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Biomedical subjects

C Redondo

Publications and source records attributed to C Redondo.

At least 37 records · Page 2Linked to original sources

Type IV phosphodiesterase inhibition in experimental allergic encephalomyelitis of Lewis rats: sequential gene expression analysis of cytokines, adhesion molecules and the inducible nitric oxide synthase.

Type IV phosphodiesterase inhibitors are able to suppress EAE. To investigate the effects of this therapy in the central nervous system, we serially analyzed from days 7 to 17 postinoculation the gene expression pattern of tumor necrosis factor (TNF), lymphotoxin, interferon-gamma, interleukin-1beta, the inducible nitric oxide synthase (iNOs), interleukin-10, the vascular cell adhesion molecule-1 (VCAM-1) and the intercellular adhesion molecule-1 (ICAM-1) in the spinal cord of Lewis rats with actively induced EAE, treated with Rolipram. Treated rats had a delayed and milder disease, and reduced numbers of infiltrates in the nervous tissue. The gene expression profile was similar to that of untreated rats, although delayed, with no evidence of IL-10 upregulation during the observation period. The delayed inflammation was not associated with changes in the expression of VCAM-1 and ICAM-1. In peripheral blood mononuclear cells, TNF mRNA levels were decreased and interleukin-10 was unchanged. This therapy did not alter the proliferative ability of T lymphocytes against myelin basic protein. The encephalitogenic potential of splenocytes from treated animals was also unaffected. The high levels of both iNOs mRNA and nitric oxide (NO) found before the appearance of clinical signs, suggests that NO generation might be a contributing factor to the therapeutic benefit achieved by Rolipram in the rat.

Animals↗

Collagenous colitis in Spain: a report of nine new cases.

BACKGROUND: collagenous colitis is a clinicopathological entity that causes chronic watery diarrhea. The patients are predominantly women in the sixth or seventh decade of life. Radiological and endoscopic studies are usually normal or nonspecific. It is diagnosed by the presence in colonic biopsies of a thickened subepithelial band of collagen and an inflammatory infiltrate in the mucosa. METHODS: 9 cases diagnosed in our hospital and 18 previously described in Spain have been reviewed. RESULTS: all the cases showed chronic watery diarrhea. In 17 patients symptoms were present since at least one year before diagnosis. Five of the 27 patients had been taking nonsteroidal antiinflammatory drugs. Rheumatological and autoimmune diseases were found in 6 patients. Colonoscopy was normal or showed nonspecific findings except in one of our patients, in which aphthous ulcers and pseudomembranes were found. Different treatments had been employed, including antidiarrheal agents, sulfasalazine, 5-ASA and omeprazole. CONCLUSIONS: collagenous colitis is uncommon but should be considered in patients with long-standing chronic watery, nonbloody diarrhea. Collagenous colitis is probably more common than we think, as biopsies are not usually taken in cases of chronic diarrhea with normal endoscopic findings.

Adult↗

Suppression of HIV-1 infection in linomide-treated SCID-hu-PBL mice.

BACKGROUND: Proinflammatory cytokine overproduction, as well as synthesis of the inducible form of nitric oxide synthase (iNOS), are known to play a major role in HIV-1-triggered disease. AIDS patients show increased serum tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma levels, which synergize with HIV-1-produced nitric oxide (NO) to augment viral replication. Linomide has strong immunomodulatory effects in animals and humans, yielding promising clinical benefits in several pathological disorders including septic shock and autoimmune disease, processes largely mediated by overproduction of these cytokines. In peripheral T cells, linomide also prevents apoptosis triggered by a variety of stimuli, including superantigens, dexamethasone and vaccinia virus. DESIGN AND METHODS: Linomide inhibits production of proinflammatory cytokines such as TNF-alpha, interleukin-1 beta and IFN-gamma, as well as iNOS synthesis. The SCID-hu-PBL mouse model was used to analyse the effect of linomide on HIV-1 infection. T-cell frequency was characterized in reconstituted animals, and the frequency of infected mice and viral load of infected animals were studied. RESULTS: Linomide promotes an increase in human CD4+ T-cell counts in the peritoneal cavity of HIV-1-infected, linomide-treated mice. Linomide also prevents human TNF-alpha and IFN-gamma production, as well as iNOS expression and affects the viral load, promoting potent suppression of HIV-1 infectivity as detected in peritoneal cavity and spleen. CONCLUSIONS: The combination of linomide's properties, namely, blockage of proinflammatory cytokine and NO production, as well as prevention of apoptosis, is of paramount interest, making linomide a potential candidate for combating HIV-1 infection or preventing some of its associated pathological manifestations.

Adjuvants, Immunologic↗

[Treatment of low-grade gastric MALT lymphoma with Helicobacter pylori eradication. Follow-up of the histological and molecular response].

BACKGROUND: Low grade gastric MALT lymphoma is associated to infection with Helicobacter pylori. Also, H. pylori eradication can produce histologic regression of the lymphoma. PATIENTS AND METHODS: This study reports the follow-up of a prospective series of 11 patients with low grade gastric MALT lymphoma, stage I, treated with eradicative therapy for H. pylori. After treatment, patients were followed up with sequential endoscopies to asses the histological and molecular regression of the lymphoma, using a score of the histological lesions and the amplification of the IgH gene with PCR analysis. RESULTS: Helicobacter pylori was eradicated in all patients. In 10(90.9%) histological regression of the lymphoma was demonstrated, in 6 of them in the first control after treatment. In the 10 patients with histological response, PCR analysis demonstrated a polyclonal rearrangement of the IgH gene in 6 (60%) and a clonal band in 4 (40%), that eventually disappeared at 12 (SD 4) months after treatment. In 4 patients with a previous polyclonal rearrangement, a clonal band was occasionally detected in any sequential controls; in 2 of these cases the clonal band disappeared 5 and 7 months after treatment and in the remaining 2 its evolution is not yet known. Nine patients have been followed up and are in remission 18 (SD 8) months after treatment. CONCLUSIONS: Eradication of H. pylori can produce histologic regression in stage I low grade gastric MALT lymphoma, and should be the first therapeutic option. Despite histological regression of the lymphoma, PCR analysis can detect a clonal rearrangement of the IgH gene in 40% of the cases, but its significance remains unknown. Sequential and prolonged follow-up is essential to assess whether this lymphoma can be actually cured with eradication therapy for H. pylori.

Adult↗

[new one-week triple therapies with metronidazole for the eradication of Helicobacter pylori: clarithromycin or amoxycillin as the second antibiotic].

BACKGROUND: To compare the efficacy of two "new" one-week triple therapies (with omeprazole, metronidazole and clarithromycin or amoxycillin) for the eradication of Helicobacter pylori and healing duodenal ulcer. METHODS: Randomised therapeutic trial. Eighty-eight consecutive duodenal ulcer patients with H. pylori infection were studied. At endoscopy, biopsies from both gastric antrum and body were obtained for histologic study (H&E). Two different therapies were administered for one week: omeprazole (O) (20 mg b.i.d.) and metronidazole (M) (500 mg b.i.d.) associated with clarithromycin (C) (500 mg b.i.d.) (group OMC, n = 44) or amoxycillin (A) (1 g b.i.d.) (group OMA, n = 44). Endoscopy with biopsies was repeated one month after completing therapy, and a 13C-urea breath test was also performed. Compliance was evaluated by tablet count. Analysis of data: multiple logistic regression, intention-to-treat. Eradication was defined as the absence of H. pylori by all diagnostic methods. RESULTS: Mean age (standard deviation) was 45(14) years, 75% males. Distribution of variables was similar in both therapeutic groups. Forty-two patients in each group completed the protocol. Eradication was achieved in 90.5% (95% CI = 78-96%) in group OMC and in 57% (42-71%) in group OMA (p < 0.001). In the multivariate analysis the type of therapy was the only variable which influenced on H. pylori eradication (OR = 7.1; CI = 2.2-24; p = 0.001). Ulcer healing was demonstrated in 88% (75-95%) of patients in group OMC and in 71% (56-83%) in group OMA (p = 0.1). Ulcer healing was higher when eradication was achieved (90%; 80-95%) than in H. pylori-positive patients (50%; 31-69%) (p < 0.001). Eradication of H. pylori was the only variable which influenced on ulcer healing (OR = 9.3; CI = 2.8-31; p < 0.001). CONCLUSION: The "new" triple therapy with omeprazole, metronidazole and clarithromycin (administered in a twice-a-day basis and only for one week) had an excellent efficacy for the eradication of H. pylori, significantly higher than that obtained with amoxycillin instead of clarithromycin. Both therapies achieved a high ulcer healing rate when H. pylori was eradicated, even with omeprazole administered only for one week.

Adult↗

Transthyretin Tyr77 familial amyloid polyneuropathy: a clinicopathological study of a large kindred.

More than 40 point mutations (producing different clinical manifestations) have been described in diverse points of the plasma protein transthyretin (TTR). The Met30 is considered the most common mutation, the Tyr77 mutation being the second most prevalent. However, data from patients with this late mutation are scarce, and usually come from isolated case reports or tables. The Tyr77 mutation is not as well characterized as the Met30 mutation, especially with respect to such aspects as prognosis or possible treatment by liver transplantation. We therefore present the clinical and pathological features of an extensive family with the Tyr77 TTR mutation, comprising 12 affected individuals over four generations. Six living individuals were followed over a 10-year period. Retrospective data were obtained with regard to the deceased family members. We found that an initial and sometimes prolonged carpal tunnel syndrome, beginning between the 6th and 7th decades, characterizes the Tyr77 mutation. In most cases this evolved to generalized peripheral nerve involvement, restrictive cardiomyopathy, and intestinal malabsortion. Although survival is usually high, there are progressive cases that should be candidates for liver transplant, before severe impairment has developed.

Aged↗

Ureaplasma urealyticum reduces motility and induces membrane alterations in human spermatozoa.

The in-vitro effects of several concentrations of Ureaplasma urealyticum on the motility, membrane integrity and morphology of washed spermatozoa from healthy donors were studied. A significant reduction in sperm motility and signs of membrane alteration, directly related to U.urealyticum concentration and contact time were observed. Scanning electron microscopy examination showed masses of U. urealyticum attached to the head and middle piece of some of deformed spermatozoa. It is suggested that U.urealyticum is involved in sperm changes leading to male infertility, particularly when there is heavy U. urealyticum colonization or specific infections with this microorganism.

Bacterial Adhesion↗

Erosive duodenitis: prevalence of Helicobacter pylori infection and response to eradication therapy with omeprazole plus two antibiotics.

OBJECTIVES: To study the prevalence of Helicobacter pylori infection in patients with erosive duodenitis (ED), the associated gastric histological lesions and their response to eradication therapy with omeprazole plus two antibiotics. METHODS: A prospective study was made of 57 patients with ED (mean age 46 +/- 16 years, 72% males). At endoscopy, biopsies from gastric antrum and body were obtained for histological study (haematoxylin and eosin). A 13C-urea breath test was also performed. Omeprazole 20 mg twice daily plus two antibiotics (amoxycillin 1 g twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily) were administered for 1 week. Endoscopy and breath test were repeated 1 month after completing therapy, and the breath test was performed again at 6 months. RESULTS: All patients were H. pylori positive. Overall eradication was achieved in 86% (95% CI 75-93%). Duodenal erosion healing was obtained in 45 patients (79%). Healing was achieved in 86% (CI 73-93%) of cases with successful eradication therapy, but only in 3/8 (37%; CI 8.5-75%) patients with therapy failure (P < 0.01). In the multivariate analysis, H. pylori eradication was the only variable which correlated with erosion healing (odds ratio 10; CI 2-51; P < 0.01). Histological improvement, in both the gastric antrum and body, was demonstrated when eradication was achieved (P < 0.001). Six months after diagnosis H. pylori absence was confirmed in all patients with initial therapy success (all of them asymptomatic), and infection was confirmed in the eight patients who were H. pylori positive after therapy (six of them symptomatic). At 6-month follow-up, endoscopy was normal in 6/7 H. pylori-negative patients with previously persistent ED, while erosions were still present in 4/5 H. pylori-positive patients with previously persistent ED. CONCLUSION: A high prevalence (100%) of H. pylori infection in patients with ED was observed. A 1-week twice daily therapy with omeprazole plus two antibiotics (clarithromycin plus amoxycillin or metronidazole) was very effective in H. pylori eradication, duodenal erosion healing, symptomatic improvement, and in disappearance of associated histological gastritis. These observations suggest that ED should be considered a variant form of duodenal ulcer disease and treated accordingly; that is, with H. pylori eradication therapy.

Adult↗

Relation between histologic subtypes and location of gastric cancer and Helicobacter pylori.

BACKGROUND: Epidemiologic studies have consistently shown an association between Helicobacter pylori infection and gastric cancer, and it is now widely accepted that this organism plays a role in the pathogenesis of this tumor. Nevertheless, there are discrepant results on its relationship with the histologic type and location of gastric cancer within the stomach. The aim of this study was to determine the seroprevalence of H. pylori in a group of gastric cancer patients and the association between H. pylori and specific histologic types of gastric cancer and tumor location within the stomach. METHODS: Systemic IgG antibodies against H. pylori were assayed using an enzyme-linked immunosorbent assay technique in 48 patients (male to female ratio, 31:17; age range, 39-88 years; mean, 69 years) with histologically confirmed gastric cancer and 50 controls (male to female ratio, 33:17; age range, 40-77 years, mean, 64 years). RESULTS: Thirty-one cases of gastric cancer were of the intestinal type, and 12 of the diffuse type; the remaining 5 were unclassified. Thirteen gastric cancers were located in the distal stomach (antrum/pylorus), 12 in the body, and 5 in the proximal stomach (cardia/fundus); the remaining 17 were unclassified because the tumor extended towards more than one location. The overall seroprevalence of H. pylori in patients with gastric cancer and controls was 85.4% and 66%, respectively (P < 0.05). The seroprevalence increased with increasing age in cancer patients, but the difference was not significant. H. pylori seroprevalence among patients with the intestinal type of gastric cancer was higher than in those with the diffuse type (P < 0.05). The prevalence of H. pylori infection was higher among patients with the cancer located distally than in those with the cancer located proximally (P < 0.05). CONCLUSIONS: H. pylori seroprevalence was higher in gastric cancer patients than in controls. The prevalence of H. pylori infection in intestinal-type gastric cancer was clearly higher than in the diffuse type and in the control group. An association was found between H. pylori infection and tumors located distally (antrum/pylorus).

Adenocarcinoma↗

Helicobacter pylori eradication for the treatment of low-grade gastric MALT lymphoma: follow-up together with sequential molecular studies.

BACKGROUND: Helicobacter pylori infection is associated with low-grade gastric MALT lymphoma, and available data support that the eradication of the H. pylori can cause histological regression of the lymphoma. PATIENTS AND METHODS: Nine patients with low-grade gastric MALT lymphoma were treated with amoxicillin, metronidazole, and omeprazole for 14 days in a prospective study. Patients were followed up with sequential endoscopy, mapping gastric biopsies, and molecular studies with PCR amplification of the IgH gene in order to assess the response to H. pylori eradication and the evolution of the histological molecular responses. RESULTS: H. pylori was eradicated in all patients and reinfections were not demonstrated. After H. pylori eradication treatment, the lymphoma regressed both endoscopically and histologically in eight of the nine patients (88.8%). In four of the eight histologically cured patients, no clonal band was detected by PCR; in the remaining four patients; PCR identified a clonal band, which disappeared in all patients after a mean of 12 +/- 4 months. No clonal band was detected by the PCR analysis in any of the eight patients with histological regression after a median of 7 +/- 6 months (range 1-20). The seven followed-up patients have a persistent clinical and histological remission after a median of 14 +/- 5 months. CONCLUSIONS: (1) Low-grade gastric MALT lymphoma can be histologically cured with eradication therapy for H. pylori. (2) After histological regression, PCR amplification of the IgH gene can identify an eventually persisting clonal population. (3) Sequential histological and molecular studies are essential for the assessment of the evolution of the lymphoma. (4) The clonal population tends to disappear, but its disappearance may be delayed for months. (5) Patients with histological regression but with a persistent clonal band should not be treated unless the lymphoma can be histologically demonstrated. All these observations suggest that gastric lymphoma can be effectively cured, but the ultimate fate of these patients is unknown until long-term follow-up studies are available.

Aged↗

Linomide prevents the lethal effect of anti-Fas antibody and reduces Fas-mediated ceramide production in mouse hepatocytes.

Fas is an apoptosis-signaling receptor molecule expressed in vivo on thymocytes, liver, heart, and ovary. In vivo administration of the anti-Fas Jo2 antibody in mice induces severe apoptotic liver damage leading to fulminant hepatitis and death. Linomide, a quinoline 3-carboxamide, inhibits apoptosis of B and T cells induced by various stimuli including viruses, superantigens, and glucocorticoids. Mice treated with linomide survived the lethal effect of anti-Fas antibody, did not accumulate ceramide in hepatocytes, and recovered liver structure and function within 96 h of anti-Fas injection, as confirmed by histology and glutamic oxalacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase levels. Surviving mice showed severe depletion of cortical thymocytes, but medullar thymic cells expressing high CD3 and Fas levels also survived the treatment with anti-Fas in the presence of linomide. Heart, lung, and ovary showed no signs of apoptosis promoted by Fas ligation. These results suggest that linomide prevents cell death triggered by Fas ligation and can be useful for therapeutic intervention in fulminant hepatitis.

Animals↗

Basal and stimulated gastrin levels and gastric acid output five months after therapy for Helicobacter pylori eradication in duodenal ulcer patients.

The aim of our study was to demonstrate the effect of Helicobacter pylori eradication on basal and stimulated serum gastrin levels and gastric acid output 5 months after therapy of patients with duodenal ulcer. Thirty-two patients (24 men and eight women with a mean age of 45 years) who had had endoscopy and were diagnosed as having duodenal ulcer entered the study. In all patients three biopsy specimens were taken from the duodenal bulb, gastric antrum, body, and fundus. These specimens were then sent for microbiological and histological examination. Triple therapy consisting of bismuth, metronidazole, and tetracycline was administered. Endoscopy was repeated 1 and 5 months after therapy, and biopsy specimens were again taken from the gastric antrum and body. Before treatment, serum samples were taken to measure basal and stimulated (90 min) gastrin levels after ingestion of two beef cubes, and basal and stimulated acid outputs (after pentagastrin) were studied. Measurements of gastrin and gastric acid output were repeated 5 months after therapy. H. pylori was eradicated in 26 patients (81.3%). Basal gastrin levels (mean +/- SD) at diagnosis and after eradication were 44 +/- 12 and 35.8 +/- 2 pg/ml, respectively (p < 0.05). Similarly, stimulated gastrin levels (integrated values) decreased from 5,303 +/- 1,526 pg/ml/min before therapy to 3,779 +/- 1,204 pg/ml/min after eradication (p < 0.001). However, basal (4.9 +/- 4mEq/h) and stimulated (28.5 +/- 10mEq/h) acid output did not vary after eradication (3.9 +/- 4 mEq/h and 26.2 +/- 12 mEq/h, respectively). We conclude that basal and stimulated gastric acid output are not changed by H. pylori eradication in duodenal ulcer patients 5 months after therapy, in spite of its association with a significant decrease in basal and stimulated gastrin levels.

Adult↗

Verification of decreased basal and stimulated serum pepsinogen-I levels is a useful non-invasive method for determining the success of eradication therapy for Helicobacter pylori.

BACKGROUND: We wanted to demonstrate the effect of Helicobacter pylori eradication on basal and stimulated pepsinogen-I levels in duodenal ulcer patients and to verify whether modification of such levels is a useful method for determining the success of eradication therapy. METHODS: Thirty-two patients (24 men; mean age, 45 years) with active duodenal ulcer were studied. In all patients three biopsy specimens were taken from the duodenal bulb, gastric antrum, body and fundus for microbiologic and histologic examination. Triple therapy consisting of bismuth, metronidazole, and tetracycline was administered. Endoscopy was repeated 1 month after completing therapy, and biopsy specimens were again taken from the gastric antrum and body. Serum samples were taken at initial and repeat endoscopies, to measure basal and stimulated (120 min) pepsinogen-I levels after injection of pentagastrin. RESULTS: H. pylori was eradicated in 26 patients (81%). Significant histologic improvement, in both the antrum and body, was observed (p < 0.001). Basal pepsinogen-I levels (mean and 95% confidence interval) at diagnosis and after eradication were 106 (92-119) and 87 (74-100) ng/ml, respectively (P < 0.001). Similarly, stimulated pepsinogen-I levels (integrated values) decreased from 4790 (4199-5381) before therapy to 3970 (3383-4557) ng/ml.min after eradication (P < 0.001). Pepsinogen I levels did not change in patients in whom H. pylori was not eradicated. The area under the receiver operating characteristic curve for decreased basal and stimulated pepsinogen-I levels was 0.77 (SE, 0.09) and 0.79 (SE, 0.1), respectively. CONCLUSION: H. pylori eradication in duodenal ulcer patients was associated with a significant decrease in basal and stimulated pepsinogen-I levels. Measurement of these levels could determine how successful response to therapy has been in both the eradication and resolution of associated gastritis. Other advantages of this procedure are that it has low cost and results are evident at an early stage.

Adult↗

[Basal levels of blood pepsinogen I and Helicobacter pylori infection in patients with duodenal ulcer and normal endoscopy].

AIM: To study basal pepsinogen I levels in patients with duodenal ulcer and in subjects with normal endoscopy, depending on Helicobacter pylori status. METHODS: One-hundred and one patients with duodenal ulcer and 74 controls with normal endoscopy were studied. Mean age and gender distribution were: 46 vs 42 years, and 74% vs 43% males, respectively. At endoscopy biopsies from the gastric antrum and body were obtained for histologic (H&E) and microbiologic (Gram and culture) study. Basal levels of serum pepsinogen I were measured (RIA). RESULTS: Among the subjects with a normal endoscopy, those with H. pylori infection had higher pepsinogen I levels (m +/- SD) than non-infected patients (77 +/- 27 vs 62 +/- 28 ng/ml; p < 0.05). Basal levels in duodenal ulcer patients were 107 +/- 38 ng/ml, higher (p < 0.001) than in the group with normal endoscopy (both with and without H. pylori). In multivariate analysis pepsinogen I levels were correlated with H. pylori infection (regression coef.= 17; SE= 8.1), duodenal ulcer (regr. coef.= 22; SE= 5.8) and smoking habit (regr. coef.= 24; SE= 5.2). CONCLUSION: Basal pepsinogen I levels were significantly higher in duodenal ulcer patients than in H. pylori infected subjects with normal endoscopy. The lowest levels corresponded to non-infected patients. Therefore, an additional factor other than H. pylori infection is likely involved in the hyperpepsinogenemia classically reported in duodenal ulcer patients.

Adult↗