Three patients with history of documented hypotension, near syncope, or syncope before or after the administration of isoproterenol during head-up tilt table are reported. Severe bradycardia was also noted in one patient. All three patients responded to the administration of 2.5 mg of oral dextroamphetamine 45 minutes prior to a repeat head-up tilt table study. The potent central and peripheral adrenergic agonist pharmacological proper-ties of this drug permitted the prevention of severe vasodepressor syncope in these patients.

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency with less than 2% of normal enzyme activity is characterized by neurological abnormalities, atherosclerotic changes, and thromboembolism. We have discovered a "new" variant of MTHFR deficiency which is characterized by the absence of neurological abnormalities, an enzyme activity of about 50% of the normal value, and distinctive thermolability under specific conditions of heat inactivation. In this study, lymphocyte MTHFR specific activities in the thermolabile variant and control groups were 5.58 +/- 0.91 and 10.33 +/- 2.89 nmol formaldehyde formed/mg protein/h, respectively. The difference was significant (P less than .01). However, there was overlap among the individual values from the two groups. On the other hand, residual MTHFR activity after heat inactivation was 11.2 +/- 1.43% in the thermolabile variant and 36.3 +/- 5.18% in the controls. There was no overlap. Enzyme studies in 10 subjects with thermolabile MTHFR and their family members support the hypothesis that thermolabile MTHFR is inherited as an autosomal recessive trait. To elucidate the association of thermolabile MTHFR with the development of coronary artery disease, we determined the thermostability of lymphocyte MTHFR in 212 patients with proven coronary artery disease and in 202 controls without clinical evidence of atherosclerotic vascular disease. Thermolabile MTHFR was found in 36 (17.0%) cardiac patients and 10 (5.0%) controls. The difference in incidence between the two groups was statistically significant (P less than .01). The average age at onset of clinical coronary artery disease in 36 patients with thermolabile MTHFR was 57.3 +/- 7.6 years (35-72 years). The mean total plasma homocysteine concentration in patients with thermolabile MTHFR was 13.19 +/- 5.32 nmol/ml and was significantly different from the normal mean of 8.50 +/- 2.80 nmol/ml (P less than .05). There was no association between thermolabile MTHFR and other major risk factors. We conclude that thermolabile MTHFR is a variant(s) of MTHFR deficiency which is inherited as an autosomal recessive trait. In addition, it is positively associated with the development of coronary artery disease. Determination of in vitro thermostability of lymphocyte MTHFR is a reliable method for identifying subjects with this abnormality.

• A 58-year-old woman had a unilateral, solitary breast lesion determined by biopsy to be due to giant cell arteritis. Clinical, laboratory, and pathological findings in this patient and in other patients reviewed from the literature revealed that characteristically patients with giant cell arteritis of the breast have (1) tender unilateral or bilateral nodules at times mimicking breast carcinoma; (2) significant constitutional symptoms of anorexia, weight loss, myalgias, fever, and arthralgias; (3) marked elevation of the erythrocyte sedimentation rate; (4) normal or mildly decreased hemoglobin values and normal or slightly elevated leukocyte counts; (5) normal temporal artery biopsy findings; (6) rare organ involvement; and (7) rapid improvement after prednisone therapy or frequent spontaneous resolution. This mode of presentation suggests features of a unique syndrome since many patients had no systemic involvement, require no treatment at all, and had a self-limited clinical course. (Arch Intern Med.1990;150:900-904)

• A 58-year-old woman had a unilateral, solitary breast lesion determined by biopsy to be due to giant cell arteritis. Clinical, laboratory, and pathological findings in this patient and in other patients reviewed from the literature revealed that characteristically patients with giant cell arteritis of the breast have (1) tender unilateral or bilateral nodules at times mimicking breast carcinoma; (2) significant constitutional symptoms of anorexia, weight loss, myalgias, fever, and arthralgias; (3) marked elevation of the erythrocyte sedimentation rate; (4) normal or mildly decreased hemoglobin values and normal or slightly elevated leukocyte counts; (5) normal temporal artery biopsy findings; (6) rare organ involvement; and (7) rapid improvement after prednisone therapy or frequent spontaneous resolution. This mode of presentation suggests features of a unique syndrome since many patients had no systemic involvement, require no treatment at all, and had a self-limited clinical course. (Arch Intern Med.1990;150:900-904)

A 35-year-old woman with morbid obesity was admitted to Rush-Presbyterian—St Luke's Medical Center, Chicago, for a gastric plication procedure. She had a five-year history of intermittent palpitations, worsening over the preceding four months, associated with sharp precordial pains and dyspnea. Multiple abdominal surgical procedures had been done in the past, including several ovarian cystectomies, a total abdominal hysterectomy, and, one year prior to admission, a gastric plication that had failed. Two years prior to admission a subclavian catheter had been placed for three weeks of central hyperalimentation. An automobile accident six months prior to admission had resulted in superficial chest trauma. The findings on physical examination were remarkable for obesity. Vital signs were normal, and a grade 2/6 systolic murmur was noted along the left sternal border, not changing with respirations. The jugular venous pulsations were normal. The lungs were clear, and no peripheral edema was noted. Rhythm strips and

A 35-year-old woman with morbid obesity was admitted to Rush-Presbyterian—St Luke's Medical Center, Chicago, for a gastric plication procedure. She had a five-year history of intermittent palpitations, worsening over the preceding four months, associated with sharp precordial pains and dyspnea. Multiple abdominal surgical procedures had been done in the past, including several ovarian cystectomies, a total abdominal hysterectomy, and, one year prior to admission, a gastric plication that had failed. Two years prior to admission a subclavian catheter had been placed for three weeks of central hyperalimentation. An automobile accident six months prior to admission had resulted in superficial chest trauma. The findings on physical examination were remarkable for obesity. Vital signs were normal, and a grade 2/6 systolic murmur was noted along the left sternal border, not changing with respirations. The jugular venous pulsations were normal. The lungs were clear, and no peripheral edema was noted. Rhythm strips and

Exercise electrocardiography and selective coronary arteriography was per formed in 24 consecutive patients with complete bundle branch block. The criteria for a positive exercise electrocardiogram (E-ECG) were a 1 mm depres sion or elevation in the J point from the control state, as well as in the ST segment measured at 0.04 seconds from the J point. Eleven of 12 patients with complete left bundle branch block had a positive E-ECG. Nine of them had normal coronary arteriograms, except one with less than 50% lesions in two arteries. Two patients had severe three-vessel disease. Only one patient had a true negative exercise test. No patient had a false negative test. Nine of 12 patients with complete right bundle branch block had a positive E-ECG. One of these 9 had minimal nonobstructive disease, while the other 8 had severe two- or three-vessel coronary artery disease. Three of the 12 right bundle branch block patients had a negative E-ECG. Two of them had a true negative exercise test, and one a false negative test. Because of a high incidence of probably false positive results, E-ECG appears to be unreliable in detecting coronary artery disease in patients with complete left bundle branch block. But it can provide useful information in the non- invasive evaluation of coronary artery disease in patients with complete right bundle branch block.

One hundred and fifteen consecutive symptomatic patients undergoing graded exercise testing, selective coronary angiography and left ventriculography were retrospectively evaluated. The sensitivity, specificity, and false negative response rates of the exercise tests were 79%, 81%, and 21%, respectively. Although the magnitude of a positive ST-segment response was related to more extensive vascular disease, the frequency of false negative responses was nearly identical in patients with single, double, or triple vessel disease (22%, 21%, 19%). Analysis of the false negative group demonstrated significant ventriculographic and hemodynamic abnormalities when compared to the true positive responders. Five out of six patients with the most serious motion disorders in the study fell into the false negative group. There were no significant differences in the extent, distribution and severity of vascular involvement, or in the development of collateral circulation in the two groups. However, occluded vessels supplied abnormal ventricular segments more frequently in the false negative group (88% vs 38%); the absence of an "ischemic response" and the presence of segments of abnormal myocardium may be related. Left ventricular dysfunction appears to be an important reason for a false negative response to exercise.

The findings in two patients with angiographically proven massive pulmonary embolism and with clinical and phonocardiographic evidence of abnormal respiratory movement of the pulmonic sound are reported. One patient with complete right bundle-branch block and another with normal conduction had a wide and fixed split second sound with a loud pulmonic component. Both patients had a moderate degree of pulmonary hypertension. Approximately two weeks after administration of heparin, the pulmonic sound moved normally during respiration in both patients. Thromboembolic pulmonary hypertension regressed in one patient and remained unchanged in the other. Changes in impedance through the large pulmonary arteries are are postulated to be responsible for the abnormal movement of the pulmonic valve during both phases of respiration. Wide expiratory splitting of the second sound should be an important clue in the diag nosis of acute massive pulmonary embolism, and the reappearance of a normal inspiratory splitting could be used at the beside to assess indirectly the rate of resolution of the blood clots.

The mechanisms and potential mediator of hypercapneic pulmonary hypertension are incompletely understood. We studied 18 dogs, anaesthetised and spontaneously breathing both room air and after the inhalation of a gas mixture containing 10% CO2, 20.9% O2, and 69.1% N2, to determine the role of histamine, serotonin, and acidaemia in pulmonary hypertension produced by hypercapnia. Hypercapnia increased the mean pulmonary artery pressure by 0.33 kPa (2.5 mmHg) while wedge pressure and pulmonary arteriolar resistance did not change. Cardiac output significantly increased, indicating that the pulmonary hypertensive effect of hypercapnia is mainly flow related. Neither chlorpheniramine nor methysergide had significant effects on hypercapneic pulmonary hypertension. The infusion of sodium bicarbonate corrected the pH; pulmonary artery pressure and cardiac output increased while pulmonary arteriolar resistance dropped, suggesting that the increased cardiac output masked the effect of pH on pulmonary arteriolar resistance. The lack of effect of chlorpheniramine or methysergide on pulmonary resistances indicates that the vasoconstrictive effect of increased hydrogen ion concentration which accompanies hypercapnia is attributable neither to histamine nor to serotonin release.

During exposure to 8 percent oxygen inhalation, 18 dogs experienced an average increase of 5.4 mm Hg in mean pulmonary arterial pressure. The administration of promethazine and chlorpheniramine during an initial exposure to hypoxia significantly decreased the pulmonary hypoxic pressor response; the administration of diphenhydramine did not. However, these 3 antihistaminic agents prevented the development of pulmonary hypertension during a second exposure to hypoxia (P = 0.3 × 10−6). Five dogs received progressive doses of chlorpheniramine, thus showing that the effectiveness of this drug can be demonstrated at a dose of less than 0.3 mg/kg body weight. The amounts of diphenhydramine and promethazine needed to achieve effectiveness equivalent to that of chlorpheniramine are sufficiently great as to restrict their applicability to man in acceptable doses. This study lends further support to the hypothesis that histamine mediates hypoxic pulmonary hypertension.

Two patients found to have congenital absence of the circumflex coronary artery are reported. The clinical, electrocardiographic, vectorcardiographic, and cineangiographic findings are presented. No distinctive clinical or laboratory abnormalities were found except for the unusual anatomical posterior origin of the ostium of the main left coronary artery.

The occurrence of cardiovascular lesions in individuals with rheumatoid arthritis has been recognized for many years.1Manifestations attributed to the rheumatoid process include valvular, myocardial, and pericardial lesions,2-6as well as systemic arteritis.7,8Arteritis of the coronary vessels has been found at autopsy in as many as 20% of the cases,9but only rarely has this complication been diagnosed during life. The clinical diagnosis of acute myocardial infarction due to rheumatoid coronary arteritis was not reported until as recently as 1967,10,11although the pathological association had been previously recognized.5,7,12 We describe the clinical and coronary cineangiographic features of a patient with rheumatoid coronary arteritis in whom angina pectoris was treated by a saphenous vein aortocoronary bypass. Patient Summary A 35-year-old white woman was admitted to Rush-Presbyterian-St. Luke's Medical Center on May 9,1971. For several years, the patient had been experiencing oppressive precordial pain and