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Biomedical subjects

W Rodriguez

Publications and source records attributed to W Rodriguez.

At least 37 records · Page 2Linked to original sources
PubMed1995

Ceftibuten vs. penicillin V in group A beta-hemolytic streptococcal pharyngitis. Members of the Ceftibuten Pharyngitis International Study Group.

The efficacy and safety of a 10-day course of ceftibuten oral suspension (9 mg/kg once daily) were compared with those of penicillin V (25 mg/kg/day in 3 divided doses) in children 3 to 18 years old treated for symptomatic pharyngitis and scarlet fever caused by group A beta-hemolytic streptococci (Streptococcus pyogenes). The study was prospective, randomized, multicenter and investigator-blinded; patients were randomized in a 2:1 ratio (ceftibuten:penicillin V). Overall clinical success (cure/improvement) at the primary end point of treatment (5 to 7 days posttherapy) was achieved in 97% (285 of 294) of ceftibuten-treated patients vs. 89% (117 of 132) of penicillin V-treated patients (P < 0.01). Elimination of infecting streptococci 5 to 7 days posttherapy was achieved in 91% (267 of 294) of ceftibuten-treated patients vs 80% (105 of 132) of penicillin V-treated patients (P < 0.01). A significant rise in anti-streptolysin O or anti-DNase B was observed in approximately 30% of patients in both treatment groups. No patient developed rheumatic fever or nephritis. Treatment-related adverse events were similar between the two groups; mild vomiting (2%) was most frequently reported. These data suggest that once daily ceftibuten is as safe as and more effective than three times daily penicillin V for the treatment of group A beta-hemolytic streptococcal pharyngitis.

Adolescent↗
PubMed1995

Changes in viral expression and cytokine profile induced by a polyantigenic immunomodulator in HIV-infected peripheral blood mononuclear cells.

This is the first time, to our knowledge, that evidence is presented showing that a polyantigenic immunomodulator (PAI), acting as a biological response modifier, can either induce or suppress HIV expression depending on the viral load of infected PBMC. PAI consists of a mixture of inactivated bacteria with influenza virus vaccine. PBMC from HIV-infected patients (asymptomatic, age 22-36, symptomatic, age 30-59 and pediatric, < 2 years old) were co-cultured with PHA-stimulated PBMC from uninfected individuals in medium containing IL-2 and PAI. Parallel co-cultures were carried out in a PAI-free medium. Cultures were fed with PHA-stimulated PBMC from uninfected donors on a weekly basis. HIV-p24 ag and cytokine profiles (IL-1 beta, IL-2, IL-4, IFN-gamma and TNF-alpha) were determined on supernatants on day 14. Peripheral blood samples from each patient were evaluated at the beginning of the experiment as to total CD3, total CD19, CD3/CD4, CD3/CD8, CD16/CD56, CD8/HLA-DR and CD8/CD38 markers through flow cytometry. PAI was able to induce viral expression (up to 11,881 pg/ml of p24 antigen) in cultures showing a low (less than 16 pg/ml) or no viral titer. In contrast, in those cultures with high viral titer (10(2)-10(5) pg/ml), a substantial reduction on the titer was observed upon exposure to PAI. PAI was able to induce the production of IFN-gamma and TNF-alpha while that of IL-4 and IL-1 beta was reduced. The predominant cell type detected in the blood samples of the studied subjects were CD8+, CD8+/CD38+ or CD8+/HLA-DR+.(ABSTRACT TRUNCATED AT 250 WORDS)

ADP-ribosyl Cyclase↗
PubMed1994

Effective short-course treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis. Ten days of penicillin V vs 5 days or 10 days of cefpodoxime therapy in children.

OBJECTIVE: To compare bacteriologic and clinical efficacy and safety of 10 vs 5 days of cefpodoxime proxetil vs 10 days of penicillin V potassium for the treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis in children. DESIGN: Prospective, randomized, observer-blind, multicenter study. PATIENTS/INTERVENTIONS: Four hundred eighty-four children (age range, 2 to 17 years) with signs and symptoms of acute tonsillopharyngitis were enrolled; 377 had a positive throat culture for group A beta-hemolytic streptococci and were fully evaluable. One hundred twenty-one patients received cefpodoxime once a day for 10 days, 126 received cefpodoxime twice a day for 5 days, and 130 received penicillin V three times a day for 10 days. RESULTS: Cefpodoxime for 10 days vs cefpodoxime for 5 days vs penicillin V for 10 days produced bacteriologic eradication at the end of therapy in 95%, 90%, and 78% of the patients, respectively. The 10- and 5-day cefpodoxime treatment regimens were more efficacious than penicillin V (P = .003 and P = .02, respectively). The cumulative bacteriologic failure rate among assessable patients by the 32- to 38-day posttreatment visit was 20 (17%) of 121 patients who were treated with cefpodoxime for 10 days, 24 (19%) of 125 patients who were treated with cefpodoxime for 5 days, and 45 (35%) of 130 patients who were treated with penicillin V for 10 days (P = .001 and P = .005, respectively). Clinical cure or improvement was observed at the end of therapy in 96%, 94%, and 91% of the patients, respectively (P = not significant). Adverse events were infrequent and similar in all three treatment groups, with minor gastrointestinal side effects predominating. CONCLUSIONS: Five days of treatment with cefpodoxime is as efficacious in bacteriologic eradication and clinical response (cure plus improvement) as 10 days of cefpodoxime therapy, and both cefpodoxime regimens produced superior bacteriologic efficacy compared with a 10-day regimen of penicillin V in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children.

Acute Disease↗
PubMed1994

Enrichment of rab11, a small GTP-binding protein, in gastric parietal cells.

Parietal cell secretion of acid requires the coordinated fusion of H(+)-K(+)-adenosinetriphosphatase (ATPase)-containing tubulovesicles with a secretory canalicular target membrane. We have previously reported the presence of rab2 on parietal cell tubulovesicles (L. H. Tang, S. A. Stoch, I. M. Modlin, and J. R. Goldenring. Biochem. J. 285: 715-719, 1992). Since 60% of the small GTP-binding protein sequences obtained from parietal cells were > 95% homologous with human rab11 (J. R. Goldenring, K. R. Shen, H. D. Vaughan, and I.M. Modlin. J. Biol. Chem. 268: 18419-18422, 1993), we sought to study rab11 in gastric parietal cells. A complete rab11 sequence was obtained, and the deduced amino acid sequence of rabbit rab11 was identical to that for human. Rab11 mRNA was present throughout the gastrointestinal mucosa. mRNA for both rab11 and rab2 were enriched in isolated parietal cells compared with chief cells. A polyclonal antiserum against rab11 labeled a single 25-kDa band in isolated parietal cells. Immunostaining of rat fundic tissue demonstrated prominent staining of parietal cells. Rab11 staining cosegregated with alpha-H(+)-K(+)-ATPase staining in enriched preparations of rabbit parietal cell tubulovesicles. These results suggest that rab11 is enriched in parietal cells and is associated with intracellular tubulovesicles.

Amino Acid Sequence↗
PubMed1993

Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome.

The pharmacokinetics and safety of HA-1A (Nebacumab), a human IgM monoclonal antibody with specificity for the lipid A region of endotoxin, were evaluated in a multicenter trial of pediatric patients with sepsis syndrome or septic shock. Forty-two patients received a total of 44 infusions of drug, at a dose of 3 mg/kg (maximum 100 mg). The mean age was 7 years 10 months (range, 11 months to 16 years 7 months). The pharmacokinetic behavior of HA-1A during 36 hours was best described by a one-compartment open model. Clearance (6.1 +/- 2.0 ml/kg per hour) and apparent volume of distribution at steady state (0.11 +/- 0.03 L/kg) were larger than values reported previously in adults with sepsis syndrome. Elimination half-life (14.5 +/- 6.8 hours) and plasma concentration after infusion (30.7 +/- 14.5 mg/L) were similar to adults' values. In an additional three patients studied for 72 hours after administration, a biexponential function (i.e., two-compartment open model) best described the pharmacokinetic behavior of HA-1A: clearance (1.5 +/- 1.4 ml/hr per kilogram) and apparent volume of distribution at steady state (0.2 +/- 0.02 L/kg) were different (p < 0.002) from values observed in children's blood samples during 36 hours. Within the pediatric population, no age-related differences in pharmacokinetics could be detected. Drug disposition was unaffected by renal or hepatic dysfunction. Decreased blood pressure was the most frequently reported adverse event; 4 (9%) episodes in 44 infusions were considered possibly related to the study drug. Gram-negative bacteremia was documented in 23 (55%) of 42 patients. The overall mortality rate was 31%. Enterobacter cloacae was the most common pathogen isolated. Haemophilus influenzae type b was isolated from one child with sepsis syndrome. We conclude that infusion of HA-1A in children is associated with a low incidence of side effects. The pharmacokinetic-pharmacodynamic behavior of HA-1A in children requires further study to determine whether developmental differences exist and how these differences might affect drug administration. Efficacy remains to be studied.

Adolescent↗
PubMed1993

[Neurocysticercosis in a hospital of the city of Buenos Aires: study of 11 cases].

Eleven patients with diagnosis of possible neurocistycercosis were studied in our Department since 1986. All of them were adults. Eight were Bolivian citizens. The commonest neurological clinical manifestation were seizures and/or headache. Brain CT scans showed cystic lesions and calcifications in 5 patients, only calcifications in 3, enlarged ventricles in 2 and an isolated frontal cystic lesion in 1. Six out of 7 patients who were submitted to spinal fluid ELISA test showed positive response for cysticercosis. Patients were put on praziquantel (50 mg/Kg/d) or albendazol (15 mg/Kg/d) with good outcome for all them. Surgery was carried on for treatment of enlarged ventricles (2 patients) and for a like-expansive lesion (1 patient). The aim of this work is to underscore the fact that in Buenos Aires city, which previously was not within the endemic latin american area for cysticercosis, is now possible to find patients with the neurological manifestations of this parasitosis, most probably due to migration of people coming from the north provinces or from countries situated at its border where the disease is endemic.

Adolescent↗
PubMed1992

Development of high-affinity 5-HT3 receptor antagonists. 2. Two novel tricyclic benzamides.

Two new classes of potent 5-HT3 agents have been developed and examined as inhibitors of cytotoxic drug induced emesis in the ferret and dog. The absolute configuration of the most active molecules 10 and 18 have been determined by X-ray crystallography. These two compounds are more potent than known 5-HT3 receptor antagonists both in vivo and in vitro in blocking 5-HT3 receptor activation and preventing chemotherapeutic induced emesis. Compared with 5-HT3 antagonists, such as GR 38032F, zacopride, BRL 43694, and ICS 205-930, compound 10 was more potent in (1) inhibiting binding to 5-HT3 receptor binding sites in rat cortex (Ki = 0.17 nM), (2) blocking the von Bezold-Jarisch effect in the rat (lowest effective dose, 1 microgram/kg iv), and (3) inhibiting 5-HT-induced contraction of guinea pig ileum (lowest effective concentration, 10(-9) M). This novel agent was as effective given po as when given iv in reducing cisplatin-induced emetic episodes in the ferret (ED50 = 4 micrograms/kg iv or po). A 1 mg/kg po dose of 10 virtually abolished cisplatin-induced emesis for 10 h in the ferret. However, it was inactive against apomorphine or copper sulfate-induced vomiting. These data, coupled with receptor binding studies of ligands for D2-dopamine, a1, a2, 5-HT1, 5-HT2, and muscarinic receptors demonstrate that 10 is a highly selective 5-HT3 receptor antagonist with remarkable potency in vivo.

Amides↗
PubMed1991

Use of intravenous gamma globulin to passively immunize high-risk children against respiratory syncytial virus: safety and pharmacokinetics. The RSVIG Study Group.

Infants with cardiopulmonary disease develop severe illness from respiratory syncytial virus (RSV) infection. Safety, feasibility, and pharmacokinetics of intravenous gamma globulin (IVIG) to prevent RSV illness were studied in 23 high-risk infants in a phase I trial. IVIG with an RSV neutralizing antibody titer of 1:1,100 in 5% solution was given monthly over a 2- to 4-h period in a clinical setting during the RSV season. The first group (n = 7) received 500 mg/kg of body weight, the second group (n = 9) received 600 mg/kg, and the third group (n =7) received 750 mg/kg. Serum was drawn prior to infusion and 2, 14, and 30 days after infusion. Total immunoglobulin G and RSV A2 and RSV B neutralizing antibody levels were obtained after the first IVIG infusion. Two children developed mild reversible pulmonary edema (group receiving 600 mg/kg per dose), and one developed hives and wheezing during one infusion (group receiving 500 mg/kg per dose). Twelve children developed subsequent RSV infection during two RSV seasons (November to April) over a 2-year follow-up period; 9 of 12 developed infection during the infusion year. Eleven illnesses were mild; one child died of progressive RSV illness (group receiving 500 mg/kg per dose). A cumulative infusion effect was not observed. IVIG appears safe and feasible in an outpatient setting, and at 750 mg/kg per dose, a target RSV antibody level of greater than or equal to 1:100 was achieved.

Child, Preschool↗
PubMed1990

Launching a multidisciplinary staff development program for liver transplantation.

This article describes a collaborative effort between specialty areas at a large urban medical center to develop a comprehensive liver transplant educational program. The historical overview, needs assessment, and program planning are discussed. The implementation, planning, and evaluation phases are examined. The process presented here can serve as a framework for clinical educators confronted with major new initiatives.

Curriculum↗
PubMed1989

The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects.

The 4.2-kilodalton (kDa) polypeptide associated with the cerebral amyloid deposits of Alzheimer's disease (AD) derives from a much larger protein that is encoded by a gene on chromosome 21. In the present study, we have used antibodies raised against portions of the amyloid protein precursor (APP) to map its normal distribution and to gain further insights into the events that lead to amyloid deposition. Antibodies raised against several different portions of APP reacted with proteins having apparent molecular sizes of 65, 67, and 132 kDa on Western blots. In sections through the normal human brain, immunocytochemistry revealed punctate concentrations of the protein in pyramidal cells of the neocortex, particularly in associative regions, and intense staining in the CA1 pyramidal cells of the hippocampus. By electron microscopy, this punctate distribution coincided with dense concentrations of the protein in secondary lysosomes. In the hippocampus of several AD cases examined, abnormally dense immunostaining in enlarged intracellular domains accompanied a severe atrophy of the CA1 neurons. These data suggest that accumulations of APP in lysosomes of particular neurons may, in AD, lead to proteolytic events that form the insoluble 4.2-kDa amyloid peptide.

Aged↗
PubMed1988

Respiratory syncytial virus infections and intravenous gamma-globulins.

The respiratory syncytial virus (RSV) is a common cause of bronchiolitis and pneumonia in infants and young children. Throughout the world annual RSV epidemics result in numerous hospitalizations, substantial morbidity and some mortality. Until the recent introduction of ribavirin only supportive therapy has been available for treating these infections. The development of animal models of RSV infection and the observation that some lots of immunoglobulin prepared for intravenous administration contained substantial RSV-neutralization antibody titers, prompted a series of studies examining the safety and efficacy of immunoglobulin prepared for intravenous administration in the prophylaxis and treatment of RSV infections. This discussion will review our published, or soon to be published, studies on the use of Sandoglobulin for both immunoprophylaxis and immunotherapy of RSV infections in cotton rats. It will summarize studies utilizing both parenteral and topical (tracheal) Sandoglobulin therapy for RSV infections in owl monkeys. Finally the results of a small double blind trial of parenteral albumin or Sandoglobulin in the therapy of RSV bronchiolitis and/or pneumonia in hospitalized children will be reviewed. The data show that immunoprophylaxis and immunotherapy of RSV infections in laboratory animals was well-tolerated, was safe and induced highly significant reductions in RSV shedding from the lower respiratory tract. Further, immunotherapy of RSV infections in children was also well-tolerated, induced no short or long term evidence of toxicity or injury and caused significant improvements in oxygenation and reductions in RSV shed from the respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Intravenous immunoglobulin treatment of respiratory syncytial virus infections in infants and young children.

Respiratory syncytial virus (RSV)-infected cotton rats (Sigmadon hispidus) and owl monkeys (Aotus trivirgatus) showed significant reductions in RSV shedding from their respiratory tracts following parenteral therapy with human intravenous immunoglobulin (IVIG) containing high titers of RSV-neutralizing antibody. Because this therapy was well tolerated and appeared safe, a double-blind, placebo-controlled IVIG immunotherapy pilot study was performed on 35 hospitalized, RSV-infected infants and children. The treatment was well tolerated and resulted in significant reductions in nasal RSV shedding and in improvements in transcutaneous oximetry readings. However, the mean duration of hospitalization was not reduced by IVIG treatment. Followup to date has revealed no harmful effects resulting from immunotherapy of RSV infections. These studies appear to refute the hypothesis that passively acquired antibody may exacerbate RSV bronchiolitis or pneumonia in infants. Studies with larger numbers of seriously ill children will be required to determine if immunoglobulin G immunotherapy of RSV infections in infants is of clinical value.

Child↗
PubMed1985

Detection of enteric adenoviruses by dot-blot hybridization using a molecularly cloned viral DNA probe.

Enteric adenoviruses (EAds) (candidate adenoviruses 40 and 41, subgroups F and G) have been implicated in the etiology of gastroenteritis in infants, but their clinical significance has been unclear because a rapid test to distinguish these agents from other adenovirus (Ad) types has not been available. We developed a dot-blot hybridization assay for EAd DNA using a cloned DNA fragment that has little homology to non-EAd DNAs. The dot-blot system detected less than 20 pg of EAd DNA, while showing minimal cross hybridization to representative strains from all other Ad groups. There was no detectable hybridization to extracts of samples known to contain other enteric viruses. It was further shown that low levels of EAds in specimens could be amplified by culturing for 1 day in 293 cells. Stool samples and tissue culture lysates prescreened by electron microscopy, cell culture or ELISA were tested in a blind fashion. Using endonuclease analysis as the standard for typing the isolates, we found the dot-blot system to have a 91% sensitivity and 71% specificity for detecting EAds and distinguishing them from other Ads. False-positive and equivocal dot-blot results appeared to be caused by other Ads.

Adenoviridae Infections↗
PubMed1978

The increasing incidence of Ampicillin-resistant Haemophilus influenzae. A cause of otitis media.

Middle ear exudate was obtained by myringotomy or aspiration from 625 suburban children, aged 1 month to 12 years, who had acute otitis media; bacterial pathogens were isolated from 71%. Haemophilus species were isolated from 212 (29%), and Streptococcus pneumoniae from 205 (28%). From 1975 to August 1977, the number of Haemophilus isolates found to be resistant to ampicillin has appreciably increased. Currently, 8% of all cases of acute otitis media in the Washington, DC, area are due to H influenzae resistant to ampicillin. Thirty-one of 35 patients with resistant H influenzae otitis were treated with an erythromycin/sulfisoxazole combination with an impressive clinical response. Twenty-six of these 31 cases had failed to have H influenzae eradicated by an average of ten days of oral ampicillin in recommended doses.

Acute Disease↗