Exercise test in patients with sarcoidosis. The importance of repolarization disturbances

The study population comprises 28 patients with sarcoidosis who all had repolarization disturbances in their exercise ECGs. None of the patients had hypertension or known cardiovascular disease, and all but two were non-smokers. The mean age was 45 years. Exercise test with beta-adrenergic blockade was performed within one month of the first examination. Persisting abnormal ST-T changes in exercise ECGs after beta-blockade were seen in 12 (43%) patients. No significant relationship was found between persisting ST-T changes and age, sex, chest X-ray stage, lung function or working capacity. In an earlier study, we found ST-T abnormalities in exercise ECG in 56 of 127 individuals (44%) in a consecutive 5-year study of patients with newly detected sarcoidosis. From this and the present report we postulate that, in our region, as much as 20% of the patients with newly detected sarcoidosis might have organic myocardial disease, possibly of sarcoid origin, as shown by repolarization disturbances in exercise ECG. If ECG abnormalities in the ST-T region are present in patients with sarcoidosis, exercise ECG with beta-blockade is a simple way of establishing suspicion of organic myocardial lesions. If exercise ECG abnormalities in the ST-T region persist after beta-blockade, careful clinical follow-up is recommended, and, in some patients early steroid therapy should be considered.     

Mast cells and lysozyme positive macrophages in bronchoalveolar lavage from patients with sarcoidosis. Valuable prognostic and activity marking parameters of disease?

In the deteriorating group of sarcoidosis patients, progress towards pulmonary fibrosis is a major problem. In order to benefit from corticosteroids, it is important for the treatment to start early. We studied a group of 45 patients with sarcoidosis. Most of them were newly detected patients and none were under or had currently received corticosteroid therapy. The patients were followed for at least six months. We found that increased amounts of polymorphonuclear neutrophils (PMN) or lysozyme-positive macrophages (Lys+MF) and mast cells (MC) in bronchoalveolar lavage (BAL) could implicate a bad prognosis.     

Bronchopulmonary dysplasia: The pulmonary pathologic sequel of necrotizing bronchiolitis and pulmonary fibrosis

A light and electroc microscopic study was carried out in 21 infants in whom the pathologic diagnosis of bronchopulmonary dysplasia had been made. All the infants except two had the respiratory distress syndrome at birth, and all 21 had been treated with respirator and oxygen therapy for various periods of time. The pathologic alterations observed in all the infants studied were primarily damage of the bronchial and bronchiolar ciliary apparatus and mucous membranes, severe necrotizing bronchiolitis, and marked bronchiolar and alveolar fibrosis. These changes were more pronounced in infants who survived the longest period of time. Such inflammatory and fibrotic changes are known to predispose to destruction of lung tissue, emphysema, and pulmonary hypertension. Six of these 21 infants developed symptoms and signs of cardiac atrial or ventricular stres, including cor pulmonale, prior to their demise. These infants were among those that survived the longest periods of time, had the longest exposure to supplemental oxygen, and showed histopathologically severe pulmonary fibrosis and emphysema.     

Detection of Myocardial Sarcoidosis by Thallium 201 Imaging

Thallium 201 myocardial perfusion scanning revealed focal left ventricular defects at rest in four of 30 patients (13 percent) with systemic sarcoidosis. All the defects decreased in size during thallium stress imaging, a finding opposite of that usually seen in myocardial ischemia. Nine patients had abnormal right ventricular visualization at rest. Thus, 11 of 30 (37 percent) had abnormal resting myocardial scand. Two of the four patients with left ventricular defects were studied serially for up to 1.5 years to evaluate response to corticosteroid therapy. The myocardial defect diminished in one patient, whereas the second patient, maintained for 2 years on low doses of steroids, had no resolution. In patients suspected of focal myocardial involvement by sarcoidosis on thallium scanning dynamic changes in scan defects can occur during exercise which are the reverse of those usually seen in coronary artery disease. These defects probably represent myocardial sarcoid. Right ventricular uptake generally appears to correlate with the severity of pulmonary involvement by sarcoidosis, yet does not appear to be a specific finding.     

The pulmonary vasculature in meconium aspiration

Some studies have suggested that pulmonary hypertension in the newborn with meconium aspiration can be attributed to a primary prenatal increase in pulmonary arterial musculature; but this concept has been controversial. To examine this question, we reviewed 62 infants autopsied at The Johns Hopkins Hospital, 24 of whom demonstrated meconium aspiration, 20 with meconium staining but no aspiration, and 18 with abruptio placentae without meconium aspiration or staining. Clinical and pathologic features were evaluated and cross-sectional arterial medial area was determined at the junction of the conducting and respiratory airways in nondistended lungs. No significant difference in arterial medial area was found between infants with meconium aspiration and those with meconium staining only or abruptio placentae. In addition, circumferentially muscularized intraacinar arteries were present in all infants with meconium aspiration and abruptio placentae, and all but one infant with meconium staining alone. Comparison of lungs with and without arterial injection and fixation in distention showed that injection does not uniformly distend vessels and that formalin distention may remove or mask meconium. The study suggests that meconium aspiration and its complications, not primary structural arterial changes, account for pulmonary hypertension in infants with meconium aspiration.     

Pulmonary arterial dissections and ruptures: to be considered in patients with pulmonary arterial hypertension presenting with cardiogenic shock or sudden death

Four unusual cases of sudden death due to pulmonary arterial hypertension complicated by dissection and/or rupture of the main pulmonary artery are reported. The patients, 3 males and 1 female, ranged from 17 to 77 years old. Each had chronic pulmonary arterial hypertension, marked pulmonary arterial dilation and degenerative medial changes of the large elastic pulmonary arteries. The first patient had a partial thickness tear of the main pulmonary artery with local dissection without external rupture and died of shock. The other three patients died after external rupture of the main pulmonary artery, based on a full thickness tear in one case, a small dissection in another and extensive dissection in the third. In the setting of pulmonary arterial hypertension, dissection, rupture, or dissection and rupture of the pulmonary artery should be considered in the differential diagnosis when patients present in cardiogenic shock or with sudden death.     

肺动脉高压患者生活质量及其影响因素

目的：了解肺动脉高压患者的生活质量状况并探讨其影响因素。方法：采用整群抽样的方法选择2014年6月至2015年6月期间在中南大学湘雅医院住院治疗的68例肺动脉高压患者作为研究对象。采用一般资料问卷、中文版简明健康调查量表(Short Form 36 Health Survey Questionnaire,SF-36)对其进行调查,运用单因素分析及多元线性回归法分析其影响因素。结果：肺动脉高压患者SF-36量表各维度评分均低于常模,差异均有统计学意义(P<0.05)。影响生活质量生理健康的因素为性别、6分钟步行试验距离(6-minute walking distance,6MWD)、是否合并右心衰竭、是否坚持氧疗;影响生活质量心理健康的因素为性别、文化程度、有无医疗保险。结论：肺动脉高压患者生活质量不高。医护人员应对女性、文化程度低、无医疗保险、6MWD短、合并右心衰竭、未坚持氧疗的患者给予更多的关注。     

Renal insufficiency in sarcoidosis. A clinical and pathologic study

The relationship of sarcoidosis to renal insufficiency is not widely known by pathologists or clinicians. During an 8-year period beginning in 1980, we observed six patients with sarcoidosis and clinically significant renal insufficiency (serum creatinine, greater than 260 mumol/L). In one of these patients with long-standing sarcoidosis, renal insufficiency was attributed to unrelated primary renal disease until renal biopsy specimen showed interstitial noncaseating granulomas. The four patients with renal insufficiency at presentation differed from the typical patient with sarcoidosis because they were white men who lacked the usual clinical constellation of skin, eye, and pulmonary involvement. All four had noncaseating granulomas on their initial biopsy (bone marrow [3 patients], and lymph node [1 patient]), suggesting each had sarcoidosis, yet each had two or more follow-up biopsies before the diagnosis of sarcoidosis was accepted and appropriate therapy initiated. One of these four patients underwent long-term antifungal and antituberculous therapy. The major causes of renal insufficiency in these six patients were complications of hypercalcemia and interstitial granulomatous nephritis. Except in one patient with nephrocalcinosis, prednisone therapy resulted in a dramatic fall in serum creatinine level with resolution of hypercalcemia. Sarcoidosis is a rare, but treatable, cause of renal insufficiency. Early recognition by clinicians and pathologists may spare patients from undergoing unnecessary biopsies and result in more timely initiation of therapy.     

Pulmonary hypertension in sickle cell hemoglobinopathy: a clinicopathologic study of 20 cases

Pulmonary hypertension is one of the major causes of morbidity and mortality of patients with sickle cell hemoglobinopathy (SCH). Although a clinically recognized complication of sickle cell disease (SCD), there are few published pathologic studies of pulmonary findings in these patients. The aim of this study was to define the pulmonary pathologic changes and to investigate correlation between the pathologic changes, the antemortem diagnosis of pulmonary hypertension, and the severity of SCH. Cases of SCH were identified from the autopsy database using Snomed codes. Clinical and echocardiograph data were collected for correlation with the pathologic data. A total of 20 adult patients (12 males and 8 females) were identified. Hemoglobin electrophoresis results were available for 16 patients, with hemoglobin S fraction percentages ranging from 23% to 97.8%. Eleven patients had SCD, 5 patients had sickle cell trait (SCT), and the remaining 4 patients without hemoglobin electrophoresis were included in the SCT group. The mean age of the SCT group was higher than that of the SCD group (P = 0.03). Histologically, all 20 patients demonstrated changes in pulmonary vasculature considered diagnostic of pulmonary hypertension grade I to grade IV, associated with plexiform lesions in 60% of patients. Medial hypertrophy and intimal hyperplasia/fibrosis, considered potentially reversible lesions, were seen in all patients. A weak association was found between SCD and plexiform lesions. Fibroelastic degeneration of small arteries, arterioles, and venules was identified in almost all (95%) cases. Clinically, tricuspid regurgitation was detected by echocardiogram in 10 of 20 (50%) patients; 6 of these 10 had significant regurgitation to allow estimation of systolic pressure. Sudden death occurred in 8 patients, with males having a significantly higher incidence. Cardiomegaly was present in 95% of patients, however, autosplenectomy and hepatic cirrhosis/hemochromatosis were observed almost exclusively in patients with SCD. Cirrhosis was found to have a strong positive association with SCD. This study demonstrates pulmonary hypertensive changes in all 20 autopsied patients who had SCH but died from various causes. We conclude that a high prevalence of pulmonary hypertension is associated with SCH with consequent high mortality. Therefore, patients with SCH would benefit from a regular periodic assessment for pulmonary hypertension regardless of age, sex, and severity of hemoglobinopathy.     

Pulmonary vascular involvement in sarcoidosis: granulomatous angiitis and microangiopathy in transbronchial lung biopsies

Summary To evaluate the occurrence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis, transbronchial lung biopsy specimens were examined from 174 cases with sarcoidosis. Granulomatous angiitis was seen in 72 cases, which corresponded to 53% of the cases with granulomata. Granulomatous angiitis showed venous involvement (65%), both venous and arterial involvement (24%) or arterial involvement only (11%). There was no significant difference in occurrence of granulomatous angiitis between upper and lower lobes. The cases with granulomatous angiitis in the lung had a higher frequency of ophthalmic symptoms and elevated serum angiotensin converting enzyme level. Basal lamina layering in the microvasculature was more often observed in the bronchial mucosa than in the alveolar walls and is not exclusively related to granulomata. Endothelial proliferation and basal lamina alterations in granulomatous angiitis may be closely associated with granulomas. The present study revealed coexistence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis and suggests that both may participate in the development of pulmonary sarcoidosis.     

Vascular remodeling process in reversibility of pulmonary arterial hypertension secondary to congenital heart disease

Pulmonary vascular remodeling process was analyzed using morphometry in lung biopsy specimens taken from 26 children, aged 6 to 160 months, who had congenital heart disease and significant pulmonary arterial hypertension. Reparative surgery was performed in 22 patients and palliative surgery was performed in four patients. One patient expired postoperatively and four others after hospital discharge. Vascular remodeling examination revealed a characteristic pathological picture: pronounced medial thickening with increased collagen content (fibrosis), without significant arterial intimal proliferation. At a mean follow-up of 44 months, 72% of the survivors were asymptomatic with no medication. Diagnosed by echocardiogram, 22% of these patients were shown to have pulmonary arterial hypertension. The characteristic pathological features described above occurred in 38% of the patients who either expired or had pulmonary hypertension postoperatively. These findings were an aid to identifying a high risk group in which the outcome does not meet expectations for the classical grade I and II changes. We concluded that the presence of isolated medial thickening does not ensure either survival or a normal postoperative pulmonary arterial pressure at late follow-up and that the collagen content can be a better reference for good outcome. Early intracardiac repair is recommended before the development of significant medial fibrosis.     

Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases

Pulmonary arterial hypertension is a severe complication of connective tissue diseases. It is currently well established that pulmonary arterial hypertension associated with connective tissue diseases such as systemic sclerosis is frequently less responsive or even refractory to pulmonary vasodilator therapies. In that setting, pulmonary venoocclusive disease is believed to contribute to treatment failures. We therefore hypothesized that pulmonary arterial hypertension associated with connective tissue diseases may be associated with obstructive lesions of pulmonary veins. Lung samples from 8 patients with pulmonary arterial hypertension associated with connective tissue disease (4 limited systemic sclerosis, 2 systemic lupus erythematosus, 1 mixed connective tissue diseases, and 1 rheumatoid arthritis) were studied by light microscopy and analyzed by immunohistochemistry (5 postmortem samples, 3 explants after lung transplantation). Findings were compared with 29 pulmonary arterial hypertension cases from patients displaying neither connective tissue diseases nor associated conditions. We found that (a) 6 (75%) of 8 patients with pulmonary arterial hypertension associated with connective tissue diseases showed significant obstructive pulmonary vascular lesions predominating in veins/preseptal venules, as compared with 5 (17.2%) of 29 non-connective tissue diseases control pulmonary arterial hypertension; (b) lesions of small muscular arteries were consistently present in pulmonary arterial hypertension associated with connective tissue diseases, showing mostly intimal fibrosis and thrombotic lesions; and (c) 6 of 8 lung samples from patients with pulmonary arterial hypertension associated with connective tissue diseases revealed perivascular inflammatory infiltration. In conclusion, our study highlights the fact that pulmonary arterial hypertension complicating the course of connective tissue diseases may be characterized by a more frequent involvement of pulmonary veins and may thus explain why these patients are less prone to respond to specific pulmonary arterial hypertension treatment as compared with idiopathic pulmonary arterial hypertension.     

Sleep apnea and pulmonary hypertension

Summary The pulmonary artery pressure values of 65 patients with sleep apnea syndrome were measured at rest and during ergometer exercise up to 100 W. Pulmonary hypertension at rest was found in 13, and during exercise in 31 more patients. Only 8 patients with pathological pressure findings suffered from pulmonary hypertension in combination with a pulmonary or cardiac disease. In the other 36 patients, no indication of a primary cause of pulmonary hypertension apart from sleep apnea syndrome could be found. Out of the 65 patients, 11 with a finding of more than 20 apnea episodes per hour's sleep underwent polysomnographic recordings in the sleep laboratory. The hemodynamic parameters were continuously measured. All 11 patients had a finding of severe sleep apnea with more than 300 apnea episodes during the night of recording. In 6 patients, the appearance of apnea episodes was accompanied by only moderate changes in pulmonary artery pressure. In 5 patients, there were critical increases in pulmonary artery pressure, which went along with increases in cardiac output and in pulmonary capillary wedge pressure. Increases in pulmonary vascular resistance were established in 3 out of these 5 patients, and a slight decrease in 2. The mechanism of hypoxic vasoconstriction of the pulmonary arteries may account for the pressure increases in 3 of our patients, but fails to explain the findings in the other 2 patients. Nocturnal changes in pulmonary artery pressure in patients with sleep apnea may therefore have different causes. Pulmonary hypertension constitutes a severe complication in patients with sleep apnea. As 55% of all sleep apnea patients were found to suffer from pulmonary hypertension without any indication of a primary pulmonary or cardiac disease, the possibility that pulmonary hypertension results should not be underestimated in patients with suspected sleep apnea syndrome. Measurements of the pulmonary artery pressure must therefore be included in the examination regimen of such patients.Abbreviations ECG electrocardiogram - REM rapid eye movement     

Morphofunctional characteristics of pulmonary and bronchial arteries in bronchial asthma, chronic obstructive lung disease, idiopathic fibrosing alveolitis

Morphological and morphometric studies have shown that secondary pulmonary hypertension is characterized by more pronounced pathological changes in the pulmonary arterial branches in severe chronic obstructive lung disease (COLD) than in idiopathic fibrosing alveolitis. Secondary pulmonary hypertension does develop in atopic bronchial asthma. Moreover, there are more significant pathological changes in the pulmonary arteries than in the bronchial ones. In severe COLD, the development of emphysema affects that of pulmonary arterial hypertension.     

Vascular lesions in systemic lupus erythematosus (SLE) with pulmonary hypertension

An autopsy case with SLE suffering from Raynaud's phenomenon and pulmonary hypertension was reported. Histological examinations revealed systemically marked fibrous intimal thickening of arteries and arterioles with or without thrombus throughout the whole body, especially of the pulmonary arteries and arterioles. Pulmonary arterial changes in the present case were compared with those in 52 autopsied cases with SLE without pulmonary hypertension, but there were no cases with such marked arterial changes as the present case. In addition, the incidence of pulmonary thrombosis was significantly higher in the cases with Raynaud's phenomenon than the cases without this phenomenon. However, the relation between pulmonary hypertension and Raynaud's phenomenon, pulmonary thrombosis, fibrous pericarditis, or type of lupus nephritis in SLE could not be clarified with a significant difference.     

Pulmonary vascular disease and hypertension after valve surgery for mitral stenosis

The reduction of pulmonary hypertension that occurs within 24 hours of valve replacement for mitral stenosis is well documented, but patients who die after surgery have not been adequately studied. Clinical and autopsy data for 16 patients who died following mitral valve replacement were reviewed. The emphasis was on preoperative and postoperative pulmonary arterial pressure and pulmonary vascular disease, including arterial, venous, and capillary changes. Morphologic features were graded and summed to obtain an additive histologic assessment (AHA). Patients were divided into three groups: 1) those who had uneventful operations and early postoperative periods but died prior to discharge; 2) those who had postoperative difficulty, with identifiable acute anatomic causes of death; and 3) those who had postoperative difficulty, with no apparent acute anatomic cause of death. In group 1 (n = 4) the preoperative pulmonary arterial pressure was 43 +/- 17 mm Hg, and AHA ranged from 0 to 4; in group 2 (n = 5) the preoperative pulmonary arterial pressure was 60 +/- 15 mm Hg, but AHA ranged only from 2 to 5. In group 3 (n = 7) the preoperative pulmonary arterial pressure was 59 +/- 12 mm Hg; AHA ranged from 6 to 9, significantly higher than that of the other groups (P less than 0.005). Three patients from group 3 had elevated pulmonary arterial pressure (60, 52, and 50 mm Hg three, six, and 15 days after surgery, respectively). Two additional patients had right heart failure with normally contracting left ventricles terminally. It is concluded that some patients with mitral stenosis who die after surgery with persistently elevated pulmonary arterial pressure have sufficiently severe pulmonary vascular disease to account for their persistent pulmonary hypertension and death.     

Clinical manifestations of sarcoidosis among inner-city African-American dwellers

OBJECTIVES: To characterize clinical, radiographic and physiological features of sarcoidosis among African Americans residing in inner-city Chicago. METHODS: This is a retrospective review of medical records of 75 African Americans with biopsy-proven sarcoidosis from internal medicine and pulmonary clinics at three inner-city, acute care hospitals in Chicago. RESULTS: The number of organs involved was 1.77 +/- 0.94 (mean +/- SD). The most common sites for tissue diagnosis were lung (49%), skin (19%) and lymph nodes (16%). Thirty-six (48%) patients had stage-2 and -3 disease on chest x-ray. Electrocardiographic changes and ocular involvement were detected in 23% and 21% of patients, respectively. Nineteen (25%) patients had obstructive defect (FEV1 1.71 +/- 0.78 L/s), 15 (20%) had a restrictive defect [TLC 4.1 +/- 1.2 L (63.9 +/- 9.2% predicted)]. Three patients had both restrictive and obstructive defect. Forced vital capacity and FEV1 declined by 0.26 L and 0.09 L/s per year, respectively, in patients with an obstructive defect. Most patients (91%) were treated with prednisone for 3.8 +/- 3.9 years (range 0-20 years). CONCLUSIONS: African Americans with sarcoidosis residing in inner-city Chicago express a high rate of chronic progressive disease necessitating corticosteroid therapy. Further studies are warranted to elucidate the reasons underlying this paradigm.     

Pathologic features of conduction system in myocardial infarction

Coronary artery disease and myocardial infarction are frequently associated with major conduction abnormalities, but the correlation between the vascular disease and the specific conduction system is not obvious. Anyhow, in cases of acute occlusive vascular disease, the correlation might be more obvious. 31 cases of acute coronary arterial occlusion with myocardial infarction were studied correlating with ECG changes as well as pathologic lesions present in the conduction system. Results showed that histologic changes of the conductive system were usually related with the condition of blood supply and the site and size of the infarction. Additionally, the area of the damaged conductive tissue should be large enough to produce ECG changes. Otherwise the functional changes might be compensated or recovered. Myofibrillar degeneration was obtained in the conduction tissue in the majority of the cases reported, and its clinical significance remains to be clarified.     

高原肺水肿患者血流动力学变化及对吸氧反应的测定

目的:探讨高原肺水肿的发病机理。方法:采用右心漂浮导管检测法, 对9例高原肺水肿患者及9例同海拔高原健康人的血流动力学指标进行了检测, 同时也观察了吸入纯氧对高原肺水肿患者血流动力学的影响。结果:高原肺水肿患者发病时, 肺动脉平均压、肺血管阻力、心脏指数均明显高于同海拔高度健康人, 而患者肺动脉楔压, 右心房压力同对照组相比, 未见显著差异;吸氧后, 高原肺水肿患者心率、肺动脉平均压力, 肺血管阻力及心脏指数均较吸氧前明显下降, 特别是肺动脉平均压及肺血管阻力下降尤为明显, 肺动脉平均压力在吸氧1min后即明显下降, 吸氧5min后, 下降至最低值, 但吸氧20min后仍未达对照组水平。结论:高原肺水肿是非心源性肺水肿, 肺动脉高压在其发病中起重要作用。