Extrapulmonary nontuberculous mycobacterial infections: a guide for the general physician.

Non-tuberculous mycobacteria (NTM) infections predominantly present as pulmonary disease. Although relatively rare, 20-30 % originate from extrapulmonary sites resulting in a wide range of clinical syndromes. Immunocompromised individuals are particularly susceptible. Clinical manifestations include skin and soft-tissue infections, lymphadenitis, musculoskeletal infections and disseminated disease. Diagnosing extrapulmonary NTM is challenging, and management is complex, often involving multiple radiological and microbiological investigations, long courses of combination antibiotic regimens and may require adjuvant surgical interventions. We highlight both the importance of involving NTM experts at an early stage and the role of a multidisciplinary approach in the diagnosis and management of these infections.

Is the combination of UV-C light and bleach less effective than bleach alone for intensive care unit surface disinfection?

Background: Chlorine-based disinfectants, such as bleach, are commonly used for cleaning in healthcare settings to prevent the transmission of nosocomial pathogens. To enhance the efficacy of disinfection, ultraviolet-C (UV-C) light systems have been proposed to supplement standard cleaning procedures. As bleach decomposes in UV light, we hypothesised that the use of UV-C light as an adjunct to manual cleaning with bleach, may decrease the efficacy of disinfection instead. Methods: In the laboratory, stainless steel sheets and plastic keyboards were inoculated with Pseudomonas aeruginosa (∼106 CFU/ml) and subjected to treatment with either UV-C light only, bleach only or a combination of UV-C light and bleach. The residual bioburden (CFU/ml) was quantified through conventional microbiological techniques. Results were compared to non-exposed control surfaces and against each treatment strategy. Results: On tested surfaces, there were statistically significant reductions in P. aeruginosa when surfaces were treated with UV-C light only (>2.5 log10 reduction), bleach only (>5.6 log10 reduction) and a combination of UV-C light and bleach (>6.3 log10 reduction) compared to positive control (P < 0.001, all treatment strategies). No significant differences were observed when surfaces were treated with the addition of UV-C light to bleach compared to treatment with bleach alone. Conclusion: There was no difference in the efficacy of disinfection against P. aeruginosa with the combined treatment strategy of UV-C light and bleach compared to bleach alone under laboratory conditions. Further studies are warranted to elucidate the effectiveness of this technology on other healthcare-associated pathogens.

Changing Incidence and Characteristics of Nontuberculous Mycobacterial Infections in Scotland and Comparison With Mycobacterium tuberculosis Complex Incidence (2011 to 2019).

Background: An increase in infections with nontuberculous mycobacteria (NTM) has been noted globally, and their incidence has overtaken that of Mycobacterium tuberculosis complex (MTBc) in many countries. Using data from a national reference laboratory, we aimed to determine if this trend could be observed in Scotland. Methods: We undertook a retrospective review of all NTM isolates received by the Scottish Mycobacteria Reference Laboratory (SMRL) over 9 years from 2011 to 2019 inclusive. Clinical episodes were defined as per 2017 British Thoracic Society and 2020 American Thoracic Society/European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases/Infectious Diseases Society of America NTM guidelines. These rates were compared with Scottish tuberculosis rates over the same period. Results: Of 8552 NTM isolates from 4586 patients in 2011 to 2019, 7739 (90.5%) were considered clinically relevant. These represented 2409 episodes of NTM infection, with M. avium, M. intracellulare, and M. abscessus complex being most common. A total of 1953 (81.1%) were pulmonary NTM infection episodes from 1470 patients and 456 extrapulmonary episodes from 370 patients. We estimated a rise in incidence from 3.4 to 6.5 per 100 000 person-years (2011-2019 inclusive), with an increase in NTM incidence over MTBc incidence in Scotland by 2017. Conclusions: The incidence of NTM infection in Scotland has overtaken MTBc incidence. NTM infection leads to a costly health care burden, possibly as much as UK£1.47 million (US$ and €1.73 million) annually. We recommend standardization of isolate referral with clinical surveillance and implementation of agreed standards of care delivered through multidisciplinary teams. This would improve diagnosis and patient management as well as assessment of diagnostics and novel treatments through clinical trials.

Biting the hand that feeds you: Management of human and animal bites.

Bites from animal and humans represent a very small proportion of all the patients presenting to emergency departments, However, they require prompt medical and surgical intervention in order to minimise the risk of infection, that may lead to limb and life-threatening complications. In this review article we synthesise the existing literature for treatment of human and animal bites and offer practical considerations when managing bite injuries.

Obesidad e inflamación en estudiantes de una universidad pública colombiana / Obesity and inflammation in students of a Colombian public university

RESUMEN Objetivo Describir la relación entre obesidad y variables proinflamatorias en la población estudiantil de la Universidad del Quindío. Métodos Estudio descriptivo de corte transversal en el cual participaron 155 estudiantes. En primer lugar se midió la glicemia -por métodos convencionales-, la insulinemia y las citocinas -mediante la prueba ELISA-; también se calculó IMC e índice HOMA-IR. Luego, esta información se analizó en el software Statgraphics con el fin de establecer relaciones entre las variables a través de regresión múltiple. Así, se llegó a una diferencia estadísticamente significativa cuando el valor de p fue ≤0,05. Resultados La prevalencia de obesidad por IMC fue de 4,6%; la de sobrepeso, 20,5%; y la de obesidad abdominal por perímetro de cintura fue de 18,5%. El promedio de insulinemia fue de 8,5 pUI/ml±6,4 y el índice HOMA-IR, de 1,7. El 18,5% presentaron resistencia a la insulina. El interferón gamma se encontró en 4,6±12,0 pg/mL; la IL-6, en 5,1±15,5 pg/mL; y el TNF alfa, en 3,2±11,1 pg/mL. La mayor variación explicada (R2) la presentan la insulinemia, el índice cintura/cadera y el índice Homa-IR. La IL-6 fue la citocina que presentó la mayor variación explicada. Conclusiones Se evidencia que existe una relación entre citocinas inflamatorias como la IL-6 con el índice cintura/cadera, la insulinemia y el índice Homa-IR y la presión diastólica.

ABSTRACT Objective To describe the relationship between obesity and proinflammatory variables in the student population of the University of Quindío. Methods A cross-sectional descriptive study in which 155 students participated. Firstly, the glycemia was made by conventional methods, the insulinemia and the cytokines were measured by ELISA; IMC and HOMA-IR index were calculated. Then, the information was analyzed in the Statgraphics software to establish relationships between the variables were established through multiple regression and thus statistically significant difference was considered when the p value was ≤0.05. Results The prevalence of obesity by BMI was of 4.6%, of overweight 20.5% and of abdominal obesity by waist circumference was of 18.5%. The average insulinemia was 8.5 pUI/ml ±6.4 and the HOMA-IR index was 1.75. 18.5% had insulin resistance. Interferon gamma was found at 4.6±12.0 pg/mL, IL-6 at 5.1±15.5 pg/mL and TNF alpha at 3.2±11.1 pg/mL. The greatest variation explained (R2) is presented by insulinemia, the waist/hip index and the Homa-IR index. IL-6 was the cytokine that presented the greatest variation explained. Conclusions There is a relationship between inflammatory cytokines such as IL-6 with the waist/hip index, diastolic pressure, insulinemia and the Homa-IR index.

[Obesity and inflammation in students of a Colombian public university]. / Obesidad e inflamación en estudiantes de una universidad pública colombiana.

OBJECTIVE: To describe the relationship between obesity and proinflammatory variables in the student population of the University of Quindío. METHODS: A cross-sectional descriptive study in which 155 students participated. Firstly, the glycemia was made by conventional methods, the insulinemia and the cytokines were measured by ELISA; IMC and HOMA-IR index were calculated. Then, the information was analyzed in the Statgraphics software to establish relationships between the variables were established through multiple regression and thus statistically significant difference was considered when the p value was ≤0.05. RESULTS: The prevalence of obesity by BMI was of 4.6%, of overweight 20.5% and of abdominal obesity by waist circumference was of 18.5%. The average insulinemia was 8.5 pUI/ml ±6.4 and the HOMA-IR index was 1.75. 18.5% had insulin resistance. Interferon gamma was found at 4.6±12.0 pg/mL, IL-6 at 5.1±15.5 pg/mL and TNF alpha at 3.2±11.1 pg/mL. The greatest variation explained (R2) is presented by insulinemia, the waist/hip index and the Homa-IR index. IL-6 was the cytokine that presented the greatest variation explained. CONCLUSIONS: There is a relationship between inflammatory cytokines such as IL-6 with the waist/hip index, diastolic pressure, insulinemia and the Homa-IR index.

OBJETIVO: Describir la relación entre obesidad y variables proinflamatorias en la población estudiantil de la Universidad del Quindío. MÉTODOS: Estudio descriptivo de corte transversal en el cual participaron 155 estudiantes. En primer lugar se midió la glicemia -por métodos convencionales-, la insulinemia y las citocinas -mediante la prueba ELISA-; también se calculó IMC e índice HOMA-IR. Luego, esta información se analizó en el software Statgraphics con el fin de establecer relaciones entre las variables a través de regresión múltiple. Así, se llegó a una diferencia estadísticamente significativa cuando el valor de p fue ≤0,05. RESULTADOS: La prevalencia de obesidad por IMC fue de 4,6%; la de sobrepeso, 20,5%; y la de obesidad abdominal por perímetro de cintura fue de 18,5%. El promedio de insulinemia fue de 8,5 pUI/ml±6,4 y el índice HOMA-IR, de 1,7. El 18,5% presentaron resistencia a la insulina. El interferón gamma se encontró en 4,6±12,0 pg/mL; la IL-6, en 5,1±15,5 pg/mL; y el TNF alfa, en 3,2±11,1 pg/mL. La mayor variación explicada (R2) la presentan la insulinemia, el índice cintura/cadera y el índice Homa-IR. La IL-6 fue la citocina que presentó la mayor variación explicada. CONCLUSIONES: Se evidencia que existe una relación entre citocinas inflamatorias como la IL-6 con el índice cintura/cadera, la insulinemia y el índice Homa-IR y la presión diastólica.

Non-typeable Haemophilus influenzae-associated early pregnancy loss: an emerging neonatal and maternal pathogen.

OBJECTIVES: There is increasing evidence indicating an association between invasive non-typeable Haemophilus influenzae (NTHi) infection in pregnancy and early pregnancy loss. As the diagnosis relies on microbiological investigation of post-mortem placental and foetal samples, a significant proportion of NTHi-related pregnancy loss remains unrecognised. To better characterise NTHi in septic abortion, we report NTHi cases associated with early pregnancy loss. METHODS: We reviewed all post-mortems at <24 weeks gestation with histologically proven acute chorioamnionitis on placental histology and enrolled cases with at least one matched foetal and placental sample culture positive for NTHi. The study was approved by the NHS Lothian Caldicott Guardian. RESULTS: In our cohort, invasive NTHi has accounted for 20% of infections associated with early pregnancy loss prior to 24 weeks gestation. All patients were young and healthy pregnant women at < 20 weeks' gestation who presented with abdominal pain, PV bleed /discharge and were septic at the time of presentation. One patient with previous history of miscarriage who presented with cervical incompetence had more severe pathology suggestive of early intrauterine pneumonia. CONCLUSION: The burden of invasive NTHi disease in early pregnancy loss is likely to be much larger than currently recognised. NTHi should be considered in pregnant women presenting with abdominal pain and PV bleed/discharge in whom clinical signs of sepsis are present. Active surveillance should be considered in this patient group including septic abortion to capture the true prevalence of this emerging pathogen to inform preventative and therapeutic approaches.

Sonographic Evaluation of Fetal Adrenal Gland in Gestational Diabetes: Relation to Fetal Growth and Maternal Biochemical Markers.

OBJECTIVES: To relate measurements and volume of the fetal adrenal gland in third trimester ultrasound in diabetic pregnancies (1) to birth weight; (2) to other sonographic markers of diabetic fetopathy (expected fetal weight, sectional area, and fractional volume in fetal limbs); and (3) to maternal biochemical markers of diabetes (HbA1c, leptin). METHODS: Fetal adrenal gland measurements were obtained between 32 and 34 weeks. The gland length, width, depth, and volume (by Virtual Organ Computer-Aided Analysis [VOCAL]) were measured for total gland and fetal zone. Fetal total and fat sectional area and fractional volume were obtained in arm and thigh. A maternal blood sample was obtained. Univariate and multivariate models were used to assess the associations. RESULTS: Thirty-nine diabetic pregnancies were included. Birth weight related significantly to total and fetal zone adrenal depth, and total adrenal volume in third trimester. Total adrenal length and corrected adrenal gland volume also showed a significant correlation to birth weight percentile in univariate and multivariate models. Total adrenal volume associated significantly to total and fat areas and volumes in fetal limbs. Both maternal leptin and HbA1c levels found a significant positive relation to fetal total adrenal volume and corrected adrenal gland volume. Total adrenal gland volume showed a significant association to maternal HbA1c level in multivariate model. CONCLUSIONS: An enlargement of the fetal adrenal gland may be observed in gestational diabetes, not only related to birth weight, but also to distinctive features of diabetic pregnancies, such as fat tissue fetal deposits or maternal biochemical markers.

Weight-related and analytical maternal factors in gestational diabetes to predict birth weight and cord markers of diabetic fetopathy.

OBJECTIVE: The objective was to determine the value of clinical and analytical maternal factors to predict birth weight and umbilical cord biochemical markers of diabetic fetopathy. METHODS: Prospective evaluation of gestational diabetes pregnancies (n = 50). Maternal weight-related clinical and analytical factors were collected during pregnancy. After birth, an umbilical cord sample was taken. RESULTS: Univariate linear regression analysis showed relationship between maternal weight, glycated hemoglobin (HbA1c) and insulin-like growth factor 1 (IGF1) with birth weight percentile. A significant association was found between maternal weight and cord insulin and C-peptide. Maternal HbA1c, leptin and insulin during pregnancy showed a positive linear association to cord leptin, insulin and C-peptide. In multivariate analysis models, final maternal BMI showed an independent positive association with cord C-peptide. CONCLUSIONS: Maternal weight-related and analytical parameters show diagnostic value to birth weight and cord markers.

Efecto del ejercicio sobre las subpoblaciones HDL, la enzima lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol en estudiantes de Medicina / Effect of exercise in HDL subpopulations, lecithin-cholesterol acyltransferase enzyme (LCAT) and ester transfer proteincholesterol (CETP) in medical students

Objetivo: Evaluar el efecto del ejercicio físico sobre los niveles de las subpoblaciones HDL, enzima lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol en estudiantes de Medicina. Método: La población se dividió de manera voluntaria en 2 grupos: ejercicio y no ejercicio. Se midieron perímetro abdominal e índice de masa corporal, subfracciones de HDL2 y HDL3 por precipitación iónica, y enzima lecitina-colesterol acil-transferasa y proteína transportadora de ésteres de colesterol mediante Enzyme-Linked Immuno Sorbent Assay (ELISA). Resultados: El perfil lipídico de riesgo aumentó en ambos grupos: las HDL, HDL3 y HDL2 disminuyeron en ambos grupos, pero solo las HDL2 lo hicieron de forma significativa en el grupo que realizó ejercicio. La lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol permanecieron sin cambios significativos. Sin embargo, en el grupo que hizo ejercicio hubo disminución estadísticamente significativa de HDL2 y lecitina-colesterol acil-transferasa, en las mujeres. Conclusiones: El ejercicio logra modificar algunas variables como el perímetro abdominal, el índice de masa corporal y las HDL3. Estas modificaciones son dependientes del género, pero, a pesar de la intervención de 3 meses con un programa de ejercicio, este no logra reducir los factores de riesgo lipídico en esta población de estudiantes de Medicina, debido a que su entorno hace muy compleja la respuesta metabólica al ejercicio.

Objective: To evaluate exercise effect on HDL subpopulations, lecithin-cholesterol acyltransferase enzyme and ester transfer protein cholesterol levels in medical students. Method: Population was divided voluntarily into 2 groups, exercise and no exercise. Waist circumference and body mass index were measured; subfractions HDL2 and HDL3 by ion precipitation and LCAT and CETP enzymes Enzyme-Linked Immuno-Sorbent Assay (ELISA). Results: Lipidrisk profile increased in both groups; HDL, HDL2 and HDL3 decreased in both groups, but only the HDL2 decreased significantly in students who exercised. LCAT and CETP remained without significant changes, however, in the exercise group, there was statistically significant decrease in HDL2 and LCAT in women. Conclusions: This study shows that exercise does alter some variables such as waist circumference, body mass index and HDL3. These changes are dependent on gender, but despite the intervention of 3 months with an exercise program, it fails reducing lipid risk factors in this medical student populations, given their environment, which complicates their metabolic response to exercise.

Fetal limb soft tissue assessment for prediction of birth weight and umbilical cord blood analytes in gestational diabetes.

OBJECTIVE: To evaluate the value of third trimester ultrasound (estimated fetal weight, cheek-to-cheek diameter, sectional Wharton's jelly area, sectional areas and fractional volumes in extremities) to predict birth weight and cord biochemical markers at birth (leptin, insulin, c-peptide, IGF1, erythropoietin and ferritin) in diabetic pregnancies. METHOD: Prospective study in 49 patients with gestational diabetes. An ultrasound was performed between 32 and 34 weeks. Clinical data were collected, and a blood sample was obtained from cord after birth. ROC curve models were evaluated for 75(th) and 90(th) birth weight percentile. Univariate and multivariate models were used to assess the association between ultrasound and neonatal outcomes. RESULTS: Sectional areas and fractional volumes showed significant differences and highest AUC values for predicting birth weight. A significant association was found for extremities measurements with total birth weight and its percentile. The only marker which showed a significant association to estimated fetal weight was erythropoietin. Sectional areas and fractional volumes related to cord leptin, erythropoietin, insulin and c-peptide. CONCLUSION: Sectional areas and fractional volumes improve the predictive value of estimated fetal weight in diabetic pregnancies. They also show a predictive association to biochemical changes in cord (leptin, insulin and erythropoietin) related to increased adiposity and risk of fetal hypoxia. © 2015 John Wiley & Sons, Ltd.

Differential response to bacteria, and TOLLIP expression, in the human respiratory tract.

OBJECTIVES: The observation that pathogenic bacteria are commonly tolerated in the human nose, yet drive florid inflammation in the lung, is poorly understood, partly due to limited availability of primary human cells from each location. We compared responses to bacterial virulence factors in primary human nasal and alveolar cells, and characterised the distribution of Toll-interacting protein (TOLLIP; an inhibitor of Toll-like receptor (TLR) signalling) in the human respiratory tract. METHODS: Primary cells were isolated from nasal brushings and lung tissue taken from patients undergoing pulmonary resection. Cells were exposed to lipopolysaccharide, lipoteichoic acid, peptidoglycan, CpG-C DNA or tumour necrosis factor (TNF). Cytokines were measured in cell supernatants. TOLLIP was characterised using quantitative real-time PCR and immunofluorescence. RESULTS: In primary alveolar, but not primary nasal, cells peptidoglycan significantly increased secretion of interleukin (IL)-1ß, IL-6, IL-8, IL-10 and TNF. TLR2 expression was significantly higher in alveolar cells and correlated with IL-8 production. TOLLIP expression was significantly greater in nasal cells. CONCLUSION: In conclusion, primary human alveolar epithelial cells are significantly more responsive to peptidoglycan than primary nasal epithelial cells. This may partly be explained by differential TLR2 expression. TOLLIP is expressed widely in the human respiratory tract, and may contribute to the regulation of inflammatory responses.

Unilateral and pruritic papules: segmental Darier-White disease.

Darier-White disease is an uncommon disorder, which presents in a localized pattern in about 10% of patients, usually without nail, mucosa, or acral involvement. Type-1 is the most common of the segmental Darier-White disease types: papules have unilateral distribution along Blaschko lines. A 36-year-old woman diagnosed with type-1 segmental Darier-White disease is reported herein.

Efecto del ejercicio en subpoblaciones de lipoproteínas de alta densidad y en la presión arterial / Effect of exercise on high density lipoprotein subpopulations and blood pressure

Objetivo Determinar la relación del ejercicio con los niveles séricos de la apoA-I y las subpoblaciones de HDL2 y HDL3, en personas hipertensas de la Ciudad de Armenia - Quindío. Métodos La intervención fueron dos meses de ejercicio. La presión arterial se tomó con las recomendaciones del Ministerio de Salud de Colombia. Las subpoblaciones de HDL se midieron con el método del precipitado ionico y la apoA-I se midió con la técnica de nefelometría de bindig site. Resultados Los datos se analizaron con estadística descriptiva e inferencial. Se captaron 160 pacientes de los cuales 125 permanecieron hasta el final del proyecto, es decir, hubo un 78,12 % de permanencia; el 28 % hicieron ejercicio. El análisis mostró una reducción altamente significativa de la tensión arterial sistólica y diastólica mayor en las personas que hicieron que en las que no hicieron ejercicio. Las cifras de HDL estaban por debajo de lo normal antes del ejercicio aumentaron significativamente con el ejercicio pero aún se mantuvieron por debajo de los valores de referencia, las HDL2 aumentaron significativamente, mientras las HDL3 descendieroncon niveles normales de apoA-I. Conclusiones Este trabajo muestra que el ejercicio aumenta las HDL totales, pero lo más importante es que modifica la subpoblaciones de HDL en una relación que favorece aquellas que parecen tener propiedades ateroprotectivas. Y la evidencia de la interrelación entre factores protectores, aporta nuevos argumentos para las acciones en salud pública, frente al riesgo cardiovascular y la hipertensión Arterial.

Objetive Determine the relationship of exercise with serum levels of apoA-I and HDL2 and HDL3, subpopulations in hypertensive individuals from the city of Armenia - Quindío. Methods The interventions were two months of exercise. Blood pressure was taken with the recommendations of the Ministry of Health of Colombia. HDL subpopulations were measured with the method of precipitate ionicand the apoA-I was measured using nephelometry of Bindig site. Results Descriptive and inferential statistics were used for data analysis. A total of 160 patients of whom 125 remained until the end of the project were gathered, that is, there was a 78.12 % retention, 28 % did the exercise. The analysis showed a highly significant reduction of systolic and diastolic blood pressure, higher in people who did exercise. The HDL were below normal before exercise, significantly increased with exercise but still remained below the reference values, the HDL2 increased significantly, while HDL3 decreased with normal levels of apoA-I. Conclusion This study shows that exercise increases the total HDL, but the most important is that exercise modified the HDL subpopulations in a relationship that favors those which seem to have ateroprotective properties. The evidence of the interrelationship between protective factors provides new arguments for public health actions against the cardiovascular risk and hypertension.

[Effect of exercise on high density lipoprotein subpopulations and blood pressure]. / Efecto del ejercicio en subpoblaciones de lipoproteínas de alta densidad y en la presión arterial.

OBJECTIVE: Determine the relationship of exercise with serum levels of apoA-I and HDL2 and HDL3, subpopulations in hypertensive individuals from the city of Armenia - Quindío. METHODS: The interventions were two months of exercise. Blood pressure was taken with the recommendations of the Ministry of Health of Colombia. HDL subpopulations were measured with the method of precipitate ionic and the apoA-I was measured using nephelometry of Bindig site. RESULTS: Descriptive and inferential statistics were used for data analysis. A total of 160 patients of whom 125 remained until the end of the project were gathered, that is, there was a 78.12 % retention, 28 % did the exercise. The analysis showed a highly significant reduction of systolic and diastolic blood pressure, higher in people who did exercise. The HDL were below normal before exercise, significantly increased with exercise but still remained below the reference values, the HDL2 increased significantly, while HDL3 decreased with normal levels of apoA-I. CONCLUSION: This study shows that exercise increases the total HDL, but the most important is that exercise modified the HDL subpopulations in a relationship that favors those which seem to have ateroprotective properties. The evidence of the interrelationship between protective factors provides new arguments for public health actions against the cardiovascular risk and hypertension.

Application of crustacean chitin as a co-diluent in direct compression of tablets.

A "simplex-centroid mixture design" was used to study the direct-compression properties of binary and ternary mixtures of chitin and two cellulosic direct-compression diluents. Native milled and fractioned (125-250 microm) crustacean chitin of lobster origin was blended with microcrystalline cellulose, MCC (Avicel PH 102) and spray-dried lactose-cellulose, SDLC Cellactose (composed of a spray-dried mixture of alpha-lactose monohydrate 75% and cellulose powder 25%). An instrumented single-punch tablet machine was used for tablet compactions. The flowability of the powder mixtures composed of a high percentage of chitin and SDLC was clearly improved. The fractioned pure chitin powder was easily compressed into tablets by using a magnesium stearate level of 0.1% (w/w) but, as the die lubricant level was 0.5% (w/w), the tablet strength collapsed dramatically. The tablets compressed from the binary mixtures of MCC and SDLC exhibited elevated mechanical strengths (>100 N) independent of the die lubricant level applied. In conclusion, fractioned chitin of crustacean origin can be used as an abundant direct-compression co-diluent with the established cellulosic excipients to modify the mechanical strength and, consequently, the disintegration of the tablets. Chitin of crustacean origin, however, is a lubrication-sensitive material, and this should be taken into account in formulating direct-compression tablets of it.

Diagnostic importance of pulmonary interleukin-1beta and interleukin-8 in ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. The hypothesis was tested that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP. METHODS: A prospective, observational cohort study was carried out in two university hospital intensive care units recruiting 73 patients with clinically suspected VAP, and a semi-urban primary care practice recruiting a reference group of 21 age- and sex-matched volunteers. Growth of pathogens at >10(4) colony-forming units (cfu)/ml of bronchoalveolar lavage fluid (BALF) distinguished VAP from "non-VAP". Inflammatory mediators were quantified in BALF and serum. Mediators showing significant differences between patients with and without VAP were analysed for diagnostic utility by receiver operator characteristic (ROC) curves. RESULTS: Seventy-two patients had recoverable lavage-24% had VAP. BALF interleukin-1beta (IL-1beta), IL-8, granulocyte colony-stimulating factor and macrophage inflammatory protein-1alpha were significantly higher in the VAP group (all p<0.005). Using a cut-off of 10 pg/ml, BALF IL-1beta generated negative likelihood ratios for VAP of 0.09. In patients with BALF IL-1beta <10 pg/ml the post-test probability of VAP was 2.8%. Using a cut-off value for IL-8 of 2 ng/ml, the positive likelihood ratio was 5.03. There was no difference in cytokine levels between patients with sterile BALF and those with growth of <10(4) cfu/ml. CONCLUSIONS: BALF IL-1beta and IL-8 are amongst the strongest markers yet identified for accurately demarcating VAP within the larger population of patients with suspected VAP. These findings have potential implications for reduction in unnecessary antibiotic use but require further validation in larger populations.

Direct compression properties of chitin and chitosan.

Deformation and compaction properties of native amino poly-saccharides chitin and chitosan were studied and compared with those obtained with established pharmaceutical direct compression excipients. An instrumented single-punch tablet machine was used for tablet compaction. The following compression parameters were evaluated: a ratio of crushing strength and compression pressure, plasticity and elasticity factor (PF and EF), tensile strength and R-value. Chitin and chitosan were found to have a marked tendency to plastic deformation, and both showed a good compression behaviour compared with the other direct compression excipients including microcrystalline cellulose. It is concluded that chitin and chitosan are potential co-excipients for direct compression applications.

Acinetobacter baumannii lipopolysaccharides are potent stimulators of human monocyte activation via Toll-like receptor 4 signalling.

Acinetobacter baumannii is a major nosocomial pathogen and frequent cause of hospital-acquired pneumonia, surgical wound infections and sepsis. As very little is known of the endotoxic potential of A. baumannii lipopolysaccharide (LPS) with respect to human cells or of its ability to stimulate inflammatory signalling via human Toll-like receptors (TLRs), the biological activity of these endotoxins was investigated in human monocytic THP-1 cells and in TLR-deficient HEK-293 cells transfected with human TLR2 and TLR4 constructs. Endotoxins derived from five clinical isolates of A. baumannii and one of Acinetobacter 'genomospecies 9' showed high potency, which was comparable to that of Escherichia coli strain R1 NCTC 13114 LPS, in the induction of the Limulus amoebocyte reaction and interleukin 8 and tumour necrosis factor alpha release from THP-1 cells. Whole UV-killed cells of A. baumannii and Acinetobacter 'genomospecies 9' stimulated both TLR2- and TLR4-dependent signalling, whereas pure endotoxins of all investigated strains induced signalling via TLR4, but not TLR2.