Serial changes in markers of disease activity with corticosteroid treatment in sarcoidosis

Serial changes in various markers of disease activity with corticosteroid therapy were assessed in 12 patients with active sarcoidosis. After six weeks of treatment with 40 mg daily of prednisone, all but one patient demonstrated symptomatic and radiographic improvement. For the entire patient group, there were corresponding improvements in forced vital capacity, from 59.2 +/- 5.5 to 70.5 +/- 5.3 percent of the predicted value (p less than 0.001, Student paired t test), serum angiotensin-converting enzyme levels, from 66.0 +/- 12.1 to 28.2 +/- 4.0 U/ml (p = 0.003), 67gallium lung scanning scores, from 3.6 +/- 0.2 to 0.8 +/- 0.3 (p less than 0.001), serum gamma globulin levels, from 2.40 +/- 0.2 to 1.5 +/- 0.1 g/dl (p less than 0.001), and erythrocyte sedimentation rate, from 26.8 +/- 2.7 to 14.8 +/- 3.0 mm per hour (p less than 0.001). Changes in percent of bronchoalveolar lavage fluid lymphocytes were less impressive (from 28.7 +/- 4.9 to 21.2 +/- 5.1, p = 0.034), but the geometric mean number of bronchoalveolar lavage fluid-IgG-secreting cells decreased from 23,861 to 3,830 (p = 0.013). Serial evaluations in five patients treated with decreasing doses of alternate-day prednisone for an additional 10 1/2 months indicated that changes in 67gallium lung scanning scores corresponded most closely to the clinical course in five of five patients. Determination of serum angiotensin-converting enzyme levels also closely paralleled the clinical course in four of five patients, whereas the other parameters measured were more variable markers of clinical response. However, abnormalities of bronchoalveolar lavage fluid-IgG-secreting cells often persisted in the absence of clinically evident disease, and the percentages of bronchoalveolar lavage fluid lymphocytes were frequently normal in patients who responded subsequently to corticosteroids. Larger prospective studies are warranted to more extensively evaluate various measurements of disease activity, especially bronchoalveolar lavage fluid analysis, in sarcoidosis.     

Effects of oleic acid infusion on plasma free fatty acids and blood ketone bodies in the fasting rat.

Oleic acid emulsions stabilized with albumin were infused into fasted rats. Blood samples taken before and during infusion were analyzed for free fatty acids (FFA), ketone bodies, glucose, and insulin. Turnover rates of FFA and ketone bodies were also determined using constant infusion of radioactive tracers. During oleic acid infusions at a rate of 2 mumoles/min/100 g body weight, FFA concentrations increased for a short time and then decreased to preinfusion levels. The decreases in concentrations were due to decreases in the endogenous rates of appearance of FFA into the blood. When oleic acid was infused at a rate of 3.5 mumoles/min/100 g body weight, FFA concentrations increased and remained elevated throughout the infusion. Ketone body concentrations more than doubled during infusions at 2 and 3.5 mumoles/min/100 g body weight and showed no signs of decreasing even when FFA concentrations decreased. Insulin concentrations doubled during infusion and glucose concentrations decreased. Insulin injected during infusion had little effect on concentrations of FFA or ketone bodies. It was concluded that infusions of oleic acid inhibit adipose tissue lipolysis and increase blood ketone concentrations in intact fasted rats. The injection of insulin does not inhibit ketogenesis when blood FFA levels are maintained by infusion.     

Perioperative myocardial infarction related to coronary bypass surgery.

Frank lead electrocardiograms were recorded from 149 normal and abnormal adult males using four different electrode placements. All chest electrodes were placed at: (1) the fourth intercostal space level, (2) the fifth intercostal space level, (3) the fourth intercostal space level with V₄ substituted for C, and (4) the fifth intercostal space level with V₄ substituted for C.Differences in mean values of many commonly used amplitudes and orientations were not statistically significant among the four recording methods, but amplitude differences for individual subjects were often large and difficult to predict. When V₄ is substituted for C, as commonly done in some laboratories, R_x decreased and R_z increased by more than 10 per cent in about 40 per cent of the cases. In about 70 per cent of the cases, R_x and R_z changed significantly when electrode level was shifted from the fifth to the fourth intercostal space. For these 70 per cent, it does not appear possible to accurately predict increase or decrease of R_x, R_z, or QRS_m.Analysis programs which depend on individual amplitude measurements are likely to be significantly affected by electrode placement. It is suggested that criteria for analysis programs developed using a specified version of the Frank system should ideally be applied only to electrocardiograms recorded in the same manner.     

Evaluation of the chronotropic property of captopril in hypertensive patients

Captopril was administered (50 mg orally) to 88 untreated hypertensive patients (70 with essential hypertension, eight with renal arterial disease, 10 with renal parenchymal disease) and to 25 hypertensive patients treated with sympatholytic or beta-blocking agent (20 with essential hypertension, five with renal arterial disease). In the former group, captopril caused a decrease in heart rate (HR) in 18 patients and an increase in only two. As a whole, captopril caused significant decreases in blood pressure without increase in HR. Significant negative correlation was observed between change in HR and plasma renin activity obtained before captopril administration (n = 79, r = -0.425, p less than 0.0001). Hypotensive and chronotropic effects of captopril were almost identical in untreated and treated patients. Hypotensive effects caused by captopril and nifedipine (20 mg orally) were almost identical. Nifedipine caused reflex tachycardia, while captopril caused slight bradycardia. Absence of compensatory tachycardia appears to be related to reduction of endogenous angiotensin II by captopril.U     

Ventricular arrhythmias during ergonovine-induced episodes of variant angina

Of 95 consecutive patients with active variant angina who underwent ergonovine testing in the coronary care unit while off treatment, 24 (25%) developed serious ventricular arrhythmias: ventricular tachycardia in eight, bigeminy in seven, pairs in five, and frequent ventricular extrasystoles in four. Ergonovine-induced arrhythmias were observed more often in patients with anterior than inferior ST segment elevation (p less than 0.05). ST segment elevation was significantly higher (10.3 +/- 8.1 vs 3.1 +/- 2.1 mm) in patients who developed arrhythmias. All ventricular arrhythmias began within 3 minutes after the onset of ST segment elevation. The intravenous administration of nitroglycerin eliminated arrhythmias in 22 of 24 cases; in only two patients did ventricular arrhythmias develop after the administration of nitroglycerin. Serious ventricular arrhythmias were found during spontaneous variant angina attacks in 14 of 24 patients with ergonovine-induced arrhythmias compared to 16 of 71 patients without ergonovine-induced arrhythmias (p less than 0.001). We conclude that arrhythmias during ergonovine testing are most often caused by ischemia and not reperfusion. Patients with arrhythmias during ergonovine-induced attacks are more likely to have arrhythmias during spontaneous attacks.     

Sex and insulin sensitivity

To analyze whether enhanced adiposity in females as compared with males is associated with a decreased sensitivity to insulin, a group of healthy normal weight females (n = 13, age 21 ± 1 years) and males (n = 11, age 23 ± 1 year, mean ± SEM) was studied. In each subject, body composition (% fat and % muscle), maximal aerobic power (V_O2 max) and whole body insulin-mediated glucose metabolism were measured. The group of women had a higher percentage of fat to total body weight (P < 0.001) and a lower percentage of muscle (P < 0.001) than the group of men. The higher percentage of fat in women compared with males was due to enhanced peripheral fat accumulation in the arm and thigh regions. V_O2 max levels were comparable in both groups (48 ± 1 mL/kg/min for women, 53 ± 2 mL/kg/min for men, P = NS). The rate of glucose metabolism (M) was comparable in women (8.78 ± 0.74 mg/kg/min), and men (8.31 ± 0.89 mg/kg/min) when expressed per kilogram of total body weight, but when expressed per kilogram of muscle tissue (M_m), it was 45% higher in women (29.4 ± 2.4 mg/kg/min) than in men (20.2 ± 1.6 mg/kg/min, P < 0.005). Partial correlation analysis indicated that the percentage of fat was inversely related to M and M_m in both women (P < 0.05) and men (P < 0.05), but not to percentage of muscle or V_O2 max. Conclusions: (1) Insulin-mediated glucose disposal is inversely related to adiposity in normal weight healthy males and females. (2) Women and men utilize equal amounts of glucose despite a higher adiposity in females. (3) Since muscle tissue utilizes most of intravenously administered glucose, this result indicates enhanced glucose uptake by muscle tissue in females compared with males. (4) Elevated glucose uptake by muscle in women may provide a mechanism by which women are protected against excessive hyperglycemia despite their smaller amount of glucose-consuming tissue.     

Long-term survival following aortic valve replacement.

Study was made of 95 survivors of aortic valve replacement during the early years of this procedure (1964 to 1970). The average follow-up time was 50.2 months. Survival was not related to hemodynamic parameters, such as cardiac index or left ventricular pressure, and did not appear to be influenced by the type of preoperative valve lesion. A history of angina pectoris and a New York Heart Association Class IV grouping were associated with shorter survival. Associated coronary artery disease was a leading cause of death in those patients surviving less than 2 years and angina pectoris the leading cause of morbidity in the long-term survivors. Sudden death occurred in five patients. Once a patient survived 36 months after the operation, the prognosis was excellent.     

Normalization of urinary oxalate by taurine in glycolate-fed rats

Oral feeding of sodium glycolate (50 mg/d/rat for ten days) caused a significant (P less than 0.001) increase in oxalate and taurine excretion and a decrease in liver protein content (P less than 0.05), glycolic acid oxidase levels (P less than 0.01), and glycolic acid dehydrogenase levels (P less than 0.01) as compared to normal untreated rats. Taurine (100 mg/d/rat), when administered along with glycolate, prevented these effects of glycolate as evident from normal urinary excretion of oxalate, liver protein content, glycolic acid oxidase, and glycolic acid dehydrogenase levels in glycolate- plus taurine-fed animals.     

Effects of dibutyryl adenosine 3',5'-monophosphate on hepatic metabolism of free fatty acids.

The effects of dibutyryl cyclic adenosine 3',5'-monophosphate (Bu2cAMP) on metabolism of free fatty acids by perfused livers from normal fed male rats were investigated. In one group of experiments, Bu2cAMP was added to the medium and infused at a constant rate to maintain concentrations of 0, 0.4, 1.0, 4.0, or 10. 0 X 10(-5) M nucleotide in the perfusate plasma, assuming the nucleotide was not metabolized by the liver. Oleic acid was infused as the complex with albumin at the rate of 124.3 mumoles/hr. Uptake of free fatty acid by the liver was identical in all groups. Production of ketone bodies, however, increased, and output of triglyceride decreased with increasing concentration of Bu2cAMP. The nucleotide also stimulated output of glucose. Maximal effects were observed when the concentration of Bu2cAMP was approximately 2-3 X 10(-5) M. The output of very low density lipoproteins, as judged by flotation in the zonal ultracentrifuge, was also diminshed by the nucleotide. In other experiments, 1-14C-oleate was infused (120.8 mumoles/hr) along with 2 X 10(-5) M Bu2cAMP, and the disposition of 14C into CO2, ketone bodies, and esterified lipids was evaluated. Bu2cAMP depressed the proportion of 1-14C-oleate converted to triglyceride and increased the fraction converted to ketone bodies and CO2. Not only was ketogenesis stimulated, but a larger proportion of the ketone bodies was derived from exogenous fatty acid.     

Effects of the volume conductor on the apparent orientation of a known cardiac dipole

The surface electrocardiogram (EKG) is dependent on two major factors: the cardiac generator and the volume conductor. This investigation assessed the effects of the volume conductor in man on the apparent orientation of a simulated cardiac dipole. The apparent orientation of the dipole was calculated from measured surface potentials from about 60 locations on the body of five patients with implanted cardiac pacemakers. The real orientation of the dipole (an implanted pacemaker) was determined radiographically. The effects of both inhomogeneity and boundary characteristics of the volume conductor on the apparent orientation of the dipole were assessed using a new inverse algorithm. The difference between the orientation of the real and the calculated dipoles averaged 30 degrees (range 15 degrees--40 degrees) when the torso was assumed to be an infinite-homogeneous volume conductor. When the configuration of the torso was accounted for, however, the difference between the orientation of the real and calculated dipoles was reduced to 9 degrees (range 5 degrees--13 degrees). Thus, by taking into account the geometry of the torso and neglecting the inhomogeneities in the volume conductor, it is possible to calculate the orientation of a dipole in the cardiac region with an accuracy of about 9 degrees. It is reasonable to assume that the orientation of real activation wave fronts from localized areas of the heart could be calculated with a similar degree of accuracy.