Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies.

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

Seroprevalence of Bartonella species, Coxiella burnetii and Toxoplasma gondii among patients with hematological malignancies: A pilot study in Romania.

Patients receiving immunosuppressive cancer treatments in settings where there is a high degree of human-animal interaction may be at increased risk for opportunistic zoonotic infections or reactivation of latent infections. We sought to determine the seroprevalence of selected zoonotic pathogens among patients diagnosed with haematologic malignancies and undergoing chemotherapeutic treatments in Romania, where much of the general population lives and/or works in contact with livestock. A convenience sample of 51 patients with haematologic cancer undergoing chemotherapy at a referral clinic in Cluj-Napoca, Romania, was surveyed regarding animal exposures. Blood samples were obtained and tested for evidence of infection with Bartonella species, Coxiella burnetii and Toxoplasma gondii, which are important opportunistic zoonotic agents in immunocompromised individuals. 58.8% of participants reported living or working on a farm, and living or working on a farm was associated with contact with livestock and other animals. 37.5% of participants were IgG seroreactive against one or more of five Bartonella antigens, and seroreactivity was statistically associated with living on farms. Farm dwellers were 3.6 times more likely to test IgG seroreactive to Bartonella antibodies than non-farm dwellers. 47.1% of the participants tested T. gondii IgG positive and 13.7% tested C. burnetii IgG positive, indicating past or latent infection. C. burnetii IgM antibodies were detected in four participants (7.8%), indicating possible recent infection. These results indicate that a large proportion of patients with haematologic cancer in Romania may be at risk for zoonotic infections or for reactivation of latent zoonotic infections, particularly with respect to Bartonella species. Special attention should be paid to cancer patients' exposure to livestock and companion animals in areas where much of the population lives in rural settings.

Prevalence of Bartonella spp. in Canine Cutaneous Histiocytoma.

Canine cutaneous histiocytoma (CCH) is a common, benign neoplastic proliferation of histiocytes of Langerhans cell origin that often ulcerate, become secondarily infected and regress spontaneously. Bartonella is a fastidious genus of facultative intracellular pathogens that can be transmitted through arthropod bites and epidermal animal scratches and has been identified previously in the cytoplasm of histiocytes within granulomatous lesions and in skin biopsy samples of inflammatory pustules and papules. Based on the established inflammatory and oncogenic properties of Bartonella, we hypothesized that Bartonella spp. DNA could be amplified from CCH more often than from non-lesional skin and bacteria could be localized within skin tumours using indirect immunofluorescence (IIF). Paraffin wax-embedded surgical biopsy samples from dogs with CCH and non-neoplastic skin adjacent to osteosarcomas (control group selected due to wide surgical margins) were retrieved from the archive of the pathology service of North Carolina State University College of Veterinary Medicine. DNA was extracted and regions of the 16S-23S rRNA intergenic transcribed spacer (ITS) region and the pap31 and gltA genes were amplified by polymerase chain reaction (PCR) using Bartonella-specific primers. IIF was performed using a primary Bartonella henselae monoclonal antibody to localize B. henselae in tissues of PCR-positive dogs. Bartonella vinsonii subsp. berkhoffii was amplified from 1/17 (5.8%) control tissues and B. henselae was amplified from 4/29 (13.8%) CCH tissues. The prevalence of B. vinsonii subsp. berkhoffii (P = 0.37) or B. henselae (P = 0.28) did not vary statistically between study groups. B. henselae could be visualized in 2/4 (50.0%) CCH tissues using IIF. Based on this study, Bartonella spp. are unlikely to cause CCH.

New insight on the molecular aspects of glucocorticoid effects in nervous system development.

Adrenal glucocorticoids (Gc) are among the most significant hormones in the mammalian organisms; these steroids may reach and penetrate all tissues where they interact with cytoplasmic/nuclear receptors, through which they exert multiple and very multifaceted actions. The effects of physiological concentrations of Gc on brain functions have not been completely clarified, even though Gc are recognized to influence behavioral responses, emotions, cognitive processes and to take part in the neuroendocrine control of body homeostasis. Developmental programming effects of Gc in animal models and humans have been proposed. Actually, pre-natal stress, or exposure to high Gc levels, would somehow affect neuronal developmental events in some structure and this can lead to central nervous system altered functions, as the impairment of neuroendocrine activities, cognitive processes, sleep and mood disorders. Interestingly, it has been observed that these abnormalities may not be limited to the first directly exposed individuals but transmissible across generations. The establishment of animal models with localized pre-natal glucocorticoid receptors deficiency led to the accumulation of data on the possible roles of these hormones on development of the central and peripheral nervous system. The most recent findings on the effects of Gc on neuroblast development, with particular attention to neuronal migration, will be presented.

Phylogenetic diversity of bacteria isolated from sick dogs using the BAPGM enrichment culture platform.

BACKGROUND: Bartonella alpha-Proteobacteria growth medium (BAPGM) enrichment culture has proven useful for documenting Bartonella species infection and has facilitated growth of other fastidious bacteria from human samples. PURPOSE: To report non-Bartonella bacterial isolates obtained from canine samples cultured using BAPGM enrichment culture. ANIMALS: Between 2004 and 2008, 695 specimens from 513 dogs were tested by the NCSU-IPRL using the BAPGM enrichment culture. Over the same period of time, blood samples from 270 dogs were cultured by the NCSU-CML using Bactec-Plus Aerobic/F media. METHODS: BAPGM isolates were characterized using Bartonella genus primers and 16S rDNA primers followed by DNA sequencing. NCSU medical records were retrospectively reviewed. Blood culture results from the NCSU-CML were compared with BAPGM blood culture results. RESULTS: Seventy-nine non-Bartonella isolates were obtained from 69/513 dogs. The most commonly isolated phylum was Proteobacteria (48.1%) with alpha-Proteobacteria being the most commonly isolated class. Staphylococcus and Sphingomonas were the most commonly isolated genera. The majority of the remaining isolates were bacteria that are rarely isolated from canine samples. Comparison of NCSU-CML and IPRL (BAPGM) blood culture isolates showed alpha-Proteobacteria were isolated more often from BAPGM. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of insect cell culture enrichment medium, such as BAPGM, appears to enhance the growth of alpha-Proteobacteria, but also results in isolation of non-alpha-Proteobacteria from sick dogs. Future studies are needed to elucidate the utility of BAPGM and other "nonconventional" growth media and methods for isolation of fastidious organisms and to determine if these organisms play a causal role in disease development.

Koch's postulates and the pathogenesis of comparative infectious disease causation associated with Bartonella species.

In his homage to Lucretius ('Georgica'), Vergil is credited with stating: 'Felix qui potuit rerum cognoscere causas' ('Fortunate is he who knows the causes of things'). Based on numerous commentaries and publications it is obvious that clinicians, diagnosticians and biomedical research scientists continue to struggle with disease causation, particularly in the assessment of the pathogenic role of 'stealth pathogens' that produce persistent infections in the host. Bartonella species, because of their evolutionary ability to induce persistent intravascular infections, present substantial challenges for researchers attempting to clarify the ability of these stealth bacteria to cause disease. By studying the comparative biological and pathological behaviour of microbes across mammalian genera, researchers might be able more rapidly to advance medical science and, subsequently, patient care by undertaking focused research efforts involving a single mammalian species or by attempting to recapitulate a complex disease in an rodent model. Therefore, in an effort to further assist in the establishment of disease causation by stealth pathogens, we use recent research observations involving the genus Bartonella to propose an additional postulate of comparative infectious disease causation to Koch's postulates.

Exercise training performed simultaneously to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in mice.

BACKGROUND: The aim of the present study was to evaluate the protective effect of concurrent exercise in the degree of the insulin resistance in mice fed with a high-fat diet, and assess adiponectin receptors (ADIPOR1 and ADIPOR2) and endosomal adaptor protein APPL1 in different tissues. METHODS: Twenty-four mice were randomized into four groups (n = 6): chow standard diet and sedentary (C); chow standard diet and simultaneous exercise training (C-T); fed on a high-fat diet and sedentary (DIO); and fed on a high-fat diet and simultaneous exercise training (DIO-T). Simultaneously to starting high-fat diet feeding, the mice were submitted to a swimming exercise training protocol (2 x 30 minutes, with 5 minutes of interval/day), five days per week, for twelve weeks (90 days). Animals were then euthanized 48 hours after the last exercise training session, and adipose, liver, and skeletal muscle tissue were extracted for an immunoblotting analysis. RESULTS: IR, IRs, and Akt phosphorylation decreased in the DIO group in the three analyzed tissues. In addition, the DIO group exhibited ADIPOR1 (skeletal muscle and adipose tissue), ADIPOR2 (liver), and APPL1 reduced when compared with the C group. However, it was reverted when exercise training was simultaneously performed. In parallel, ADIPOR1 and 2 and APPL1 protein levels significantly increase in exercised mice. CONCLUSIONS: Our findings demonstrate that exercise training performed concomitantly to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in the hepatic, adipose, and skeletal muscle tissue.

Bartonella spp. infection in healthy and sick horses and foals from the southeastern United States.

BACKGROUND: Bartonella species bacteremia has been identified in numerous animal species. These bacteria cause, or have been associated with, a spectrum of clinical manifestations in dogs and human patients. The frequency of exposure to or infection with Bartonella spp. among healthy and sick horses has not been reported. OBJECTIVE: To test healthy and sick horses and sick foals from the southeastern United States for serological, microbiological, and molecular evidence of Bartonella infection. ANIMALS: Forty-seven healthy horses, 15 sick foals, 22 horses with musculoskeletal manifestations, and 8 horses with colic were tested for Bartonella. METHODS: IFA serology and PCR before and after BAPGM (Bartonella alpha-Proteobacteria Growth Medium) enrichment blood culture. RESULTS: Bartonella antibodies were not detected in foals or horses. Three Bartonella species, B. henselae, B. vinsonii subsp. berkhoffii (genotypes I and III), and a Bartonella species with closest homology to Candidatus Bartonella volans, were PCR-amplified and sequenced from blood or BAPGM enrichment blood culture samples from 1/47 healthy horses, 3/15 sick foals, 5/22 horses with musculoskeletal disease, and 0/8 horses with colic. CONCLUSIONS AND CLINICAL IMPORTANCE: Horses in the southeastern United States are naturally infected with B. henselae, B. vinsonii subsp. berkhofii genotypes I and III, and a bacteria most similar to Candidatus Bartonella volans. Antibodies were not detectable by indirect fluorescent antibody assay (IFA) testing in bacteremic foals or horses, and prolonged enrichment culture for periods up to 21 days were necessary to document bacteremia in most horses. Further investigation into the pathogenic potential of Bartonella spp. infection in horses is warranted.

Candidatus Mycoplasma haematoparvum and Mycoplasma haemocanis infections in dogs from the United States.

Mycoplasma haemocanis (Mhc) and Candidatus Mycoplasma haematoparvum (CMhp) have been described in dogs. Historically, microscopic visualization of hemotropic Mycoplasma spp. has occurred most often in immunocompromised or splenectomized dogs. The aim of this study was to determine the Mhc and CMhp prevalences among dogs from the United States. Novel 16S rRNA and RNAseP gene PCR assays were used to amplify hemotropic Mycoplasma species DNA for GenBank sequence alignment. Among the study population, hemoplasma prevalence was 1.3% (7 out of 506), with Mhc and CMhp prevalences of 0.6% and 0.8%, respectively. Two of six CMhp-infected dogs were co-infected with a Bartonella sp., and a third dog was seroreactive to Bartonella henselae antigens. The prevalence of Mhc and CMhp in this study was low; potential blood donors should be screened; and dogs and people can be co-infected with hemoplasma and Bartonella spp.

Identification of Bartonella henselae in 2 cats with pyogranulomatous myocarditis and diaphragmatic myositis.

Most cats infected with Bartonella henselae remain outwardly healthy carriers for years; however, self-limiting fever, transient anemia, neurologic dysfunction, lymphadenopathy, reproductive disorders, aortic valvular endocarditis, and neutrophilic myocarditis have been described in experimentally or naturally infected cats. Two cats in a North Carolina shelter died with pyogranulomatous myocarditis and diaphragmatic myositis. Bacteria were visualized in the lesions by Warthin-Starry silver impregnation and by B. henselae immunohistochemistry. B. henselae DNA was amplified and sequenced from the heart of 1 cat and from multiple tissue samples, including heart and diaphragm, from the second cat. This study supports a potential association between B. henselae and what has been historically described as "transmissible myocarditis and diaphragmitis" of undetermined cause in cats.

Molecular prevalence of Bartonella, Babesia, and hemotropic Mycoplasma sp. in dogs with splenic disease.

BACKGROUND: Among diseases that cause splenomegaly in dogs, lymphoid nodular hyperplasia (LNH), splenic hemangiosarcoma (HSA), and fibrohistiocytic nodules (FHN) are common diagnoses. The spleen plays an important role in the immunologic control or elimination of vector-transmitted, blood-borne pathogens, including Bartonella sp., Babesia sp., and hemotropic Mycoplasma sp. OBJECTIVE: To compare the prevalence of Bartonella sp., Babesia sp., and hemotropic Mycoplasma sp. DNA in spleens from dogs with LNH, HSA, and FHN. MATERIALS AND METHODS: Paraffin-embedded, surgically obtained biopsy tissues from LNH (N = 50), HSA (N = 50), and FHN (N = 37) were collected from the anatomic pathology archives. Spleens from specific pathogen-free (SPF) dogs (N = 8) were used as controls. Bartonella sp., Babesia sp., and Mycoplasma sp. DNA was amplified by PCR, followed by DNA sequencing. RESULTS: Bartonella sp. DNA was more prevalent in FHN (29.7%) and HSA (26%) as compared to LNH (10%) (P = .019, .0373, respectively) or control spleens (0.0%). The prevalence of Babesia sp. and hemotropic Mycoplasma sp. DNA was significantly lower than Bartonella sp. DNA in HSA (P = .0005, .006, respectively) and FHN (P = .003, .0004, respectively). There was no statistically significant difference in DNA prevalence among the 3 genera in the LNH group. CONCLUSIONS: The higher prevalence of Bartonella sp. in FHN and HSA warrants future investigations to determine if this bacterium plays a role in the development of these splenic diseases.

Gammopathy in a Spanish dog infected with Bartonella henselae.

Generalised pyogranulomatous disease and hyperviscosity syndrome associated with a presumed monoclonal gammopathy was diagnosed in a three-year-old intact female Pomeranian. The Bartonella henselae antibody titer was 1:64 and Bartonella species DNA was amplified from the splenic tissue. Monoclonal gammopathies in dogs are typically associated with plasma cell and lymphoid dyscrasias and other inflammatory or infectious diseases such as ehrlichiosis and leishmaniosis. Based on this case report, infection with Bartonella species should also be added to the differential diagnoses for gammopathy in dogs. To the authors' knowledge, this is the first report of molecular evidence of Bartonella species infection in a sick dog in Spain.

Molecular and serological diagnosis of Bartonella infection in 61 dogs from the United States.

BACKGROUND: Molecular diagnosis of canine bartonellosis can be extremely challenging and often requires the use of an enrichment culture approach followed by PCR amplification of bacterial DNA. HYPOTHESES: (1) The use of enrichment culture with PCR will increase molecular detection of bacteremia and will expand the diversity of Bartonella species detected. (2) Serological testing for Bartonella henselae and Bartonella vinsonii subsp. berkhoffii does not correlate with documentation of bacteremia. ANIMALS: Between 2003 and 2009, 924 samples from 663 dogs were submitted to the North Carolina State University, College of Veterinary Medicine, Vector Borne Diseases Diagnostic Laboratory for diagnostic testing with the Bartonella α-Proteobacteria growth medium (BAPGM) platform. Test results and medical records of those dogs were retrospectively reviewed. METHODS: PCR amplification of Bartonella sp. DNA after extraction from patient samples was compared with PCR after BAPGM enrichment culture. Indirect immunofluorescent antibody assays, used to detect B. henselae and B. vinsonii subsp. berkhoffii antibodies, were compared with PCR. RESULTS: Sixty-one of 663 dogs were culture positive or had Bartonella DNA detected by PCR, including B. henselae (30/61), B. vinsonii subsp. berkhoffii (17/61), Bartonella koehlerae (7/61), Bartonella volans-like (2/61), and Bartonella bovis (2/61). Coinfection with more than 1 Bartonella sp. was documented in 9/61 dogs. BAPGM culture was required for PCR detection in 32/61 cases. Only 7/19 and 4/10 infected dogs tested by IFA were B. henselae and B. vinsonii subsp. berkhoffii seroreactive, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs were most often infected with B. henselae or B. vinsonii subsp. berkhoffii based on PCR and enrichment culture, coinfection was documented, and various Bartonella species were identified. Most infected dogs did not have detectable Bartonella antibodies.

Bartonella spp. DNA in cardiac tissues from dogs in Colorado and Wyoming.

BACKGROUND: Several Bartonella species (spp.) have been identified in dogs diagnosed with infectious endocarditis (IE) or myocarditis. OBJECTIVE: To interrogate cardiac tissues of dogs with suspected IE for the presence of Bartonella spp. DNA of dogs in the Rocky Mountain states. ANIMALS: Nine dogs with a clinical diagnosis of endocarditis from January 1990 to June 2008 were included. METHODS: In this retrospective study, medical records at the Veterinary Teaching Hospital were searched. Animals were excluded if there was no diagnosis of IE in the original necropsy report. Paraffin embedded tissue blocks and medical records were available from 9 dogs. Total DNA was extracted from the cardiac tissues and assessed for Bartonella spp. DNA by 3 polymerase chain reaction (PCR) methods. For positive samples, the Bartonella spp. were determined by genetic sequencing or fluorogenic real-time PCR. RESULTS: Bartonella henselae DNA was amplified from the tissues of 7 dogs; Bartonella vinsonii subsp berkhoffii DNA was amplified concurrently from 3 dogs. Six dogs were from Colorado and 1 was from Wyoming. Flea or tick infestations were reported in 2 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Bartonella spp. should be on the differential list for dogs in the Rocky Mountain states. The results emphasize the need for routine use of external parasite control products even in regions perceived to have low risk for flea and tick infestations.

Prevention of endemic canine vector-borne diseases using imidacloprid 10% and permethrin 50% in young dogs: a longitudinal field study.

Canine vector-borne diseases (CVBDs) are highly prevalent and increasing in distribution worldwide. A longitudinal study was conducted in southern Italy to determine the incidence of and protection against CVBD-causing pathogens in dogs treated with a combination of imidacloprid 10% and permethrin 50% (ImPer). One hundred eleven autochthonous young dogs were divided into group A (n=63) and group B (n=48), both groups containing dogs positive and negative for one or more CVBD-causing pathogens. Additionally, 10 naïve male beagles were introduced in each group in May 2008. Group A was treated with ImPer on day 0 and every 21+/-2 days whereas group B was left untreated. Blood and skin samples were collected at baseline (March-April 2008) and at the first, second and third follow-up times (July and October 2008 and April 2009). Bone marrow was sampled at baseline and at the third follow-up. Serological, cytological and molecular tests were performed to detect Anaplasma platys, Babesia spp., Bartonella spp., Dirofilaria immitis, Ehrlichia canis, Hepatozoon canis and Leishmania infantum. Ectoparasites (fleas, ticks, and sand flies) were monitored throughout the study. The baseline prevalence of CVBDs was 39.6% with 44 dogs positive for at least one pathogen. A. platys (27.5%) and Babesia spp. (15.6%) were the most prevalent species and co-infections with up to two pathogens were detected in 16 (14.7%) individuals. At the end of the evaluation period, there was a 90.7% reduction in overall CVBD incidence density rate (IDR) in group A, as following: 100% reduction in L. infantum; 94.6% in E. canis; 94.4% in Babesia spp.; and 81.8% in A. platys. Initially positive treated dogs showed significantly lower pathogen prevalence at the third follow-up than untreated ones. At the end of the evaluation period, 8 of the 10 untreated beagles were infected with at least one pathogen whereas one of the treated beagles was A. platys positive at a single time point (second follow-up). Overall efficacy against ticks was 97.9%. In October 2009, samples were collected from the remaining 83 dogs (44 from group A and 39 from group B) to investigate the annual incidence of CVBDs in the same, at this time untreated, dog population. A high year incidence for tick-borne diseases (78.1%) and for L. infantum (13.6%) was detected in dogs from group A, seven months after the treatment had been withdrawn. The results demonstrate that ImPer preventive treatment against arthropods protects autochthonous and naïve beagle dogs against CVBD-causing pathogens.

Radiographic findings among children hospitalized with severe community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of childhood death. There are few published reports of radiographic findings among children with severe CAP. OBJECTIVE: To describe chest X-ray (CXR) findings and assess association between these radiographic findings and pneumococcal isolation in children with severe CAP. METHODS: A prospective, multicenter, observational study was conducted in 12 centers in Argentina, Brazil, and the Dominican Republic. Children aged 3-59 months, hospitalized with severe pneumonia, were included. On admission, blood and pleural effusion cultures were performed. Streptococcus pneumoniae was identified according to standard procedures in the respective national reference laboratory. Chest X-rays were taken on admission and read before the culture results were reported. RESULTS: Out of 2,536 enrolled patients, 283 (11.2%) had S. pneumoniae isolated, in 181 cases (7.1%) from blood. The follow radiographic patterns were observed: alveolar infiltrate (75.2%), pleural effusion (15.6%), and interstitial infiltrate (9.2%). Overall, pleural effusion was associated with pneumococcal isolation and pneumococcal bacteremia (P < 0.001). Infiltrates were unilateral (78.7%) or bilateral (21.3%), right-sided (76%) or left-sided (24%), in the lower lobe (53.6%) or the upper lobe (46.4%). Multivariate analysis including patients with affection of only one lobe showed that upper lobe affection and pleural effusion were associated with pneumococcal isolation (OR 1.8, 95% CI, 1.3-2.7; OR 11.0, 95% CI, 4.6-26.8, respectively) and with pneumococcal bacteremia (OR 1.7, 95% CI, 1.2-2.6; OR 3.1, 95% CI, 1.2-8.0, respectively). CONCLUSIONS: Three-quarters of the patients studied had alveolar infiltrates. Upper lobe compromising and pleural effusion were associated with pneumococcal invasive disease.