Identification and treatment of Strongyloides stercoralis infection in a Boston Terrier dog from south-eastern Australia.

Strongyloides stercoralis, the causative agent of strongyloidiasis, is a potentially zoonotic intestinal nematode endemic to northern Australia. Strongyloidiasis is typically observed in immunocompromised hosts and is characterised by gastrointestinal signs, respiratory symptoms and a failure to thrive. In immunocompromised hosts, hyperinfection syndrome and disseminated infections can prove life-threatening. A 24-month-old Boston Terrier dog was referred for investigation of chronic small and large intestinal watery hematochezic diarrhoea, emaciation and hematemesis. Small intestinal histology identified a nematode despite consecutive negative faecal flotations. A real-time polymerase chain reaction and Baermann test subsequently confirmed infection with S. stercoralis. The dog had received an oral parasiticide comprising milbemycin oxime and afoxolaner every month for the 11 months prior to this diagnosis. Despite fenbendazole being reported as successful in the treatment of canine strongyloidiasis, a course of fenbendazole failed to clear the infection. Eradication of S. stercoralis infection was confirmed after the administration of off-label ivermectin fortnightly for 12 doses. Attention should be paid to this nematode as the failure of routine copromicroscopic methods to diagnose S. stercoralis infections can result in misdiagnosis, mistreatment and progression of the disease. Off-label ivermectin may be an alternative to fenbendazole for the treatment of Strongyloides spp. infection in dogs.

TuLIP (Tunnelled Line Intraluminal Plasty): An Alternative Technique for Salvaging Haemodialysis Catheter Patency in Fibrin Sheath Formation.

BACKGROUND: Renal patients with a tunnelled haemodialysis line are at risk of fibrin 'sheath' formation which can lead to occlusion. Dysfunctional lines are best treated by catheter exchange with a new subcutaneous tunnel; however, there is a risk of scarring, venous stenosis, potential loss of valuable access as well as the risk of infection. METHOD: We report a retrospective review of our experience using tunnelled line intraluminal plasty (TuLIP) in 11 patients over 16 months with fibrin sheath formation on pre-existing tunnelled haemodialysis catheters. RESULT: All patients responded well to treatment with median line patency post TuLIP reaching 112 days. CONCLUSION: TuLIP may have a role in extending catheter lifespan and delaying more invasive intervention.

A strategy for monitoring and evaluating massive open online courses.

We argue that the complex, innovative and adaptive nature of Massive Open Online Course (MOOC) initiatives poses particular challenges to monitoring and evaluation, in that any evaluation strategy will need to follow a systems approach. This article aims to guide organizations implementing MOOCs through a series of steps to assist them in developing a strategy to monitor, improve, and judge the merit of their initiatives. We describe how we operationalise our strategy by first defining the different layers of interacting agents in a given MOOC system. We then tailor our approach to these different layers. Specifically, a two-pronged approach was developed, where we suggest that individual projects be assessed through performance monitoring; assessment criteria for which would be defined at the outset to include coverage, participation, quality and student achievement. In contrast, the success of an overall initiative should be considered within a more adaptive, emergent evaluation inquiry framework. We present the inquiry framework we developed for MOOC initiatives, and show how this framework might be used to develop evaluation questions and an assessment methodology. We also define the more fixed indicators and measures for project performance monitoring. Our strategy is described as it was developed to inform the evaluation of a MOOC initiative at the University of Cape Town (UCT), South Africa.

Pancreatitis associated with valproic acid: a review of the literature.

Black box warnings for valproic acid caution clinicians of the potential for fatal hepatotoxicity and teratogenicity. Since 1979, case reports of pancreatitis induced by valproic acid have been published in the medical literature. As a result, pancreatitis was added to the black box warnings for valproic acid. We performed searches of MEDLINE and International Pharmaceutical Abstracts and found valproic acid-induced pancreatitis in 45 patients from 31 published articles. Demographics, clinical characteristics, and outcomes of these patients are summarized. Recommendations for monitoring the potential for pancreatitis to develop in patients receiving valproic acid therapy are described, as are potential mechanisms for inducement of pancreatitis by valproic acid.

Unilateral diaphragmatic paralysis following bronchial artery embolization for hemoptysis.

Bronchial artery embolization is an effective treatment for patients with hemoptysis. Serious complications are rare, but may occur if the arterial supply to other structures is compromised. We present a case of unilateral diaphragmatic paralysis following bronchial artery embolization in a patient with cystic fibrosis. We believe that the diaphragmatic paralysis was due to the inadvertent obstruction of the left pericardiacophrenic artery during the embolization procedure, with compromise of the phrenic nerve blood supply. This resulted in a significant loss of lung function in our patient, who did not recover despite the subsequent return of diaphragmatic function.

Glycoproteins of trabecular meshwork, cornea and sclera.

PURPOSE: To analyse high-molecular-weight matrix glycoproteins in trabecular meshwork, cornea and sclera using SDS/PAGE and immuno- and lectin blotting. METHOD: Extracts of normal trabecular meshwork (TM), cornea and sclera were analysed under reducing conditions on SDS/ PAGE. Western blots were stained for total protein, and major high-molecular-weight components were identified by immunoblotting with antibodies to fibronectin (FN) and type VI collagen. Lectin blotting with PSA, MPA and DSA identified some of the glycoprotein glycans. RESULTS: FN antibody bound to the 240 kDa band in TM, cornea and sclera. Type VI collagen antibody bound more strongly to one band and less so to two other bands at approximately 200 kDA in normal TM and to a ladder of bands in cornea and sclera. PSA and DSA bound at 240, 200 and 140 kDa in TM, cornea and sclera. MPA bound at 240, 200 and 140 kDa in TM and at 240, 200 and approximately 120 kDA in cornea and sclera. CONCLUSIONS: FN is a component of the band at 240 kDA in TM, cornea and sclera. Normal TM was found to contain relatively more of one of the isoforms of the alpha 3 (VI) chain whilst cornea and sclera contained all the alpha 3 (VI) isoforms. Complex N-linked bi/tri-antennary glycans were localised in FN and the alpha 1, alpha 2 and alpha 3 (VI) chains in TM, cornea and sclera. O-linked glycans (identified by MPA binding) were located in FN and alpha 3 (VI) chains of TM, cornea and sclera.

Health promotion and managed care: surveys of California's health plans and population.

INTRODUCTION: The purpose was to examine whether health-promotion programs offered by California health plans are a serious attempt to improve health status or a marketing device used in an increasingly competitive marketplace. The research examined differences in the coverage, availability, utilization, and evaluation of health-promotion programs in California health plans. METHODS: A mail survey was done of the 35 HMOs (86% response) and 18 health insurance carriers (83% response) licensed to sell comprehensive health insurance in California in 1996 (some plans sell both HMO and PPO/indemnity products). The final sample included 30 commercial HMOs and 20 PPO and indemnity plans. The 1996 California Behavioral Risk Factor Survey (BRFS) of 4,000 adults was used to estimate population participation rates in health-promotion programs. RESULTS: California's HMOs in 1996 offered more comprehensive preventive benefits and health-promotion programs compared to PPO and indemnity plans. HMOs relied on a more comprehensive set of health-education methods to communicate health information to members and were more likely to open their programs to the public. HMOs are also more likely to have developed relationships with community-based and public health providers. Participation in health-promotion programs is low (2%-3%), regardless of plan type, and most health plans limit evaluations to assessment of member satisfaction and utilization. Only 35%-45% of HMOs, and no PPO/indemnity plans, assess the impact of health-promotion programs on health risks and behaviors, health status, or health care costs. CONCLUSION: For the majority of California's PPO and indemnity plans, health promotion is not an integral part of their business. For the majority of HMOs, health-promotion programs are offered primarily as a marketing vehicle. However, a substantial minority of HMOs offer health-promotion programs to achieve other organizational goals of health improvement and cost control.

Considerations for using ketoconazole in solid organ transplant recipients receiving cyclosporine immunosuppression.

Drug interactions involving cyclosporine following transplantation are a challenging issue for the transplant clinician. This is especially true when ketoconazole is the second agent used in conjunction with cyclosporine. Because both agents are metabolized by the cytochrome P-450 IIIA4 enzyme system, cyclosporine levels rise dramatically in the presence of ketoconazole. Many other agents interact with ketoconazole, either by competitive enzyme inhibition in the liver and gastrointestinal tract, or by reducing the absorption of ketoconazole by agents that increase the pH of the gastrointestinal tract. Despite the potential cost savings when using ketoconazole to reduce cyclosporine doses, adverse effects associated with ketoconazole put patients at risk when using this combination. Close monitoring of cyclosporine levels is imperative when adding ketoconazole to cyclosporine, and once the dosage adjustments are complete, the addition of a third drug that interacts with either cyclosporine or ketoconazole could result in an unexpected rejection episode or toxic cyclosporine side effect.

Glycans of the trabecular meshwork in primary open angle glaucoma.

AIMS: Glycan expression was compared in glaucomatous trabecular meshwork (TM) and normal TM in order to determine any differences which may reflect pathological changes underlying primary open angle glaucoma (POAG). METHODS: Resin embedded TM from trabeculectomy specimens from 15 eyes with POAG and from 12 eyes with normal anterior segments were probed with a panel of biotinylated lectins and an avidin-peroxidase revealing system at the light microscope level. Statistical analyses were performed on the comparative staining results. RESULTS: The lectins ConA and ePHA showed strong staining in all areas of both glaucomatous and normal TM; ePHA staining of Schlemm's canal (SC) from POAG TM was significantly less than that from normal TM (ePHA-SC p = 0.04). The lectins PSA, LCA, and SNA bound moderately strongly to SC endothelium and weakly to the endothelium of the corneoscleral meshwork (CSM); glaucomatous SC endothelial binding was significantly less than that of normal SC endothelium for PSA and LCA (PSA-SC p = 0.002, LCA-SC p = 0.002). STA and DSA showed moderately strong binding while WGA, ECA, AHA, and MPA bound weakly throughout the TM; for DSA and MPA this staining was significantly greater in POAG than in normal TM (DSA-SC p = 0.001, DSA-CSM p = 0.002, MPA-SC p = 0.01, MPA-CSM p = 0.02). Jac stained strongly throughout the TM and showed no significant difference in POAG compared with normal TM (Jac-SC p = 0.6, Jac-CSM p = 1). 1PHA, SBA, DBA, CTA, UEA-1 and LTA did not bind to glaucomatous TM or normal TM. There were no age-related changes seen. CONCLUSIONS: The expression of some complex and hybrid, bisected and non-bisected N-linked glycans is significantly diminished in glaucomatous TM compared with normal TM. Some glycans with multiple N-acetylglucosamine residues and O-linked glycans with terminal and subterminal galactosyl groups are significantly increased in POAG TM. Glycan expression does not change significantly with age in POAG or normal TM.

Glycoconjugates of the human trabecular meshwork: a lectin histochemical study.

Twelve specimens of resin-embedded human trabecular meshwork were probed with a panel of 21 biotinylated lectins, using an avidin-biotin peroxidase revealing system, in order to determine the normal pattern of saccharide expression in this tissue. High-mannose, intermediate and hybrid N-linked glycans, and complex N-linked bisected and non-bisected bi/tri-antennate glycans, as shown by the binding of Canavalia ensiformis (ConA), Pisum sativum (PSA), Lens culinaris (LCA) agglutinins and Phaseolus vulgaris erythroagglutinin (ePHA), were strongly expressed by the canal of Schlemm endothelium and juxtacanalicular tissue, but less so by the corneoscleal meshwork. Highly branced complex glycans were not found, as there was no binding by Phaseolus vulgaris leukoagglutinin (IPHA). Sialyl residues, especially those alpha 2,6-linked as demonstrated by strong Sambucus nigra (SNA) lectin staining, were also abundant in this area. N-acetyllactosamine sequences and some O-linked glycans were present in the trabecular meshwork, as shown by Solanum tuberosum (STA), Datura stramonium (DSA), and Jacalin (Jac) lectin binding, while fucose residues were not detected by Tetragonolobus purpureas (LTA) or Ulex europaeus-1 (UEA-1) agglutinins. These results indicate similarities with renal glomerular and vascular endothelium, although the lack of binding with UEA-1 agglutinin suggests differences which may relate to the specialized function of the trabecular meshwork. This study provides a baseline for comparative analysis of the glycans of human trabecular meshwork in pathological conditions such as primary open-angle glaucoma.

Localisation of alpha(2,3) and alpha(2,6) linked terminal sialic acid groups in human trabecular meshwork.

Sialic acid specific lectins were used to localise isomers of sialyl glycosides in human trabecular meshwork (TM) at the ultrastructural level. A lectin immunogold method demonstrated that sialic groups were concentrated on the endothelial surface of Schlemm's canal (SC) and in the adjacent juxta-canalicular tissue (JCT). One sialyl glycoside, alpha(2,6) linked N-acetyl neuraminic acid, was present mainly on the luminal aspect of the SC endothelium and in the cytoplasm of the JCT cells. Another, alpha(2,3) linked N-acetyl neuraminic acid, was localised predominantly to the extracellular fibrillar material of the JCT. The existence of a topographical segregation of these two sialyl glycosides within the TM supports the view that highly charged anionic molecules may be of significance in regulating aqueous outflow.

Dietary manganese deficiency decreases rat hepatic arginase activity.

This study was designed to quantify the effect of dietary manganese deficiency on rat hepatic Mn concentration and arginase activity. Weanling male Sprague-Dawley rats were randomly assigned to two groups of nine rats each and fed L-amino acid diets with 0 or 48 micrograms Mn/g diet for 21 d. After 21 d, hepatic Mn concentration (mumol/g liver dry wt, mean +/- SEM) was 0.130 +/- 0.005 for the control group but was lower (P < 0.01) in the Mn-deficient group (0.040 +/- 0.003). There were no differences in the hepatic concentrations of any other measured mineral. Hepatic arginase activity [mmol ornithine/(g hepatic protein.min)] was 1.55 +/- 0.22 in the control group and was lower (P < 0.01) in the Mn-deficient group (1.12 +/- 0.26). Plasma ammonia concentration was 301 +/- 6 mumol/L in the control group and was higher (P < 0.01) in the Mn-deficient group (480 +/- 8 mumol/L). In contrast, plasma urea concentration was higher (P < 0.01) in the control group (350 +/- 10 mumol/L) than in the Mn-deficient group (267 +/- 7 mumol/L). There were no differences in plasma concentrations of arginine or other amino acids between the control and the Mn-deficient groups. Our results demonstrate for the first time that dietary Mn deficiency results in altered plasma concentrations of ammonia and urea in association with decreased hepatic Mn concentration and arginase activity in young growing rats.

Effect of excision of occipital lobe tissue on about the 70th day of gestation on the growth and development of the sheep's brain.

A unilateral occipital excision was performed on 14 fetal lambs at about the 70th day of gestation, and the brains were examined postnatally for gross morphological and histologic changes. Three operated brains revealed a posterior shift of the principal transverse sulcus in the ipsilateral hemisphere. This sulcus is remote from the area of excision, which was usually represented by a cystic cavity. Histologic examination showed that the dorsal lateral geniculate body was reduced in size in all but three of the operated brains. In two brains with the changed gyral pattern there was also a reduction in the size of the white fiber tracts of the frontal lobe. No evidence of neural regeneration was found in any of the brains. The implications of these findings from the point of view of possible neurosurgical intervention in the fetus are considered.

Occipital lobectomies in foetal lambs.

Foetal lambs undergoing unilateral occipital lobectomy have been investigated post-natally with computed tomographic (CT) scans, visual evoked potentials (VEP) recording and histological examination of their brains. Only the lambs operated at about 100th day of gestation have so far had their investigations completed, however, the results in all the lambs suggests that the foetal brain responds to an occipital lobectomy in essentially the same way as the post-natal brain. To date no evidence of regeneration has been found in any of the brains. It seems reasonable to conclude that if the foetal brain responds to lobectomy in the same manner to the post-natal brain, then its response to disease is likely to be similar. If this is so it can be argued that remediable foetal central nervous system abnormalities should be treated as soon as possible, if necessary in utero.

The changing dynamics of graduate medical education. Implications for decision-making.

Cost-containment pressures and changes in traditional patient-care patterns are altering the process of graduate medical education. A thorough understanding of this process is a prerequisite to implementing changes that preserve the function of graduate medical education. This report describes the structure of the graduate medical education system and analyzes possible responses to the changes that are affecting it. The decision-making process within academic health centers is described, including an assessment of the roles of hospital directors, deans and faculty, as well as external regulatory agencies such as residency review committees, medical specialty boards and state licensing agencies. The activities of these participants are analyzed within the framework of the teaching hospital's service and education functions, and potential conflicts are described and illustrated by recent examples. Understanding the complex structure and functions of graduate medical education is a first step toward responding effectively to a changing environment.

The outcome of unilateral occipital lobectomy in 12 foetal lambs in about the 100th day of gestation: a preliminary report.

In this study occipital lobectomies were carried out on 12 foetal lambs on about the 100th day of gestation. Three lambs were born alive and had computed tomographic (CT) scans performed on the 13th or 18th day of life. One lamb was found to have hydrocephalus due to ventriculitis. All three lambs had low attenuation areas on their CT scans suggesting that scarring rather than regeneration of the cerebral tissues had taken place. There was no evidence that accelerated bone healing of the skull had occurred. It is speculated that the lack of regeneration cerebral tissues and poor bone healing may have been due to the procedure being performed at a comparatively late stage of gestation.

Response of the fetal rat brain to trauma during the 17th to 21st days of gestation.

Ultrasonography has made it possible to diagnose abnormalities of the human central nervous system early in pregnancy. However, more needs to be known about the response of the fetal brain before the mother and fetus are subjected to the risks of complex neurosurgical procedures. This study investigated the effects of trauma on fetal rat brains during a period equivalent to the early part of the second trimester of human pregnancy. Trauma inflicted on the fetal rat brains caused haemorrhage and necrosis of the cerebral hemisphere, which was not followed by significant regeneration of neural tissue. This preliminary study suggests that it cannot be assumed that the fetal brain will regenerate itself after injury, and that this should be considered when making plans for operative procedures on the central nervous system in utero.

Comparison of scanning electron and light microscopic appearances of sequential changes taking place in the ischemic cortex of the rat brain.

The right middle cerebral territory of rat brains was made ischemic (a) for periods varying from 30 minutes to 24 hours, and at the end of each of the times the animals were killed and their brains were fixed, or (b) for 30 minutes, and the animals were allowed to survive for between 1 week and 9 months before they were killed and their brains were fixed. The ischemic areas were examined by light and scanning electron microscopy and the findings of the two methods of examination were compared. Scanning electron microscopy allowed the tissues to be studied at a wider range of magnification than was possible with the light microscope. Scanning electron microscopy also provided a three-dimensional view of the structures so that their relationship to one another could be examined. However, because it is generally not possible to stain material for examination by scanning electron microscopy, it was sometimes difficult to identify positively the individual structures. Nevertheless, this study has shown that scanning electron microscopy provides a valuable new way of investigating the ischemic brain and is likely to prove useful in other studies in the future.