Biomedical subjects
Publications and source records attributed to F Ruiz.
A case of prune belly syndrome diagnosed by ultrasonography during the thirteenth week of gestation is described. Pathogenic data and the importance of antenatal diagnosis are discussed.
The World Health Organization (WHO) has indicated that opioid analgesics are insufficiently available, particularly in developing countries, due to a variety of reasons, including legislative, educational, and policy issues. In its effort to promote the rational use of medical opioids and the adequate treatment of patients with cancer, WHO has sponsored a meeting of Latin American representatives every 2 years, which includes health professionals and government regulators. During March 24-27, 1996, a group of 86 representatives of cancer pain relief and palliative care programs from nine Latin American countries met in Santo Domingo under the auspices of the WHO Palliative Care Program for Latin America. For the first time since the First Latin American Meeting, government regulators were present to help address the issue of opioid availability from their perspective. During the meeting, issues pertaining to cancer pain, opioid availability, and palliative care were discussed. This report summarizes some of the events and presents a summary of the conclusions of an earlier meeting in 1994, as described in the Declaration of Florianopolis, and presents its follow-up, The Santo Domingo Report, generated following the 1996 meeting.
An outbreak of postinjection abscesses occurred in Barranquilla, Colombia, and was associated with local injections of lidocaine given in a single physician's office. Over a 5-month period, 350 (18%) of approximately 2,000 injected patients developed localized cutaneous abscesses or cellulitis; of 210 abscess specimens that were cultured, 205 were positive for rapidly growing mycobacteria, subsequently identified as Mycobacterium abscessus. The source of the outbreak was not identified. M. abscessus could not be characterized by pulsed-field gel electrophoresis, but all isolates were identical in terms of drug and heavy metal resistance patterns and random amplified polymorphic DNA PCR profiles. We believe this is the first report of the use of this latter technique for investigation of an outbreak due to M. abscessus. Therapy with a combination of surgical excision and 3-6 months' administration of clarithromycin was successful for 95% of 148 patients treated in this manner; in contrast, therapy was successful for less than one-third of patients treated with surgery alone or clarithromycin alone. This is the largest of the nine known outbreaks of postinjection abscesses that have occurred due to rapidly growing mycobacteria and is the first in which an effective method of therapy was demonstrated.
Liver methionine adenosyltransferase (MAT) plays a critical role in the metabolism of methionine converting this amino acid, in the presence of ATP, into S-adenosylmethionine. Here we report that hydrogen peroxide (H2O2), via generation of hydroxyl radical, inactivates liver MAT by reversibly and covalently oxidizing an enzyme site. In vitro studies using pure liver recombinant enzyme and mutants of MAT, where each of the 10 cysteine residues of the enzyme subunit were individually changed to serine by site-directed mutagenesis, identified cysteine 121 as the site of molecular interaction between H2O2 and liver MAT. Cysteine 121 is specific to the hepatic enzyme and is localized at a "flexible loop" over the active site cleft of MAT. In vivo studies, using wild-type Chinese hamster ovary (CHO) cells and CHO cells stably expressing liver MAT, demonstrate that the inactivation of MAT by H2O2 is specific to the hepatic enzyme, resulting from the modification of the cysteine residue 121, and that this effect is mediated by the generation of the hydroxyl radical. Our results suggest that H2O2-induced MAT inactivation might be the cause of reduced MAT activity and abnormal methionine metabolism observed in patients with alcoholic liver disease.
Starting in January 1994, a group of 20 adolescents with Down's syndrome began a competition-oriented athletics training program at a public sports stadium twice a week as part of their education towards integration. They were given complete medical examinations beforehand and followed medically and professionally throughout the program. The results showed a significant improvement in the test scores measuring strength, speed and endurance and a tendency towards an athletic morphotype.
Patients with cystic fibrosis (CF) display defects in airway ion transport, but the influence of airway transport phenotype on improved prognosis is not known. We studied airway bioelectric properties in five CF patients with the rare A455E mutation that is associated with mild pulmonary disease. We also evaluated five patients possessing premature truncation mutations (G542X and R553X) for which an association with mild pulmonary disease has not been as well established. We found no evidence in vivo that a mild lung disease mutation in the CF transmembrane regulator gene (CFTR) led to correction or partial correction of: (1) unstimulated Cl- secretion; (2) beta-agonist-activated Cl- secretion; (3) basal sodium reabsorption; or (4) amiloride-sensitive airway sodium transport. Early phase therapeutic trials in CF, including human gene transfer trials, rely heavily on improvements in airway potential difference to identify promising interventions and an improved prognosis. Based on our findings in a naturally occurring group of CF patients with an improved pulmonary prognosis (A455E), one can argue that marked clinical benefit might be possible without any improvement whatsoever in airway bioelectric phenotype. Moreover, if genetic modifiers exist that influence the severity of a particular CFTR mutation (e.g., A455E), these may be independent of human airway Cl-secretion in vivo, since we detected minimal Cl--secretory responses in patients with A455E.
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We describe an outbreak of skin lesions due to Mycobacterium chelonae subsp. abscessus associated with injections of lidocaine (lignocaine) given by a 'bioenergetic' (a practitioner of alternative medicine) in Colombia. The lidocaine carpules and the lesions of the patients yielded mycobacteria with identical biochemical characteristics. Using the methodology of Sartwell and a case control design we examined the incubation period and assessed risk factors. Of 667 potentially exposed individuals, a total of 298 patients were interviewed, of whom 232 had skin lesions. The median incubation period was 30.5 days (range 15-59 days). Male sex (OR 2.85, 95% CI 1.26-6.51), increasing age (OR 1.25, 95% CI 1.03-1.53), subcutaneous injection route (OR 3.72, 95% CI 1.09-12.7) and number of injections (OR 1.01, 95% CI 1.00-1.03) were risk factors for disease. To our knowledge, this is the largest reported outbreak of M. chelonae infection, the first in which the organism has been isolated from the putative vehicle of infection, and the first in which the incubation period could be determined.
1. The dual inhibitor of enkephalin degrading enzymes, RB 101, is able to block endogenous enkephalin metabolism completely, leading to potent antinociceptive responses potentiated by blockade of CCKB receptors. In this study we have investigated the effects induced by RB 101 given alone, or with the CCKB antagonist, PD-134,308, on a model of spontaneous morphine withdrawal and substitutive maintenance in rats. 2. Animals were chronically treated with morphine for 7 days followed, 36 h after the interruption of drug administration, by a maintenance treatment for 5 days with methadone (2 mg kg-1, i.p.), clonidine (0.025 mg kg-1, i.p.), RB 101 (40 mg kg-1, i.p.), PD-134,308 (3 mg kg-1, i.p.) or a combination of RB 101 plus PD-134,308. Several behavioural observations were made during this period in order to evaluate the acute effects as well as the consequence of chronic maintenance induced on spontaneous withdrawal by the different treatments. 3. Methadone was the most effective compound in decreasing the spontaneous withdrawal syndrome after acute administration. Both, methadone and RB 101 had similar effectiveness in reducing opiate abstinence during the period of substitutive treatment. PD-134,308 did not show any effect when administered alone and did not modify the effect of RB 101. 4. Naloxone (1 mg kg-1, s.c.) failed to precipitate any sign of withdrawal when injected at the end of the chronic maintenance treatment suggesting that, under the present conditions, methadone and RB 101 did not induce significant physical opiate-dependence. 5. The mildness of the side effects induced by chronic RB 101, suggests that systemically active inhibitors of enkephalin catabolism could represent a promising treatment in the maintenance of opiate addicts.
Ciliates are of special interest owing to the multiplicity and diversity of their microtubule organizing centers (MTOCs). The subcellular localization of gamma-tubulin in these protozoa has not been extensively studied. The cloning of a gamma-tubulin gene in Euplotes (Liang, A., K. Heckmann, Gene 136, 319-322 (1993) led us to examine the localization of this protein. We used three polyclonal antibodies, JH46, R58 and R70. They had been raised against peptides common to mammalian and Aspergillus gamma-tubulins. These regions had 69%, 95%, and 75% identity with the corresponding regions of Euplotes gamma-tubulin. Immunoblotting (R70) revealed a polypeptide corresponding to the molecular mass of Euplotes gamma-tubulin. In Euplotes octocarinatus, gamma-tubulin was detected by immunofluorescence (R70) in the basal bodies, the micronucleus and the macronucleus throughout the cell cycle. The presence of gamma-tubulin in basal bodies and micronuclei was confirmed with the other two antibodies JH46 and R58. The permanent association of gamma-tubulin with basal bodies was also observed in Tetrahymena thermophila and Paramecium tetraurelia, two ciliates distantly related to Euplotes. These results not only extend to ciliates the finding that gamma-tubulin is permanently associated with ciliary basal bodies, but also demonstrate that gamma-tubulin is present in unconventional MTOCs.
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The modulatory effect of the dihydropyridine Ca2+ channel antagonist nimodipine on the analgesic action of the kappa-opioid receptor agonist U-69,593 was analyzed using the tail-flick test in rats. The antinociceptive effect of U-69,593 (0.25-4 mg/kg) was antagonized by L-type Ca2+ channel blockade with nimodipine (200 microgram/kg, i.p.), the ED50 being increased from 1.4 to 7.3 mg/kg. On the contrary, when an increase in the density of these channels was induced by means of chronic and simultaneous treatment with nimodipine (1 microgram/h, 7 days) and sufentanil (2 micrograms/h, 8 days), the analgesic effect of U-69,593 was potentiated by 5-fold. Our results suggest a functional coupling between kappa-opioid receptors and L-type Ca2+ channels in nociception.
Despite previous reports [McLaughlin (1985) Mol. Biochem. Parasitol. 15, 189-201; Ghosh, Ray, Sarkar and Bhaduri (1990) J. Biol. Chem. 265, 11345-11351; Mazumder, Mukherjee, Ghosh, Ray and Bhaduri (1992) J. Biol. Chem. 267, 18440-18446] suggesting that the plasma-membrane Ca(2+)-ATPases of different trypanosomatids differ from the Ca2+ pumps present in mammalian cells, Trypanosoma cruzi plasma-membrane Ca(2+)-ATPase shares several characteristics with the Ca2+ pumps present in other systems. This enzyme could be partially purified from epimastigote plasma-membrane vesicles using calmodulin-agarose affinity chromatography. The activity of the partially purified enzyme was stimulated by T. cruzi or bovine brain calmodulin. In addition, the enzyme cross-reacted with antiserum and monoclonal antibody 5F10 raised against human red-blood-cell Ca(2+)-ATPase, has a molecular mass of 140 kDa and forms Ca(2+)-dependent hydroxylamine-sensitive phosphorylated intermediates. These results, together with its high sensitivity to vanadate, indicate that this enzyme belongs to the P-type class of ionic pumps.
We have analyzed by radiometric procedures in rat central nervous system the changes in the properties of mu-opioid receptors associated with tolerance and supersensitivity to the opioid agonist sufentanil. This study has used [3H]-[D-Ala2,MePhe4,Gly- (ol)5(2)]-enkephalin, a highly selective ligand, to label mu-opioid receptors in both membranes and tissue sections. The induction of opioid tolerance by chronic infusion for 7 days of high doses of sufentanil, a high efficacy agonist, produced mu-opioid receptor down-regulation, with a significant decrease in their density in both cortical (-67%) and spinal cord membranes (-55%) and no changes in the affinity constant. Autoradiographic studies showed an overall decrease of[3H]-Ala2,MePhe4,Gly-(ol)5(2)]-enkephalin binding in the somatosensory cortex (around -30%). When the dihydropyridine-Ca++ channel antagonist nimodipine was administered alone for 7 days, no significant changes in the density or affinity constant of mu-opioid receptors were observed. However, the chronic and simultaneous administration of nimodipine and sufentanil (7 days), induced a pronounced modification on the density of mu-opioid receptors of the rat central nervous system and blocked the down-regulation observed in sufentanil-treated (tolerant) rats. These neurochemical findings may account for the functional interaction we have observed previously in the analgesic studies between nimodipine and sufentanil. Our data strongly suggest a functional role of L-type Ca++ channels in the mediation of opioid tolerance and super-sensitivity.
BACKGROUND: Sepsis is the commonest complication of small bowel transplantation. These infections are presumably caused by bacterial translocation, due to splanchnic ischemia. AIM: To study bacterial translocation in the immediate postoperative period after a small bowel transplantation in dogs and to relate it to splanchnic ischemia. METHODS: Three groups of dogs were studied. In group A (n = 6) spontaneous episodes of splanchnic ischemia were monitored in the first 18 h of the postoperative period. In group B (n = 5), a 60 min ischemia was induced by superior mesenteric artery occlusion, two hours after small bowel transplantation. In group C (n = 5) a 60 min ischemia was induced by occlusion of mesenteric vein, two hours after transplantation. Bacterial translocation was assessed through bacterial cultures from the mesenteric vein and splanchnic ischemia with intramucosal pH measurement (a pH < 7.2 was considered indicative of ischemia). RESULTS: Twenty eight of 83 cultures were positive, specially for Gram negative bacilli. The incidence of positive cultures was 14% for group A, 17% for group B and 79% for group C (p < 0.01 compared to groups A and B). The higher incidence of bacterial translocation occurred during the first two hours after transplantation, when the lower intramucosal pH recordings were obtained. The percentage of positive cultures was 39% during periods of ischemia, compared to 24% during periods without ischemia (p = NS). CONCLUSIONS: Bacterial translocation occurs during the first two hours after intestinal transplantation, in concomitance with the lower intramucosal pH readings.
1. In this study we evaluated, in intact awake rats, the effects of angiotensin II (AII) and vasopressin (AVP) on venous tone to explain their different hemodynamic effects. 2. Cardiac index (CI) was measured by thermodilution. AII and AVP were infused at the doses adjusted to increase mean arterial pressure 25, 50 and 70% above baseline. Lower doses of AVP than AII were necessary to increase mean arterial pressure at the same levels. 3. To study whether the different effects of AII and AVP on CI may be explained by their different actions on the venous system, changes in venous tone were evaluated by measuring mean circulatory filling pressure (MCFP) and determining the pressure gradient for venous return (PGVR). 4. AVP induced a decrease in CI from 32.5 +/- 2.2 to 23.1 +/- 1.7 and 15.4 +/- 0.8 ml/min/100 g (P < 0.01) with the second and third level of increase in afterload respectively, whereas AII at the same levels of afterload decreased CI from 34.8 +/- 1.3 to 28.3 +/- 2.3 and 23.4 +/- 1.7 ml/min/100 g (P < 0.01). Furthermore, the rise in total peripheral resistances (TPR) was greater with AVP than with AII at the highest level of afterload (P < 0.05). Heart rate significantly decreased more in the animals infused with AVP than with AII. 5. There were no changes in MCFP and PGVR with either AII or AVP. 6. These results indicate that in intact awake rats the larger fall in CI induced by AVP can not be explained only by a greater decrease in HR since at highest levels of afterload AVP decreased SV.(ABSTRACT TRUNCATED AT 250 WORDS)
A 48-year-old man presented to the emergency department with confusion, agitation, diaphoresis, and muscle rigidity after beginning treatment with fluoxetine, a serotonin reuptake inhibitor. He had discontinued treatment with tranylcypromine, a monoamine oxidase inhibitor, 2 weeks earlier. The constellation of findings was diagnostic of the serotonin syndrome.