Ventricular function curves from the cardiac response to angiographic contrast: a sensitive detector of ventricular dysfunction in coronary artery disease

Fifty cardiac catheterizations were performed in 44 patients undergoing evaluation for coronary artery disease. Ventricular function curves (VFC) were constructed by plotting the left ventricular end-diastolic pressure (LVEDP) and stroke work index (SWI) before and three to four minutes after a standard left ventricular angiogram. In an attempt to delineate the mechanism that produces changes in the post-angiogram LVEDP and SWI, 13 individuals (Group A) with no evidence of cardiac disease were compared to 14 patients with severe coronary artery disease (Group B). Cardiac output and LVEDP increased in both groups after angiogram. The increase in cardiac output was less and the increase in LVEDP greater in Group B. V_max. did not change significantly after angiogram in either group. Other measures of contractility ($\text{dp}\text{dt}$ max., peak Vce, and dp/dt/40 mm. developed pressure) changed appropriately for the large changes in preload seen after angiogram.Thirty-seven studies in patients with coronary artery disease demonstrated that VFC obtained from the cardiac response to contrast are more sensitive than resting LVEDP or ejection fraction in detecting left ventricular abnormality.VFC can be obtained from the ventricular response to angiographic contrast because of the increase in venous return produced by the hyperosmotic effect of contrast. Depressed curves occur in patients with coronary artery disease because of their stiff ventricles and not because of depression of myocardial contractility.     

Cardiac rehabilitation following coronary artery bypass surgery

Early expectations of coronary revascularization prolonging life and reducing coronary events have been modified by 15 years' experience to mostly initial palliation of ischemic symptoms. Bypass surgery represents only a single therapeutic aspect for coronary atherosclerosis. Technically successful operations often fail miserably without overall risk factor alteration and functional capacity optimization which progressive exercise initiates during the postoperative period. Regular activity program participation improves physical conditioning, raises the symptom-limited exertional level, lessens post surgical musculoskeletal discomfort, and improves morale. Yet exercise alone without comprehensive secondary prevention and risk factor modification will be no more successful at arresting atherosclerosis than any other single measure. Both operative intervention and vigorous exertion are valuable components of coronary artery disease therapy, but must be part of an all-embracing effort. Whether regular exertion combined with overall risk factor modification will prolong life and reduce future cardiac events or beneficially alter the process of atherogenesis remain areas of avid investigation.     

Atherosclerotic aneurysm of the left main coronary artery

A large calcified atherosclerotic aneurysm of the left main coronary artery was successfully treated by aortocoronary saphenous vein bypass grafting. This is the second such reported case. The implications of this clinical entity are discussed.     

Determinants of left ventricular function following aorto-coronary bypass surgery.

Ventricular function was evaluated by the development of ventricular function curves from the vulumes stress of angiographic contrast media in 30 patients before and an average of 5 months after coronary bypass surgery. Patients were grouped according to preoperative operative indications, perioperative events, and postoperative status to determine the most important factors affecting postoperative ventricular function. Progression of lesions in the native coronary circulation correlated most significantly with a decrease in postoperative ventricular function. In 18 of 19 patients the changes in native coronary circulation were progression to complete occlusion. Seventy-three per cent of these changes were associated with a patent graft distal to the change. Patients with very ischemic ventricles as evidenced by a markedly positive stress test (greater than 2 mm. ST depression) and/or main left coronary obstruction maintained or improved postoperatively ventricular function. Increase in postoperative ejection fraction was often associated with decrease in aortic mean pressure, making it difficult to use this parameter to evaluate postoperative ventricular function.     

Recent developments in thyroid hormone metabolism: interpretation and significance of measurements of reverse T3, 3,3'T2, and thyroglobulin

The development of specific radioimmunoassays has allowed measurements of 3,3',5'-triiodothyronine (reverse T3), 3,3'-diiodothyronine (3,3'T2), and thyroglobulin to be performed in serum and in various biological fluids both in normal and in altered states of thyroidal economy. The physiology, kinetics, and metabolic actions of reverse T3, 3,3'T2 and thyroglobulin are reviewed. Presently, it appears that reverse T3 and 3,3'T2 measurements in amniotic fluid and cord serum may potentially be useful in diagnosing fetal or neonatal thyroid dysfunction, and serum thyroglobulin measurements appear to be important as a measure of the efficacy of treatment of patients with differentiated thyroid carcinoma.     

The effect of T3 and reverse T3 administration on muscle protein catabolism during fasting as measured by 3-methylhistidine excretion.

Since recent studies have indicated that measurement in urine of the amino acid, 3-methylhistidine, accurately reflects the extent of muscle catabolism, and because it has been suggested that thyroid hormones may influence muscle breakdown, especially during fasting, the effect of T3 and reverse T3 (rT3) administration on the excretion of 3-methylhistidine was examined in obese subjects during fasting. The mean (+/- SE) 3-methylhistidine excretion in patients fed an egg protein diet (devoid of meat protein) was 256 +/- 35 mumoles/day and decreased to 190 +/- 14 mumoles/day during fasting. T3 administration (100 microgram/day x 5 days) increased 3-methylhistidine excretion to 304 +/- 37 mumoles/day during its ingestion and to 485 +/- 46 mumoles/day in the T3 posttreatment interval. T3 doses of 10 microgram every 4 hr (q4h) for the first 6 days of fasting also appeared capable of increasing 3-mehis excretion whereas 5 microgram T3 q4h administered during the first 6 days of fasting did not increase 3-mehis excretion. Reverse T3 administration (80 microgram q6h) during fasting was associated with a mean 3-methylhistidine of 130 +/- 13 mumoles/day, a value no higher than in patients fasted alone. These observations suggest that: (1) skeletal muscle catabolism decreases during fasting: and (2) pathophysiologic doses of T3 (60 microgram/day or more), but not reverse T3, enhance muscle catabolism during fasting.     

Failure of 3,3'-diiodothyronine administration to alter TSH and prolactin responses to TRH stimulation.

In order to determine whether elevations in serum 3,3'-diiodothyronine (3,3'T2) concentrations influence the hypothalamic-pituitary--thyroid axis, thyrotropin (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) were assessed in five patients both prior to and during 3,3'T2 administration. Mean (+/- SE) peak TSH responses to TRH were 168 +/- 64 microU/ml during 3,3'T2 administration and 168 +/- 65 muU/ml during 3,3'T2 administration. Mean basal and peak prolactin concentrations after TRH were 6 +/- 3 ng/ml and 54 +/- 26 ng/ml, whereas during 3,3'T2 administration the basal and peak prolactin levels were 6 +/- 2 ng/ml and 55 +/- 28 ng/ml, respectively. Hypothyroid rats administered triiodothyronine (10 migrogram b.i.d.) for 5 days had a mean TSH response to TRH stimulation of 0.051 +/- 0.003 mU/ml, whereas rats to whom saline or 3,3'T2 (50 microgram b.i.d.) had been given for the same time interval had mean TRH-induced TSH responses of 1.127 +/- 0.179 mU/ml and 1.324 +/- 0.286 mU/ml, respectively. None of the TSH or prolactin responses to TRH, in either human or rat studies, were apparently altered by 3,3'T2. These observations suggest that elevation of serum 3,3'T2 levels are not associated with alterations in the hypothalamic--pituitary--thyroid axis in the experimental systems employed.     

Two-dimensional echocardiography in the detection of noneffusive cardiac involvement by intrathoracic neoplasms

Two-dimensional echocardiographic (2DE) findings in four patients with predominantly noneffusive manifestations of intrathoracic neoplasms are presented. In cases Nos. 1 and 2 tumor masses were identified in the left atrioventricular groove area at a time when the left-heart border was obscured by a large pleural effusion on chest x-ray examination. Case No. 3 demonstrated distortion of right ventricular anatomy by a compressing extrinsic mass lesion. In these three cases the neoplasm itself or the complicating pleural effusion provided additional echocardiographic windows for visualizing the heart. Case No. 4 demonstrated dilation of the main pulmonary artery secondary to tumor compression of the left pulmonary artery with regression of the dilation following resection. The relative applicability of 2DE and M-mode techniques and their clinical relevance in tumor patients are delineated.     

Hypocalcemia with osteoblastic metastases in a patient with prostate carcinoma: A cause of secondary hyperparathyroidism

A 68 year old man with prostatic carcinoma and extensive painful osteoblastic metastases was discovered to have hypocalcemia (serum calcium 7.1 mg/dl) without evidence of hypoalbuminemia, renal failure or malabsorption. Baseline studies revealed hypocalciuria (24 hour urine calcium <5 mg/day), normal serum phosphate (3.4 mg/dl), low tubular reabsorption of phosphate (68 percent), undetectable serum calcitonin, normal serum 25-hydroxyvitamin D, slightly elevated serum parathyroid hormone level and increased urinary cyclic AMP (8.87 μmol/g creatinine). These studies were compatible with secondary hyperparathyroidism. The intravenous administration of parathyroid extract produced no further change in urinary phosphate but a 25-fold increase in nephrogenous cyclic AMP. Three days administration of intramuscular parathyroid extract slowly and temporarily restored serum calcium to normal levels while increasing urinary cyclic AMP and phosphate. Chemotherapy with cyclophosphamide and 5-fluorouracil rendered the patient free of pain while reducing serum acid and alkaline phosphatase levels and restoring serum total and ionized calcium and urinary cyclic AMP excretion to normal.     

Nature of suppressed TSH secretion during undernutrition: Effect of fasting and refeeding on TSH responses to prolonged TRH infusions

TSH responses to 4-hr continuous TRH infusions of approximately 0.8 μg/min were assessed during feeding (1500 Kcal), fasting, and refeeding (1500 Kcal) intervals in 9 euthyroid obese subjects. The total area under the TSH response curve was 1854 ± 322 μU/ml · 4-hr during feeding, decreased to 1359 ± 199 μU/ml · 4-hr (p < 0.01) on the 10th day of fasting, and remained low, being 1405 ± 185 μU/ml · 4-hr, despite refeeding a 1500 Kcal diet (40% carbohydrate, 40% fat, 20% protein) for 5 days. Baseline serum T3 concentrations were 167 ± 11 ng/dl during feeding, 86 ± 8 ng/dl during fasting, and 119 ± 12 ng/dl during refeeding. The observed decreases in TSH release appeared to correlate with decreased biologic action on the thyroid gland since the net rise in T3 during the infusion was less in fasting and refeeding than in the control (fed) period. Basal serum rT3 levels were 42 ± 5 ng/dl during feeding, rose as expected to 56 ± 5 ng/dl during fasting (p < 0.005), and were completely restored to normal during refeeding (36 ± 5 ng/dl). These data suggest that: (1) TSH responsiveness to prolonged TRH infusion is diminished during fasting and does not return to control (fed) values despite 5 days of refeeding a 1500 Kcal diet; (2) net T3 increases observed during the TRH infusion are greater in the fed period than in the fasting or refeeding periods; and (3) 5 days of refeeding a 1500 Kcal diet (40% carbohydrate, 40% fat, 20% protein) did not return the T3 to its original fed value whereas rT3 was completely restored to control values. Lastly, since the TSH response was lower both during the early and late phases of the infusion, the decrease in ΔTSH to a bolus of TRH during fasting appears to represent one manifestation of a more general suppression of TSH neogenesis associated with caloric deprivation.     

Normal valine disposal in obese subjects with impaired glucose disposal: Evidence for selective insulin resistance

Insulin has major effects on both glucose and branched chain amino acid metabolism. To determine whether the insulin resistance of obesity equally affects both glucose and branched chain amino acid metabolism, we measured the ability of obese and normal subjects to dispose of intravenous bolus doses of glucose (25 g) or L-valine (4 g). Basal plasma glucose levels were the same in the 18 normal and 17 obese (163 ± 8% of ideal body weight) subjects, but basal plasma insulin levels were higher in the obese group (15 ± 2 vs 6 ± 1 μU/ml; p < 0.001). The obese group had a slower glucose disappearance rate after glucose challenge (0.84 ± 0.06 vs 1.11 ± 0.07 hr^?1; p < 0.01) despite having a greater serum insulin response to the glucose load (26 ± 4 vs 11 ± 1 insulin area units; p < 0.01), confirming insulin resistance. In contrast, disposal of a valine load was the same in normal and obese subjects, as assessed by initial and second phase exponential disappearance rates, metabolic clearance rates of valine, and volumes of distribution. In normal men, disposal rates of glucose and valine after simultaneous administration of both substances were slower than corresponding disposal rates determined when each substance was given alone. We conclude that obese subjects with impaired glucose disposal have normal valine disposal, suggesting that the insulin resistance of obesity can be selective in its effect on different metabolic systems. Glucose and valine also appear to mutually antagonize each other's disposal.     

Plasmapheresis and immunosuppressive agents in antibasement membrane antibody-induced Goodpasture's syndrome

Four patients with rapidly progressive glomerulonephritis and pulmonary hemorrhage (Goodpasture's syndrome) induced by circulating anti-glomerular basement membrane (GBM) antibodies were treated with immunosuppressive agents and varying amounts of plasma exchange. All four patients showed progressive decreases in circulating anti-GBM antibody during therapy. Two patients with established renal failure before therapy showed no improvement in renal function but had a remission from pulmonary disease. In two other patients, renal failure developed early in the course of therapy and required maintenance hemodialysis. Later, their renal function improved coincident with a decrease in circulating anti-GBM antibody. Aggressive measures to reduce the levels of circulating anti-GBM antibody may have a salutory effect on the clinical course of the disease, particularly when undertaken early.     

Unusual complications of coronary bypass surgery.

Five patients after coronary bypass surgery developed unusual complications. Three developed new apical thrombi which are thought to be due to the trauma of the left ventricular vent or deterioration of the left ventricular contraction. Significant new mitral regurgitation in one patient probably is secondary to papillary muscle dysfunction as the result of stenosis distal to anastomoses. The leakage of angoigraphic material around distal anastomatic site is due to technical error. Although these unusual complications are very rare, however, they should be considered as potential source of morbidity in asymptomatic patients who leave the hospital after bypass surgery.     

Barrett's esophagus: a review

Barrett's esophagus may be defined as a columnar epithelium-lined distal esophagus. As a frequently recognized complication of gastroesophageal reflux, Barrett's esophagus has become a diagnosis of general clinical concern. Factors governing the development of this complication in patients with gastroesophageal reflux are unknown but may be congenitally determined in part. When symptoms are present, they are due to the complications of reflux, such as esophagitis, stricture, ulcer, or bleeding. Barrett's esophagus may be suspected on the basis of results of a barium meal test, endoscopy, or isotope scanning. Iodine staining at endoscopy or manometrically guided biopsy helps to localize the abnormal mucosal segment. The diagnosis is proved by biopsy. The columnar epithelium of Barrett's esophagus has a malignant predisposition, and, once the diagnosis is made, periodic endoscopy, with biopsy and cytologic study, is indicated. The treatment of Barrett's esophagus is directed toward objective cessation of gastroesophageal reflux. In refractory cases, antireflux surgery improves symptoms and complications from reflux, but the columnar epithelium generally persists along with its malignant potential. It is not known whether effective antireflux treatment will lower the incidence of adenocarcinoma.     

Skeletal responsiveness in pseudohypoparathyroidism. A spectrum of clinical disease

Three cases of pseudohypoparathyroidism with roentgenographic evidence of hyperparathyroid bone disease are described. Renal resistance to exogenous parathyroid hormone (PTH), the hallmark of pseudohypoparathyroidism, was documented by markedly blunted or absent urinary phosphate and cyclic AMP responses to parathyroid extract. At the time of diagnosis all patients were hypocalcemic and hyperphosphatemic with elevated serum alkaline phosphatase levels and subperiosteal resorption noted on skeletal films. Bone biopsy in one patient revealed a histologic appearance consistent with hyperparathyroidism. Serum PTH levels, measured in two patients while they were hypocalcemic, were elevated. None of the patients had short stature, brachydactyly, subcutaneous calcification or mental deficiency. These cases are compared to the 15 well-documented cases previously reported. The presently available information on pseudohypoparathyroidism indicates a variable skeletal response to PTH mediated by several factors extrinsic to bone and suggests that pseudohypoparathyroidism with hyperparathyroid bone disease is one extreme of a clinical spectrum of skeletal responsiveness to PTH. This disorder is part of an expanding clinical picture which makes pseudohypoparathyroidism a diagnostic consideration in any patient with unexplained hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase levels or metabolic bone disease.     

Asymptomatic coronary artery disease and coronary bypass surgery.

The actuarial survival curves of "medically treated" patients whose arteriographic studies demonstrated coronary arterial lesions of various degrees-- now used widt applicable to the asymptomatic patient. No information is available regarding the course or prognosis of the asymptomatic patient with demonstrated lesions in the coronary arteries. For the reasons explained one can propose a hypothesis that the overall prognosis of this type of patient is better than average, probably better than that shown in the best data collected on symptomatic patients. The prophylactic value of aortocoronary bypass operations in preventing myocardial infarction and death has not been established. One can therefore question the justification for the wide case-finding effort of subjecting asymptomatic persons to coronary arteriography, even in light of the low risk of this procedure, unless unusual findings suggest an especially poor prognosis (one example might be past myocardial infarction in a very young patient). Although there are exceptional instances when prophylactic surgery is indicated for asymptomatic patients, further investigation of this subject is needed before the procedure becomes generally accepted.