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Background: Different approaches to the obturator nerve have been described. However, few have focused on the injection point inferior the iliopubic ramus, specifically at the exit of the obturator canal. This study aims to anatomically evaluate the ultrasound-guided obturator nerve block at the exit of the obturator canal, detailing anatomical landmarks and solution distribution., Methods: This anatomical study was conducted using 10 cadavers to generate 20 hemipelvis samples. Ultrasound references were utilized to identify the obturator canal, iliopubic ramus, pectineus and external obturator muscles, and the obturator membrane. An ultrasound-guided obturator nerve block was performed using a low-frequency convex probe for initial identification and a high-frequency linear transducer for the injection of a methylene blue solution. Subsequent dissections were performed to evaluate the distribution of the dye within the obturator nerve., Results: The injection of methylene blue consistently stained the common trunk and anterior branch of the obturator nerve in 100% of the cases and the posterior branch in 80% of the samples. Intrapelvic staining was observed in 65% of the specimens, indicating effective diffusion of the dye. Key anatomical landmarks, such as the iliopubic ramus and the obturator membrane, were crucial for accurate identification and injection., Conclusion: In conclusion, sagittal approaches using the iliopubic ramus as an anatomical reference achieve the most complete obturator nerve block. Our anatomical study details the structures of the obturator canal and access to the obturator nerve at its exit. Future studies are needed to confirm its safety and efficacy., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Our aim in this study was to evaluate the clinical and prognostic impact of communicating microbiological information in real time for adult patients with bloodstream infections (BSIs)., Methods: We retrospectively reviewed 6225 clinical episodes of bacteremia in a teaching hospital from January 2013 to December 2019. Bacteremia-associated mortality was compared when blood culture results were relayed to the infectious diseases specialist (IDS) in real time and periods when results were relayed the following morning. The impact of information availability using mortality at 30 days was used as the main outcome of the study., Results: The initial analysis (all microorganisms included) did not show an association of mortality and information delay to the IDS (odds ratio [OR], 1.18; 95% confidence interval [CI], .99-1.42). However, information delay of BSIs caused by fast-growing microorganisms such as Enterobacterales was associated with a significant increase in the odds of death at 30 days both in the univariate (OR, 1.76; 95% CI, 1.30-2.38) and multivariate analysis (OR, 2.22; 95% CI, 1.50-3.30). Similar results were found with mortality at 14 days and 7 days in the univariate (OR, 1.54; 95% CI, 1.08-2.20 and OR, 1.56; 95% CI, 1.03-2.37, respectively) and the multivariate analysis (OR, 2.05; 95% CI, 1.27-3.32 and OR, 1.92; 95% CI, 1.09-3.40, respectively)., Conclusions: Information delivered in real time has prognostic relevance and is likely to improve survival of patients with documented BSIs. Future studies should address the prognostic impact of adequate resource allocation (microbiologist/IDS with 24/7 coverage) in BSIs., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The QuantiFERON- TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay's performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting., Methods: Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020., Results: Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2-, n=2; TB1-/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations., Conclusions: Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay's performance substantially., Competing Interests: Competing interests: MT has received QuantiFERON assays at reduced pricing or free of charge for tuberculosis diagnostics projects from the manufacturer (Cellestis/Qiagen) in the past and has received support for conference attendance from Cepheid. The manufacturers had no influence on the study design, data collection, analysis or interpretation, writing of the manuscript or decision to submit the data for publication., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Late presenters (LP) for HIV care are associated with higher morbidity and mortality rates. Our aim was to describe the characteristics associated with LP among adolescents in Spain. Identification of particular features may help in the design of strategies for improvement., Methods: Late-presenting adolescents diagnosed at 12-19 years of age and enrolled in the Spanish paediatric and adult HIV/AIDS cohorts (CoRIS-CoRISpe) from 2004 to 2019 were selected. LP were defined as those presenting with CD4 count <350 cells/mm 3 or an AIDS-defining event in the 6 months following HIV diagnosis. Confirmed low CD4 count in the next 3 months and before antiretroviral treatment initiation defined confirmed LP (cLP)., Results: Of 410 adolescents newly diagnosed with HIV, 303 (73.9%) had available data for assessing late presentation. Of these, 34.7% were LP and 23.7% were cLP. The median CD4 count for cLP was 235 cells/mm 3 (interquartile range 122-285). In a multivariable analysis, adolescents at the highest risk of late presentation were early adolescents (age 12-14 years; odds ratio [OR] 6.50; 95% confidence interval [CI] 2.61-18.2), middle adolescents (age 15-17 years; OR 1.85; 95% CI 0.92-3.59), and adolescents born abroad (OR 1.71; 95% CI 0.97-3.00), particularly those of African origin (OR 3.08; 95% CI 1.38-6.79)., Conclusions: One-quarter of adolescents presented late for HIV care in Spain. Early adolescents, middle adolescents, and those born abroad presented a sevenfold, twofold, and twofold higher risk of being cLP, respectively. Enhancing the awareness of HIV risk and the access to care, especially for younger and foreign adolescents, could help reduce late presentation and tackle the adolescent HIV epidemic., (© 2022 British HIV Association.)

Newborn screening is a public health strategy used to identify certain diseases in the first days of life and, therefore, facilitate early treatment before the onset of symptoms. The decision of which diseases should be included in a screening goes beyond the medical perspective, including reasons for public health and health economics. There are a number of characteristics to include a disease in the screening, such as that the disorder must be a significant health problem, the natural history of the disease must be well known, a feasible and accurate test must be available, there must be a treatment that is most effective when applied before the onset of clinical symptoms and a health system must be in place that is capable of performing the procedure and subsequent monitoring. Currently, newborn screening programs are currently based on the use of biochemical markers that detect metabolites, hormones or proteins, but recently, the availability of new technology has allowed the possibility of a genetic screening. In addition to technical problems, the possibility of neonatal screening also presents a number of ethical problems. We identified and discussed six areas of particular concern: type of illness, overdiagnosis or overtreatment, information management and informed consent, data confidentiality and protection, justice and legal regulation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To understand the attitudes and beliefs of nurses and physicians about managing the sexual health of patients during office visits in primary care centres., Design: A questionnaire-based, cross-sectional multi-centre study., Methods: The study was performed in 15 primary care centres in Barcelona (Spain), from December 2017-February 2018. Obtained data were analysed with descriptive and bivariate statistics., Results: Nearly half the participants believed they should manage sexual health in primary care, but a third of them disagreed this is a priority. Participants also believed patients are not comfortable speaking with them about sex. Statistically significant differences were observed between the professions as nurses more often reported receiving sexual health questions from patients and believed they had enough knowledge to appropriately respond. Most participants wanted additional education to speak with patients more comfortably and confidently about sex., Competing Interests: No conflict of interest has been declared by the authors., (© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Irritable bowel syndrome (IBS) is one of the commonest gastrointestinal disorders. Although long-time considered a pure functional disorder, intense research in past years has rendered a very complex and varied array of observations indicating the presence of structural and molecular abnormalities underlying characteristic motor and sensitive changes and clinical manifestations. Analysis of gene and protein expression in the intestinal mucosa has shed light on the molecular mechanisms implicated in IBS physiopathology. This analysis uncovers constitutive and inductive genetic and epigenetic marks in the small and large intestine that highlight the role of epithelial barrier, immune activation, and mucosal processing of foods and toxins and several new molecular pathways in the origin of IBS. The incorporation of innovative high-throughput techniques into IBS research is beginning to provide new insights into highly structured and interconnected molecular mechanisms modulating gene and protein expression at tissue level. Integration and correlation of these molecular mechanisms with clinical and environmental data applying systems biology/medicine and data mining tools emerge as crucial steps that will allow us to get meaningful and more definitive comprehension of IBS-detailed development and show the real mechanisms and causality of the disease and the way to identify more specific diagnostic biomarkers and effective treatments.

Irritable bowel syndrome (IBS), one of the most frequent digestive disorders, is characterized by chronic and recurrent abdominal pain and altered bowel habit. The origin seems to be multifactorial and is still not well defined for the different subtypes. Genetic, epigenetic and sex-related modifications of the functioning of the nervous and immune-endocrine supersystems and regulation of brain-gut physiology and bile acid production and absorption are certainly involved. Acquired predisposition may act in conjunction with infectious, toxic, dietary and life event-related factors to enhance epithelial permeability and elicit mucosal microinflammation, immune activation and dysbiosis. Notably, strong evidence supports the role of bacterial, viral and parasitic infections in triggering IBS, and targeting microbiota seems promising in view of the positive response to microbiota-related therapies in some patients. However, the lack of highly predictive diagnostic biomarkers and the complexity and heterogeneity of IBS patients make management difficult and unsatisfactory in many cases, reducing patient health-related quality of life and increasing the sanitary burden. This article reviews specific alterations and interventions targeting the gut microbiota in IBS, including prebiotics, probiotics, synbiotics, non-absorbable antibiotics, diets, fecal transplantation and other potential future approaches useful for the diagnosis, prevention and treatment of IBS.

Objective: To determine whether the standard Spanish driving test (ASDE test) was able to identify patients with Parkinson's disease (PD) at risk of unsafe driving and to examine the relationship between the ASDE test and the Useful Field of View (UFOV) as well as with a battery of neuropsychological tests in drivers with PD., Methods: Thirty-seven patients with PD and 33 controls matched by age and education level were included in an observational study. All participants were active drivers and patients with PD underwent study procedures after taking the medication in the "on" period. Subjects with a Mini-Mental State Examination (MMSE) score ≤ 24 were excluded. Neuropsychological tests (Repeatable Battery for Neuropsychological Status [RBANS], Trail Making Test [TMT-A and -B], and Block Design test), driving performance tests (ASDE Driver Test and UFOV), and daytime sleepiness (Epworth Sleepiness Scale) were assessed., Results: The PD group performed significantly worse than healthy controls in the ASDE Motor Coordination tests. No significant differences were observed in anticipation speed, multiple reaction time, concentrated attention, and resistance to monotony. All participants successfully completed the UFOV tests. Statistically significant differences between patients with PD and controls were found in processing speed (UFOV1; P =.03) and more patients with PD were found in the categories of higher driving risk levels (P =.03). In addition, patients with PD showed worse scores than healthy controls in visuospatial capacities (Line Orientation), psychomotor speed (Coding and TMT-A), memory (List Recognition, Story Recall), and executive function (TMT-B). The driving tests (ASDE and UFOV) showed a low sensitivity and a high specificity but a higher percentage of patients in the PD group failed in multiple reaction time, concentrated attention, and resistance to monotony. In addition, 18.9% of patients with PD showed a cutoff of 4 for UFOV risk. In the discriminant analysis, Line Orientation (visuospatial/constructive domain) and Figure Recall (delayed memory) were found to be statistically significant with a rate of correct classification of unsafe drivers with PD of 78.2%. In addition, normal results on the Line Orientation item were associated with a 1.5 times higher probability of non-risky driving in the multivariate analysis., Conclusions: At early stages of the disease, about 19% of patients with PD showed difficulties that may affect their driving capabilities. Line Orientation and Figure Recall are useful to alert clinicians to the risk of unsafe driving. For this reason, patients with PD should be evaluated for driving abilities more regularly to determine the extent of deficits that may influence driving performance.

Disturbed intestinal epithelial barrier and mucosal micro-inflammation characterize irritable bowel syndrome (IBS). Despite intensive research demonstrating ovarian hormones modulation of IBS severity, there is still limited knowledge on the mechanisms underlying female predominance in this disorder. Our aim was to identify molecular pathways involved in epithelial barrier dysfunction and female predominance in diarrhea-predominant IBS (IBS-D) patients. Total RNA and protein were obtained from jejunal mucosal biopsies from healthy controls and IBS-D patients meeting the Rome III criteria. IBS severity was recorded based on validated questionnaires. Gene and protein expression profiles were obtained and data integrated to explore biological and molecular functions. Results were validated by western blot. Tight junction signaling, mitochondrial dysfunction, regulation of actin-based motility by Rho, and cytoskeleton signaling were differentially expressed in IBS-D. Decreased TESK1-dependent cofilin 1 phosphorylation (pCFL1) was confirmed in IBS-D, which negatively correlated with bowel movements only in female participants. In conclusion, deregulation of cytoskeleton dynamics through TESK1/CFL1 pathway underlies epithelial intestinal dysfunction in the small bowel mucosa of IBS-D, particularly in female patients. Further understanding of the mechanisms involving sex-mediated regulation of mucosal epithelial integrity may have significant preventive, diagnostic, and therapeutic implications for IBS.

Introduction: Homecare (HC) is a service offering home medical and nursing care to the patient at home in equal quantity and quality as in the hospital. The aim of the article is to describe the changes in the HC of preterm and full-term low-birth-weight infants in our department from 2002-2014., Material and Methods: The HC database is revised. The characteristics of the newborns and the social characteristics of the family in three consecutive time periods are analysed. A satisfaction survey of parents is also presented., Results: The main changes in HC include a decrease in the weight at discharge (from 1880g in the 2002-2006 period to 1850g in the 2011-2014 period; P=.006) and at the end of HC (from 2187g to 2163g; P=.001), an increase in the duration of HC (from 10 to 11 days; P=.007) and a lower incidence of new hospitalization (from 3.4% to 1.3%; P=.019) The social characteristics of the family show a higher maternal age with more previous alive children, a family context better suited with a more appropriate housing, and an increase in exclusive breastfeeding at hospital discharge (from 25.5% to 49.0%; P<.001). The overall assessment of the program is ≥7/10 in 98.8% of responses., Conclusions: The results of the HC of preterm and low-birth-weight infants have improved over time, saving approximately 10-11 days of hospitalisation, and without compromising the quality of care or reducing family satisfaction., (Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

We report a biomarker and genetic evaluation of four patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) treated with corticosteroids. Patients presented with focal symptomatology and cognitive impairment. MRI revealed cortical microbleeds and asymmetrical hyperintense white matter lesions (WML). Cerebrospinal fluid (CSF) biomarker analyses showed increased anti-Aβ autoantibodies, t-Tau, and p-Tau and decreased Aβ40 and Aβ42. After treatment, focal symptomatology disappeared, and WML and anti-Aβ autoantibodies decreased. The APOEɛ4 allele was overrepresented. Florbetapir-PET showed cortical deposition with lower retention in swollen areas. In the case of suspected CAA-ri, both CSF anti-Aβ autoantibodies levels and Florbetapir-PET could provide highly useful data to guide the correct diagnosis.

This study explores the relationship between numerical chromosome abnormalities in sperm and age in healthy men. We performed FISH in the spermatozoa of 10 donors from the general population: 5 men younger than 40 years of age and 5 fertile men older than 60 years of age. For each chromosome, 1,000 sperm nuclei were analyzed, with a total of 15,000 sperm nuclei for each donor. We used a single sperm sample per donor, thus minimizing intra-donor variability and optimizing consistent analysis. FISH with a TelVysion assay, which provides data on aneuploidy of 19 chromosomes, was used in order to gain a more genome-wide perspective of the level of aneuploidy. Aneuploidy and diploidy rates observed in the younger and older groups were compared. There were no significant differences in the incidence of autosomal disomy, sex chromosome disomy, total chromosome disomy, diploidy, nor total numerical abnormalities between younger and older men. This work confirms that aneuploidy of the sex chromosomes is more common than that of autosomes and that this does not change with age. Our results suggest that some probe combinations have a tendency to indicate higher levels of diploidy, thus potentially affecting FISH results and highlighting the limitations of FISH., (© 2016 S. Karger AG, Basel.)

Objectives: To validate the American fatigue scale HIV-Related Fatigue Scale (HRFS) and present the Spanish version called Integrated Fatigue Assessment Scale to assess fatigue in HCV and co-infected patients., Method: Psychometric study with cross-sectional design was used. The HRFS was translated into Spanish using the back-translation method-later to be validated. Participants completed the questionnaire adapted to a self-report form, as well as a sociodemographic questionnaire. The reliability and validity of the Spanish version was evaluated., Results: A total of 7 public service hospitals and two prisons in Catalonia participated in the evaluation. The sample consisted of 122 subjects selected by consecutive sampling in the fourth week of treatment of hepatitis C with combination therapy or triple therapy. The Cronbach alpha for the total scale was 0.958. Content Validity Index (I-CVI) varied from 0.5 to 1. Validity Scale Content-level (S-CVI) was 0.85. Pearson correlations between the three dimensions were between 0.49 and 0.68., Conclusions: The process followed for the cultural adaptation and validation shows that the Spanish version of the HRFS) is a valid and reliable instrument that can be used in clinical practice and in the investigation of fatigue in patients with hepatitis C., (Copyright © 2015 Elsevier España, S.L.U. All rights reserved.)

Proline residues in transmembrane helices have been found to have important roles in the functioning of membrane proteins. Moreover, Pro residues occur with high frequency in transmembrane alpha-helices, as compared to alpha-helices for soluble proteins. Here, we report several properties of the bacteriorhodopsin mutants P50A (helix B), P91A (helix C) and P186A (helix F). Compared to wild type, strongly perturbed behaviour has been found for these mutants. In the resting state, increased hydroxylamine accessibility and altered Asp-85 pKa and light-dark adaptation were observed. On light activation, hydroxylamine accessibility was increased and proton transport activity, M formation kinetics and FTIR difference spectra of M and N intermediates showed clear distortions. On the basis of these alterations and the near identity of the crystalline structures of mutants with that of wild type, we conclude that the transmembrane proline residues of bacteriorhodopsin fulfil a dynamic role in both the resting and the light-activated states. Our results are consistent with the notion that mutation of Pro to Ala allows the helix to increase its flexibility towards the direction originally hindered by the steric clash between the ring Cgamma and the carbonyl O of the i-4 residue, at the same time decreasing the mobility towards the opposite direction. Due to their properties, transmembrane Pro residues may serve as transmission elements of conformational changes during the transport process. We propose that these concepts can be extended to other transmembrane proteins.

Background: A physiological increase in muscle glutathione after training is not seen in patients with chronic obstructive pulmonary disease (COPD), indicating abnormal peripheral muscle adaptations to exercise., Objective: We hypothesized that oxidative stress is primarily associated with low body mass index (BMI)., Methods: Eleven patients with preserved BMI (BMI(N): 28.2 +/- 1.2 kg.m(-2)), 9 patients with low BMI (BMI(L): 19.7 +/- 0.60 kg.m(-2)) and 5 age-matched controls (26.5 +/- 0.9 kg.m(-2)) were studied before and after 8 weeks of high-intensity endurance training. Reduced glutathione (GSH) and gamma-glutamyl cysteine synthase heavy-subunit chain mRNA expression (gammaGCS-HS mRNA) were measured in the vastus lateralis., Results: After training, exercise capacity increased (DeltaVO(2)PEAK, 13 +/- 5.2%; 10 +/- 5.6% and 15 +/- 4.3% in BMI(L), BMI(N) and controls, respectively; p < 0.05 each). GSH levels decreased in BMI(L) (from 5.2 +/- 0.7 to 3.7 +/- 0.8 nmol/mg protein, DeltaGSH -1.5 +/- 0.7 nmol/mg protein, p < 0.05); no changes were seen in BMI(N) (from 5.4 +/- 0.7 to 6.7 +/- 0.9 nmol/mg protein, DeltaGSH 1.3 +/- 0.9 nmol/mg protein), whereas GSH markedly increased in controls (from 4.6 +/- 1 to 8.7 +/- 0.4 nmol/mg protein, DeltaGSH 4.1 +/- 1 nmol/mg protein, p < 0.01). DeltaGSH in BMI(L) was different from DeltaGSH in BMI(N) and controls (p < 0.05, each). Consistent changes were observed in gammaGCS-HS mRNA expression., Conclusions: GSH depletion after training in BMI(L) may suggest that oxidative stress plays a key role in muscle wasting in COPD patients.

The role of the extracellular Glu side chains of bacteriorhodopsin in the proton transport mechanism has been studied using the single mutants E9Q, E74Q, E194Q, and E204Q; the triple mutant E9Q/E194Q/E204Q; and the quadruple mutant E9Q/E74Q/E194Q/E204Q. Steady-state difference and deconvoluted Fourier transform infrared spectroscopy has been applied to analyze the M- and N-like intermediates in membrane films maintained at a controlled humidity, at 243 and 277 K at alkaline pH. The mutants E9Q and E74Q gave spectra similar to that of wild type, whereas E194Q, E9Q/E194Q/E204Q, and E9Q/E74Q/E194Q/E204Q showed at 277 K a N-like intermediate with a single negative peak at 1742 cm(-1), indicating that Asp(85) and Asp(96) are deprotonated. Under the same conditions E204Q showed a positive peak at 1762 cm(-1) and a negative peak at 1742 cm(-1), revealing the presence of protonated Asp(85) (in an M intermediate environment) and deprotonated Asp(96). These results indicate that in E194Q-containing mutants, the second increase in the Asp(85) pK(a) is inhibited because of lack of deprotonation of the proton release group. Our data suggest that Glu(194) is the group that controls the pK(a) of Asp(85).

The aim of this work was to develop a low-cost circuit for real-time analog computation of the respiratory mechanical impedance in sleep studies. The practical performance of the circuit was tested in six patients with obstructive sleep apnea. The impedance signal provided by the analog circuit was compared with the impedance calculated simultaneously with a conventional computerized system. We concluded that the low-cost analog circuit developed could be a useful tool for facilitating the real-time assessment of airway obstruction in routine sleep studies.

Background and Objective: The development of prothrombotic and procoagulant states may be regulated by direct platelet-leukocyte contact mediated by membrane receptors. We have investigated the role of CD11b integrin in polymorphonuclear leukocytes (PMN) on fibrin formation and platelet reactivity with vascular subendothelium., Methods: Studies were carried out following a well-established perfusion model, employing either citrated blood, where fibrin formation is blocked, or blood anticoagulated with low molecular weight heparin, which allows thrombin and fibrin formation. Isolated PMN or platelets were treated with specific monoclonal antibodies to CD11b or to CD62P, respectively, and incorporated in reconstituted blood., Results: Treatment of PMN with anti-CD11b significantly decreased the percentage of surface covered with a thick layer (> 5 microns) of fibrin (34.8 +/- 3.3% vs 53.3 +/- 4.9% in control, p < 0.05); it also reduced the average height of fibrin layer and the number of adherent leukocytes (7.9 +/- 1.2 microns vs 10.6 +/- 1.4 microns in control, p < 0.05; and 87 +/- 8 PMN/mm2 vs 186 +/- 25 PMN/mm2 in control, p < 0.05) respectively. Treatment of PMN with CD11b did not significantly affect the attachment of platelets onto the subendothelium when using citrated blood, though a slight decrease in platelet adhesion was observed in the heparinized samples. Treatment of platelets with anti-CD62P did not significantly modify any of the parameters studied., Interpretation and Conclusions: Our results indicate that PMN have a role in promoting fibrin deposition under flow conditions, through the participation of CD11b integrin. Under our experimental conditions, this effect does not seem to be influenced by CD62P expressed on activated platelets.

Recent studies suggest that inhaled corticosteroids can adversely affect bone metabolism. The objective of this study was to evaluate the importance of these adverse effects in a case-control study. Bone mineral density (BMD) was measured in 48 asthmatic adults (15 males and 33 females) treated with inhaled steroids (beclomethasone or budesonide) and in 48 gender and age-matched healthy subjects at baseline and at 2 yrs. Vertebral BMD was measured by dual energy X-ray densitometry. Patients had been treated with a dose of 662 +/- 278 micrograms (range 300-1,000 micrograms) of beclomethasone dipropionate or budesonide for more than 1 yr (mean duration of treatment 10.6 yrs, range 1-16 yrs). Twenty four patients had needed 1-6 short courses of oral steroids and seven had received oral corticosteroids (mean daily dose 6.2 mg prednisone) for 2-15 yrs more than 4 yrs prior to the BMD measurements. During the follow-up, 14 patients required 1-3 short courses of oral steroids. There was no correlation either between inhaled corticosteroid doses or duration of treatment and BMD values. There were no significant differences in BMD baseline values between patients and healthy controls. BMD significantly decreased in both groups at 2 yrs, from 1.08 +/- 0.19 to 1.05 +/- 0.19 g.cm-2 (p = 0.002) in asthmatics versus 1.12 +/- 0.17 to 1.09 +/- 0.18 g.cm-2 (p = 0.008) in controls. There were no significant differences in BMD loss between patients and healthy controls. Furthermore, no differences were found in bone loss when pre- and postmenopausal women were compared with their healthy control counterparts. No differences in baseline BMD were found between patients who had received regular oral corticosteroid therapy or booster courses of oral corticosteroids and those who had not. Inhaled corticosteroid treatment at a mean dose of 662 micrograms.day-1 and sporadic booster courses of oral corticosteroids do not further increase bone mass loss with respect to that expected from natural bone mass loss.

Osteoporosis is one of the most serious adverse effects experienced by patients receiving long term corticosteroid therapy. Bone loss occurs soon after corticosteroid therapy is initiated and results from a complex mechanism involving osteoblastic suppression and increased bone resorption. There are a number of factors that may increase the risk of corticosteroid-induced osteoporosis [smoking, excessive alcohol (ethanol) consumption, amenorrhoea, relative immobilisation, chronic obstructive pulmonary disease, inflammatory bowel disease, hypogonadism in men, organ transplantation]. The initial assessment of patients about to start taking corticosteroids should include measurement of spinal bone density, urinary calcium level and plasma calcifediol (25-hydroxycholecalciferol) level; serum testosterone levels should also be measured when hypogonadism is suspected. Many different drugs have been used to prevent osteoporosis in patients receiving long-term corticosteroid therapy, including thiazide diuretics, cholecalciferol (vitamin D) metabolites, bisphosphonates, calcitonin, fluoride, estrogens, anabolic steroids and progesterone. At present, however, published studies have failed to demonstrate a reduction in the rate of fracture using different preventive pharmacological therapies in patients being treated with corticosteroids on a continuous basis. Among the drugs studied, bisphosphonates (pamidronic acid and etidronic acid) and calcitonin appear to be effective in increasing bone density. Cholecalciferol preparations have been reported to be effective in some, but not all, studies. Limited data have shown positive results with thiazide diuretics, estrogen, progesterone and nandrolone. When treating patients with corticosteroids, the lowest effective dose should be used, with topical corticosteroids used whenever possible. Auranofin may be considered in patients with corticosteroid-dependent asthma. Patients should take as much physical activity as possible, maintain an adequate daily intake of calcium (1000 mg/day0 and cholecalciferol (400 to 800 U/day), stop smoking and avoid excessive alcohol intake. It is important to detect and treat hypogonadism in men, if present, and to replace gonadal hormones in postmenopausal women or amenorrhoeic premenopausal women, and to detect and correct cholecalciferol deficiency. A thiazide diuretic should be considered if hypercalciuria is present (urinary calcium excretion in excess of 4 mg/kg/day). High-risk patients and those with established osteoporosis should be treated with bisphosphonates (cyclical etidronic acid or intravenous pamidronic acid), nasal calcitonin, or calcifediol or calcitriol. Patients receiving cholecalciferol preparations should be carefully monitored for hypercalciuria and hypecalcaemia.

Background: An abnormal platelet release of oxygen-free radicals has been described in acetylsalicylic acid (aspirin)-induced asthma, a finding which might suggest the existence of an intrinsic, specific platelet abnormality of arachidonic acid metabolism in these patients. The objective of this study was to evaluate platelet arachidonic acid metabolism in asthmatic patients with or without intolerance to aspirin., Methods: Thirty subjects distributed into three groups were studied: group 1, 10 healthy subjects; group 2, 10 asthmatic patients with aspirin tolerance; and group 3, 10 aspirin-intolerant asthmatics. Platelets were isolated from blood, preincubated with 3H-arachidonic acid for 30 minutes and then incubated for 10 minutes with platelet activating factor (PAF) and aspirin. Cyclo-oxygenase (thromboxane, PGE2, PGF2 alpha, and HHT) and lipoxygenase (12-HETE) arachidonic acid metabolites were measured by high pressure liquid chromatography. Release of oxygen free radicals after incubation with PAF and aspirin was measured by chemiluminescence. Platelet levels of glutathione peroxidase (GSH-Px) were also measured using spectrophotometry., Results: Platelets from aspirin-intolerant asthmatic patients produced higher quantities of arachidonic acid metabolites than the control group at baseline conditions. This increase was significant only for lipoxygenase products. No differences were found amongst the three groups in the response of arachidonic acid metabolism to PAF and aspirin. Incubation with aspirin but not with PAF caused an increase in oxygen-free radical production in aspirin-intolerant patients whereas in aspirin-tolerant patients PAF, rather than aspirin, was the more potent stimulus for oxygen-free radical production. No differences in GSH-Px levels were found amongst the three groups., Conclusions: These results suggest that the platelet lipoxygenase pathway is activated in aspirin-intolerant patients and that the production of oxygen-free radicals may differentiate aspirin-tolerant from aspirin-intolerant asthmatic subjects. Our study, however, does not support the hypothesis that an increase in lipoxygenase products may be responsible for oxygen-free radical production. Moreover, a lowered platelet GSH-Px activity does not seem to be involved in this phenomenon.

Background: Injectable calcitonin is effective in reducing spinal bone loss in steroid-dependent asthma but side effects are frequent. In contrast, a nasal spray presentation has been shown to be effective and well tolerated in involutional osteoporosis. To test the efficacy of nasal calcitonin a two year prospective trial was conducted in 44 steroid-dependent asthmatic patients., Methods: All patients received a calcium supplement of 1000 mg and were allocated randomly into two groups treated with either salmon calcitonin nasal spray (200 IU every other day, n = 22) or calcium alone (n = 22) for two years. All patients completed the first year of the study. Five patients in each group dropped out during the second year. In the calcitonin group one patient developed generalised pruritus and four lost steroid dependence, and in the calcium alone group five were no longer dependent on steroids. The efficacy of treatment was evaluated as follows: bone turnover assessed by biochemical markers, bone loss assessed by serial measurement of lumbar spine density, and rates of bone fractures., Results: The bone mass in the calcitonin group increased by 2.7% in the first year while in the group receiving calcium alone it decreased by 2.8%; this difference was significant. Calcitonin prevented more bone loss during the second year while the calcium alone group continued losing bone mass (-7.8%). The difference between means was 0.1077 (95% CI 0.0381 to 0.1773). Three new fractures occurred in both groups. No changes in biochemical parameters were detected in either group., Conclusions: Calcitonin given intranasally increased spinal bone mass during the first year of treatment and maintained bone mass in a steady state during the second year. These results suggest that calcitonin may be a useful agent to prevent steroid-induced osteoporosis. However, the lack of effect of calcitonin on the rate of vertebral fractures does not permit its recommendation for routine use in preventing steroid-induced osteoporosis.

Background: Although the nose and the bronchi are both involved in the process of regulating respiratory heat exchange, thermal changes may precipitate airway obstruction during exercise but rarely cause nasal obstruction in patients with rhinitis. The cause of the different response of the nose and bronchial tree has hardly been investigated. This study was performed to assess the response of the nose during exercise in the presence of rhinitis, asthma, and in normal controls., Methods: Ten healthy subjects (group 1), 15 patients with asthma and rhinitis (group 2), 10 with rhinitis only (group 3), and 11 with asthma only (group 4) were included in the study. Exercise was performed on a bicycle ergometer for six minutes, reaching a heart rate of 80% of predicted. Bronchial and nasal responses were measured by forced expiratory volume in one second (FEV1) and posterior rhinomanometry, respectively. A drop in the FEV1 of 20% or more was considered a positive exercise induced asthma challenge test., Results: Heart rate and ventilation increased by a similar proportion in the four groups. The FEV1 significantly decreased in asthmatic patients (groups 2 and 4) but it did not change in healthy subjects (group 1) or in those with rhinitis (group 3). Thirteen asthmatic patients developed exercise induced asthma. Nasal patency increased with exercise by a similar proportion in all groups, and no differences were detected between those with rhinitis (groups 2 and 3) and those without (groups 1 and 4). Nasal patency had returned to basal values at 25 minutes after completion of exercise in the four groups. The nose of patients with exercise induced asthma, however, remained significantly more patent than in patients without exercise induced asthma between 10 and 30 minutes after exercise., Conclusions: These results suggest that the nose responds differently from the bronchi during exercise induced airway obstruction: whereas the bronchial tree responds by becoming narrowed, the nose becomes more patent. These findings suggest that the mechanisms regulating the response of the nose to exercise are different from those involved in the response of the bronchial tree.

Influx of inflammatory cells in the nose was evaluated in 14 patients with rhinitis and 11 healthy subjects. Nasal secretions were obtained by nasal lavages. Total cell count and differential count were carried out with a Neubauer chamber and in cytospin slides, respectively. Cells were classified according to their morphology as epithelial cells without nuclei (degenerated), epithelial nucleated cells, neutrophils, eosinophils, and other. Total protein and albumin concentration were measured by the Lowry method and a nephelometric assay respectively. A statistically significant difference was found in total nucleated epithelial cells (P < .01), total neutrophils (P < .01), and total eosinophils (P < .05) between patients and healthy subjects. A significant correlation was found between albumin/total protein concentration with eosinophil numbers (r = .83, P < .001) in patients with rhinitis. These findings suggest that eosinophils participate in the inflammatory process taking place in rhinitis. Since the cellularity present in the nose of rhinitic patients is similar to that usually found in the bronchial secretions of asthmatic patients obtained by bronchoalveolar lavage, our results also suggest that nasal lavage may be used in the study of the inflammatory cells involved in airway diseases.

Background: A report has recently been published concerning a patient with a cryptogenic fibrosing alveolitis who showed a striking improvement after being treated with the antiviral drug ribavirin (tribavirin, Virazid). The objective of this study was to further evaluate, in an open trial, the efficacy of rivabirin in cryptogenic fibrosing alveolitis., Methods: Ten patients (eight women) with advanced cryptogenic fibrosing alveolitis received aerosolised ribavirin (6 g/day for 15 days). Chest radiographs, lung function, and severity of dyspnoea were evaluated before and after two weeks of rivabirin treatment and also at three and 12 months., Results: No differences in radiographs, lung function impairment, or severity of dyspnoea were found after treatment. No side effects were detected., Conclusions: Administration of high doses of aerosolised ribavirin has no beneficial effects in patients with advanced cryptogenic fibrosing alveolitis.

Background: Reduced bone mass predisposes patients to the development of vertebral fractures. Measurement of bone mass by non-invasive methods is used to detect patients with involutional osteoporosis at risk from fractures. These methods have not been assessed in patients with steroid dependent osteoporosis. The objective of this study was to assess the value of a predictive fracture threshold value of bone density in patients with steroid dependent asthma., Methods: Three groups of patients were studied. Group 1 (67 patients) had steroid dependent asthma (mean daily dose of prednisone 11.7 mg) and no vertebral fractures, group 2 (32 patients) had steroid dependent asthma (mean daily dose of prednisone 12 mg) and vertebral fractures, and group 3 (55 patients) were not taking steroids but had involutional osteoporosis and a recent non-traumatic vertebral fracture. Bone mineral density was measured by dual photon absorptiometry and vertebral fractures by radiography of the lumbar spine. A fracture threshold was determined in the two groups with fractures as the 90th percentile of the mean bone mineral density measured in the lumbar spine., Results: Bone mineral density was significantly higher in the steroid dependent group with fractures (group 2) than in group 3 patients, who had involutional osteoporosis and fractures (0.946 (0.18) g/cm2 v 0.830 (0.16) g/cm2). The fracture threshold value was therefore higher for patients with steroid related vertebral fractures (group 2, 1.173 g/cm2) than for those with involutional osteoporosis (group 3, 0.979 g/cm2). Vertebral fractures were more likely to occur in steroid dependent asthmatic patients with bone density above the fracture threshold value (obtained from subjects with involutional osteoporosis) than in subjects in group 3 (34% v 9%)., Conclusion: Vertebral fractures occur in patients treated with steroids in the presence of higher bone mineral density than is the case with patients with involutional osteoporosis. The findings suggests that the assessment of the efficacy of preventive treatment requires measurement of bone mineral density and radiology.

A secondary hyperparathyroidism resulting from decreased intestinal calcium (Ca) absorption has been proposed as a contributory factor to glucocorticoid-induced osteoporosis. Inhaled steroids do not usually suppress adrenal gland function unless daily doses above 1,500 microgram are used. A recent study, however, has shown a reduced total body calcium in patients on regular beclomethasone treatment. In theory, osteopenia in these patients could be due to a direct effect of inhaled steroids on bone or due to an impaired intestinal calcium absorption. In this study, Ca absorption and parathyroid hormone (PTH) secretion were evaluated in three groups: 1) asthmatics on continuous oral and inhaled steroid treatment (11.3 +/- 4.4, range 5-33.5 mg.day-1 prednisone and 660 +/- 265, range 400-1,600 microgram.day-1 beclomethasone, respectively); 2) asthmatics on regular beclomethasone therapy (585 +/- 210, range 400-1,200 microgram.day-1); and 3) healthy subjects. The prevalence of vertebral fractures was evaluated by a spinal X-ray. No differences were found in either Ca absorption or PTH serum levels between asthmatics and healthy subjects (analysis of variance-ANOVA). Vertebral fractures were significantly more frequent in patients from group 1 (14 of 25) than in those from group 2 (2 or 25). We conclude that both prolonged oral steroid treatment and inhaled steroids, at doses lower than 1,600 microgram.day-1 do not cause Ca malabsorption, and that hyperparathyroidism does not contribute to osteoporosis in these patients.