Inhalational lung diseases.

The term inhalational lung disease comprises a group of entities that develop secondary to the active aspiration of particles. Most are occupational lung diseases. Inhalational lung diseases are classified as occupational diseases (pneumoconiosis, chemical pneumonitis), hypersensitivity pneumonitis, and electronic-cigarette-associated lung diseases. The radiologic findings often consist of nonspecific interstitial patterns that can be difficult to interpret. Therefore, radiologists' experience and multidisciplinary teamwork are key to ensure correct evaluation. The role of the radiologist is fundamental in preventive measures as well as in diagnosis and management, having an important impact on patients' overall health. It is crucial to take into account patients' possible exposure to particles both at work and at home.

Prevalence of metabolic syndrome and its association with lower urinary tract symptoms and sexual function. / Prevalencia del síndrome metabólico y su asociación con síntomas del tracto urinario inferior y función sexual.

OBJECTIVES: To estimate the frequency of metabolic syndrome (MetS) in a daily urology practice and to determine its association with lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). MATERIAL AND METHODS: A retrospective study was conducted. Data from all male patients aged ≥40 years who attended our outpatient urology clinic from 2010 to 2011 was collected. Prevalence of MetS was determined, and LUTS and ED were assessed. A logistic model was used to determine possible associations, controlling for confounders and interaction factors. RESULTS: A total of 616 patients were included. MetS was observed in 43.8% (95% CI 39.6-48.3). The bivariate model showed an association between MetS and LUTS (p<0.01), but not between MetS and ED. The logistic model showed an association between MetS and the International Prostate Symptom Score (IPSS), while controlling for other variables. Patients exhibiting moderate LUTS had a greater risk for MetS than patients with mild LUTS (OR 1.83, 95% CI 1.14-2.94). After analyzing for individual components of MetS, positive associations were found between diabetes and severe LUTS (OR 1.3, 95% CI 1.24-7.1), and between diabetes and ED (OR 2.57, 95% CI 1.12-5.8). CONCLUSION: This study was able to confirm an association between MetS and LUTS, but not for ED. Specific components such as diabetes were associated to both. Geographical differences previously reported in the literature might account for these findings. Given that MetS is frequent among urological patients, it is advisable that urologists actively screen for it.

Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To determine efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection. METHODS: Prospective, multicentre, randomized study in children presenting with FN at five hospitals in Santiago, Chile, evaluated at admission for diagnosis of bacterial and viral pathogens including PCR-microarray for 17 respiratory viruses. Children positive for a respiratory virus, negative for a bacterial pathogen and with a favourable evolution after 48 h of antimicrobial therapy were randomized to either maintain or withhold antimicrobials. Primary endpoint was percentage of episodes with uneventful resolution. Secondary endpoints were days of fever/hospitalization, bacterial infection, sepsis, admission to paediatric intensive care unit (PICU) and death. RESULTS: A total of 319 of 951 children with FN episodes recruited between July 2012 and December 2015 had a respiratory virus as a unique identified microorganism, of which 176 were randomized, 92 to maintain antimicrobials and 84 to withdraw. Median duration of antimicrobial use was 7 days (range 7-9 days) versus 3 days (range 3-4 days), with similar frequency of uneventful resolution (89/92 (97%) and 80/84 (95%), respectively, not significant; OR 1.48; 95% CI 0.32-6.83, p 0.61), and similar number of days of fever (2 versus 1), days of hospitalization (6 versus 6) and bacterial infections throughout the episode (2%-1%), with one case of sepsis requiring admission to PICU in the group that maintained antimicrobials, without any deaths. CONCLUSIONS: The reduction of antimicrobials in children with FN and respiratory viral infections, based on clinical and microbiological/molecular diagnostic criteria, should favour the adoption of evidence-based management strategies in this population.

A prime-boost vaccination of mice with attenuated Salmonella expressing a 30-mer peptide from the Trichinella spiralis gp43 antigen.

Protection against Trichinella infections has been achieved using various parasite antigens and adjuvants. Recently, we reported that immunization of mice with an attenuated Salmonella strain displaying a 30-mer peptide (residues 210-239) from the Trichinella spiralis gp43 antigen using the ShdA autotransporter induced partial protection against T. spiralis infection. To improve the efficacy of vaccination, we used the MisL autotransporter system to display the Ts30mer peptide on the surface of Salmonella enterica ser. Typhimurium in combination with a prime-boost vaccination strategy. This vector and immunization regimen induced superior protection against T. spiralis when compared to our previously reported approach. Data presented herein showed a significant reduction in adult worm and muscle larvae burdens, high IgG titers, and increased production of intestinal mucus with entrapped adult worms. This prime-boost vaccination scheme is a suitable strategy to elicit enhanced protective immunity against T. spiralis.

First Report in Hawai'i of Xanthomonas citri pv. mangiferaeindicae Causing Bacterial Black Spot on Mangifera indica.

Bacterial black spot of mango (Mangifera indica) caused by Xanthomonas citri pv. mangiferaeindicae (Xcm), is an economically important disease in tropical and subtropical areas (3). Xcm can infect a wide range of mango cultivars and induces raised, angular, black leaf lesions, sometimes with a chlorotic halo. Fruit symptoms appear as small, water-soaked spots on the lenticels that become star-shaped, erumpent, and exude an infectious gum (3). The bacterium can also cause latent infections (2). Immature mango fruit with black spots on the epidermis were collected in August 2012 from mango trees of the cvs. Raposa and Pirie at a residence in Pukalani, Hawai'i, on the island of Maui. Similar symptoms were seen on a tree of the mango cv. Common (also known as 'Spanish' or 'Lahaina') at a nearby golf course. Mango fruit with black lesions, and leaves showing black lesions with yellow halos, were collected in August 2012 from mango trees of the cv. Haden at a residence in Kaimuki, Hawai'i, on the island of O'ahu. Xanthomonas-like bacterial colonies were isolated on TZC agar. Suspect colonies were non-pigmented on YDC agar. A fruit strain of the bacterium from Maui (A6081A) and a strain from each of a fruit (A6081B) and a leaf (A6082) from O'ahu were each gram-negative, oxidative, positive for both starch and esculin hydrolysis, and negative for nitrate reduction, resulting in presumptive identification as a Xanthomonas sp. The three strains were further characterized by Microlog (Biolog, Inc. Hayward, CA), which showed the closest match with X. campestris. In addition, 16S rDNA PCR assays showed the closest match (99% similarity) with X. citri strains, and RIF marker analysis of dnaA (4) grouped the three strains with Xcm strain LMG 941 (Accession No. CAHO01000002.1). Hypersensitivity responses typical of xanthomonads were observed when these strains were infiltrated into tobacco leaves, whereas no response was observed using sterile water. Leaves of 3-week-old mango seedlings were infiltrated using 10 µl (~108 CFU/ml) of each strain suspended in sterilized water (six to eight inoculations per leaf, four leaves per plant, and three replicate plants per strain). The negative control treatments consisted of inoculation with sterile water, as well as an incompatible pathogen, X. hortorum pv. vitians (A6076), isolated from lettuce. Typical symptoms of bacterial black spot were observed for all strains assayed approximately 2 weeks after inoculation. No lesions were observed on the negative control plants. Koch's postulates were satisfied following reisolation and identification of the Xanthomonas strains from the infected plant tissues, using the biochemical and PCR methods described above. Results for strains from the two islands confirmed published descriptions of the pathogen, indicating that the pathogen causing symptoms on these mango trees is Xcm (1). Cultures and infected plant samples were sent to USDA APHIS and CPHST NPGLB facilities where this identification was confirmed. To our knowledge, this is the first report of bacterial black spot of mango in Hawai'i or anywhere in the United States. It is unknown whether this disease is a new occurrence or has not been reported previously. The origin of the primary inoculum is unknown. References: (1) B. Manicom and F. Wallis. Int. J. Syst. Bacteriol. 34:77, 1984. (2) O. Pruvost et al. Microbial Ecol. 58:928. (3) O. Pruvost et al. Plant Dis. 95:774, 2011. (4) K. Schneider et al. PLoS 6:e18496, 2011.

[The risk of defects in the neural tube caused by valproic acid and carbamazepine]. / Riesgo de defectos del tubo neural con ácido valproico y carbamacepina.

OBJECTIVE: To determine the risk, if any, of carbamazepine and valproic acid use on the foetus with respect to neural tube defects. MATERIALS AND METHODS: Databases such as MEDLINE, EMBASE, SCISEARCH, The Cochrane Library and LILACS were consulted to have access to published literature from January 1966 to September 2004. All articles published in English and Spanish were considered. A manual review of the references presented in each produced article was done in order to identify the articles that the electronic search may have not found itself. However, articles which seemed ambiguous as to the title and/or abstract were completely analyzed to establish their relevance. Studies that examined the effects of systematic exposure to carbamazepine or valproic acid during pregnancy and that assessed neural tube defects in the infants were eligible. The data was extracted in the form of 2 x 2 tables. The odds ratio (OR), relative risk (RR) and 95% confidence interval (CI) was calculated for each of the studies. RESULTS: The pooled relative risk of neural tube defects among the exposed to valproic acid was 0.61 (95% CI: 0.06-6.72). The risk among the exposed to carbamazepine was 1.10 (95% CI: 0.16-7-75). CONCLUSIONS: Due to the methodologic limitations of most of the studies where the data was insufficient, only three studies could be included in the meta-analysis. There is not enough evidence to establish the risk raised in the objective of the study.

Methylphenidate and amphetamine modulate differently the NMDA and AMPA glutamatergic transmission of dopaminergic neurons in the ventral tegmental area.

Behavioral and neurochemical studies suggest that the induction of behavioral sensitization to psychostimulants involves transient changes at the synapses of the ventral tegmental area's dopaminergic neurons (VTA-DA). Differences in the behavioral response to amphetamine (Amph) and methylphenidate (MPD) were observed. In an attempt to understand these behavioral differences at the neuronal level, the dose-response characteristics of these two psychostimulants on electrophysiologically identified VTA-DA neurons at the glutamatergic synapse were investigated. Miniature excitatory post-synaptic currents (mEPSCs) and electrically induced EPSCs were recorded from horizontal midbrain slices of rats that had been pretreated intraperitoneally (i.p.) with saline (control), Amph (2.5, 5.0, 10.0 or 20.0 mg/kg), or MPD (2.5, 5.0, 10.0 or 20.0 mg/kg) 24 h before the recording. Perfusion of Amph through the bath (2.5, 5.0, 10.0 or 20.0 microM) increased the frequency (p<0.01) and the amplitude (p<0.05) of mEPSCs in dose-response characteristics, while MPD perfusion through the bath (2.5, 5.0, 10.0, or 20.0 microM) increased only the frequency (p<0.05) of the mEPSC. Both psychostimulants increased the prefrontal cortex's (PFC) glutamatergic EPSC in the VTA-DA neurons. However, only the higher doses of MPD induced significant effects (p<0.05) on the N-methyl-D-aspartate (NMDA) receptor-mediated EPSC but had no effects on the EPSC mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA/kainate) receptors. Contrarily, Amph increased both kinds of mediated EPSC, but mainly the EPSC mediated by AMPA/kainate receptors (p<0.01). These electrophysiological differences could represent the underlying mechanism responsible for the differences of behavioral effects, such as behavioral sensitization, elicited by MPD and Amph.

Dopaminergic ventral tegmental neurons modulated by methylphenidate.

Treatment of psychostimulants leads to the development of behavioral sensitization, an augmented behavioral response to drug re-administration. The induction of behavioral sensitization to psychostimulants such as amphetamine and cocaine occurs at the ventral tegmental area's dopaminergic neurons (VTA-DA). Currently, there is limited experimental data about the physiological properties of methylphenidate (MPD) on VTA-DA neurons. Behavioral and electrophysiological experiments using male rats were performed before and after MPD treatment. The behavioral experiment included dose-response (0.6, 2.5, and 10.0 mg/kg MPD) study to select the most effective dose for the electrophysiological study. Methylphenidate increased locomotion in typical dose response characteristics. Based on this experiment, the 10.0 mg/kg MPD was used in two types of electrophysiological recordings: 1) intracellular recording of neuronal activity performed on horizontal 275-300 microm brain slices and 2) whole-cell patch clamping before and after electrical stimulation to study post-synaptic currents on neurophysiologically identified VTA-DA neurons. Methylphenidate suppressed the neuronal activity of these neurons for 210 +/- 30 sec. Stimulation of the prefrontal cortex afferent fibers to these VTA-DA neurons in the presence of TTX, saclofen, and picrotoxin led to the conclusion that this input is mediated via NMDA and kainate/AMPA receptors and may participate to induce behavioral sensitization to psychostimulants.

Tratamiento del cáncer de cérvix localmente avanzado (estadíos IB BULKY-IIIB) con dosis bajas bisemanales de gemcitabina más cisplatino semanal en forma concurrente con radioterapia / Treatment cervix uteri carcinoma (IB-BULKY IIIB) with low close biweekly gemcitabine and weekly cisplatin combined with radiation therapy

El tratamiento estándar para el CCLA consiste en radioterapia más qiomioterapia en forma concurrente. El agregado de gemcitabina al cisplatino es factible sin agregarle toxicidad (Abs.2150 ASCO 2001). Basándonos en esos resultados, diseñamos un estudio evaluando la eficacia y toxicidad de la radioterapia con dosis bajas bisemanales de gemcitabina más cisplatino en el CCLA. Se incluyeron 60 pacientes; la edad media fue de 49 años (r:25-76). Los estadíos en el momento del diagnóstico se distribuyeron de la siguiente manera: 17 (28 por ciento): estadíos IIIB; 40 (66,6 por ciento): IIAB; y 3: IB Bulky (la paciente tenía contraindicada la cirugía). Se administró radioterapia externa a la pelvis total en 23 fracciones, alcanzando 46 Gys. en 5 semanas, con 2 inserciones de braquiterapia al final de la tercera y quinta semana. El total de la dosis administrada al punto A fue de 85 to 90 Gys. La quimioterapia consistió en gemcitabina 20 mg/m²/d 2 veces por semana (comenzando 3 días previo a la radioterapia) y cisplatino 30 mg/m² semanalmente. Toxicidad: 60 pacientes son evaluables para toxicidad y respuesta. Tres pacientes tuvieron que demorar 1 semana la primera braquiterapia debido a toxicidad gastrointestinal. Seis pacientes debieron omitir una aplicación de QT por toxicidad hematológica y gastrointestinal. Hubo 1 muerte durante el tratamiento, no relacionada con el tratamiento. No hubo alopecia ni mucositis. Cinco pacientes tuvieron trombocitopenia G2; 1 paciente: G3. Ocho pacientes experimentaron neutropenia G2, mientras que una sola paciente tuvo G3, y una G4...

Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia.

A risk prediction model for invasive bacterial infection (IBI) was prospectively evaluated among children presenting with cancer, fever, and neutropenia. The model incorporated assessment of 5 previously identified risk factors: serum level of C-reactive protein (CRP) >/=90 mg/L, hypotension, identification of relapse of leukemia as the cancer type, platelet count of

Induction of apoptosis by nitric oxide in macrophages is independent of apoptotic volume decrease.

Apoptosis occurs through a sequence of specific biochemical and morphological alterations that define the progress of cell death. The changes of the mitochondrial inner membrane potential (DeltaPsi(m)), the release of cytochrome c to the cytosol, the apoptotic volume decrease (AVD) and the activation of caspases have been measured in RAW 264.7, HeLa and Jurkat T cells incubated with molecules that induce apoptosis through the mitochondrial pathway. Our data show that NO, staurosporine, etoposide and camptothecin increased DeltaPsi(m) in macrophages but not in HeLa and Jurkat cells, that exhibited a DeltaPsi(m) decrease. Moreover, the apoptosis induced by NO in macrophages, but not that promoted by staurosporine, might occur in the absence of AVD. Analysis of the sequence of apoptotic manifestations shows that DeltaPsi(m) precedes AVD and caspase activation in RAW 264.7 cells. Inhibition of AVD abrogates apoptosis in HeLa and Jurkat T cells regardless of the stimuli used. These data suggest that the changes of DeltaPsi(m) are cell-type dependent and that AVD is dispensable for apoptosis in macrophages.

Intracellular water motion decreases in apoptotic macrophages after caspase activation.

Triggering of the macrophage cell line RAW 264.7 with lipopolysaccharide and interferon-gamma promoted apoptosis that was prevented by inhibitors of type 2 nitric oxide synthase or caspase. Using (1)H NMR analysis, we have investigated the changes of the intracellular transverse relaxation time (T(2)) and apparent diffusion coefficient (ADC) as parameters reflecting the rotational and translational motions of water in apoptotic macrophages. T(2) values decreased significantly from 287 to 182 ms in cells treated for 18 h with NO-donors. These changes of T(2) were prevented by caspase inhibitors and were not due to mitochondrial depolarization or microtubule depolymerization. The decrease of the intracellular values of T(2) and ADC in apoptotic macrophages was observed after caspase activation, but preceded phosphatidylserine exposure and nucleosomal DNA cleavage. The changes of water motion were accompanied by an enhancement of the hydrophobic properties of the intracellular milieu, as detected by fluorescent probes. These results indicate the occurrence of an alteration in the physicochemical properties of intracellular water during the course of apoptosis.

Activation of caspases occurs downstream from radical oxygen species production, Bcl-xL down-regulation, and early cytochrome C release in apoptosis induced by transforming growth factor beta in rat fetal hepatocytes.

Most of the morphologic changes that are observed in apoptotic cells are caused by a set of cysteine proteases (caspases) that are activated during this process. In previous works from our group we found that treatment of rat fetal hepatocytes with transforming growth factor beta1 (TGF-beta1) is followed by apoptotic cell death. TGF-beta1 mediates radical oxygen species (ROS) production that precedes bcl-xL down-regulation, loss of mitochondrial transmembrane potential, release of cytochrome c, and activation of caspase-3 (Herrera et al., FASEB J 2001;15:741-751). In this work, we have analyzed how TGF-beta1 activates the caspase cascade and whether or not caspase activation precedes the oxidative stress induced by this factor. Our results show that TGF-beta1 activates at least caspase-3, -8, and -9 in rat fetal hepatocytes, which are not required for ROS production, glutathione depletion, bcl-xL down-regulation, and initial cytochrome c release. However, caspase activation mediates cleavage of Bid and Bcl-xL that could originate an amplification loop on the mitochondrial events. An interesting result is that transmembrane potential disruption occurs later than the initial cytochrome c release and is mostly blocked by the pan-caspase inhibitor Z-VAD.fmk, indicating that the decrease in mitochondrial transmembrane potential (Delta(Psi)m) may be a consequence of caspase activity rather than the mechanism by which TGF-beta induces cytochrome c efflux. Finally, although Z-VAD.fmk completely blocks nucleosomal DNA fragmentation, it only delays cell death, which suggests that activation of the apoptotic program by TGF-beta in fetal hepatocytes inevitably leads to death, with or without caspases.

Prospective, multicenter evaluation of risk factors associated with invasive bacterial infection in children with cancer, neutropenia, and fever.

PURPOSE: To identify clinical and laboratory parameters present at the time of a first evaluation that could help predict which children with cancer, fever, and neutropenia were at high risk or low risk for an invasive bacterial infection. PATIENTS AND METHODS: Over a 17-month period, all children with cancer, fever, and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto a prospective protocol. Associations between admission parameters and risk for invasive bacterial infection were assessed by univariate and logistic regression analyses. RESULTS: A total of 447 febrile neutropenic episodes occurred in 257 children. Five parameters were statistically independent risk factors for an invasive bacterial infection. Ranked by order of significance, they were as follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2; 95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95% CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to 2.3); platelet count less than or equal to 50,000/mm(3) (RR, 1.7; 95% CI, 1.4 to 2.2); and recent (< or = 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6). Other previously postulated risk factors (magnitude of fever, monocyte count) were not independent risk factors in this study population. CONCLUSION: In a large population of children, common clinical and laboratory admission parameters were identified that can help predict the risk for an invasive bacterial infection. These results encourage the possibility of a more selective management strategy for these children.