Sterile granulomatous panuveitis in dogs in the United Kingdom: A review of 33 cases.

PURPOSE: To describe the clinical and histopathological features of a sterile granulomatous panuveitis syndrome in 33 dogs that underwent enucleation and ocular histopathology. METHODS: Retrospective review of the medical records and ocular histopathology reports of 33 cases. Inclusion criteria were enucleation in conjunction with characteristic clinical and histopathological features. RESULTS: Thirteen breeds were represented (including crossbreeds). Panuveitis was acute and fulminating, and secondary glaucoma was common (n = 27). Interval from initial presentation to enucleation was 99 days (median 33 days, range 5-605 days). The mean age at enucleation was 6.7 years. Ocular signs were initially unilateral (n = 18) or bilateral (n = 15). The disease became bilateral in 18/25 cases that initially underwent unilateral enucleation, resulting in enucleation or euthanasia in 9/18 (mean interval of 168 days). Seven out of 59 eyes had a good outcome following topical anti-inflammatory and systemic immunosuppressive therapy. None of the dogs had travel history nor relevant systemic signs from presentation to follow-up (mean 619 days, range 16-3012 days). Histopathology revealed histiocytic and lymphoplasmacytic panuveitis with pigment dispersion, and no infectious agents were identified on light microscopy. CONCLUSION: To the authors' knowledge, this is the first report of a sterile granulomatous panuveitis syndrome in dogs in the UK. The clinical signs are severe, with rapid progression, and can result in bilateral enucleation or euthanasia in affected dogs. There does not appear to be an age or breed predisposition, however further research is necessary in this regard. Early and aggressive intervention, with both topical and systemic immunosuppressive therapy, is recommended to reduce the risk of blindness, enucleation, and euthanasia.

The impact on relationships following disclosure of transgenderism: a wife's tale.

WHAT IS KNOWN ON THE SUBJECT?: The experiences of transgender people are becoming increasingly more visible in popular culture, biographical literature and the media. The topic has received little attention within the psychiatric and mental health nursing literature. There is a paucity of literature exploring the impact on relationships following a disclosure of transgenderism. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: A narrative account of the consequences for the wife of one transwoman and their relationships with friends and family following the disclosure of transgenderism. The article identifies a range of issues that require further attention in relation to healthcare provision. These include the mental health needs of partners and spouses; attitudes of healthcare professionals towards transgender issues; and the adequacy of the formal support offered to partners and spouses of transgender people. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: There is a need for healthcare practitioners to explore their understanding of transgender issues and how these may impact on the mental health of partners and spouses. It is important that healthcare professionals provide a hopeful and supportive environment to enable couples to explore their relationships following disclosure of transgenderism.

Growing older with post-traumatic stress disorder.

WHAT IS KNOWN ON THE SUBJECT?: The needs of older people with long-term mental illness are not very well addressed in policy and research. Older people are not a homogenous group and people ageing with long-term mental illness have potentially unique or specific needs. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: A unique example of the idiosyncratic and contextual nature of individual strengths and the abilities in managing personal recovery when experiencing long-term mental illness. Emotional exhaustion experienced after long-term mental health compromises the ability to manage feelings, potentially a special feature of life time mental ill health. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Recognition that the hard work involved in successfully managing long-term personal recovery may be important in preventing suicide in later life. The need to understand a person's life story to make sense of their experience of mental illness and to recognize long-term mental illness to later life as part of a persons' established identity. The importance of appreciating the place of early memories for understanding older person's mental health in their present. ABSTRACT: Introduction Ageing with mental illness is a neglected area of research and policy. People who grow older to later life with ongoing mental health problems may not have their needs well understood. This understanding is important if mental health services are to ensure direct or indirect age discrimination is avoided. Aim This paper aims to explore issues relating to later life and ageing with mental illness focused on the story of Bernard (who was 84 years of age at the time of writing) who lived with a diagnosis of post-traumatic stress disorder (PTSD). Method The paper is co-authored by Bernard and the researcher he originally told his story to as a participant in a biographical research study exploring mental ill health through the life course. In the original research study, Bernard completed a curriculum vitae (CV) of his life which informed two personalised interviews. An edited version of this is presented in this paper. Implications for practice are discussed in the context of life course, recovery, self-help and preventing suicide. The narrative illustrates how time, memory and meaning interweave and how ageing with mental illness become part of a person's ongoing identity.

A study on the experience of insomnia in a psychiatric inpatient population.

Complaints of insomnia among psychiatric inpatients are high. Many technical studies about insomnia are available in the literature, but few make reference to individual experience. This study examines the subjective experience of insomnia for psychiatric patients in one mental health unit. A random purposive sample of seven subjects was selected from the population of patients complaining of insomnia. Subjective experience was examined using a tape-recorded semistructured interview. The data were analysed using Burnard's content analysis framework. Ten categories were identified: control, wants and desires, holistic, assessment, individualisms, beliefs, conflict, communication, resignation and sleep signatures. Biographical data, and data from clinical notes about sleep were also collected. Results show that the impact of insomnia should not be underestimated and that attention to this aspect of a patient's experience could have a general effect on their mental health and well-being.

Clinical effectiveness on an acute in-patient psychiatric unit.

The paper outlines a model for addressing clinical effectiveness, and an illustration of how this is practically implemented through team working in a multidisciplinary in-patient environment. This is particularly relevant given the number of recent reports that highlight the need to develop and invest in the in-patient services. The difficulty in implementing evidence-based practice for mental health interventions is also addressed and initiatives being developed to enable a realistic approach in such an environment are described. The paper describes a structure and a process, using examples from audit, research and other initiatives particular to the unit, in providing accessible evidence based interventions for ward based staff, and improved clinical effectiveness generally.

The day hospital debate--a contribution.

OBJECTIVE: To compare the prevalence of difficult behaviours in confused older people attending a National Health Service (NHS) day hospital with those attending non-NHS day care facilities. DESIGN: A behavioural rating scale was completed and referral information collected for people with dementia attending day care services. SETTING: One day hospital and seven day care facilities in one UK health authority. PATIENTS: All 20 attenders at an NHS day hospital and 64 attending day care, the latter identified by the staff as 'confused'. MEASURES: A 15-item behaviour rating scale. RESULTS: The quantitative ratings showed more disturbance (restlessness, friction, sexual disinhibition), poorer memory and decreased mobility in the NHS attenders. These small differences concealed much greater qualitative differences in the methods of operation of the two types of facility, with the focus being on assessment and throughput in the day hospital and social support in the day care services. CONCLUSIONS: In the light of recent debate, this study has demonstrated small but measurable behavioural differences between an NHS day hospital and non-specialist day care. However, a focus on rating of behaviour alone conceals much greater differences in why people are referred, by whom and for what reasons. The day hospital has its own role and is not merely plugging a gap.

Preoxygenation before laryngoscopy in children: how long is enough?

The ideal preoxygenation period prior to laryngoscopy in children is unclear. This study was performed to determine an appropriate duration of preoxygenation for infants and children prior to laryngoscopy using endtidal oxygen (FE'O2) criteria. Healthy paediatric patients for elective day surgery procedures were studied. An inflatable mask connected to an oxygen-primed paediatric anaesthesia semiclosed circuit was placed on the face while patients breathed spontaneously during 6.min-1 oxygen flow. An FE'O2 of 0.9 was considered the endpoint, and if not achieved in two min the protocol was ended. Fifty-eight children were studied. Six patients never achieved an FE'O2 of 0.9 and were not considered in the analysis. The times (in seconds with mean +/- SD and range) to achieve a minimum endtidal (FE'O2) of 0.9 for under six months were 36 +/- 11.4(20-50), 7-12 months were 35.5 +/- 13.3(20-60), 13-36 months were 42.6 +/- 18.7(20-90), 37-60 months were 50.8 +/- 18.5(30-90), > 60 months were 68.4 +/- 24.1(30-100). Logistic regression curves were determined for each age group describing the probability of achieving an FE'O2 of 0.9 against time of preoxygenation. All children with satisfactory mask fit were able to preoxygenate to an FE'O2 of 0.9 within 100 s.

Beneficial impact of aorto-coronary graft markers on post-operative angiography.

OBJECTIVE: When coronary and graft angiography is required for patients with prior coronary artery bypass (CAB) graft surgery, it is often difficult to localize the proximal aorto-coronary graft anastamosis. Our goal was to quantify the potential benefit during subsequent angiography if the proximal anastamosis is marked by an aorto-coronary graft marker at the time of CAB. METHODS: Retrospective review of 414 angiograms that were performed for patients with prior CAB. Cohorts with an without graft markers were compared. RESULTS: In the group with aorto-coronary graft markers and > or = 2 aorto-coronary grafts, there were significant reductions in fluoroscopy time (30.5%, p < 0.0001), contrast volume (21.7%, p < 0.0001), and numbers of angiographic catheters used (17.0%, p = 0.0001). If only one aorto-coronary graft was placed and marked, a trend toward reduced fluoroscopy time was observed (23.8%, p = 0.07). CONCLUSIONS: This study demonstrates the objective benefit supporting routine placement of circumferential aorto-coronary graft markers during CAB, particularly if > 1 graft is required.

Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium.

OBJECTIVE: To determine the sensitivity of calcium injected into pancreatic arteries in localizing insulin-secreting tumors to regions of the pancreas. DESIGN AND PATIENTS: To stimulate the release of insulin, 25 patients with surgically proven insulinomas (average diameter, 15 mm) had calcium gluconate (0.025 mEq Ca++/kg body weight) injected before surgery into the arteries supplying the pancreatic head (gastroduodenal and superior mesenteric arteries) and the body and tail (splenic artery) of the pancreas. SETTING: Tertiary referral hospital. MEASUREMENTS: Insulin levels were measured in samples taken from the right and left hepatic veins before and 30, 60, and 120 seconds after calcium injection. A twofold increase in insulin level in the sample taken from the right hepatic vein 30 or 60 seconds after injection localized the insulinoma to the segment of the pancreas supplied by the selectively injected artery. Localization done using calcium stimulation was compared with localization done using transcutaneous ultrasonography (n = 22), computed tomography (n = 23), magnetic resonance imaging (n = 21), arteriography (n = 25), and portal venous sampling (n = 9). RESULTS: Calcium stimulation localized 22 of 25 insulinomas (sensitivity, 88% [95% CI, 68% to 97%]) to the correct region of the pancreas. The sensitivities of the other imaging methods were 9% for ultrasonography (CI, 1% to 23%), 17% for computed tomography (CI, 5% to 39%), 43% for magnetic resonance imaging (CI, 22% to 66%), 36% for arteriography (CI, 18% to 57%), and 67% for portal venous sampling (CI, 30% to 93%). Calcium stimulation added only a few minutes to the time needed for pancreatic arteriography and caused no morbid conditions. CONCLUSION: Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas.

Mutational analysis of the NH2-terminal glycosylation sites of the insulin receptor alpha-subunit.

The insulin receptor is synthesized as a single chain of 190 kiloDaltons, which is processed to disulfide-linked mature alpha- and beta- subunits, containing N- and O-linked oligosaccharides and fatty acids. Previously (Collier E, Carpentier J-L, Beitz L, Caro LHP, Taylor SI, Gorden P: Biochemistry 32:7818-23, 1993), site directed mutagenesis of the asparagine in the first four sites of N-linked glycosylation to glutamine resulted in a receptor that was retained in the endoplasmic reticulum and not processed past the proreceptor form. In this study, mutation of these sites individually and in various combinations is studied. Mutation in the first or second glycosylation site does not significantly impair processing of the receptor; the receptor is found on the cell surface and binds insulin normally. If both the first and second sites are mutated, a significant reduction occurs in the amount of receptor found on the cell surface and in insulin binding. There is some processing of the receptor in cells expressing this mutant compared with the four-part mutant. If only the third and fourth sites are mutated, processing is impaired less than in the mutant with the first and second sites mutated. However, the amount of receptor found on the cell surface is less than in the mutant of only the first or only the second site. In all of these glycosylation mutants, the amount of receptor on the cell surface correlates with the level of 125I-labeled insulin binding on the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Specific glycosylation site mutations of the insulin receptor alpha subunit impair intracellular transport.

The insulin receptor is a transmembrane protein found on multiple cell types. This receptor is synthesized as a 190-kDa proreceptor which is cleaved to produce mature alpha and beta subunits. The proreceptor contains 18 potential sites for N-linked glycosylation: 14 on the alpha subunit and 4 on the beta subunit. The codons for asparagine in the first four sites at the amino terminus of the alpha subunit were mutated to code for glutamine. This mutant receptor cDNA was stably transfected into NIH 3T3 cells. The insulin receptor produced in these cells remained in the proreceptor form; no mature alpha and beta subunits were produced. The proreceptor was slightly smaller on SDS-PAGE gels than the wild-type proreceptor and contained four less oligosaccharide chains by tryptic peptide mapping. The carbohydrate chains on the mutant proreceptor remained endoglycosidase H sensitive. However, in the presence of brefeldin A, these oligosaccharide chains could be processed to endoglycosidase H resistant chains. By immunofluorescence, the mutant proreceptor was shown to be localized to the endoplasmic reticulum. No insulin receptors could be found on the cell-surface either with cell surface labeling with biotin or with 125I-insulin binding. Thus, glycosylation of the first four N-linked glycosylation sites of the insulin receptor is necessary for the proper processing and intracellular transport of the receptor. This is in contrast to glycosylation at the four sites on the beta subunit which appear not to be important for processing but necessary for signal transduction. Therefore, N-linked glycosylation of the insulin receptor at specific sites has multiple distinctive roles.

Characterization of purified autoantibodies to the insulin receptor from six patients with type B insulin resistance.

Anti-insulin-receptor autoantibodies are present in the serum of patients with the type B syndrome of extreme insulin resistance. Sera from six patients with this syndrome were purified over protein-A agarose to remove insulin and other serum factors and obtain an immunoglobulin fraction. These purified fractions were used to quantitatively determine the antibodies' activity in three separate assays. The ability to inhibit insulin binding was determined in an assay using fibroblasts that overexpress the human insulin receptor; the ability to immunoprecipitate the receptor was determined in an assay using biosynthetically labeled insulin receptors rather than insulin cross-linked receptors; and the ability to stimulate glucose oxidation was determined in isolated adipocytes. We show that the ability of these antibodies to inhibit insulin binding is tightly coupled to their ability to immunoprecipitate the biosynthetically labeled receptor, but neither assay predicts the bioactivity of these immunoglobulins. We suggest that the inability to show this tight coupling in the past may be due to methodological differences. We find no evidence that these antibodies are anti-idiotypic antibodies.

O-linked oligosaccharides on insulin receptor.

The insulin receptor, an integral membrane glycoprotein, is synthesized as a single-chain precursor that is cleaved to produce two mature subunits, both of which contain N-linked oligosaccharide chains and covalently linked fatty acids. We report that the beta-subunit also contains O-linked oligosaccharides. The proreceptor, alpha-subunit, and beta-subunit were labeled with [3H]mannose and [3H]galactose in the presence or absence of an inhibitor of O-linked glycosylation. Tryptic peptides from each component were separated by reverse-phase high-performance liquid chromatography. N- and O-linked oligosaccharide chains were identified on these peptides by specific enzymatic digestions. The proreceptor and alpha-subunit contained only N-linked oligosaccharides, whereas the beta-subunit contained both N- and O-linked oligosaccharides. The O-linked oligosaccharide chains were attached to a single tryptic fraction of the beta-subunit, which also contained N-linked chains. This fraction was further localized to the NH2-terminal tryptic peptide of the beta-subunit by specific immunoprecipitation with an anti-peptide antibody with specificity for this region. Binding of insulin and autophosphorylation of the beta-subunit were not dependent on O-linked glycosylation, because cells grown in the presence of the inhibitor exhibited a normal dose response to insulin. Therefore, the insulin receptor contains O-linked oligosaccharides on the NH2-terminal tryptic peptide of the beta-subunit, and these O-linked oligosaccharides are not necessary to the binding or autophosphorylation function of the receptor.

Congenital esophageal stenosis. A rare cause of food impaction in the adult.

When esophageal peristalsis is preserved, the presentation of congenital esophageal stenosis may be delayed until adulthood. Serial Maloney dilations are a safe and effective method of treating muscular congenital esophageal stenosis.

Biosynthesis and regulation of the insulin receptor.

The insulin receptor is an integral glycoprotein of the plasma membrane in most mammalian cells. The gene encodes a 190 kDa proreceptor that undergoes a number of processing steps. The gene is constitutively expressed, but at least one form of regulation has been demonstrated. Glucocorticoids increase the number of insulin receptors on the surface of cultured human lymphocytes, a process which is accompanied by an increase in transcription of the gene. N-linked glycosylation and amide-linked acylation occur as co-translational events. Subsequently, the proreceptor is cleaved into alpha and beta subunits; the subunits then undergo an ester-linked acylation step and N-linked complex glycosylation. In addition, O-linked glycosylation has been recently described in the beta subunit. The mature insulin receptor is inserted into the plasma membrane as an alpha 2-beta 2 disulfide-linked heterodimer. The receptor can be further regulated on the cell surface by insulin binding and receptor-mediated endocytosis. The receptor concentration on the cell surface then becomes a function of the internalization rate and the receptor recycling rate. Receptor regulation is a relevant feature of many forms of clinical insulin resistance, and recently genetic mutations have been described that determine both the binding properties of the receptor and its translocation and processing properties.