Plasma lipid alterations in leukemia and lymphoma

Plasma lipids and lipoproteins were studied at presentation in 25 patients with acute leukemia and non-Hodgkin's lymphoma. All patients demonstrated an abnormality in at least one plasma lipid fraction, and most exhibited a predictable pattern of lipid alterations that consisted of extremely low levels of high-density lipoprotein cholesterol (median [Xm] = 23), elevated triglyceride (Xm =165) and elevated very-low-density lipoprotein (Xm = 26). Patients restudied during remission demonstrated a return to normal values. The degree of lipid abnormality was directly related to the underlying tumor burden and particularly to the presence of bone marrow involvement. However, even patients with minimal tumor bulk demonstrated plasma lipid abnormalities. The results suggest that an abnormality in systemic lipid metabolism, possibly in triglyceride clearance, is present in these patients and that its incidence in this population is high.     

Protective role of collaterals in patients with coronary artery occlusion

We reviewed the clinical, hemodynamic and angiographic data of 105 patients with right coronary artery occlusion and of 82 patients with left anterior descending coronary artery occlusion, subdivided into 3 groups by the presence and quality of collaterals to the occluded coronary (absent, poor or good collaterals). We found that patients with right coronary artery occlusion and good collaterals had a lower frequency of diaphragmatic myocardial infarction (60%) than patients with absent collaterals (100%) (P < 0.01). In addition, in patients with old diaphragmatic myocardial infarction, both poor and good collaterals were associated with a lower frequency of severe asynergy of the diaphragmatic left ventricular segments at left ventriculography (54% and 14%, respectively), compared to patients with no collaterals to the right coronary artery (92%, P < 0.02 vs. poor collaterals, P < 0.001 vs. good collaterals). In contrast, in patients with left anterior descending coronary artery occlusion, the presence of either poor or good collaterals to the left anterior descending coronary artery was not associated with a lower frequency of old anterior myocardial infarction, or, in patients with old anterior myocardial infarction, with a less severe asynergy of the anterior left ventricular segments.Our results suggest that collaterals are effective in protecting the diaphragmatic left ventricular wall in patients with right coronary artery occlusion, but not the anterior left ventricular wall in patients with left anterior descending coronary artery occlusion.     

Concomitant presence of left anterior hemiblock and inferior myocardial infarction: Electrocardiographic recognition of each entity

The ECGs of 72 patients with an unequivocal vectorcardiographic diagnosis of either left anterior hemiblock (LAH) or inferior myocardial infarction (IMI) or both were reviewed. Our intention was to identify definite electrocardiographic criteria for the diagnosis of the left anterior hemiblock and of inferior myocardial infarction when both were present vectorcardiographically. All patients with left anterior hemiblock, accompanied or not by IMI, had a left axis deviation, a negative terminal deflection (S wave) in leads II, III and aVF; the majority of them also had a terminal r wave in lead aVR (50 of 52, 96%). The diagnosis of LAH was therefore always possible in the concomitant presence of both entities. A negative initial deflection (Q wave) significant in size or not significant was present in a minority of patients with both LAH and IMI (9 of 24, 37.5% in lead II; 7 of 24, 25% in lead III; and 12 of 24, 50% in lead aVF). In the patients with insignificant Q waves, as well as in the rest of the patients with rS configuration, the electrocardiographic diagnosis of IMI was not possible due to the concomitant presence of LAH.     

Recent studies on the chemistry of human, bovine and porcine parathyroid hormones

The amino acid sequence of the NH₂-terminal 34 residues of human parathyroid hormone (PTH) has been determined and duplicated synthetically to produce a peptide that is biologically active. In the amino acid sequences of the bovine and porcine hormones, the glutamic acid function at position 22 has been revised to glutamine. Among these initial 34 residues, human PTH differs from bovine PTH by 5 residues and from porcine PTH by 4 residues. Native human PTH and the synthetic human PTH (1–34) peptide are not rigid structures, and significant changes in conformation were observed during pH titration. In addition, at physiologic pH, native human PTH appeared to differ in structure from human PTH (1–34) in the region of the tryptophan residue (residue 23). The fluorescence spectrum of human PTH revealed a maximum at 344 nm, but the spectrum of human PTH (1–34) had a peak at 343 nm; the spectrum of human PTH (1–34) was normalized to 346 nm in 6 M guanidine hydrochloride, but there was no shift with the intact hormone. Fluorescence titration of human PTH in the alkaline region revealed no loss of tryptophanyl fluorescence in aqueous solution or in 6 M guanidine hydrochloride. The synthetic human PTH (1–34) peptide, however, showed an approximately 25 per cent loss of indole fluorescence during alkaline titration which could be normalized with denaturing reagents. These studies suggest that synthetic fragments of the native hormone may not have the same tertiary conformation as the same sequence in the intact hormone. These findings may be of major significance with regard to the biologic activity and immunologic cross reactivity of synthetic fragments and the native hormone.     

Local methacholine but not bradykinin potentiates insulin-mediated glucose uptake in muscle in vivo by augmenting capillary recruitment

Aims/hypothesis Insulin has nitric-oxide-dependent vasodilatory effects in muscle, including capillary recruitment, that enhance access for itself and glucose. However, nitric-oxide-dependent vasodilators other than methacholine do not enhance insulin action. Our hypothesis is that methacholine, unlike bradykinin, enhances insulin-mediated glucose uptake in muscle by augmenting capillary recruitment.Methods Local infusion of either methacholine or bradykinin into one leg of the anaesthetised rat was made during physiological insulin (3 mU·kg^–1·min^–1) infusion under euglycaemic conditions and without affecting systemic blood pressure. Whole-body glucose infusion was determined, as was femoral blood flow, 2-deoxyglucose uptake into calf muscles and the metabolism of infused 1-methylxanthine, a measure of capillary recruitment for each leg.Results Methacholine alone (0.3 µmol·l^–1) increased femoral arterial blood flow, increased capillary recruitment but had no effect on 2-deoxyglucose uptake of the test leg relative to the contra-lateral control leg. Insulin alone (systemically) required a glucose infusion rate of 8.7 mg·kg^–1·min^–1 to maintain euglycaemia, increased 2-deoxyglucose uptake and capillary recruitment, but was without effect on femoral blood flow in either leg. Local methacholine with systemic insulin infusion increased femoral blood flow, 2-deoxyglucose uptake and capillary recruitment in the test leg only. Bradykinin (0.07 µmol·l^–1), alone or with insulin, administered in a manner that increased femoral blood flow similarly to methacholine, did not affect 2-deoxyglucose uptake or capillary recruitment.Conclusions/interpretation Methacholine but not bradykinin enhances insulin-mediated muscle glucose uptake in vivo. We conclude that methacholine acts at specific sites in the vasculature of muscle to stimulate capillary recruitment and thereby enhance insulin access.     

Nonrandom occurrence of single-vessel coronary artery disease

The location of obstructive coronary artery lesions in single-vessel disease is nonrandom. The circumflex coronary artery is protected relative to the right coronary artery. This may have important implications regarding the causation of coronary obstructive lesions.     

Intravenous and oral prenalterol in congestive heart failure. Effects on systemic and coronary hemodynamics and myocardial catecholamine balance

Systemic and coronary hemodynamic effects of prenalterol, a beta-1 receptor agonist, were determined in patients with chronic congestive heart failure, initially after intravenous administration (10 patients) and then after oral administration (eight patients). Cardiac index increased by 33 percent and 30 percent after intravenous and oral prenalterol, respectively. The increase in stroke volume index and stroke work index and decrease in pulmonary capillary wedge pressure and systemic vascular resistance were not significant. Myocardial oxygen consumption and coronary sinus blood flow increased in the majority of patients, although these changes were not statistically significant. There were no significant changes in transmyocardial norepinephrine or epinephrine balance. The systemic and coronary hemodynamic effects of both intravenous and oral prenalterol were similar. Major side effects included sudden death (two patients) and hypotension and bradycardia (three patients) during oral prenalterol treatment. It is concluded that improved left ventricular function following both intravenous and oral prenalterol may be associated with increased myocardial oxygen consumption, and serious adverse effects may occur during prenalterol therapy.     

Thyroid function in patients undergoing maintenance hemodialysis: unexplained low serum thyroxine concentration.

Thyroid function was studied in 55 patients undergoing maintenance hemodialysis who were all judged to be clinically euthyroid. The dialysis patients, in comparison to normal control subjects, had significantly lower mean values for serum T4 (4.0 +/- 1.4 [SD] microgram/dl versus 7.9 +/- 1.5 microgram/dl, p less than 0.001), T3 (118 +/- 31 ng/dl versus 147 +/- 28 ng/dl, p less than 0.001), free T4 measured by equilibrium dialysis (1.22 +/- 0.38 ng/dl versus 2.15 +/- 0.67 ng/dl, p less than 0.001), free T3, free T4 index, and free T3 index. Serum TBG, measured by radioimmunoassay, was similar to that of the controls and serum TSH, 2.2 +/- 1.3 micromicron/ml, was also similar to that of control values, 2.0 +/- 1.1 micromicron/ml. The serum PBI did not change during the dialysis procedure, but serum inorganic iodine fell slightly from 2.1 +/- 1.1 microgram/dl before dialysis to 1.2 +/- 0.6 microgram/dl after dialysis (p less than 0.05). The marked reduction in serum total T4 and free T4 concentrations and the moderate reduction in serum total T3 and free T3 levels in apparently euthyroid patients undergoing hemodialysis has not been explained. The normal serum TSH levels in the face of these low concentrations of thyroid hormone suggests an abnormality in the control of TSH secretion in these patients.     

Computed tomographic scanning versus radioisotope imaging in adrenocortical diagnosis

Referral patterns from internists to departments of nuclear medicine or radiology are important determinants of whether adrenal glands are imaged by computed tomography (CT) or by radioisotope scintigraphy. To assist clinicians in making an informed choice, computed tomographic scans were compared with isotope scintigrams using 131I-19-iodocholesterol (19-IC) and 131I-6 beta-iodomethyl-19-norcholesterol (NP-59). In general, imaging techniques serve to localize diseases that are diagnosed on the basis of biochemical tests of adrenal function. Computed tomographic scanning and NP-59 scanning are of comparable diagnostic accuracy. Both are superior to 19-IC scanning in the diagnosis of Cushing's syndrome and primary aldosteronism. Computed tomographic scanning is faster and less expensive, and involves lower radiation doses to the patient than scintigraphy. Adrenocortical isotope scanning as a routine procedure has been superseded by computed tomographic scanning at the Mayo Clinic.     

Comparison of effectiveness of thyrotropin-suppressive doses of d- and l-thyroxine in treatment of hypercholesterolemia

In an attempt to compare the cholesterol-lowering effects of equivalent doses of d- and l-thyroxine, 10 euthyroid, hypercholesterolemic subjects were treated with graded doses of each medication in a cross-over design using thyrotropin suppression following thyrotropin-releasing hormone administration as the end-point. The mean thyrotropin-suppressive dose of d-thyroxine was 2.4 ± 0.66 mg per day, which resulted in mean reductions of 10 percent in total plasma cholesterol, 10 percent in plasma low-density lipoprotein cholesterol, and 11 percent in plasma high-density lipoprotein cholesterol. The mean thyrotropin-suppressive dose of l-thyroxine was 135 ± 46 μg per day, which resulted in mean reductions of 7 percent in total plasma cholesterol, 6 percent in plasma low-density lipoprotein cholesterol, and 14 percent in plasma high-density lipoprotein cholesterol. The reductions in total, low-density, and high-density cholesterol achieved with d-thyroxine were not significantly different from those achieved with l-thyroxine. Neither medication produced a significant increase in heart rate or ventricular ectopy as determined by Holter monitoring. These data do not support the belief that d-thyroxine has a preferential cholesterol-lowering effect in humans when compared with equivalent doses of l-thyroxine. In addition, both d- and l-thyroxine reduced plasma high-density lipoprotein cholesterol.