Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity: a randomised cross-over trial.

BACKGROUND AND AIMS: Several studies have shown that moderate alcohol consumption reduces the risk of coronary heart disease, a disease related to oxidative stress. However, the effects of different alcoholic beverages on antioxidant status are not fully known. Our aim was therefore to compare the effects of a moderate intake of an alcoholic beverage with high polyphenol content (red wine) and another without polyphenol content (gin) on plasma antioxidant vitamins, lipid profile and oxidability of low-density lipoprotein (LDL) particles. METHODS AND RESULTS: Forty healthy men (mean age, 38 years) were included in a randomised cross-over trial. After a 15-day washout period, subjects received 30 g/ethanol/d as either wine or gin for 28 days. Diet and exercise were monitored. Before and after each intervention, we measured serum vitamins, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase activities, lipid profile, oxidized LDL and LDL resistance to ex-vivo oxidative stress. Compared to gin intervention, wine intake reduced plasma SOD activity [-8.1 U/gHb (95% confidence interval, CI, -138 to -25; P=0.009)] and MDA levels [-11.9 nmol/L (CI, -21.4 to-2.5; P=0.020)]. Lag phase time of LDL oxidation analysis also increased 11.0 min (CI, 1.2-20.8; P=0.032) after wine, compared to gin, whereas no differences were observed between the two interventions in oxidation rate of LDL particles. Peroxide concentration in LDL particles also decreased after wine [-0.18 nmol/mL (CI, -0.3 to-0.08;P=0.020)], as did plasma oxidized LDL concentrations [-11.0 U/L (CI,-17.3 to -6.1; P=0.009)]. CONCLUSION: Compared to gin, red wine intake has greater antioxidant effects, probably due to its high polyphenolic content.

A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome.

Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at theta = 0 (P<0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.

High alcohol intake as a risk and prognostic factor for community-acquired pneumonia.

OBJECTIVE: To evaluate whether high alcohol intake is an independent risk factor for community-acquired pneumonia in middle-aged people and whether it confers a poor prognosis. METHODS: A two-phase study was performed. Risk factors for community-acquired pneumonia were evaluated in a case-control study of 50 patients and 50 controls. Prognostic factors and microbiologic and clinical features were then evaluated in a cohort study of the 50 middle-aged patients with community-acquired pneumonia. RESULTS: In the first study, the only independent risk factor for community-acquired pneumonia was high alcohol intake (P < .02). In the second study, patients with chronic alcoholism had a higher incidence of pneumonia caused by gram-negative bacilli (P < .03), as well as a higher incidence of Candida albicans (P < .03), Staphylococcus aureus (P < .0001), and gram-negative bacilli (P < .001) in the cultures of pharyngeal smears than did the nonalcoholics. Compared with nonalcoholic patients, alcoholic patients with pneumonia showed more severe clinical symptoms (P < .02), required longer intravenous treatment (P < .02) and longer hospital stay (P < .01), and had multilobar involvement and pleural effusion (both P < .01), as well as slower resolution of pulmonary infiltrates. The only prognostic factor for mortality was high alcohol intake (P < .03). CONCLUSIONS: High alcohol intake is the main risk factor for developing community-acquired pneumonia in middle-aged people. This situation also confers a worse prognosis in these patients, who should be treated with broad-spectrum antibiotics for a longer period.

Aging is associated with increased lipid peroxidation in human hearts, but not with mitochondrial respiratory chain enzyme defects.

BACKGROUND: Aging is associated with increased oxidative damage at multiple cellular and tissular levels. A decrease in mitochondrial function has repeatedly been advocated as a primary key event, especially on the basis of analysis of skeletal muscle mitochondria. However, some doubts on this issue have arisen when confounding variables (such as physical activity or smoking habit) have been taken into account in the analysis of mitochondrial respiratory chain (MRC) enzyme activities or when additional analytical parameters such as enzyme ratios have been considered. OBJECTIVE: To determine whether oxidative damage and enzyme activities of the MRC are influenced by the aging process in human hearts. PATIENTS AND METHODS: We studied cardiac muscle obtained from 59 organ donors (age: 56+/-12 years, 75% men). Oxidative membrane damage was evaluated through the assessment of lipid peroxidation. Absolute and relative enzyme activities (AEA and REA, respectively) of complex I, II, III and IV of the MRC were spectrophotometrically measured. Stoichiometric relationships among MRC complexes were also assessed through calculating MRC ratios. Linear regression analyses were employed to disclose any potential correlation between mitochondrial dysfunction and aging. RESULTS: We found a progressive, significant increase of heart membrane lipid peroxidation with aging (P<0.05). Conversely, neither AEA nor REA decreased with age (P=n.s. for all complexes). Similarly to observations in other tissues, we found that stoichiometry of the MRC enzymes is maintained within a narrow range in human hearts. When the effects of aging on MRC ratios were explored, we failed again in demonstrating any subtle disarray. CONCLUSION: MRC enzymes remain preserved in heart with aging, and thus they cannot be considered the main cause of the increased oxidative damage associated with aging.

Oral calcium supplementation reduces intraplatelet free calcium concentration and insulin resistance in essential hypertensive patients.

We evaluated the effect of oral calcium supplementation on blood pressure, calcium metabolism, and insulin resistance in essential hypertension. After receiving a standard diet with 500 mg of calcium per day during a 4-week period, 20 nondiabetic, essential hypertensive patients were randomized in a double-blind fashion to receive oral calcium supplementation (1500 mg of calcium per day) or placebo for 8 weeks. At the end of the 4-week period of low-calcium diet and after the 8-week period of intervention, we measured blood pressure (by both office and 24-hour ambulatory blood pressure monitoring), calcium-regulating hormones [urinary hydroxyproline and serum osteocalcin, parathormone, and 1,25(OH)2-vitamin D3], intraplatelet free calcium concentration, fasting plasma glucose and insulin levels, and the insulin-sensitivity index (euglycemic-hyperinsulinemic clamp). Compared with patients maintained at low calcium intake, essential hypertensive patients under oral calcium supplementation significantly reduced serum osteocalcin (from 22.2 +/- 1.9 to 17.9 +/- 2.0 micrograms/L; P = .0015), parathormone (from 4.20 +/- 0.38 to 3.30 +/- 0.36 pmol/L; P = .0003), and 1,25(OH)2-vitamin D3 (from 98.0 +/- 11.0 to 61.6 +/- 5.7 pmol/L; P = .0062). Likewise, we found a significant reduction in intraplatelet free calcium concentration (from 35.9 +/- 1.2 to 26.5 +/- 0.8 nmol/L; P = .0005) and fasting plasma insulin levels (from 71.8 +/- 5.9 to 64.6 +/- 6.2 pmol/L; P = .05) and a significant increase in the insulin-sensitivity index (from 2.89 +/- 0.77 to 4.00 +/- 0.95 mg.kg-1.min-1; P = .0007). None of these parameters were significantly modified in patients maintained at low calcium intake. Office and 24-hour mean values of systolic and diastolic blood pressure did not change after 8 weeks of oral calcium supplementation or placebo.

Increased activity of the Mg2+/Na+ exchanger in red blood cells from essential hypertensive patients.

Epidemiological, clinical, and experimental evidence suggests a relation between Mg2+ metabolism and essential hypertension. The aim of the present study was the detection of abnormalities of the erythrocyte Mg2+/Na+ exchanger in essential hypertensive patients. We studied 66 untreated essential hypertensive patients and 36 normotensive control subjects. Maximal efflux rates of total Mg2+ efflux and the Na(+)-dependent and Na(+)-independent components of Mg2+ efflux were determined in Mg(2+)-loaded red blood cells. Mg2+/Na+ exchanger was calculated as the Na(+)-dependent component of the Mg2+ efflux. Mean values of Mg2+/Na+ exchanger were clearly elevated in hypertensive subjects with respect to normotensive control subjects [184.7 +/- 15.7 versus 84.4 +/- 6 mumol(L.cell.h)-1; P < .001]. This elevation was due primarily to the increased total Mg2+ efflux [324.2 +/- 21.9 versus 257.9 +/- 17.3 mumol(L.cell.h)-1; P < .05], whereas the Na(+)-independent component was not significantly different between the groups [154.5 +/- 11.8 versus 173.4 +/- 15.5 mumol(L.cell.h)-1; P = NS]. Moreover, total erythrocyte Mg2+ content was slightly reduced in hypertensive patients with respect to normotensive control subjects (1.84 +/- 0.04 versus 2.07 +/- 0.04 mmol/L.cell; P < .001). Using the 99% confidence limits of the normotensive population as the normal range, 30 (45.5%) hypertensive subjects showed values of Mg2+/Na+ exchanger higher than 160 mumol(L.cell.h)-1. The Mg2+/Na+ exchanger was inversely correlated with basal intraerythrocyte Mg2+ content (r = -.323; P = .001). From a clinical point of view, we found a positive correlation between diastolic blood pressure values and Mg2+/Na+ exchanger (r = .246; P < .05) in the sample of essential hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of alcohol abstinence on blood pressure: assessment by 24-hour ambulatory blood pressure monitoring.

Several studies have shown that cessation of alcohol drinking reduces blood pressure (BP). However, attempts to reproduce these findings by ambulatory BP monitoring (ABPM) have shown inconsistent results. The aim of the present study was to assess the effect of 1 month of proven abstinence from alcohol on the 24-hour BP profile in heavy alcohol drinkers. Forty-two men who were heavy drinkers (>100 g of pure ethanol per day) were consecutively admitted to a general ward for voluntary alcohol detoxification. On the day of admission, they received a total dose of 2 g/kg of ethanol diluted in orange juice in 5 divided doses, and a 24-hour ABPM was performed. A new 24-hour BP monitoring in the same environmental conditions was performed after 1 month of proven alcohol abstinence while the subjects were receiving the same amount of fluid but without the addition of alcohol. After 1 month of proven alcohol abstinence, BP and heart rate (HR) significantly decreased. The reduction was 7.2 mm Hg for 24-hour systolic BP (SBP) (95% CI, 4.5 to 9.9), 6.6 mm Hg for 24-hour diastolic BP (DBP) (95% CI, 4.2 to 9.0), and 7.9 bpm for HR (95% CI, 5.1 to 10.7). The proportion of alcoholic patients considered hypertensive on the basis of 24-hour BP criteria (daytime SBP >/=135 mm Hg or daytime DBP >/=85 mm Hg) fell from 42% during alcohol drinking to 12% after 1 month of complete abstinence. Abstinence did not modify either the long-term BP variability, assessed by SD of 24-hour BP, or its circadian profile. We conclude that abstinence in heavy alcohol drinkers significantly reduces BP assessed by 24-hour ABPM and that this reduction is clinically relevant. These results show that heavy alcohol consumption has an important effect on BP, and thus cessation of alcohol consumption must be recommended as a priority for hypertensive alcohol drinkers.

Erythrocyte sodium transport, intraplatelet pH, and calcium concentration in salt-sensitive hypertension.

We evaluated changes in erythrocyte sodium transport systems, platelet pH, and calcium concentration induced by low and high salt intakes in a group of 50 essential hypertensive patients classified on the basis of their salt sensitivity. Patients received a standard diet with 20 mmol NaCl daily for 2 weeks supplemented in a single-blind fashion by placebo tablets the first 7 days and NaCl tablets the following 7 days. Salt sensitivity, defined as a significant rise (P <.05) in 24-hour mean blood pressure obtained by ambulatory blood pressure monitoring, was diagnosed in 22 (44%) patients. The remaining 28 (56%) were considered to have salt-resistant hypertension. In the entire group of hypertensive patients, high salt intake promoted a significant increase (P <.05) in the maximal rate of erythrocyte NA(+)-Li(+) countertransport (from 271 +/- 19 to 327 +/- 18 microM/(L cells/h) and of the Na(+)-dependent HCO3(-)-CL(-) exchanger (from 946 +/- 58 to 1237 +/- 92 microM/L cells/h) as well as in platelet pH (from 7.15+/-0 0.01 to 7.19+/-0.02 and calcium concentration (from 49+/-2 to 57 +/-2 nmol/L). Depending on salt sensitivity, high salt intake promoted opposing changes in some of the sodium transport systems studied. Salt-sensitive patients increased the maximal rate of the erythrocyte Na(+)-K(+) pump (fom 7.0 +/- 0.4 to 8.8 +/- 0.4 mmol/(L cells/h), Na(+)-K(+)-Cl(-) cotransport (from 416 +/- 37 to 612 +/- 41 micromol/(L cells/h), Na(+)-Li(+) countertransport (from 248 +/- 20 to 389 +/- 17 micromol/(L cells/h) at the end of the high salt period. Conversely, salt-resistant patients decreased the Na(+)-K(+) pump (from 8.0 +/- 0.4 to 6.9 +/- 0.3 mmol/(L cells/h) and Na(+)-K(+)-Cl(-) cotransport (from 578 +/- 53 to 481 +/- 43 micromol/(L cells/h). We conclude that modulation of erythrocyte sodium transport systems by high salt intake depends on salt sensitivity. The Na(+)-K(+) pump, Na(+)-K(+)-Cl(-) cotransport, and Na(+)-Li(+) countertransport increase in salt-sensitive patients, whereas the activity of these sodium transport systems tends to decrease in salt-resistant patients. Independent of salt sensitivity, high salt intake promotes a significant increase in the erythrocyte Na(+)-dependent HCO3(-)-Cl(-) exchanger, platelet pH, and calcium concentration in essential hypertensive patients.

Autonomic and peripheral neuropathies in patients with chronic alcoholism. A dose-related toxic effect of alcohol.

OBJECTIVE: To assess autonomic and peripheral nervous system function in patients with chronic alcoholism. DESIGN: A cross-sectional study. PATIENTS: A consecutive sample of 107 alcoholic patients and 61 controls. MAIN OUTCOME MEASURE: For autonomic assessment, heart rate variations during deep breathing and Valsalva maneuver and on standing were measured. Blood pressure response to standing up and to sustained handgrip were also evaluated. For assessment of the peripheral nervous system, an electrophysiologic examination was performed. RESULTS: Alcoholic patients exhibited reduced heart rate variability compared with controls (P < .01, on all parasympathetic tests), whereas no differences in the mean values of the blood pressure responses between both groups were found. Twenty-six patients (24.3%) had criteria of autonomic neuropathy, and 34 (32%) had electrophysiologic criteria of peripheral neuropathy. None of the controls exhibited criteria of autonomic neuropathy, and only one had criteria of peripheral neuropathy. The estimated total lifetime dose of alcohol correlated inversely with the parasympathetic indexes (r = -.48 to -.51; P < .001 on all parasympathetic tests) and the sensory potential amplitudes of upper and lower limbs (r = -.43; P < .001, both limbs). Finally, a significant correlation between autonomic and peripheral neuropathies was observed (P = .01). By contrast, these lesions were not related to age, nutritional status, or other alcohol-related diseases. CONCLUSIONS: Autonomic and peripheral neuropathies are common among hospitalized alcoholic patients. Alcohol appears to be toxic to autonomic and peripheral nerves in a dose-dependent manner.

Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease.

Different abnormalities in mitochondrial electron transport chain activity have been demonstrated in muscle and other tissues of patients with idiopathic Parkinson's disease (PD). We studied eight Spanish patients with PD to evaluate the functional activity of the electron transport chain in muscle mitochondria from patients of this country. We found lower complex I activity (nmol.min-1.mg-1) in patients (245.8 +/- 42.8) than in controls (331.6 +/- 60.1) (p = 0.004) and lower complex IV activity in patients (46.1 +/- 9) than in controls (144.1 +/- 42.3) (p = 0.00001). Complex V activity was also decreased in two patients and complex II and III activities were normal in all of them. Although these results strongly suggest an alteration in mitochondrial DNA in PD, the various electron transport chain defects in different tissues seem to be nonspecific.

Inflammatory myopathy associated with chronic graft-versus-host disease.

Damage of skeletal muscle in association with graft-versus-host disease (GvHD) has been referenced exceptionally. Eighteen months after bone marrow transplantation, a 22-year-old man developed polymyositis associated with manifestations of chronic GvHD, such as peripheral eosinophilia and localized morphea. Diagnosis of polymyositis was established by clinical, electromyographic, and histopathologic findings. His clinical condition improved with immunosuppressive therapy. At electronmicroscopy, some close and broad contacts between lymphocytes with activated appearance and degenerated muscle fibers were observed, suggesting a lymphocytotoxic mechanism. The findings support the idea that polymyositis can be considered a manifestation of chronic GvHD.

Na+-Li+ countertransport in essential hypertension.

Several studies on Na+-Li+ countertransport have reported higher rates in essential hypertensive than in normotensives, with a distribution pattern which is dependent on racial and ethnic background. However, it is not well established whether this abnormality in Na+ transport is associated with an abnormal clinical setting. In the present study we have performed a kinetic analysis of the interaction of the Na+-Li+ countertransport system with internal Na+ in erythrocytes from a sample of 72 essential hypertensives and 30 normotensive controls. A significant increase in mean values of the maximal rate of Li+-stimulated Na+ efflux (Vmax; 375.1 +/- 23.8 versus 213.7 +/- 8.5 mumol/l cells per h; mean +/- s.e.m.; Mann-Whitney test: U = 500; P less than 0.0001), as well as in the apparent affinity constant for internal Na+ (KNa; 10.03 +/- 0.08 versus 6 +/- 0.4 mmol/l cells; Mann-Whitney test: U = 718; P less than 0.0079), were observed in essential hypertensives with respect to normotensives. Using the 95% confidence interval of Vmax in normotensives as the normal range, 29 (40.3%) of the essential hypertensives exhibited values above the normal upper limit. The maximal rate (Vmax) and the internal Na+ content required for half-maximal stimulation (K50%) of Na+-K+ ATPase and outward Na+-K+ cotransport, and the rate constant of Na+ leak (KPNa) in this subset were similar to the values observed in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional cerebral blood flow-SPECT in chronic alcoholism: relation to neuropsychological testing.

To determine the prevalence of central nervous system damage due to ethanol, we evaluated 40 asymptomatic chronic alcoholics and 20 age-matched controls. Studies included neuropsychological testing, brain 99mTc-HMPAO SPECT, and morphometric analysis by CT scan. In the qualitative analysis, 30 of the 40 alcoholics showed hypoperfused areas on SPECT scan. In the semiquantitative analysis, alcoholics exhibited significant reduction in regional cerebral blood flow (rCBF) ratio of all brain lobes compared to controls (p < 0.001). The rCBF ratio was mainly reduced in frontal lobes (65%). Only 11 alcoholics showed significant frontal lobe atrophy in the morphometric analysis; most also had abnormalities on SPECT scan. Alcoholics exhibited significant impairment of frontal tasks and visuospatial skills. Frontal test impairment was independently related to both frontal atrophy and hypoperfusion. In a group of ten alcoholics in whom another SPECT scan was performed after 2 mo of ethanol abstinence, rCBF ratio of the frontal lobes normalized in eight, without frontal atrophy. In patients without frontal atrophy, reduced rCBF ratio of the anterior portion of the frontal lobes correlated negatively with frontal test results (r = -0.6535, p < 0.001). A significant negative correlation between cerebral perfusion and the amount of ethanol consumed in the month prior to study was observed (r = -0.6289, p < 0.001). In conclusion, asymptomatic chronic alcoholics frequently showed reversible frontal lobe hypoperfusion, which is related to recent ethanol intake, reflects brain function impairment and is independent of brain atrophy.

Differential effects of moderate or heavy alcohol consumption on circulating adhesion molecule levels.

Epidemiological studies suggest that moderate but not heavy alcohol consumption provides protection against coronary heart disease. We assessed the relationship between alcohol consumption and serum levels of adhesion molecules involved in the pathogenesis of early atherosclerosis. One-hundred apparently healthy men with similar cardiovascular risk factors were divided into four groups according to ethanol intake. Moderate drinkers (20-40 g/day) showed lower serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels than abstainers (p < 0.05; both), as well as lower serum ICAM-1, VCAM-1 and E-selectin levels than heavy drinkers (p = 0.01; all). The latter also showed higher serum ICAM-1 and E-selectin levels than abstainers (p < 0.001; both). We conclude that moderate drinkers show a significant reduction of soluble endothelial adhesion molecule levels compared to abstainers and heavy drinkers, that may contribute to the protective effect of moderate alcohol consumption against atherosclerosis.

Comparison of alcoholic cardiomyopathy in women versus men.

To compare the prevalence and cardiac status of male and female alcoholics with alcoholic cardiomyopathy during a 5-year period, all chronic alcoholics with dilated cardiomyopathy who had clinical symptoms of heart failure were included. Alcoholic cardiomyopathy was diagnosed in 10 chronic alcoholic women and in 26 men; the prevalence of alcoholic cardiomyopathy was similar in both sexes. No significant differences were observed in age, nutritional parameters, and clinical and radiologic data of heart failure between the 2 groups. Alcoholic women reported a significantly lower daily dose of ethanol (p = 0.002), a shorter duration of alcoholism (p = 0.017), and a lower total lifetime dose of ethanol consumption (p = 0.001), and had a lower New York Heart Association functional class than men. Women also had lesser ventricular dysfunction than men. In a multivariate analysis, left ventricular systolic dysfunction was related to the total lifetime dose of ethanol consumption (p <0.04), but not to gender. Finally, when patients were matched for left ventricular ejection fraction, women had consumed a lower total lifetime dose of ethanol than men (p <0.001). The prevalence of alcoholic women with dilated cardiomyopathy was found to be similar to that of alcoholic men, although women required a lower total lifetime dose of ethanol to develop the disease.

Vitamin D metabolite-mediated hypercalcemia in Wegener's granulomatosis.

Hypercalcemia may occur during the course of various granuloma-forming diseases. Herein we describe a patient who had symptomatic hypercalcemia as a prominent sign of Wegener's granulomatosis. We observed a direct correlation between the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] and both the serum and the urinary calcium levels. Administration of prednisone and cyclophosphamide led to a substantial decrease in the levels of calcium and serum 1,25(OH)2D, but the serum levels of 25-hydroxyvitamin D remained unchanged. Two months after admission of the patient, the levels of calcium and 1,25(OH)2D increased; after we increased the dose of cyclophosphamide, these levels decreased (the dose of corticosteroids was not changed). We suggest that the excessive synthesis of 1,25(OH)2D was inhibited by a direct or indirect action not only of prednisone but also of cyclophosphamide on the 1 alpha-hydroxylation of 25-hydroxyvitamin D in the activated macrophage of Wegener granulomas. Furthermore, in view of this case and two other recently reported cases, we believe that Wegener's granulomatosis must be definitively added to the list of granulomatous diseases that are responsible for 1,25(OH)2D-mediated hypercalcemia.

Congenital and metabolic myopathies of childhood or adult onset.

OBJECTIVES: To investigate the clinical presentation, histological findings, and outcome of patients with congenital and metabolic myopathies (CM and MM) in whom the disease was diagnosed in childhood or adulthood. PATIENTS AND METHODS: We reviewed the diagnosis of all skeletal muscle biopsies performed by our group between 1984 and 1996 (13 years). All patients with CM and MM of childhood or adult onset were included in the study. Patients with mitochondrial myopathies were excluded because they are multisystemic disorders with a more distinct picture than that observed in other MM. We retrospectively reviewed the clinical history, with special emphasis on the clinical patterns of presentation, histological findings, and outcome. RESULTS: Among 1,865 biopsies, 28 (1.5%) fulfilled the diagnostic criteria for CM (seven nemaline myopathies, four multicore myopathies, three centronuclear myopathies) or MM (five adult-onset acid maltase deficiency, three myophosphorylase deficiency, three phosphofructokinase deficiency, two carnitine palmitoyl transferase deficiency, and one carnitine deficiency). In nearly half of the patients, mild stable weakness was the major complaint, whereas in one third muscular symptoms were intermittent and related to exercise. In a small number of cases, a persistently raised serum creatine kinase in an asymptomatic patient was the reason for muscle biopsy. Histological examination of skeletal muscle was highly indicative of a specific muscle disease in 26 of the 28 cases. After a mean follow-up of 7 years, the outcome has generally been good, and in most patients the myopathy did not worsen, most remaining ambulatory. CONCLUSION: CM and MM presenting in childhood or adulthood are infrequent; the symptoms are usually mild or moderate, and the prognosis generally is good.

Microvascular changes in skeletal muscle in idiopathic inflammatory myopathy.

Open deltoid muscle biopsy specimens from patients with idiopathic adult dermatomyositis, paraneoplastic dermatomyositis, childhood dermatomyositis, and idiopathic polymyositis, and from control patients were studied. Qualitative and morphometric capillary analysis by phase and electron microscopy was carried out. In the morphologic analysis the most striking difference was the presence of capillary damage and a higher capillary depletion in dermatomyositis as well as a higher capillary density in polymyositis. By electron microscopy, capillaries from patients with dermatomyositis showed mainly microtubuloreticular structures, loss of endothelial plasma membranes, and the appearance of abnormal cytoplasmic organelles. In contrast, capillaries from patients with polymyositis exhibited only minimal changes. By morphometric analysis, muscle capillaries in dermatomyositis had a significantly higher mean endothelial thickness than those in polymyositis. Finally, a significant topographic association between capillary damage and muscle fiber changes was observed only in patients with dermatomyositis. On the other hand, paraneoplastic dermatomyositis showed fewer structural and morphometric capillary changes than the other forms of dermatomyositis. We conclude that dermatomyositis is characterized by microvascular alterations that are absent in polymyositis. The topographic proximity of capillary changes to muscle fiber injury suggests that capillary damage may play a role in the pathogenesis of the muscle lesions observed in patients with dermatomyositis.

Reduced steady-state levels of mitochondrial RNA and increased mitochondrial DNA amount in human brain with aging.

The contribution of the mitochondrial genetic system in the degenerative processes of senescence remains unclear. This study deals with age-related changes in brain mtDNA expression in humans. Brain tissue from the frontal lobe cortex was obtained from autopsy of 13 humans aged between 21 and 84 years. No structural changes were detected in mtDNA, increased mtDNA content and reduced steady-state level of mitochondrial transcripts and transcription ratio (mtRNA/mtDNA) were associated with aging. These findings suggest that the increase of the mtDNA levels could be considered as an inefficient compensatory mechanism to maintain the normal levels of mtRNA transcripts. This unbalanced mitochondrial condition could play a role in the process of senescence in human brain.

Myasthenia gravis after allogeneic bone marrow transplantation: report of a new case and pathogenetic considerations.

A 21-year-old caucasian man with T acute lymphoblastic leukemia underwent a bone marrow transplantation (BMT) and developed classic myasthenia gravis (MG) 46 months later. The association of almost all published cases with HLA B35 is discussed, as are the clinical aspects suggesting that BMT survivors are at risk for developing MG as part of the spectrum of chronic graft-versus-host disease.