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Biomedical subjects

R G Haller

Publications and source records attributed to R G Haller.

18 recordsLinked to original sources
PubMed1992

MRI evaluation of amyloid myopathy.

Amyloid myopathy is a rare complication of primary amyloidosis. The magnetic resonance imaging (MRI) features of two patients with amyloid myopathy were studied. Slight prolongation of muscle T1 and T2 relaxation times was evident but the striking abnormality was marked reticulation of the subcutaneous fat. The clinical findings of indurated extremities far exceeds the minimal signal intensity alteration seen in the muscles. The MR appearance of amyloid myopathy differs from that of other neuromuscular conditions in the minimal changes found in muscle, but the striking abnormality seen in subcutaneous fat makes it distinct from many neuromuscular conditions.

Amyloid↗
PubMed1992

Effect of deficient muscular glycogenolysis on extramuscular fuel production in exercise.

Hormonal, metabolic, and cardiovascular responses to 21 min of cycling in three saline- or glucose-infused men with McArdle's disease were compared with those of matched controls to elucidate whether mobilization of extramuscular fuel is enhanced to compensate for the lack of intramuscular glycogenolysis in patients with McArdle's disease. During exercise, all saline-infused patients compared with controls working at both the same absolute and at similar relative work rates had higher glucose production (31 +/- 7 vs. 19 +/- 5 and 26 +/- 4 mumol.min-1.kg-1) and utilization (34 +/- 8 vs. 22 +/- 2 and 28 +/- 4 mumol.min-1.kg-1); higher plasma glycerol (155 +/- 19 vs. 75 +/- 20 and 90 +/- 22 mumol/l), free fatty acids (487 +/- 175 vs. 295 +/- 47 and 202 +/- 52 mumol/l), growth hormone (7.7 +/- 2.8 vs. 2.6 +/- 1.1 and 3.6 +/- 3.4 mU/l), and cortisol (530 +/- 168 vs. 268 +/- 8 and 367 +/- 80 nmol/l), greater decrease in insulin (delta 57 +/- 4 vs. delta 11 +/- 8 and delta 11 +/- 23 pmol/l), and similar glucose concentrations. Furthermore, norepinephrine, epinephrine, and adrenocorticotropic hormone levels were higher and heart rate and cardiac output were higher during exercise in all patients than in controls at the same absolute work rate. Glucose infusion induced hyperglycemia and hyperinsulinemia in patients and inhibited the exercise-induced increases in glucose production, glycerol, free fatty acids, catecholamines, growth hormone, cortisol, and heart rate. In conclusion, feedback from metabolism in contracting muscle enhances hormonal responses and extramuscular substrate mobilization during exercise in McArdle's disease.

Adult↗
PubMed1991

Glucose-induced exertional fatigue in muscle phosphofructokinase deficiency.

BACKGROUND: The exercise capacity of patients with muscle phosphofructokinase deficiency is low and fluctuates from day to day. The basis of this variable exercise tolerance is unknown, but our patients with this disorder report that fatigue of active muscles is more rapid after a high-carbohydrate meal. METHODS AND RESULTS: To determine the effect of carbohydrate on exercise performance, we asked four patients with muscle phosphofructokinase deficiency to perform cycle exercise under conditions of differing availability of substrate--i.e., after an overnight fast, and during an infusion of glucose or triglyceride (with 10 U of heparin per kilogram of body weight) after an overnight fast. As compared with fasting and the infusion of triglyceride with heparin, the glucose infusion lowered plasma levels of free fatty acids and ketones, reduced maximal work capacity by 60 to 70 percent, and lowered maximal oxygen consumption by 30 to 40 percent. Glucose also increased the relative intensity of submaximal exercise, as indicated by a higher heart rate at a given workload during exercise. The maximal cardiac output (i.e., oxygen delivery) was not affected by varying substrate availability, but the maximal systemic arteriovenous oxygen difference was significantly lower during glucose infusion (mean +/- SE, 5.5 +/- 0.3 ml per deciliter) than after fasting (7.6 +/- 0.4 ml per deciliter, P less than 0.05) or during the infusion of triglyceride with heparin (8.9 +/- 1.3 ml per deciliter, P less than 0.05). CONCLUSIONS: In muscle phosphofructokinase deficiency, the oxidative capacity of muscle and the capacity for aerobic exercise vary according to the availability of blood-borne fuels. We believe that glucose infusion lowers exercise tolerance by inhibiting lipolysis and thus depriving muscle of oxidative substrate (plasma free fatty acids and ketones); this impairs the capacity of working muscle to extract oxygen and lowers maximal oxygen consumption.

Adolescent↗
PubMed1991

Basal and insulin-mediated carbohydrate metabolism in human muscle deficient in phosphofructokinase 1.

Biopsies were obtained from the quadriceps femoris muscle of two male patients deficient in phosphofructokinase (PFK) 1. In the basal state the patients had markedly higher contents of UDP-glucose (approximately 5-fold), hexose monophosphates (approximately 7- to 13-fold), inosine monophosphate (IMP) (approximately 15-fold), and fructose 2,6-bisphosphate (F-2,6-P2; approximately 6-fold) than controls. Fructose 1,6-bisphosphate was not detectable, and phosphocreatine was lower (33 and 54 mmol/kg dry wt) than in controls [72 +/- 4 (SD)]. Patients had normal fasting plasma glucose and insulin levels and basal glucose turnover rates and responded normally to a 75-g oral glucose challenge. Patients were also studied during euglycemic hyperinsulinemia (approximately 95 mg/dl; 40 and 400 mU.m-2.min-1). Whole body glucose disposal rates were normal during both insulin infusion rates. Biopsies taken after the 400 mU insulin infusion showed decreases in acetylcarnitine and citrate and increases in the fractional activity of glycogen synthase. It is suggested that the high basal levels of F-2,6-P2 are, at least partly, a consequence of the high levels of fructose 6-phosphate, which will stimulate flux through PFK-2 and inhibit fructose-2,6-bisphosphatase. The low phosphocreatine and high IMP contents indicate that carbohydrate availability is important for control of high-energy phosphate metabolism, even in the basal state. The insulin-mediated decreases in acetylcarnitine and citrate suggest an activation of the tricarboxylic acid cycle in skeletal muscle but an absence of the normal response to replenish these intermediates.

Carbohydrate Metabolism↗
PubMed1991

Abnormal oxidative metabolism and O2 transport in muscle phosphofructokinase deficiency.

Humans who lack availability of carbohydrate fuels may provide important models for the study of physiological control mechanisms. We compared seven patients who had unavailability of muscle glycogen and blood glucose as oxidative fuels due to muscle phosphofructokinase deficiency (PFKD) with five patients who had a selective defect in long-chain fatty acid oxidation due to carnitine palmitoyltransferase deficiency (CPTD) and with six healthy subjects. Peak cycle exercise work rate, peak O2 uptake (Vo2), and arteriovenous O2 difference were markedly lower (P less than 0.001) for PFKD patients (23 +/- 6 W, 14 +/- 2 ml.min-1.kg-1, and 7.1 +/- 0.5 ml/dl, respectively) than for CPTD patients (142 +/- 33 W, 31 +/- 4 ml.min-1.kg-1, and 15.0 +/- 0.8 ml/dl, respectively) or healthy subjects (171 +/- 17 W, 36 +/- 1 ml.min-1.kg-1, and 16.4 +/- 0.7 ml/dl, respectively). Peak cardiac output (Q) was similar (P less than 0.05) in all three groups, but the slope of increase in Q (l/min) on Vo2 (l/min) from rest to exercise (delta Q/ delta Vo2) was more than twofold greater (P less than 0.001) for PFKD patients (11.2 +/- 1.2) than for CPTD patients (4.6 +/- 0.6) and healthy subjects (4.6 +/- 0.2). Increasing availability of blood-borne oxidative substrates capable of metabolically bypassing the defect at phosphofructokinase (by fasting plus prolonged moderate exercise to increase plasma free fatty acids or by iv lactate infusion) increased peak work rate, Vo2, and arteriovenous O2 difference, lacked consistent effect on peak Q, and normalized delta Q/ delta Vo2 in PFKD patients. The results extend our previous observations in patients with a block in muscle glycogen but not blood glucose oxidation due to phosphorylase deficiency and imply that specific unavailability of muscle glycogen as an oxidizable fuel is primarily responsible for abnormal muscle oxidative metabolism and associated exercise intolerance and exaggerated delta Q/ delta Vo2 in muscle PFKD. The findings also endorse the concept that factors closely linked with muscle oxidative phosphorylation participate in regulating delta Q/ delta Vo2, likely via activation of metabolically sensitive muscle afferents.

Adenine Nucleotides↗
PubMed1991

Abnormal high-energy phosphate metabolism in human muscle phosphofructokinase deficiency.

We studied the pattern of high-energy phosphate metabolism in five patients with phosphofructokinase deficiency (PFKD) and five healthy subjects (HS) during graded rhythmic handgrip performed for 5 min at 17, 33, 50, and 100% of maximal voluntary contraction (MVC). The range of MVC was similar in both groups. Force production was recorded, and intracellular concentrations of phosphorus compounds and pH were measured in the flexor digitorum profundus of the active forearm. At exercise intensities greater than or equal to 50% MVC, changes in concentrations of high-energy phosphate metabolites were abnormal in PFKD. During maximal effort, [ADP], calculated from the creatine kinase reaction, was 64.3 +/- 13.5 (SE) mumol/kg in PFKD vs. 25.7 +/- 4.0 in HS (P less than 0.05). Ammonia (NH3), a product of AMP deamination and an index of muscle [AMP], increased approximately twofold more in venous effluent during maximal forearm exercise in PFKD than in HS (P less than 0.05). Phosphocreatine concentration was 9.4 +/- 1.3 (SE) mmol/kg in HS and 13.0 +/- 1.7 in PFKD (P less than 0.05). Inorganic phosphate concentration was 15.8 +/- 1.4 mmol/kg in HS and 7.4 +/- 0.5 in PFKD (P less than 0.05). During strenuous exercise, PFKD patients exhibit an impairment in the rephosphorylation of ADP related to a subnormal oxidative capacity, an absence of glycolysis, and an attenuated breakdown of phosphocreatine.

Adenosine Diphosphate↗
PubMed1991

Absence of exercise-induced MRI enhancement of skeletal muscle in McArdle's disease.

To assess the role of glycogenolysis in mediating exercise-induced increases in muscle water as monitored by changes in muscle proton relaxation times on magnetic resonance imaging (MRI) and cross-sectional area (CSA), five patients with myophosphorylase deficiency (MPD) were compared with seven controls. Absolute and relative work loads were matched during ischemic handgrip and graded cycling, respectively. Relaxation times of active muscle did not increase after handgrip in MPD (T1: 1 +/- 14%, P greater than 0.1; T2: 4 +/- 4%, P greater than 0.1) but did in controls (T1: 59 +/- 30%, P less than 0.005; T2: 26 +/- 9%, P less than 0.005). The volume of exercised muscles, estimated by CSA, increased in both groups after handgrip (controls: 13.8 +/- 3.5%, n = 7, P less than 0.0001; MPD: 7.5 +/- 1.5%, n = 4, P less than 0.005), but the change was greater in controls (P less than 0.02). Ischemic handgrip in controls resulted in a large increase in finger flexor signal intensity (SI) on short tau-inversion recovery images (25 +/- 7%, n = 3; P less than 0.005 compared with preexercise) and a further increase with subsequent reflow (43 +/- 11%, n = 3; P less than 0.001 compared with rest); in MPD, SI did not increase. The ratio of active to inactive muscle SI did not increase from rest to maximal cycle exercise in MPD (0 +/- 20%, n = 2, P greater than 0.1) but did in normals (73 +/- 36%, n = 3; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle.

Aconitate Hydratase↗
PubMed1991

Locomotor system assessment by muscle magnetic resonance imaging.

Clinical evaluation of the locomotor system has long been hampered by difficulty in assessing the morphologic and functional integrity of skeletal muscles. Diagnostic imaging represents a major advance in the diagnosis and management of patients with locomotor dysfunction through the possibility of probing beyond overlying soft tissues to identify muscle lesions, determine their extent, characterize their composition, direct invasive procedures, and monitor therapies. Magnetic resonance imaging (MRI) appears to be the most promising of available imaging methods, because of its great sensitivity to changes in muscle water distribution and fat content. Also, it can distinguish between individual deep and superficial muscles. Serial evaluations of many muscles are practical because of the safety of MRI. While the cost effectiveness in the workup of locomotor dysfunction remains to be determined, the scientific and practical clinical information now available merits further investigation by clinicians and radiologists alike. The purpose of this review is to describe the potential role of skeletal muscle MRI in evaluating the locomotor system.

Humans↗
PubMed1990

Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle's disease.

Two patients with muscle phosphorylase deficiency [McArdle's disease (McA)] were studied during bicycle exercise at 40 (n = 2) and 60 W (n = 1). Peak heart rate was 170 and 162 beats/min, corresponding to approximately 90% of estimated maximal heart rate. Muscle samples were taken at rest and immediately after exercise from the quadriceps femoris. Lactate content remained low in both muscle and blood. Acetylcarnitine, which constitutes a readily available form of acetyl units and thus a substrate for the tricarboxylic acid cycle, was very low in McA patients both at rest and during exercise, corresponding to approximately 17 and 11%, respectively, of that in healthy subjects. Muscle NADH was unchanged during exercise in McA patients in contrast to healthy subjects, in whom NADH increases markedly at high exercise intensities. Despite low lactate levels, arterial plasma NH3 and muscle inosine 5'-monophosphate increased more steeply relative to work load in McA patients than in healthy subjects. The low postexercise levels of lactate, acetylcarnitine, and NADH in McA patients support the idea that exercise performance is limited by the availability of oxidative fuels. Increases in muscle inosine 5'-monophosphate and plasma NH3 indicate that lack of glycogen as an oxidative fuel is associated with adenine nucleotide breakdown and increased deamination of AMP. It is suggested that the early onset of fatigue in McA patients is caused by an insufficient rate of ADP phosphorylation, resulting in transient increases in ADP.

Acetylcarnitine↗
PubMed1990

Impairment of sympathetic activation during static exercise in patients with muscle phosphorylase deficiency (McArdle's disease).

Static exercise in normal humans causes reflex increases in muscle sympathetic nerve activity (MSNA) that are closely coupled to the contraction-induced decrease in muscle cell pH, an index of glycogen degradation and glycolytic flux. To determine if sympathetic activation is attenuated when muscle glycogenolysis is blocked due to myophosphorylase deficiency (McArdle's disease), an inborn enzymatic defect localized to skeletal muscle, we now have performed microelectrode recordings of MSNA in four patients with McArdle's disease during static handgrip contraction. A level of static handgrip that more than doubled MSNA in normal humans had no effect on MSNA and caused an attenuated rise in blood pressure in the patients with myophosphorylase deficiency. In contrast, two nonexercise sympathetic stimuli, Valsalva's maneuver and cold pressor stimulation, evoked comparably large increases in MSNA in patients and normals. The principal new conclusion is that defective glycogen degradation in human skeletal muscle is associated with a specific reflex impairment in sympathetic activation during static exercise.

Adenosine Diphosphate↗
PubMed1976

Avoidance behavior and ileum motility post-cingulumotomy in monkey.

Two experiments were conducted utilizing rhesus monkeys to determine (i) the effects of cingulumotomy on conditioned-avoidance acquisition and extinction and (ii) the effects of avoidance learning on distal ileum motility in control- and cingulum-lesioned animals. Active (AAR) and passive (PAR) avoidance schedules singly or in combination were employed during short daily periods (less than 2 hr) of "shaping," training, acquisition, and extinction. The data indicated that the control-lesion and cingulum groups did not differ in the acquisition or extinction of an AAR. The cingulum group, however, showed a significant deficit in the acquisition of a PAR and a noticeably slower rate of lever pulling during avoidance trials in the combined avoidance training sessions. The results also suggested that ileum motility and avoidance behavior parallel on another, i.e., if either changed the other often changed in the same direction; that cingulum monkeys seemed to be less "reactive" than control-lesion monkeys; and that cingulum animals may been somewhat more regular in their percent daily motility patterns than the control animals.

Animals↗
PubMedDate not supplied

Effect of perfusion on exercised muscle: MR imaging evaluation.

An ischemic clamp model of exercise was used to evaluate the potential role of blood flow in mediating changes in the magnetic resonance imaging appearance of skeletal muscle. Proton relaxation times of muscle were serially estimated in 10 healthy subjects (a) before exercise, (b) after exercise in the presence of vascular occlusion (VO1), (c) during vascular reocclusion after 1 minute of reperfusion (VO2), and (d) after reinstitution of continuous flow. T1 and T2 of active muscles were increased during VO1. During VO2, there were additional increases in relaxation times of active muscles. Reinstitution of continuous flow was associated with a continuous decrease in the T2 of exercised muscle. Hence, blood flow was not required for increases in T1 and T2 with exercise. Additional relaxation time increases occurred after a brief period of reperfusion; however, continuous flow was associated with a decrease in T2.

Adult↗
PubMedDate not supplied

Physiologic measurement of exercise and fatigue with special reference to chronic fatigue syndrome.

Oxidative metabolism is the major source of energy for muscle activity, and maximal oxygen uptake (VO2max), the product of maximal cardiac output and maximal arteriovenous oxygen difference, indicates individual capacity for oxidative metabolism and performance of exercise by the large muscles. Strength, a function of muscle cross-sectional area, motor-unit recruitment, and neuromuscular coordination, is the ability to develop force in a single, brief, maximal-effort voluntary contraction of rested muscle. Weakness is a diminished ability of rested muscle to exert maximal force. Fatigue is a loss of maximal force-generating capacity that develops during muscular activity, likely originates within muscle itself, and persists until muscle is fully recovered. Individual perception of motor effort can be determined with standardized rating scales. These concepts are discussed in detail, their relevance to the pathophysiology of exercise in chronic fatigue syndrome is analyzed, and a general strategy of exercise evaluation pertinent to chronic fatigue syndrome is presented.

Exercise↗