Biomedical subjects
Publications and source records attributed to E Rodriguez.
An unusual case of multiple lesions of tuberculosis verrucosa cutis and colliquative forms is reported. We emphasize a rapid response to conventional therapy.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A common pattern of hypoxic-ischemic cerebral injury in the term newborn involves predominantly cerebral cortex and subcortical white matter. We describe 20 term newborns with moderate or severe acute hypoxic-ischemic encephalopathy who exhibit a different pattern of abnormalities on computed tomography, with evidence of decreased tissue attenuation predominantly in thalami and basal ganglia and relative preservation of cerebral cortex and white matter. Profound, acute hypoxic-ischemic insult (eg, umbilical cord prolapse, uterine rupture, or massive placental abruption) was documented in 16 of 20 infants (80%). Characteristic clinical features during the newborn period included irritability, tonic posturing of limbs, and persistent lower cranial nerve dysfunction, often with prominent tongue fasciculations. This pattern of central injury appears to be highly predictive of poor outcome; 7 newborns (35%) died, and all survivors who had follow-up to 18 months of age (11) had major neurological sequelae (eg, spastic quadriplegia, choreoathetosis, and persistent feeding problems). This pattern of hypoxic-ischemic cerebral injury corresponds closely to experimental animal models of "acute total" perinatal asphyxia.
BACKGROUND: We hypothesized that small amounts of thrombin desensitize the platelet thrombin receptor during cardiopulmonary bypass (CPB), resulting in postoperative platelet dysfunction and bleeding. METHODS: Seventy-nine patients were entered into a study designed to measure changes in platelet thrombin receptor function during CPB and to correlate them to postoperative bleeding. In addition to measurements of clinical blood loss, platelet function tests of aggregation, activation, and cell-cell adhesion were used. The thrombin receptor agonist peptide (TRAP) was used to activate the platelets. Flow cytometry was used to measure various platelet surface markers and platelet-white cell interactions during CPB. RESULTS: Compared with preoperative values, both aggregometry and flow cytometry measured a significant reduction of TRAP-induced activation immediately and up to 24 hours after CPB. The response of other activating agents returned to normal by 24 hours. Postoperatively, 8 of 79 patients required excessive blood transfusion (> or = 10 units of blood products) and had significantly decreased TRAP-induced aggregation response. CONCLUSIONS: Our results show that (1) platelet activation, aggregation, and adhesion to leukocytes induced by TRAP are reduced after CPB, (2) decreased thrombin receptor responsiveness is associated with excessive postoperative blood loss, and (3) because the aggregation and activation responses are different for TRAP and thrombin, there may be a second thrombin receptor on platelets that is protected from damage during CPB. These results imply that prevention of the CPB-induced effects on the thrombin receptor will lessen postoperative morbidity associated with blood transfusion.
Extraction of the roots of the Amazonian medicinal plant, Piper piscatorum Trelease and Yuncker, with MeOH and subsequent bioassay guided fractionation using the guppy, Girardina guppii yielded the active amide, N-isobutyl-6-(p-methoxyphenyl) 2E, 4E-hexadieneamide (piperovatine) and a second inactive amide, N-isobutyl-(E)-7-(3,4-methylenedioxyphenyl)hept-2-enamide (pipercallosidine). The former displayed an LC50 of 115 ng/ml in toxicity tests and proved to be the constituent responsible for the dual ethnobotanical uses of this plant: that of fish stupefacient (barbasco) and oral local anesthetic.
Ninety patients with tuberous-sclerosis complex (TSC) were tested for subtle mutations in the TSC2 gene, by means of single-strand conformational analysis (SSCA) of genomic DNA. Patients included 56 sporadic cases and 34 familial probands. For all patients, SSCA was performed for each of the 41 exons of the TSC2 gene. We identified 32 SSCA changes, 22 disease-causing mutations, and 10 polymorphic variants. Interestingly, we detected mutations at a much higher frequency in the sporadic cases (32%) than in the multiplex families (9%). Among the eight families for which linkage to the TSC2 region had been determined, only one mutation was found. Mutations were distributed equally across the gene; they included 5 deletions, 3 insertions, 10 missense mutations, 2 nonsense mutations, and 2 tandem duplications. We did not detect an increase in mutations either in the GTPase-activating protein (GAP)-related domains of TSC2 or in the activating domains that have been identified in rat tuberin. We did not detect any mutations in the exons (25 and 31) that are spliced out in the isoforms. There was no evidence for correspondence between variability of phenotype and type of mutation (missense versus early termination). Diagnostic testing will be difficult because of the genetic heterogeneity of TSC (which has at least two causative genes: TSC1 and TSC2), the large size of the TSC2 gene, and the variety of mutations. More than half of the mutations that we identified (missense, small in-frame deletion, and tandem duplication) are not amenable to the mutation-detection methods, such as protein-truncation testing, that are commonly employed for genes that encode proteins with tumor-suppressor function.
A 10-fold increase in patients with Mycobacterium tuberculosis-positive specimens in one hospital laboratory prompted an investigation. Clinical and epidemiological data, along with M tuberculosis DNA fingerprinting results, indicated that laboratory contamination led to nine false-positive M tuberculosis cultures. Pseudo-infection should be considered in patients with unusual tuberculosis presentations, negative acid-fast bacilli smears, and only one positive culture with a low colony count.
Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the unavailability of temperature monitoring in the early version of the Navistar catheter, the location of the arrhythmia, and the history of arrhythmia control with flecainide. No attempt was made to limit fluoroscopy time in our study population. Nevertheless, despite data acquisition from 120-320 anatomically distinct sites during global and more detailed focal atrial mapping, total fluoroscopy exposure was typically < 30 minutes and was as little as 12 minutes. The detailed display capabilities of the CARTO system appear to offer the potential of enhancing our understanding of atrial anatomy, atrial activation, and their relationship to surface ECG P wave morphology during focal atrial tachycardias.
Bidirectional isthmus conduction block has been associated with a low recurrence rate after atrial flutter ablation. We present the case of a type I, typical or "counterclockwise" atrial flutter ablation guided by stimulation and recordings obtained from a basket catheter, which allowed for constant electrogram recording from splines positioned along the right lateral free wall and septum. After atrial flutter termination with radiofrequency application, the ability to record and stimulate from multiple sites in the atrium using the basket catheter was useful to detect residual bidirectional slow conduction through the isthmus. Complete isthmus block could be documented after additional radiofrequency energy applications.
Traditional herbal remedies have increased in popularity in Europe and the United States in recent years but have always been important to people living in rural Mexico and to their Mexican American/Chicano descendants in the United States. Mexican American patients will often be ingesting herbal teas at the same time that they are being treated for their ailments with antibiotics or antiinflammatory agents. The plant family Asteraceae (Compositae) has contributed the largest number of plants to this pharmacopoeia; the reasons for the importance of this family include its large number of species in Mexico and its wide array of natural products that are useful in the treatment of the maladies that have afflicted the inhabitants of rural Mexico. These natural products include sesquiterpene lactones, polyacetylenes, alkaloids, monoterpenes, and various phenolics such as flavonoids. In this review, we emphasize the sesquiterpene lactones, a large group of compounds with antiinflammatory properties and the ability to relax smooth muscles and thereby relieve gastrointestinal distress. These compounds also readily form adducts with glutathione or free thiols and can thereby affect the metabolism, activity, and toxicology of a wide array of pharmacological agents.
PURPOSE: We identify risk factors associated with chronic postoperative penile pain after inflatable prosthesis insertion. MATERIALS AND METHODS: We performed a case control study to determine the incidence of prolonged penile pain in 65 men who underwent prosthesis insertion. The association of various potential risk factors, including diabetes mellitus, incision site, prosthesis type, patient age and history of pelvic surgery, was assessed. In addition, the penis was examined for physical findings, and penile magnetic resonance imaging (MRI) was done as an in situ evaluation of the anatomical position and functional status of the inflatable prosthesis. RESULTS: A total of 14 patients (21.5%) with prolonged pain were compared to the remaining 51 with no pain. All parameters evaluated were similar in both groups except for MRI findings. Of the 14 patients with pain 12 (85.7%) had buckling of the cylinders in the flaccid state compared to only 1 of the 51 controls (1.9%). Statistical analysis showed a highly significant association between buckling and penile pain (odds ratio 300, p <0.0001). Surgical correction of buckling resolved pain in 5 patients. CONCLUSIONS: Prolonged postoperative penile pain after prosthesis insertion is strongly associated with cylinder buckling. This buckling may be the consequence of an excessively long cylinder or an appropriate size cylinder that fails to reach the crural end. The method of accurately diagnosing these alterations is MRI of the penis.
OBJECTIVE: To examine the linkages, cultural/ecological factors, and major psychosocial risk factors as they relate to drug use in a sample from Colombia, South America. METHOD: The participants were 1.687 adolescents living in mixed urban-rural communities in Colombia, South America. An individual interview was administered to youths in their homes by Colombian interviewers. The scales used were based on item intercorrelations grouped into the following risk categories: (1) adolescent personality, (2) family traits, (3) peer factors, and (4) cultural/ecological variables. RESULTS: Pearson correlations were computed for each variable and the frequency of marijuana use. Results show that each of the domains was related to adolescent marijuana use, with some notable gender differences. As regards the interrelation of domains, a mediational model was operative. CONCLUSIONS: Findings support a family interactional theory. The domains of family, personality, and peer factors had a direct effect on the adolescents' marijuana use. Implications for prevention are also addressed.
A high-performance liquid chromatographic method to determine glutathione, cysteine and N-acetylcysteine in rabbit retina, vitreous and lens has been developed. The thiols are separated using a 25 x 0.46-cm octadecylsilane column with 0.5 M phosphate buffer, pH 3, as mobile phase. The detection, at 412 nm, involves a post-column derivatization with 5,5-dithiobis(2-nitrobenzoic acid) in presence of cationic micelles of hexadecyltrimethylammonium bromide that enhances the sensitivity. The detection limits are 0.21, 0.92 and 0.61 mumol/g wet sample for glutathione, cysteine and N-acetylcysteine, respectively.
BACKGROUND: This study describes the functioning of primary care patients with major depressive disorder, the relationship of medical comorbidity to functional status, and the effects of depression-specific treatment on functional status after 8 months. METHODS: Patients were randomized to a protocol intervention (nortriptyline hydrochloride or interpersonal psychotherapy) or to usual care with the patient's physician in a clinical trial of primary care treatments of depression. Their functional status was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and the Global Assessment Scale. Medical comorbidity was assessed with the Duke Severity of Illness Checklist. The Hamilton Rating Scale for Depression and Beck Depression Inventory were used to measure depressive severity. Assessments were conducted at baseline and at 1, 2, 4, and 8 months after randomization. RESULTS: At baseline, patients reported substantial impairments in the functional domains as assessed by the SF-36 and Global Assessment Scale. Severity of general medical illness and depression were not correlated. Greater medical comorbidity was associated with diminished physical, but not psychological, functioning. Mean scores on SF-36 scales and the Global Assessment Scale improved significantly during the 8 months of follow-up. Patients assigned to protocol treatments showed greater improvement, compared with those assigned to usual care, on the SF-36 mental summary scale and most individual scales but not on the SF-36 physical summary scale. However, patients who completed protocol treatment also experienced significant improvement on the physical summary scale. Medical comorbidity was only a weak predictor of outcome. CONCLUSIONS: Primary care patients with major depressive disorder report substantial impairments in physical, psychological, and social functioning on initial assessment. Severity of baseline medical comorbidity did not correlate with severity of depression and only weakly correlated with functional status at 8 months. Functional impairments improve with time, but standardized depression-specific treatment is associated with greater improvement in more domains of functioning than is a physician's usual care.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder of benign tumor formation, hamartomata, and hamartias. TSC has been shown to be genetically heterogeneous, with one causative gene mapping to chromosome 9q (denoted TSC1) and at least one other gene on chromosome 16p (denoted TSC2). The TSC2 gene was recently cloned. We have tested 88 TSC probands with the TSC2 cDNA by Southern blotting searching for gross deletions/rearrangements/insertions. We detected two deletions and a rare intragenic polymorphic variant. This is a similar rate of mutation detection (2/88; 2.3%) to that in the original report (10/260/; 3.8%). The rare polymorphic variant was initially detected in the proband of a chromosome 9-linked multiplex TSC family. The polymorphism segregated with previously tested markers on chromosome 16 independently of the disease gene, verifying that the variation was unrelated to TSC status. We have also begun searching for subtle mutations by SSCA and direct sequencing. After screening three exons, we found two intragenic polymorphic variants. Both polymorphisms are common, making them useful for linkage studies in known affected families.
This study examined whether the treatment of streptozotocin (STZ)-diabetic rats with gliclazide (5 mg/kg body weight twice daily orally) increases muscle glucose uptake. Rats were treated (group G, n = 10) or untreated (group D, n = 11) for 12 days. Normal rats served as controls (group C, n = 11). At the end of the treatment, both basal and insulin-stimulated glucose uptake by the perfused hindquarters were measured. In gastrocnemious muscles, the protein content of GLUT4 and the insulin binding and tyrosine kinase activity of partially purified solubilized insulin receptors were measured. Group G had a lower mean glycemic value during the treatment period than group D (mean +/- SEM, 17 +/- 0.6 v 19.7 +/- 0.5 mmol/L, P < .05), without differences in serum insulin levels. Basal glucose uptake by the hindquarters was significantly higher in group G versus group D (2.8 +/- 0.3 v 1.3 +/- 0.2 mumol/g/h, P < .05), and was not different versus group C (3.6 +/- 0.2 mumol/g/h). Insulin-stimulated glucose uptake was higher (P < .05) in group C compared with the two groups of diabetic rats. Glucose uptake at 10(-7) mol/L insulin was higher in group G than in group D (9.2 +/- 0.6 v 7.0 +/- 0.6 mumol/g/h, P < .05). Both insulin binding and tyrosine kinase activity were similar in muscle insulin receptors from both groups of diabetic rats. The GLUT4 protein content was higher in group G than in group D (95 +/- 10 v 57 +/- 7 arbitrary units [AU]/microgram protein, P < .05) and similar to that of group C (113 +/- 13 AU/microgram protein). In conclusion, gliclazide has a glucose-lowering effect in STZ-diabetic rats that could be attributed to an increase in muscle glucose clearance by a post-insulin receptor mechanism, probably related to a normalization of GLUT4 content.
Functional evolution of an arsenic resistance operon has been accomplished by DNA shuffling, involving multiple rounds of in vitro recombination and mutation of a pool of related sequences, followed by selection for increased resistance in vivo. Homologous recombination is achieved by random fragmentation of the PCR templates and reassembly by primerless PCR. Plasmid-determined arsenate resistance from plasmid pl258 encoded by genes arsR, arsB, and arsC was evolved in Escherichia coli. Three rounds of shuffling and selection resulted in cells that grew in up to 0.5 M arsenate, a 40-fold increase in resistance. Whereas the native plasmid remained episomal, the evolved operon reproducibly integrated into the bacterial chromosome. In the absence of shuffling, no increase in resistance was observed after four selection cycles, and the control plasmid remained episomal. The integrated ars operon had 13 mutations. Ten mutations were located in arsB, encoding the arsenite membrane pump, resulting in a fourfold to sixfold increase in arsenite resistance. While arsC, the arsenate reductase gene, contained no mutations, its expression level was increased, and the rate of arsenate reduction was increased 12-fold. These results show that DNA shuffling can improve the function of pathways by complex and unexpected mutational mechanisms that may be activated by point mutation. These mechanisms may be difficult to explain and are likely to be overlooked by rational design.