Acute bulbar weakness: thyrotoxicosis or myasthenia gravis?
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Bulbar Palsy, Progressive↗
Biomedical subjects
R Rojas
Publications and source records attributed to R Rojas.
Behavioral model of chronic tinnitus in rats.
An animal model of tinnitus was developed to study chronic salicylate-induced tinnitus in rats. Novel features of the model included oral dosing of salicylate, test stimuli that included a range of pure tones and silence, and assessment of tinnitus for several months. Experimental subjects were given sodium salicylate in their drinking water while control subjects received normal tap water. Subjects were conditioned to press a lever for food in the presence of continuous white noise. At random intervals, offset of the noise was paired with a noxious stimulus, resulting in cessation of lever pressing during the silent test periods. At other randomly scheduled intervals, a test tone was substituted for the white noise, unpaired with noxious stimuli. When the test stimuli were pure tones, the salicylate-treated subjects suppressed less than the control subjects. One explanation for this result is that the experimental subjects' sensations of tones were noisier than those of the controls because experimental subjects were experiencing tinnitus.
Acoustic Stimulation↗
Allogeneic bone marrow transplantation vs chemotherapy for the treatment of childhood acute lymphoblastic leukaemia in second complete remission (revisited 10 years on).
In 1989 we carried out a trial comparing allogeneic BMT to chemotherapy (CT) in 76 children with relapsed acute lymphoblastic leukaemia (ALL). Ten years on we have clinically revised outcome to firmly establish the role of each treatment, to analyse the importance of length of first remission and to provide long-term actuarial results for disease-free survival (DFS) and relapse rate in each group. For 21 patients within the transplantation group, probability of DFS and relapse are 42.8 +/- 10.8% and 40.2 +/- 11.7% (s.e.), respectively. In the chemotherapy group, probability of DFS is 10.0 +/- 4.74% (P = 0.001) and probability of relapse 87.5 +/- 5.2% (P = 0.0004). These results strongly reflect those at initial analysis, confirming a key role of BMT in the management of ALL in second remission. Moreover, on univariate analysis only two factors influenced DFS: treatment group and length of first complete remission (less or more than 30 months from first CR). Thus, it seems clear that the best therapeutic option in early relapse is BMT, whereas DFS in late relapse is at the limit of significance (P = 0.07), with a higher relapse rate in the CT group. Although encouraging results using intensified rotational combination chemotherapy have been published, prospective randomised studies are needed to assess with certainty the best therapeutic option in these patients.
Adolescent↗
Modulation of endocytic traffic in polarized Madin-Darby canine kidney cells by the small GTPase RhoA.
Efficient postendocytic membrane traffic in polarized epithelial cells is thought to be regulated in part by the actin cytoskeleton. RhoA modulates assemblies of actin in the cell, and it has been shown to regulate pinocytosis and phagocytosis; however, its effects on postendocytic traffic are largely unexplored. To this end, we expressed wild-type RhoA (RhoAWT), dominant active RhoA (RhoAV14), and dominant inactive RhoA (RhoAN19) in Madin-Darby canine kidney (MDCK) cells expressing the polymeric immunoglobulin receptor. RhoAV14 expression stimulated the rate of apical and basolateral endocytosis, whereas RhoAN19 expression decreased the rate from both membrane domains. Polarized basolateral recycling of transferrin was disrupted in RhoAV14-expressing cells as a result of increased ligand release at the apical pole of the cell. Degradation of basolaterally internalized epidermal growth factor was slowed in RhoAV14-expressing cells. Although apical recycling of immunoglobulin A (IgA) was largely unaffected in cells expressing RhoAV14, transcytosis of basolaterally internalized IgA was severely impaired. Morphological and biochemical analyses demonstrated that a large proportion of IgA internalized from the basolateral pole of RhoAV14-expressing cells remained within basolateral early endosomes and was slow to exit these compartments. RhoAN19 and RhoAWT expression had little effect on these postendocytic pathways. These results indicate that in polarized MDCK cells activated RhoA may modulate endocytosis from both membrane domains and postendocytic traffic at the basolateral pole of the cell.
3,3'-Diaminobenzidine↗
Association between giardiasis and allergy.
BACKGROUND: Previous studies have indicated that there may be an association between infection by the intestinal protozoan Giardia lamblia and the expression of allergic disease. OBJECT: We evaluated a group of children who attended the Outpatient Clinic of the Children's Hospital in Caracas, Venezuela, a group in which both allergic disease and giardiasis were common. METHODS: We performed feces examination and measured total and specific serum IgE (immunoglobulin E) in these children. RESULTS: We found that 70% of the children infected with G. lamblia presented symptoms of allergy, in contrast to 43% of the non-Giardia parasitized group (P <.05). In addition, the G. lamblia parasitized children showed significantly higher levels of total serum IgE (1194 IU/mL) than the non-Giardia group (822 IU/mL) (P <.005). Children infected with G. lamblia showed higher levels of specific serum IgE antibody against food allergens compared both with the non-parasitized group (P <.0001) and children infected with parasites other than Giardia (P <.05). In contrast, IgE responses against the house dust mite Dermatophagoides pteronyssinus were similar in all the groups studied. CONCLUSIONS: These results reveal a clear relationship between giardiasis and allergy, possibly because infection by this protozoon enhances sensitization towards food antigens, due to increased antigen penetration through damaged intestinal mucosa.
Antibodies, Protozoan↗
Autologous peripheral blood stem cell transplantation (PBSCT) mobilized with G-CSF in AML in first complete remission. Role of intensification therapy in outcome.
In order to determine if peripheral blood stem cells (PBSC) collected after priming with G-CSF in AML in first complete remission (CR) can be used for autologous transplantation and to evaluate the efficacy of early intensification therapy as in vivo purging, we studied 35 consecutive patients with AML in first CR. After standard induction and consolidation chemotherapy, 24 of them were treated with one (10 patients) or two (14 patients) cycles of high-dose cytarabine plus etoposide prior to PBSC collection. G-CSF was used as the priming agent. Of the 35 patients scheduled for peripheral blood stem cell transplantation (PBSCT), three relapsed before transplantation, and the 32 remaining underwent PBSCT. High-dose therapy consisted of either total body irradiation plus cyclophosphamide or busulphan plus cyclophosphamide. The median number of CD34+ cells infused was 3.24 x 10(6)/kg (range 0.15-14). The median times to reach a PMN count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l were 12 (8-28) and 30 (11-345) days, respectively. There was no transplant-related mortality. Twelve patients relapsed between 2 and 21 months post-PBSCT. With a median follow-up of 28 months, actuarial disease-free survival (DFS) is 52.41 +/- 9% in the intent-to-treat group and 57.4 +/- 9.8% in patients who underwent PBSCT. The probability of DFS is significantly higher for patients who receive early intensification therapy prior to both PBSC collection and PBSCT as compared with patients that do not: 68.8 +/- 10.27% vs 35.5 +/- 12.6%, P = 0.0418. These results indicate the feasibility of PBSCT in AML using G-CSF-mobilized PBSC. The use of intensification treatment as 'purging in vivo' prior both to collection of PBSC and PBSCT significantly reduces the risk of relapse in this group of patients.
Adolescent↗
Pyoderma gangrenosum associated with Fanconi's anemia.
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Child↗
Cysticercosis. Clinical classification based on imaging studies.
Cysticercosis is a pleomorphic disease in which the diagnosis, treatment, and prognosis greatly vary in relation to the location, number, and stage of the lesions. A new classification is proposed that includes the information gathered by magnetic resonance imaging and computed tomography, supplemented by immunodiagnostic studies and clinical data. The different clinical entities produced by cysticercosis are grouped by the frequency and location of the parasites, including valuable data as the number and stage of the lesions as well as the degree of the inflammatory response from the host to the parasite. In this way, the disease can be individualized to define the reliability of diagnostic studies and to design specific therapeutic approaches that depend on the characteristics that the disease acquires in every location.
Brain↗
Cadmium levels in maternal, cord and newborn blood in Mexico City.
Blood samples were withdrawn from n = 49 mothers and their children at the moment of birth to assess blood cadmium levels of the mother, the newborn and the cord. A questionnaire was applied to the mothers in order to obtain data about possible sources of cadmium exposure. Maternal blood cadmium was found significantly correlated (r2 = 0.578) with cord blood cadmium levels, while cord blood was correlated (r2 = 0.499) with newborn blood cadmium. Nevertheless, maternal blood cadmium and newborn blood cadmium were not correlated at all (r2 = 0.047). Previous smoking habits of the mother increased maternal blood cadmium concentrations significantly, but it did not modify cadmium concentrations of either the cord or the newborn. The latter result suggests the existence of a placental barrier for cadmium. Birthweight was found to be inversely associated (P < 0.06) only with cord blood cadmium levels. The results of the study suggest that cord blood cadmium holds information about both maternal and newborn cadmium status and also about cadmium effects on birthweight.
Adolescent↗
Higher milk intake during pregnancy is associated with lower maternal and umbilical cord lead levels in postpartum women.
Lead exposure and its deleterious effects continue to be a problem in many countries. The lack of effective and safe treatments for low-level intoxication has promoted environmental interventions to control different sources of lead. In this study we evaluated the effect of milk consumption in 1849 mother-and-child pairs participating in the lead surveillance program in Mexico City. The mean lead levels were 11.2 micrograms/dL for maternal blood lead (MBL) and 10.8 micrograms/dL in umbilical cord. The correlation between blood lead and umbilical cord lead was r = 0.74. Forty-eight percent of the MBL exceeded 10 micrograms/dL and 9.5% exceeded 20 micrograms/dL. Maternal blood lead was positively related to the use of lead-glazed ceramic were and to traffic exposure and was inversely related to the consumption of milk and orange juice. Women who reported the consumption of more than 7 glasses of milk per week had a blood lead level of 8.7 micrograms/dL; in comparison, those women who reported a consumption of less than 7 glasses per week had a blood lead level of 11.1 micrograms/dL. Similar findings were observed for lead measured in umbilical cord. The association between lead levels and milk intake remained unchanged after taking in consideration other predictors of blood lead. This study suggests that a simple intervention could reduce lead burden among women and their newborns.
Animals↗
The role of angiogenesis in the spread of oral squamous cell carcinoma.
Microvessels were counted in 41 primary oral squamous cell carcinomas using JC70 antibody to PECAM (CD31). The counts were compared with clinical and pathological indicators of tumour behaviour including lymph node status, tumour stage, type of histological differentiation, size and velocity of tumour growth. Tumour microvessel counts correlated with lymph node metastasis (p < 0.001). This association was independent of tumour size, velocity and type of histological differentiation and when all the variables were analysed by multivariate analysis only vascular count showed a significant association with lymph node metastasis.
Carcinoma, Squamous Cell↗
Inhibition of apoptotic cell death in B-CLL by interferon gamma correlates with clinical stage.
Apoptosis was evaluated in B cells from 41 patients with B-CLL and 20 healthy aged-matched controls. B cells were cultured with and without gamma-IFN and other cytokines; apoptosis was quantified at regular intervals throughout a 5-day culture period. According to Rai's criteria, 17 patients were classified as good risk, 16 as intermediate and eight as high risk. In vitro, purified B cells from B-CLL patients were evaluated for apoptosis. Maximal apoptosis (44.12%) was observed at day 5 in cells from patients with poor prognosis. The addition of gamma-IFN to the culture media prevented apoptosis in a dose-dependent manner. Maximal inhibition of apoptosis was achieved with 100 IU/ml of gamma-IFN. The degree of inhibition of apoptosis by gamma-IFN was greater in cells from the high-risk group patients than in those from the intermediate and good prognosis group (P < 0.0001). The expression of gamma-IFN receptors in B-CLL cells was evaluated using a MnAb against the extracellular domain of gamma-IFN receptor. After 4 days in culture with gamma-IFN, only cells from the intermediate- and high-risk groups showed an increase in the density of gamma-IFN receptors (P < 0.001). gamma-IFN was not detected in the sera of our study patients. However gamma-IFN was detectable in the media from both normal B cells and B-CLL cells in culture; there was no difference in the amount of gamma-IFN released by cells from the three groups of patients studied. Our results show that in vivo gamma-IFN inhibits apoptosis of B cells from B-CLL patients. The inhibitory effect of gamma-IFN on apoptosis correlates directly with the severity of the disease and this is likely explained by a marked upregulation of gamma-IFN receptors in cells from patients in the high-risk group.
Aged↗
Cavernous hemangiomas of the dura mater at the convexity. Report of a case and therapeutical considerations.
A rare case of cavernous angioma of the dura mater at the convexity is presented. In comparison with the more common cavernous hemangiomas that arise from dural sinuses, the ones on the convexity have a much better prognosis. They do not seem to be associated with spontaneous hemorrhage, their removal is simpler and, transoperatory bleeding, if it occurs, is scanty. Computerized tomography detects the presence of cavernous angiomas of the convexity in only 70% of the cases, magnetic resonance imaging in 100%.
Aged↗
Strict glycemic control in women with pregestational insulin-dependent diabetes mellitus.
OBJECTIVE: To determine the efficacy of strict glycemic control in women with pregestational insulin-dependent diabetes mellitus (IDDM). METHODS: The records of 62 pregnant women with pregestational IDDM who had attended the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Virgen de las Nieves General Hospital, Granada, Spain, between 1982 and 1992, were reviewed. The women had received several daily doses of a mixture of rapid action (regular) and intermediate action insulin with the aim of keeping preprandial glucose levels lower than 95 mg/dl and postprandial glucose levels lower than 120 mg/dl. Perinatal outcomes were compared with those of a control group consisting of 96 randomly selected, normal, pregnant women who gave birth at approximately the same time. RESULTS: Mean glycemic profile in the first assay at an insulin dose of 33.1 +/- 15.9 IU/day was 153.7 +/- 52.3 mg/dl and the HbA1c was 7.7 +/- 2.3%. In the last assay before delivery patients received an insulin dose of 68.2 +/- 30.7 IU/day and had a mean glycemic profile of 94.4 +/- 18.1 mg/dl and an HbA1c of 5.9 +/- 1.4% (P < 0.001 for all parameters). The perinatal mortality of newborn infants of the diabetic mothers was 48 per 1000, and 11.3 per 1000 had some congenital malformations. CONCLUSIONS: Our results verify that strict glycemic control decreases the elevated perinatal mortality normally suffered by IDDM patients. However, if it is to reduce the number of congenital malformations, it must be initiated before the early gestational stages.
Adult↗
"Simulated molecular evolution" or computer-generated artifacts?
1. The authors define a function with value 1 for the positive examples and 0 for the negative ones. They fit a continuous function but do not deal at all with the error margin of the fit, which is almost as large as the function values they compute. 2. The term "quality" for the value of the fitted function gives the impression that some biological significance is associated with values of the fitted function strictly between 0 and 1, but there is no justification for this kind of interpretation and finding the point where the fit achieves its maximum does not make sense. 3. By neglecting the error margin the authors try to optimize the fitted function using differences in the second, third, fourth, and even fifth decimal place which have no statistical significance. 4. Even if such a fit could profit from more data points, the authors should first prove that the region of interest has some kind of smoothness, that is, that a continuous fit makes any sense at all. 5. "Simulated molecular evolution" is a misnomer. We are dealing here with random search. Since the margin of error is so large, the fitted function does not provide statistically significant information about the points in search space where strings with cleavage sites could be found. This implies that the method is a highly unreliable stochastic search in the space of strings, even if the neural network is capable of learning some simple correlations. 6. Classical statistical methods are for these kind of problems with so few data points clearly superior to the neural networks used as a "black box" by the authors, which in the way they are structured provide a model with an error margin as large as the numbers being computed.7. And finally, even if someone would provide us with a function which separates strings with cleavage sites from strings without them perfectly, so-called simulated molecular evolution would not be better than random selection.Since a perfect fit would only produce exactly ones or zeros,starting a search in a region of space where all strings in the neighborhood get the value zero would not provide any kind of directional information for new iterations. We would just skip from one point to the other in a typical random walk manner.
Amino Acid Sequence↗
Autoimmune haemolytic anaemia presenting 9 years prior to Castleman's disease.
Castleman's disease (CD) is a rare disease of unknown aetiology and pathogenesis. We present an unusual case of abdominal CD in whom the first manifestation was an autoimmune haemolytic anaemia presenting 9 years before the diagnosis. The Coombs test became negative 2 months after surgical resection of the mass, suggesting that the mass was the source of the autoantibody. CD may be present in autoimmune haemolytic anaemia in patients with no evidence of any other disease.
Adult↗
Educational contracts in family medicine residency training.
An educational contract for family medicine residency training and evaluation addresses many of the difficulties and challenges of current postgraduate medical education. This article identifies important principles for developing a contractual approach; describes the contract used in one program and its implementation; and discusses its theory, advantages, and limitations.
Clinical Competence↗
Efficacy of a 1-week, once-daily regimen of terbinafine 1% cream in the treatment of tinea cruris and tinea corporis.
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Administration, Cutaneous↗