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Biomedical subjects

J M Grau

Publications and source records attributed to J M Grau.

At least 19 recordsLinked to original sources
PubMed1999

Endothelial cell activation in muscle biopsy samples is related to clinical severity in human cerebral malaria.

To test the hypothesis of vascular sequestration of parasitized erythrocytes in Plasmodium falciparum malaria in vivo, a pathologic and immunohistochemical study was done of the microvasculature of skeletal muscle biopsy samples from P. falciparum malaria patients at different stages of severity. Parasitized red blood cells sequestered in the skeletal muscle vessels were observed in samples from necropsies but were never demonstrated in biopsy specimens. Vascular cell adhesion molecule-1 and E-selectin expression was consistent only in specimens from cerebral malaria patients. Samples from such patients had strong staining of the constitutive endothelial adhesion molecules tested. The staining intensity gradually decreased in samples from persons with milder forms of the disease. Four of 13 patients with severe malaria had aggregates of red blood cells, occasionally parasitized inside the muscle fibers. These data suggest that skeletal muscle biopsy could be a useful model for the study of the pathogenesis of malaria in vivo.

Adolescent↗
PubMed1998

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.

Adult↗
PubMed1998

Association between strong inflammatory response and low risk of developing visual loss and other cranial ischemic complications in giant cell (temporal) arteritis.

OBJECTIVE: To identify clinical and biochemical parameters that have good predictive value for identifying giant cell (temporal) arteritis (GCA) patients who are at high or low risk of developing cranial ischemic events. METHODS: In this multicenter study, records of patients at 3 university hospitals in Barcelona were reviewed retrospectively. Two hundred consecutive patients with biopsy-proven GCA were studied. RESULTS: Thirty-two patients developed irreversible cranial ischemic complications. The duration of clinical symptoms before diagnosis was similar in patients with and those without ischemic events. Patients with ischemic complications less frequently had fever (18.8% versus 56.9%) and weight loss (21.9% versus 62%) and more frequently had amaurosis fugax (32.3% versus 6%) and transient diplopia (15.6% versus 3.6%). Patients with ischemic events had lower erythrocyte sedimentation rates (ESR) (82.7 mm/hour versus 104.4 mm/hour) and higher concentrations of hemoglobin (12.2 gm/dl versus 10.9 gm/dl) and albumin (37.4 gm/liter versus 32.7 gm/liter). Clinical inflammatory status and biologic inflammatory status were defined empirically (clinical: fever and weight loss; biologic: ESR > or =85 mm/hour and hemoglobin < 11.0 gm/dl). Patients not showing a clinical and biologic inflammatory response were at high risk of developing ischemic events (odds ratio [OR] 5, 95% confidence interval [95% CI] 2.05-12.2). The risk was greatly reduced among patients with either a clinical (OR 0.177, 95% CI 0.052-0.605) or a biologic (OR 0.226, 95% CI 0.076-0.675) inflammatory reaction. No patient with both a clinical and a biologic response developed ischemic events. CONCLUSION: The presence of a strong acute-phase response defines a subgroup of patients at very low risk of developing cranial ischemic complications. Our findings provide a rationale for testing less aggressive treatment schedules in these individuals. Conversely, a low inflammatory response and the presence of transient cranial ischemic events provide a high risk of developing irreversible ischemic complications and require a prompt therapeutic intervention.

Aged↗
PubMed1998

Dynamic pattern of endothelial cell adhesion molecule expression in muscle and perineural vessels from patients with classic polyarteritis nodosa.

OBJECTIVE: To investigate endothelial cell adhesion molecule expression in vessels from patients with classic polyarteritis nodosa (PAN). METHODS: Frozen sections of 21 muscle and 16 nerve samples from 30 patients with biopsy-proven PAN and 12 histologically normal muscle and 2 histologically normal nerve samples from 12 controls were studied immunohistochemically, using specific monoclonal antibodies (MAb) that recognize adhesion molecules. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), and very late activation antigen 4 (VLA-4). Neutrophils were identified with a MAb recognizing neutrophil elastase. Endothelial cells were identified with the lectin ulex europaeus. RESULTS: In early lesions, expression of PECAM-1, ICAM-1, ICAM-2, and P-selectin was similar to that in control samples, and VCAM-1 and E-selectin were induced in vascular endothelium. In advanced lesions, immunostaining for adhesion molecules diminished or disappeared in luminal endothelium, whereas these molecules were clearly expressed in microvessels within and surrounding inflamed vessels. Staining in endothelia from vessels in a healing stage tended to be negative. A high proportion of infiltrating leukocytes expressed LFA-1 and VLA-4, and only a minority expressed L-selectin. No relationship between the expression pattern of adhesion molecules and clinical features, disease duration, or previous corticosteroid treatment was observed. CONCLUSION: Endothelial adhesion molecule expression in PAN is a dynamic process that varies according to the histopathologic stage of the vascular lesions. The preferential expression of constitutive and inducible adhesion molecules in microvessels suggests that angiogenesis contributes to the persistence of inflammatory infiltration in PAN.

Adult↗
PubMed1998

[Anatomopathological bases of latent ventricular dysfunction in insulin-dependent diabetics].

INTRODUCTION AND OBJECTIVES: The natural history of diabetic cardiomyopathy remains unclear, mainly due to concurrent coronary disease or hypertension. Since the presence of confounding factors is less likely in youngsters, they constitute a suitable study model to analyze early stages of diabetic cardiomyopathy. PATIENTS AND METHODS: We screened 33 young normotensive asymptomatic patients with type I diabetes mellitus. Mean age was 28 +/- 8 y (range 18 to 46 y) and there were 14 men. RESULTS: 2-D Echo showed normal left ventricular size and wall motion in all patients but one. Radionuclide basal ejection fraction was 56.5 +/- 6.6% and increased to 63 +/- 7.4% (p < 0.02) on exercise. According to Rozansky criteria, 16 patients had an abnormal response. Abnormal stress sestamibi was detected in 18 patients and only 3 had reversible defects. Coronary angiography was performed in 11 patients with at least one abnormal non-invasive study response. Coronary angiography revealed normal vessels in all patients and left anterior descending blood flow velocity (Doppler) increased 4 fold after papaverine infusion. Left ventricular biopsies showed hypertrophy (either nuclear or cellular) in 11, myocytolysis in 6, interstitial fibrosis in 9 and lipid deposits in 4. Morphometric analysis of cardiac samples comparing the diabetic group and a control group showed that the volume fraction of fibrosis (0.19 +/- 0.06 vs 0.10 +/- 0.06; p < 0.01), fiber area -mu2- (1,062 +/- 547 vs 600 +/- 167; p < 0.02) and fiber diameter -mu- (24.2 +/- 3.3 vs 15.1 +/- 3.4; p < 0.001) were higher in the former; and volume fraction of the myocytes was higher in the latter (0.71 +/- 0.006 vs 0.89 +/- 0.07; p < 0.001). CONCLUSIONS: Left ventricular dysfunction, not related to coronary atherosclerosis or small vessel disease, is frequent in asymptomatic young diabetic patients. Abnormal pathologic findings are common in the type of cell hypertrophy, interstitial fibrosis, myocytolysis and lipid deposits.

Adolescent↗
PubMed1998

Large vessel vasculitides.

During the past few years remarkable progress has been achieved in the understanding of the pathogenic mechanisms leading to vascular inflammation and injury in giant cell (temporal) arteritis. T lymphocytes are activated by specific recognition of a putative antigen residing in the arterial wall and, subsequently, activate macrophages that undergo a functional differentiation and contribute to vessel damage through various pathways. Vascular response to inflammation amplifies the inflammatory response through neovascularization and adhesion molecule expression. We are beginning to appreciate that products released by infiltrating inflammatory cells may play an important role in vessel occlusion and resulting ischemic complications. Concomitantly, synovitis underlying polymyalgia rheumatica musculoskeletal symptoms has been immunopathologically characterized and the nature of its relationship to giant cell arteritis is discussed. Although some components of the disease are highly corticosteroid responsive, other underlying pathogenic mechanisms may remain active. Long-term outcome is heterogeneous in patients with giant cell arteritis. Much less is known about the pathogenesis of Takayasu's arteritis. Recent work supports its association with HLA class I antigens, which may differ in different geographic areas or ethnic groups. Because Takayasu's disease expression may vary in different ethnic settings, this possibility has led to the proposal of new diagnostic criteria. Finally, the role of new imaging techniques in diagnosis and assessment of disease activity is discussed.

Angiography↗
PubMed1998

[Skeletal muscle graft on the terminal ileum as a substitute for ileocecal valve: experimental study].

Behavior of a free skeletal muscle graft in contact with intestinal wall is analyzed in rats. On first phase, survival of the graft muscle in relation with previous denervation is studied. Nondenervated muscles suffer necrosis and fibrosis, whereas when denervated 4 weeks before grafting, the muscles are viable. On a second phase, the grafted muscle was studied on the long term. From 8th post-transplant week on, the structural and metabolic features of the graft were similar to normal. On the third phase the efficacy of the muscle implant as a substitute of the ileocecal valve is checked. Germs on either side of the valve (ileum and cecum) are counted in normal rats, rats after valve excision and rats with substitution of the valve by a free skeletal muscle implant. There haven been significant differences between normal and no-valve rats (P < 0.001) and between no-valve and artificial valve rats (P < 0.005). There has not been significant difference between normal rats and artificial valve rats. We conclude that free skeletal muscle survives transplant to intestine, and it prevents bacterial reflux from colon to ileum.

Animals↗
PubMed1998

Histological and biochemical assessment of mitochondrial function in dermatomyositis.

OBJECTIVE: Mitochondrial dysfunction in idiopathic inflammatory myopathies (IIM) remains a controversial issue. The aim of the present study was to investigate the correlation between histological abnormalities and the biochemical function of the skeletal muscle mitochondria from patients with dermatomyositis (DM). METHOD: We evaluated 10 patients with a new diagnosis of DM and 15 healthy individuals, matched by age and gender. Muscle biopsy was routinely processed for histochemical studies and biochemical analysis of pure mitochondria. The percentages of ragged-red fibres (RRF), cytochrome c oxidase (COX)-negative fibres and succinic dehydrogenase (SDH) hyper-reactive fibres were calculated, oxygen utilization using different substrates was assessed polarographically, and enzymatic activity of individual complexes of the electron transport chain (ETC) and ATPase was measured spectrophotometrically. RESULTS: We found an increased percentage of COX-negative and SDH hyper-reactive fibres in DM patients (0.82 and 1.82%, respectively) compared to controls (0.26 and 0.22%; P < 0.05 and P = 0.001, respectively); however, oxidation rates of different substrates and enzymatic activities of ETC and ATPase did not differ significantly between both groups. CONCLUSION: The overall function of ETC from skeletal muscle mitochondria is not affected in DM.

Adenosine Triphosphatases↗
PubMed1997

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.

Adult↗
PubMed1997

["Multicore" myopathy: report of 5 cases].

Five cases (three of them from a same family) of multicore myopathy are presented. The age at diagnosis ranged from 4 to 38 years. In 2 cases muscle complaints developed early in childhood while in the remaining 3 cases raised CK serum levels lead to perform a muscle biopsy. Malignant hyperthermia occurred in a young boy among the three affected relatives. Other family members are probably affected, suggesting an autosomal dominant inheritance. In none of the patients progressive disabling myopathy has occurred after a long term follow-up. A review of the bibliography is included, and clinical and evolutive characteristics of this myopathy are commented.

Adolescent↗
PubMed1997

[Chronic fatigue syndrome: study of the clinical course of 28 cases].

BACKGROUND: Chronic fatigue syndrome (CFS) is an entity of unknown etiopathogenesis without specific markers. The diagnosis is based on clinical criteria. There are few studies evaluating the natural evolution and prognosis-related factors in CFS. OBJECTIVES: a) to evaluate the outcome of patients suffering from CFS, and b) to detect predictive factors associated with a better prognosis. MATERIAL AND METHODS: Clinical records of all patients diagnosed of CFS between January 1986 and December 1992 were retrospectively reviewed. Of these patients, we included those fulfilling the CDC criteria for CFS, with a follow-up period greater than one year. We evaluated epidemiological, clinical and evolutive data recorded by their usual physicians. Moreover, the patients were interviewed in order to know their own appreciation with respect to their current clinical status, as well as their present working situation. RESULTS: Twenty-eight patients were included in the present study. Their mean age was 38 +/- 7. Seventy-five percent of them were women. The mean time of clinical follow-up was of 3.2 +/- 1.8 years. According to evaluation, 21% of patients improved or became asymptomatic. A similar percentage (28%) of improvement was obtained from the interview. Forty-eight percent of cases had transitory or definitive laboral incapacity. Regarding to prognostic factors, we could not find any statistical differences among the analyzed variables except for marital status. In this variable, married patients had better outcome than unmarried patients. CONCLUSION: CFS is an entity with a poor outcome, since it evolves towards to chronicity in an important number of cases. In addition, strong functional disability may be present, leading frequently to laboral incapacity.

Adult↗
PubMed1997

[Cardiopulmonary resuscitation in hospitalized patients in conventional units. Prospective study of 356 consecutive cases. Commission for Care of Cardiorespiratory Arrest].

BACKGROUND: Information regarding to the system functioning and to the outcome of patients in whom cardiopulmonary resuscitation (CPR) was performed during their in hospital period in non intensive care units are essentially lacking in Spain. The objectives of the present work were: 1) to define clinical and demographic characteristics of the patients who develop cardiopulmonary arrest in general hospitalization wards; 2) to analyze immediate and late (at discharge) survival rates as well as the frequency of severe sequelae in final survivors; 3) to identify prognostic factors in relationship to survival, and 4) to detect possible internal deficiencies in the organized system of CPR. PATIENTS AND METHODS: All patients who develop cardiac and pulmonary arrest through their hospitalization in general wards during a three year period, were prospectively included. Clinical and demographic data from all the patients as well as data related to the internal functioning of the system were recorded. RESULTS: From 356 included cases, 196 (55%) were initially recovered and 128 (36%) were discharged from the hospital. Among the latter group, 12.5% remained with severely disabling neurologic damage. Age under 80 years, resuscitation maneuvers for less than 20 minutes and respiratory arrest as the ultimate event leading to cardiopulmonary arrest were associated with better prognosis. The internal deficiencies most commonly recorded in the system were false calling to the emergency team, the wrong identification of the location in the hospitalization unit and several abnormalities in the content of CPR sets. CONCLUSIONS: With the currently available organized system directed towards CPR for patients admitted in general hospitalization wards, our rates of success are good and similar to those achieved in some intensive care units. Thus, a similar policy may be encouraged in large hospitals. Since most of the detected deficiencies in internal functioning are easy to rectify, a close monitoring is warranted in order to optimize the results.

Aged↗
PubMed1997

Circulating soluble adhesion molecules in patients with classical polyarteritis nodosa.

The objective was to evaluate whether changes in circulating soluble adhesion molecule levels reflect disease activity in patients with systemic polyarteritis nodosa (PAN). A sandwich ELISA was used to measure soluble (s) intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), E-selectin, L-selectin and P-selectin in sera and plasma from 22 patients with active PAN, in sera from 13 of these patients taken serially during follow-up, and in sera from 13 healthy controls. At the time of diagnosis, sICAM-1, sVCAM-1 and sE-selectin levels (488.5 +/- 201.3, 1176.5 +/- 514.1 and 60.6 +/- 27 ng/ml, respectively) were significantly higher in patients than in controls (P < 0.0001, P = 0.001 and P = 0.003, respectively). In contrast, sL-selectin levels tended to be lower in patients than in controls. Within the first 7 days after starting treatment, there was a significant increase in sICAM-1 concentrations, which fell thereafter, but did not completely reach normal levels when patients achieved clinical remission. sE-selectin also remained elevated during follow-up. Only sVCAM-1 decreased, tending to reach normal values in inactive disease. Increased levels of sICAM-1, sVCAM-1 and sE-selectin, and decreased levels of sL-selectin, in active PAN suggest immune and endothelial stimulation during disease activity. Abnormal levels of soluble adhesion molecules in clinically inactive patients might reflect persistence of immune activation and/or endothelial cell exposure to a remaining inflammatory microenvironment.

Adult↗
PubMed1997

Clinical features in patients with permanent visual loss due to biopsy-proven giant cell arteritis.

The objective was to determine associated clinical findings in patients with visual loss due to giant cell arteritis (GCA) by means of a record review of 146 patients with biopsy-proven GCA. Twenty-three (15.75%) patients had lost vision. All of these patients complained of classical GCA cranial symptoms for an average of 1.3 months, 34.8% had an apparent isolated polymyalgia rheumatica for an average of 10.8 months and 65.2% had premonitory visual symptoms before visual loss for an average of 8.5 days. A clear delay in diagnosis and treatment was present in 15 patients (65.2%) who complained of at least two classical cranial symptoms for longer than 3 weeks and/or who had presented premonitory visual symptoms for longer than 72 h before blindness. Two additional patients lost vision while receiving standard steroid therapy. In conclusion, a high proportion of patients with permanent visual loss have a delayed diagnosis and treatment. A wider recognition of the disease would potentially reduce the prevalence of irreversible visual loss among GCA patients.

Biopsy↗