Carcinoid syndrome with right-sided valve involvement - a case report and review of the literature.

BACKGROUND: The survival of patients with neuroendocrine tumors has substantially improved with modern treatment options. Although the associated carcinoid syndrome can be diagnosed early and controlled effectively, cardiologists still encounter patients with cardiac manifestations, particularly among individuals with persistently high levels of vasoactive mediators. Treatment options have been limited to surgical valve replacement in fully manifested disease. Since surgery is not always feasible, transcatheter valve implantation is becoming an interesting alternative. CASE: A case of a 50-year-old woman with carcinoid syndrome and right-sided valvular heart disease is presented. Moderate pulmonary valve stenosis and severe tricuspid valve regurgitation were diagnosed during the evaluation and treatment of neuroendocrine tumor. The possibility of rare valve involvement and the need for interdisciplinary cooperation in the diagnosis, monitoring and treatment of patients with neuroendocrine tumors producing vasoactive substances must be emphasized. CONCLUSION: The patient had a typically presenting carcinoid syndrome with a rare cardiac manifestation. Although monitoring and treatment were carried out in accordance with recommendations and appropriate to the clinical condition, rapid progression of the metastatic disease ultimately precluded invasive cardiac intervention.

Predictors of survival in patients with pulmonary hypertension and acute right heart failure.

OBJECTIVES: The aim of this study was to analyse survival of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) hospitalized due to an acute right heart failure (ARHF) with emphasis on risk factors and effectiveness of treatment following current guidelines. METHODS: We retrospectively analysed 117 hospitalizations of 70 patients (59 PAH patients; 11 CTEPH patients, mean age 53.1 ± 16.77 years, 54 % females) between 2004 and 2013. RESULTS: 96 cases were hospitalized at cardiology wards (CW) while 21 at intensive care unit (ICU). The overall hospital mortality was 12.8 %, CW mortality was 4 %, and ICU mortality was 52.4 %. Higher risk of in-hospital mortality was associated with younger age, lower sodium levels, severe forms of PAH (heritable PAH, CTD-PAH) and need of PAH combination treatment. The one-year survival from the first ARHF hospitalization was 67.6 % (95 % CI 57.1-80 %), the two-year survival was 41.9 % (95 % CI 30.8-56.9 %). The presence of ascites was a predictor of long-term mortality. CONCLUSIONS: Mortality in patients with PH and ARHF remains very high. Identification of its risk factors could be used as basis of risk-adapted therapy (Tab. 5, Fig. 2, Ref. 14).

Eisenmenger syndrome - an electrocardiographic and echocardiographic assessment of the right ventricle.

BACKGROUND: Eisenmenger syndrome represents severe, irreversible, and end-stage pulmonary arterial hypertension (PAH) associated with congenital heart defects. For long-term outcome optimal right ventricular (RV) adaptation is crucial with precise assessment of its hypertrophy, dilatation and function. OBJECTIVES: Associations of electrocardiographic (ECG) and echocardiographic (ECHO) RV characteristics were analyzed. METHODS: Included were 52 patients (39F/13M), median age 45 years (24-78). Following ECG parameters were analyzed: Butler-Leggett formula (B-L), Sokolow-Lyon criterion (S-L), QRS duration (QRS), maximum spatial QRS vector magnitude (QRS max); and ECHO parameters: RV diameter (RVd), RV wall thickness (RVAW), RV/LV function. RESULTS: Following significant ECG-ECHO associations were demonstrated: S-L criterion and B-L formula with RVAW (p 120 ms only with severely dilated RV (RVd > 45 mm), while QRS max 33 mm); A new combined scoring system was introduced. CONCLUSIONS: In Eisenmenger syndrome RV hypertrophy is compensatory; diagnosis of prognostically unfavorable RV dilatation is therefore important. Combined ECG-ECHO analysis enables more accurate risk stratification. QRS duration > 120 ms seems to be a late marker; QRS max together with ECHO parameters may help to distinguish patients at higher risk for clinical deterioration (Tab. 3, Fig. 8, Ref. 53).

Double aortic arch anomalies in Children: A Systematic 20-Year Single Center Study.

Aortic arch anomalies underlie numerous congenital disorders. Effectively diagnosing and treating them requires close understanding of cardiovascular embryology. As our Center serves the entire pediatric population of our country, we performed a comprehensive retrospective analysis of all aortic arch anomalies diagnosed at our Center over the past 20 years. We analyzed 40 children with aortic arch anomalies, distinguishing two defect types: Group 1 displayed ring-forming anomalies, and Group 2 other types of aortic arch anomalies that did not form a vascular ring. We performed detailed morphological analyses using echocardiography, angiography, computed tomography, or magnetic resonance imaging and generated a catalog of all aortic arch anomalies present. Group 1 was represented by 25 patients; 40% with persistent both aortic arches, and 60% with various forms of right aortic arch and an incomplete left aortic arch. Group 2 was represented by 15 patients with complex heart defects. On the basis of our dataset, the incidence of all aortic arch anomalies was 0.033%, and of ring-forming pathologies 0.021%. Although aortic arch anomalies are rare, it is important to diagnose them correctly. It is critical to distinguish ring-forming types. Although in complex defects the aortic arch anomaly represents only an additive diagnosis, its correct definition could be crucial for further management. Cumulatively, this unique, long-term study provides a systematic patient registry and offers critical epidemiological data to aid the study of rare congenital cardiovascular defects. Clin. Anat. 30:929-939, 2017. © 2017 Wiley Periodicals, Inc.

Risk factors detection in chronic thromboembolic pulmonary hypertension, a tool for risk quantification?

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by chronic thromboembolic obstruction in the pulmonary bed. The definitive pathogenesis remains incompletely explained, although multiple risk factors of CTEPH have been identified. The purpose of the study was to evaluate the risk profile of patients with CTEPH and the representativeness of risk factors, identify possible new CTEPH risk factors and specify the epidemiology of CTEPH in our country. METHODS: In 81 patients with CTEPH, well known risk factors were analyzed, and a detailed analysis of selected hematological parameters was investigated at a specialized hematology laboratory. RESULTS: CTEPH risk factors were identified as follows: pulmonary embolism (PE), deep vein thrombosis (DVT), thyreopathy, blood type other than "0", inflammatory bowel disease, malignancy, splenectomy, pacemaker. When compared to healthy controls, the following was observed: a significant decrease in platelet count, higher mean platelet volume, higher spontaneous platelet aggregation, increase in von Willebrand factor and fibrinogen. The median of risk factors representativeness was 3 (PE, DVT, blood type other than "0"). The prevalence of CTEPH in adult population in our country is estimated to be 1.8 per 100,000 inhabitants. CONCLUSION: In the study we confirmed multiple established risk factors of CTEPH, set their representativeness, identified some platelet abnormalities which could be a potential new risk marker and specified the prevalence of CTEPH (Tab. 5, Ref. 35).

Postpericardiotomy syndrome - post-cardiac injury syndrome.

INTRODUCTION: Postpericardiotomy syndrome is a non specific belated reaction of pericardium, epicardium and pleural cavity after cardiac or pericardial injury. It is considered to be a common complication in cardiosurgery with occurrence of 3 to 30 percent. Most likely, the primary cause is a common immunopathic process. It develops within days or even up to six months after either cardiac or pericardial injury or both. AIM: Echocardiography is the leading method in determination of postpericardiotomy syndrome due to the frequency of occurrence, non- specific clinical symptoms (fever, chest pain, cough, dizziness), inaccurate interpretation of examination methods (ECG, X-ray, laboratory tests). We would like to show how to determine the exactly diagnose, how to treat it and what is prognosis of this illness. RESULTS: We have performed a retrospective analysis of 1344 patients, who underwent cardiac surgery in the year 2009. The incidence of post- cardiac surgery syndrome was 12.4 %. In 2.6 % of the studied cases, surgical intervention was needed due to a cardiac tamponade. Int other cases similar to acute pericarditis, symptomatic treatment in duration of several weeks or months with non-steroid antireumatics, salicylic acid or colchicine is sufficient. Therapeutic options in refractory forms are long term oral corticoids or pericardiectomy. During our follow-up, pericardiectomy was necessary to perform in one patient. CONCLUSION: Postpericardiotomy syndrome, which occurs in early postoperative period, prolongs hospitalisation. In spite of non specific symptoms huge pericardial effusion might be present and can cause cardiac tamponade with haemodynamic failure in later periods. Transthoracic echocardiography is the golden standard in determination of accurate diagnosis (Fig. 6, Ref. 15).

[ECG markers in patients with hypertrophic cardiomyopathy]. / Elektrokardiografické markery u pacientov s hypertrofickou kardiomyopatiou.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited disease of the heart muscle whose main characteristic is unexplained hypertrophy of the left ventricle and/or right ventricle. It is considered to be the most common genetically determined cardiovascular disease with the prevalence in the population approximately 1 to 500 inhabitants. The disease is associated with severe complications such as heart failure, arrhythmias and sudden cardiac death (SCD). Nowadays the aim of intensive clinical research is to judge the contribution of noninvasive methods in the risk stratification of HCM patients. Abnormal electrocardiogram occurs in 75-95% and it often presents the first point for HCM suspicion although it is nonspecific. AIM: The aim of our study was to evaluate the electrocardiographic (standard 12-lead) and certain echocardiographic markers in patients with recurrent syncope of unknown origin in comparison with patients without these episodes. PATIENTS AND METHODS: 42 patients (17 men a 25 women) with verified HCM diagnosis underwent extensive clinical, standard 12-lead electrocardiographic and echocardiographic testing to compare these parameters in the subgroup of patients with syncope (n = 17) of unknown origin and patients without syncope (n = 23). RESULTS: As for the electrocardiographic signs we found that more than one half of patients had positive Sokolow-Lyon index (55.6%), prolonged QTc interval (63.2%). Depression of ST segment was present in 60.5%. We also found positive correlation between prolonged QTc interval and maximal left ventricle thickness. We observed that patients with syncope had statistically significantly left ventricle end-diasotlic diameter in comparison with patients without syncope. CONCLUSION: Standard electrocardiography represents a "gold standard" in the diagnostics of HCM patients. We found positive correlation between prolonged QTc interval and maximal left ventricle thickness. Patients with syncope had statistically significantly smaller left ventricle end-diastolic diameter in comparison with patients without syncope.

Long-term cardiac effects of treatment for childhood leukemia.

Late cardiac complications in cancer survivors may develop from subclinical myocardial damage. Biochemical correlates of minimal myocardial changes can be analyzed using a commercially available rapid assay. Biomarkers are considered more sensitive markers of subclinical cardiotoxicity than conventional electrocardiographic and echocardiographic methods. The aim of this study was to determine the values of plasma N-terminal pro brain natriuretic peptide (NT-pro-BNP) and cardiac troponin T (cTnT) in asymptomatic childhood leukemia survivors after anthracycline therapy in comparison with healthy volunteers. The survivors also underwent a detailed echocardiography. Twenty six survivors of leukemia previously treated with anthracyclines with total cumulative dose 95-600 (median 221) mg/m(2) were evaluated. Analyses of cTnT and NT-proBNP from blood samples and echocardiography were performed 5-25 years after completion of therapy for childhood leukemia. Control group for biochemical analyses consisted of 22 age- and gender- matched apparently healthy volunteers. Values of NT-proBNP were significantly elevated in ANT group compared to controls (35.1 +/- 37.8 vs. 9.6 +/- 6.7 pg/ml, P<0.010). CTnT remained below the diagnostic cut-off values in both groups. All echocardiographic parameters of patients remained normal. In conclusion, differences in NT-proBNP values between patients treated with anthracyclines and healthy volunteers might signal an initial stage of anthracycline-induced myocardial damage. The potential of this biomarker to detect subclinical anthracycline-induced myocardial alterations before development of echocardiographic and clinical changes is promising.

Effect of warfarin anticoagulation on thrombin generation in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Oral anticoagulant therapy is recommended for patients with pulmonary arterial hypertension (PAH). The rationale for the use of anticoagulant treatment is based on thrombophylic predisposition in PAH and improvement of survival in patients treated with anticoagulation. However, the target INR value has not been evaluated. The aim of this study was to analyze thrombin generation in patients with PAH treated with warfarin anticoagulation. METHODS: The study was performed in 58 patients with idiopathic PAH treated with warfarin at stable doses. Thrombin generation assay was performed in all subjects and three parameters were derived from the thrombin generation curves: lag time, maximal concentration of formed thrombin (peak thrombin) and area under the curve (AUC). Thrombin generation parameters were correlated with INR and compared between the patient groups with different intensity of anticoagulant therapy. RESULTS: Significant correlation between the lag time and INR was observed (r = 0.495, p < 0.001). Significant negative correlation between the maximal concentration of formed thrombin and INR and between the area under the curve of thrombin generation and INR was observed (r = -0.709, p < 0.001 and r = -0.784, p < 0.001, respectively). Thrombin generation was significantly reduced in patients with INR between 1.5 and 2.5. CONCLUSIONS: Low-intensity warfarin anticoagulation with target INR between 1.5 and 2.5 could be effective and sufficient to suppress thrombin generation in patients with idiopathic PAH (Fig. 3, Tab. 4, Ref. 12). Full Text in free PDF www.bmj.sk.

Genetic screening of patients with hypertrophic cardiomyopathy--a new diagnostic strategy for risk stratification?

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited disease of the heart muscle and its main characteristic is unexplained hypertrophy of the left and/or the right ventricle. HCM is the most common genetically determined cardiovascular disease and is prevalent in approximately in 1 of 500 of the population. The most serious complication of HCM is sudden cardiac death (SCD) which can be the first manifestation of the disease. However, there are other forms of benign prognosis which do not jeopardize patient's health or life. The clinical symptoms of HCM are partly dependent on mutations in affected sarcomere genes. Different mutations in the same gene can present as malign with a high risk of SCD, while other mutations can be benign. The clinical symptomatology can also be influenced by other factors such as the presence of polymorphisms in other genes. Nowadays the aim of intensive clinical research is to access the contribution of molecular genetic methods in HCM diagnostics as well as in risk stratification of SCD. It is expected that genetic analyses will have an important consequence in the screening the relatives of HCM patients and also in the prenatal diagnostics and genetic counseling (Tab. 2, Fig. 1, Ref. 45). Full Text (Free, PDF) www.bmj.sk.

Risk factors for chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by nonresolving pulmonary thromboemboli that can be treated by surgical pulmonary endarterectomy (PEA). The authors of the present study sought to confirm known and to identify novel CTEPH risk factors in a controlled retrospective cohort study of prevalent CTEPH cases collected in three European centres offering PEA. Data from CTEPH patients were compared with nonthromboembolic pre-capillary pulmonary arterial hypertension cohorts at the participating institutions. The study population comprised 687 patients assessed at the time of diagnosis between 1996 and 2007. Ventriculo-atrial shunts and infected pacemakers (odds ratio (OR) 76.40, 95% confidence interval (CI) 7.67-10,351), splenectomy (OR 17.87, 95% CI 1.56-2,438), previous venous thromboembolism (VTE; OR 4.52, 95% CI 2.35-9.12), recurrent VTE (OR 14.49, 95% CI 5.40-43.08), blood groups other than 0 (2.09, 95% CI 1.12-3.94), and lupus anticoagulant/antiphospholipid antibodies (OR 4.20, 95% CI 1.56-12.21) were more often associated with CTEPH. Thyroid replacement therapy (OR 6.10, 95% CI 2.73-15.05) and a history of malignancy (OR 3.76, 95% CI 1.47-10.43) emerged as novel CTEPH risk factors. In conclusion, the European database study confirmed previous knowledge of chronic thromboembolic pulmonary hypertension risk factors, and identified thyroid replacement therapy and a history of malignancy as new medical conditions associated with chronic thromboembolic pulmonary hypertension.

Clinical and hemodynamic picture of Eisenmenger syndrome.

Eisenmenger syndrome represents a very specific form of pulmonary arterial hypertension (PAH). Unlike patients with idiopathic PAH, in Eisenmenger syndrome the clinical and cardiac status is often relatively stable for a long time. On the other hand, due to cyanosis and due to maladaptive body reactions many noncardiac complications may occur. Fourteen patients (pts) with Eisenmenger syndrome were analyzed, with the mean age 41 years. Invasively measured pre-capillary pulmonary hypertension was severe (mean pulmonary arterial pressure 79 mmHg) and a statistically significant difference according to the site of defect was found (pre-tricuspid shunts vs post-tricuspid shunts = 57,5 mmHg vs 88 mmHg; p = 0.01). It is neccessary to keep in mind that non-cardiac events and complications may lead to death sooner then the right ventricular dysfunction or PAH (Tab. 7, Fig. 21, Ref. 16).

Natriuretic peptides: biochemical markers of anthracycline cardiac toxicity?

Patients with cancer are often treated with potentially cardiotoxic chemotherapeutics. Cardiotoxicity ranges from relatively benign arrhythmias to serious conditions such as myocardial ischemia/infarction, congestive heart failure, and cardiomyopathy. In spite of different diagnostic methods, with echocardiography as a gold standard, there is an intensive search for new diagnostic tools for the early detection of myocardial abnormalities. Available data suggest that the levels of circulating cardiomarkers can monitor the extent and severity of the myocardial damage. The role of routinely used cardiomarkers is controversial and limited in this setting. Natriuretic peptides have shown promising results in assessment and monitoring of both acute and late clinical and subclinical damage of the myocardium in association with chemotherapy. This article reviews clinical studies evaluating the role of natriuretic peptides in the early diagnosis of anthracycline cardiotoxicity, and their use in the management of cancer survivors.

Initial experiences with novel therapy for pulmonary hypertension in Slovakia.

Pulmonary hypertension (PH) is the most serious and potentially devastating chronic disorder of the pulmonary circulation with diverse etiologies and pathogenesis characterized by abnormal increased vasoconstriction and vascular remodelling. Current specific therapy of PH is based on an understanding of its pathogenesis and is acting through pathogenic pathways and therefore changes therapeutic strategy, effectively improves clinical course and prolongs life. The authors discuss the actual classification, pathogenesis in short and particularly actual treatment modalities and the impact on the natural history of this disorder. In chronic thromboembolic pulmonary hypertension is pulmonary endarterectomy if correct indicated the curable method, warranted substantial improvement of life quality and survival. These novel therapies of PH were absent in Slovakia until recently. The authors present initial experiences, results of PH management up to date on the basis of cooperation with PH centres in Austria and Czech Republic (Tab. 1, Fig. 6, Ref. 32).

Value of echocardiography in results evaluation of transcatheter atrial septal defect closure in adults.

Transcatheter closure of secundum atrial septal defect using Amplatzer occluder is accepted treatment modality. Transthoracic (TTE) and transoesophageal (TEE) echocardiography provides indispensable informations in the selection of eligible atrial septal defects, evaluates the exact size, location and morphology of the defect. In the closure procedure assistance of TEE enables precise determination of device size, correct placement of the device and immediate and follow-up closure results assessment. The present prospective study was performed in order to investigate the value of both approaches--TTE and TEE in the intermediate-term follow-up. Before, during transcatheter defect closure and in the follow-up echocardiography studies [TTE and TEE] were performed in 33 adult patients with secundum atrial septal defect with fulfilled TEE criteria. Correct placement of the device without interference with surrounding structures under TEE monitoring was possible in all patients. Immediate complete closure was achieved in 49% of patients, after 3 months in 94%. TEE findings corresponded well with TTE. In the follow-up echocardiographic signs of right ventricle overload retreated. Results indicate that TEE provides valued data for the selection and closure procedure. TTE is a sufficient reliable approach for results evaluation in intermediate follow-up. Echocardiography plays crucial role in the safety and efficacy assessment of transcatheter treatment of secundum atrial septal defect.

Pulmonary function alterations after correction of mitral stenosis.

The aims of the study is to demonstrate the degree of pulmonary function reversibility after successful correction of mitral stenosis, transvenous as well as surgical. Before and in the short- and long-term follow-up after mitral stenosis correction (mitral valve replacement and percutaneous balloon mitral valvuloplasty) echocardiographic and pulmonary function studies were performed in 125 patients with pure or dominant mitral stenosis in order to investigate the influence of hemodynamic changes on pulmonary function. Immediately after procedure moderation of bronchial obstruction could be detected although only in balloon valvuloplasty group. In pts after surgery dramatic decline of pulmonary function due to thoracotomy was found. In the long-term follow-up substantial improvement of all ventilatory parameters in both groups was revealed, diffusing capacity remained unchanged. The favourable evolution was comparable in both groups. The explanation are time consuming beneficial peripheral metabolic, circulatory and organic pulmonary changes, what implies also irrelevant changes of PF in the early phase and unalterable diffusing capacity. (Tab. 1, Fig. 4, Ref. 15.)

Echocardiography and exercise electrocardiography in the assessment of long-term outcome after percutaneous mitral valvuloplasty.

Before and immediate (invasive examination) and long-term follow-up (4.5 year; echocardiography, exercise electrocardiography) studies after percutaneous transvenous mitral valvuloplasty (PTMV; Inoue technique) were prospectively performed in 123 consecutive patients with pure or dominant mitral stenosis. These patients consisted of two groups: Group A with suitable valve morphology (n = 108, mean age 49.6 years, echocardiographic score 8.2 +/- 1.5), and Group B with less favourable valve morphology (n = 15, mean age 59.3 years, echocardiographic score 11.3 +/- 2.3) rejected for surgery because of high surgical risk. PTMV is a safe and effective nonsurgical method of treatment for symptomatic mitral stenosis and has long-lasting results in patients with pliable mitral valve as well as in patients with less suitable valve morphology. Echocardiography (Doppler approach) is the most efficient noninvasive method for assessment of PTMV effect. Exercise electrocardiography test is a valuable complementary method for objective measurement of patient working capacity and to confirm the success of PTMV.

[Changes in respiratory mechanics after cardiac surgery]. / Zmeny mechaniky dýchania po operáchii srdca.

Cardiac surgery involves a complex of factors adversely affecting the pulmonary function (PF). Among them mainly pleurotomy and hypothermic phrenic nerve injury may potentially deteriorate postoperative PF. In a prospective study of 236 patients undergoing cardiac surgery, pre-, early and late postoperative PFs were evaluated. The impact of different techniques of coronary artery bypass grafting, of pleurotomy and diaphragmatic dysfunction and the effect of COPD on the postoperative modification of PF was investigated. The analysis revealed a substantial impairment of postoperative PF especially when pleural cavity was entered, the patients had COPD history, diaphragmatic dysfunction, or multiple pulmonary complications were present. These aspects should be considered in optimizing the pre-, per- and postoperative management of cardiac patients. (Tab. 5, Fig. 6, Ref. 34.)

[Pulmonary complications after heart surgery]. / Plúcne komplikácie po operácii srdca.

The authors present a detailed analysis of pulmonary complications after open-heart surgery and of their risk factors. The results of the presented study indicate that COPD patients with functional impairments are more sensitive to complicated postoperative outcome and to respiratory infections, in general. There is a clear relationship between artificial violation of the pleural cavity, diaphragmatic dysfunction and pleural effusion. Diaphragmatic dysfunction appears more frequently in mammarocoronary bypass patients in consequence of pleurotomy. The incidence of dysfunction could be reduced by the use of phrenic nerve insulation. Patients with pulmonary complications suffer from serious pulmonary function deficit. The possibilities of identification of the patients at risk, as well as the prevention and prophylaxis are analysed. (Tab. 7, Fig. 2, Ref. 71.)

[Lungs and their function in heart disease]. / Pl'úca a ich funkcia pri chorobách srdca.

Pulmonary manifestations of cardiac diseases are reviewed and the contribution of pulmonary function assessment in diagnosis, management and prognosis of these diseases is being emphasized. Inborn and acquired diseases of the heart exert pathological effects on pulmonary hemodynamics and later on also on lung structure, clinically manifested by pulmonary symptomatology and abnormalities in pulmonary function. The basic mechanisms of pulmonary function derangement include pulmonary congestion and hyperreactivity of the airways as a consequence of increased blood pressure or flow in the pulmovascular network (postcapillary or hyperkinetic pulmonary hypertension). The severity of the given cardiac disease determines also the condition of pulmonary function. Thus examinations of pulmonary function substantially contribute to the classification of the functional state and to optimal choices in therapeutic strategy. Appropriate surgical or medical therapeutic procedures can improve the hemodynamic conditions in the pulmonary vascular network. This, in turn, leads to partial regression of morphological changes in the pulmonary parenchyma and thus to gradual improvement of pulmonary function. (Tab. 4, Fig. 4, Ref. 62.)