Guillermo Vázquez

Subcutaneous adipocyte apoptosis in Hiv-1 protease inhibitor-associated lipodystrophy

BACKGROUND Inhibitors of HIV-1 protease produce a rapid decrease in plasma HIV-1 RNA, with concomitant immune reconstitution. However, severe metabolic side effects together with a previously unseen form of lipodystrophy have been associated with long-term use of protease-inhibitor therapy. The pathogenic mechanisms underlying HIV-1 protease inhibitor-associated lipodystrophy are still largely unknown. METHODS Fourteen HIV-infected patients with HIV-1 protease inhibitor-associated lipodystrophy had a biopsy of subcutaneous fat performed in the antero-lateral aspect of the right leg. The samples were submitted for standard pathologic study together with a careful search for adipocyte apoptosis. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end labelling (TUNEL) method, using the ApopTag kit (Oncor, Gaithersburg, Maryland, USA). The procedure was performed between three and five times for each sample. Appropriate positive and negative controls were used. Controls which were subcutaneous fat biopsies from patients with untreated melanoma were also examined for the presence of apoptosis. RESULTS Fourteen HIV-infected patients with a mean exposure to HIV-1 protease inhibitors of 12.6 +/- 3.7 months (range: 6-21 months), developed the characteristic features of HIV-1 protease inhibitor-associated lipodystrophy. All but one patient had an abnormal waist:hip ratio, and they all exhibited an abnormal serum lipid profile. Pathologically, subcutaneous fat atrophy was a constant feature, along with focal lipogranuloma formation and vascular proliferation. One of the eleven assessable biopsy samples was negative for the presence of apoptosis, six showed focally positive apoptotic cells, and the remaining four biopsies demonstrated moderate positivity. Apoptotic changes were also detected in endothelial cells. Apoptotic changes were more pronounced in patients with higher increases in CD4 and CD8 counts, and in those with a greater decay in plasma viral load. CONCLUSIONS Subcutaneous adipocyte apoptosis occurs in lipoatrophic areas of patients with HIV-1 protease inhibitor-associated lipodystrophy.

Outcome Predictors of Pneumonia in Elderly Patients: Importance of Functional Assessment

Objectives: To evaluate the outcome of elderly patients with community‐acquired pneumonia (CAP) seen at an acute‐care hospital, analyzing the importance of CAP severity, functional status, comorbidity, and frailty.

Infection caused by Nocardia farcinica: case report and review.

Abstract Nocardia farcinica is a rare Nocardia species causing localised and disseminated infections. A case of Nocardia farcinica infection is presented, and 52 cases previously reported in the literature are reviewed. The hosts usually had predisposing conditions (85%), and acquired the infection through the respiratory tract or skin; the infection then often spread to the brain, kidney, joints, bones and eyes. Pulmonary or pleural infections (43%), brain abscesses (30%) and wound infections (15%) which failed to respond to conventional antimicrobial therapy were the more frequent forms of infection. Nocardia farcinica was frequently isolated from pus (100% of samples), bronchial secretions (41%) and biopsy specimens (63%), but isolation from blood and urine, as in the case presented here, is rare. Antibiotic therapy was adequate in 61% of the patients in whom it was specified, the agents most frequently given being trimethoprim-sulfamethoxazole (54%), amikacin combined with imipenem (7%) and amoxicillin-clavulanate (7%). The high mortality (31%) can be attributed to the severe underlying diseases present, difficulties encountered in identifying the pathogen, inappropriate therapy and late initiation of therapy. Although an infrequent pathogen, Nocardia farcinica should be kept in mind as a cause of infection especially in immunosuppressed patients with indolent infections not responding to third-generation cephalosporins.

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.

Associations between Fc gamma receptor IIA polymorphisms and the risk and prognosis of meningococcal disease

BACKGROUND In vitro studies have shown that the neutrophil Fc gamma receptor IIA (FcgammaRIIA) polymorphism influences the phagocytic capacity of neutrophils and the removal of encapsulated bacteria from the bloodstream. In particular, the R/R131 allotype is associated with less phagocytic activity. SUBJECTS AND METHODS We performed a case-control study to determine the influence of the FcgammaRIIA polymorphism (R/R131, R/H131, H/H131) on the risk and outcome of meningococcal disease. The polymorphisms were measured in 130 patients with microbiologically proven meningococcal disease diagnosed from 1987 to 1998 (cases) and 260 asymptomatic sex-matched blood donors (controls). Clinical manifestations and complications of meningococcal disease were recorded, and a prognostic score (based on age, hemorrhagic diathesis, neurologic signs, and the absence of preadmission antibiotic) therapy was calculated. RESULTS The distributions of FcgammaRIIA allotypes were similar in cases and controls. However, among patients with meningococcal infection, fulminant meningococcal disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.0 to 16; P = 0.04) and meningococcemia without meningitis (OR = 3.0; 95% CI: 1.4 to 7.8; P = 0.004) were more common in those with the FcgammaRIIA-R/R131 allotype. Complications were also significantly more frequent in these patients. Of the 42 patients with the R/R131 allotype, 31 (74%) had an adverse prognostic score, compared with 7% (4 of 59) of those with the R/H131 allotype and 3% (1 of 29) of those with the H/H131 allotype (P <0.0001). CONCLUSION The FcgammaRIIA-R/R131 allotype is associated with more severe forms of meningococcal disease.

Morbidity Associated with Long-Term Use of Totally Implantable Ports in Patients with AIDS

To determine the morbidity associated with long-term use of a totally implantable central venous access device (Port-A-Cath [PAC]) in patients with AIDS, we studied 68 consecutive patients with AIDS requiring 79 such devices for long-term use, inserted over a period of 5 years. The total number of PAC-days was 20,159. At least one PAC-related complication occurred with 40 of 79 PACs (50.6% [95% confidence interval (CI): 39.6%-61.6%]), and 16 devices (20.2% [95% CI, 11.4%-29.0%]) had to be removed because of complications. Device-related infection occurred with 33 of 79 PACs (41.7% [95 CI, 30.8%-52.6%]). The predominant infection occurring with PACs was chamber infection, with an incidence of 0.16 per 100 PAC-days. The predominant organisms isolated from patients with chamber infections but also from those with device-related bacteremia were gram-positive cocci (79.4%). The presence of neutropenia (odds ratio [OR] = 9.72; 95% CI, 3.0-31.3; P < .001) and a CD4 cell count lower than 0.025 x 10(9)/L (OR = 6.14; 95% CI, 1.9-19.2; P = .002) were independent predictors of infection. The antibiotic lock technique was associated with decreased device loss when compared with isolated systemic antibiotic therapy (OR = 0.05; 95% CI, 0.0-0.59; P = .008). This technique may be useful to treat PAC infection in patients with AIDS, for whom the risk of PAC-related complications is very high.

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 (FcγRIIA), the tumor necrosis factor alpha (TNF-α) 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 FcγRIIA, TNF-α, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcγRIIA-R/R 131 allotype scored ≥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-α and PAI-1 polymorphisms were not.

Unmasking Influenza Virus Infection in Patients Attended to in the Emergency Department

Abstract.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 laboratoryconfirmed 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 ≥ 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.

Group A Streptococcal Meningitis in the Antibiotic Era

Abstract A case of group A streptococcal meningitis is reported and the 51 cases reported in the literature since 1966 reviewed. A total of 24 men and 24 women were included in the study; the mean age (±SD) was 20.9±25.5 years. Fifty-eight percent of the patients had comorbid conditions, 80% had a distant focus of infection, and 65.8% had blood cultures positive for group A streptococci. Seventy-five per cent of the patients were treated with penicillin. The overall case-fatality rate was 12% (6 patients). Sequelae were more prevalent among children (44%) than among adults (7.7%) (OR=9.43; 95% CI, 1.02–438.95;P=0.03). Group A streptococcus is a rare cause of pyogenic meningitis, affecting mainly children or adults with co-morbidity. Although the case-fatality rate is relatively low, neurological sequelae are frequent among survivors, especially children.

Optimized symbolic dynamics approach for the analysis of the respiratory pattern

Traditional time domain techniques of data analysis are often not sufficient to characterize the complex dynamics of respiration. In this paper, the respiratory pattern variability is analyzed using symbolic dynamics. A group of 20 patients on weaning trials from mechanical ventilation are studied at two different pressure support ventilation levels, in order to obtain respiratory volume signals with different variability. Time series of inspiratory time, expiratory time, breathing duration, fractional inspiratory time, tidal volume and mean inspiratory flow are analyzed. Two different symbol alphabets, with three and four symbols, are considered to characterize the respiratory pattern variability. Assessment of the method is made using the 40 respiratory volume signals classified using clinical criteria into two classes: low variability (LV) or high variability (HV). A discriminant analysis using single indexes from symbolic dynamics has been able to classify the respiratory volume signals with an out-of-sample accuracy of 100%.