The JAK inhibitor ruxolitinib reduces inflammation in an ILC3-independent model of innate immune colitis.

Innate immunity contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms of IBD mediated by innate immunity are incompletely understood and there are limited models of spontaneous innate immune colitis to address this question. Here we describe a new robust model of colitis occurring in the absence of adaptive immunity. RAG1-deficient mice expressing TNFAIP3 in intestinal epithelial cells (TRAG mice) spontaneously developed 100% penetrant, early-onset colitis that was limited to the colon and dependent on intestinal microbes but was not transmissible to co-housed littermates. TRAG colitis was associated with increased mucosal numbers of innate lymphoid cells (ILCs) and depletion of ILC prevented colitis in TRAG mice. ILC depletion also therapeutically reversed established colitis in TRAG mice. The colitis in TRAG mice was not prevented by interbreeding to mice lacking group 3 ILC nor by depletion of TNF. Treatment with the JAK inhibitor ruxolitinib ameliorated colitis in TRAG mice. This new model of colitis, with its predictable onset and colon-specific inflammation, will have direct utility in developing a more complete understanding of innate immune mechanisms that can contribute to colitis and in pre-clinical studies for effects of therapeutic agents on innate immune-mediated IBD.

Magnetic resonance based texture parameters as potential imaging biomarkers for predicting long-term survival in locally advanced rectal cancer treated by chemoradiotherapy.

AIM: The study aimed to investigate whether textural features of rectal cancer on MRI can predict long-term survival in patients treated with long-course chemoradiotherapy. METHOD: Textural analysis (TA) using a filtration-histogram technique of T2-weighted pre- and 6-week post-chemoradiotherapy MRI was undertaken using TexRAD, a proprietary software algorithm. Regions of interest enclosing the largest cross-sectional area of the tumour were manually delineated on the axial images and the filtration step extracted features at different anatomical scales (fine, medium and coarse) followed by quantification of statistical features [mean intensity, standard deviation, entropy, skewness, kurtosis and mean of positive pixels (MPP)] using histogram analysis. Cox multiple regression analysis determined which univariate features including textural, radiological and histological independently predicted overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS). RESULTS: MPP [fine texture, hazard ratio (HR) 6.9, 95% CI: 2.43-19.55, P < 0.001], mean (medium texture, HR 5.6, 95% CI: 1.4-21.7, P = 0.007) and extramural venous invasion (EMVI) on MRI (HR 2.96, 95% CI: 1.04-8.37, P = 0.041) independently predicted OS while mean (medium texture, HR 4.53, 95% CI: 1.58-12.94, P = 0.003), MPP (fine texture, HR 3.36, 95% CI: 1.36-8.31, P = 0.008) and threatened circumferential resection margin (CRM) on MRI (HR 3.1, 95% CI: 1.01-9.46, P = 0.046) predicted DFS. For OS, EMVI on MRI (HR 4.23, 95% CI: 1.41-12.69, P = 0.01) and for DFS kurtosis (medium texture, HR 3.97, 95% CI: 1.44-10.94, P = 0.007) and CRM involvement on MRI (HR 3.36, 95% CI: 1.21-9.32, P = 0.02) were the independent post-treatment factors. Only TA independently predicted RFS on pre- or post-treatment analyses. CONCLUSION: MR based TA of rectal cancers can predict outcome before undergoing surgery and could potentially select patients for individualized therapy.

Towards a framework for analysis of eye-tracking studies in the three dimensional environment: a study of visual search by experienced readers of endoluminal CT colonography.

OBJECTIVE: Eye tracking in three dimensions is novel, but established descriptors derived from two-dimensional (2D) studies are not transferable. We aimed to develop metrics suitable for statistical comparison of eye-tracking data obtained from readers of three-dimensional (3D) "virtual" medical imaging, using CT colonography (CTC) as a typical example. METHODS: Ten experienced radiologists were eye tracked while observing eight 3D endoluminal CTC videos. Subsequently, we developed metrics that described their visual search patterns based on concepts derived from 2D gaze studies. Statistical methods were developed to allow analysis of the metrics. RESULTS: Eye tracking was possible for all readers. Visual dwell on the moving region of interest (ROI) was defined as pursuit of the moving object across multiple frames. Using this concept of pursuit, five categories of metrics were defined that allowed characterization of reader gaze behaviour. These were time to first pursuit, identification and assessment time, pursuit duration, ROI size and pursuit frequency. Additional subcategories allowed us to further characterize visual search between readers in the test population. CONCLUSION: We propose metrics for the characterization of visual search of 3D moving medical images. These metrics can be used to compare readers' visual search patterns and provide a reproducible framework for the analysis of gaze tracking in the 3D environment. ADVANCES IN KNOWLEDGE: This article describes a novel set of metrics that can be used to describe gaze behaviour when eye tracking readers during interpretation of 3D medical images. These metrics build on those established for 2D eye tracking and are applicable to increasingly common 3D medical image displays.

Evaluating patients' preferences for type of bowel preparation prior to screening CT colonography: convenience and comfort versus sensitivity and specificity.

AIMS: To explore the relative value patients place on comfort and convenience versus test sensitivity and specificity in the context of computed tomographic colonography (CTC) screening. MATERIALS AND METHODS: Twenty semi-structured interviews were carried out with patients attending hospital for radiological tests unrelated to CTC. Preferences for CTC with different types of bowel preparation for CTC screening were examined and interviews were analysed thematically. The discussion guide included separate sections on CTC, bowel preparation methods (non-, reduced- and full-laxative), and sensitivity and specificity. Patients were given information on each topic in turn and asked about their views and preferences during each section. RESULTS: Following information about the test, patients' attitudes towards CTC were positive. Following information on bowel preparation, full-laxative purgation was anticipated to cause more adverse physical and lifestyle effects than using reduced- or non-laxative preparation. However, stated preferences were approximately equally divided, largely due to patients anticipating that non-laxative preparations would reduce test accuracy (because the bowel was not thoroughly cleansed). Following information on sensitivity and specificity (which supported patients' expectations), the predominant stated preference was for full-laxative preparation. CONCLUSIONS: Patients are likely to value test sensitivity and specificity over a more comfortable and convenient preparation. Future research should test this hypothesis on a larger sample.

Diffusion weighted MRI: overview and implications for rectal cancer management.

Diffusion weighted imaging (DWI) is an MRI technique that quantifies the movement of water molecules at a cellular level. As the diffusion properties of water vary in areas of necrosis, high cellularity, inflammation and fibrosis, this technique is inherently sensitive to different pathologies. Having become a well-established adjunct to standard sequences during neurological MRI, technological advances have enabled extrapolation to abdominopelvic imaging, including staging of rectal cancer. Scan acquisitions can be performed rapidly using widely available equipment and consequently there has been rapid dissemination into routine practice. However, while DWI shows promise for detecting, staging and monitoring rectal cancer response to therapy, the evidence base remains scant with no current consensus for technical protocols, interpretation or integration into rectal cancer management. Moreover, those studies available to date have a small sample size and few observers, and their results may not be generalizable to daily practice. This article outlines the physical principles of DWI, reviews the literature and suggests avenues for future research into this important technical development.

An interview study analysing patients' experiences and perceptions of non-laxative or full-laxative preparation with faecal tagging prior to CT colonography.

AIM: To compare patients' experiences of either non- or full-laxative bowel preparation with additional faecal tagging and subsequent computed tomographic (CT) colonography using in-depth interviews to elicit detailed responses. MATERIALS AND METHODS: Patients who received CT colonography after non- (n = 9) or full-laxative (n = 9) preparation participated in a semi-structured telephone interview at least 2 days after the investigation. Full-laxative preparation consisted of magnesium citrate and sodium picosulphate administered at home (or polyethylene glycol, if contraindicated), followed by hospital-based faecal tagging with iohexol. Non-laxative preparation was home-based barium sulphate for faecal tagging. Interviews were transcribed and thematically analysed to identify recurrent themes on patients' perceptions and experiences. RESULTS: Experiences of full-laxative preparation were usually negative and characterized by pre-test diarrhoea that caused significant interference with daily routine. Post-test flatus was common. Non-laxative preparation was well-tolerated; patients reported no or minimal changes to bowel habit and rapid return to daily routine. Patients reported worry and uncertainty about the purpose of faecal tagging. For iohexol, this also added burden from waiting before testing. CONCLUSION: Patients' responses supported previous findings that non-laxative preparation is more acceptable than full-laxative preparation but both can be improved. Faecal tagging used in combination with laxative preparation is poorly understood, adding burden and worry. Home-based non-laxative preparation is also poorly understood and patients require better information on the purpose and mechanism in order to give fully informed consent. This may also optimize adherence to instructions. Allowing home-based self-administration of all types of preparation would prevent waiting before testing.

WE-E-213CD-03: Inverse-Consistent Symmetric Registration of Inner Colon Surfaces Derived from Prone and Supine CT Colonography.

PURPOSE: Robust registration of prone and supine colonie surfaces acquired during CT colonography may lead to faster and more accurate detection of colorectal cancer and polyps. Any directional bias when registering one surface to the other could precipitate incorrect anatomical correspondence and engender reader error. Despite this, non-rigid registration methods are often implemented asymmetrically, which could negatively influence the registration. We aimed to reduce directional bias and so increase robustness by adapting a cylindrical registration algorithm to be both symmetric and inverse-consistent. METHODS: The registration task can be simplified by mapping both prone and supine colonie surfaces onto regular cylinders. Spatial correspondence can then be established in cylindrical space using the original surfaces' local shape indices. We implemented a symmetric formulation of the popular non-rigid B-spline image registration method in cylindrical space. A symmetric similarity measure computes the sum of squared differences between both cylindrical representations of prone-to-supine and supine-to-prone directions simultaneously. Inverse consistency of the transformation is enforced by adding an appropriately weighted penalty term to the optimisation function. RESULTS: We selected 8 CT colonography patient cases with marked variation in luminal distension and surface morphology. We randomly allocated 4 of these for tuning an optimal set of registration parameters and 4 for validation. The mean inverse-consistency error was reduced by 32% from 4.8mm to 3.2mm by the new symmetric formulation. The mean registration error improved from 8.2mm to 7.3mm for 330 manually chosen reference points on the 4 validation sets. CONCLUSIONS: A symmetric formulation of prone and supine surface registration improves the quality of registration. Information from both prone-to-supine and supine-to-prone directions helps enforce convergence towards a more accurate solution due to reduced directional bias. A more robust and accurate registration will facilitate interpretation of CT colonography and has the potential to improve existing computer-aided detection methods. The authors gratefully acknowledge financial support for this work from the NIHR program: â€Å“Imaging diagnosis of colorectal cancer: Interventions for efficient and acceptable diagnosis in symptomatic and screening populationsâ€.

CT colonography: who attends training? A survey of participants at educational workshops.

AIM: To obtain information regarding the demographics of attendees of computed tomography colonography (CTC) training workshops organized by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), in particular their prior expertise and current practice. MATERIALS AND METHODS: Attendees at five CTC training workshops conducted in Edinburgh (UK), Malmo (Sweden), Amsterdam (Netherlands), Pisa and Stresa (Italy) between February 2007 and April 2010 completed an online questionnaire. Responses were collated and descriptive statistics produced. RESULTS: Three hundred and forty-eight delegates responded; a response rate of 73%. There was wide geographical variability encompassing 20 European member-states and seven countries outside Europe. The overwhelming majority were radiologists (336; 97%). Of the respondents, 299 (86%) were already interpreting CTC in clinical practice but of these, 158 (54%) had no prior formal training in CTC whereas 21 (8%) had attended a previous workshop. Furthermore, of those reporting CTC, 227 (76%) had interpreted fewer than 50 cases. CONCLUSIONS: Despite political imperatives for other groups to interpret CTC, the vast majority of those attending training are radiologists. Worryingly, a significant proportion of these are apparently reporting CTC in clinical practice without adequate training.

Prophylactic total gastrectomy (PTG) for hereditary diffuse gastric cancer (HDGC): the Newfoundland experience with 23 patients.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) results from truncating mutations of the CDH1 (E-cadherin) gene. It is an autosomal dominant cancer susceptibility syndrome with a lifetime risk of diffuse gastric cancer (DGC) of 60-80%, with a mean age of onset of 37 years. There exists no adequate screening test for DGC. Early intramucosal diffuse/signet-ring cell carcinomas have been found in prophylactic total gastrectomy (PTG) specimens following normal preoperative endoscopy. Total gastrectomy has been advocated on a prophylactic basis. The aim of this study was to report our experience with PTG in 23 patients from the Canadian province of Newfoundland and Labrador. This is the largest series worldwide. METHODS: A retrospective study of consecutive patients undergoing PTG for HDGC was performed. All patients were confirmed to have a truncating mutation of the CDH1 gene. RESULTS: Twenty-three patients underwent PTG between February 2006 and November 2008. Major complications were found in 4/23 patients (17%), with no mortality. Two of 23 patients (9%) had positive mucosal biopsies on preoperative EGD. Twenty-two of 23 patients (96%) had evidence of diffuse/signet-ring carcinoma on final standardized pathological evaluation. Therefore, 21/23 (91%) were not picked up by preoperative EGD screening. CONCLUSIONS: PTG can be performed in patients with HDGC with a low rate of serious complications. Methods of reconstruction incorporating a pouch reservoir and preservation of the postgastric branches of the vagus nerves need to be explored. More refined penetrance estimates, effective screening protocols, and long-term psychological and functional outcomes following PTG require organized multicenter collaborative efforts.

T cell-independent interleukin 15Ralpha signals are required for bystander proliferation.

Cytokine driven or "bystander" proliferation of T cells occurs in vivo independently of major histocompatibility complex-T cell receptor interactions. This process may be important for supporting T cell homeostasis and facilitating T cell responses to microbial antigens, and may involve the cytokine interleukin (IL)-15. In this study, we find that IL-15Ralpha-deficient (IL-15Ralpha(-/-)) mice fail to undergo poly I:C or IL-15 driven bystander proliferation of CD8(+) T cells. Surprisingly, IL-15Ralpha(-/-) CD8(+) T cells proliferate in response to poly I:C when adoptively transferred into normal mice, and normal CD8(+) T cells fail to proliferate in IL-15Ralpha(-/-) mice. Normal mice reconstituted with IL-15Ralpha(-/-) bone marrow cells also fail to exhibit bystander responses. Thus, CD8(+) T cell independent IL-15Ralpha signals from radiation sensitive hematopoietic cells are likely required for bystander responses. Moreover, normal CD8(+) T cells proliferate in IL-15Ralpha(-/-) mice after treatment with IL-15. Therefore, IL-15Ralpha signals may mediate a positive feedback loop involving the further physiological production of IL-15. These findings provide new insights into how IL-15Ralpha supports memory phenotype CD8(+) T cell proliferation, and suggest novel mechanisms by which memory CD8(+) T cells are maintained in vivo.

Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells.

BACKGROUND & AIMS: Because short-chain fatty acids (SCFAs) and heat shock proteins (hsps) confer protection to intestinal epithelia cells (IECs), we studied whether SCFAs modulate IEC hsp expression. METHODS: Hsp 25, hsp72, and hsc73 protein expression in rat intestinal tissues and IEC-18 cells were determined by Western blot and immunohistochemistry. Cell survival under conditions of oxidant stress (monochloramine) was determined using (51)Cr release in hsp25 cDNA anti-sense and sense-transfected cells expressing minimal and increased hsp25, respectively. RESULTS: Butyrate induces a time- and concentration-dependent increase in hsp25, but not hsp72 or hsc73, protein expression in rat IEC-18 cells but not 3T3 fibroblasts. Other SCFAs, including the poorly metabolized isobutyate, also induced selective expression of hsp25. Butyrate treatment significantly improved the ability of IEC-18 cells to withstand oxidant (monochloramine) injury. This effect could be blocked in cells in which hsp25 induction by butyrate was blocked by stable hsp25 antisense transfection. Additionally, hsp25-transfected overexpressing IEC-18 cells showed increased resistance to monochloramine. In vivo, increasing dietary fiber increased colonic, but not proximal, ileal hsp25 while having no effect on hsp72 or hsc73 expression. CONCLUSIONS: SCFAs, the predominant anions of colonic fluid derived from bacterial flora metabolism of luminal carbohydrates, protect IECs against oxidant injury, an effect mediated in part by cell-specific hsp25 induction.

Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice.

A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor kappaB (NF-kappaB) activity and tumor necrosis factor (TNF)-mediated programmed cell death (PCD). TNF dramatically increases A20 messenger RNA expression in all tissues. Mice deficient for A20 develop severe inflammation and cachexia, are hypersensitive to both lipopolysaccharide and TNF, and die prematurely. A20-deficient cells fail to terminate TNF-induced NF-kappaB responses. These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB responses in vivo.

Phantom limb, residual limb, and back pain after lower extremity amputations.

This study describes the sensations and pain reported by persons with unilateral lower extremity amputations. Participants (n = 92) were recruited from two hospitals to complete the Prosthesis Evaluation Questionnaire which included questions about amputation related sensations and pain. Using a visual analog scale, participants reported the frequency, intensity, and bothersomeness of phantom limb, residual limb, and back pain and nonpainful phantom limb sensations. A survey of medication use for each category of sensations also was included. Statistical analyses revealed that nonpainful phantom limb sensations were common and more frequent than phantom limb pain. Residual limb pain and back pain were also common after amputation. Back pain surprisingly was rated as more bothersome than phantom limb pain or residual limb pain. Back pain was significantly more common in persons with above knee amputations. These results support the importance of looking at pain as a multidimensional rather than a unidimensional construct. They also suggest that back pain after lower extremity amputation may be an overlooked but very important pain problem warranting additional clinical attention and study.

Caspase-3 in the rat ovary: localization and possible role in follicular atresia and luteal regression.

Apoptosis, the cellular mechanism of ovarian follicular atresia and luteal regression, is triggered by the activation of a proteolytic cascade of cysteine aspartate-specific proteases (caspases). The principle downstream effector of cell death is caspase-3, but little is known about the role or regulation of this enzyme in ovarian apoptosis. Two substrates of caspase-3, actin and poly(ADP-ribose) polymerase (PARP), are inhibitors of DNase I, which is the endonuclease responsible for ovarian apoptotic DNA degradation. We therefore investigated the proteolytic cleavage of actin and PARP as well as the localization of caspase-3 during follicular atresia (induced by gonadotropin withdrawal) and luteal regression (induced by prostaglandin F2alpha) in the rat ovary. Apoptotic DNA degradation was evident during both follicular atresia and luteal regression, but cleavage of PARP and actin was observed only during luteal regression. Caspase-3 was localized in luteal cells of healthy corpora lutea (CL) and in theca, but not in granulosa cells of healthy follicles. However, caspase-3 immunostaining was evident in granulosa cells of atretic follicles in a pattern similar to that of the localization of granulosa cell death. There was no difference between healthy and apoptotic CL in the distribution or intensity of caspase-3 staining. These results demonstrate that the cleavage of actin and PARP are not necessary for activation of apoptotic DNA degradation during ovarian apoptosis. In addition, the presence of caspase-3 in granulosa cells of atretic, but not healthy, follicles suggests that the expression of this enzyme is regulated by gonadotropin and may be up-regulated as part of the apoptotic process in granulosa cells.

Granulosa cell apoptosis induced at the penultimate stage of follicular development is associated with increased levels of Fas and Fas ligand in the rat ovary.

Apoptosis of granulosa cells is the cellular mechanism of ovarian follicular atresia, and cytokines have been implicated as potential atretogenic factors. We therefore investigated the possible role of the cytokine Fas ligand (FasL) and its receptor Fas in apoptosis during ovarian follicular atresia induced by gonadotropin withdrawal. Immature rats pretreated with eCG were injected 24 h later with an antiserum generated against eCG (antibody group) or preimmune rabbit serum (control), and ovaries were removed 1 and 24 h after treatment. The eCG antiserum caused a dose-dependent inhibition of the significant increase in ovarian weight observed between 24 and 48 h after eCG treatment. In situ detection of fragmented DNA in histological sections identified cell death in atretic but not healthy small and medium-sized antral follicles of the antibody group. Cell death was distributed in a scattered pattern throughout the granulosa cell layer of small atretic follicles but was localized primarily in granulosa cells lining the antral cavity of atretic medium antral follicles. Immunohistochemistry of adjacent histological sections revealed intense positive immunostaining for Fas and FasL in granulosa cells of atretic small and medium antral follicles in a pattern coincidental to the localization of cell death. Intense FasL staining was evident in the theca cells of healthy small antral follicles. An increase in low molecular weight DNA (DNA "ladders") indicative of apoptosis was evident in granulosa cells of the antibody group. Western analysis demonstrated increased levels of both Fas and FasL in the granulosa cells of the antibody group. These results demonstrate that both Fas and FasL are present in ovarian granulosa cells and that FasL may be the signal that induces granulosa cell apoptosis during atresia at the penultimate stage of ovarian follicular development.

Cotton-wool spots and the early diagnosis of giant cell arteritis.

BACKGROUND: Giant cell arteritis is a common cause of severe visual loss in older individuals. Patients often present to the ophthalmologist having already lost vision in one eye. Detection of early ophthalmoscopic signs that precede irreversible visual loss in giant cell arteritis would allow preventative treatment in an otherwise frequently blinding disease. METHODS: Case presentations. RESULTS: Seven patients with mild visual symptoms and results of an ophthalmologic examination significant for cotton-wool spots were found to have giant cell arteritis. On specific questioning, six of seven patients described constitutional symptoms consistent with giant cell arteritis. Six patients had an abnormally elevated Westergren erythrocyte sedimentation rate. Temporal artery biopsy confirmed giant cell arteritis in six patients. The seventh patient received a diagnosis of polymyalgia rheumatica. Prompt treatment with corticosteroids led to preservation of vision and uneventful resolution of the cotton-wool spots in all seven patients. CONCLUSION: Cotton-wool spots are an early ophthalmoscopic finding in giant cell arteritis and can precede severe visual loss. Recognition of the significance of cotton-wool spots, use of laboratory studies, and prompt treatment may preserve vision in an otherwise frequently blinding disease.

Stimulation of progesterone secretion in dispersed cells of rat corpora lutea by antioxidants.

Antioxidants were used to investigate the role of free radicals in control of luteal steroidogenesis. Corpora lutea from pseudopregnant rats were enzymatically dispersed, the cells were incubated with antioxidants, and progesterone production was measured. Addition of the antioxidants nordihydroguaiaretic acid (NDGA), butylated hydroxytoluene (BHT), and the gonadotropin luteinizing hormone (LH) resulted in a dose-dependent increase in progesterone secretion. However, the response pattern to these treatments differed with the age of the corpora lutea, and unlike LH neither NDGA nor BHT treatment resulted in an increase in the intracellular second messenger cAMP. Nevertheless, LH and antioxidant-induced progesterone stimulation could be blocked by the addition of either aminoglutethimide or ketoconazole, cytochrome P450 side-chain cleavage (cytochrome P450 SCC) enzyme inhibitors, which prevent the conversion of cholesterol to pregnenolone and thus block steroid hormone synthesis. Also, unlike exposure to LH, exposure to antioxidants resulted in an additional increase in progesterone production in luteal tissue saturated with 25 hydroxycholesterol, a soluble cholesterol analog which serves as a substrate for cytochrome P450 SCC. This study suggests that the site of antioxidant action in affecting progesterone secretion may be at the cytochrome P450 SCC enzyme. Based on these results and on studies in other steroid hormone-producing cells, it appears that free radicals may be involved in regulating synthesis by modulating activity of cytochrome P450 SCC enzyme in rat luteal tissue.

Relaxing retinotomy with silicone oil or long-acting gas in eyes with severe proliferative vitreoretinopathy. Silicone Study Report 5. The Silicone Study Group.

In the Silicone Study, 117 of 404 eyes (29%) with severe proliferative vitreoretinopathy (> or = C-3, full-thickness retinal folds in three or more quadrants) enrolled in the study were treated with vitrectomy, underwent a relaxing retinotomy, and were randomly assigned to treatment with long-acting gas or silicone oil. Forty-six eyes (20%) had undergone no previous vitrectomy (group 1); 71 eyes (42%) had undergone previous vitrectomy (group 2) with intraocular gas tamponade (P < .001). Group 1 eyes not undergoing retinotomy had better anatomic (six months) and visual (six and 24 months) outcomes and less hypotony (six months) than eyes that did regardless of tamponade (P < .05). For eyes undergoing retinotomy, silicone oil decreased the likelihood of hypotony (six months, P < .05). These differences were not found in group 2 eyes. We conclude that eyes undergoing a vitreous operation for the first time for the treatment of proliferative vitreoretinopathy can in most instances be successfully treated by conventional techniques without the need for relaxing retinotomy. Retinotomy may be required more often in patients undergoing repeat vitreous surgery for proliferative vitreoretinopathy, in which case both silicone oil and long-acting perflouropropane gas appear to be equally effective.

A critical view of the yawn-sigh as a voice therapy technique.

The purpose of this study was to take a critical look at a voice therapy technique known as the yawn-sigh. The voiced sigh as an approach in voice therapy has had increased use in recent years, particularly with problems of vocal hyperfunction. In this study, the physiology of the yawn-sigh was studied with video nasoendoscopy in eight normal subjects; their taped voices were also studied acoustically for possible fundamental frequency and format changes in producing selected vowels under normal and sigh conditions. Although each subject was given a model by the examiner of a yawn-sigh, one of the eight subjects could not produce a true yawn-sigh. Endoscopic findings for seven of the eight subjects performing the yawn-sigh demonstrated retracted elevation of the tongue, a lower positioning of the larynx, and a widened pharynx. Acoustic analyses for the seven subjects producing the sigh found a marked lowering of the second and third formants. Implications for using the yawn-sigh in voice therapy are given, such as using a modified "silent" yawn-sigh, as an easy method for producing greater vocal tract relaxation.

Arachidonic acid and cell signalling in the ovary and placenta.

Arachidonic acid (AA) and its metabolites make up a diverse group of signalling molecules important to mediation of metabolic and endocrine function of ovarian and placental cell membranes. This paper reviews recent literature examining AA and eicosanoid involvement in the functional dynamics of follicular development, ovulation and corpus luteum function. The putative roles of AA metabolites in establishment and maintenance of pregnancy are reviewed with reference to decidualization, trophoblast invasion and implantation, maintenance of perfusion of the feto-placental unit and lipid transfer. Finally, recent evidence implicating AA metabolism in mediation of enzyme activity following hormone-receptor coupling within various cells types comprising the placental membranes is reviewed.