SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer.

BACKGROUND: Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance. PATIENTS AND METHODS: In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m2 every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety. RESULTS: A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel [median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144]. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively. CONCLUSIONS: Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports.

Eosinophilic granulomatosis with polyangiitis: sequential use of mepolizumab following rituximab for inadequate asthma control despite vasculitis remission.

We report the case of a 54-year-old woman with antineutrophilic cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis presenting with mononeuritis multiplex, intestinal hemorrhage, cardiomyopathy, fever, and worsening asthma symptoms. She was initially treated with steroids and cyclophosphamide but eventually required rituximab to control a vasculitis flare. However, her asthmatic symptoms did not improve, despite attaining vasculitis remission. Symptoms abated only after the treatment transition to mepolizumab. After a 1-year interval, there were no further episodes of asthma exacerbation and no requirement for systemic steroid therapy. This report reinforces the use of rituximab for induction and maintenance of remission in patients with eosinophilic granulomatosis with polyangiitis and predominant vasculitic manifestations, whereas mepolizumab demonstrated better control of the persistent eosinophilic manifestations, ensuing sustained remission and improved quality of life.

Physiologic and behavioural signs during a dental appointment in children and teenagers with Cerebral Palsy: a comparative cross-sectional study.

AIM: To evaluate the heart rate (HR) and behaviour of children and teenagers with Cerebral Palsy (CP) when having a dental appointment. METHODS: A comparative cross-sectional study was carried out with 60 participants with CP, between 2 and 14 years old (study group-SG), and 60 normotypical individuals (CG). The sample was paired according to age, gender and socioeconomic status. Behaviour was evaluated during dental prophylaxis using the Frankl Scale, and HR was measured at five moments: before the appointment, when sitting in the dental chair, during the clinical examination, during prophylaxis and immediately after prophylaxis. Mann-Whitney, Friedman and Chi-square tests were applied at a significance level of 5%. RESULTS: SG presented significantly higher HR (p < 0.001) and more participants with uncooperative behaviour (p < 0.001) than CG in all observational periods. Furthermore, SG participants with uncooperative behaviour presented higher HR values than those in SG who were cooperative in all observational periods (p ≤ 0.002). CONCLUSIONS: Individuals with CP have a higher HR before and during the clinical session, and are frequently more uncooperative with the procedure than normotypical individuals.

The Iberian legacy into a young genetic xeroderma pigmentosum cluster in central Brazil.

In central Brazil, in the municipality of Faina (state of Goiás), the small and isolated village of Araras comprises a genetic cluster of xeroderma pigmentosum (XP) patients. The high level of consanguinity and the geographical isolation gave rise to a high frequency of XP patients. Recently, two founder events were identified affecting that community, with two independent mutations at the POLH gene, c.764 + 1 G > A (intron 6) and c.907 C > T; p.Arg303* (exon 8). These deleterious mutations lead to the xeroderma pigmentosum variant syndrome (XP-V). Previous reports identified both mutations in other countries: the intron 6 mutation in six patients (four families) from Northern Spain (Basque Country and Cantabria) and the exon 8 mutation in two patients from different families in Europe, one of them from Kosovo. In order to investigate the ancestry of the XP patients and the age for these mutations at Araras, we generated genotyping information for 22 XP-V patients from Brazil (16), Spain (6) and Kosovo (1). The local genomic ancestry and the shared haplotype segments among the patients showed that the intron 6 mutation at Araras is associated with an Iberian genetic legacy. All patients from Goiás, homozygotes for intron 6 mutation, share with the Spanish patients identical-by-descent (IBD) genomic segments comprising the mutation. The entrance date for the Iberian haplotype at the village was calculated to be approximately 200 years old. This result is in agreement with the historical arrival of Iberian individuals at the Goiás state (BR). Patients from Goiás and the three families from Spain share 1.8 cM (family 14), 1.7 cM (family 15), and a more significant segment of 4.7 cM within family 13. On the other hand, the patients carrying the exon 8 mutation do not share any specific genetic segment, indicating an old genetic distance between them or even no common ancestry.

Injuries to the Stomatognathic System in Brazilian Jiu-Jitsu Athletes.

As a contact sport, Brazilian jiu-jitsu requires the fighter to expose his/her stomatognathic system to the adversary, making him/her more susceptible to oral and maxillofacial injuries and disorders. The aim of the present study was to determine the prevalence of injuries and disorders of the stomatognathic system and associated factors among practitioners of Brazilian jiu-jitsu. A total of 179 athletes were interviewed and submitted to a physical examination. The majority was male, in the beginner category and had participated in competitions. Athletes with more experience had a higher frequency of orofacial injuries (PR = 1.77; 95% CI: 1.01-1.38), such as oral mucous lacerations and skin abrasions in the facial region, which mainly occurred during training sessions. A mouthguard is not mandatory for the sport and many athletes (both beginners and more experienced athletes) do not use one due to difficulty breathing with the device. A prefabricated (type II) mouthguard was the most common among the athletes who used this equipment, although it does not offer adequate protection. Athletes on more advanced levels wore mouthguards significantly more often (PR = 1.96; 95% CI: 1.11-2.45). In conclusion, more experienced jiu-jitsu athletes had a higher frequency of orofacial injuries, such as lacerations and abrasions, and are more likely to wear a mouthguard. However, longitudinal studies are needed in order to assess the possible causes and risks.

Spatial clustering, social vulnerability and risk of leprosy in an endemic area in Northeast Brazil: an ecological study.

BACKGROUND: Despite the global decline in the detection of leprosy cases, its incidence has remained unchanged in certain settings and requires the determination of the factors linked to its persistence. We examined the spatial and space-time distribution of leprosy and the influence of social vulnerability on the occurrence of the disease in an endemic area of Northeast Brazil. METHODS: We performed an ecological study of all leprosy cases reported by Sergipe state, Northeast Brazil from 2001 to 2015, to examine the association of the Social Vulnerability Index and the prevalence and persistence of leprosy among the State's municipalities. Socio-economic and leprosy surveillance information was collected from the Brazilian information systems, and a Bayesian empirical local model was used to identify fluctuations of the indicators. Spatial and space-time clusters were identified using scan spatial statistic tests and to measure the municipalities' relative risk of leprosy. RESULTS: Leprosy clusters and burden of disease had a strong statistical association with the municipalities' Social Vulnerability Index. Municipalities with a high social vulnerability had higher leprosy incidence, multibacillary leprosy and newly diagnosed cases with grade 2 disability than areas with low social vulnerability. CONCLUSION: Social vulnerability is strongly associated with leprosy transmission and maintenance of disease incidence. Leprosy control programmes should be targeted to the populations with high social vulnerability.

Biological variability of the sweat chloride in diagnostic sweat tests: A retrospective analysis.

BACKGROUND: The sweat test is the current gold standard for the diagnosis of cystic fibrosis (CF). CF is unlikely when sweat chloride (Clsw) is lower than 30mmol/L, Clsw>60 is suggestive of CF, with intermediate values between 30 and 60mmol/L. To correctly interpret a sweat chloride value, the biological variability of the sweat chloride has to be known. METHODS: Sweat tests performed in two centers using the classic Gibson and Cooke method were retrospectively reviewed (n=5904). Within test variability of Clsw was measured by comparing results from right and left arm collected on the same day. Between test variability was calculated from subjects with sweat tests performed on more than one occasion. RESULTS: Within test variability of Clsw calculated in 1022 subjects was low with differences between -3.2 (p5) and +3.6mmol/L (p95). Results from left and right arm were classified differently in only 3 subjects. Between test variability of Clsw in 197 subjects was larger, with differences between -18.2mmol/L (p5) and +14.1mmol/L (p95) between repeat tests. Changes in diagnostic conclusion were seen in 55/197 subjects, the most frequent being changing from indeterminate to 'CF unlikely' range (48/102). CONCLUSION: Variability of sweat chloride is substantial, with frequent changes in diagnostic conclusion, especially in the intermediate range.

Colon Cancer Staging in Vulnerable Older Adults: Adherence to National Guidelines and Impact on Survival.

BACKGROUND: There is concern that elders are not adequately evaluated prior to colon cancer surgery. We sought to determine adherence with ACOVE-3 (Assessing Care of Vulnerable Elders) quality indicators for pre-operative staging prior to colectomy for colon cancer utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database (1992-2005). METHODS: We determined the proportion of patients aged 75 and older who had preoperative staging prior to colectomy for colon adenocarcinoma. Preoperative staging was defined as abdominopelvic computed tomography or magnetic resonance imaging scan (SCAN) and colonoscopy or flexible sigmoidoscopy (SCOPE). Multivariate logistic regression identified predictors of adherence. Odds ratios were adjusted for comorbidity, socioeconomic status, and disease severity. The association of adherence to ACOVE-3 and survival was quantified. RESULTS: Of the 37,862 patients, the majority were 75-84 years, 28% of the patients were ≥85 years. Regarding preoperative staging in the 6-month interval prior to surgical resection, 8% had neither SCAN nor SCOPE, 6% had only SCAN, 43% had only SCOPE, and 43% had both SCAN and SCOPE. Compared to patients who were not staged, those evaluated with either SCOPE alone or SCAN plus SCOPE had lower odds of 3-year mortality. Patients who were staged with SCAN alone had an increased odds of death compared to those who had neither SCAN or SCOPE. CONCLUSIONS: These data demonstrate that the majority of vulnerable elders with colon cancer did not receive appropriate preoperative staging prior to resection. The findings also confirm that adherence to ACOVE-3 guidelines is associated with improved long-term survival.

Caracterização anatômica, histoquímica e de classes de metabólitos secundários de folhas de Guzmania lingulata (L. ) Mez / Anatomical, histochemical and class characterization of secondary metabolites in leaves of Guzmania lingulata (L. ) Mez

Na medicina natural pouco se sabe sobre a importância curativa da maior parte das espécies pertencentes à Bromeliaceae. Tal fato evidencia a necessidade da realização de investigações para a comprovação de possíveis potenciais fitoterápicos em espécies dessa família. Guzmania lingulata é caracterizada como sendo uma das espécies de bromélia mais comercializada e conhecida popularmente, a qual é amplamente propagada no Brasil. O presente trabalho objetivou a caracterização anatômica e a identificação de classes de metabólitos secundários presentes em G. lingulata, por meio de análises anatômicas, histoquímicas e químicas. As folhas foram fixadas em FAA 50 e transferidas para etanol 50%. Para o estudo anatômico, secções transversais da porção mediana das lâminas foliares foram obtidas à mão livre e submetidas ao processo de dupla coloração com safranina e azul de astra, sendo, logo após, montadas em gelatina glicerinada. Para a triagem das classes de metabólitos secundários foram coletadas 10 folhas frescas que passaram pelo processo de maceração em solução hidroalcoólica 70% por sete dias, à temperatura ambiente. O filtrado resultante da filtração a vácuo foi evaporado sob vácuo a temperatura de 50ºC até a remoção total do etanol, sendo obtido desta forma o extrato bruto hidroalcoólico a frio (EBHF). Os resultados das secções histológicas permitiram a caracterização anatômico-foliar baseada na qualidade das secções manuais obtidas. Os testes em relação às classes de metabólitos secundários revelaram a presença de antocianinas e taninos e ausência de flavonóides e saponinas. Esses resultados estimulam a realização de estudos mais aprofundados para identificar e quantificar os compostos dessas e de outras classes de metabólitos.

In natural medicine, little is known about the healing importance of most of the species belonging to the family Bromeliaceae. Such a fact points tothe need to perform investigations toprovethe possible phytotherapic potentials in species of the family. Guzmania lingulata is characterized as one of the most popular well-known and commercialized species of bromeliads, being widely spread in Brazil. This work aimed at the anatomic characterization and identification of classes of the secondary metabolites present in G. lingulata, by anatomic, histochemical and chemical analysis of the leaves. The leaves were fixed in FAA 50 and, afterwards, transferred to 50% ethanol. For the anatomic study, transverse sections of the middleproportion of the leafblades were obtained by hand and exposed to the process of double coloration with safranin and astra blue, being, right after that, mounted on glycerin jelly. For the sorting of the classes of secondary metabolites, 10 fresh leaves were collected and then put through the maceration process in 70% hydroalcoholic solution for 7 days, at room temperature. The resulting filtered solution from the vacuum filtration was evaporated under vacuum at 40ºC until the complete removal of the ethanol, obtaining, this way, the cold crude hydroalcoholic extract (EBHF). The results ofhistological sectionsallowed the anatomical characterization based onthe quality ofthe manual sectionsobtained. The testsin relationto the classes of secondary metabolitesrevealed the presence ofanthocyanins andtannins andabsence of flavonoids and saponins. These results encourage the completionoffurther studies to identify and quantify the compounds of these and other classes of metabolites.

Testes fitoquímicos em extratos foliares de Oeceoclades maculata Lindl. (Orchidaceae) / Phytochemical tests in Oeceoclades maculata Lindl. (Orchidaceae) leaf extracts

O presente trabalho teve por objetivo determinar a capacidade antioxidante de Oeceoclades maculata. A atividade foi determinada de acordo com a capacidade do extrato hidroalcoólico das folhas reduzir o radical DPPH. Os resultados obtidos permitem concluir que os conteúdos de polifenóis e flavonas/flavonóis são maiores no extrato preparado a frio (EBHF) do que no extrato preparado a quente (EBHQ), sugerindo que o aquecimento usado na preparação do extrato altera esses componentes ativos. Portanto, para esta espécie deve ser realizado o método de extração a frio para conservar as substâncias que possuem atividade antioxidante.

This work aimed to determine the antioxidant capacity of Oeceoclades maculata. The antioxidant activity was determined in accordance with the ability of the hydroalcoholic extract of the leaves to reduce the DPPH radical. The results showed that the polyphenol and flavonoid contents are greater in the cold extract (EBHF) than in the hot extract (EBHQ), which suggests that the heating effect in the preparation of the extract modifies these active compounds. Therefore, for this species, the cold extraction method must be carried in order to conserve the substances with antioxidant activity.

Qualidade do corpo lúteo e do embrião de ovelhas Santa Inês superovuladas com FSH associado à rbST / Quality of corpus luteum and embryo of Santa Inês ewes superovulated with FSH associated with rbST

Avaliou-se o efeito da somatotropina bovina recombinante (rbST) sobre a qualidade do corpo lúteo e do embrião e sobre a concentração de progesterona (P4), em ovelhas da raça Santa Inês doadoras de embriões. Foram utilizadas 13 doadoras, distribuídas aleatoriamente em dois grupos, G1 (n=7) e G2 (n=6). Em ambos os grupos, as doadoras foram sincronizadas com implante vaginal por 14 dias, receberam 100µg de PGF2α (Ciosin®) no sétimo dia e foram superovuladas, a partir do 12º dia, com 250UI de FSH (Folltopin-V®) em seis doses decrescentes. No dia da retirada do implante, as doadoras do G2 receberam 125mg de rbST (Boostin®) e foram cobertas por macho Santa Inês a cada 12 horas até o final do estro. No sexto dia após a primeira cobrição, foram avaliadas, por laparoscopia, a resposta superovulatória e a quantidade e a qualidade dos corpos lúteos. Após as avaliações, as colheitas embrionárias foram realizadas por laparotomia. A administração da rbST no protocolo de superovulação promoveu aumento significativo (P<0,05) no número de corpos lúteos do tipo I (9,00 x 5,28) e na qualidade embrionária (4,33 x 2,00).

We evaluate the effect of recombinant bovine somatotropin (rbST) on the quality of the corpus luteum and embryo and on the concentration of progesterone (P4) in donors embryo sheep Santa Ines. 13 donors were used, randomly assigned to two groups, G1 (n=7) and G2 (n=6). In both groups, the donors were synchronized with vaginal implant for 14 days and received 100µg of PGF2α (Ciosin®) on the seventh day and were superovulated, from the 12th day, with 250IU of FSH (Folltopin-V®) in six decreasing doses. On the day of implant removal the donor G2 received 125mg of rbST (Boostin®), and were covered by Santa Inês male every 12 hours until the end of estrus. In the sixth day after the first mating were evaluated by laparoscopy, superovulatory response and the amount and quality of the corpus luteum. After the evaluations, the embryonic harvests were performed by laparotomy. The administration of rbST in superovulation protocol promoted a significant increase (P <0.05) in the number of corpus luteum of type I(9.00 x 5.28) and embryo quality (4.33 x 2.00).

Aerosol delivery to the lung is more efficient using an extension with a standard jet nebulizer than an open-vent jet nebulizer.

BACKGROUND: Open-vent jet nebulizers are frequently used to promote drug deposition in the lung, but their clinical efficacy and indications are not clear. Our study compared lung deposition of amikacin using two different configurations of a jet nebulizer (Sidestream(®)): one vented (N1) and one unvented with a corrugated piece of tubing (N2). METHODS: In vitro nebulizer performance was assessed by laser diffraction and filtering. Lung delivery was evaluated by scintigraphy in baboons as a child model, and by amikacin urinary drug concentration in seven healthy spontaneously breathing volunteers. Subjects were randomly assigned to the two nebulizer systems (N1 and N2). RESULTS AND CONCLUSIONS: In vitro results showed a higher efficiency of N2 than N1 in terms of lung deposition prediction (95±3 mg vs. 70±0 mg; p<0.0001). Radioactivity deposition in the baboons' lungs was lower with N1 than with N2 (1.8% vs. 4.7% of nebulizer charge; p<0.05). The total daily amount of amikacin urinary excretion was lower with N1 than with N2 (29.5 mg vs. 40.1 mg; p<0.01). Conversely, in vivo drug output rate was higher with N1 than with N2 (3.1 mg/min vs. 2.2 mg/min; p<0.05). Using a corrugated piece of tubing with standard jet nebulizers delivers higher doses to the lungs than open-vent jet nebulizers. The open-vent jet nebulizer might be recommended for rapid administration of a lower dose to the lungs and the standard jet nebulizer with corrugated piece of tubing for a higher dose in the lungs.

CFTR biomarkers: time for promotion to surrogate end-point.

In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis. Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts. The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed. This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.

[Mucoviscidosis: CFTR mutation-specific therapy: a ray of sunshine in a cloudy sky]. / Mucoviscidose : l'espace bleu entre les nuages ?

There is a need to find a cure for pulmonary disease in cystic fibrosis (CF), though full benefit of this approach will be restricted to those patients with well-preserved lungs. The most promising route is currently that of a pharmacological mutation-specific approach aiming at correcting the mechanism by which mutations lead to impairment of chloride conductance across respiratory epithelial cells. In the past 14years, 7 candidate drugs (CPX, 4PBA, gentamicin, PTC124, VX-770 or Ivacaftor, VX-809 or Lumacaftor, and Miglustat) have been investigated in CF patients. A postulate of 14 out of the 15 published studies has been that an effective agent had to improve total chloride secretion as assessed in vivo by nasal potential difference measurements. The present review casts a critical look at these studies. Apparent inconsistencies are discussed as well as possible limitations of nasal potential difference measurements as outcome parameters in these trials. Primarily targeting a mutation carried by less than 2% of French CF patients, the 2 Ivacaftor studies could well be a milestone on the long road toward a cure for CF. However, further data on safety and long-term efficacy are obviously needed and the current price of this medication in the US would make it unaffordable for European patients.

Inhaled phosphodiesterase type 5 inhibitors restore chloride transport in cystic fibrosis mice.

Sildenafil and vardenafil, two selective inhibitors of phosphodiesterase type 5 (PDE5) are able, when applied by intraperitoneal injection, to activate chloride transport in cystic fibrosis (CF) mice homozygous for the F508del mutation. Oral treatment with the drugs may be associated with adverse haemodynamic effects. We hypothesised that inhaled PDE5 inhibitors are able to restore ion transport in F508del CF airway epithelium. We developed a restraint-free mouse chamber for inhalation studies. PDE5 inhibitors were nebulised for 15 min at concentrations adjusted from recommended therapeutic oral doses for male erectile dysfunction. We measured in vivo nasal transepithelial potential difference 1 h after a single inhalation of sildenafil, vardenafil or tadalafil in F508del CF and normal homozygous mice. After nebulisation with the drugs in F508del mice, chloride transport, evaluated by perfusing the nasal mucosa with chloride-free buffer containing amiloride followed by forskolin, was normalised; the forskolin response was increased, with the largest values being observed with tadalafil and intermediate values with vardenafil. No detectable effect was observed on sodium conductance. Our results confirm the role of PDE5 inhibitors in restoring chloride transport function of F508del CF transmembrane conductance regulator protein and highlight the potential of inhaled sildenafil, vardenafil and tadalafil as a therapy for CF.

Plasma lipoproteins in visceral leishmaniasis and their effect on Leishmania-infected macrophages.

This work aimed at investigating the lipid profile of zoonotic visceral leishmaniasis (VL) patients' sera and the effect of lipoproteins on the in vitro production of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10 and IL-12 by Leishmania infantum-infected and uninfected macrophages. Lipids were quantified in 26 VL patients' sera and 26 healthy controls from a VL endemic area. The patients' sera had higher triglyceride and very low density lipoprotein (VLDL) levels, and much lower apolipoprotein A1, total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) levels than the control sera. Lipoprotein fractions were obtained by ultracentrifugation of sera. The addition of LDL and HDL to Leishmania-infected and uninfected macrophages, in physiological concentrations, enhanced the production of IL-6 and IL-10, but not of IL-12. LDL stimulated the production of TNF-alpha only in infected macrophages, whereas HDL stimulated the production of lower amounts of TNF-alpha in both infected and uninfected macrophages. VLDL stimulated only the production of IL-10. It is proposed herein that LDL may influence the development of VL by promoting the production of TNF-alpha by infected macrophages. A decrease in plasma LDL in some VL patients (to 20 mg/mL or less); however, would tend to reduce the production of TNF-alpha and therefore to limit the development of immune-mediated pathology, not withstanding the fact that it would perhaps increase the permissiveness of macrophages to Leishmania growth.

Early referral to cystic fibrosis specialist centre impacts on respiratory outcome.

BACKGROUND: Published studies concerning the impact of specialist care on lung disease in cystic fibrosis remain limited and most are either biased due to comparison with historical controls and/or underpowered. METHODS: In this retrospective multicentric study, data from all CF children fulfilling the following criteria were collected: 1) Age 6-<18 at the end of 2003; 2) diagnosis before 8 y; 3) follow-up in an accredited CF Belgian centre; 4) at least 1 spirometry and respiratory culture available for 2003. Group A included children referred > or =2 years after the diagnosis. Patients from Group A were then matched with a single early referred patient on the basis of 2 criteria: same centre, as closest age as possible (Group B). RESULTS: Data from 217 children were collected (Group A: 67/217). Late referred patients had a lower FEV(1) (77.2%+/-22.4 vs 86.7% pred.+/-19.4, p=0.01) and a higher prevalence of Pseudomonas aeruginosa (38.6 vs 17.5%, p<0.05). CONCLUSION: In this population of CF children, a delay of 6.1 y (vs 0.1 y) between diagnosis and referral to a specialist clinic resulted in poorer respiratory outcome at age 13.

Sweat potassium concentration may help to identify falsification of sweat test: a case report.

OBJECTIVES: To document the relevance of sweat potassium concentration in a reported case of a white Caucasian 27-month-old boy who presented with non-specific respiratory symptoms and several abnormal sweat test results compatible with cystic fibrosis (CF). DESIGN AND METHODS: Repeated sweat tests using the Gibson-Cooke technique in the presence and absence of the mother. RESULTS: The high within- and between-test variability, the very low sweat potassium concentrations, several aspects of the family's history and a negative exhaustive genetic analysis to identify any CFTR mutation, raised suspicion for pediatric condition falsification. Two additional sweat tests performed in the absence of the mother were normal. CONCLUSION: CF diagnosis was then discarded and a Munchausen syndrome by proxy diagnosis was proposed.