INTRODUCCIÓNListeria monocytogenes (LM) es un bacilo gram positivo asociado a infecciones en mujeres embarazadas y responsable de sepsis neonatal. En adultos no gestantes es una infrecuente pero severa infección que usualmente afecta a pacientes inmunodeprimidos.En este trabajo describimos nuestra experiencia en listeriosis del adulto resaltando factores predisponentes, curso clí-nico, respuesta terapéutica y pronóstico en una serie de 10 casos. CASOS APORTADOSPresentamos un estudio retrospectivo efectuado en el hospital de Cabueñes (grupo 2 del antiguo Insalud ahora SESPA) que atiende a una población cercana a los 300.000 habitantes en Gijón, Principado de Asturias, y que carece de los servicios de neurocirugía, cirugía vascular y maxilofacial, y en el que no se realizan transplantes de órganos. Nosotros revisamos las historias de todos los pacientes con cultivo positivo para LM entre enero de 1991 y diciembre de 2002. Se consideró caso de listeriosis del adulto al episodio de enfermedad compatible en paciente con aislamiento de LM en localización habitualmente estéril, en mayores de 14 años. Se definió como sepsis primaria cuando los hemocultivos fueron positivos, en ausencia de infección en otros lugares del organismo. Se diagnosticó de meningitis o meningoencefalitis al hallazgo de LM en líquido cefalorraquí-deo (LCR), y en los casos con cultivo negativo del LCR en los que se observaron signos citoquímicos de inflamación meníngea siempre que los hemocultivos fueran positivos. Se definió caso adquirido en la comunidad aquel cuyo periodo de tiempo entre la fecha de ingreso y la fecha de aislamiento del microorganismo en relación con la toma de la muestra, fuese inferior a 72 horas, mientras que se consideró nosocomial aquel con un periodo superior o igual a 3 días.Se hallaron 10 casos cuyas principales características se describen en la tabla I. El rango de edad fue de 28 a 81 años con una media 31 [0212-7199 (2004)

Heterozygous carriers of ATM (ataxia telangiectasia mutated gene) mutations have increased risk of breast cancer (BC). We have estimated the prevalence of mutations in the ATM gene among Spanish patients with early-onset BC. Forty-three patients diagnosed with BC before the age of 46 years, and negative for BRCA1 and BRCA2 mutations, were analysed for the presence of ATM mutations. A total of 34 ATM sequence variants were detected: 1 deleterious mutation, 10 unclassified variants and 23 polymorphisms. One patient (2.3%) carried the ATM deleterious mutation (3802delG that causes ataxia telangiectasia in the homozygous state) and 13 patients carried the 10 ATM unclassified variants. The truncating mutation 3802delG and eight of the rare variants were not detected in a control group of 150 individuals. Different bioinformatic sequence analysis tools were used to evaluate the effects of the unclassified ATM changes on RNA splicing and function protein. This in silico analysis predicted that the missense variants 7653 T>C and 8156 G>A could alter the splicing by disrupting an exonic splicing enhancer motif and the 3763 T>G, 6314 G>C, and 8156 G>A variants would affect the ATM protein function. These are the initial results concerning the prevalence of germline mutations in the ATM gene among BC cases in a Spanish population, and they suggest that ATM mutations can confer increased susceptibility to early-onset BC.

ObjectivesInsulin resistance in viral infections is common. We have explored the effectiveness of metformin for alleviating insulin resistance in HIV-infected patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM) rs11212617 variant in the clinical response with the rationale that metformin modulates cellular bioenergetics in an ATM-dependent process. MethodsHIV-infected patients (n = 385) were compared with controls recruited from the general population (n = 300) with respect to the genotype distribution of the ATM rs11212617 variant and its influence on selected metabolic and inflammatory variables. We also followed up a subset of male patients with HIV and hepatitis C virus (HCV) coinfection (n = 47) who were not receiving antiviral treatment and for whom metformin was prescribed for insulin resistance, which tends to have a higher incidence and severity in coinfected patients. ResultsAmong the HIV-infected patients, human cytomegalovirus (91.9%) and HCV (62.3%) coinfections were frequent. Selected metabolic and/or inflammatory variables were significantly altered in infected patients. Treatment with metformin in HIV and HCV coinfected patients was well tolerated and significantly increased the sensitivity of peripheral tissues to insulin. The minor allele (C) of the rs11212617 variant was associated with treatment success and may affect the course of insulin resistance in response to metformin (odds ratio 1.21; 95% confidence interval 1.07-1.39; P = 0.005). There were no differences between treated and untreated patients in viral loads or variables measuring immune defence, indicating that toxicity is unlikely. ConclusionsWe provide novel data suggesting that identification of the ATM rs11212617 variant may be important in assessing the glycaemic response to metformin treatment for insulin resistance in HIV-infected patients. [3,6,7].In a previous study, we showed the benefits of metformin treatment in terms of visceral fat accumulation, the fasting lipid profile and endothelial function in HIV-infected patients with lipodystrophy [8,9]. The response to the drug varied widely, an effect initially attributed to the influence of antiretroviral therapy [10]. A recent pharmacogenomic study suggested that the genetic variant rs11212617 at the locus containing the ATM gene is robustly associated with metformin response in diabetic patients and established a link between glucose homeostasis and the DDR. Further, ATM acts upstream of AMPK and is required for a full response to metformin [11]. Hence, genetic variations affecting the function of ATM may contribute to the varying success of metformin treatment via AMPK activation or inhibition. We reasoned that this may also be applicable to patients with viral infections and insulin resistance and that understanding ATM-related associations may help to establish metformin as a useful coadjuvant in HIV-infected patients. Clinically, insulin resistance is a relatively common condition in HIV-infected patients. It is even more frequent, for poorl...