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Biomedical subjects

J M Grau

Publications and source records attributed to J M Grau.

At least 73 records · Page 4Linked to original sources

[Critical illness polyneuropathy].

Critical illness polyneuropathy (CIP) is a recently identified entity for which reliable data is unavailable and of which the prevalence is unknown. Although the percentage of patients suffering CIP is low, more cases, including subclinical ones, are likely to be detected through the use of electroneurography. Any aged patient may be affected by CIP. It usually occurs a long stay in the intensive care unit (ICU) and is generally associated with sepsis, severe trauma and so-called multiple organ failure. The main clinical sign is distal weakness in the lower extremeties, although finding one or more of the following signs is not uncommon: quadriparesis, quadriplegia, difficult weaning, loss of osteo-tendon reflexes and muscle atrophy. The pathophysiology of CIP is unknown, although such mechanisms as cell dehydration, increased proteolysis and the activation of certain cytokins have been suggested. Before diagnosing CIP, other neuromuscle diseases and several recently described toxic myopathies must be ruled out. Electroneuromyographic study of axonal lesions may be of great utility, whereas analyses have low specificity. Histologic examination, when possible, allows axonal lesions (but never demyelinization) to be observed along with the non specific changes of myopathy. Although no specific treatment is available, the long-term prognosis is good if the underlying disease that gave rise to ICU admission is controlled, and if rehabilitation therapy is started early.

Age Factors↗

Leucocyte/endothelial cell adhesion receptors in muscle biopsies from patients with idiopathic inflammatory myopathies (IIM).

Interactions between leucocytes and endothelial cells through specific adhesion receptors play an increasingly recognized crucial role in the development of inflammatory infiltrates in chronic inflammatory diseases. In this study we investigated adhesion molecule expression in muscle biopsies from 18 dermatomyositis, six polymyositis, five inclusion-body myositis patients and from eight normal controls. Immunohistochemical detection of leucocyte integrins LFA-1 and VLA-4, their endothelial counter-receptors intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and the endothelial cell markers CD31 and von Willebrand factor-related antigen (vWFAg) was performed using specific MoAbs and an alkaline phosphatase anti-alkaline phosphatase technique. ICAM-1 expression was up-regulated and VCAM-1 induced in muscle capillaries of dermatomyositis samples. In both dermatomyositis and polymyositis, endothelial cells from vessels surrounded by inflammatory infiltrates strongly expressed ICAM-1 and VCAM-1. Infiltrating leucocytes were intensively LFA-1- and VLA-4-positive. These data suggest that leucocyte/endothelial cell interactions mediated by the receptor/ligand pairs LFA-1/ICAM-1 and VLA-4/VCAM-1 actively participate in the development of muscle inflammatory infiltrates in the major inflammatory myopathies. In addition, ICAM-1 and VCAM-1 over-expression by capillary endothelial cells in dermatomyositis supports the hypothesis that capillary activation and/or injury is a major feature in this disease.

Adolescent↗

[A comparative study of the clinical and histological characteristics between classic nemaline myopathy and that associated with the human immunodeficiency virus].

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.

Adult↗

[Progressive external ophthalmoplegia and the Kearns-Sayre syndrome: a clinical and molecular study of 6 cases].

The Kearns-Sayre syndrome (KSS) associates progressive external ophthalmoplegia initiating prior to the age of 20 years and pigmentary retinitis with a series of other heterogeneous clinical manifestations. The incomplete syndrome is usually denominated progressive external ophthalmoplegia (PEO)-plus which is a sporadically appearing mitochondrial cytopathy associated with large deletions of a variable proportion of mitochondrial DNA (mtDNA) molecules. Six patients with PEO-plus/KSS in whom muscle biopsy was performed following a complete clinical study are described. The muscle was processed by conventional histochemical techniques, electron microscopy, and genetic study (Southern transference, polymerase chain reaction, restriction cartography and both manual and automatic sequencing). The percentage of mutated mtDNA molecules for each patient was obtained by densitometry. The 6 patients presented multiorganic clinical manifestations characteristics of most mitochondrial diseases. The presence of destructured red fibers were observed in all the biopsies. All the patients presented a deletion in the mtDNA of a size between 4,861 to 7,437 base pairs (bp). All the deletions appeared flanked by direct repetitions from 4 to 13 bp and one also presented inverse repetitions from 5 to 6 bp in the zone next to the rupture point. In the 6 cases heteroplasmia was observed with a variable percentage of deleted molecules from 23 to 56%. The molecular basis of progressive external ophthalmoplegia-plus/Kearns-Sayre syndrome appears to be the existence of sole, large deletions in the mitochondrial DNA with the varying in location and percentage conditioning the appearance of different phenotypes similar among themselves. The 7,437 base pair deletion was the most frequently observed in the patients analyzed.

Adolescent↗

Membrane attack complex deposits in cutaneous lesions of dermatomyositis.

BACKGROUND AND DESIGN: The presence of membrane attack complex of complement (MAC) deposits in the intramuscular vasculature of biopsy specimens taken from patients with dermatomyositis (DM) has been implicated in the pathogenesis of this myopathy. The purpose of this study was to investigate the presence of MAC deposition in the skin lesions of patients with DM. Using immunohistochemical methods, we examined 22 biopsy specimens from lesional skin, six biopsy specimens from uninvolved skin, and 12 muscle biopsy specimens from patients with DM for the presence of MAC and vitronectin and CD59, two regulatory proteins of complement. RESULTS: The deposition of MAC was demonstrated in a large percentage of biopsy specimens obtained from the lesional skin of patients with DM. Deposits were found along the dermoepidermal junction in 19 (86%) of 22 biopsy specimens. Deposits on the vessel walls of the dermis were found in 17 (77%) of 22 biopsy specimens; but only in six of these biopsy specimens (27%) were deposits present in more than 10% of blood vessels. In contrast, deposits along the dermoepidermal junction and the vessel walls of the dermis were absent in specimens from uninvolved skin. In 12 muscle biopsy specimens obtained simultaneously from these patients, MAC deposits were found on the vessel walls in nine (75%), but only in six (50%) were deposits found in more than 10% of the intramuscular vessels. The pattern of vitronectin immunoreactivity in skin and muscle biopsy specimens obtained from patients with DM was similar to MAC deposits. The expression of CD59 was normal in all skin and muscle biopsy specimens. CONCLUSIONS: The deposition of MAC was found in a high percentage of biopsy specimens from the lesional skin of patients with DM; it was absent in uninvolved skin. These findings suggest that the complement system may be involved in the pathogenesis of the skin lesions of DM.

Adolescent↗

Acute axonal Guillain-Barré syndrome with IgG antibodies against motor axons following parenteral gangliosides.

We studied 7 patients with an acute motor axonal Guillain-Barré syndrome (GBS), manifested 5 to 15 days after parenteral injection of a commercial ganglioside preparation given for nonspecific pain syndromes. The serum IgG and IgM antibody response to ganglioside was studied serially and the recognition of epitopes on the peripheral nerves and motor end-plates was examined using biotinylated IgG extracted from the patient's serum. Sera from 8 patients treated with the same ganglioside preparation who did not develop neuropathy and from 25 patients with classic GBS never treated with gangliosides were studied concurrently. All patients with ganglioside-related GBS had a rather severe axonal degeneration, incomplete recovery, and high IgG, but not IgM, antiganglioside antibody titers, ranging from 1:320 to 1:10,240. Seven (28%) of the 25 GBS patients had IgG antibody titers, ranging from 1:160 to 1:10,240. None of the ganglioside-treated patients who did not develop GBS and none of the 50 disease control subjects had IgG GM1 antibodies. Purified IgG from the patients with high GM1, antibodies, but not from the others, recognized epitopes at the nodes of Ranvier and the distal motor nerve terminals at the end-plate. We conclude that exogenous ganglioside injections can be immunogenic, triggering IgG antiganglioside antibodies with specificity for motor nerve-terminals. In some patients with axonal GBS such antibodies may be markers or mediators of axonal involvement.

Antibodies↗

Significance of type II fiber atrophy in chronic alcoholic myopathy.

To determine the significance of type II fiber atrophy in alcoholic myopathy and its relationship with ethanol-related diseases a prospective study was carried out in 100 chronic alcoholics who showed clinical suspicion of skeletal myopathy. Measurement of muscle strength, laboratory analysis, nutritional assessment and open biopsy of deltoid muscle were performed in each case, as well as electrophysiological testing for peripheral neuropathy. Hepatic ultrasonography and liver biopsy, echocardiography and radionuclide cardiac scanning were carried out in selected subjects. According to histomorphometric analysis, type II fiber atrophy was found in 33 cases (33%), being selective for type II B fiber in 23 (70%). Skeletal myopathy was diagnosed in 61 cases, alcoholic cardiomyopathy in 26, peripheral neuropathy in 23 and cirrhosis in 12. Patients with type II fiber atrophy had a significantly higher total lifetime dose of ethanol, presented a greater incidence of skeletal myopathy and peripheral neuropathy, and exhibited significantly lower values of percentage of ideal body weight and lean body mass than their counterparts. However, the only independent factors for developing type II fiber atrophy were the coexistence of caloric malnutrition (p = 0.004) and the presence of skeletal myopathy (p = 0.043). Selective type II fiber atrophy is a non-specific finding in alcohol-induced muscle damage appearing, overall, in the patients with caloric malnutrition as well as in those with histologic evidence of myopathy.

Adult↗

Effect of chronic alcoholism on human muscle glycogen and glucose metabolism.

To determine the effect of alcohol on carbohydrate metabolism, 48 human muscle biopsies from chronic alcoholics were studied. The level of glycogen and the activities of the enzymes catalyzing glycogen and glucose metabolism were analyzed. Chronic alcohol intake produced an increase in glycogen concentration and a decrease in pyruvate kinase activity before the first signs of myopathy appeared. When myopathy was present, glycogen decreased. These changes may contribute to the decline in skeletal muscle performance in these patients.

Adult↗

Abnormal sensory nerve conduction in multifocal demyelinating neuropathy with persistent conduction block.

Two patients exhibited chronic, slightly asymmetric weakness and wasting with fasciculations of the upper limb and hand muscles. Motor nerve conduction studies showed features of multifocal conduction block in nerve segments other than those usually involved in entrapment syndromes. The F wave was markedly delayed in the median and ulnar nerves. Transcranial cortical and cervical root magnetic stimulation showed bilaterally delayed thenar responses with normal central conduction time. Needle electromyography demonstrated a chronic denervation pattern with large polyphasic motor units in several muscles of the upper limbs. Sensory symptoms were mild and limited to paresthesias in the fingertips. Sensory nerve conduction velocity and sensory nerve action potential amplitudes were normal in elbow-to-wrist and wrist-to-finger segments of the median and ulnar nerves, but there was a delayed cortical response and unrecognizable Erb's point and cervical responses in the somatosensory evoked potentials to median nerve electrical stimulation. Electrophysiologic examination was normal in most nerves of the lower limbs. These two patients, meeting clinical and electrophysiologic criteria of multifocal neuropathy with conduction block, demonstrate that sensory fibers may also be involved in this syndrome.

Action Potentials↗

[Cerebral vascular complications in Conn's disease: report of two cases].

We report two patients with arterial hypertension (AHT) secondary to Conn's disease and cerebral vascular accident (CVA). Both had histories of long-standing AHT that had been poorly controlled with drugs, though no complications had developed up to the time of presentation. One CVA was a hemorrhage in the right capsular-lenticular region and the other was a cerebral ischemic infarction. Blood tests done upon admission found low potassium levels. The final clinical-pathological diagnosis was primary hyperaldosteronism secondary to suprarenal adenoma. After laparoscopic surgery AHT reverted to normal in one patient. Although Conn's disease is a rare cause of AHT, early diagnosis and treatment can provide a cure and prevent the development of severe complications.

Adenoma↗

[Acute myopathy related to the administration of glucocorticoids and neuromuscular blockers].

Two cases of acute myopathy following the administration of high doses of glucocorticoids in patients requiring mechanical ventilation and who were also administered neuromuscular blockers are presented. The patients were two women of 57 and 73 years of age. The doses of methylprednisolone administered were of 810 and 1,180 mg during the first 7 and 17 days, respectively. With regard to the total doses of neuromuscular blockers the first patient received 76 mg of pancuronium over 4 days while the second received 1,180 mg of atracurium over 17 days. This myopathy is characterized by a clinical and histological picture which differs from that associated to the chronic use of glucocorticoids being attributed to a toxic action of these drugs somewhat favored by immobilization due to the use of neuromuscular blockers. Given the lack of references in the literature on this entity in Spain a review was undertaken with the need for correct early diagnosis allowing differentiation from other causes of weakness such as ischemia of the cerebral trunk, polyradiculoneuritis and polyneuritis of critical patients being of note. Muscular biopsy is therefore very useful since very suggestive signs of this myopathy may be found. The disease is reversible with no effective treatment. An early rehabilitation program is the only method of shortening the convalescence period.

Acute Disease↗

The relation of alcoholic myopathy to cardiomyopathy.

OBJECTIVE: To evaluate the relation between skeletal muscle disease (myopathy) and degenerative changes in cardiac muscle (cardiomyopathy) in patients with chronic alcoholism. DESIGN: A cross-sectional study. SETTING: University medical center. PARTICIPANTS: Group A included 24 patients with chronic alcoholism who had dilated cardiomyopathy; group B, 24 patients with chronic alcoholism who had normal cardiac function; group C, 12 patients with dilated cardiomyopathy because of coronary heart disease; group D, 12 patients with idiopathic dilated cardiomyopathy; group E, 24 normal participants; and group F, 5 young men who died suddenly in traffic accidents. MEASUREMENTS: Clinical assessment of muscle strength, echocardiography, radionuclide cardiac angiography (groups A to E), muscle biopsy (groups A, B, E), endomyocardial biopsy of the left ventricle (group A), and examination of postmortem specimens of the left ventricle (group F). RESULTS: Alcoholic patients with cardiomyopathy had less muscle strength than did alcoholic patients with normal cardiac function, patients with idiopathic dilated cardiomyopathy, and patients with coronary heart disease (all P < 0.01). Among alcoholic patients with cardiomyopathy, 20 of 24 (83%) had histologic findings of skeletal myopathy compared with 1 of 24 (4%) alcoholic patients with normal cardiac function (P < 0.001). Interstitial fibrosis occurred in all cardiac biopsy specimens, hypertrophy of the myocytes occurred in 95%, and myocytolysis occurred in 83%. Those patients with more severe cellular hypertrophy and interstitial fibrosis of the myocardium had a greater decrease in deltoid muscle strength and had worse histologic myopathy. CONCLUSIONS: Diseases of skeletal and cardiac muscle in patients with chronic alcoholism are clinically and histologically related. The presence of muscle weakness in an alcoholic person suggests the likelihood of an accompanying cardiomyopathic abnormality.

Adult↗

Immunohistochemical characterization of inflammatory cells and immunologic activation markers in muscle and nerve biopsy specimens from patients with systemic polyarteritis nodosa.

OBJECTIVE: To investigate the phenotype of infiltrating cells in classic lesions of polyarteritis nodosa (PAN). METHODS: Twenty-one muscle and 10 sural nerve biopsy samples from 24 patients with systemic PAN were studied using avidin-biotin-peroxidase and alkaline phosphatase-anti-alkaline phosphatase immunohistochemical techniques. RESULTS: The inflammatory infiltrates consisted mainly of macrophages (41%) and T lymphocytes (41%), particularly of the CD4+ subset. Granulocytes were present in varying quantities (0-45%) and were more abundant in heavily infiltrated vessels and in those with fibrinoid necrosis. Dendritic cells could be identified in 4 samples. Proliferating and interleukin-2 receptor-expressing cells, present in 71% and 79% of the patients, respectively, were more frequent in untreated patients. CONCLUSION: T cell-mediated immune mechanisms may play a role in the development and perpetuation of PAN lesions.

Adult↗