Cut-off Points for Muscle Mass - Not Grip Strength or Gait Speed - Determine Variations in Sarcopenia Prevalence.

OBJECTIVES: The European Working Group on Sarcopenia in Older People (EWGSOP) has proposed different methods and cut-off points for the three parameters that define sarcopenia: muscle mass, muscle strength and physical performance. Although this facilitates clinical practice, it limits comparability between studies and leads to wide differences in published prevalence rates. The aim of this study was to assess how changes in cut-off points for muscle mass, gait speed and grip strength affected sarcopenia prevalence according to EWGSOP criteria. METHODS: Cross-sectional analysis of elderly individuals recruited from outpatient clinics (n=298) and nursing homes (n=276). We measured muscle mass, grip strength and gait speed and assessed how changes in cut-off points changed sarcopenia prevalence in both populations. RESULTS: An increase from 5.45 kg/m2 to 6.68 kg/m2 in the muscle mass index for female outpatients and nursing-home residents increased sarcopenia prevalence from 4% to 23% and from 9% to 47%, respectively; for men, for an increase from 7.25 kg/m2 to 8.87 kg/m2, the corresponding increases were from 1% to 22% and from 6% to 41%, respectively. Changes in gait speed and grip strength had a limited impact on sarcopenia prevalence. CONCLUSION: The cut-off points used for muscle mass affect the reported prevalence rates for sarcopenia and, in turn, affect comparability between studies. The main factors influencing the magnitude of the change are muscle mass index distribution in the population and the absolute value of the cut-off points: the same difference between two references (e.g., 7.5 kg/m2 to 7.75 kg/m2 or 7.75 kg/m2 to 8 kg/m2) may produce different changes in prevalence. Changes in cut-off points for gait speed and grip strength had a limited impact on sarcopenia prevalence and on study comparability.

Prevalence of sarcopenia in healthy community-dwelling elderly in an urban area of Barcelona (Spain).

INTRODUCTION: The purpose of this study was to evaluate the prevalence of sarcopenia in a cohort of healthy community-dwelling elderly in an urban area in Barcelona (Spain) for native benchmarks and compare them with those published in other geographical areas. MATERIAL AND METHODS: We prospectively evaluated a series of 200 healthy elderly in the community with preserved functional capacity and absence of cognitive impairment. We performed a comprehensive geriatric assessment and determined anthropometric data, muscle mass (MM) and the muscle mass index (MMI). Assessment of muscle mass was performed by bioelectrical impedance analysis (BIA). The cut-off point for defining sarcopenia MMI was established as less than 2 SD of the mean of a reference group comprising 220 healthy volunteers (20-42 years) in the same area. Results were compared with studies undertaken in the USA, France and Taiwan. RESULTS: The cut-off points obtained were 8.31 Kg/m(2) for men and 6.68 Kg/m2 for women, being similar to those observed in France and Taiwan but different from the USA. The prevalence of sarcopenia observed was 33% for elderly women and 10% for males. On comparison of the prevalence of sarcopenia in the four populations, we observed some differences, particularly in males. CONCLUSIONS: We have defined reference values for sarcopenia, determined by BIA, in our setting. We also observed a remarkable prevalence of sarcopenia in the healthy elderly community, especially in females, showing some differences from those in other geographical regions.

Infecciones en el anciano

A pesar de los grandes avances que ha experimentado la medicina a lo largo de las últimas décadas, las enfermedades infecciosas continúan siendo una de las principales causas de muerte en el mundo, y en nuestro entorno una causa importante de morbimortalidad, en especial en las personas mayores. Lascaracterísticas diferenciales del anciano hacen que las infecciones se manifiesten, en ocasiones, de forma peculiar, por lo que su conocimiento permitirá un mejor manejo y tratamiento que repercutirá en una mejoría en la supervivencia y en su calidad de vida (AU)

Muscle angiogenic growth factor gene responses to exercise in chronic renal failure.

Patients with chronic renal failure (CRF) have impaired exercise capacity even after erythropoietin treatment. We recently showed that although this is explained in part by reduced convective O(2) delivery to muscles, there is also an impairment of O(2) transport from muscle capillaries to the mitochondria. Given the importance of the capillary surface area for capillary mitochondrial O(2) transport and reports of reduced capillarity in CRF, we hypothesized that the angiogenic gene response to exercise is impaired in such patients. Six patients with CRF and six control subjects matched for age, size, and sedentary lifestyle exercised on a single occasion for 1 h at similar work intensities averaging 50% of maximal capacity. Exercise was confined to the knee extensors of a single leg by means of a specially designed leg-kick ergometer. A percutaneous biopsy of the quadriceps was taken within 30 min of cessation of exercise and compared with a similar biopsy done at different times without any prior exercise for 24 h. Conventional Northern blots were prepared and probed for vascular endothelial growth factor (VEGF; the major putative angiogenic growth factor for muscle), basic fibroblast growth factor (bFGF), and transforming growth factor (TGF)-beta(1). Data during both rest and exercise were successfully obtained in four subjects of each group. We also assessed muscle capillarity and mitochondrial oxidative capacity to relate to these changes. Mitochondrial oxidative capacity was normal, whereas capillary number per fiber was 12% lower than in normal subjects. VEGF mRNA abundance was increased after exercise by about one order of magnitude, with no reduction in response in CRF. For bFGF and TGF-beta(1), exercise elicited no response in either group. Reduced muscle capillarity in CRF does not, therefore, stem from reduced transcription of VEGF. To the extent that VEGF is important to exercise-induced angiogenesis in muscle, we suspect a posttranscriptional aberration in this response occurs in CRF to explain reduced capillarity.

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.

[Evaluation of functional capability after hospital admission of nonagenarian patients]. / Valoración de la capacidad funcional después de un ingreso hospitalario en pacientes nonagenarios.

BACKGROUND: Hospitalisation in nonagenarians patients may causes functional decline. PATIENTS AND METHOD: The study sample included all nonagenarians patients admitted during three months in two teaching hospitals. RESULTS: We studied 125 patients (24 [19%] died). In the remaining 101 patients the previous Barthel index (BI) was 75, at admission 33 (p < 0.0001), and at discharge 43 (p < 0.001). The decline in BI at discharge was remarkable ( 32; p < 0.0001) and persisted after 3 months (12, p < 0.003). CONCLUSION: After three months of hospitalisation in nonagenarians patients persist a functional decline.

Acute quadriplegic myopathy with myosin-deficient muscle fibres after liver transplantation: defining the clinical picture and delimiting the risk factors.

BACKGROUND: In the last few years, rare cases of acute quadriplegic myopathy (AQM*) with myosin-deficient muscle fibres occurring after solid organ transplantation has been reported. The aim of the present study was to review all cases of AQM with myosin deficient fibres seen at our institution among a large series of patients after orthotopic liver transplants (OLT), with special attention to clinical aspects and associated risk factors. Additionally, an extensive review of all ultrastructurally demonstrated cases of AQM in transplant recipients is also included. PATIENTS AND METHODS: Among patients involved in 281 consecutive liver transplant procedures performed in a 4-year period, 3 men and 1 woman developed an arreflexic, flaccid quadriplegia in the immediate postoperative period of OLT. After ruling out other causes of weakness, a muscle biopsy was performed and a loss of thick (myosin) filaments was confirmed by ultrastructural analysis in all cases. Accurate clinical, epidemiological, and evolutive data were recorded. RESULTS: Corticosteroids had been used at usual dosage given to liver transplant recipients; all four patients had several intra- and postoperative complications leading to receiving significantly higher amounts of hemoderivates, to develop renal failure in all cases, and to require a significantly higher number of reoperations within a few days after transplantation than our contemporaneous global series of liver transplant recipients. AQM patients required a significantly longer intensive care unit and hospital stay. Muscular recovery was the rule, but currently a mild myopathic gait remains in three patients. These and other reported cases of AQM do not histologically and clinically differ from AQM seen in other critically ill patients who have not had transplants. CONCLUSIONS: Patients with a complicated intra- and postoperative course of OLT who develop newly acquired acute muscle weakness should be suspected as having acute AQM with myosin-deficient muscle fibres. In this setting, differential diagnosis with other causes of weakness should be carried out, because the prognosis of this myopathy is good with early muscle rehabilitation therapy.

Clinical, histological and molecular reversibility of zidovudine myopathy.

The use of zidovudine in the treatment of human immunodeficiency virus infection has been associated with toxic mitochondrial myopathy. There are some reported cases of improvement after stopping the drug, but in only one were molecular studies performed. We therefore studied three patients with toxic AZT myopathy during AZT treatment and after drug withdrawal. Clinical complaints disappeared within the next three months after drug cessation. In all cases, histological data of mitochondrial abnormalities also disappeared. Molecular studies showed an initial depletion of the total amount of mitochondrial DNA with respect to healthy controls which was reversible after AZT withdrawal. This work demonstrates that AZT myopathy is reversible not only at a clinical and histological, but also at a molecular level.

Skeletal muscle studies in patients with HIV-related wasting syndrome.

Previous reports have suggested that HIV-related wasting syndrome may be considered as a form of myopathy. The aim of the present study was to investigate histopathological muscle changes in HIV-related wasting syndrome in order to know if there is a common substrate and whether muscle plays a primary or secondary role in its development. Patients with wasting syndrome diagnosed by Centers for Disease Control (CDC) criteria were prospectively evaluated. Clinical, analytical, nutritional, anthropometrical and muscular data were recorded. The patients were subdivided into two groups: group A was constituted by patients in whom wasting syndrome was the AIDS-defining illness, and group B by patients in whom AIDS diagnosis was previously made. In all cases muscle biopsy was performed and processed for conventional stainings and histochemical reactions. Thirty patients were included (group A, 12; group B, 18). Clinical, analytical, nutritional and anthropometrical data did not essentially differ between the two groups. All patients were malnourished with respect to controls. Histopathological findings in muscle biopsy were heterogeneous and similar in both groups, except for HIV-related myopathies, which were more frequently seen in the patients from group A (P=0.05). In five cases (17%) an unsuspected and potentially treatable myopathy was diagnosed. Patients with polyarteritis nodosa (two) or polymyositis (one) were treated with prednisone, which improved their wasting syndrome. By contrast, patients with AZT-myopathy (two) did not improve when the drug was discontinued. We conclude that in most cases the wasting syndrome cannot be considered as a true myopathy, and probably metabolic and/or nutritional factors may account for wasting development. However, in a subset of patients muscle biopsy allows the diagnosis of a treatable myopathy leading to the improvement of wasting syndrome.

Interstitial lung disease related to dermatomyositis. Comparative study with patients without lung involvement.

OBJECTIVE: To compare clinical and histopathological data and outcome of patients with dermatomyositis (DM) with and without interstitial lung disease (ILD). METHODS: Patients diagnosed with definite DM were prospectively evaluated. Clinical and analytical data were recorded and muscle biopsies were performed. In patients with respiratory symptoms an extensive pulmonary evaluation was done. RESULTS: 104 patients were diagnosed with idiopathic inflammatory myopathy, 63 with DM. Eight of the patients with DM (13%) also had associated ILD. Arthralgia and fever were more frequently seen in the ILD group and there was no associated malignant condition. Either atypical or nonspecific cutaneous lesions were more frequently seen in ILD patients. Anti Jo-1 antibodies were positive in 75% of the patients with ILD and in 3% of patients with DM without ILD (p < 0.001). Bronchoalveolar lavage measured for cell count showed an increased lymphocyte count in 3/5 cases in which this data was recorded. Lung biopsies showed interstitial pneumonitis in 2 cases and desquamative interstitial pneumonitis in one. All patients achieved complete remission of muscular involvement. With respect to lung disease, 4/8 obtained complete remission, and the other 4 showed partial improvement. No significant statistical differences in terms of survival were found between the 2 groups. CONCLUSION: ILD associated with DM represents a subgroup of DM with clinical and biological differences. However, such patients do not have poorer prognosis than patients without ILD if they are managed aggressively with immunosuppressive drugs.

Polyarteritis nodosa in human immunodeficiency virus infection: report of four cases and review of the literature.

Four patients with HIV infection were diagnosed as having panarteritis nodosa type vasculitis in muscle samples taken by biopsy. Fever, weight loss and neuromuscular symptoms were the major complaints. All but one were successfully treated with a low dose of prednisone. The other patient refused treatment, but her muscular complaints did not worsen during 9 months of follow-up. Previously reported cases in the literature are reviewed.

Symptomatic myopathies in HIV-1 infected patients untreated with antiretroviral agents--a clinico-pathological study of 30 consecutive patients.

OBJECTIVE: To assess the clinico-pathological profile of symptomatic myopathies developing in HIV-1 infected patients before use of any antiretroviral therapy. DESIGN: Prospective, cross-sectional study. SETTING: University-referral, tertiary care Hospital. PATIENTS: Thirty consecutively admitted, HIV-1 infected patients untreated with antiretrovirals and with clinically suspected skeletal myopathy or raised serum creatinkinase levels. INTERVENTIONS: Clinical assessment of muscle strength and open muscle biopsy regarding to histopathological features. RESULTS: Most of the HIV-1 infected patients were weaker when compared to the matched healthy control group. Only a few patients presented with myalgia. In one third of the cases an inflammatory condition (microvasculitis, myositis) was evident. In another third minor myopathic changes were observed, while in the remaining cases muscle biopsy was normal. Abnormal values of CK correlated poorly with pathologic diagnosis. CONCLUSIONS: In a significant proportion of HIV-1 infected symptomatic patients a specific treatment can be given when the existence of an inflammatory condition is diagnosed by muscle biopsy.

Lack of muscle toxicity with didanosine (ddI). Clinical and experimental studies.

Currently, 2',3'-dideoxyinosine (ddI) is used in AIDS therapy. To investigate the possible myotoxicity of ddI in patients infected with human immunodeficiency virus (HIV), we examined the effect of ddI in vitro in tissue cultures of skeletal muscles of rats exposed to ddI at doses equivalent to plasma ddI levels obtained in the treatment of HIV patients. Control cultures were exposed to normal saline and zidovudine (AZT). After 4 weeks no changes were noted in the ddI and normal saline cultures, but AZT cultures showed abnormal accumulation of mitochondria. The creatine kinase values in culture supernatants were all normal. We also reviewed the clinical, nutritional and biological parameters, AZT and ddI dosage, and histochemical findings in muscle specimens of 14 HIV patients receiving ddI therapy. All patients had previously received AZT. The mean cumulative dose of ddI was 91.6 gm. Two patients had myalgia, 9 muscle atrophy, and 13 weakness. All patients were malnourished. Five patients had mitochondrial myopathy related to AZT, 4 had ddI-associated neuropathy and 2 patients had only selective type 2 fiber atrophy. One patient had necrotizing vasculitis, one had scattered necrotic fibers and type 2 fiber atrophy and 2 had a normal muscle biopsy. On the basis of the results, we have been unable to implicate ddI as a cause of skeletal myopathy.

[A comparative study of the clinical and histological characteristics between classic nemaline myopathy and that associated with the human immunodeficiency virus]. / Estudio comparativo de las características clínicas e histológicas entre la miopatía nemalínica clásica y la asociada al virus de la inmunodeficiencia humana.

BACKGROUND: Several cases of nemaline myopathy (NM) have been described in patients with human immunodeficiency virus (HIV) infection. The clinical and histological characteristics of classical NM are known, but remain to be defined in HIV positive patients. METHODS: A retrospective review of the NM over a 12-year period (1982-1993) was carried out. The clinical and histological data of the classical NM were compared with those associated to the HIV. RESULTS: Eight cases of NM were collected: five in HIV negative patients (classical NM) and three in HIV positive patients. The latter patients with NM were all males with no family history of myopathy. Motor development had been normal and was not associated with disorders in other systems and the muscular symptoms were slight. On muscle biopsy a lower percentage of fibers with nemaline bodies and type 2 muscle fiber atrophy were observed, as well as slight alterations in the oxidative reactions. A second muscle biopsy performed two years after in one of these patients was normal. Females predominated in the group of HIV negative patients with family history, motor retardation during infancy and different extramuscular alterations being frequent. The muscle symptoms were more marked and severe in the two cases with respiratory musculature involvement. Histologic study demonstrated a higher percentage of nemaline bodies, predominance of type 1 muscle fiber atrophy and frequent alterations in the oxidative reactions. CONCLUSION: Nemaline myopathy presented in patients with HIV infection differs from the classically described form. The presence of nemaline bodies on muscle biopsy in HIV positive patients may be interpreted more as an epiphenomenon in relation with HIV infection than as a primary myopathy.

Idiopathic inflammatory myopathies. Immunohistochemical analysis of the major histocompatibility complex antigen expression, inflammatory infiltrate phenotype and activation cell markers.

Muscle biopsies from 21 dermatomyositis (DM) and 7 polymyositis (PM) patients were studied by conventional histoenzymatic reactions and immunoreacted with antibodies against T cells and subsets, B cells, macrophages, activated T cells, proliferating cells, transferrin and IL-2 receptors, and natural killer cells. The expression of both class I and II molecules from the major histocompatibility complex (MHC) was also tested. As control groups we used muscle biopsies from normal healthy people, from chronic alcoholics and from a cohort of HIV-1 infected patients. In DM cases, severe muscle fiber necrosis, predominant perivascular infiltrates, fibrosis and perifascicular atrophy were the rule whereas in PM cases, endomysial infiltrates and the existence of partially invaded non-necrotic cells were more frequent. Perivascular B cells were found only in some DM cases. Transferrin and IL-2 receptors, proliferating cells and NK cells were detected in some cases from both diseases. MHC class I molecules were detected mainly in perifascicular fibres in DM while in PM the stronger expression was demonstrated in non-necrotic partially invaded cells, suggesting for the latter a MHC-restricted T-cell cytotoxicity. MHC Class II molecules expression in endothelial cells was detected in a variable fashion in both diseases, probably reflecting different stages of activation of such cells.

Human immunodeficiency virus type 1 infection and myopathy: clinical relevance of zidovudine therapy.

Fifty consecutive patients infected with human immunodeficiency virus type 1 (HIV-1) were evaluated regarding the prevalence of HIV-related myopathies and the relevance of zidovudine-related mitochondrial myopathy. Disease stage, total lifetime intake of zidovudine, anthropometric and nutritional parameters, muscle strength, and histochemical and immunohistochemical findings in muscle specimens were recorded. The series was divided into two groups, patients with a total lifetime intake of zidovudine under 200 gm and those with a total lifetime intake over 200 gm. A control group included 50 healthy people matched for age and sex. HIV-related myopathy was defined by the presence of at least one of the classic pathological reactions in muscle, while zidovudine-related myopathy was defined by the presence of ragged red fibers in any percentage. Lower values of the nutritional parameters were detected in the HIV cohort, when compared with normal control values. HIV-related myopathy was detected in 13 (26%) of the 50 patients. There were no differences between groups except for the development of mitochondrial myopathy that occurred in 1 of the 26 patients in Group 1 and in 16 of the 24 in Group II. Six patients who had a total intake of more than 200 gm of zidovudine and demonstrated red ragged fibers in their muscle specimens were absolutely asymptomatic. There was a positive correlation between total intake of zidovudine and the percentage of red ragged fibers in muscle biopsy specimens.

[Toxic myopathies: clinical, etiologic, and histologic study of 74 cases]. / Miopatías tóxicas: estudio clínico, etiológico e histológico de 74 casos.

BACKGROUND: Toxic myopathies are a frequent cause of acquired myopathy in adults. The type of drugs or toxins involved varies greatly according to the epidemiologic context in which they are evaluated. An etiological, clinical and histological review of the toxic myopathies diagnosed in a group of study of muscular diseases in a third level hospital was carried out. METHODS: An eight year retrospective study of clinical and histological review of patients in whom muscle biopsy was performed to diagnose toxic myopathies in the Hospital Clinic i Provincial of Barcelona was performed. RESULTS: The most frequent causes of toxic myopathy with clinical relevance were those due to the consumption of zidovudin, ethanol, prednisone, heroin, and neuroleptic, hypolipemiant and diuretic drugs, with other causes being less frequent. In 52% of the cases an elevation of muscle enzymes (creatinkinase) was observed. In 51% it was attributed to the administration of a drug at therapeutic doses, in 34% to voluntary intoxication (attempt at autolysis or drug dependence) and in 15% the cases were accidental. The histologic study of the muscle biopsy was normal in 10% of the cases and changes indicative of a determined etiology were observed in 65% and were non-specific in the remaining 25%. More than a half of the patients were asymptomatic at 3 months of initiation of the symptoms. CONCLUSIONS: Toxic myopathies often follow a paucisymptomatic form. Most have a non-specific histologic substrate and improve upon suppression of the producing cause. The performance of muscle biopsy gives positive or negative clinically useful information in 60% of the cases, by discarding other possible causes of myopathy.

Analysis of the outcome of idiopathic inflammatory myopathies with particular emphasis on muscle capillary damage.

The objective of this study was to assess the outcome of our series of idiopathic inflammatory myopathies (IIM) with special consideration of capillary damage as a prognostic indicator. We have classified our series of patients with the diagnosis of IIM according to the presence or absence of capillary damage in muscle biopsies, and determined their outcome by means of survival analysis statistical techniques. The follow-up of our patients seems to demonstrate that the patients without capillary damage present a more indolent form of IIM, with a slower response to treatment. The presence of capillary damage indicates a more acute disease, with more morbidity and mortality, but with a faster response to immunosuppression. The presence or absence of capillary damage seems to determine two forms of IIM with differentiated outcome and prognostic.

[Seroprevalence of human immunodeficiency virus infection at an emergency service of an urban area]. / Seroprevalencia de la infección por el virus de la inmunodeficiencia humana en un servicio de urgencias de un área urbana.

BACKGROUND: Objectification of the seroprevalence of infection by the human immunodeficiency virus (HIV) among patients consulting in a hospital emergency ward of an urban area is presented. Detection of unknown carriers of HIV is also reported as well as an evaluation of the reasons for consultation by these patients in emergency wards. METHODS: A prospective study was carried out in the emergency ward of internal medicine with the random selection of 500 patients. In each case the following were evaluated: previous epidemiology of HIV, reason for consultation and clinical suspicion of HIV infection. The determination of HIV antibodies was carried out in all patients by ELISA with a further ELISA and Western blot being performed for seropositivity. RESULTS: 8.4% of the patients included were previously known carriers of HIV. In addition, 1.1% presented positive serology vs previously unknown HIV. The most frequent reason for consultation was a febrile syndrome followed by digestive and respiratory symptomatology. CONCLUSIONS: There is a high seroprevalence of HIV carriers among patients consulting in emergency wards with an unnegligible percentage of unknown carriers. The profile of previously unknown HIV carriers is that of male between 25-35 years of age consulting for a febrile syndrome of no apparent focus who pertains or has previously pertained to a risk group.