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Biomedical subjects

P Domingo

Publications and source records attributed to P Domingo.

At least 19 recordsLinked to original sources
PubMed2005

Tumour necrosis factor alpha in fat redistribution syndromes associated with combination antiretroviral therapy in HIV-1-infected patients: potential role in subcutaneous adipocyte apoptosis.

BACKGROUND: The pathogenesis of fat redistribution syndromes (FRS) observed in the setting of highly active antiretroviral therapy (HAART) for the treatment of HIV-1-infection remains elusive. A dysregulation of the tumour necrosis factor alpha (TNF-alpha) system occurs in HIV-infected patients with FRS. MATERIALS AND METHODS: The study looked at both the in vivo and in vitro relationship between TNF-alpha and the degree of subcutaneous adipocyte apoptosis in 60 HIV-1-infected patients on HAART with FRS, another 60 HIV-1-infected patients on HAART without FRS and 60 uninfected control patients. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP (deoxyuridine 5'-triphosphate)-digoxigenin Nick End Labelling (TUNEL) method. Soluble receptors of TNF-alpha were determined by the sandwich enzyme immunoassay technique. The in vitro viability was assessed by staining with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and apoptosis by TUNEL. RESULTS: HIV-1-infected patients with FRS had significantly higher degrees of subcutaneous adipocyte apoptosis than those without FRS (P = 0.0001) and uninfected controls (P < 0.0001). There was a statistically significant association between serum levels of soluble TNF-alpha receptors #1 and #2 and the degree of subcutaneous adipocyte apoptosis in patients with and without FRS (P < 0.0001 for both receptors). In vitro, the addition of TNF-alpha (10 ng mL(-1)) to an adipocyte culture embedded with indinavir, either alone or in clinically relevant combinations with stavudine (d4T) and lamivudine (3TC), significantly decreased adipocyte viability (P = 0.0001) and increased adipocyte apoptosis (P < 0.0001) with respect to that observed with the addition of antiretrovirals alone. CONCLUSIONS: TNF-alpha plays a significant role in subcutaneous adipocyte apoptosis, which occurs in the setting of FRS in HIV-1-infected patients on highly active antiretroviral therapy.

3T3 Cells↗
PubMed2004

Relevance of genetically determined host factors to the prognosis of meningococcal disease.

To assess the relevance of genetically determined host factors for the prognosis of meningococcal disease, Fc gamma receptor IIA (FcgammaRIIA), the tumor necrosis factor alpha (TNF-alpha) gene promoter region, and plasminogen-activator-inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with meningococcal disease and in 290 healthy controls matched by sex. Distribution of FcgammaRIIA, TNF-alpha, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcgammaRIIA-R/R 131 allotype scored > or =1 point in the Barcelona prognostic system more frequently than patients with other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1-49.0, P<0.0001), and they had a higher risk of sequelae (odds ratio, 3.5; 95% confidence interval, 1.1-11.7; P=0.03). Fc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

Adolescent↗
PubMed2004

Unmasking influenza virus infection in patients attended to in the emergency department.

BACKGROUND: Infection by the influenza virus may pass undetected in many adult patients attended to in the emergency department because its diagnosis usually relies on clinical manifestations, which can be distorted by symptoms of a preexisting disease, superposed complications or nontypical manifestations of influenza virus infection (confusing symptoms). PATIENTS AND METHODS: We performed this observational, prospective study with an antigen detection test by indirect immunofluorescence assay (IFA) to estimate the presence of influenza virus infection in such patients. No confirmatory test was performed to validate a positive or negative IFA result. Then we compared those who were antigen positive to those who were negative and also analyzed those who were positive classified by age, comorbidity and clinical presentation. We also evaluated the use of medical and hospital resources and vaccination status. Posterior pharynx swab specimens from 136 consecutive adult patients, 74 women and 62 men with a mean age of 68.7 +/- 17.9 (range: 18-97) years attended to in the emergency department of a university hospital in Barcelona during the 1999-2000 influenza epidemic were examined. Tested patients presented either a classical influenza syndrome, a deterioration of a previous condition or any abrupt onset of symptoms without an obvious cause. RESULTS: Influenza A virus antigen was detected in 99 (72.8%) of the 136 patients included in the study. Confusing symptoms were present in 86 patients with laboratory-confirmed influenza and 40 of them lacked influenza syndrome. Prostration, aching and fever out of proportion to catarrhal symptoms (disproportionate prostration) and cough were independent predictors for this diagnosis (OR = 5.14; 95% CI: 1.98-13.35, p = 0.001 and OR = 4.40, 95% CI, 1.65-11.75, p = 0.03, respectively). Among the 99 patients who tested positive, 72 were >or= 65 years of age. This older positive group compared to the 27 also positive < 65 (non-old) had a tendency to show symptoms mediated by cytokines less frequently: malaise was present in 76.4% of the older positive patients vs 92.6% in the non-old positive ones, p = 0.07. The equivalent percentages for muscle ache were: 56.9% vs 77.8%, p = 0.06; for dysthermia: 54.2% vs 70.4%, p = 0.08; for headache: 35.2% vs 66.7%, p = 0.005, and for disproportionate prostration: 47.2% vs 66.7%, p = 0.08. Cough was more frequent in the older positive group: 94.4% vs 77.8%, p = 0.02. Older positive patients were also hospitalized and received antibiotics more frequently than the non-old positive ones: 65.3% vs 40.7%, p = 0.03 and 81.9% vs 63.0%, p = 0.046, respectively. Hospitalization was independently correlated with the presence of complications (OR = 4.5, 95% IC 1.27-15.95, p = 0.02). Patients with the highest comorbidity, evaluated with the Charlson scale, were more inadequately vaccinated than those with moderate or low comorbidity. CONCLUSION: Influenza virus infection has a great and underestimated impact in the emergency department during influenza epidemics. High frequency of confusing symptoms, which overcome classical influenza syndrome in adult people with comorbidity, may explain this effect. Disproportionate prostration and cough are symptoms that independently predict its diagnosis in the global adult population, whereas in the elderly, fever and cough should arouse this suspicion whether or not they present classic symptoms. In our setting, individuals with high comorbidity are inadequately vaccinated.

Adult↗
PubMed2004

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Anti-HIV Agents↗
PubMed2001

Switching to nevirapine decreases insulin levels but does not improve subcutaneous adipocyte apoptosis in patients with highly active antiretroviral therapy-associated lipodystrophy.

Subcutaneous adipocyte apoptosis occurs in lipotrophic areas of patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. Fourteen patients with HAART-associated lipodystrophy had 2 subcutaneous biopsies for evidence of adipocyte apoptosis, the second after a randomized change to nevirapine (n=8) or after remaining on a regimen of indinavir-based HAART (n=6). Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end-labeling method. Patients who were switched to nevirapine had a significant decrease in insulinemia and a significant increase in the glucose:insulin ratio. Overall, subcutaneous adipocyte apoptosis increased in 3 patients who were switched to nevirapine and in 3 who continued to receive indinavir but decreased in 2 patients switched to nevirapine and another 2 who continued to receive indinavir. Subcutaneous adipocyte apoptosis continues to occur in lipotrophic areas of patients with HAART-associated lipodystrophy despite switching from indinavir to nevirapine, suggesting that such a strategy will be useless for reversal of lipoatrophy.

Adipocytes↗
PubMed2001

Drug resistance in patients experiencing early virological failure under a triple combination including indinavir.

OBJECTIVE: To assess the pattern of drug resistance mutations selected in HIV-1-infected patients failing a first line triple combination therapy including indinavir. PATIENTS AND METHODS: Plasma samples from 87 patients collected at the time of the first virological rebound (> 50 HIV-RNA copies/ml) were examined for the presence of drug-resistant genotypes. RESULTS: The mean level of plasma viraemia at rebound was 7824 HIV-1 RNA copies/ml in 73 subjects with good compliance, whereas it was 359,460 HIV-1 RNA copies/ml in 14 patients who admitted to poor adherence. Genetic sequence analysis yielded results for 51 (70%) of the patients having good adherence. More than half of them (26/51, 51%) carried primary mutations associated with resistance to nucleoside analogues. In contrast, primary protease inhibitor resistance mutations were recognized less frequently (14/51, 27%; P < 0.05). Moreover, in 23 (45%) patients there was no evidence of drug-resistant viruses at all. The most frequent drug-resistant genotypes in the reverse transcriptase gene were at codons 184 (n = 19), 215 (n = 14) and 41 (n = 8), whereas for the protease they were at codons 46 (n = 10), 82 (n = 9) and 90 (n = 7). No resistance genotypes were found among non-compliant patients. CONCLUSION: The overall rate of drug-resistant HIV genotypes was 38% (28/73) in patients with good adherence and who were experiencing a first virological failure under a triple combination regimen including indinavir; resistance to nucleoside analogues was more frequent than resistance to indinavir. Therefore, treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.

Adult↗
PubMed2001

Failure of a short-term prednisone regimen to prevent nevirapine-associated rash: a double-blind placebo-controlled trial: the GESIDA 09/99 study.

OBJECTIVES: Rash is the most frequent adverse event associated with nevirapine. The use of prednisone has been controversial in this setting. A double-blind placebo-controlled study was performed to evaluate its efficacy in nevirapine-induced rash prevention. DESIGN: Multicentered, randomized, double-blind, placebo-controlled clinical trial with prednisone (30 mg/day x 2 weeks). INCLUSION CRITERIA: HIV-1 infection; CD4 count >200 cells/mm3; plasma viral load (PVL) <5 log10 copies/ml; nevirapine (200 mg/day x 2 weeks, followed by 200 mg twice daily) plus stavudine and didanosine. Clinical follow-up was performed at 15, 30, and 60 days and thereafter every 2 months. RESULTS: In all, 75 evaluable patients were enrolled (39 prednisone/36 placebo). Median baseline CD4 + cell count was 390 cells/mm3 and PVL, 20,200 copies/ml. Overall, nine cases of rash (12.5%) were detected, seven (18%) in the prednisone group and two (5.5%) in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 0.65-29.3; p =.11). Incidence of moderate-to-severe rashes leading to nevirapine withdrawal was 13.5% (5 of 37) in the prednisone group and 3% (1 of 35) in the placebo group ( p =.2). Median time to rash in both groups was 16 days. Adverse events that motivated withdrawal of therapy appeared in 6 patients from the prednisone group (15.4%) and 3 from the placebo group (8.3%) ( p =.3). CONCLUSION: Short-term prednisone administration does not prevent nevirapine rash, but might even increase its incidence.

Adult↗
PubMed2001

Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with hiv-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study.

BACKGROUND: Simpler and less toxic antiretroviral strategies are needed to maximize treatment compliance without sacrificing potency, at least for drug-experienced HIV-infected patients currently on regimens containing protease inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of PI-sparing regimens on lipodystrophy. OBJECTIVES: To assess the virologic, immunologic, and clinical benefit of switching the PI to nevirapine in patients with HIV-associated lipodystrophy and sustained viral suppression before entry in the study. DESIGN: Open-labeled, prospective, randomized, multicenter study. SETTING: Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS: One hundred six HIV-infected adults with clinically evident lipodystrophy who sustained HIV-RNA suppression for at least 6 months with PI-containing antiretroviral combinations. INTERVENTION: Replacement of the PI with nevirapine during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS: Several virologic and immunologic analyses, standard and specific biochemical tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS: At week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of patients in Groups A and B, respectively, whereas 74% and 72% of patients had viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in both groups compared with baseline values, and a significant decrease in CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no significant changes in anthropometric or body shape measurements were found after 48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A (but not in Group B) compared with baseline values (p <.05), although no significant differences were seen between groups at the end of the study. Subjects in Group A reported a better quality of life (QOL) index than controls (p <.001), with the main reason reported being the greater simplicity of the new drug regimen. CONCLUSIONS: Protease inhibitor-sparing regimens, including nevirapine, seem to be an effective alternative for PI-experienced patients. Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels and improve the immunologic response at 48 weeks of follow-up in patients with prior sustained virologic suppression. The switch to nevirapine significantly improved the lipidic profile in Group A, although there were no differences between groups at the end of the study. Additionally, no significant changes were seen in terms of lipodystrophy-related body shape changes 1 year after the PI substitution. Finally, nevirapine-containing regimens have a simpler dosing schedule, and this facilitates high adherence and improves QOL.

Adult↗
PubMed2001

Herpes zoster as an immune reconstitution disease after initiation of combination antiretroviral therapy in patients with human immunodeficiency virus type-1 infection.

BACKGROUND: Initiation of combination antiretroviral therapy may be followed by inflammatory reactions. We studied the epidemiology of herpes zoster infection among patients with human immunodeficiency virus (HIV) infection who were treated with combination antiretroviral therapy. SUBJECTS AND METHODS: Of 316 patients who initiated combination antiretroviral therapy, 24 (8%) were treated for herpes zoster within 17 weeks of starting therapy. The characteristics of these cases were compared with those of a control group of 96 HIV-1-infected patients, who were matched by age, sex, plasma HIV-1 RNA concentration and CD4 cell counts, and length of follow-up. RESULTS: The incidence of herpes zoster associated with combination antiretroviral therapy was 9 episodes per 100 patient-years. There were no significant differences between cases and controls in age, sex, years of HIV infection, history of herpes zoster, previous acquired immune deficiency syndrome, or baseline mean CD4 and CD8 cell counts before beginning combination antiretroviral therapy. However, patients who developed herpes zoster had a significantly greater mean (+/- SD) increase in the number of CD8 cells than did controls (347 +/- 269 vs. 54 +/- 331 cells/mL, P = 0.0006). In a multivariate analysis, the only factor that was associated with the development of herpes zoster was the increase in CD8 cells from before initiation of combination antiretroviral therapy to 1 month before development of herpes zoster (odds ratio 1.3 per percentage increase; 95% confidence interval: 1.1 to 1.5; P = 0.0002). CONCLUSION: The initiation of combination antiretroviral therapy in HIV-1-infected patients was often associated with the development of herpes zoster, especially in those in whom the number of CD8 cells increased after therapy.

Adult↗
PubMed2001

A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98.

BACKGROUND: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. METHODS: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. RESULTS: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years). CONCLUSIONS: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

AIDS-Related Opportunistic Infections↗
PubMed2001

Hypertrichosis lanuginosa acquisita preceding extraskeletal Ewing's sarcoma.

A 62-year-old woman with acquired hypertrichosis lanuginosa as a paraneoplastic presenting sign of an extraskeletal Ewing's sarcoma is described. Despite initial comprehensive screening to rule out an associated malignancy, a definitive diagnosis of sarcoma was established only 1 year after the onset of the cutaneous symptoms. To the best of our knowledge, this is the first report of hypertrichosis lanuginosa acquisita associated with a soft tissue sarcoma. Our observation expands the spectrum of malignancies associated with this uncommon paraneoplastic disorder.

Female↗
PubMed2001

Group B Streptococcal sacroiliitis: case report and review.

Streptococcus agalactiae, or group B Streptococcus (GBS), is the major cause of neonatal meningitis and sepsis but is an uncommon infection in adults. GBS arthritis is rare, and axial involvement with sacroiliitis is even more uncommon. Microbiological diagnosis frequently relies upon positive blood cultures as synovial fluid cultures are usually negative. Severe joint damage may result due to delay in the initiation of antibiotic treatment.

Adult↗