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Biomedical subjects

R Arroyo

Publications and source records attributed to R Arroyo.

At least 19 recordsLinked to original sources

An IFNG polymorphism is associated with interferon-beta response in Spanish MS patients.

Interferon-beta is a biological treatment widely used in multiple sclerosis (MS). However, not every patient responds equally well to this therapy. In this study, our aim was to evaluate the influence of a dinucleotide microsatellite located in the first intron of the interferon-gamma gene on relapse eradication in a group of interferon-beta-treated patients. Our results show a very different allelic distribution when patients with relapses were compared with relapse-free patients.

Dinucleotide Repeats↗

Corticosteroids, ibuprofen, and acetaminophen for IFNbeta-1a flu symptoms in MS: a randomized trial.

OBJECTIVE: To compare the efficacy of acetaminophen, ibuprofen, and prednisone in the treatment of interferon beta-1a (IFNbeta-1a) flu-like syndrome (FLS). METHODS: Patients with relapsing-remitting multiple sclerosis initiating treatment with IM IFNbeta-1a were randomized in a multicenter, randomized, double-blind, controlled trial to receive acetaminophen 500 mg before and 6 and 12 hours after each injection, ibuprofen 400 mg before and 6 and 12 hours after each injection, or prednisone 60 mg daily for 1 week, plus tapering. Patients were instructed to keep a daily diary of fever severity, myalgia, chills, headache, and asthenia for 27 days. The sum of the scores of individual symptoms was used to obtain a daily FLS index. The primary outcome was the FLS index area under the curve (AUC) corrected by the number of measurement days. RESULTS: Eighty-four patients were randomized at 11 hospitals: acetaminophen (n = 28), ibuprofen (n = 28), and corticosteroids (n = 28). No differences were detected between treatments in the mean AUC of the FLS index. With limitation of the analysis to the days of IM IFNbeta-1a injection, differences favoring ibuprofen were observed in the mean FLS index (p = 0.0007). CONCLUSIONS: No prophylactic treatment for flu-like syndrome seems to be superior to another in terms of overall well-being during the first month of IM IFNbeta-1a therapy. However, ibuprofen confers better control of symptoms immediately following IM IFNbeta-1a injection.

Acetaminophen↗

TNF-376A marks susceptibility to MS in the Spanish population: A replication study.

This study was designed as a reappraisal of the association between the TNF-376A promoter polymorphism and susceptibility to multiple sclerosis found in the Spanish population but not in other populations. With a new dataset of patients (n = 241) and control subjects (n = 288), the association was confirmed (p = 0.018). The authors' data suggest that this association is specific of the Spanish white (or related) population or, alternatively, that only studies in their population have the adequate statistical power because of the higher frequency of an extended, conserved haplotype carrying the TNF-376A allele.

Adult↗

Pulmonary nocardiosis in heart transplant recipients: treatment and outcome.

BACKGROUND: Nocardial infections typically affect patients receiving immunosuppressants, occurring early after surgery in 3% to 40% of heart transplant (HTx) recipients. The emergence of antibiotic resistance and occurrence of disease recurrences in AIDS population has engendered controversy about the treatment for immunodepressed HTx patients. METHODS: We present a retrospective study of the diagnosis, treatment and outcome of 560 HTx recipients between 1984 and 2002. RESULTS: Among the five cases of Nocardia infection (0.9%), three cases developed late after HTx (between 3.1 and 11 years follow-up). All patients had pulmonary disease and one in addition had subcutaneous nodules. Microbiological diagnosis required open lung biopsy in one case. All patients were treated primarily with trimethoprim-sulphamethoxazole, but evidence of resistance to sulfonamides led us to change the antimicrobial combination in two cases. Four patients who received one year of antibiogram-guided therapy showed complete healing without recidivism. Three patients died, all due to non-related causes, at follow-ups between 1 and 5 years. In one case a cutaneous recurrence of disease was attributed to noncompliance. CONCLUSIONS: Nocardiosis in current HTx is less common than previously reported. Its incidence seems to be delayed in time with modern immunosuppressants. Given the high incidence of sulfamide resistance, treatment must be guided by antibiotic sensitivity. We believe that maintenance therapy for a whole year is the appropriate option in order to avoid recidivism in this population.

Anti-Bacterial Agents↗

High incidence of severe infections in heart transplant recipients receiving tacrolimus.

BACKGROUND: Tacrolimus (FK) is being increasingly used as an alternative to cyclosporine (CyA) in heart transplantation (HTx). It is believed to engender slightly more powerful protection against acute rejection. However, the increased immunosuppression could result in an excess of infectious complications. METHODS: Our study compared the incidence of major infections (MInf), defined as life-threatening infectious episodes requiring admission and intravenous (IV) antimicrobial therapy, among a series of HTx recipients treated with either FK (n=30) or CyA (n=84). RESULTS: A total of 21 patients received FK in an elective protocol and 9 patients initially treated with CyA were converted to FK. Tacrolimus was combined with azathioprine and prednisone in 21 cases, and with mycophenolate mofetil and steroids in 8 recipients. After a follow-up between 6 and 37 months, 11 patients (37%) in the FK group developed 13 episodes of MInf, most (85%) occurring during the first posttransplant year. Conversely, CyA patients (n=84), a group with similar characteristics and follow-up, showed a MInf incidence of 12% (P<.05). Among the FK group, the most common site of MInf was pulmonary (69%). A variety of opportunistic agents caused MInf in 54% of cases, whereas the remaining ones were attributed to nosocomial bacteria. There were three deaths (27% of all MInf), all in azathioprine-treated patients with initial FK therapy. CONCLUSIONS: Tacrolimus therapy seems to be associated with an increased incidence of severe infections in HTx recipients. We recommend aggressive diagnostic and therapeutic approaches for patients on FK who develop signs or symptoms of infection in the first year after HTx.

Aged↗

Prevalence of herpesvirus DNA in MS patients and healthy blood donors.

OBJECTIVES: The aim of this study is to determine the DNA prevalence of different members of Herpesviridae in multiple sclerosis (MS) patients and to describe the possible effect of beta-interferon treatment on such prevalence. MATERIAL AND METHODS: With a nested polymerase chain reaction (PCR) assay we have studied the DNA of the peripheral blood mononuclear cells (PBMCs) of 204 whole blood samples, [102 from patients with relapsing-remitting MS (RRMS), of which 62 were treated with beta-interferon, and 102 from healthy blood donors]. RESULTS: We only found a statistically significant difference for human herpesvirus type 6 (HHV-6) DNA prevalence (P < 0.0001): HHV-6 is 2.26 times more frequent in MS patients than in healthy donors. There was no difference in the HHV-6 prevalence between beta-interferon treated and untreated patients. CONCLUSION: 1. Among the herpesviruses, HHV-6 was the only one showing altered prevalence. This either indicates that HHV-6 is involved in the pathogenesis of MS, or it simply indicates that MS influences latency or reactivation of HHV-6 without any direct involvement of HHV-6 in the disease process of MS. 2. Treatment with beta-interferon does not make a difference on the DNA prevalence of the herpesviruses studied in our MS patients.

Adjuvants, Immunologic↗

Differences between coding and non-coding regions in the Trichomonas vaginalis genome: an actin gene as a locus model(1).

The sequence of a cloned genomic fragment of Trichomonas vaginalis containing a complete actin gene was determined. An uninterrupted open reading frame of 1128 nucleotides was found that codes for an actin gene. Two overlapped consensus promoter sequences for T. vaginalis were found 12 nucleotides upstream the actin initiation codon. In addition to actin, two incomplete open reading frames were found at the 5' and 3' ends of the clone. These two sequences are expressed and showed similarity to adenylate cyclase genes and a yeast hypothetical protein. The overall sequence showed a higher G+C content and a lower frequency of repeated sequences in the coding regions when compared with the non-coding regions. A similar unequal nucleotide distribution was found in various T. vaginalis genes retrieved from data bases.

Actins↗

[Hormone replacement therapy in ischemic heart disease prevention in women. Arguments against].

Hormone replacement therapy is one of the most difficult issues women and their doctors face. Epidemiological studies have consistently found that women using hormone replacement therapy are at a substantially lower risk of developing coronary heart disease. Observational data are supported by findings demonstrating that hormone replacement therapy improves several risk factors o coronary heart disease, specially the favourable changes in lipid profile. However, no study has clearly established hormones help prevent heart disease. In women without heart disease, the benefits of hormone replacement therapy are unclear. However, recent clinical trials have sown that the use of hormone replacement therapy does not provide cardiovascular benefits in women with established heart disease.

Adult↗

Vasculitis following treatment of rheumatoid arthritis with extracorporeal staphylococcal protein a immunoadsorption column (prosorba).

We report a case of vasculitis after Prosorba treatment in a patient with rheumatoid arthritis. The patient is a 66-year-old white male with long standing rheumatoid arthritis and hepatitis B. He was treated with the standard regimen for Prosorba treatment. He improved and met criteria for an American College of Rheumatology (ACR) 20% response. While on therapy he developed a nonhealing ulcer. Approximately 2 weeks after treatment was completed, he developed palpable purpura and mononeuritis multiplex. Deep dermal biopsy confirmed the presence of both small and medium vessel vasculitis. Nerve conductions studies were consistent with neuropathic conduction delays. He was treated with 1mg/kg/day of oral prednisone. Prosorba has been reported to cause leukocytoclastic vasculitis during treatment, but has not been noted to involve medium sized vessels. This patient's history and presentation are most consistent with rheumatoid arthritis associated vasculitis, though the Prosorba treatment cannot be ruled out as a cause or a contributing factor. Importantly, although Prosorba treated his synovitis, it did not prevent concomitant vasculitis.

Journal Article↗

Trichomonas vaginalis: chromatin and mitotic spindle during mitosis.

The mitotic phases and the changes that the chromatin and mitotic microtubules undergo during mitosis in the sexually transmitted parasite Trichomonas vaginalis are described. Parasites arrested in the gap 2 phase of the cell cycle by nutrient starvation were induced to mitosis by addition of fresh whole medium. [(3)H] Thymidine labeling of trichomonad parasites for 24 h showed that parasites have at least four synchronic duplications after mitosis induction. Fixed or live and acridine orange (AO)-stained trichomonads analyzed at different times during mitosis by epifluorescence microscopy showed that mitosis took about 45 min and is divided into five stages: prophase, metaphase, early and late anaphase, early and late telophase, and cytokinesis. The AO-stained nucleus of live trichomonads showed green (DNA) and orange (RNA) fluorescence, and the nucleic acid nature was confirmed by DNase and RNase treatment, respectively. The chromatin appeared partially condensed during interphase. At metaphase, it appeared as six condensed chromosomes, as recently reported, which decondensed at anaphase and migrated to the nuclear poles at telophase. In addition, small bundles of microtubules (as hemispindles) were detected only in metaphase with the polyclonal antibody anti-Entamoeba histolytica alpha-tubulin. This antibody showed that the hemispindle and an atractophore-like structure seem to duplicate and polarize during metaphase. In conclusion, T. vaginalis mitosis involves five mitotic phases in which the chromatin undergoes different degrees of condensation, from chromosomes to decondensed chromatin, and two hemispindles that are observed only in the metaphase stage.

Acridine Orange↗

A novel cysteine proteinase (CP65) of Trichomonas vaginalis involved in cytotoxicity.

The goal of this study was to demonstrate the participation in cellular damage of a Trichomonas vaginalis proteinase with a molecular mass of 65 kDa (CP65). By two dimensional gelatin-gel electrophoresis of trichomonad proteins we detected four spots with proteolytic activity on the 65 kDa region, but only one, pI 7.2, binds to the HeLa cell surface. By indirect immunofluorescence, rabbit antibodies against this proteinase localized the CP65 on the plasma membrane and in the cytoplasm of T. vaginalis. Pretreatment of parasites with the specific anti-CP65 antibody reduced trichomonal cytotoxicity to HeLa cell monolayers. The specific cysteine proteinase inhibitor, L-3-carboxy-2, 3-trans-epoxypropionyl-leucylamido (4-guanidino) butane (E64) abrogated the proteinase activity and reduced cytotoxicity levels of T. vaginalis in cell culture monolayers, indicating that the trichomonad CP65 is a cysteine proteinase. Activity of the CP65 proteinase was optimal at pH 5.5 and 37 degrees C, conditions similar to those of patients with trichomonosis. Also, this proteinase degraded some of the proteins found in the vagina, i.e. collagen IV and fibronectin, but not laminin-1 or haemoglobin. Finally, immunoprecipitation assays showed that sera and vaginal washes from trichomonosis patient possess anti-CP65 antibodies. In conclusion, results presented in this work demonstrate that the CP65 is a surface cysteine proteinase involved in T. vaginalis cytotoxicity to HeLa cell monolayers, as a virulence factor. It is immunogenic during human infection and degrades some extracellular matrix proteins, i.e. collagen IV and fibronectin.

Animals↗

Hearing results in the second stage of open mastoidectomy: A comparison of the different techniques.

OBJECTIVE: The goal of this study was to compare the hearing results obtained through different hearing-restoration techniques in open-cavity mastoidectomy. METHODS AND MATERIAL: A total of 116 ears operated on during the second stage of open mastoidectomy were studied. The hearing gain was registered as the difference between preoperative and 1-year postoperative conversational frequency means (500, 1000, 2000 Hz). High-pitched frequencies (4000 Hz) were used equally. Two groups of studies were carried out: in one study the stapes was intact, and in the other the stapes arch was absent. The columella techniques we examined, from a hearing point of view, are total and partial ossicular replacement prostheses, ossiculoplasty, cartilage with or without perichondrium, and the myringostapediopexy. RESULTS AND CONCLUSIONS: In the group of patients in whom the stapes was intact, the differences in high-pitched frequencies found between the different techniques were negligible, but the differences were quite significant in conversational frequencies, where the partial ossicular replacement prosthesis turned out to be the technique with the worst results. In ears in which only the footplate was present, the total ossicular replacement prosthesis gave better results than any other technique, both in conversational frequencies and in 4000-Hz frequency.

Adult↗

CP30, a cysteine proteinase involved in Trichomonas vaginalis cytoadherence.

We describe here the participation of a Trichomonas vaginalis 30-kDa proteinase (CP30) with affinity to the HeLa cell surface in attachment of this parasite to host epithelial cells. The CP30 band is a cysteine proteinase because its activity was inhibited by E-64, a thiol proteinase inhibitor. In two-dimensional substrate gel electrophoresis of total extracts of the trichomonad isolate CNCD 147, three spots with proteolytic activity were detected in the 30-kDa region, in the pI range from 4.5 to 5.5. Two of the spots (pI 4.5 and 5.0) bound to the surfaces of fixed HeLa cells corresponding to the CP30 band. The immunoglobulin G fraction of the rabbit anti-CP30 antiserum that recognized a 30-kDa band by Western blotting and immunoprecipitated CP30 specifically inhibited trichomonal cytoadherence to HeLa cell monolayers in a concentration-dependent manner and reacted with CP30 at the parasite surface. CP30 degraded proteins found on the female urogenital tract, including fibronectin, collagen IV, and hemoglobin. Interestingly, CP30 digested fibronectin and collagen IV only at pH levels between 4.5 and 5.0. Moreover, trichomonosis patients whose diagnosis was confirmed by in vitro culture possessed antibody to CP30 in both sera and vaginal washes, and CP30 activity was found in vaginal washes. Our results suggest that surface CP30 is a cysteine proteinase necessary for trichomonal adherence to human epithelial cells.

Animals↗

Strategies by which some pathogenic trichomonads integrate diverse signals in the decision-making process.

The interaction between each one of Trichomonas vaginalis and Tritrichomonas foetus with their hosts is a complex process in which components associated to the cell surfaces of both parasites and host epithelial cells, and also to soluble components found in vaginal/urethral secretions, are involved. Either cytoadhesion or the cytotoxicity exerted by parasites to host cells can be dictated by virulence factors such as adhesins, cysteine proteinases, laminin-binding proteins, integrins, integrin-like molecules, a cell detachment factor, a pore-forming protein, and glycosidases among others. How trichomonads manipulate informations from the extracellular medium, transduce such informations, and respond to them by stimulating the activities of some surface molecules and/or releasing enzymes are the aspects concerning trichomonal virulence which are here briefly reviewed and discussed.

Animals↗