14
15
16
17
18
ous pulmonary venous return: Surgical considerations and results of operation. J Thorac Cardiovasc Surg 60: 116, 1971 Mustard WT, McKeon WJ, Trusler GA: Transposition of the great arteries and transposition of the lesser veins: 2. Transposition of the lesser veins ( total anomalous pulmonary venous drainage). Prog Cardiovasc Dis 11:145, 19'68 Serrato M, Bucheleres HG, Arevado F, et al: Total anomalous pulmonary venous connection without obstruction: Hemodynamic and prognostic significance of foramen ovale size. Circulation 36 ( suppl 2) :232, 1967 ( abstract) Bedford DE, Sellers TH, Somerville W, et al: Atrial septal defect and its surgical treatment. Lancet 1:1255, 1957 Billig DM, Hallman GL, Bloodwell RD, et al: The surgical treatment of cardiac defects associated with variations in cardiac position. J Thorac Cardiovasc Surg 55:80, 1968 Gilbert EF, Nishimura K, Wedum BG: Congenital malformations of the heart associated with splenic agenesis: With a report of five cases. Circulation 17:72, 1958
Acromegaly, the Systolic Click Syndrome, and Group D Streptococcal Endocarditis* B. ]ugdutt, M.B., Ch.B.;"" C. B@ualdo, M.D.;t H. Freeman, M.D.;t and P. Crockford, M.D.§
A syndrome consisting of an apical systolic click and late systolic murmur appeared over a period of three months in a patient with acromegaly. Levels of growth hormone were highest during this interval. As a result of group D streptococcal endocarditis three months later, the patient sustained cerebral embolism and acquired free mitral regurgitation from ruptured chordae tendineae. During follow-up over 18 months, neither the level of growth hormone nor the degree of mitral regurgitation changed significantly.
A !though
acromegaly has been known to be associated with disproportionate cardiomegaly, systemic hypertension, premature coronary arterial disease, arrhythmias, intraventricular conduction defects, congestive heart failure, and a specific cardiomyopathy,' the syndrome consisting of a systolic click and late systolic murmur has not been described in this disease. We observed the evolution of a mitral valvular prolapseclick syndrome into moderate mitral regurgitation as a result of bacterial endocarditis in a patient with acromegaly. "From the University of Alberta Hospital, Edmonton. ""Chief Resident in Cardiology. tAssociate Professor, Division of Cardiology. tSenior Resident in Medicine. §Professor and Director, Division of Endocrinology and Metabolism.
Reprint requests: Dr. ]ugdutt, University of Alberta Hospital, Edmonton, Alberta, Canada
690 JUGDUTT, ET AL
CASE REPORT
A 48-year-old man presented with acromegaly in June 1973. Classic clinical features were present. The diagnosis was confirmed by finding an expanded sella turcica on skull xray films, an intrasellar lesion on fractional pneumoencephalographic examination, and elevated plasma levels of growth hormone (greater than 50 ng/ml) by radioimmunoassay,2,3 unsuppressed by hypoglycemia. Other abnormal findings were glucose intolerance, a low plasma level of testosterone, and elevated urinary levels of hydroxyproline.4 There was neither past nor family history of cardiac disease. In July 1973, the patient underwent a transsphenoidal hypophysectomy for an eosinophil adenoma. Plasma levels of growth hormone fell below 50 ng/ml afte'l" surgery, and the patient was discharged on a treatment regimen of cortisone and testosterone. In June 1973, the patient had no cardiac complaints. Examination then revealed a blood pressure of 140/100 mm Hg, no cardiac murmurs, no cardiomegaly on. chest radiographs, and atrioventricular conduction delay ( PR interval, 0.22 second) on the electrocardiogram. Prior to surgery in July 1973, two additional cardiac findings were present: a grade 2/6 late systolic murmur at the apex, and inverted T waves in leads 2, 3, and a VF on the ECG. In September 1973, a systolic click was an additional auscultatory finding, and this was confirmed by phonocardiographic studies (Fig 1 ) . The click migrated towards the first heart sound with inspiration or following the administration of nitroglycerin and introduced a grade 2/6 late systolic murmur, which was loudest at the apex and towards the lower left sternal border and was poorly transmitted to the axilla. Chest radiographs revealed mild left ventricular enlargement. During the ensuing two months, the patient experienced several episodes of ill-defined pain in the left side of the chest. In December 1973, he was readmitted with a 24-hour history of progressive drowsiness, expressive dysphagia, and fever ( 39°C [102.2° F]). Examination revealed sinus tachycardia, tachypnea, splinter hemorrhages, purpuric lesions on both plantar surfaces, and mild hepatosplenomegaly. The jugular venous pressure was elevated ( 13 em H 2 0 ) , and the blood pressure was 130/90 mm Hg. A systolic thrill was palpable at the apex, which was displaced beyond the left midclavicular line. Auscultation and phonocardiographic studies both revealed a normal first heart sound and a grade-
_,
1 SEC
-------
BEFORE NITROGLYCER JNE
' CAROTID
P!-IONO LSB FIGURE 1. Phonocardiogram before endocarditis, showing systolic click (arrowheads) 0.1 second after normal first sound followed by late systolic murmur. LSB, Left sternal border.
CHEST, 69: 5, MAY, 1976
4/6 crescendo-decrescendo pansystolic murmur which tapered off to a normal second sound. There was no systolic click, but a third heart sound was heard. Crepitations were present over both lungs. Relevant laboratory findings were as follows: hemoglobin level, 9.1 gm/100 ml; white blood cell count, 7,800/cu mm, with 81 percent neutrophils; and an elevated erythrocytic sedimentation rate (50 mmlhr). Group D Streptococcus ( S faecalis) was isolated from two consecutive sets of blood cultures. Cerebral angiographic studies revealed a left middle cerebral embolus. Diagnoses of bacterial endocarditis, moderately severe mitral regurgitation ( due to ruptured chordae tendineae), pulmonary venous congestion, and a cerebral embolus were made. Treatment consisted of therapy with digoxin, diuretics, cortisone, and insulin and six weeks of antibiotic therapy. Initially, penicillin (four mega units every four hours) and gentamicin ( 1 mg/lcg every eight hours) were used; three weeks later, ampicillin ( 2 gm every four hours) was substituted for penicillin on the basis of studies on minimal inhibitory concentrations, bactericidal titers, and synergism. The fever subsided after 24 hours of antibiotic therapy, although conjunctival petechiae appeared eight days later and Roth's spots 15 days later. By February 1974, the hemogram was normal, and the erythrocytic sedimentation rate was 34
mm/hr.
Cardiac status was reevaluated in March 1974. The phonocardiogram (Fig 2) was unchanged from that of December 1973. Graded exercise testing (bicycle ergometer) did not precipitate angina or arrhythmia. Cardiac catheterization revealed no evidence for an intracardiac shunt; and intracardiac pressures were as follows: right atrium (mean), 5 mm Hg; right ventricle, 20/4 mm Hg; pulmonary artery, 20/10 mm Hg; wedge, a, 12 mm Hg, and v, 15 mm Hg; aorta, 93/68 mm Hg; and left ventricle, 96/13 mm Hg. Left ventricular angiographic studies revealed moderate mitral regurgitation with the typical posterior hump sign at the end of systole caused by prolapse 9f the posterior leaflet of the mitral valve. Findings from selective coronary angiographic studies were normal, Blood cultures were negative. ·· On follow-up in December 1974, moderate mitral regurgitation with left ventricular enlargement were present; ·and the phonocardiogram, as well as the plasma level of growth hormone, remained unchanged. DISCUSSION
In the few reports of systolic murmurs in acromegaly'· 5 in the literature, neither hemodynamic F'KG
nor phonocardiographic data are presented. The syndrome of systolic click and late systolic murmur and its progression in our patient were studied by phonocardiography and external recordings and later by cardiac catheterization. The development of the syndrome in this patient who already had some evidence of cardiovascular involvement (mild hypertension and atrioventricular conduction delay) may have been incidental; however, several features consistent with the syndrome were present: vague chest pain with normal coronary arteriograms; 6 • 7 endocarditls, 8 which was associated with embolic phenomena and worsening of the mitral regurgitation; and electrocardiographic changes, 6 • 7 although the latter were not diagnostic of inferolateral ischemia. Two questions were prompted by the appearance of the mitral valvular prolapse-click syndrome in this acromegalic patient, but neither could be answered satisfactorily. First, does excessive growth hormone exert a myocardiopathic effect?9 Goodwin' s5 description of an acromegalic patient with mitral regurgitation, congestive cardiac failure, and severe myocardial dysfunction may support this contention. Although McGuffin et al 1 found two further cases of acromegalic cardiomyopathy in a prospective study of 57 patients whom they observed over an average of 5" years, they could not correlate concentrations of growth hormone with the presence or absence of cardiac disease. Se~ondly, since myxomatous degeneration of the mitral valve usually underlies the mitral valvular prolapse syndrome, 6 •10 was this likely in our patient? No evidence for myxomatous degeneration has been described in acromegaly where pathologic study of the heart' has revealed only hypertrophy and fragmentation of the myofibrils with diffuse fibrous-tissue proliferation. On the basis of a patient with a floppy aortic valve, Marfan's syndrome, and "nodular acidophilic hyperplasia" of the anterior pituitary, Read et al 11 postulated that the floppy valve syndrome could be an expression of pituitary and mucopolysaccharide dysfunction; however, their patient had Marfan's syndrome, in which myxomatous degeneration of the aortic and mitral valves is common. 12
..
/r. . \'-~-____l_S_E_C--___,..-It-'•·.___ _ __
~~~~----~·b~.~~~-------.O~M~~~~--~7\:--~-·~----~
CA~OTID
---------___,"fW::V,:f!lv~.\'~•.Ill~ ...../v,.,_, PSHONOB ~·~~ ., ''•: i';
L
CHEST, 69: 5, MAY, 1976
FIGURE 2. Phonocardiogram showing pansystolic murmur three months after onset of endocarditis. No cliclc is present. LSB, Left sternal border.
ACROMEGALY, SYSTOLIC CLICK SYNDROME, AND ENDOCARDmS 891
:8EFE:RENCI!'3 1 McGuffin WL Jr, Sherman BM, Roth J, et al: Acromegaly and cardiovascu1ar disorders: A prospective study. Ann Intern Med 81:11-18, 1974 2 Samols E, Billcins D: A comparison of insulin immunoassays. Proc Soc Exp Bioi Med 115:79-84, 1964 3 Hunter WM, Greenwood FC: Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature 194:495-496, 1962 4 Hejtmancik MR, Bradfield JY, Hermann GP : Acromegaly and the heart: Aclinical and pathologic study. Ann Intern Med 34:1445-1456, 1951 5 Goodwin JF: Clinical demonstrations. Postgrad Med J 48:722-731, 1972 6 Jeresaty RM : Mitral valve prolapse-click syndrome. Prog Cardiovasc Dis 15:623-652, 1973 7 Lobstein ,fiP, Horwitz LD, Curry G, et al: Electrocardiographic abnormalities and coronary arteriograms in the mitral click-murmur syndrome. N Eng! J Med 289:127131, 1973 8 LeBauer J, Perloff JK, Keliher T: The isolated systolic click with bacterial endocarditis. Am Heart J 73:534-537, 1967 9 Pepine CJ, Aloia J: Heart muscle disease in acromegaly. Am J Med 48:530-534, 1970 10 Jeresaty RM: Etiology of the mitral valve prolapse-click syndrome. Am J Cardiol36:110-113, 1975 11 Read RC, White JH, Palacios E : F1oppy valve syndrome: A possible expression of pituitary and mucopolysaccharide dysfunction. Surg Clin North Am 47:1427-1435, 1967 12 McKusick VA: Heritable Disorders of Connective Tissue (4th ed). St. Louis, CV Mosby Co, 1972, pp 119-128
DiHuse Interstitial Fibrosing Pneumonitis and Adenovirus Infection•
might be responsible. The existence of inclusion bodies in affected lung specimens has often been reported; 2- 5 however, direct evidence of viral infection has not been confirmed except for one case reported by O'Shea and Yardleye who found Herpes simplex virus or cytomegalovirus-like particles in alveolar lining cells on electron microscopy. In our patient, adenovirus particles were found in the nuclei of biopsied type II alveolar epithelial cells, plasma cells and alveolar macrophages by electron microscopy. Adenoviral infection was also suggested by demonstration of specific fluorescence in the nuclei of alveolar epithelial cells employing anti-type 12 adenovirus serum raised in rabbits.
CASE REPoRT A 54-year-old Japanese man noticed a slight productive cough in 1969 which did not interfere with his daily work. In 1971, he underwent a routine general physical examination and the chest roentgenogram disclosed a diffuse bilateral nodular infiltrate. A diagnosis of pneumoconiosis was entertained, but he was not treated until 1972 when he was given expectorants and antitussive agents which were not effective. In early March, 1974, he complained of slight dyspnea and was admitted to the Keio University Hospital for evaluation. Family history was noncontributory, but he was affected with syphilis at age 22. On admission, his pulse rate was 88 with respirations of 24 per minute. No cyanosis was noted, but moderate clubbing of the digits was present. On auscultation, crepitant rales (typical Velcro rales) were noted diffusely throughout both lung fields on inspiration and expiration. The liver and spleen were not palpable. No lymphadenopathy or joint involvement was observed. Chest roentgenogram disclosed diffuse reticular shadows which were prominent peripherally and were partly forming honeycombs. Laboratory Findings
Erythrocyte sedimentation rate was 65 mm per hour. Leukocyte count was 13,700 with a differential count of 77.5
Takeshi Kawai, M.D., F.C.C.P.;•• Tatsuji Fujiwara,t Yuzo Aoyama, M.D.;§ Yoshiharu Aizawa, M.D.;•• Yoslrihiro Ytlf'IIOda, M.D.;•• Teruo Aoyagi, M.D., F.C.C.P.;•• Atsuo Mikata, M.D.;t and Keizo Kageyama, M.D.t
With electron microscopy, adenovirus particles, wblch were almost round, variable In density, and 60-80 mp.ln diameter, were observed In the nuclei of typeD alveolar epithelial cells, infiltrated plasma cells and alveolar macrophages of a man with chronic Interstitial fibrosing pneumonitis. The immunofluorescent technique also suggested adenovirus Infection. I
~he
etiology of diffuse interstitial fibrosing pneumois unknown, although Hamman and Riehl speculated that an infectious agent, presumably li virus,
J! nitis
•From the Department of Medicine, • • the Electron Microscopy Laboratory,t the Department of Pathologyt of the Keio University School of Medicine, Tokyo; and the Department of Pathology, the Institute of Medical Science, the Tokyo University, Tokyo.§ Reprint requests: Dr. Kawai, Keio Medical School, Shinft,Jcu, Tokyo, Japan 160
892 KAWAI ET AL
FIGURE 1. Extensive proliferation of interstitial fibers and muscle bundles, marked mononuclear cell infiltration of the alveolar walls, and remarkable exudation, infiltration and desquamation filling the alveolar spaces, and glandular appearance of proliferated alveolar lining cells were noted. Proliferation of lymphoid follicles was also observed ( Hematoxylin and eosin stain; original magnification X 25) .
CHEST, 69: 5, MAY, 1976
15
16
17
18
ous pulmonary venous return: Surgical considerations and results of operation. J Thorac Cardiovasc Surg 60: 116, 1971 Mustard WT, McKeon WJ, Trusler GA: Transposition of the great arteries and transposition of the lesser veins: 2. Transposition of the lesser veins ( total anomalous pulmonary venous drainage). Prog Cardiovasc Dis 11:145, 19'68 Serrato M, Bucheleres HG, Arevado F, et al: Total anomalous pulmonary venous connection without obstruction: Hemodynamic and prognostic significance of foramen ovale size. Circulation 36 ( suppl 2) :232, 1967 ( abstract) Bedford DE, Sellers TH, Somerville W, et al: Atrial septal defect and its surgical treatment. Lancet 1:1255, 1957 Billig DM, Hallman GL, Bloodwell RD, et al: The surgical treatment of cardiac defects associated with variations in cardiac position. J Thorac Cardiovasc Surg 55:80, 1968 Gilbert EF, Nishimura K, Wedum BG: Congenital malformations of the heart associated with splenic agenesis: With a report of five cases. Circulation 17:72, 1958
Acromegaly, the Systolic Click Syndrome, and Group D Streptococcal Endocarditis* B. ]ugdutt, M.B., Ch.B.;"" C. B@ualdo, M.D.;t H. Freeman, M.D.;t and P. Crockford, M.D.§
A syndrome consisting of an apical systolic click and late systolic murmur appeared over a period of three months in a patient with acromegaly. Levels of growth hormone were highest during this interval. As a result of group D streptococcal endocarditis three months later, the patient sustained cerebral embolism and acquired free mitral regurgitation from ruptured chordae tendineae. During follow-up over 18 months, neither the level of growth hormone nor the degree of mitral regurgitation changed significantly.
A !though
acromegaly has been known to be associated with disproportionate cardiomegaly, systemic hypertension, premature coronary arterial disease, arrhythmias, intraventricular conduction defects, congestive heart failure, and a specific cardiomyopathy,' the syndrome consisting of a systolic click and late systolic murmur has not been described in this disease. We observed the evolution of a mitral valvular prolapseclick syndrome into moderate mitral regurgitation as a result of bacterial endocarditis in a patient with acromegaly. "From the University of Alberta Hospital, Edmonton. ""Chief Resident in Cardiology. tAssociate Professor, Division of Cardiology. tSenior Resident in Medicine. §Professor and Director, Division of Endocrinology and Metabolism.
Reprint requests: Dr. ]ugdutt, University of Alberta Hospital, Edmonton, Alberta, Canada
690 JUGDUTT, ET AL
CASE REPORT
A 48-year-old man presented with acromegaly in June 1973. Classic clinical features were present. The diagnosis was confirmed by finding an expanded sella turcica on skull xray films, an intrasellar lesion on fractional pneumoencephalographic examination, and elevated plasma levels of growth hormone (greater than 50 ng/ml) by radioimmunoassay,2,3 unsuppressed by hypoglycemia. Other abnormal findings were glucose intolerance, a low plasma level of testosterone, and elevated urinary levels of hydroxyproline.4 There was neither past nor family history of cardiac disease. In July 1973, the patient underwent a transsphenoidal hypophysectomy for an eosinophil adenoma. Plasma levels of growth hormone fell below 50 ng/ml afte'l" surgery, and the patient was discharged on a treatment regimen of cortisone and testosterone. In June 1973, the patient had no cardiac complaints. Examination then revealed a blood pressure of 140/100 mm Hg, no cardiac murmurs, no cardiomegaly on. chest radiographs, and atrioventricular conduction delay ( PR interval, 0.22 second) on the electrocardiogram. Prior to surgery in July 1973, two additional cardiac findings were present: a grade 2/6 late systolic murmur at the apex, and inverted T waves in leads 2, 3, and a VF on the ECG. In September 1973, a systolic click was an additional auscultatory finding, and this was confirmed by phonocardiographic studies (Fig 1 ) . The click migrated towards the first heart sound with inspiration or following the administration of nitroglycerin and introduced a grade 2/6 late systolic murmur, which was loudest at the apex and towards the lower left sternal border and was poorly transmitted to the axilla. Chest radiographs revealed mild left ventricular enlargement. During the ensuing two months, the patient experienced several episodes of ill-defined pain in the left side of the chest. In December 1973, he was readmitted with a 24-hour history of progressive drowsiness, expressive dysphagia, and fever ( 39°C [102.2° F]). Examination revealed sinus tachycardia, tachypnea, splinter hemorrhages, purpuric lesions on both plantar surfaces, and mild hepatosplenomegaly. The jugular venous pressure was elevated ( 13 em H 2 0 ) , and the blood pressure was 130/90 mm Hg. A systolic thrill was palpable at the apex, which was displaced beyond the left midclavicular line. Auscultation and phonocardiographic studies both revealed a normal first heart sound and a grade-
_,
1 SEC
-------
BEFORE NITROGLYCER JNE
' CAROTID
P!-IONO LSB FIGURE 1. Phonocardiogram before endocarditis, showing systolic click (arrowheads) 0.1 second after normal first sound followed by late systolic murmur. LSB, Left sternal border.
CHEST, 69: 5, MAY, 1976
4/6 crescendo-decrescendo pansystolic murmur which tapered off to a normal second sound. There was no systolic click, but a third heart sound was heard. Crepitations were present over both lungs. Relevant laboratory findings were as follows: hemoglobin level, 9.1 gm/100 ml; white blood cell count, 7,800/cu mm, with 81 percent neutrophils; and an elevated erythrocytic sedimentation rate (50 mmlhr). Group D Streptococcus ( S faecalis) was isolated from two consecutive sets of blood cultures. Cerebral angiographic studies revealed a left middle cerebral embolus. Diagnoses of bacterial endocarditis, moderately severe mitral regurgitation ( due to ruptured chordae tendineae), pulmonary venous congestion, and a cerebral embolus were made. Treatment consisted of therapy with digoxin, diuretics, cortisone, and insulin and six weeks of antibiotic therapy. Initially, penicillin (four mega units every four hours) and gentamicin ( 1 mg/lcg every eight hours) were used; three weeks later, ampicillin ( 2 gm every four hours) was substituted for penicillin on the basis of studies on minimal inhibitory concentrations, bactericidal titers, and synergism. The fever subsided after 24 hours of antibiotic therapy, although conjunctival petechiae appeared eight days later and Roth's spots 15 days later. By February 1974, the hemogram was normal, and the erythrocytic sedimentation rate was 34
mm/hr.
Cardiac status was reevaluated in March 1974. The phonocardiogram (Fig 2) was unchanged from that of December 1973. Graded exercise testing (bicycle ergometer) did not precipitate angina or arrhythmia. Cardiac catheterization revealed no evidence for an intracardiac shunt; and intracardiac pressures were as follows: right atrium (mean), 5 mm Hg; right ventricle, 20/4 mm Hg; pulmonary artery, 20/10 mm Hg; wedge, a, 12 mm Hg, and v, 15 mm Hg; aorta, 93/68 mm Hg; and left ventricle, 96/13 mm Hg. Left ventricular angiographic studies revealed moderate mitral regurgitation with the typical posterior hump sign at the end of systole caused by prolapse 9f the posterior leaflet of the mitral valve. Findings from selective coronary angiographic studies were normal, Blood cultures were negative. ·· On follow-up in December 1974, moderate mitral regurgitation with left ventricular enlargement were present; ·and the phonocardiogram, as well as the plasma level of growth hormone, remained unchanged. DISCUSSION
In the few reports of systolic murmurs in acromegaly'· 5 in the literature, neither hemodynamic F'KG
nor phonocardiographic data are presented. The syndrome of systolic click and late systolic murmur and its progression in our patient were studied by phonocardiography and external recordings and later by cardiac catheterization. The development of the syndrome in this patient who already had some evidence of cardiovascular involvement (mild hypertension and atrioventricular conduction delay) may have been incidental; however, several features consistent with the syndrome were present: vague chest pain with normal coronary arteriograms; 6 • 7 endocarditls, 8 which was associated with embolic phenomena and worsening of the mitral regurgitation; and electrocardiographic changes, 6 • 7 although the latter were not diagnostic of inferolateral ischemia. Two questions were prompted by the appearance of the mitral valvular prolapse-click syndrome in this acromegalic patient, but neither could be answered satisfactorily. First, does excessive growth hormone exert a myocardiopathic effect?9 Goodwin' s5 description of an acromegalic patient with mitral regurgitation, congestive cardiac failure, and severe myocardial dysfunction may support this contention. Although McGuffin et al 1 found two further cases of acromegalic cardiomyopathy in a prospective study of 57 patients whom they observed over an average of 5" years, they could not correlate concentrations of growth hormone with the presence or absence of cardiac disease. Se~ondly, since myxomatous degeneration of the mitral valve usually underlies the mitral valvular prolapse syndrome, 6 •10 was this likely in our patient? No evidence for myxomatous degeneration has been described in acromegaly where pathologic study of the heart' has revealed only hypertrophy and fragmentation of the myofibrils with diffuse fibrous-tissue proliferation. On the basis of a patient with a floppy aortic valve, Marfan's syndrome, and "nodular acidophilic hyperplasia" of the anterior pituitary, Read et al 11 postulated that the floppy valve syndrome could be an expression of pituitary and mucopolysaccharide dysfunction; however, their patient had Marfan's syndrome, in which myxomatous degeneration of the aortic and mitral valves is common. 12
..
/r. . \'-~-____l_S_E_C--___,..-It-'•·.___ _ __
~~~~----~·b~.~~~-------.O~M~~~~--~7\:--~-·~----~
CA~OTID
---------___,"fW::V,:f!lv~.\'~•.Ill~ ...../v,.,_, PSHONOB ~·~~ ., ''•: i';
L
CHEST, 69: 5, MAY, 1976
FIGURE 2. Phonocardiogram showing pansystolic murmur three months after onset of endocarditis. No cliclc is present. LSB, Left sternal border.
ACROMEGALY, SYSTOLIC CLICK SYNDROME, AND ENDOCARDmS 891
:8EFE:RENCI!'3 1 McGuffin WL Jr, Sherman BM, Roth J, et al: Acromegaly and cardiovascu1ar disorders: A prospective study. Ann Intern Med 81:11-18, 1974 2 Samols E, Billcins D: A comparison of insulin immunoassays. Proc Soc Exp Bioi Med 115:79-84, 1964 3 Hunter WM, Greenwood FC: Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature 194:495-496, 1962 4 Hejtmancik MR, Bradfield JY, Hermann GP : Acromegaly and the heart: Aclinical and pathologic study. Ann Intern Med 34:1445-1456, 1951 5 Goodwin JF: Clinical demonstrations. Postgrad Med J 48:722-731, 1972 6 Jeresaty RM : Mitral valve prolapse-click syndrome. Prog Cardiovasc Dis 15:623-652, 1973 7 Lobstein ,fiP, Horwitz LD, Curry G, et al: Electrocardiographic abnormalities and coronary arteriograms in the mitral click-murmur syndrome. N Eng! J Med 289:127131, 1973 8 LeBauer J, Perloff JK, Keliher T: The isolated systolic click with bacterial endocarditis. Am Heart J 73:534-537, 1967 9 Pepine CJ, Aloia J: Heart muscle disease in acromegaly. Am J Med 48:530-534, 1970 10 Jeresaty RM: Etiology of the mitral valve prolapse-click syndrome. Am J Cardiol36:110-113, 1975 11 Read RC, White JH, Palacios E : F1oppy valve syndrome: A possible expression of pituitary and mucopolysaccharide dysfunction. Surg Clin North Am 47:1427-1435, 1967 12 McKusick VA: Heritable Disorders of Connective Tissue (4th ed). St. Louis, CV Mosby Co, 1972, pp 119-128
DiHuse Interstitial Fibrosing Pneumonitis and Adenovirus Infection•
might be responsible. The existence of inclusion bodies in affected lung specimens has often been reported; 2- 5 however, direct evidence of viral infection has not been confirmed except for one case reported by O'Shea and Yardleye who found Herpes simplex virus or cytomegalovirus-like particles in alveolar lining cells on electron microscopy. In our patient, adenovirus particles were found in the nuclei of biopsied type II alveolar epithelial cells, plasma cells and alveolar macrophages by electron microscopy. Adenoviral infection was also suggested by demonstration of specific fluorescence in the nuclei of alveolar epithelial cells employing anti-type 12 adenovirus serum raised in rabbits.
CASE REPoRT A 54-year-old Japanese man noticed a slight productive cough in 1969 which did not interfere with his daily work. In 1971, he underwent a routine general physical examination and the chest roentgenogram disclosed a diffuse bilateral nodular infiltrate. A diagnosis of pneumoconiosis was entertained, but he was not treated until 1972 when he was given expectorants and antitussive agents which were not effective. In early March, 1974, he complained of slight dyspnea and was admitted to the Keio University Hospital for evaluation. Family history was noncontributory, but he was affected with syphilis at age 22. On admission, his pulse rate was 88 with respirations of 24 per minute. No cyanosis was noted, but moderate clubbing of the digits was present. On auscultation, crepitant rales (typical Velcro rales) were noted diffusely throughout both lung fields on inspiration and expiration. The liver and spleen were not palpable. No lymphadenopathy or joint involvement was observed. Chest roentgenogram disclosed diffuse reticular shadows which were prominent peripherally and were partly forming honeycombs. Laboratory Findings
Erythrocyte sedimentation rate was 65 mm per hour. Leukocyte count was 13,700 with a differential count of 77.5
Takeshi Kawai, M.D., F.C.C.P.;•• Tatsuji Fujiwara,t Yuzo Aoyama, M.D.;§ Yoshiharu Aizawa, M.D.;•• Yoslrihiro Ytlf'IIOda, M.D.;•• Teruo Aoyagi, M.D., F.C.C.P.;•• Atsuo Mikata, M.D.;t and Keizo Kageyama, M.D.t
With electron microscopy, adenovirus particles, wblch were almost round, variable In density, and 60-80 mp.ln diameter, were observed In the nuclei of typeD alveolar epithelial cells, infiltrated plasma cells and alveolar macrophages of a man with chronic Interstitial fibrosing pneumonitis. The immunofluorescent technique also suggested adenovirus Infection. I
~he
etiology of diffuse interstitial fibrosing pneumois unknown, although Hamman and Riehl speculated that an infectious agent, presumably li virus,
J! nitis
•From the Department of Medicine, • • the Electron Microscopy Laboratory,t the Department of Pathologyt of the Keio University School of Medicine, Tokyo; and the Department of Pathology, the Institute of Medical Science, the Tokyo University, Tokyo.§ Reprint requests: Dr. Kawai, Keio Medical School, Shinft,Jcu, Tokyo, Japan 160
892 KAWAI ET AL
FIGURE 1. Extensive proliferation of interstitial fibers and muscle bundles, marked mononuclear cell infiltration of the alveolar walls, and remarkable exudation, infiltration and desquamation filling the alveolar spaces, and glandular appearance of proliferated alveolar lining cells were noted. Proliferation of lymphoid follicles was also observed ( Hematoxylin and eosin stain; original magnification X 25) .
CHEST, 69: 5, MAY, 1976
