Using Nomograms Wisely: Predicting Sentinel Node Positivity in Melanoma.

BACKGROUND: Four externally validated sentinel node biopsy (SNB) prediction nomograms exist for malignant melanoma that each incorporate different clinical and histopathologic variables, which can result in substantially different risk estimations for the same patient. We demonstrate this variability by using hypothetical melanoma cases. METHODS: We compared the MSKCC and MIA calculators. Using a random number generator, 300 hypothetical thin melanoma "patients" were created with varying age, tumor thickness, Clark level, location on the body, ulceration, melanoma subtype, mitosis, and lymphovascular invasion (LVI). The chi-square test was used to detect statistically significant differences in risk estimations between nomograms. Multivariate linear regression was used to determine the most relevant contributing pathologic features in cases where the predictions diverged by > 10%. RESULTS: Of 300 randomly generated cases, 164 were deleted as their clinical scenarios were unlikely. The MSKCC nomogram generally calculated a lower risk than the MIA (p < 0.001). The highest risk score attained for any "patient" using MSKCC calculator was 15% achieved in one of 136 patients (0.7%), whereas using the MIA nomogram, 58 of 136 patients (43%, p < 0.001) had predicted risk >15%. Regression analysis on patients with >10% difference between nomograms revealed LVI (26, p < 0.001), mitosis (14, p < 0.001), and melanoma subtype (8, p < 0.001) were the factors with high coefficients within MIA that were not present in MSKCC. CONCLUSIONS: Nomograms are useful tools when predicting SNB risk but provide risk outputs that are quite sensitive to included predictors.

Factors Affecting Complete Oral Rehabilitation in Patients With Vascularized Free Fibula Flap Mandibular Reconstruction: A 10-Year Retrospective Study.

The fibula is the preferred bone flap for mandibular reconstructions due to its many advantages, including the possibility to insert dental implants. All patients who received a mandibular reconstruction with a vascularized free fibula flap at the Uppsala University Hospital between 2009 and 2019 were retrospectively examined regarding the proportion of implant insertion and factors that affected implant outcome. Forty-one patients had 42 fibula flap reconstructions. Eleven patients (27%) received dental implants and 8 (20%) completed dental rehabilitation. Patient death and cancer recurrence were the main reasons for not receiving implants. The survival rates of implants placed in irradiated and nonirradiated fibulas were 15% and 76%, respectively. Less than 20% of reconstructed patients received an implant-supported prosthesis. Implants placed in an irradiated fibula should be considered at high risk for implant loss.

Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers.

Multi-drug delivery systems constructed from a basic polymeric scaffold, and which have the ability to target a variety of biomedical applications, can streamline the development of nanomedicine to provide both environmental and economical relief. Herein, amphiphilic ABA-triblock copolymers are synthesized and assembled sequentially into micelles and nanogels as drug delivery systems following a thorough evaluation on advanced in vitro models to explore their potential for the treatment of cancer and bacterial infections. Short blocks of 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) are oligomerized from PEG6k and thereafter functionalized with dihydroxyphenylalanine (dopa)-functional thiols using thiol-ene coupling (TEC) click chemistry. The copolymers self-assemble into well-defined micelles in aqueous solution and are further formulated into nanogels via UV-induced TEC. The resulting spherical micelles and nanogels are stable nanoparticles, with sizes ranging between 100 and 200 nm. The nanogels are found to be non-toxic to a panel of cell lines and mask the toxicity of the potent drugs until their release. The nanogels would be superior to micelles for the elimination of cancer cells supported by both 2D cell culture and a 3D spheroid model. The opposite conclusion could be drawn for bacteria inhibition.

Sibship and dispensing patterns of asthma medication in young children-a population-based study.

PURPOSE: Our aim was to study the association between sibship and dispensing patterns of asthma medication in young children, focusing on incidence and persistence, and taking sibship status, asthma diagnoses, and siblings' medication into account. METHODS: A register-based cohort study including all children (n = 50 546) born in Stockholm, Sweden 2006 to 2007, followed up during 2006 to 2014. Exposure was sibling status; outcome was incidence of dispensed asthma medication and persistence over time. A Cox model was used to study the association between sibship and asthma medication. Persistence was defined using two different time windows (4 and 18 months) in a refill sequence model including siblings' and unrelated control children's medication. RESULTS: After 1 year of age, the adjusted hazard ratio of dispensed asthma medication was 0.85 (95% CI 0.80-0.90) among children with siblings compared with singletons. The estimated proportion of children with persistent controller medication was 7.2% (4-month model) and 64.5% (18-month model). When including the siblings' controller medication, the estimated proportion was 8.8% (4 months) and 7.8% for control children (relative risk (RR) 0.89, 95% CI 0.81-0.98). The persistence was lower for those with siblings compared with singletons (adj. RR 0.72, 95% CI 0.62-0.85 for 4 months) with similar estimates for older, younger, and full siblings and regardless of asthma diagnoses. CONCLUSIONS: Siblings have different dispensing patterns of asthma medications compared with singletons regardless of asthma diagnoses. After including the siblings' asthma medication and compared with control children, the proportion of children with persistent medication increased which may indicate that siblings share asthma medications.

Medicine use and disease control among adolescents with asthma.

PURPOSE: Pharmacological treatment is a cornerstone in asthma management, but there is limited evidence on how adolescents use their medication and to what extent their asthma is under control. Therefore, the aim of this study was to compare self-reported and register-based medicine use in asthmatic adolescents. Furthermore, we investigated the association between medicine use, patient characteristics, and degree of asthma control. METHODS: Cross-sectional analyses of 331 adolescents with asthma from a population-based birth cohort linked to data from the Swedish Prescribed Drug Register. Adolescents' asthma medicine use was assessed with three approaches: self-reported medicine use, self-reported use of someone else's medicines, and dispensed medicines from pharmacies during an 18-month period. Medicine use in adolescents with and without asthma control were compared. RESULTS: In total, 82% reported use of asthma medicines, 10 % reported use of someone else's medicines, and 62% were dispensed asthma medicines from pharmacies. Among adolescents with self-reported medicine use, 22% (n = 60) were neither dispensed medicines nor using someone else's medicines. The majority of those using someone else's medicines had also been dispensed asthma medicine (22 out of 33). Among adolescents with asthma, 176 were fully controlled and 155 were uncontrolled. Also, boys had higher odds of having asthma control than girls. CONCLUSION: Most adolescents with asthma reported use of asthma medicines, but a considerable proportion were neither dispensed any medicines nor using someone else's medicines. Girls were less likely to achieve asthma control. It is important to combine data sources to understand medicine use among adolescents with asthma.

Feasibility of a cross-face reconstruction of the mental nerve-A cadaveric simulation study with histomorphometric analysis.

INTRODUCTION: The inevitable sacrifice of the inferior alveolar nerve during oncologic resections results in substantial sensory impairment, impacting crucial functions such as speech, saliva retention, and mastication. This study investigated the feasibility of sensory restoration through cross-face reconstruction of the mental nerve via a contralateral mental nerve branch. METHODS: The cross-face reconstruction procedure was simulated in five formalin-fixed cadavers in both sides to evaluate the anatomic fundamentals and the nerve gap between the mental nerve main trunk and transferred contralateral mental nerve branch. Furthermore, a histomorphometric analysis was performed to assess the cross-sectional area and axon counts. RESULTS: The mean gap distance between the main mental nerve trunk and transferred contralateral branch was 15.3 mm. End-to-end coaptation was achieved in nine out of ten simulations. The mean cross-sectional area was 0.996 mm2 at the main mental nerve trunk and 0.253 mm2 at the coaptation site of the nerve branch. The mean donor-to-recipient axon ratio was found to be 0.3:1. CONCLUSION: The cadaveric simulation demonstrates the feasibility of a cross-face reconstruction of the mental nerve with only minimal gapping. Advantages of the proposed technique include the use of shorter nerve grafts, to minimize donor site morbidity and enable fast reinnervation. This technique may offer a promising method to enhance the quality of life in patients by increasing survival rates and life expectancy.

Caenorhabditis elegans numb inhibits endocytic recycling by binding TAT-1 aminophospholipid translocase.

Numb regulates endocytosis in many metazoans, but the mechanism by which it functions is not completely understood. Here we report that the Caenorhabditis elegans Numb ortholog, NUM-1A, a regulator of endocytic recycling, binds the C isoform of transbilayer amphipath transporter-1 (TAT-1), a P4 family adenosine triphosphatase and putative aminophospholipid translocase that is required for proper endocytic trafficking. We demonstrate that TAT-1 is differentially spliced during development and that TAT-1C-specific splicing occurs in the intestine where NUM-1A is known to function. NUM-1A and TAT-1C colocalize in vivo. We have mapped the binding site to an NXXF motif in TAT-1C. This motif is not required for TAT-1C function but is required for NUM-1A's ability to inhibit recycling. We demonstrate that num-1A and tat-1 defects are both suppressed by the loss of the activity of PSSY-1, a phosphatidylserine (PS) synthase. PS is mislocalized in intestinal cells with defects in tat-1 or num-1A function. We propose that NUM-1A inhibits recycling by inhibiting TAT-1C's ability to translocate PS across the membranes of recycling endosomes.

Socioeconomic status and the quality of prescribing asthma drugs in Sweden.

INTRODUCTION: Socioeconomic status (SES) is strongly associated with morbidity as well as with health care utilization and expenditure. The association between SES and quality of prescribing of asthma drugs is less studied. OBJECTIVES: The aim of this study was to examine the association between socioeconomic factors, i.e. education, income and country of birth, and the prevalence, incidence and adherence to guidelines for antiasthmatic drugs. METHODS: This registry study includes all Swedish citizens aged 25-44 years who redeemed at least one prescription of an antiasthmatic drug during 2010. Incidence and prevalence was calculated. The adherence to guidelines was studied using two defined quality indicators. Heavy users were also assessed. RESULTS: Incidence for antiasthmatic drugs was 18.4 per 1000 person-years and the prevalence 50.9 per 1000 inhabitants. Previously untreated patients who redeemed fixed combination ranged from 45% to 49%. Patients who purchase long-acting beta-2-adrenoceptor agonists (LABA) without inhaled corticosteroid ranged from 43% to 59%. Six percent of the population was classified as heavy users. CONCLUSION: The study showed a high incidence and prevalence of asthma drug use with a poor adherence to guidelines for rational drug prescribing. Fixed combination as first line asthma treatment as well as purchasing LABA without concomitant ICS was more common in patients born outside Scandinavia. Heavy users of short-acting bronchodilators were associated with male sex, high age, low income levels and low levels of education.

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months. Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.

Adherence to guidelines for drug treatment of asthma in children: potential for improvement in Swedish primary care.

BACKGROUND: Adherence to guidelines in general is poor. Because asthma is the most common chronic disease in Swedish children, identifying areas for improvement regarding drug treatment for asthma is crucial. AIM: To explore the utilisation patterns of anti-asthmatic drugs in children with asthma in relation to evidence-based guidelines. METHOD: All children visiting 14 primary healthcare centres in Stockholm, Sweden, who had their first prescription of anti-asthmatic agents dispensed between July 2006 and June 2007 were followed over 24 consecutive months. The children (1033 in total) were divided in two age groups: 0-6 years and 7-16 years. The outcome measurements were: the characteristics of the physicians initiating drug treatment; the extent to which the children were initiated on the drugs recommended in the guidelines; and the amount and frequency of drugs dispensed over time and whether the dosage texts on the prescriptions contained adequate information. RESULTS: In 54% of the older children and 35% of the younger children, only one prescription for anti-asthmatic drugs was dispensed during two years of follow-up following the first prescription. In school-aged children, 50% were initiated on inhaled short-acting bronchodilating beta2-agonists (SABA) in monotherapy. Among preschool children, 64% were initiated on SABA and inhaled corticosteroids in combination. In 41% of the prescriptions dispensed, the indication was stated and in 25% the mechanism of action was stated. Drug therapy was initiated by a general practitioner in 42% of the younger children and 72% of the older children. CONCLUSION: There is a need for improvement in adherence to guidelines in important areas. Asthma, especially among children aged 7-16 years, is usually a chronic disease and should, in many cases, be treated with anti-asthmatics counteracting inflammation. However, this was not the case in our study. In addition, the dosage texts written by the physicians did not follow recommendations and may negatively influence patient safety.

Regional variation and adherence to guidelines for drug treatment of asthma.

AIMS: To describe the utilization of antiasthmatic drugs in Sweden and to explore regional variations in drug utilization and adherence to guidelines for rational drug prescribing of antiasthmatics and their rationale. METHODS: Data on antiasthmatic drugs dispensed between July 2005 and December 2008 to all Swedish citizens aged between 18 and 44 years were obtained from the Swedish National Prescribed Drug Register. The period prevalence was determined by analyzing the number of users/1000 inhabitants, and the incidence by analyzing the number of new users after an 18-month drug-free wash-out period. Three drug-related indicators were used to assess the adherence to guidelines. All measures were analyzed by gender and region. RESULTS: A total of 161,000 patients were dispensed antiasthmatics in 2007, corresponding to a prevalence of 4 and 6% among men and women, respectively; the incidence rates were 2 and 3%, respectively. The total drug utilization and adherence to guidelines varied between regions. The total drug expenditures of antiastmatics were 258 million SEK (28 million euro), with fixed dose combinations accounting for 46% of the expenditure. No relation was found between models for allocating prescribing budgets or clear Drug and Therapeutics Committee recommendations and adherence to guidelines. CONCLUSION: There are large regional variations in the utilization of antiasthmatics between Swedish regions, with substantial room for improvement in the adherence to guidelines. New methods of influencing physician behavior may be needed in the future to enhance adherence.

The influence of structured information and monitoring on the outcome of asthma treatment in primary care: a cluster randomized study.

BACKGROUND: In clinical trials of asthma, the outcomes are often good, but when the same treatment regimens are implemented in primary care, equally good results are not obtained. OBJECTIVE: To investigate if addition of structured patient information and monitoring by an asthma diary in primary care improves asthma control. METHODS: 141 patients from 19 primary care centres were studied. The centres were randomised to a standard care group or to an intervention group. The intervention group received structured written and oral information about asthma and asthma medication, and were instructed to keep an asthma diary. The primary outcome was asthma control as assessed by the Asthma Control Questionnaire. Secondary outcomes were costs of asthma medication, the Mini Asthma Quality of Life Questionnaire score and lung function. RESULTS: Asthma Control Questionnaire score changes differed between the study groups (p < 0.05). In the intervention group, these changes (M = -0.45) in asthma control were close to clinical significance (minimal important difference approximately 0.5). Both groups improved in disease-specific quality of life scores. For the intervention group, which changed the most (p < 0.05), the change exceeded the threshold for the minimal important difference (0.5). The costs of medications increased significantly in the intervention group, where adjustments of medication were made more often than in controls. CONCLUSION: Disease-specific quality of life of asthma patients could be improved by adding structured information and monitoring by diary to standard care.

Asthma severity in primary care asthma patients: a comparative study of four different approaches to severity classification.

AIMS: To explore the factor structure of asthma severity and asthma control and to compare the results of different approaches to asthma severity classification on the distribution of costs of asthma medication. METHODS: Comparison of four different approaches to asthma severity classification and factor analysis of asthma control descriptors. A correlation analysis between costs and the different approaches to severity classification was performed. RESULTS: The factor analysis suggests that asthma control consists of at least two factors. Four approaches to severity classification were explored and all except the 'GINA EXPANDED' classification tended to place patients in the most severe category. The pharmaceutical costs varied between 0 and 75 SEK per day (0 and 5.31 GBP; 0 and 7.68 EURO). CONCLUSIONS: There is a considerable overlap between asthma control and asthma severity. None of the approaches used in this study present a superior satisfactory solution to the classification problem.

Validation of the clinical COPD Questionnaire (CCQ) in primary care.

BACKGROUND: Patient centred outcomes, such as health status, are important in Chronic Obstructive Pulmonary Disease (COPD). Extensive questionnaires on health status have good measurement properties, but are not suitable for use in primary care. The newly developed, short Clinical COPD Questionnaire, CCQ, was therefore validated against the St George's Respiratory Questionnaire (SGRQ). METHODS: 111 patients diagnosed by general practitioners as having COPD completed the questionnaires twice, 2-3 months apart, without systematic changes in treatment. Within this sample of patients with "clinical COPD" a subgroup of patients with spirometry verified COPD was identified. All analyses was performed on both groups. RESULTS: The mean FEV1 (% predicted) was 58.1% for all patients with clinical COPD and 52.4% in the group with verified COPD (n = 83). Overall correlations between SGRQ and CCQ were strong for all patients with clinical COPD (0.84) and the verified COPD subgroup (0.82). The concordance intra-class correlation between SGRQ and CCQ was 0.91 (p < 0.05). Correlations between CCQ and SGRQ were moderate to good, regardless of COPD severity. CONCLUSION: The CCQ is a valid and reliable instrument for assessments of health status on the group level in patients treated for COPD in primary care but its reliability may not be sufficient for the monitoring of individual patients.

Eliminated patient fee and changes in dispensing patterns of asthma medication in children-An interrupted time series analysis.

In 2016, all prescription drugs included in the reimbursement system in Sweden were made available for children (age 0-17 years) without any patient fees. Our aim was to estimate the association between this intervention and the dispensing patterns of asthma medications among children. Dispensing data on asthma medications for all children living in Stockholm County during 2014-2017 were selected to include two years before (January 2014-December 2015) and after (January 2016-December 2017) the intervention. In an uncontrolled before and after study, the measures of utilization were as follows: the proportion of children with at least one dispensed asthma medication (prevalence); the number of children initiated on treatment after an 18-month drug-free period (incidence); the number of defined daily doses (DDDs) dispensed per child; and the number of children with at least two prescriptions with controller medication (inhaled corticosteroid or leukotriene receptor antagonist) dispensed during 18 months (persistence). In an interrupted time series (ITS) analysis, all measures were included except for persistence. Socio-economic status was defined using Mosaic data. The prevalence increased after the intervention (from 11.9% to 13.0%). However, the ITS analysis showed a positive trend already before the intervention, and consequently, the increase was not attributable to the intervention. For incidence, similar patterns were observed. There was an increase in dispensed volumes related to the intervention, 46.3 DDDs/child/month before and 51.1 after the intervention (P-value 0.01). The proportion of children with persistent asthma medication increased from 46.0% to 51.9% in children with low socio-economic status. In conclusion, the intervention was only modestly associated with changes in the dispensing patterns of asthma medication, with the volume dispensed per child increasing slightly, particularly in children with low socio-economic status.

Exploring Radiation Response in Two Head and Neck Squamous Carcinoma Cell Lines Through Metabolic Profiling.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide. Radiotherapy, with or without surgery, represents the major approach to curative treatment. However, not all tumors are equally sensitive to irradiation. It is therefore of interest to apply newer system biology approaches (e.g., metabolic profiling) in squamous cancer cells with different radiosensitivities in order to provide new insights on the mechanisms of radiation response. In this study, two cultured HNSCC cell lines from the same donor, UM-SCC-74A and UM-SCC-74B, were first genotyped using Short Tandem Repeat (STR), and assessed for radiation response by the means of clonogenic survival and growth inhibition assays. Thereafter, cells were cultured, irradiated and collected for subsequent metabolic profiling analyses using liquid chromatography-mass spectrometry (LC-MS). STR verified the similarity of UM-SCC-74A and UM-SCC-74B cells, and three independent assays proved UM-SCC-74B to be clearly more radioresistant than UM-SCC-74A. The LC-MS metabolic profiling demonstrated significant differences in the intracellular metabolome of the two cell lines before irradiation, as well as significant alterations after irradiation. The most important differences between the two cell lines before irradiation were connected to nicotinic acid and nicotinamide metabolism and purine metabolism. In the more radiosensitive UM-SCC-74A cells, the most significant alterations after irradiation were linked to tryptophan metabolism. In the more radioresistant UM-SCC-74B cells, the major alterations after irradiation were connected to nicotinic acid and nicotinamide metabolism, purine metabolism, the methionine cycle as well as the serine, and glycine metabolism. The data suggest that the more radioresistant cell line UM-SCC-74B altered the metabolism to control redox-status, manage DNA-repair, and change DNA methylation after irradiation. This provides new insights on the mechanisms of radiation response, which may aid future identification of biomarkers associated with radioresistance of cancer cells.

Influence of contextual factors on quality of primary care in children with asthma.

OBJECTIVE: Asthma is a common chronic disease among children, quality assurance is thus important. Adherence to pre-specified quality indicators of practice guidelines could be used to assess the quality of asthma care. The aim was to estimate which contextual factors that had an influence on the primary health care centres (PHCs) adherence to the quality indicators as stated in the practice guidelines. METHOD: A pragmatic cross-sectional study was performed comprising 14 PHCs in Sweden. Included contextual factors were socio-demographic characteristics, organizational characteristics, and indicators regarding engagement in asthma care. Documentation on adherence to the quality indicators was retrieved from the medical health care records. Quality indicators included documentation of history of allergy and risk factors, diagnostics and patient support performed, and pharmacological treatment. To score adherence, a composite quality indicator (CQI) was computed for each PHC. A multivariable regression analysis was performed by orthogonal projection to latent structures (OPLS). By this analysis, the relationship between the result variable (CQI) and 26 pre-specified contextual factors was assessed. RESULTS: There was a wide variation of CQI between the PHCs. The OPLS analysis identified that 10 of the contextual factors influenced CQI. The most pronounced influences were found in more time scheduled for asthma care, a lower age-limit for performing spirometry, a lower duty-grade for general practitioners, and a higher activity at asthma educational seminars. We found no influence of socio-demographic contextual factors. CONCLUSION: We found that some of the contextual factors at the PHCs influenced the quality of performed care. Evidence-based care in paediatric asthma may thus be presumed to be facilitated by allocating time, by improving interprofessional collaboration, and by creating structures and opportunities for commitment to asthma care.

Modified Ritgen's maneuver for anal sphincter injury at delivery: a randomized controlled trial.

OBJECTIVE: To investigate whether Ritgen's maneuver decreases the risk of third- to fourth-degree perineal tears compared with simple perineal support. METHODS: A total of 1,623 nulliparous women in term labor, singleton pregnancy, and cephalic presentation were randomly assigned to Ritgen's maneuver or standard care. Ritgen's maneuver denotes extracting the fetal head, using one hand to pull the fetal chin from between the maternal anus and the coccyx, and the other on the fetal occiput to control speed of delivery. Ritgen's maneuver was performed during a uterine contraction, rather than, as originally recommended, between contractions. Our standard care entailed perineal support with one hand and control of the speed of crowning with the other, and use of Ritgen's maneuver only on specific indications. Women delivered by cesarean delivery (n=10) or instrumentally (n=142) were excluded, as well as 39 erroneously included women (parous or in preterm labor), six inaccurately assigned participants, one with missing data, and two participants who withdrew consent. For the remaining 1,423 women, the result was analyzed according to intention to treat. RESULTS: Ritgen's maneuver was performed in 554 (79.6%) of 696 women randomly assigned to this procedure and in 31 (4.3%) of 727 women randomly assigned to simple perineal support. The rate of third- to fourth-degree tears was 5.5% (n=38) in women assigned to Ritgen's maneuver and 4.4% (n=32) in those assigned to simple perineal support (relative risk 1.24; 95% confidence interval 0.78-1.96). CONCLUSION: Ritgen's maneuver does not decrease the risk of anal sphincter injury at delivery, at least not when performed during a contraction.

Differential pattern of human blood neutrophil activation after stimulation with organic dust in vitro and in vivo.

OBJECTIVE: To study activation of blood neutrophils in subjects after in vitro and in vivo stimulation. METHODS: Blood from healthy volunteers was collected before and after their exposure to organic dust in a pig farm. Surface markers of neutrophil activation were analyzed by flow cytometry. RESULTS: In vivo, there was a diurnal variation in basal levels of CD11b. Swine dust exposure increased the number of blood neutrophils and the levels of myeloperoxidase without effects on CD11b or Cys-X-Cys receptor 1 (CXCR-1) expression. However, a positive correlation between changes of myeloperoxidase and CD11b expression was observed. In vitro, N-formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS), leukotriene (LT)B4, LTD4, and swine dust stimulated the expression of CD11b. fMLP, LPS, and LTB4 diminished the expression of CXCR-1. CONCLUSIONS: Exposure to swine dust in vitro activated neutrophils and inhalation of swine dust caused neutrophilia.