Chronic thromboembolic occlusion of main pulmonary artery or primary branches. Case report and review of the literature.

Chronic thromboembolic occlusion of the left pulmonary artery in a 36 year old woman is described, and similar cases reported in the past 15 years are discussed. On review, this disease remains a rare entity. In the majority of cases, the etiology is thrombophlebitis and acute pulmonary embolism. Associated cardiopulmonary disease is uncommon. The most common presenting symptom is unexplained dyspnea, and the majority of patients have past histories of hemoptysis. Acute cardiovascular collapse is distinctly rare. Most physical signs and laboratory tests are normal or nonspecific. The perfusion lung scan, although nonspecific, is the best screening test. Antemortem diagnosis, with rare exception, is established by pulmonary angiography. Eleven patients have been operated on: thromboembolectomy in nine, saphenous vein graft in one and pneumonectomy in one. Operative mortality was 36 per cent (four of 11), definite improvement was seen in 46 per cent (five of 11), and 18 per cent (two of 11) survived the operation with no improvement. The role of medical therapy in this disease is considered.     

A new look at an old problem: Mushroom poisoning: Clinical presentations and new therapeutic approaches

Two families are described in which seven members of a total of 19 were found to have hypersensitivity pneumonitis due to exposure to avian antigens. Diagnosis was made on the basis of characteristic roentgenologic changes together with respiratory function and immunologic studies. The latter included screening for precipitins, macrophage migration inhibition (MMI) to specific antigens in avian serum and droppings, quantitation of immunoglobulin and alpha₁ antitrypsin (AAT) levels and assessment of the complement system.Specific precipitins to pigeon and/or budgerigar serum were found in the serum of only four of the seven patients. Six of these seven patients, however, had a positive MMI. Thus, the MMI test, at least in this group of patients appeared to be a more sensitive indicator of active disease.The finding of seven members of two families with disease led to a search for predisposing factors, either genetic or environmental. Evidence for a genetic predisposition came from tissue typing studies. In the first family, both paternal haplotypes were associated with disease; the maternal haplotype HLA3,7 was not inherited by any child with disease. In the second family, the disease developed in three of four members with the haplotype HLA2, W15, who were significantly exposed to avian antigen. In the light of recent studies showing an association between immune response (Ir) genes, histocompatibility antigens and disease susceptibility, these findings were interpreted as possible evidence for a subtle genetically linked immune defect in hypersensitivity pneumonitis. Evidence for an environmental predisposition was less clear cut, but it is interesting that members of both families used a gamma isomer of hexachlorobenzene (Nickoff^®) to eradicate mite infestations in their birds which might have damaged the bronchial mucosa or acted as an immunologic adjuvant in a person with underlying susceptibility to disease.The presence of subclinical respiratory disease in two family members is reported, and the importance of performing a range of investigations of respiratory function in order to detect disease and monitor its progress is emphasized.     

Cardiac amyloidosis: Diagnosis by transvenous endomyocardial biopsy

Endomyocardial tissue, obtained from two patients presenting with restrictive cardiomyopathies, demonstrated amyloid infiltration. The percutaneous transvenous cardiac biopsy technic, using a modified Konno-Sakakibara cardiac bioptome, was safe and quick. Physical examination and catheterization data may not provide a definite differential diagnosis between restrictive and constrictive myocardial disease. Confirmation by biopsy of the cardiac amyloidosis assisted in providing optimum diagnostic and therapeutic care for these patients.     

Life-threatening arrhythmias in the mitral valve prolapse syndrome

This study describes seven patients with the mitral valve prolapse or click-murmur syndrome who have survived one or more episodes of life-threatening ventricular arrhythmias. These arrhythmias include cardiac arrest due to ventricular fibrillation, recurrent ventricular tachycardia causing syncope or sustained ventricular tachycardia requiring electroversion. These patients were seen over a two-year period in a single medical center. Five of the seven had repolarization abnormalities in the resting electrocardiogram. Premature ventricular contractions were present in the routine resting electrocardiograms of six of the seven patients and were frequent during treadmill testing and ambulatory electrocardiographic monitoring in all six tested. There were electrolyte abnormalities or changes in medications known to affect myocardial repolarization during the week before the episode in three of the four patients with cardiac arrest. The diagnosis of mitral valve prolapse click-murmur syndrome was made prior to the episode of life-threatening arrhythmia in only two of the seven patients. Varying forms of antiarrhythmic therapy were given to these patients during follow-up periods of five to 26 months. Although the incidence of fatal arrhythmias in the mitral prolapse syndrome is probably small, we suggest that such arrhythmias may not be extremely rare, particularly among those patients who have repolarization abnormalities in the resting electrocardiogram and frequent premature beats. Patients with unexplained ventricular arrhythmias should be screened for mitral valve prolapse.     

The prehospital course of patients with chest pain. Analysis of the prodromal, symptomatic, decision-making, transportation and emergency room periods

In order to determine whether prehospitalization characteristics of patients with chest pain are useful in predicting their subsequent course, we analyzed the precoronary care course in 211 consecutive patients admitted because of suspected myocardial infarction. On the basis of serial electrocardiograms and enzymes, 61 patients had a definite myocardial infarction on admission, 30 patients evolved criteria for an infarction during hospitallzation, 102 patients had cardiac pain without infarction, and 18 patients were judged to have noncardiac pain. The mean patient delay from onset of chest pain to arrival at the hospital was 456 ± 703 minutes (median 210 minutes). The decision to seek medical help consumed a mean 307 ± 575 minutes of this delay, whereas transportation to the hospital required only a mean of 17 ± 49 minutes. Known heart disease, known stable angina and progressive unstable angina tended to prolong the patient's decision to seek medical help. Of 140 patients who contacted a physician, 67 (48 per cent) were sent to the emergency room; whereas 71 had an additional mean 180 ± 436 minutes (median 38 minutes) of physician-advised delay consisting of office visits (59 patients), house call (five patients) and other attempted therapy (seven patients). The presence of prodromas or chest pain consistent with unstable angina was not significantly different in any patient group. We conclude that prodromas, although common, are not helpful in differentiating those with infarction from those without infarction among the patients hospitalized because of chest pain. Furthermore, the mean patient delay of over 6 hours and median delay of 3 $\text{1}\text{2}\text{hours}$ indicates that this delay is the most immediate problem to be solved in order to decrease out of hospital mortality.     

Diverticulum of the left ventricle in hypertrophic cardiomyopathy.

An unusual case of diverticulum of the left ventricle is presented. The most distinctive feature was the presence of a circumferential mid-ventricular contraction ring with histologic abnormalities similar to those described in patients with asymmetric septal hypertrophy. This abnormal ring of tissue obstructed emptying of the ventricular apex and isolated it from the rest of the ventricle. The obstructed apex assumed the appearance of a muscular diverticulum, and the residual portion of the ventricle was markedly diminished in volume. In addition, the abnormal mid-ventricular hypertrophy interfered with papillary muscle function, producing mitral valve prolapse and mitral regurgitation. The patient's age was equally unusual; she was 65 at the time of diagnosis, probably the oldest known patient with ventricular diverticulum. She was treated surgically by transapical myotomy and myectomy of the mid-ventricular contraction ring, in order to increase effective ventricular volume. The relationship of this entity to other types of ventricular deiverticula and aneurysms, and to hypertrophic cardiomyopathy, is discussed.     

Cardiac transplantation in man. Review of first three years' experience

A one year follow-up of the first 29 patients who underwent cardiac transplantation at Stanford University Medical Center from January 1968 to January 1971 is reported. Actuarial survival is 49 per cent at six months, 37 per cent at 12 and 18 months, and 30 per cent at two years. Recipient selection is important for the best long-term results; the ideal candidate is a relatively young patient with recent severe cardiac disability which has been unresponsive to optimal medical and surgical therapy.In our series, three patients died within 72 hours after transplantation secondary to severe fixed pulmonary hypertension. Nine additional patients died in the hospital; in seven of these death was related to unremitting rejection or infection.Thirteen patients were discharged from the hospital, with a 60 per cent actuarial chance of living two years. Evaluation has documented “normal denervated” cardiac function in eight patients one year, and in one of two patients two years after transplantation. Chronic rejection appears to be manifested by cardiac arrhythmias, coronary artery intimal hyperplasia, atherosclerosis and subsequent myocardial infarction.Improved diagnosis and treatment of acute rejection has resulted in yearly improvement in the short-term survival. These patients return to normal activities after hospital discharge and are not limited by their cardiac function. Their long-term survival appears to be limited by coronary arterial changes related to chronic rejection.     

Successful treatment by overdrive pacing of recurrent quinidine syncope due to ventricular tachycardia

A 54 year old patient who experienced recurrent ventricular tachycardia subsequent to quinidine administration for conversion of atrial fibrillation is described. Over a 10 hour period, 25 sustained episodes of ventricular tachycardia occurred for which electrical cardioversion was required in addition to numerous self-terminating paroxysms. Medical therapy with lidocaine, procainamide and propranolol was unsuccessful in controlling the arrhythmia. However, placement of a transvenous right ventricular pacemaker with overdrive pacing at a rate of 110 beats/min abrupty terminated all further ventricular ectopic activity during the period of quinidine elimination. Temporary overdrive pacing may be the treatment of choice for refractory, recurrent, ventricular tachycardia associated with quinidine therapy.     

A-V conduction disturbances in Reiter's syndrome

High grade atrioventricular (A-V) block is a rarely described complication of Reiter's syndrome. This 65 year old man had recurrent episodes of arthritis, conjunctivitis and urethritis beginning at age 16. A prolonged P-R interval was first noted at age 32. The conduction disturbance progressed to intermittent episodes of high grade and complete heart block by age 65. His bundle electrograms located the site of block above the level of the bundle of His. Atrial pacing to rates of 150/min produced 5:1 A-V block, whereas exercise and atropine administration resulted in 1:1 A-V conduction. In view of these results, artificial pacemaker therapy is not indicated. The association of conduction disorders and Reiter's syndrome is reviewed.     

Hereditary nephritis, deafness and abnormal thrombopoiesis. Study of a new kindred.

A fourth kindred displaying the triad of hereditary nephritis, deafness and thrombocytopenia with giant platelets is described. Renal involvement, a common cause of death amongst afflicted subjects, appears to have a better prognosis in the affected members of this family. Although the electron microscopic appearance of the megakaryocytes in the present case appears similar to that in previously reported cases, we suggest that the "giant" platelets may result from a degenerative process of megakaryocytes leading to nuclear regression and cytoplasmic fragmentation, rather than the usual blebbing process.     

Studies on circulatory response to hypoxia in the denervated transplanted human heart

The relative importance of centrally mediated reflex responses versus the release of circulating humoral substances in the heart's response to acute hypoxia was studied in the transplanted human heart with its residual innervated recipient atrium and denervated donor atrium. The sinus node rates of both the donor and recipient atria were compared by monitoring P wave activity on the standard electrocardiogram in six patients during control and hypoxic conditions. Breathing 13 per cent oxygen for 10 minutes resulted in an average oxygen saturation of 75 per cent and an oxygen tension (pO₂) of 40 mm Hg, and was associated with a 16 per cent (p 0&;#x030C;.05) increase in the recipient sinus node rate, but with no change in the donor sinus node rate. Pretreatment with atropine abolishes this increase in the innervated recipient sinus node. Breathing 10 per cent oxygen resulted in an oxygen saturation of 55 per cent and a pO₂ of 25 mm Hg, with an associated 10 per cent increase in both donor and recipient sinus node rate. These studies indicate that changes in heart rate during mild degrees of hypoxemia are mediated by a central reflex mechanism which leads to the release of normal vagal parasympathetic tone. The increase in heart rate that occurs in both the innervated and denervated sinus node rates during more severe degrees of hypoxia is probably due to the release of circulating humoral substances, since reinnervation has not been documented in the human cardiac allograft.     

A syndrome of congenital cardiomyopathy with mitral regurgitation, complete heart block and atrial arrhythmia

A distinctive syndrome of cardiomyopathy with mitral regurgitation, complete heart block and atrial arrhythmia was noted in four male patients aged 19 to 49 years. Each presented with cardiac enlargement and varying degrees of left ventricular failure. One patient was known to have had complete heart block from infancy and another patient from 13 years of age. Each had chronic atrial fibrillation or flutter, with a regular ventricular rhythm at 35 to 45/min. Hemodynamic studies showed dilatation and poor contractility of the left ventricle, considerable mitral regurgitation, reduced resting cardiac output and elevated left ventricular end-diastolic pressures. The clinical course in follow-up periods of up to 5 years has been one of relatively mild, slowly progressive congestive heart failure. Mitral valve replacement and permanent pacemaker installation in one patient had no effect on the clinical course. The mitral valve showed redundant leaflet tissue with mucoid degenerative changes. This syndrome appears to represent a form of congenital cardiomyopathy which involves degeneration or fibrotic changes in both the myocardium and the conduction system. Familial occurrence has not been recognized.     

Intrarenal heterogeneity. The case for two functionally dissimilar populations of nephrons in the mammalian kidney

In the past few years evidence has established that the rat kidney has at least two functionally dissimilar groups of nephrons, corresponding to known anatomic differences: the superficial nephron, comprising the bulk of nephrons in most species; and the juxtamedullary nephron, constituting the remainder. The filtration rate, the composition of tubule fluid in Henle's loop, the response to acute and chronic salt loads, and the effect of chronic hypertension have been shown to differ between the two kinds of nephrons. It may be useful to bear in mind the concept of two nephron populations in the study of renal disease, since certain diseases have been observed by morphologists to have a predilection for specific anatomic regions within the kidney. Interpreting function with an eye to underlying structure may prove as rewarding today as it was to William Bowman 131 years ago.     

1,25-dihydroxyvitamin D resistance,rickets, and alopecia

Two unrelated kindreds with four affected children having 1,25-dihydroxyvitamin D resistance, rickets, and alopecia are described. The children exhibited early onset of severe rickets with hypocalcemia, hypophosphatemia, elevated serum alkaline phosphatase levels, and secondary hyperparathyroidism. Radiography showed diffuse demineralization and classic changes of rickets. All affected children had total-body alopecia. Serum levels of 1,25-dihydroxyvitamin D₃ were elevated and rose to extremely high values during treatment, with no apparent change in the mineral disorder. However, secondary hyperparathyroidism and hypophosphatemia did remit during treatment despite persistently low calcium levels. Skin biopsy was performed in the parents and affected children in one kindred. Analysis of 1,25-dihydroxyvitamin D₃ receptors in cultured fibroblasts Indicated apparent normal receptors in the parents and undetectable receptors In both affected children. After long periods of treatment with vitamin D metabolites and mineral replacement, healing took place in the older child in each kindred. These data suggest that the healing occurred spontaneously as the children reached seven to nine years of age rather than as a result of the treatment. The biochemical lesion in these children appeared to be a genetically transmitted defect in the 1,25-dihydroxyvitamin D₃ receptor. The mechanisms by which healing was initiated and maintained remain to be elucidated.     

Complications of therapeutic apheresis,including a fatal case with pulmonary vascular occlusion

A high incidence of anaphylactic reactions has been observed in patients undergoing therapeutic plasma exchange. In three of 22 patients who underwent multiple exchanges, urticaria, bronchospasm, and hypotension developed during a course of plasma exchange that responded to treatment with steroids, antihistamines, and epinephrine. Fatal pulmonary microvascular occlusion with platelets and granulocytes developed in an additional patient eight hours following an apheresis procedure involving albumin replacement. The mechanism for the latter complication is not known but did not appear to invoke complement activation. This unexpectedly high risk of potentially fatal complications must be considered when a course of therapeutic apheresis, particularly involving treatment of a chronic disease, is planned.     

Factitious and fraudulent fever

The task of elucidating the etiology of fever of undetermined origin remains a major undertaking. Factitious fever is uncommonly considered of major importance in the differential diagnosis of fever of undetermined origin although it is a readily identifiable syndrome and one that is easily excluded once it has been considered. Early identification may reduce the necessity for prolonged, expensive and potentially hazardous hospitalizations for such patients.A retrospective study identified 2.2 per cent (11 of 506) of all patients whose fever on their charts was coded as fever of undetermined origin as having factitious fever. These patients either created factitious fever by manipulation of the thermometer or fraudulent fever by self-induced means. A review of the literature yielded an additional 70 cases in which fever was either the sole factitious sign or part of a larger, more complex factitious illness. Patients were typically young, female and often associated with the medical profession.Patients with factitious fever differ from those with the stereotyped Munchausen's syndrome and may be difficult to recognize. Signs leading to the recognition of this syndrome are emphasized. Since the nature of the psychiatric Illness may vary from patient to patient, early discovery may facilitate psychiatric intervention as such patients may be more amenable to therapy.     

Acute myelogenous leukemia in two patients treated with azathioprine for nonmalignant diseases

Two patients receiving long-term azathioprine therapy for immunosuppression of nonmalignant conditions (chronic active hepatitis and renal transplantation) were admitted to Stanford University Hospital with acute myelogenous leukemia. Possible mechanisms of leukemogenesis are discussed. A review of the literature reveals these to be the first reported instances of acute myelogenous leukemia occurring after azathioprine immunosuppression for nonmalignant illness.     

Estimating prognosis in systemic lupus erythematosus

Knowledge of prognosis is critical for rational choice of therapy. Systemic lupus erythematosus, with its broad clinical spectrum, presents an example of the problem of prognostication for the individual patient. The life table method can provide prognostic information. It need not be limited to estimation of survivorship, and its utility can be multiplied by a computer databank. Analysis of prognosis for different groups of patients, from different events in their course, over different time periods, and to different end points can then be performed. Using this technic, specific clinical variables in systemic lupus erythematosus were assessed for their effect upon particular outcomes. Clinical variables representing functional organ impairment were found to carry a worse prognosis than the popular serologic indicators. New abnormalities were found to occur less frequently in later years of the disease. Different subpopulations of patients have strikingly different expectations, and these differences carry important therapeutic implications.     

Surreptitious diuretic ingestion and pseudo-Bartter's syndrome

A patient with profound hypokalemia satisfied the criteria for Bartter's syndrome, including hyperreninemia, aldosteronism, normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. Two screening tests of urine and one of plasma for diuretic agents gave negative results. A third urinary sample gave negative results for thiazide but positive for furosemide; the fourth and fifth samples gave negative results for furosemide but positive for thiazide. Urinary prostaglandin excretion was normal. We conclude that this apparent case of Bartter's syndrome was caused by long term surreptitious diuretic ingestion and suggest this may occur more frequently than is generally appreciated.