in the treatment of chronic heart failure The incidence of chronic heart failure is high in the developed countries (1-4/1000 per year). Treatment of chronic heart failure is a therapeutic challenge. A great improvement in mortality and morbidity of heart failure patients was achieved by the introduction of beta-adrenoceptor blockers in the treatment of chronic heart failure. However only 39% of heart failure patients are treated with a beta-adrenoceptor blocker in Europe. This review outlines pathophysiology of the beta-adrenergic system during human heart failure and its alterations induced by beta-adrenoceptor blockade. Based on the results of large clinical trials, experimental-pharmacological properties of beta-adrenoceptor blockers as well as the main aspects of its clinical use are discussed.

The preferential beta3-adrenoceptor agonist BRL 37344 increases force via beta1-/beta2-adrenoceptors and induces endothelial nitric oxide synthase via beta3-adrenoceptors in human atrial myocardium.

1 The present study investigated the effects of the preferential beta(3)-AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca(2+)-transient and eNOS-activity in human right atrial myocardium. 2 BRL concentration-dependently caused an increase in FOC that was paralleled by an increase in Ca(2+)-transient and a shortening of time to half peak relaxation (T0.5T). These effects were abolished in the presence of propranolol (0.3 micro M). 3 BRL acted as a competitive antagonist towards isoprenaline and in binding experiments it was shown to have a distinct affinity towards beta(1/2)-AR. 4 In immunohistochemical experiments BRL (10 micro M) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 micro M). 5 BRL increased directly detected NO in DAF-staining experiments. This increase was significantly smaller in the presence of the NO-inhibitor L-NAME. 6 The inotropic effects of BRL were not changed in the presence of L-NMA. 7 These results suggest that the inotropic effects of BRL in human atrium are mediated via beta(1/2)-AR, whereas the increase of atrial eNOS-activity is due to beta(3)- adrenergic stimulation. This increase in eNOS-activity did not influence atrial myocardial contractility. In conclusion, this study shows that beta(3)-adrenergic stimulation is present in human atrium, but may not be functionally as significant as in the left ventricle.

Effects of the Ca2+ sensitizers EMD 57033 and CGP 48506 on myocardial contractility and Ca2+ transients in human ventricular and atrial myocardium.

Ca2+ sensitizers like EMD 57033 (EMD) and CGP 48506 (CGP) may be advantageous for the treatment of human heart failure, as they increase force of contraction without increasing the intracellular Ca2+ transients or energy consumption. However, whether or not Ca2+ sensitizers differ in their mode of action in human myocardium is not fully understood. The present study investigates the influence of EMD and CGP on force of contraction (FOC) and the intracellular Ca2+ transient (fura-2 ratio method) in left ventricular papillary muscle strips from left ventricular failing human myocardium (DCM, n = 28) as well as in right atrial trabeculae (RA, n = 21) obtained from patients undergoing cardiac bypass surgery. In isolated trabeculae of DCM, FOC was more efficacious and potently increased after application of EMD (EC50 EMD: 4.7 +/- 1.0 mumol/l, max. PIE EMD: + 12.0 +/- 2.0 mN/mm2) than CGP (EC50: 16.9 +/- 7.6 mumol/l, max. PIE: +6.4 +/- 2.8 mN/mm2). Similar results were obtained in RA. Application of carbachol (100 mumol/l) had no effect on the positive inotropic effect of EMD or CGP. Both Ca2+ sensitizers significantly increased time to half peak relaxation as well as diastolic tension in DCM. EMD (10 mumol/l) and CGP (30 mumol/l) did not affect the Ca2+ transients in RA. The Ca2+ sensitizers EMD and CGP increase cAMP and Ca2+ independently from the force of contraction in the human myocardium. However, their therapeutic use in human heart failure may be limited as they impair relaxation.

[Unclear pulmonary infiltrates with eosinophilia, a problem of differential diagnosis]

Unclear pulmonary infiltrates with eosinophilia, a problem of differential diagnosis. HISTORY AND ADMISSION FINDINGS: A 60-year-old woman was admitted for the diagnosis of pulmonary infiltrates. A year before she had been exposed to tuberculosis when working as a doctor in Manila, the Philippines. Ten days before admission she had spent 10 days in Sao Paulo, Brazil. On admission she complained of fatigue, dry cough and nocturnal sweating. Her body temperature was 37.8; C. At auscultation of the chest fine rales were heard with diminished percussion sounds over both lungs. INVESTIGATIONS: The chest radiogram showed bilateral apical infiltrates. Blood count indicated normal white and red cells, but platelets were raised to 606 x 10 9/l. The differential blood count revealed an eosinophilia of 30%, ESR was raised at 91 mm/h and C-reactive protein increased to 103 mg/l. Angiotensin-converting enzyme, IgG, IgA, IgM, IgE, C3 and C4, paraproteins, antinuclear antibodies and double-strand DNA antibodies were all within normal limits. There was no direct or indirect evidence of tuberculosis and no parasites were found in sputum, stool, urine and blood. DIAGNOSIS, TREATMENT AND COURSE: After bronchoscopy with bronchial biopsy had failed to establish a diagnosis, an open lung biopsy with partial lung resection was performed. This revealed histologically an eosinophilic pneumonia with intra-alveolar protein precipitation and multinucleated giant cells, as well as interstitial fibroblast proliferation without demonstrable mincroorganisms. Under cortisone administration there was striking improvement of symptoms within a few days, and C-reactive proteins fell to 3 mg/l, ESR to 25 mm/h and the eosino-philia to 2%. CONCLUSION: Eosinophilic pneumonia should be included in the differential diagnosis of unclear pulmonary infiltrations with eosinophilia, once parasitological and malignant diseases, tuberculosis and allergic pulmonary aspergillosis have been excluded.