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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 91 records · Page 5Linked to original sources
PubMed1998

Review of psychosocial stress and asthma: an integrated biopsychosocial approach.

Environmental stressors may impact asthma morbidity through neuroimmunological mechanisms which are adversely impacted and/or buffered y social networks, social support, and psychological functioning. In addition, life stress may impact on health beliefs and behaviours that may affect asthma management. Whereas earlier psychosomatic models have supported a role for psychological stress in contributing to variable asthma morbidity among those with existing disease, a growing appreciation of the interactions between behavioural, neural, endocrine, and immune processes suggest a role for these psychosocial factors in the genesis of asthma as well. While a causal link between stress and asthma has not bee established, this review provides a framework in which we can begin to see links between these systems that might provide new insights to guide future explorations. The complexity of these interactions underscore the need for a multidisciplinary approach which combines the idea that the origin of asthma is purely psychogenic in nature with the antithetical consideration that the biological aspects are all important. These distinctions are artificial, and future research that synthesizes biological, psychological, sociocultural, and family parameters is urgently needed to further our understanding of the rising burden of asthma.

Asthma↗
PubMed1998

A unique population of circulating autoantibodies promotes central nervous system remyelination.

In previous studies we demonstrated that the humoral immune response directed against unique central nervous system (CNS) antigens enhanced CNS remyelination in the Theiler's virus experimental model of multiple sclerosis (MS). To expand on this observation, a mouse IgM kappa monoclonal antibody (mAb) which enhances CNS remyelination, was raised against normal mouse spinal cord homogenate. Characterization of this mAb revealed that it is polyreactive towards variety of intracellular antigens but also reacts to an unidentified surface antigen on oligodendrocytes. The mAb is encoded by germline immunoglobulin genes without somatic mutations consistent with the observation that it is a natural autoantibody. Recently we generated another mouse IgM kappa mAb raised against normal spinal cord homogenate, which also promotes CNS remyelination. Further characterization revealed that both mAbs which promote remyelination have similar binding characteristics. Conventionally Abs which recognize normal CNS components, especially oligodendrocytes or myelin, have been considered to be a disease marker or be involved in the pathogenesis of MS. However, we have identified a unique population of circulating autoantibodies which are beneficial for myelin repair. Therefore this observation indicates the need to reevaluate autoantibody production against myelin components in CSF and blood as markers of disease activity versus repair in MS.

Animals↗
PubMed1998

Second-line therapy with paclitaxel and carboplatin for recurrent disease following first-line therapy with paclitaxel and platinum in ovarian or peritoneal carcinoma.

PURPOSE: The combination of paclitaxel and a platinum compound is the most active first-line regimen for advanced ovarian carcinoma. The current study was undertaken to evaluate this combination in the re-treatment of patients with ovarian or peritoneal carcinoma who had disease recurrence > or = 6 months following this combination. METHODS: Twenty-five patients with recurrent ovarian or peritoneal carcinoma > or = 6 months after a complete clinical response with first-line paclitaxel and platinum chemotherapy were studied. Recurrent disease was documented by computed tomography (CT), elevated CA 125 level, or surgical findings. Second-line chemotherapy consisted of paclitaxel 135 mg/m2 as a 24 hour infusion and carboplatin at an area under the concentration-time curve (AUC) of 5 to 6 every 21 days. Response to therapy was classified as measurable or assessable. RESULTS: The median time to recurrence after first-line therapy was 10 months (range, 6 to 30). Among 20 measurable and assessable patients, 14 (70%) demonstrated a complete clinical response and four (20%) a partial clinical response. The response rate with measurable disease was 91% and with assessable disease was 89%. The median progression-free interval for all patients was 9.0+ months (range, 2 to 15). The median progression-free interval for patients with measurable or assessable disease was 9.0+ months and for nonassessable disease was 7.0+ months. Fifteen patients (60%) have developed recurrence after secondary therapy at a median interval of 9.0 months (range, 2 to 15). Only two patients have died with a median survival after secondary therapy of 10.0+ months (range, 2.0 to 21.0+). CONCLUSION: The use of this combination, in this sensitive population, has a high response rate and long progression-free interval. In a chemotherapy-sensitive population, the activity of alternative second-line agents must be interpreted with this perspective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Health care utilization in multiple sclerosis: a population-based study in Olmsted County, MN.

OBJECTIVE: The authors sought to determine acute ambulatory- and hospital-billed charges for the Olmsted County, Minnesota Multiple Sclerosis (MS) Disability Prevalence Cohort and compare them to those incurred by the general population. METHODS: Billed charges for 155 people with clinically definite or laboratory-supported MS were compared with those of age- and gender-matched non-MS controls. Billing data, including all inpatient and outpatient acute and rehabilitative medical care charges over a 5-year period surrounding a December 1, 1991 prevalence date, were analyzed. Data were correlated with level of disability using the Minimal Record of Disability for MS. RESULTS: Median total annual billed charges for most individuals with MS, including those with less severe ($1,277) and relapsing-remitting illness ($1,348), did not differ from those for controls ($1,327, p=0.075). Only those with severe MS (22.6%) had median annual medical charges higher than controls ($5,440, p < 0.001). Male patients with MS had higher median annual total charges ($2,353) than male controls ($762, p=0.003). Total charges for female patients with MS ($1,440) were not different from those for female controls ($1469). Median annual outpatient charges were 15% more for the MS group ($1,418) than for controls ($1,231). Patients with MS had a mean of 0.2 hospital admissions annually compared with 0.1 annual admissions per control patient. Among variables collected on persons with MS, the Expanded Disability Status Scale was the strongest predictor of level of charges (p < 0.001). CONCLUSION: Acute ambulatory- and hospital-billed charges for most patients with MS do not differ from those of the general population.

Cohort Studies↗
PubMed1998

Major histocompatibility complex class II alleles and the course and outcome of MS: a population-based study.

BACKGROUND: The major histocompatibility complex (MHC) has been consistently associated with susceptibility to MS and the course of several other human autoimmune diseases. A putative association between the course and severity of MS and the MHC remains controversial. METHODS: DR and DQ genotyping by either restriction fragment length polymorphism or sequence-specific PCR-based typing in 119 patients representing 73.4% of the population with MS evaluated in a cross-sectional disability survey and 100 healthy controls from Olmsted County, Minnesota. RESULTS: We found a positive association between MS susceptibility and the DR15-DQ6 and DR13-DQ7 haplotypes, and we found a negative association with the DR1-DQ5 haplotype. We found a trend to a positive association of primary progressive MS with DR4-DQ8 and DR1-DQ5 and an association of "bout onset" MS with DR17-DQ2. We did not find an association with disease severity, as defined by EDSS/duration. CONCLUSION: Lack of consistency between different studies may be due to regional variation in MS and limitations of power but likely indicate a minor effect of MHC class II genes on the course and severity of MS.

Adult↗
PubMed1998

High phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro.

Phosphate retention plays an important role in the pathogenesis of secondary hyperparathyroidism in patients with renal failure. In in vitro studies, high extracellular phosphate levels directly stimulate PTH secretion in rat and bovine parathyroid tissue. The present study evaluates the effect of high phosphate levels on the secretion of PTH and the production of prepro PTH mRNA in human hyperplastic parathyroid glands. The study includes parathyroid glands obtained from patients with primary adenomas and from hemodialysis and kidney-transplant patients with diffuse and nodular secondary hyperplasia. The experiments were performed in vitro using small pieces of parathyroid tissue. The ability of high calcium levels to decrease PTH secretion was less in adenomas than in secondary hyperplasia; among the secondary hyperplasia, nodular was less responsive to an increase in calcium than diffuse hyperplasia. In diffuse hyperplasia, PTH secretion was increased in response to 3 and 4 mM phosphate compared with 2 mM phosphate, despite a high calcium concentration in the medium; prepro PTH mRNA levels increased after incubation in 4 mM phosphate. Similar results were obtained with nodular hyperplasia, except that the elevation of PTH secretion in response to 3 mM phosphate did not attain statistical significance. In adenomas, high calcium concentrations (1.5 mM) did not result in inhibition of PTH secretion, independent of the phosphate concentration, and the prepro PTH mRNA was not significantly increased by high phosphate levels. In conclusion, first, the PTH secretory response to an increase in calcium concentration is less in nodular than diffuse hyperplasia; second, high phosphate levels directly affect PTH secretion and gene expression in patients with advanced secondary hyperparathyroidism.

Analysis of Variance↗
PubMed1998

Acute disseminated encephalomyelitis after accidental injection of a hog vaccine: successful treatment with plasmapheresis.

Acute disseminated encephalomyelitis, an inflammatory demyelinating disease of the central nervous system, can occur after viral infections or vaccinations. We report the clinical and neuroimaging findings in a 52-year-old man in whom acute disseminated encephalomyelitis developed after accidental self-injection of an industrial hog vaccine. The protracted and progressive clinical course, despite high-dose parenteral corticosteroid therapy, was altered by aggressive plasmapheresis.

Accidents, Occupational↗
PubMed1998

Epstein-Barr virus and oral squamous cell carcinoma in patients without HIV infection: viral detection by polymerase chain reaction.

In order to test the hypothesis that Epstein-Barr virus (EBV) may be a cofactor for oral squamous cell carcinoma (OSCC) the authors evaluated tumour cells from OSCC of 108 patients without HIV infection, for the presence of EBV DNA by polymerase chain reaction. The sequences of oligonucleotides used in the amplification and hybridization included a set for the DNA polymerase region. The amplification was detected using an ELISA assay with peroxidase. EBV DNA was detected in 17.59% of the tumours. Inhibition studies showed that the ability to detect EBV DNA was not affected by the pathological material, suggesting that the negative PCR results in these samples were not caused by PCR inhibitors in the biopsy. Results revealed that 63.1% of the tumours (12 cases) were DNA positive affecting the lateral margin of the tongue, and were statistically significant (p < 0.001; chi 2). In the pool of tumours with EBV DNA only 26.3% (5 of 19 cases) were well differentiated OSCCs whereas the remaining 73.7% (14 of 19 cases) were moderately and poorly differentiated OSCCs, with a statistical significance of p = 0.08; chi 2. This study suggests a relationship between OSCC and EBV.

Adult↗
PubMed1998

Psychosocial adjustment among Central American immigrants with disabilities: an exploratory study.

This is an exploratory study that investigated factors influencing the psychosocial adjustment of Central American immigrants with disabilities. The relationships between stress, and perception of disability severity and (a) depression and (b) anxiety were assessed. Furthermore, this study investigated whether social support moderated the impact of stress and severity of disability on depression and anxiety. Stress, severity of disability, and social support explained a high percentage (54%) of the variance in depression. High levels of stress, increased perceptions of severity of disability, and low social support were associated with increased depression. The interactions between support and stress and between support and disability severity did not significantly add to the original model which predicted depression. Main effects were found for stress, disability severity, and the interaction between support and disability severity. Stress and social support significantly accounted for 31% of the variance in anxiety. Increased stress and decreased social support were associated with greater levels of anxiety. The interaction between support and stress did not significantly predict anxiety. Implications of the study in terms of future research and intervention programs targeting mental health outcomes for Latino immigrants with disabilities are discussed.

Acculturation↗
PubMed1998

Teaching community-oriented primary care through longitudinal group projects.

BACKGROUND: Though community-oriented primary care (COPC) has been advocated as an effective way of addressing health problems of communities, it is neither widely understood nor frequently practiced. Because COPC requires an extended period of time, as well as an approach and skills not generally learned in medical training, effectively incorporating COPC training into medical education is difficult and not frequently attempted. This paper describes a COPC curriculum for family practice residents based on required participation in a longitudinal group project. METHODS: Residents participated in successive groups that completed a COPC project over a 2-year period. Twenty-two of 26 PGY-2 residents completed an attitude and knowledge test before and after participation in the curriculum. A qualitative evaluation of the curriculum was also performed. RESULTS: Pretest and posttest responses showed significant improvement in residents' knowledge about COPC and a small but significant decline in attitudes toward COPC. Residents' reactions to the curriculum in the qualitative evaluation were both positive and negative. Residents enjoyed the group process and found it intellectually stimulating. Many reported, however, that they did not feel ownership of the project, that working through the four-step systematic COPC process was slow and cumbersome, and that they had learned only part of the COPC process. Residents consistently reported becoming more aware of the importance of discussing the focus of the project (i.e., childhood discipline or domestic violence) with their patients and feeling more comfortable initiating such discussions. CONCLUSIONS: A COPC curriculum based on required participation in a 2-year group project promoted completion of substantial projects. There were trade-offs in resident experience, including loss of continuity for individual residents. Effectively teaching COPC and engaging residents in community-oriented activities remains a challenge.

Community Health Services↗
PubMed1998

Computed tomography, magnetic resonance imaging and positron emission tomography in non-Hodgkin's lymphoma.

Certain aspects of the use of CT, MR imaging and PET were evaluated in patients with non-Hodgkin's lymphoma (NHL) with the aim of determining whether these methods may provide practical guidance for improving the management of these patients. Subjective evaluation of the tumor pattern on CT images, and quantification of tracer uptake using 11C methionine (11C Met) and [18F] fluorodeoxyglucose (18FDG) PET in patients with NHL, were performed to determine their relations to malignancy grade. An inhomogeneous tumor pattern (I) was found on CT in 75% of high-grade tumors, whereas 68% of low-grade tumors were homogeneous (H). Sixteen (94%) of the 17 tumors with a severely inhomogeneous pattern (I) were high-grade NHL, while 22 (72%) of the 29 homogeneous tumors (H) were low-grade. All tumors were clearly visualized with both 11C Met and 18FDG PET. The uptake values for 18FDG were significantly-higher in high- than in low-grade tumors, while no significant differences between the prognostic groups were found for 11C Met. A subjective evaluation of the tumor pattern on CT and on MR images was performed. An inhomogeneity index (IH8) was also used in MR images to make a quantitative assessment of the degree of inhomogeneity to determine their relation to prognosis. Patients with localized NHL, treated with radiotherapy, had an excellent prognosis irrespective of the degree of inhomogeneity, while patients with generalized disease, treated with chemotherapy, had a poor prognosis if the tumors were heterogeneous. Among chemotherapy-treated patients, all 9 patients with high IH8 values (> 2.56) on MR images and 9 out of 11 patients with severe inhomogeneities on CT images died. All patients with gastric NHL except for one patient with low-grade NHL of the MALT type displayed high 18FDG uptake at PET corresponding to the pathological findings at endoscopy and/or CT. 18FDG correctly excluded gastric NHL in a patient with benign gastric ulcer, but was unable to discriminate between gastric NHL and gastric carcinoma. The results suggest that 18FDG PET may demonstrate the extension of NHL in the gastric wall more accurately than CT and endoscopy. The prognostic importance of the size of a residual mass after completion of chemotherapy, and of tumor regression rates during chemotherapy, was evaluated in patients with high-grade NHL. Neither a large tumor size before treatment nor a large residual tumor after treatment correlated with relapse. It appears, however, as if the response rate halfway through the therapy may predict the recurrence rate, although statistical significance was not reached.

Adolescent↗
PubMed1997

Rapid movement of newly synthesized chicken apolipoprotein AI to trans-Golgi network and its secretion in Madin-Darby canine kidney cells.

MDCK cells were utilized to study the biosynthesis and secretion of chicken apolipoprotein AI (apoAI). A full-length apoAI cDNA in an eukaryotic expression vector was transfected into a MDCK-TGG cell line, expressing a trans-Golgi network (TGN) marker (TGG), and stable clones expressing apoAI were selected. Pulse-chase and cell fractionation studies showed that, compared to gp 80 (an endogenous secretory protein), apoAI was rapidly transported from RER to Golgi complex within 5 min and released from the Golgi complex to the cell exterior by 30 min. Immunofluorescence and three-dimensional laser scanning confocal microscopy revealed that at steady state apoAI was predominantly localized in the TGN. Transferrin uptake experiments showed that apoAI, localized in the TGN, was derived primarily from biosynthetic and not from endocytic routes. ApoAI was secreted in a nonpolarized manner. We suggest that apoAI stays transiently in the TGN prior to its secretion and that the major events of apoAI biosynthesis in vivo and in MDCK cells are conserved. Possible mechanisms of rapid ER to Golgi transport and TGN localization of apoAI are discussed.

Animals↗
PubMed1997

Monoclonal remyelination-promoting natural autoantibody SCH 94.03: pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis.

Chronic inflammatory demyelination of the central nervous system is usually incompletely repaired. However, we previously reported that in vivo treatment with monoclonal antibody SCH 94.03 (produced using spinal cord homogenate as an immunogen) increased myelin repair 4-fold in the Theiler's virus mouse model of chronic progressive multiple sclerosis (Miller et al., 1994; J. Neurosci. 14: 6230-6238). A major issue regarding site and mechanism of action of this antibody is whether SCH 94.03 enters demyelinated CNS lesions and reacts with oligodendrocytes and myelin. To address this question, we radiolabeled SCH 94.03 and studied its distribution into tissues, pharmacokinetics, and binding to cells within demyelinating spinal cord lesions in vivo. SCH 94.03 distributed widely into extracellular water following intraperitoneal injection and was eliminated with a terminal half-life of 3-4.5 days. Only a portion of the total dose (0.4%) entered brain and spinal cord. SCH 94.03 accumulated 1.5-2.0-fold in brain between 1 and 7 days after injection, but its pharmacokinetics were otherwise similar to those of an isotype control IgMkappa antibody. Oligodendrocytes, myelin sheaths and, less frequently, axons were labeled within demyelinating lesions as detected by light and electron microscopic autoradiography. These findings suggest that remyelination-promoting autoantibodies could act within the demyelinating lesion of the central nervous system by binding to the oligodendrocyte, myelin, or axon.

Animals↗
PubMed1997

Peptide ligands of pp60(c-src) SH2 domains: a thermodynamic and structural study.

Thermodynamic measurements, structural determinations, and molecular computations were applied to a series of peptide ligands of the pp60(c-src) SH2 domain in an attempt to understand the critical binding determinants for this class of molecules. Isothermal titration calorimetry (ITC) measurements were combined with structural data derived from X-ray crystallographic studies on 12 peptide-SH2 domain complexes. The peptide ligands studied fall into two general classes: (1) dipeptides of the general framework N-acetylphosphotyrosine (or phosphotyrosine replacement)-Glu or methionine (or S-methylcysteine)-X, where X represents a hydrophobic amine, and (2) tetra- or pentapeptides of the general framework N-acetylphosphotyrosine-Glu-Glu-Ile-X, where X represents either Glu, Gln, or NH2. Dipeptide analogs which featured X as either hexanolamine or heptanolamine were able to pick up new hydrogen bonds involving their hydroxyl groups within a predominantly lipophilic surface cavity. However, due to internal strain as well as the solvent accessibility of the new hydrogen bonds formed, no net increase in binding affinity was observed. Phosphatase-resistant benzylmalonate and alpha,alpha-difluorobenzyl phosphonate analogs of phosphotyrosine retained some binding affinity for the pp60(c-src) SH2 domain but caused local structural perturbations in the phosphotyrosine-binding site. In the case where a reversible covalent thiohemiacetal was formed between a formylated phosphotyrosine analog and the thiol side chain of Cys-188, deltaS was 25.6 cal/(mol K) lower than for the nonformylated phosphotyrosine parent. Normal mode calculations show that the dramatic decrease in entropy observed for the covalent thiohemiacetal complex is due to the inability of the phosphotyrosine moiety to transform lost rotational and translational degrees of freedom into new vibrational modes.

Amino Acid Sequence↗
PubMed1997

Nocturnal hypoglycaemia in IDDM patients younger than 18 years.

The present multicentre study was undertaken to assess the prevalence of nocturnal hypoglycaemia and its determining factors in 117 diabetic children and adolescents, aged 2-18 years and diabetes duration > 1 year in Spain. Each child made 3 measurements of blood glucose (BG) at home at night (between 0000 h and 0600 h) on nine separate nights. A hypoglycaemic event occurred in 12-14% of children in any one night. This is lower than rates for nocturnal hypoglycaemia reported in literature, perhaps because of relatively late mealtimes and different meal content, in Spanish children. Children aged < 7 years were at higher risk of nocturnal hypoglycaemia than older children (p < 0.05). Mean HbA1c from the year before the study and mean HbA1c measured during the closest time to the study were significantly lower in those with nocturnal hypoglycaemia (p < 0.0001). Blood glucose concentrations 2 h before hypoglycaemia did not predict nocturnal hypoglycaemia. The occurrence of low or very low blood glucose concentrations before breakfast was related to a higher risk for nocturnal hypoglycaemia (chi 2 22.97; p < 0.001). No previous symptoms were detectable in 89% of cases.

Adolescent↗
PubMed1997

Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system.

Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-alpha in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes are a target of immune attack. TNF-alpha also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-alpha at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage/microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-alpha in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin or oligodendroglia.

Animals↗
PubMed1997

Differential generation of class I H-2D- versus H-2K-restricted cytotoxicity against a demyelinating virus following central nervous system infection.

Despite the fact that both H-2K and D molecules are up-regulated in the central nervous system (CNS) following Theiler's murine encephalomyelitis virus (TMEV) infection, resistance in this virus model of multiple sclerosis maps exclusively to D. To address this paradox, we examined the ability of the K and D molecules to present viral antigens to cytotoxic T lymphocytes (CTL). Whereas no virus-specific CTL were detected in the CNS of susceptible B10.Q and B10.S mice 7 days post-infection, D-restricted CTL were identified readily in the CNS of resistant B10 animals. There was no evidence of K-restricted CTL in the CNS of B10 mice at day 7 post-infection. The presence of both K- and D-restricted virus-specific CTL in the spleen of immunized B10 mice demonstrates that the exclusive use of D molecules by CTL in the CNS of mice 7 days post-infection is not due to the inability of the K molecules to present viral peptides to lymphocytes. We conclude that the prominent role of the D locus in determining resistance or susceptibility to TMEV-induced demyelination is determined by factors governing the regulation of the immune response, and not by the presence or absence of CTL precursors capable of recognizing viral peptides presented by the K and D antigen-presenting molecules, or by differences in the ability of the K and D molecules to present viral peptides.

Animals↗