José A. Maradona

IL-1β (+3954C/T) polymorphism could protect human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treatment (HAART) against lipodystrophic syndrome

Purpose: To evaluate the impact of acquired and inherited factors on the development of lipodystrophic syndrome in patients on highly active antiretroviral therapy.Methods: Two hundred forty-three human immunodeficiency virus-infected Caucasians on highly active antiretroviral therapy were prospectively followed-up for 3 years. Eleven were naÍve and 232 were on antiretrovirals (mean, 93.0 months ± 43.8 months). Lipodystrophic syndrome was diagnosed clinically with a lipodystrophy severity grading scale. Polymorphisms of cytokines (IL-1β, IL-6, TNF-α), TLR4, and NOS genes were genotyped.Results: Ninety (37%) patients developed lipodystrophic syndrome. The polymorphic T allele of the (+3954C/T) polymorphism of IL-1β was less frequent in patients with lipodystrophic syndrome compared with those without (17.8% vs. 27.0%, P = 0.03). Factors significantly associated with lipodystrophic syndrome were time on stavudine (P < 0.001), use of stavudine (P = 0.001), absence of the T allele of the (+3954C/T) IL-1β polymorphism (P = 0.02), acquired immune deficiency syndrome diagnosis (P = 0.005), nadir levels of CD4 (P = 0.003), and time on highly active antiretroviral therapy (P = 0.003). Of these factors, only the time on stavudine (hazard ratio [95% confidence intervals] 1.007 [1.001–1.013]), use of stavudine (1.678 [1.048–2.68]), and absence of the T allele of the IL-1β (+3954C/T) polymorphism (0.569 [0.347–0.931]) were significantly associated with lipodystrophic syndrome by Cox regression.Conclusions: Genotyping of the (+3954C/T) polymorphism of IL-1β could be useful in patients starting highly active antiretroviral therapy, especially in potential users of stavudine, to predict their risk of developing lipodystrophic syndrome.

Perirenal Fat Diameter Measured by Echography Could Be an Early Predictor of Lipodystrophy in HIV Type 1—Infected Patients Receiving Highly Active Antiretroviral Therapy

Echographically measured thicknesses of perirenal and subcutaneous fat, as well as serum metabolic and anthropometric parameters, were evaluated in 74 human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy (HAART), 22 of whom were HAART-naive at baseline, who were followed-up for 27 months to detect predictive factors of lipodystrophy. Perirenal fat diameter (PRFD) at baseline differed in HAART-naive and HAART-experienced patients (P<.001), and it was the best predictor of lipodystrophy changes after 12 months of follow-up in the HAART-naive patients (hazard ratio, 7.34; 95% confidence interval, 1.18-45.49; P=.032). In addition, HAART-experienced patients in whom lipodystrophy improved had thinner baseline perirenal fat than those in whom lipodystrophy did not improve (P=.04). A PRFD of >2.6 mm at baseline or >4.9 mm during receipt of HAART suggested lipodystrophy predisposition. PRFD correlated significantly with other metabolic and anthropometric parameters. Echographically measured PRFD is associated with lipodystrophy and could be used as an early predictor of this syndrome in treatment-naive patients starting HAART.

IL‐1α (− 889) promoter polymorphism is a risk factor for osteomyelitis

As osteomyelitis (OM) induces the synthesis of inflammatory cytokines and IL‐1 mediates bone resorption by osteoclasts we determined if there is an association between certain common polymorphisms of the genes encoding proinflammatory cytokines (IL‐1α and β, IL‐6, TNF‐α) and OM in adults. The IL‐1α (− 889) TT genotype was significantly more frequent among 52 OM patients than in 109 healthy controls (13/52, [25.0%] vs. 9/109, [8.3%], P = 0.0081, χ2 = 7.01, OR = 3.7, 95% CI, 1.35–10.34). Patients who were homozygous for the T allele were younger than the rest of the OM patients (mean age 35.7 ± 11.5 vs. 58.1 ± 18.6 years, P = 0.001). IL‐1β TT (+ 3953) polymorphism was also more frequent in OM patients (P = 0.014, χ2 = 5.12, OR = 5.1, 95% CI, 1.21–52.14), but IL‐1β is in linkage disequilibrium with the IL‐1α *T (P < 0.001). Route of infection, chronicity of the infection, type of microorganism isolated, and frequency of relapses were similar in patients with and without the IL‐1α TT genotype. There were no associations between OM and polymorphisms of other cytokines genes. IL‐1α serum levels were significantly increased in all the OM patients independently of their IL‐1 genotype compared to the controls (P = 0.021). Although IL‐1α serum levels were not significantly higher in patients with the IL‐1α (− 889) polymorphism, this does not exclude a difference in production of IL‐1α by osteoclasts or other inflammatory cells at the site of infection.

Visceral leishmaniasis and other severe infections in an adult patient with p47-phox-deficient chronic granulomatous disease.

SummaryWe report a rare case of a male patient without known immunodeficiency consecutively diagnosed with visceral leishmaniasis, brain abscess and cavitating pneumonia in the 3rd decade of life. Chronic granulomatous disease (CGD) was diagnosed by a nitroblue tetrazolium test. A p47-phox mutation of the NADPH oxidase of the leukocytes was suspected by immunoblotting and confirmed by DNA analysis. The patient was homozygous for this mutation while his mother and sister were heterozygous asymptomatic carriers. After the CGD diagnosis the patient started a chronic prophylactic regimen with subcutaneous interferon-γ (0.05 mg/m2 of body surface/three times a week), and oral trimethoprim-sulfamethoxazole and itraconazole (both at 5 mg/kg/day) with no subsequent infections after 12 months of follow-up.

Eikenella corrodens Brain Abscess after Repeated Periodontal Manipulations Cured with Imipenem and Neurosurgery

Eikenella corrodens is a facultatively anaerobic gramnegative rod that colonizes the oral cavity and very rarely produces central nervous system (CNS) infections. Frontal lobe abscesses are occasionally associated with a dental source of infection. We report a case of an adult man with overzealous dental cleaning habits who developed a right frontal brain abscess caused by E. corrodens. He underwent neurosurgical drainage of the pus and was successfully treated with imipenem 4 g/iv/day for 4 weeks with no complications. Repeated periodontal trauma could explain the Eikenella brain abscess in this case.

Imipenem therapy of brain abscesses.

The efficacy of imipenem versus standard chemotherapy (both in addition to neurosurgery) in the treatment of brain abscess was compared in a retrospective study. Cure was obtained in 52 of 60 (86.7%) patients in the standard group, and in 15 of 15 (including 5 patients with multiple brain abscesses) in the imipenem group. Cure without neurosurgery was observed in 2 of 60 (3.3%) and 3 of 15 (20%) of the cases, respectively (p = 0.08). Levels of imipenem in blood, cerebrospinal fluid, and brain pus were above the minimum inhibitory concentrations of most of the abscess isolates. Side effects of imipenem were rare and tolerance was excellent. Imipenem monotherapy (3–4 g/day) for five weeks seems a reasonable therapeutic choice for treatment of bacterial brain abscesses.

Factors Influencing the Development of Lipodystrophy in Human Immunodeficiency Virus-infected Patients

238 human immunodeficiency virus-infected patients on highly active antiretroviral therapy (HAART) were studied, 67 of whom (28.2%) developed lipodystrophy. The presence of hyperlipidaemia (p=0.002) and of hepatitis C virus coinfection (p=0.014) were associated with lipodystrophy, but only the duration of HAART was significantly predictive of lipodystrophy (p<0.0001) in the multivariate analysis.

Bactericidal effect of ADP and acetic acid on Bacillus subtilis.

Abstract.Bacillus subtilis is a ubiquitous soil bacterium used for measuring the β-lysin activity and in other bioassays. We observed a complete bactericidal effect of ADP on B. subtilis at concentrations of 50–100 μM at pH values <5.5, which disappeared at pH values above 6. The effect was also found for acetic acid at concentrations >17.4 μM and similar pH values. ATP, adenosine, and HCl were not bactericidal. We used BCECF-AM, a pH-sensitive probe, and found that the killing of B. subtilis was due to a change in the intracellular pH caused by the passage across the cell membrane of these weak organic acids when incubated with B. subtilis at pH values near the pK. More experiments are needed to determine the biological meaning of these in vitro findings.

Successful treatment of recurrent cerebral empyema and brain abscesses with Imipenem

Imipenem was successfully used to treat a case of subdural empyema complicated by multiple cerebral abscesses, in which surgery and therapy with other antibiotics had previously failed. Imipenem concentrations in serum, cerebrospinal fluid and the cerebral abscess were much higher than the MICs for the infecting organisms, qualifying this antibiotic as an effective option in therapy of suppurative intracranial infections.