Evaluation of salivary tumor necrosis factor α as a diagnostic biomarker in oral submucosal fibrosis and squamous cell carcinoma of the oral cavity and oropharynx: a cross sectional observational study.

Introduction: Tumor necrosis factor α (TNF-α) is known to be associated with chronic inflammation, and its expression has been shown to increase in advanced cancers. Chronic inflammation is a characteristic feature of oral submucous fibrosis (OSMF), which is a potentially malignant disorder (PMD). Squamous cell carcinoma (SCC) is associated with considerable mortality and morbidity and an early detection or monitoring would greatly help in achieving an effective cure. TNF-α was thus evaluated for use as a biomarker in the present study according to the stage of OSMF and histological grade of SCC in the oral cavity and oropharynx. Methods: This study included 45 patients divided into 3 groups-OSMF group, SCC group and control group-each comprising 15 participants. Saliva samples were collected from each patient, and salivary TNF-α levels were estimated using an ELISA kit. Results: Statistical analysis revealed no significant differences in TNF-α levels among the OSMF, SCC and control groups; however, there was an increase in the salivary TNF-α level in patients with stage 3 disease according to the clinical stage of OSMF, for which the p value was 0.027. Discussion: An increase in the TNF-α concentration with increasing clinical stage suggested a role for TNF-α in the spread of OSMF involvement in anatomical structures of the oral cavity and oropharynx. No significant difference in salivary TNF-α levels was noted among the OSMF, SCC and control groups. Conclusion: The study showed a positive correlation of TNF-α with increasing stages of OSMF but was not a reliable biomarker in the categorization of the same.

A qualitative study of the impact of endometriosis on male partners.

STUDY QUESTION: What is the impact of endometriosis on male partners of women with the condition? SUMMARY ANSWER: Endometriosis significantly impacts men across several life domains and can negatively impact emotional well-being. WHAT IS KNOWN ALREADY: Endometriosis has been shown to negatively impact women's quality of life and may strain intimate relationships. Little is known about the impact on male partners. STUDY DESIGN, SIZE, DURATION: The ENDOPART study was a cross-sectional, qualitative study of 22 women with endometriosis and their male partners (n = 44) in the UK (2012-2013). PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria: laparoscopic diagnosis of endometriosis; the presence of symptoms for at least a year; partners living together. Data were collected via face to face, semi structured interviews with partners interviewed separately. Data were analysed thematically, assisted by NVivo 10. MAIN RESULTS AND THE ROLE OF CHANCE: Men reported that endometriosis affected many life domains including sex and intimacy, planning for and having children, working lives and household income. It also required them to take on additional support tasks and roles. Endometriosis also had an impact on men's emotions, with responses including helplessness, frustration, worry and anger. The absence of professional or wider societal recognition of the impact on male partners, and a lack of support available to men, results in male partners having a marginalized status in endometriosis care. LIMITATIONS REASONS FOR CAUTION: Self-selection of participants may have resulted in a sample representing those with more severe symptoms. Couples included are in effect 'survivors' in relationship terms, therefore, findings may underestimate the contribution of endometriosis to relationship breakdown. WIDER IMPLICATIONS OF THE FINDINGS: The study extends knowledge about the impact of endometriosis on relationships, which thus far has been drawn largely from studies with women, by providing new insights about how this condition affects male partners. Healthcare practitioners need to take a more couple-centred, biopsychosocial approach toward the treatment of endometriosis, inclusive of partners and relationship issues. The findings demonstrate a need for information and support resources aimed at partners and couples. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Economic and Social Research Council (reference ES/J003662/1). The authors have no conflicts of interest.

The Percutaneous shunting in Lower Urinary Tract Obstruction (PLUTO) study and randomised controlled trial: evaluation of the effectiveness, cost-effectiveness and acceptability of percutaneous vesicoamniotic shunting for lower urinary tract obstruction.

BACKGROUND: Congenital lower urinary tract obstruction (LUTO) is a disease associated with high perinatal mortality and childhood morbidity. Fetal vesicoamniotic shunting (VAS) bypasses the obstruction with the potential to improve outcome. OBJECTIVE: To determine the effectiveness, cost-effectiveness and patient acceptability of VAS for fetal LUTO. DESIGN: A multicentre, randomised controlled trial incorporating a prospective registry, decision-analytic health economic model and preplanned Bayesian analysis using elicited opinions. Patient acceptability was evaluated by interview in a qualitative study. SETTING: Fetal medicine departments in the UK, Ireland and the Netherlands. PARTICIPANTS: Pregnant women with a male singleton fetus with LUTO. INTERVENTIONS: In utero percutaneous VAS compared with conservative care. MAIN OUTCOME MEASURES: The primary outcome was survival to 28 days. Secondary outcome measures were survival and renal function at 1 year of age, cost of care and cost per additional life-year and per disability-free survival at the end of 1 year. RESULTS: The trial stopped early with 31 women randomised because of difficulties in recruitment. Of those randomised to VAS and conservative management, 3/16 (19%) and 2/15 (13%), respectively, did not receive their allocated intervention. Based on intention-to-treat analysis, survival at 28 days was higher if allocated VAS (50%) than conservative management (27%) [relative risk (RR) 1.88, 95% confidence interval (CI) 0.71 to 4.96, p = 0.27]. At 12 months survival was 44% in the VAS arm and 20% in the conservative arm (RR 2.19, 95% CI 0.69 to 6.94, p = 0.25). Neither difference was statistically significant. Of survivors at 1 year, two in the VAS arm had no evidence of renal impairment and four in the VAS arm and two in the conservative arm required medical management. One baby in the conservative arm had end-stage renal failure at 1 year. VAS was more expensive because of additional surgery and intensive care. VAS cost £15,500 per survivor at 1 year and £43,900 per disability-free year. Elicited expert opinions showed uncertainty in the effect of VAS at 28 days. In a Bayesian analysis combining elicited opinion with the results, uncertainty of the benefit of VAS remained (RR 1.31, 95% credible interval 0.84 to 2.18). The acceptability study identified visualisation of the fetus during ultrasound scanning, perceiving a personal benefit, and altruism as positive influences on recruitment. Fear of the VAS procedure and the perceived severity of LUTO influenced non-participation. The need for more detailed information about the condition and its implications during pregnancy and following delivery was a further important finding of this research. Recruitment was hampered by logistical and regulatory difficulties, a lower incidence of LUTO and lower antenatal diagnosis rate [estimated to be 3.34 (95% CI 2.95 to 3.72) per 10,000 total births and 47%, respectively, in an associated epidemiological study] and high termination of pregnancy rates. In the registry women also demonstrated a clear preference for conservative management. CONCLUSIONS: Survival to 28 days and 1 year appears to be higher with VAS than with conservative management, but it is not possible to prove benefit beyond reasonable doubt. Notably, prognosis in both arms for survival and renal function is poor. VAS was substantially more costly and unlikely to be regarded as cost-effective based on the 1-year data. Parents should be counselled about the risks of pregnancy loss with or without VAS insertion. The National Institute for Health and Care Excellence interventional procedures guidance (IPG 202) should be updated to reflect this new evidence. Babies in the PLUTO trial should be followed up long term for the different outcomes. TRIAL REGISTRATION: ISRCTN53328556. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 17, No. 59. See the NIHR Journals Library website for further project information.

AIDS related Kaposi's sarcoma presenting with palatal and eyelid nodule.

UNLABELLED: Kaposi sarcoma is a low-grade vascular neoplasm associated with Human Herpesvirus-8 (HHV8) infection. Although India has a large HIV infected population, Kaposi's sarcoma is rare and only 12 cases of AIDS related Kaposi's sarcoma from India have been reported in the published literature to our knowledge. The 50% of total cases in India has been reported from Mumbai. The incidence of AIDS related Kaposi's sarcoma is increasing as more than 50% of the cases are reported in 2008 to 2010. SUMMARY: We report a case of 26-year-old, HIV seropositive, Indian male with multiple, non-blanching, purplish blue nodular swellings in the palate and right upper eye lid. Similar lesions were also present on the face and the extremities. On the basis of clinical and histopathological examination, a diagnosis of AIDS related Kaposi's sarcoma was made.

Comparative study of clinicofunctional staging of oral submucous fibrosis with qualitative analysis of collagen fibers under polarizing microscopy.

OBJECTIVE: The aim of the study was to assess the severity of the disease in oral submucous fibrosis (OSF), correlate the clinical, functional staging with histopathological staging, and analyze collagen distribution in different stages of OSF using the picrosirius red stain under polarizing microscopy. MATERIALS AND METHODS: The study included randomly incorporated 50 subjects, of whom 40 were patients with OSF, and 10 were in the control group. Clinical, functional staging in OSF cases was done depending upon definite criteria. A histopathological study was conducted using the hematoxylin and eosin stain and picrosirius red stain. Collagen fibers were analyzed for thickness and polarizing colors. Furthermore, clinical, functional, and histopathological stages were compared. STATISTICAL ANALYSIS: Descriptive data which included mean, SD, and percentages were calculated for each group. Categorical data were analyzed by the chi-square test. Multiple group comparisons were made by one-way ANOVA followed by Student's t-test for pairwise comparisons. For all tests, a P-value of 0.05 or less was considered for statistical significance. RESULTS: As the severity of the disease increased, clinically, there was definite progression in subjective and objective symptoms. Polarized microscopic, examination revealed, there was a gradual decrease in the green-greenish yellow color of the fibers and a shift to orange red-red color with increase in severity of the disease. Thereby, it appeared that the tight packing of collagen fibers in OSF progressively increased as the disease progressed from early to advanced stages. We observed that the comparison of functional staging with histopathological staging was a more reliable indicator of the severity of the disease. CONCLUSION: In the present study, we observed that mouth opening was restricted with advancing stages of OSF. The investigation also points to the importance of assessing the cases of OSF, especially with regard to functional and histological staging in planning the treatment.

Systematic reviews of qualitative evidence: what are the experiences of women with endometriosis?

Just as systematic reviews of quantitative research have developed over the last two decades, the use of a systematic review is also superseding narrative non-systematic reviews in qualitative research in an attempt to bring rigour to reviewing research evidence. Qualitative research is concerned with the subjective world and the way in which people interpret and make sense of the reality of their lives. This paper describes procedures for conducting a systematic review on qualitative research, and the methods for assessing the quality of qualitative research papers, using published qualitative research on endometriosis as an example to demonstrate these. The conclusion from the systematic review carried out is that the values and methods utilised for a systematic review can usefully be applied to qualitative research. The review of endometriosis research revealed that despite the impact of endometriosis on the lives of women sufferers, little qualitative research has been conducted, and much of that which exists lacks rigour in a number of key areas.

A model of non-uniform lung parenchyma distortion.

A finite element model of mammalian lung parenchyma is used to study the effect of large non-uniform distortions on lung elastic behaviour. The non-uniform distortion is a uni-axial stretch from an initial state of uniform pressure expansion. For small distortions, the parenchymal properties are linearly isotropic and described by two elastic moduli. However, for large distortions, the parenchyma has anisotropic non-linear elastic properties described by five independent elastic moduli dependent on the degree of distortion; they are computed for a range of distortions and initial pressures. Ez, the Young's modulus in the direction of stretch, increases significantly with distortion (epsilon(z)) while Ex, the Young's modulus in the plane perpendicular to the stretch, is approximately constant. The greater the initial pressure, the bigger the difference between the two moduli at larger distortion strains. The shear modulus G(xz) is approximately independent of degree of distortion except at the highest initial pressure. The Poisson's ratio, nu(xz) is approximately constant with distortion strain for lower initial pressures, but increases significantly with epsilon(z) at higher pressures. Model predictions of the relation between G(xz) and initial uniform inflation pressure show a good correlation with reported experimental data for small distortion strains in a range of species. The model also exhibits similar behaviour to the experimentally measured uni-axial large deformations of a tri-axially pre-loaded block of parenchyma (Hoppin et al., 1975, Journal of Applied Physiology 39, 742-751).

Voluntary hyperventilation into a simple mixing chamber relieves high altitude hypoxia.

Involuntary hyperventilation is a critical factor in acclimatization to a high altitude. Unacclimatized subjects do poorly when acutely exposed to high altitude. This may not be due to hypocapnia itself, but rather an associated symptom which inhibits hypoxic respiratory stimulation. In an unacclimatized individual, voluntary hyperventilation may greatly relieve hypoxia and may be an alternative to involuntary hyperventilation. However, subjects voluntarily hyperventilating may overventilate and become disabled from severe hypocapnia. A simple mixing chamber is described which makes voluntary hyperventilation easier, safer, and possibly more effective. A subject breathing into a mixing chamber was able to maintain an SaO2 of 90% at 20,000 ft.

Viscoelastic behavior of a lung alveolar duct model.

A study is conducted into the oscillatory behavior of a finite element model of an alveolar duct. Its load-bearing components consist of a network of elastin and collagen fibers and surface tension acting over the air-liquid interfaces. The tissue is simulated using a visco-elastic model involving nonlinear quasi-static stress-strain behavior combined with a reduced relaxation function. The surface tension force is simulated with a time- and area-dependent model of surfactant behavior. The model was used to simulate lung parenchyma under three surface tension cases: air-filled, liquid-filled, and lavaged with 3-dimenthyl siloxane, which has a constant surface tension of 16 dyn/cm. The dynamic elastance (Edyn) and tissue resistance (Rti) were computed for sinusoidal tidal volume oscillations over a range of frequencies from 0.16-2.0 Hz. A comparison of the variation of Edyn and Rti with frequency between the model and published experimental data showed good qualitative agreement. Little difference was found in the model between Rti for the air-filled and lavaged models; in contrast, published data revealed a significantly higher value of Rti in the lavaged lung. The absence of a significant increase in Rti for the lavaged model can be attributed to only minor changes in the individual fiber bundle resistances with changes in their configuration. The surface tension was found to make an important contribution to both Edyn and Rti in the air-filled duct model. It was also found to amplify any existing tissue dissipative properties, despite exhibiting none itself over the small tidal volume cycles examined.

Modelling impact-initiated wave transmission through lung parenchyma in relation to the aetiology of exercise-induced pulmonary haemorrhage.

Recently we proposed that exercise-induced pulmonary haemorrhage (EIPH) results from locomotory-impact-induced trauma by impact of the scapula on the chest wall during footfall and the consequent transmission of waves through the lung. A computational model has been developed to demonstrate that wave amplification and focusing occur in the dorsocaudal tip of the lung for waves originating on the anterior subscapular surface. The propagation of an acoustic wave was investigated in a simplified 2-dimensional representation of a vertical anterio-dorsal section of horse lung. It was demonstrated that a complicated pattern of waves is transmitted from the scapula to the dorsal region. Wave motion was characterised using the instantaneous rate of change of pressure with time (dp/dt) which is associated with lung injury. Due to wave reflection and focusing, dp/dt is transiently very high on the spinal and diaphragmatic lung walls, particularly in the vicinity of the dorsal tip. The model therefore predicts that lung injury may occur in the region in which EIPH is reported to originate.

Exercise-induced pulmonary haemorrhage (EIPH) in horses results from locomotory impact induced trauma--a novel, unifying concept.

Exercise-induced pulmonary haemorrhage (EIPH) in horses, although of major welfare and economic importance worldwide, is of uncertain cause. It is accepted that the dorsocaudal region of the lung is particularly prone to the condition, but present theories of causation cannot satisfactorily explain the mechanism or pattern of occurrence. We propose that EIPH results from locomotory impact induced trauma; the mechanism being similar to that producing lung tissue damage following thoracic impact injury. In impact injury, the localised impulsive load on the chest wall is transmitted by pressure waves through the lung at a slower speed than in the chest wall. The waves are subsequently reflected from the distal chest wall and other structures, producing a complex pattern of wave motion; waves travelling from regions of large cross-section to narrower ones are amplified in magnitude, consequently these regions can experience very high local stresses. Compression/dilation and shear waves are produced within the parenchyma and the latter particularly have been implicated as the cause of parenchymal damage and rupture with oedema and haemorrhage. This form of soft tissue damage has been shown to occur at remarkably low loads with an impact velocity greater than about 11 m/s and pressure exceeding approximately 14 kPa. In the horse, the lung is subjected to comparable levels of locomotory derived impulsive force during moderate to high speed exercise and this is the basis of the mechanism causing EIPH. During locomotion, the force following ground-strike of the front legs is transmitted, with some attenuation, through the forelimbs to the scapulae. The anatomical arrangement of the scapula, coupled with the direction of the force at the shoulder (scapulo humeral joint) produces an impulsive force on the rib cage, approximately just below mid height of the frontal aspect of the chest approximately over the fourth rib. As a result, pressure waves are transmitted through the lung parenchyma towards the dorsal and caudal regions; these waves are subsequently reflected at the distal chest wall, spine and diaphragm causing a complex pattern of wave interaction. The observed locations of EIPH are at the sites where wave intensity is expected to be greatest due to changes in cross section and reflection. Based on available information, it is estimated that impulsive forces of more than 100 kPa, lasting approximately 10 ms, would be applied to the chest wall by each scapula in a 500 kg horse when galloping; this level of force would be sufficient to cause oedema and haemorrhage as observed in impact induced injury.

Relationships between alveolar size and fibre distribution in a mammalian lung alveolar duct model.

A finite element model, comprising an assemblage of tetrakaidecahedra or truncated octahedra, is used to represent an alveolar duct unit. The dimensions of the elastin and collagen fibre bundles, and the surface tension properties of the air-liquid interfaces, are based on available published data. Changes to the computed static pressure-volume behavior with variation in alveolar dimensions and fibre volume densities are characterized using distensibility indices (K). The air-filled lung distensibility (Ka) decreased with a reduction in the alveolar airspace length dimensions and increased with a reduction of total fibre volume density. The saline-filled lung distensibility (Ks) remained constant with alveolar dimensions and increased with decreasing total fibre volume density. The degree of geometric anisotropy between the duct lumen and alveoli was computed over pressure-volume cycles. To preserve broadly isotropic behavior, parenchyma with smaller alveolar airspace length dimensions required higher concentrations of fibres located in the duct and less in the septa in comparison with parenchyma of larger airspace dimensions.

The second missing link: Bible nursing in 19th century London.

The London Bible and Domestic Female Mission was founded in 1857 by Ellen Ranyard. A nursing mission was added in 1868. The structure and work of the mission can be used to exemplify three strategies utilized in Victorian philanthropy. First, the use of working class women in the maintenance of social order, secondly the utilization of the middle class household to exemplify relations between the social classes, and thirdly the creation of districts in an attempt to recreate a 'golden age' of rural communities. Ranyard created a women's mission to women. As such it did not display the gender division of labour apparent in much health and caring work, but a hierarchical division of labour based on social class is evident.

A mathematical model for the morphology of the pulmonary acinus.

A computational method is proposed for the construction of a three-dimensional space-filling model of an acinar ventilatory unit. Its geometry consists of truncated octahedra arranged in a cuboidal block. The ducts and alveoli are formed by opening specific common faces between polyhedra. The branching structure is automatically computed using algorithms solely to maximise the number of alveoli and minimise the average path lengths; it is not formed with reference to published experimental data. Properties of the model such as the total alveolar and ductal volumes, the distribution of individual path lengths to the alveolar sacs, and the average number of ducts per generation are calculated. The predicted morphology of the model compares well with published data for rat lungs.

Letters from a Nightingale nurse.

Mary Cadbury was one of six daughters in a wealthy Birmingham family, all of whom took up professional or unpaid philanthropic work. In 1873 Mary began nurse training at the Nightingale School, St Thomas's Hospital, and regularly sent letters to family and friends, which provide a graphic account of the experience of a nurse in the latter half of the nineteenth century.

The mechanical behavior of a mammalian lung alveolar duct model.

A model for the mechanical properties of an alveolar duct is analyzed using the finite element method. Its geometry comprises an assemblage of truncated octahedral alveoli surrounding a longitudinal air duct. The amounts and distributions of elastin and collagen fiber bundles, modeled by separate stress-strain laws, are based upon published data for dogs. The surface tension of the air-liquid interface is modeled using an area-dependent relationship. Pressure-volume curves are computed that compare well with experimental data for both saline-filled and air-filled lungs. Pressure-volume curves of the separate elastin and collagen fiber contributions are similar in form to the behavior of saline-filled lungs treated with either elastase or collagenase. A comparison with our earlier model, based upon a single alveolus, shows the duct to have a behavior closer to reported experimental data.

The experience of in vitro fertilization and gamete intra-fallopian transfer.

Research was conducted using qualitative techniques, in order to bridge the gap between radical feminist perspectives on in vitro fertilization programmes, which are usually theoretical in nature, and quantitative research which considers the experiences of women and couples involved in these programmes. Semi-focused interviews were carried out with 10 women who were currently undergoing, or had recently undergone, in vitro fertilization or gamete intra-fallopian transfer, in order to explore the experiences and the emotions associated with participation in these programmes. By utilizing a woman-centred approach, a richness of experiential data was obtained, which would not have been achievable by quantitative means, and yet the women involved were able to retain some control over the research process.