PubMed Health⌕ Search

Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 37 records · Page 2Linked to original sources

[Optimization of use of levodopa in Parkinson's disease: role of levodopa-carbidopa-entacapone combination].

Levodopa remains the mainstay treatment for Parkinson's disease (PD). Chronic treatment is associated with motor complications (MC) that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible. We here review recent data regarding the mechanism of action of levodopa and its application in clinical practice on the light of the marketing of the combination levodopa-carbidopa- entacapone. Accumulated evidence indicates that MC are mainly the consequence of disease severity governing the degree of dopaminergic depletion and the "pulsatile" dopaminergic stimulation provided by levodopa short plasma half-life. There is no in vivo or clinical evidence of a relevant neurotoxic effect of levodopa. In fact, the recent ELLDOPA study may suggest a neuroprotective effect. Entacapone reduces homocysteine plasma levels which could provide a mechanism to reduce cell death in PD. Currently, the combination levodopa-carbidopa-entacapone is particularly indicated for the treatment of "wearing off" fluctuations. Experimental evidence suggests that early treatment with levodopa-carbidopa-entacapone may substantially ameliorate the incidence of MC. Such a clinical study in "de novo" patients is underway. At present, the combination levodopa-carbidopa-entacapone is indicated when levodopa is judged necessary.

Akathisia, Drug-Induced↗

Filamentation of femtosecond light pulses in the air: turbulent cells versus long-range clusters.

The filamentation of ultrashort pulses in air is investigated theoretically and experimentally. From the theoretical point of view, beam propagation is shown to be driven by the interplay between random nucleation of small-scale cells and relaxation to long waveguides. After a transient stage along which they vary in location and in amplitude, filaments triggered by an isotropic noise are confined into distinct clusters, called "optical pillars," whose evolution can be approximated by an averaged-in-time two-dimensional (2D) model derived from the standard propagation equations for ultrashort pulses. Results from this model are compared with space- and time-resolved numerical simulations. From the experimental point of view, similar clusters of filaments emerge from the defects of initial beam profiles delivered by the Teramobile laser facility. Qualitative features in the evolution of the filament patterns are reproduced by the 2D reduced model.

Journal Article↗

Multiple filamentation of terawatt laser pulses in air.

The filamentation of femtosecond light pulses in air is numerically and experimentally investigated for beam powers reaching several TW. Beam propagation is shown to be driven by the interplay between intense, robust spikes created by the defects of the input beam and random nucleation of light cells. Evolution of the filament patterns can be qualitatively reproduced by an averaged-in-time (2D+1)-dimensional model derived from the propagation equations for ultrashort pulses.

Journal Article↗

Association of APOE polymorphisms with disease severity in MS is limited to women.

The authors studied the association of an exon 4 (E4*epsilon2/3/4) and three promoter polymorphisms of APOE with disease course and severity stratified by gender in 221 patients with multiple sclerosis from two overlapping population-based prevalence cohorts. Women carriers of the E4*epsilon2 allele took longer to attain an Expanded Disability Status Scale score of 6 (p = 0.015) and had more favorable ranked severity scores than noncarriers (p = 0.009). There was no association in men. Alleles epsilon3 or epsilon4 and promoter polymorphisms were not associated with disease course or severity.

Adult↗

Disability profile of MS did not change over 10 years in a population-based prevalence cohort.

OBJECTIVE: To assess whether the level of multiple sclerosis (MS) -related disability in the Olmsted County population has changed over a decade, and to evaluate how the rate of initial progression to moderate disability impacts further disability. METHODS: The Minimal Record of Disability (MRD) measured impairment, disability, and handicap for the 2000 (n = 201) prevalence cohort. The authors compared these results with the 1991 (n = 162) cohort; 115 patients were in both cohorts. The authors assessed retrospectively intervals at which Expanded Disability Status Scale (EDSS) scores of 3 (moderate disability), 6 (cane), and 8 (wheelchair) were reached. RESULTS: The distribution of the 2000 EDSS and MRD scores were not significantly different from the 1991 distribution. The median time from MS diagnosis, for the entire cohort, to EDSS scores of 3 and 6 was 17 and 24 years, respectively. At 20 years after onset, only 25% of those with relapsing-remitting MS had EDSS scores > or =3. The median time from diagnosis to EDSS score of 6 for the secondary and primary progressive groups was 10 and 3 years, respectively. Rate of progression from onset or diagnosis to EDSS score of 3 did not affect the rate of further disease progression. However, once an EDSS score of 3 was reached, progression of disability was more likely, and rate of progression increased. CONCLUSIONS: The distribution of multiple sclerosis disability in the Olmsted community has remained stable for 10 years. Progression of disability for patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis may be more favorable than reported previously. Once a clinical threshold of disability is reached, rate of progression increased.

Adolescent↗

Change in MS-related disability in a population-based cohort: a 10-year follow-up study.

OBJECTIVE: S: To study the change in disability over 10 years in individual patients constituting the 1991 Olmsted County, MN, multiple sclerosis (MS) prevalence cohort. METHODS: The authors reassessed this 1991 cohort in 2001. The authors determined the Expanded Disability Status Scale scores (EDSS) for each patient still alive, and within the year prior to death for those who died. The authors analyzed determinants of potential prognostic significance on change in disability. RESULTS: Follow-up information was available for 161 of 162 patients in the 1991 cohort. Only 15% had received immunomodulatory therapy. The mean change in EDSS for the entire cohort over 10 years was 1 point and 20% worsened by >or=2 points. For patients with EDSS <3 in 1991 (n = 66), 83% were ambulatory without a cane 10 years later. For patients with EDSS of 3 through 5 in 1991 (n = 33), 51% required a cane to ambulate (48%) or worse (3%). For patients with EDSS 6 to 7 in 1991 (n = 39), 51% required a wheelchair or worse in 2001. Gait impairment at onset, progressive disease, or longer duration of disease were associated with more worsening of disability (p < 0.002). The 10-year survival was decreased compared with the Minnesota white population for both men and women. CONCLUSIONS: Although survival was reduced and 30% of patients progressed to needing a cane or wheelchair or worse over the 10-year follow-up period, most remained stable or minimally progressed. Patients within the EDSS 3.0 through 5.0 range are at moderate risk of developing important gait limitations over the 10-year period. The authors did not identify factors strongly predictive of worsening disability in this study.

Adult↗

Blood melatonin and prolactin concentrations in dairy cows exposed to 60 Hz electric and magnetic fields during 8 h photoperiods.

Two experiments were conducted to test the hypothesis that electric and magnetic field (EMF) exposure may result in endocrine responses similar to those observed in animals exposed to long days. In the first experiment, 16 lactating, pregnant Holstein cows were assigned to two replicates according to a crossover design with treatment switchback. All animals were confined to wooden metabolic cages and maintained under short day photoperiods (8 h light/16 h dark). Treated animals were exposed to a vertical electric field of 10 kV/m and a horizontal magnetic field of 30 microT (EMF) for 16 h/day for 4 weeks. In a second, similar experiment, 16 nonlactating, nonpregnant Holstein cows subjected to short days were exposed to EMF, using a similar protocol, for periods corresponding to the duration of one estrous cycle. In the first experiment, circulating MLT concentrations during the light period showed a small numerical decrease during EMF exposure (P < .05). Least-square means for the 8 h light period were 9.9 versus 12.4 pg/ml, SE = 1.3. Melatonin concentrations during the dark period were not affected by the treatment. A similar trend was observed in the second experiment, where MLT concentrations during the light period tended to be lower (8.8 pg/ml vs. 16.3 pg/ml, P < .06) in the EMF exposed group, and no effects were observed during the dark period. Plasma prolactin (PRL) was increased in the EMF exposed group (16.6 vs. 12.7 ng/ml, P < .02) in the first experiment. In the second experiment, the overall PRL concentrations found were lower, and the mean plasma PRL concentration was not affected by treatment. These experiments provide evidence that EMF exposure may modify the response of dairy cows to photoperiod.

Animals↗

Parathyroid gland function in the uremic rabbit.

Rabbits with renal failure have been reported to be hypercalcemic and to have decreased parathyroid hormone (PTH) concentrations. Thus, it would seem that uremic rabbits are resistant to secondary hyperparathyroidism (HPT). The work reported here was designed to investigate parathyroid gland function in uremic rabbits and the effect of diets with different calcium (Ca) and phosphorus (P) content. The relationship between PTH and ionized calcium (Ca2+), parathyroid gland size and parathyroid cell cycle were studied in three groups of rabbits: Group I, rabbits with normal renal function on a standard diet (Ca = 1.2%, P = 0.6%); Group II, partially nephrectomized rabbits on a standard diet; and Group III, partially nephrectomized rabbits on a low Ca (0.6%)-high P (1.2%) diet. Group I rabbits had baseline Ca2+ = 1.71 +/- 0.05 mmol/l and PTH = 26.9 +/- 3.2 pg/ml. During hypo- and hypercalcemic stimulation PTH reached maximal values (PTHmax) of 94.4 +/- 5.5 pg/ml and minimal concentrations (PTHmin) of 3.2 +/- 0.2 pg/ml. Rabbits from Group II were hypercalcemic (baseline Ca2+ = 2.03 +/- 0.06 mmol/l) and had very low PTH levels (1.7 +/- 0.5 pg/ml); however, they reached a PTHmax that was similar to Group I, 92 +/- 8.7 pg/ml. Group III rabbits were hypocalcemic (baseline Ca2+ = 1.22 +/- 0.08 mmol/l) and had very high basal PTH levels (739 +/- 155 pg/ml). Their PTHmax and PTHmin were 801 +/- 169.4 pg/ml and 102.2 +/- 22.2 pg/ml, respectively. Both parathyroid gland size and parathyroid cell proliferation were increased in Group III. In conclusion, our results show that the Ca and P content of the diet markedly influence PTH secretion in the uremic rabbit and that when placed on a low Ca-high P diet uremic rabbits develop secondary HPT.

Analysis of Variance↗

Multivisceral transplantation for pediatric intestinal pseudo-obstruction: single center's experience of 16 cases.

Chronic intestinal pseudo-obstruction (CIPO) in children may be life-threatening due to the complications of parenteral nutrition (PN) or catheter-related sepsis. Multivisceral transplantation (MVTx) is a lifesaving option but limited experience is available. We report our experience with MVTx in pediatric CIPO patients. Sixteen children with CIPO underwent MVTx at median age of 4 years. Indications for MVTx were liver failure (n = 10), loss of venous access (n = 3), or sepsis (n = 3). Modified MVTx without the liver was performed in six patients. Induction immunosuppression included tacrolimus, steroid with adjunctive agent in period I (April 1996 to December 2000), namely, OKT3 (n = 1), mycophenolate mofetil (n = 4), or daclizumab (n = 2); and in period II (January 2001 to present), Campath 1H (n = 4) or daclizumab (n = 5). The grade of rejection was severe in 12.5% and mild to moderate in 87.5% of cases. Isolated rejection of the transplanted stomach or pancreas was not diagnosed during clinical course or on autopsy. Actuarial patient survival for 1 year/2 years for period, I and II were 57.1%/42.9% and 88.9%/77.8%. None of the long-term survivors is on PN and all tolerate enteral feedings. Pancreatic enzyme supplementation or insulin therapy is not needed in survivors. Gastric emptying was substantially affected in one case. Bladder function did not improve in those with urinary retention problems. MVTx for CIPO offers a lifesaving option with excellent function of the transplanted pancreas and stomach among survivors.

Child↗

Effects of cryopreservation and thawing on the structure of vascular segment.

The objective of this study was to analyze the importance of the quality of the vascular segment to be cryopreserved and the influence of storage in a gas phase, a liquid phase, or after accidental immersion in liquid nitrogen. In addition, we investigated the effects of rapid versus slow thawing on the occurrence of fractures and changes in the structure of the vessel wall. The tissue sources were whole thoracic and abdominal aortas from 15 pigs. Each aorta was cut into equal segments and randomly assigned to each study group. One segment of fresh unfrozen aorta of the same size was used as a control. The samples were cryopreserved using a programmed apparatus. After 2 weeks the arterial segments were thawed rapidly or slowly. A great variation in the results was obtained depending on the quality of the control. Although endothelial cells were better preserved in the liquid phase, the internal elastic lamina and elastic lamelli showed better preservation and fewer microfractures in the gas phase. The internal elastic lamina showed a greater number of microfractures when an accidental immersion in liquid nitrogen had taken place. Furthermore, better preservation of the structure of the vascular segment was observed with a slow thawing method. In general, the conditions of storage and the method of thawing seem to damage the structure of vascular segments. It is necessary to use a severe protocol of donor and vascular segment selection to optimize the post-thaw quality of the cryopreserved samples.

Animals↗

Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma.

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1-19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27-42) and 29% (95% CI 22-36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.

Acute Disease↗

Use of powdered egg yolk vs fresh egg yolk for the cryopreservation of ovine semen.

Egg yolk is a common additive to sperm cryopreservation diluents. Because of its animal origin, however, it also represents a potential risk of microbiological contamination in the diluent. This potential contamination can be avoided by using powdered egg yolk, instead of fresh egg yolk, as it is pasteurized. This study was conducted to determine ram sperm cryosurvival was affected by the type of egg yolk used (powdered egg yolk or fresh egg yolk) and by yolk concentration (10, 15 or 20%) in the diluent. Microbiological analyses were also performed to quantify the microbiological contamination in the diluents containing the two types of egg yolk. Sperm cryosurvival was determined by motility and morphology analyses after thawing. Motility parameters were assessed using a computer-assisted sperm analysis (CASA) system, and the percentage of sperm with a normal apical ridge was evaluated using a differential interference contrast microscope. No significant differences were observed between diluents in the percentage of sperm with normal apical ridge. However, higher percentages of total motile cells were observed for samples containing powdered egg yolk (69%) compared to samples containing fresh egg yolk (60%). However, sperm in diluents containing fresh egg yolk, exhibited higher values for average-path velocity, straight-line velocity and beat cross frequency and lower values for amplitude of lateral head displacement (p <0.05), compared to cells in diluents containing powdered egg yolk. Microbiological contamination was similar (<200 CFU/ml) in both diluents, and no bacterial growth was observed in either, when antibiotics were added. Therefore, powdered egg yolk can be effective used in diluents for the freezing of ram semen. However, the in vivo fertility of sperm frozen in diluents containing powdered egg yolk should be tested, as some motility parameters were different for sperm treated with powdered egg yolk compared to fresh egg yolk.

Animals↗

Distinct promoters regulate tissue-specific and differential expression of kallikrein 6 in CNS demyelinating disease.

Kallikrein 6 is a serine protease expressed abundantly in normal adult human and rodent CNS, and therein is regulated by injury. In the case of CNS demyelinating disease, K6 expression in CNS occurs additionally in perivascular and parenchymal inflammatory cells suggesting a role in pathogenesis. Herein we describe two unique transcripts that occur within the human and mouse K6 genes that differ in their 5'-untranslated regions. These transcripts have identical translation initiation sites in exon 3, are expressed in a tissue-specific fashion and are differentially regulated in response to CNS injury. While the human and mouse 5'-transcripts differ in sequence they are identical in genomic organization and tissue-specific expression. The most 5'-transcript, designated transcript 1, includes exon 1-7, and was detectable in all CNS regions, but not in any non-CNS tissues examined (spleen, thymus, liver, kidney, pancreas, submandibular gland and peripheral nerve). In contrast, transcript 2 lacks exon 1, but contains a unique sequence at the 5'-end of exon 2, designated exon 2A. Transcript 2 was expressed both in CNS and in each peripheral tissue. In a murine model of human CNS demyelinating inflammatory disease induced by Theiler's picornovirus, mouse K6 transcript 1 was up-regulated in brain and spinal cord at acute and more chronic phases of CNS inflammation and demyelination, while overall transcript 2 expression was not significantly altered. However, in isolated splenocyte cultures, transcript 2 was up-regulated two-fold by cellular activation. Tissue-specific expression patterns and differential regulation in CNS disease indicates that each K6 5'-transcript is probably regulated by unique promoter elements and may serve as a molecular target to treat inflammatory demyelinating disease.

Animals↗

Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions.

Multiple sclerosis is considered to be an immune-mediated disease of the central nervous system, characterized by chronic inflammation, primary demyelination and axonal damage. The mechanisms of demyelination and axonal injury are heterogeneous and complex. One possible mechanism is direct damage of oligodendrocytes and neurons by Class I MHC restricted cytotoxic T-cells. In this study we analyzed the expression of functional MHC class I molecule complex, consisting of alpha-chain and beta2-microglobulin, in a large sample of human autopsy material, containing 10 cases of acute MS, 10 cases of chronic active MS, 10 cases of chronic inactive MS and 21 controls. To examine the expression of MHC class I and II molecules on the different cell-types in brain, we used quantitative immunohistochemical techniques, double staining and confocal laser microscopy scans on paraffin embedded sections. We found constitutive expression of MHC class I molecule on microglia and endothelial cells. A hierarchical up-regulation of MHC class I was present on astrocytes, oligodendrocytes, neurons and axons, depending upon the severity of the disease and the activity of the lesions. MHC class II molecules were expressed on microglia and macrophages, but not on astrocytes. These data indicate that in MS lesions all cells of the central nervous system are potential targets for Class I MHC restricted cytotoxic T-cells.

Adult↗

Contrasting murine models of MS.

There are two main animal model systems currently used to study MS: experimental autoimmune/allergic encephalomyelitis (EAE) and experimental viral infection, including the Theiler's murine encephalomyelitis virus (TMEV). Both models have led to a greater understanding of MS and the development of clinical therapies. These systems have allowed in-depth study of the immune system and inflammatory mechanisms potentially involved in MS pathophysiology. Analysing therapeutic successes and failures with both models may also help the development of more directed, positive treatments for MS that have fewer negative effects.

Animals↗

Incidence and prevalence of multiple sclerosis in Olmsted County, Minnesota, 1985-2000.

BACKGROUND: Epidemiologic data for multiple sclerosis (MS) in Olmsted County, MN, have been recorded for almost 100 years and have indicated that the increasing prevalence rate was likely due in part to an increasing incidence rate. METHODS: All cases of MS diagnosed from 1985 to 2000 were identified using the centralized diagnostic index at the Mayo Clinic and the Rochester Epidemiology Program Project, a shared database of all medical practitioners in the county. Patients were required to have established residency at least 1 year prior to diagnosis of MS. Results were also age- and sex-adjusted to control for shifts in the population structure. RESULTS: The raw prevalence of MS was determined to be 177 per 100,000 on December 1, 2000, and the raw incidence rate was 7.5 per 100,000 person-years at risk from 1985 to 2000. CONCLUSIONS: After age and sex adjustment to a common population, these prevalence and incidence rates of MS appear to have been stable rather than increasing over the past 20 years.

Adolescent↗

White-light filaments for atmospheric analysis.

Most long-path remote spectroscopic studies of the atmosphere rely on ambient light or narrow-band lasers. High-power femtosecond laser pulses have been found to propagate in the atmosphere as dynamically self-guided filaments that emit in a continuum from the ultraviolet to the infrared. This white light exhibits a directional behavior with enhanced backward scattering and was detected from an altitude of more than 20 kilometers. This light source opens the way to white-light and nonlinear light detection and ranging applications for atmospheric trace-gas remote sensing or remote identification of aerosols. Air ionization inside the filaments also opens promising perspectives for laser-induced condensation and lightning control. The mobile femtosecond-terawatt laser system, Teramobile, has been constructed to study these applications.

Journal Article↗