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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 379 records · Page 21Linked to original sources

Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis.

Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is characterized by a defect in bone matrix formation and mineralization without an increase in osteoid thickness. The prevalence and pathogenesis of ABD in predialysis patients is largely unknown. We prospectively studied 92 unselected predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/- 2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P < 0.05) than non-diabetic patients. However, diabetes was not clearly associated with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P = 0.1). A second bone biopsy was obtained in eleven ABD patients after a period of 16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl. Bone histology was unchanged in 10 patients, and one evolved to mild hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus 20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of steroids in the management of metastatic carcinoma to the brain. A pilot prospective trial.

This prospective study attempted to evaluate the indications for glucocorticoids which are commonly given to patients with brain metastases. Twelve patients with histologically confirmed malignancies and radiographically documented brain metastases were enrolled. Patients were scored for general performance status and neurologic function class. All subjects were given high-dose dexamethasone (HDD) for 48 hours and then randomized to receive either intermediate-dose dexamethasone (IDD) or no steroids with cranial radiotherapy. Of these 12 study patients, 3 achieved a complete response, 1 partial response, and 8 nonresponses to HDD. Seven patients had IDD, while five received no IDD. Although a small sample size prevented any statistical analysis, this study does suggest that the place for using glucocorticoids in treating patients with metastatic carcinoma to the brain remains uncertain and should be evaluated in a cooperative prospective trial.

Adult↗

Proteolipid protein gene expression in demyelination and remyelination of the central nervous system: a model for multiple sclerosis.

We asked whether nonlethal injury to the oligodendrocyte as manifested by altered myelin gene expression is an early event in the pathogenesis of demyelinating disease and subsequent remyelination. Using simultaneous in situ hybridization and immunocytochemistry, we studied expression of proteolipid protein (PLP) antigen and mRNA in spinal cords of normal adult mice and of mice infected with Theiler's virus which provides an excellent model for multiple sclerosis. Downregulation of PLP mRNA was observed within 3 days and persisted for as long as 367 days following intracerebral virus infection of SJL/J mice which are susceptible to chronic demyelination. Downregulation of myelin gene products preceded the development of prominent inflammation and demyelination observed following virus infection. In contrast, no change from control uninfected mice was observed in the expression of PLP mRNA following infection of C57BL/10SNJ mice which are resistant to demyelination. Treatment of chronically infected susceptible SJL/J mice with a regimen which promotes CNS-type (oligodendroglial) remyelination resulted in a 3- to 4-fold increase in PLP mRNA expression in oligodendrocytes. Actin mRNA expression in PLP antigen-positive cells was unchanged following TMEV-induced demyelination or remyelination indicating up- or downregulation of myelin gene products as compared to constitutively expressed actin gene. These experiments support the hypothesis that early regulation of myelin gene expression may be an important determinant in demyelination and in remyelination following nonlethal injury to oligodendrocytes.

Animals↗

Heterosexual transmission of hepatitis C virus and the possible role of coexistent human immunodeficiency virus infection in the index case. A multicentre study of 423 pairings.

OBJECTIVES: To define the role that sexual transmission plays in the spread of hepatitis C virus (HCV) infection, and to examine the influence of coexistent human immunodeficiency virus (HIV) infection on this mode of transmission. DESIGN: A multicentre, seroprevalence study of anti-HCV performed in the stable heterosexual partners (SHP) of index cases reactive for anti-HCV. SETTING: Department of Internal Medicine and Section of Gastroenterology of three University Hospitals, Spain. SUBJECTS: A total of 423 stable heterosexual partners of index cases reactive for anti-HCV. This included a group of 142 intravenous drug users (IVDU), 120 of whom were coinfected with HIV. Additionally, 2886 first-time voluntary blood donors selected at random were included to compare the prevalence of anti-HCV. MAIN OUTCOME MEASURES: Serum samples were screened for anti-HCV by a commercially available, second-generation enzyme-linked immunoassay. Tests repeatedly reactive for anti-HCV were analysed by a four-antigen, recombinant immunoblot assay. Anti-HIV was tested by enzyme immunoassay and Western blot was used for confirmation of positive cases. RESULTS: The prevalence of anti-HCV, was 7.1% in SHP and 1.2% in random donors (P < 0.001). This prevalence was higher in SHP of index cases coinfected with HIV in comparison with that shown in the SHP of index cases only reactive for the anti-HCV (9.1 vs. 6.3%; P = 0.2), particularly when a younger and more homogeneous group such as the SHP of IVDU index cases was considered alone (9.2 vs. 0%; P = 0.1). However, the SHP of IVDU index cases coinfected with HIV were almost three times more likely to be infected with HIV than HCV (24.2 vs. 9.2%). CONCLUSIONS: These data suggest that HCV infection may be sexually transmitted but with low efficiency, and this could be increased in the presence of coexistent HIV infection in the index case.

Adolescent↗

Detection of Bm86 antigen in different strains of Boophilus microplus and effectiveness of immunization with recombinant Bm86.

The control of tick populations by using conventional strategies poses several problems, including the appearance of organophosphate resistant strains, among others. The possibility of using alternative strategies such as vaccination with tick antigens has been suggested by several authors. One particular antigen (Bm86) has been described and shown to be able to induce a protective immunity against the cattle tick Boophilus microplus. In this paper we demonstrate by means of immunohistochemical staining that this antigen is conserved among several strains of this species. These results correlate with those showing that animals vaccinated with a preparation of recombinant Bm86 were protected against challenge with the four different strains tested, including one resistant to organophosphates. These results favour the immunization with recombinant Bm86 for the control of the cattle tick B. microplus.

Animals↗

Defective G2 repair in Down syndrome: effect of caffeine, adenosine and niacinamide in control and X-ray irradiated lymphocytes.

Lymphocytes from both Down syndrome (DS) patients and age-matched control donors have been investigated to identify a possible disturbance in chromosomal G2 repair. Analyses of caffeine treatments during G2 have shown that the frequency of chromosomal aberrations is higher in DS lymphocytes than in normal lymphocytes. Likewise, G2 duration is longer in DS cells than in normal cells. In both control and DS lymphocytes, caffeine treatments increase the frequencies of chromatid breakages and decrease the average of G2 duration. The reversal of the caffeine potentiation effect by adenosine and niacinamide is higher in DS cells than in normal cells. Furthermore, ATP content per cell in DS lymphocytes is one third of that estimated in normal lymphocytes. The increase of ATP level produced by adenosine or niacinamide generally correlates with the reversal of the caffeine effect on chromosome aberrations. Under the experimental conditions tested, a good negative exponential correlation between ATP level and chromosome aberrations has been detected in both normal and DS lymphocytes which were or were not X-irradiated. Finally, we postulate a decrease in G2 repair capability of DS lymphocytes caused by a low availability of ATP and/or some other factor correlating with it.

Adenosine↗

YY1 represses rat serum amyloid A1 gene transcription and is antagonized by NF-kappa B during acute-phase response.

Serum amyloid A (SAA), one of the major acute-phase proteins, increases several hundredfold in concentration in plasma following acute inflammation, primarily as a result of a 200-fold increase in its transcriptional rate. Functional analysis of the rat SAA1 promoter has identified a 65-bp cytokine response unit (CRU; positions -135 to -71) that could confer cytokine responsiveness on a heterologous promoter. Within this CRU, two cis-regulatory elements, corresponding to NF-kappa B- and C/EBP-binding sites, were found to be functionally important and exerted synergistic effects on induced SAA1 expression. In this report, we show that a third transcription factor interacts with the CRU through a region located between the NF-kappa B- and C/EBP-binding sites. On the basis of its gel mobility shift patterns, ubiquitous binding activity, sequence specificity of DNA binding, zinc-dependent binding activity, and gel mobility supershift by specific antibodies, we concluded that this factor is identical to YY1. Methylation interference studies revealed that YY1 binding sequences overlapped with those of NF-kappa B, and gel mobility studies showed that NF-kappa binding to the CRU was effectively inhibited by YY1. Consistent with its presumed antagonistic role to NF-kappa B, YY1 exerted a negative effect on SAA1 expression, whereas disruption of its binding in the promoter elevated basal and cytokine-induced activities. Furthermore, overexpression of YY1 trans-repressed SAA1 promoter activity. Thus, our results demonstrate that SAA1 expression is tightly regulated by an on-off switch of activators and repressors, presumably to ensure that it is expressed only under appropriate physiological conditions.

Acute-Phase Reaction↗

Motor response to apomorphine and levodopa in asymmetric Parkinson's disease.

The motor responses of 14 patients with Parkinson's disease (six previously untreated and eight chronically receiving levodopa) with pronounced asymmetry in the severity of motor signs between the left and right sides of the body were studied. The effects of a short (60 minutes) and a long (16-22 hours) intravenous levodopa infusion as well as of subcutaneous apomorphine (1-6 mg bolus) were assessed. Four different tapping tests were used to measure motor function. For all pharmacological tests, the more affected side showed a shorter response duration, increased latency, and greater response magnitude than the less affected side. These differences were more pronounced in those patients receiving chronic levodopa treatment. As apomorphine is not dependent on dopamine storage capacity, these findings suggest that postsynaptic mechanisms play an important part in the origin of motor fluctuations in Parkinson's disease.

Apomorphine↗

Intravenous immunoglobulin therapy in multiple sclerosis: progress from remyelination in the Theiler's virus model to a randomised, double-blind, placebo-controlled clinical trial.

No treatment has been found which reverses long-standing neurological dysfunction in patients with multiple sclerosis (MS). Observations in animal models of MS show that immunoglobulins directed against CNS components promote oligodendroglial proliferation and new myelin synthesis. Preliminary studies in inflammatory-demyelinating diseases of the human peripheral and central nervous system suggest that the repeated intravenous administration of polyclonal human immunoglobulin (IVIg) is sometimes followed by clinical improvement. A randomised, placebo-controlled, double-blind, clinical trial was designed to test the hypothesis that repeated administration of IVIg will result in a meaningful degree of recovery of apparently irreversibly lost neurological function (weakness). A total of 76 patients with MS will participate in the study. These patients had developed a fixed, apparently permanent weakness that had not improved in the preceding four to 18 months. If effective, IVIg administration may benefit the large proportion of patients with MS who have active disease by enhancing the potential for myelin repair in the evolution of the inflammatory-demyelinating lesion.

Animals↗

Promotion of remyelination by polyclonal immunoglobulin in Theiler's virus-induced demyelination and in multiple sclerosis.

Spontaneous remyelination occurs in experimental models of demyelination and in patients with multiple sclerosis, although to a limited extent. This enables the search for factors that promote remyelination. Using the Theiler's virus model of central nervous system demyelination, promotion of remyelination was observed after passive transfer of CNS-specific antiserum and transfer of CNS-specific purified immunoglobulin. Mouse polyclonal immunoglobulin from normal non-syngeneic mice, comparable with the human immunoglobulin preparation, also promotes CNS remyelination in the Theiler's virus model of multiple sclerosis. These experimental findings further bridge the gap with a pilot study that suggests clinical improvement after polyclonal immunoglobulin administration, possibly due to remyelination, in some multiple sclerosis patients with stable, steroid-unresponsive optic neuritis. In view of these experimental and clinical data, the physiological role of myelin in demyelination and remyelination is discussed, and the role of IgG solely as a deleterious molecule in the pathophysiology of multiple sclerosis and experimental demyelination is addressed.

Animals↗

Impairment, disability, and handicap in multiple sclerosis: a population-based study in Olmsted County, Minnesota.

We studied functional status of MS patients in a geographically based cohort in Olmsted County, Minnesota. The 162 definite MS patients who were alive and residing in the study area on December 1, 1991, constituted the MS prevalence disability cohort. We identified 179 cases of definite or probable MS, providing an overall sex- and age-adjusted prevalence rate of 167.5 per 100,000. Median duration of MS from onset was 15.4 years, and median age on prevalence date was 47.5 years. The Minimal Record of Disability for MS determined the degree of impairment, disability, and handicap of the entire cohort within 4 months of the prevalence date. The frequency of Expanded Disability Status Scale scores of the MS prevalence cohort showed a bimodal distribution with peaks at 1 and 6.5 (3.5 [1 to 9.5], median [range]). Approximately one-third of the cohort had marked paraparesis, paraplegia, or quadriplegia. One-fourth of all patients needed intermittent or almost constant catheterization for bladder dysfunction. Few patients (3.7%) reported severe decrease in mentation or dementia requiring supervision. Many patients (53.1%) were working full-time. Most patients (72.2%) maintained their usual financial standard without external support. There were no differences in level of impairment, disability, or handicap observed between the subgroup of 122 patients (75.3%) who are incident cases (onset of disease as residents of Olmsted County) compared with the entire prevalence cohort. This geographically based study of MS demonstrates that the functional status is more favorable than previously recognized.

Activities of Daily Living↗

Influence of deletion of T cell receptor V beta genes on the Theiler's virus model of multiple sclerosis.

To determine the role of TCR V beta genes in a model of multiple sclerosis (MS), we studied Theiler's virus infection in congenic mice with deletion of TCR V beta chromosome. Congenic mice expressing the V beta a [50% deletion of TCR V beta] or V beta c 70% deletion of TCR V beta] haplotype were generated in mice resistant [B10 (H-2b)], intermediate [B10.K (H-2k), B10.RIII (H-2r)] or susceptible [B10.S (H-2s), and B10.Q (H-2q)] to Theiler's virus induced demyelination. Deletion of TCR V beta genes (V beta a or V beta c) did not convert B10 or B10.K congenic mice to susceptibility. In contrast, congenic B10.RIII-V beta c developed prominent demyelination and 10- to 100-fold increase in virus-antigen expression in spinal cord compared to B10.RIII mice. No effect on the extent of demyelination was observed in B10.S-V beta a, B10.S-V beta c or B10.Q-V beta c mice. These experiments illustrate the critical interactions between MHC, TCR, and background genes in susceptibility to immune-mediated disease.

Animals↗

Epidemic cholera in Trujillo, Peru 1992: utility of a clinical case definition and shift in Vibrio cholerae O1 serotype.

Epidemic cholera continues in Peru. Since 1991, cholera surveillance in Peru has been based mainly on clinical recognition. To determine the proportion of reported cholera patients who actually have cholera and to evaluate the clinical case definition used in surveillance, we cultured rectal swabs from patients presenting with acute diarrhea in March 1992 in Trujillo, Peru. Of 197 patients meeting the clinical case definition, 174 (88%) had confirmed Vibrio cholerae O1 infection. In this epidemic setting, watery diarrhea of sudden onset in a person of any age presenting for treatment is highly predictive of cholera. Of note, 90% of the current V. cholerae O1 El Tor isolates were of serotype Ogawa, while a year earlier, all were of serotype Inaba.

Acute Disease↗

Left ventricular function determined by Doppler echocardiography in adolescents with type I (insulin-dependent) diabetes mellitus.

Sixty-one children with insulin-dependent diabetes mellitus and twenty-three healthy subjects were investigated. The patients with diabetes mellitus aged 4 to 20 years (13.4 +/- 4.0) had had diabetes for 1 to 16 years (6.4 +/- 3.5). There were no cardiovascular risk factor other than diabetes. Patients received no medication other than insulin. The following echocardiographic and Doppler parameters of the left ventricle were analyzed in both groups: systolic and diastolic dimensions, systolic time intervals, fractional shortening, mean velocity of circumferential fiber shortening, percent relaxation of the left ventricular posterior wall at 50% of diastole, peak velocity of early (E) and late atrial (A) mitral flow. E/A ratio, deceleration of the E-wave, and the isovolumetric relaxation time. None of the parameters were significantly different between the groups. There was no relation observed between duration of diabetes and any of the parameters analyzed. It is concluded that there is not echocardiographic data to support the concept of diabetic cardiomyopathy in adolescents with type I (insulin-dependent) diabetes mellitus.

Adolescent↗

[Cerebral abscesses. The clinical and evolutionary aspects of 17 cases treated surgically].

Seventeen cases of cerebral abscesses undergoing surgery were reviewed, underlying the characteristics of predisposing factors, infectious sources, microbiological and radiological studies, as well as clinical and evolutive aspects. The average age of the patients was 34 years, with a higher incidence in the second (35%) and sixth (22%) decades. The young patients (< 40 years) showed a greater frequency of adjacent infectious sources (83%) and the older patients (> 40 years), distant infectious sources (75%). The average time gap between the onset of symptoms and the diagnosis was 7 +/- 13 days. CAT showed in all the patients typical hypodense images with a peripheral ring; three patients had multiple abscesses and the remainder, single abscesses. In 12 patients (70.5%), microbiological cultures were positive, 3 (25%) for aerobe germs, 7 (50.3%) for anaerobe germs, 1 (8.33%) for multiple germs and 1 (8.33%) for fungi. Eleven patients underwent surgical drainage, four of which required latter exeresis. Six other patients underwent exeresis as the only surgical treatment. One patient died and the remainder showed a positive evolution. The hospital length of stay was 42.3 +/- 52.3 days. The most frequent sequela was the epilepsia present in 23.5% of the patients. Our findings are similar to the results of recent works, although in our series, there is a higher frequency of anaerobe germs. No differences were observed between the surgical techniques used nor between the past and current antibiotherapy patterns.

Adolescent↗

Monoclonal autoantibodies promote central nervous system repair in an animal model of multiple sclerosis.

Susceptible strains of mice infected intracerebrally with Theiler's murine encephalomyelitis virus develop a chronic, progressive, immune-mediated CNS demyelinating disease similar both pathologically and clinically to multiple sclerosis. Previous reports indicated that polyclonal immunoglobulins from mice injected with homogenized spinal cord promote CNS remyelination when given to SJL/J mice chronically infected with Theiler's virus. To explore further both the mechanism(s) and potential therapeutic usefulness of antibodies in the treatment of CNS demyelinating diseases, we made a panel of monoclonal antibodies derived from splenocytes of SJL/J mice injected with homogenized spinal cord, and screened them for their autoantigen-binding capability. Monoclonal IgM autoantibodies from two clones, designated SCH94.03 and SCH94.32, promoted fourfold more CNS remyelination than controls when given to chronically infected SJL/J mice. CNS remyelination, assessed morphologically by the presence of abnormally thin myelin sheaths relative to axonal diameter, correlated with the absence of clinical disease progression. In titration experiments, treatment with SCH94.03 and remyelination had a positive dose-response relationship, and as little as 10 micrograms of antibody promoted remyelination. Both SCH94.03 and SCH94.32 showed multiorgan autoreactivity, and recognized both surface and cytoplasmic determinants on glial cells. We propose that this model provides a unique system to elucidate the mechanism(s) and test the reparative potential of autoantibodies in the treatment of CNS injury.

Animals↗