Normal in vivo skeletal muscle oxidative metabolism in sporadic inclusion body myositis assessed by 31P-magnetic resonance spectroscopy.

Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pathogenesis. The common findings of ragged red fibres, cytochrome c oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle of patients with s-IBM have suggested that a deficit of energy metabolism may be of pathogenic relevance. To test this hypothesis we used 31P magnetic resonance spectroscopy to assess in vivo skeletal muscle mitochondrial function in the calf muscles of 12 patients with definite s-IBM.

Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle.

It has been shown previously that some patients with chronic fatigue syndrome show an abnormal increase in plasma lactate following a short period of moderate exercise, in the sub-anaerobic threshold exercise test (SATET). This cannot be explained satisfactorily by the effects of 'inactivity' or 'deconditioning', and patients with abnormal lactate responses to exercise (SATET +ve) have been found to have significantly fewer Type 1 muscle fibres in quadriceps biopsies than SATET -ve patients. We performed phosphorus magnetic resonance spectroscopy on forearm muscles of 10 SATET +ve patients, 9 SATET -ve patients and 13 sedentary volunteers.

Correlative MR imaging and 31P-MR spectroscopy study in sarcoglycan deficient limb girdle muscular dystrophy.

We combined magnetic resonance (MR) imaging and phosphorus magnetic resonance spectroscopy (31P-MRS) to study skeletal muscle in seven patients with limb girdle muscular dystrophy (LGMD) with a variable deficiency of the alpha-, beta-, and gamma-sarcoglycan but normal dystrophin expression on muscle biopsy. T1- and T2-weighted spin-echo axial leg images showed the highest degree of fat replacement in soleus, tibialis anterior and peroneal muscles while gastrocnemius and tibialis posterior were less affected. In LGMD patients as a group, calf muscle phosphorylated compound content did not differ from controls, but the cytosolic pH was increased (P = 0.

Deficit of brain and skeletal muscle bioenergetics and low brain magnesium in juvenile migraine: an in vivo 31P magnetic resonance spectroscopy interictal study.

We used phosphorus magnetic resonance spectroscopy (31P MRS) to investigate in vivo the brain and skeletal muscle energy metabolism of 15 children with migraine with aura in interictal periods. Brain 31P MRS disclosed low phosphocreatine and high inorganic phosphate contents, and high intracellular pH in all patients. Calculated [ADP] and the relative rate of mitochondrial oxidation were higher in the brain of patients than in control subjects, whereas the phosphorylation potential was lower.

In vivo skeletal muscle mitochondrial function in Leber's hereditary optic neuropathy assessed by 31P magnetic resonance spectroscopy.

We used 31P magnetic resonance spectroscopy (31P-MRS) to assess in vivo skeletal muscle mitochondrial function in 10 Leber's hereditary optic neuropathy patients/carriers with a mitochondrial DNA (mtDNA) mutation at one of three nucleotide positions, 11,778, 14,484, and 3,460. We studied one affected patient for each mutation and two unaffected carriers with the 11,778 or 3,460 mutation and three carriers with 14,484. All subjects were homoplasmic except the two 3,460 carriers, who showed 80% and 15% of mutated mtDNA.

In vivo assessment of human skeletal muscle mitochondria respiration in health and disease.

One of many problems to be faced when assessing in vivo human muscle mitochondria respiration by phosphorus magnetic resonance spectroscopy (31P-MRS) is the definition of the correct reference population and the values of reference range. To take into account most factors that influence muscle activity as age, sex, physical activity; nutritional state etc., an exceedingly high number of different reference groups are needed.

Coenzyme Q10 improves mitochondrial respiration in patients with mitochondrial cytopathies. An in vivo study on brain and skeletal muscle by phosphorous magnetic resonance spectroscopy.

With phosphorus magnetic resonance spectroscopy (31P-MRS) we studied in vivo the effect of six-month coenzyme Q10 treatment on the efficiency of brain and skeletal muscle mitochondrial respiration in six patients with different mitochondrial cytopathies. Before CoQ we found a low phosphocreatine content (average of 25% decrease from controls) in the occipital lobes of all patients. Calculated [ADP] and the relative rate of ATP synthesis were high (as an average, 57% and 16% above control group respectively), whereas the cytosolic phosphorylation potential was low (as an average, 60% of control value).

Influence of cytosolic pH on in vivo assessment of human muscle mitochondrial respiration by phosphorus magnetic resonance spectroscopy.

The authors present an in vivo phosphorus magnetic resonance spectroscopy systematic study on the effects of cytosolic pH on skeletal muscle mitochondrial respiration in human calf muscle. In 49 normal subjects, the effect of cytosolic pH on kinetics of phosphocreatine and adenosine diphosphate recovery and on maximum rate of mitochondrial adenosine triphosphate production (Q(MAX)) was evaluated. The results show a strong relationship between the rate of postexercise phosphocreatine recovery and the lowest value of cytosolic pH reached during recovery from exercise (termed minimum pH; r = 0.

Brain and skeletal muscle bioenergetic failure in familial hypobetalipoproteinaemia.

Objective: To determine whether a multisystemic bioenergetic deficit is an underlying feature of familial hypobetalipoproteinaemia.

Methods: Brain and skeletal muscle bioenergetics were studied by in vivo phosphorus MR spectroscopy (31P-MRS) in two neurologically affected members (mother and son) and in one asymptomatic member (daughter) of a kindred with familial hypobetalipoproteinaemia. Plasma concentrations of vitamin E and coenzyme Q10 (CoQ10) were also assessed.

Failure of muscle energy metabolism in a patient with adenylosuccinate lyase deficiency. An in vivo study by phosphorus NMR spectroscopy.

31P-nuclear magnetic resonance spectroscopy was used to investigate in vivo the energy metabolism of the calf muscle in a 10-year-old patient with adenylosuccinate lyase deficiency and severe psychomotor retardation. The patient showed a markedly reduced PCr/P(i) molar ratio, known to well represent the cytosolic phosphorylation potential, due to low PCr and high P(i) content in resting muscle. Moreover, intracellular ATP concentration was significantly lower than in the control group both at rest and at the end of post-exercise recovery.

Clinical and brain bioenergetics improvement with idebenone in a patient with Leber's hereditary optic neuropathy: a clinical and 31P-MRS study.

We used phosphorus magnetic resonance spectroscopy (31P-MRS) to study in vivo brain and muscle bioenergetics in a male patient with Leber's hereditary optic neuropathy (LHON) and mtDNA mutation at 11,778 bp who developed spastic paraparesis with white matter lesions on brain MR imaging. The study was performed before and during treatment with idebenone (135 mg t.i.

Results of surgical resection in patients over the age of 70 years with non small-cell lung cancer.

Methods: From January 1989 to October 1993, at the Department of Cardio-Thoracic Surgery of the University of Modena, 806 patients underwent thoracotomy and curative pulmonary resection for non small-cell lung cancer. Eighty five patients were 70 years old or older (mean 73.4 years, range 70-88).

Quantitative analysis of skeletal muscle bioenergetics and proton efflux in migraine and cluster headache.

Phosphorus MR spectroscopy (31P-MRS) was used to quantify skeletal muscle bioenergetics and proton efflux in 63 patients with migraine (23 with migraine without aura, MwoA, 22 with migraine with aura, MwA, and 18 with prolonged aura or stroke, CM) and in 14 patients with cluster headache (CH), all in an attack-free period. At rest mitochondrial function was abnormal only in CM, as shown by a low phosphocreatine (PCr) concentration. At the end of a mixed glycolytic/aerobic exercise all three migraine groups showed a significantly smaller decrease of cytosolic pH compared to controls with a similar end-exercise PCr breakdown, while end-exercise pH was normal in cluster headache patients.

[Color Doppler ultrasonography in retinitis pigmentosa. Preliminary study].

Purpose: Retinitis pigmentosa is a bilateral retinal degeneration. The primary disorder is still debated.

Methods: We performed a prospective investigation of the ocular circulation directly by color Doppler imaging (CDI).

Phosphorus magnetic resonance spectroscopy in cluster headache.

We performed in vivo MR spectroscopy phosphorus (31P-MRS) on the brain and skeletal muscles of 14 patients affected with cluster headache (CH). We examined patients in interictal periods, and also examined nine of them during the cluster period, although not during the attack. Brain 31P-MRS showed reduced phosphocreatine (PCr) levels, an increased ADP concentration (calculated from the creatine kinase equilibrium), a reduced phosphorylation potential, and a high relative rate of ATP biosynthesis (V/Vmax %).

Inorganic phosphate is transported into mitochondria in the absence of ATP biosynthesis: an in vivo 31P NMR study in the human skeletal muscle.

We used 31-phosphorus magnetic resonance spectroscopy to study in vivo the transport of inorganic phosphate (Pi) from cytosol into mitochondria as assessed by the kinetics of Pi recovery during ischemia after aerobic exercise in human skeletal muscle. In all subjects during the first 30 s of ischemia inorganic phosphate showed a marked decrease from the value measured at the end of exercise, whilst phosphocreatine maintained the same value reached at the end of exercise. Our results show that Pi transport from cytosol into mitochondria is active in the absence of ATP biosynthesis and lasts 30 s possibly as a consequence of a decreased pH gradient, due to symport of Pi and H+ associated with an inactive electron transport chain during ischemia.

Effect of oral phosphocreatinine on human skeletal muscle shown by in vivo 31P-NMR.

We used the non-invasive method of in vivo phosphorus magnetic resonance spectroscopy to investigate the effect of oral administration of phosphocreatinine on muscle energy metabolism during graded work and post-exercise recovery in humans. Phosphocreatinine administration results in a smaller depletion of phosphocreatine at high work rates accompanied by a smaller cytosolic acidification during work and recovery. Our findings suggest that oral phosphocreatinine increases the readily available energy for muscle contraction by interfering directly or indirectly with the reaction equilibria involving phosphocreatine.

Autosomal dominant limb girdle myopathy with ragged-red fibers and cardiomyopathy. A pedigree study by in vivo 31P-MR spectroscopy indicating a multisystem mitochondrial defect.

We describe a late-onset autosomal dominant limb girdle myopathy, associated with dilated cardiomyopathy and mental deterioration. In two affected members of the pedigree with histochemical (ragged-red and cytocrome c oxidase - negative fibers) and ultrastructural abnormalities of muscle mitochondria, in vivo muscle phosphorus MR spectroscopy disclosed a slow rate of phosphocreatine resynthesis after exercise. Brain phosphorus MR spectroscopy revealed a defect of the energy metabolism in the two patients and in a third asymptomatic member, as shown by a significantly low phosphocreatine, increased ADP and decreased phosphorylation potential.

Partial block of glycolysis in late-onset phosphofructokinase deficiency myopathy.

A late-onset, myopathic variant of phosphofructokinase (PFK) deficiency has been previously described in two patients of Ashkenazic descent. We report here on a non-Ashkenazic woman with the onset, at the age of 48 years, of a progressive limb girdle myopathy that was not preceded by a history of exercise intolerance. Muscle biopsy findings at the age of 58 years showed deposition of amylopectin-like material in muscle fibers and the absence of histochemical PFK activity.

Improvement of pulmonary graft after storage for twenty-four hours by in vivo administration of lazaroid U74389G: functional and morphologic analysis.

Background: We examined the effects of in vivo administration of a potent inhibitor of iron-dependent lipid peroxidation, lazaroid U74389G, on lung preservation.

Methods: Lungs isolated from Sprague-Dawley rats (n = 23) were either immediately reperfused after removal (control, n = 8) for 2 hours by means of an isolated, pulsatile blood perfusion system or reperfused after cold storage (4 degrees C) for 24 hours in the University of Wisconsin solution with (n = 7) or without (n = 8) lazaroid. The lazaroid group had in vivo infusion of lazaroid U74389G (6 mg/kg) before lung harvest plus addition to the perfusate (50 mu mol/L) at the onset of reperfusion.

Defective brain and muscle energy metabolism shown by in vivo 31P magnetic resonance spectroscopy in nonaffected carriers of 11778 mtDNA mutation.

In vivo phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective brain and muscle energy metabolism in three affected siblings in a family with Leber's hereditary optic neuropathy (LHON) with the 11778 mtDNA mutation. We studied 14 nonaffected members of the same pedigree by 31P-MRS and molecular genetics. Nine of 14 individuals studied had the 11778 mtDNA mutation, with various degrees of heteroplasmy.

Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy.

A woman affected by chronic progressive external ophthalmoplegia and muscle mitochondrial DNA deletion was studied by phosphorus magnetic resonance spectroscopy (31P-MRS) prior to and after 1 and 7 months of treatment with oral lipoic acid. Before treatment a decreased phosphocreatine (PCr) content was found in the occipital lobes, accompanied by normal inorganic phosphate (Pi) level and cytosolic pH. Based on these findings, we found a high cytosolic adenosine diphosphate concentration [ADP] and high relative rate of energy metabolism together with a low phosphorylation potential.