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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 451 records · Page 25Linked to original sources
PubMed1992

Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole.

A cerebral demyelinating disease developed in 3 patients during adjuvant therapy with 5-fluorouracil and levamisole for adenocarcinoma of the colon. None of the patients had evidence of metastatic disease or prior neurological disease. The duration of chemotherapy before onset of neurological symptoms ranged from 15 to 19 weeks. The total dose of 5-fluorouracil was 9.7 to 15.7 gm. The total dose of levamisole was 2.7 to 3.75 gm. Two patients presented with a subacute (2-3 weeks) progressive decline in mental status and ataxia. The third patient had two unexplained episodes of loss of consciousness. In each, magnetic resonance imaging with gadolinium demonstrated prominent multifocal enhancing white matter lesions. Cerebral biopsy was performed stereotaxically in 2 patients. The morphological features were those of active demyelinating disease. The myelin loss was associated with numerous dispersed as well as vasocentric macrophages, sparing of axons, and perivascular lymphocytic inflammation. Electron microscopy confirmed the light microscopic findings. All 3 patients improved after cessation of chemotherapy and a short course of corticosteroid therapy. Our patients represent the first reported examples of an inflammatory leukoencephalopathy associated with the administration of 5-fluorouracil and levamisole. This syndrome may represent the pathological basis for 5-fluorouracil neurotoxicity, although we cannot completely exclude the role of levamisole.

Adenocarcinoma↗
PubMed1992

Revised estimate of the prevalence of multiple sclerosis in the United States.

Using three adjustments, we have revised a 1976 prevalence count for multiple sclerosis in the United States. The adjustments were made to data from a US national survey; they used 1990 population projections from the US Bureau of the Census, and results of investigations conducted in Weld and Larimer Countries, Colorado, and Olmsted County, Minnesota. It is estimated that approximately 250,000 to 350,000 persons in the United States in 1990 had physician-diagnosed multiple sclerosis.

Age Factors↗
PubMed1992

Prediction of severe coronary artery disease using computerized ECG measurements and discriminant function analysis.

This study tested the hypothesis that discriminant function analysis of clinical and exercise-test variables including computerized ST measurements could improve the prediction of severe coronary artery disease. Secondary objectives were to demonstrate the effect of digoxin and/or resting electrocardiographic (ECG) abnormalities, and to evaluate the relative importance of ST measurements made during the recovery phase and in the three lead group areas. The design was a retrospective analysis of data collected during exercise testing and coronary angiography. The ECG data were gathered and stored in digital format on optical discs and all ST measurements were made off-line using the authors' own software. Univariate and multivariate analytic methods were used to analyze all pretest characteristics as well as hemodynamic and computerized ECG responses to exercise. A 1,000-bed Veterans Affairs Medical Center served as the setting. The study included 446 male veterans who underwent a sign or symptom limited treadmill exercise test and coronary angiography. Analysis was also performed on a subset of this population formed by excluding patients receiving digoxin or with resting ECGs exhibiting left ventricular hypertrophy or ST depression (n = 328). In the total study population, the authors derived a treadmill score using discriminant function analysis. This score included: (1) the time-slope area in lead V5 during recovery; (2) delta heart rate; (3) angina pectoris during the exercise test; and (4) presence of diagnostic Q waves on the resting ECG. This score was effective in predicting triple vessel/left main disease and outperformed exercise-induced ST depression for predicting severe coronary artery disease. After exclusion of patients with ECGs exhibiting left ventricular hypertrophy or resting ST depression and patients receiving digoxin, discriminant function analysis chose: (1) the time-slope area in lead V5 during recovery and (2) delta heart rate. Exclusion of these patients resulted in a nonsignificant decrease in specificity of all ST criteria. ST-segment amplitude or slope in lead V5 at 3.5 minutes in recovery clearly outperformed the maximal exercise measurements in both groups. Summing the depressions or selecting the most depression in the three areas (ie, lateral-V5, inferior-II, anterior-V2) did not improve test performance. Leads other than V5 did not contain significant diagnostic information. A quantitative approach to exercise testing using discriminant function analysis enhanced the tests' performance for predicting severe coronary disease. The inclusion of patients taking digoxin or with resting ECG abnormalities nonsignificantly decreases the specificity of all ST criteria.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

An improved method for carotid artery infusion without vessel occlusion.

This is an simple, non-time-consuming and advantageous procedure for catheterization and drug administration in thin arteries of small animals. The cannulation method consists of implanting polyimide-coated silica capillary tubing. To avoid vascular tear during puncture, the tubing tip is beveled. The cannula is stuck to the wall of the artery without artery ligation, using a small drop of a fast cyanoacrylate adhesive. The surgical procedure can be completed in 15 min and has the following properties: 1) it is wise but not indispensable to perfuse a solution continually through the cannula; 2) the dead volume is low and drugs may be injected in a very low solution volume; 3) it is not necessary to close the lumen of the vessel during catheterization; 4) the drug solution may be perfused into a normal bloodstream and thus its kinetic behavior is not modified by undesired cul-de-sac effects presented after artery ligation.

Animals↗
PubMed1992

Human anti-F(ab')2 antibodies show preferential reactivity for F(ab')2 molecules bearing lambda light chains.

In order to evaluate binding specificities of anti-F(ab')2 antibodies from patients with systemic lupus erythematosus (SLE) and from normal healthy controls, F(ab')2 fragments were prepared from 24 IgG myelomas with defined isoelectric points, DNA-associated idiotypes, and kappa/lambda light chain types. Using ELISA and hemagglutination assays, anti-F(ab')2 antibodies from 12 healthy controls and 29 SLE patients were observed to exhibit preferential binding (lambda > kappa) to myeloma F(ab')2 fragments composed of lambda light chains (P < 0.0001). No correlation of anti-F(ab')2 binding and presence of cationic, neutral, or anionic isoelectric points or for DNA-associated idiotypes on monoclonal F(ab')2 was detected. Anti-F(ab')2 antibodies, often elevated in SLE during remission, show preferential specificity for F(ab')2 fragments bearing lambda light chains.

Adult↗
PubMed1992

Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease.

The mechanisms of myelin injury and repair were studied in acute multiple sclerosis lesions and in a murine model of demyelination induced by a virus. Injury to oligodendrocytes resulting in degeneration of inner glial loops and inner myelin lamellae (dying-back oligodendrogliopathy) was observed by electron microscopy in brain biopsies of acute demyelinating lesions. Attempts at central nervous system remyelination as manifested by thinly myelinated axons and proliferation of oligodendrocytes were observed at the edge of many acute plaques. To develop therapeutic strategies to inhibit demyelination or promote remyelination, mice infected intracranially with Theiler's virus (a picornavirus) were studied. Experimental manipulation of Theiler's virus-infected mice by treatment during chronic demyelinating disease with immunoglobulins directed at normal spinal cord antigens or with monoclonal antibodies which deplete CD4 or CD8-positive T cells resulted in augmentation of new myelin synthesis. These observations suggest that disturbances in the myelinating function of oligodendrocytes, events not accompanied by death of these cells, may be among the earliest pathological events in multiple sclerosis. Experiments using the Theiler's virus model of demyelination indicate that manipulation of the immune response has the potential to promote central nervous system remyelination and functional recovery in multiple sclerosis.

Animals↗
PubMed1992

Dopaminergic neuron development in rats: biochemical study from prenatal life to adulthood.

Dopaminergic cell development has been studied mainly using morphological techniques and especially histofluorescence. However, the biochemical characteristics of dopamine (DA) neuron development and its physiological role during ontogeny are much less known. In the present article, the biochemical development of DA neurons, from day 13 of prenatal life to adulthood, is evaluated in Sprague-Dawley rats. DA was first detected on day 14 of gestation. The brain increase in this neurotransmitter begins on day 17 in the proencephalon and on day 18 in the mesencephalon, reaching on day 20 a level similar to that found during adulthood in the latter but not in the former. DA levels in the proencephalon rise slowly to adulthood level when compared to DA in the mesencephalon. The modifications observed in tyrosine levels are also largely similar to those reported for DA. Finally, the study of the first 48 h of life shows an increase in tyrosine levels and a decrease in dihydroxyphenylacetic acid levels (with a reduction of DA turnover) during the first 4-5 h of postnatal life. Since the serotonergic modification was completely different from DA modification, we conclude that the biochemical alteration of DA neurons during early postnatal development is specific. The present data suggest that DA neurons play different roles before and after reaching adult development.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

African horse sickness in Spain.

The aetiology, pathogenesis and epizootiology of African horse sickness (AHS) are reviewed with special reference to recent outbreaks in the Iberian peninsula. AHS is a highly fatal insect-borne viral disease of Equidae. It is caused by an Orbivirus (family Reoviridae) and nine serotypes are recognised. Outbreaks occurred in central Spain in 1987 and in southern regions of the Iberian peninsula in 1988, 1989 and 1990. All were associated with serotype 4 of the virus, whereas other occurrences of AHS outside Africa have all been caused by serotype 9. The clinical picture in the outbreaks was mainly of the acute (pulmonary) form except in 1988 when the subacute (cardiac) form of disease predominated. Several hundred horses died or were destroyed as a result of the outbreaks. Further spread was contained by a combination of slaughter of sick animals, movement controls, and vaccination which was extended over an increasingly wide area in successive years. The 1987 outbreak is believed to be associated with infected zebras imported from Africa. Possible explanations for the recurrence of disease in Spain in successive years are considered to include (a) the climatic conditions in Southern Spain, which could permit continuous vector activity, (b) the relative clinical resistance of mules and donkeys, which may permit subclinical circulation of the virus, (c) incomplete population immunity among horses due to possible gaps in the vaccination strategy.

African Horse Sickness↗
PubMed1992

Coexpression of class I major histocompatibility antigen and viral RNA in central nervous system of mice infected with Theiler's virus: a model for multiple sclerosis.

Chronic infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in central nervous system (CNS) demyelination similar to multiple sclerosis. Demyelination induced by TMEV is mediated, in part, by class I-restricted CD8+ T lymphocytes. For these T cells to function, they must recognize virus-infected CNS targets in the presence of class I major histocompatibility complex (MHC) antigen. Therefore, we studied in vivo expression of class I MHC antigen and viral antigen-RNA in prototypic mouse strains that are susceptible (SJL/J) or resistant (C57BL/10SNJ) to TMEV-induced demyelination. In brains of resistant mice, viral antigen-RNA expression peaked on day 3 after infection and was effectively diminished by day 5 such that few virus-infected cells were ever detected in the spinal cord. In contrast, susceptible mice demonstrated delay in clearance of TMEV from the brain and a subsequent increase and persistence of viral antigen-RNA in the spinal cord for as long as 277 days. Viral infection resulted in "upregulation" of class I MHC expression in the CNS. Class I MHC antigens were expressed as early as 1 day after infection in the choroid plexus of both strains of mice before detection of viral antigen or inflammation. In resistant mice, class I MHC expression predominated in the gray matter of the brain and spinal cord on day 7 after infection but returned to undetectable levels by day 28. In susceptible mice, class I MHC expression in the CNS persisted and was intense in the white matter of the spinal cord throughout chronic infection and demyelination. No class I MHC expression was detected in the CNS of uninfected mice. Coexpression of viral RNA and class I MHC antigen was demonstrated in CNS cells by using simultaneous in situ hybridization and immunoperoxidase technique. These results support the hypothesis that a class I-restricted immune response directed against virus-infected cells may be important in the mechanism of demyelination.

Animals↗
PubMed1992

Laterality, alternation, and perseveration relationships on the T-maze test.

The T-maze test has been used to study several entirely different issues: spontaneous alternation behavior (SAB), perseveration behavior (PB), and behavioral lateralization. Despite the fact that in this test the behavior studied is always the same one (i.e., side choice), the possible relationships among SAB, PB, and lateralization have not been previously evaluated. The present study investigated the relationships among these functions. The results demonstrated that (a) shock increases PB and lateralization but decreases SAB, (b) practice increases lateralization and decreases SAB but does not modify PB, and (c) there are sex differences for alternation and SAB. Because these functions are expressed by the same behavioral pattern, they must be quantified simultaneously to avoid mistaken conclusions when the T-maze test is used.

Animals↗
PubMed1992

NOVP and radiotherapy for early-staged Hodgkin's disease: an interim analysis.

Modern treatment plans for early staged Hodgkin's disease must focus on optimal disease-free survival results without laparotomy, minimal acute toxicity, and reduced long-term complications. We have treated 69 adult patients with stage I-II Hodgkin's disease, 40 of whom had bulky disease, B symptoms, or hilar disease, and 22 with stage III disease with 3 cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) and radiotherapy. Only patients with stage III1 disease involving the celiac axis without para-aortic or pelvic involvement, had to undergo laparotomy prior to treatment. Three patients did not respond to NOVP: two of these did not respond to MOPP or ABDIC, and two are currently without relapse following bone marrow transplant. With a median follow-up of 18 months, 62 with stage I-II and 19 with stage III remain without relapse, and 91 patients are alive. Tolerance to therapy was excellent with minimal nausea, myalgias, and alopecia. We conclude that this regimen for Hodgkin's disease provides good results for clinically staged I-III disease, but longer follow-up may demonstrate prognostic factors which will influence our results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Factors associated with detection of human papillomavirus E4 and L1 proteins in condylomata acuminata.

The E4 and L1 gene products of human papillomavirus (HPV) types 6 and 11 are detected in variable amounts in condylomata acuminata. To study factors associated with detection of these proteins, biopsy specimens containing HPV-6 or -11 were analyzed for E4 protein, L1 protein, and HPV copy number. Seventeen of 50 women biopsied were pregnant. Nine men were also biopsied. Both the E4 and L1 proteins were found more frequently in lesions from pregnant women than from nonpregnant women or men. Both proteins were more often detected in lesions from women than from men. E4 gene products were more often detected in lesions in which L1 protein was detected and a higher HPV copy number was present. Detection of E4 gene products correlates with the detection of L1 protein in condylomata acuminata caused by HPV-6 or -11.

Adult↗
PubMed1992

Differences in the motor response to apomorphine between untreated and fluctuating patients with Parkinson's disease.

Behavioral hyposensitivity to repeated apomorphine administration has been observed in fluctuating parkinsonian patients. To investigate whether a similar phenomenon occurs in patients never treated with levodopa, we studied the response to apomorphine in 20 de novo patients with Parkinson's disease. Six patients showed no or minimal improvement after apomorphine injections (maximal dose 3.5 mg). Fourteen patients responded and were then given up to four repeated subcutaneous injections of apomorphine [minimal effective dose (MED)]. The responses of de novo patients were compared with responses in 10 patients with motor fluctuations previously studied by the same protocol. There was no significant difference in latency and duration of motor responses after repeated apomorphine injections in de novo patients. MED was similar in de novo and fluctuating patients, but duration of improvement induced by each apomorphine bolus was longer in the de novo group. These results indicate that response duration to apomorphine is longer in previously untreated patients and that behavioral tolerance associated with pulsatile dopaminergic stimulation by apomorphine occurs mainly in patients with more advanced disease under chronic levodopa therapy.

Adult↗
PubMed1992

Pathogenesis of early and late disease in mice infected with Theiler's virus, using intratypic recombinant GDVII/DA viruses.

Intratypic recombinant Theiler's viruses prepared between GDVII and DA strains were used to identify genomic sequences important in neurovirulence, virus persistence, and demyelination and to clarify the mechanisms involved in disease induction. The coding region between 1B and 2C of the highly virulent GDVII strain contains a determinant partly responsible for neurovirulence (early paralysis and death) which correlates with elevated levels of infectious virus and the presence of virus antigen within neurons of the brain stem and gray matter of the spinal cord. Both the GDVII and the DA strains of virus contain genetic determinants for late demyelination in spinal cord. However, quantitative analysis of demyelination produced by recombinant GDVII/DA viruses suggest that multiple gene segments influence the number and extent of demyelinating lesions.

Animals↗
PubMed1992

Silent and expressed sister Mup genes are located within distinct chromatin domains: analysis by pulsed-field gel electrophoresis and polymerase chain reaction-supplemented DNase I digestion.

We have recently described a subfamily of two genes, Mup-1.5a and Mup-1.5b, which exist as a nonallelic pair in most inbred strains of mice. The Mup-1.5a and Mup-1.5b genes are more than 99.9% homologous, yet they are differentially expressed. While the Mup-1.5a gene is expressed at a high level in the submaxillary gland, the Mup-1.5b gene does not appear to be expressed either in this or in any other tissue. The Mup-1.5b gene can, however, be expressed as a transgene with the tissue specificity of its sister gene, Mup-1.5a. We have shown before that both the Mup-1.5a and Mup-1.5b genes are located on chromosome 4, closely linked to the Mup-1 locus. In this report, we demonstrate the two genes are located within distinct chromosomal domains, separated by at least 150 to 200 kb of DNA. Using a novel method, detailed in this report, we show that in the submaxillary gland, the Mup-1.5a gene is five- to sixfold more susceptible to DNase I digestion than is the Mup-1.5b gene. This finding suggests that the inactivity of the Mup-1.5b gene is brought about by long range-acting mechanisms that establish a chromatin structure in the vicinity of this gene incompatible with transcription.

Animals↗
PubMed1992

Abnormal muscle and skin mitochondria in family with myoclonus, ataxia, and deafness (May and White syndrome).

A mother and two of her daughters had deafness and cortical reflex myoclonus; the mother also had mild truncal ataxia. Muscle and skin biopsy specimens revealed abundant ragged-red fibres and abnormal mitochondria. The son of one of the daughters had sensorineural deafness. Three other grandchildren were asymptomatic. The two daughters also had diabetes mellitus, hypertension and cardiomyopathy. Another daughter died of renal failure. The mother lost her hearing in her 70s, one daughter in her 30s, and the other daughter and the grandson in their 20s. The mother has had transient episodes (24-48 hours) of temporal disorientation, severe action myoclonus, and ataxia for about eight years. This is the first reported family with inherited deafness, myoclonus, and ataxia with mitochondrial pathology.

Adolescent↗