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This chapter serves as a guide to gastrointestinal (GI) endoscopy for the histopathologist for benign pathology and outlines the value to endoscopists of GI biopsies. It sets out to explain to a histopathology audience the decision-making process that endoscopists undertake when performing an endoscopic procedure and, crucially, what they need in return in a pathology report. There are explanations as to the thought processes that lead to endoscopic biopsies both in macroscopic disease and, perhaps more importantly, when appearances are normal. There is a guide to each anatomical area detailing how, where, and when to take samples from each region from the oesophagus to the rectum, followed by detailed up-to-date explanations on the latest guidelines for endoscopic sampling for each disease state. For each anatomical area there are practice point summaries and for some diseases detailed endoscopic pictures. The goal of this chapter is to enhance the pathologist’s knowledge of endoscopy, benign GI disease, and national and international sampling guidelines. Finally, we hope it serves as a guide for enhanced discussion between endoscopists and pathologists and encourages a collaborative approach to disease diagnosis.
Pompe disease is a type-II glycogen storage disease, and clinical manifestations include hypertrophic cardiomyopathy and generalised muscular hypotonia. Enzyme replacement therapy has proven to be effective in reversing the ventricular hypertrophy. The outcomes are variable depending on time to diagnosis and severity of the cardiac disease. We describe two contrasting cases of patients with infantile-onset Pompe disease. The first child was diagnosed late and had severe cardiac hypertrophy with respiratory decompensation and ventilator dependence and eventual death. The second case was diagnosed at birth with early initiation of therapy resulting in a good outcome. Our cases highlight the importance of early initiation of enzyme replacement therapy to improve clinical outcomes.
By providing the first comprehensive account of the role of the British and Indian press in war propaganda, this article makes an intervention in the global history of the First World War. The positive propaganda early in the war, intertwined with a rhetoric of loyalism, contrasted with how the conservative British press affixed blame for military defeats in Mesopotamia upon the colonial regime's failure to effectively mobilize India's resources. Using a highly emotive and enduring trope of the ‘Mesopotamia muddle’, the Northcliffe press was successful in channelling a high degree of public scrutiny onto the campaign. The effectiveness of this criticism ensured that debates about the Mesopotamian debacle became a vehicle for registering criticism of structures of colonial rule and control in India. On the one hand, this critique hastened constitutional reforms and devolution in colonial India and, on the other, it led to demands that the inadequacy of India's contribution to the war be remedied by raising war loans. Both the colonial government and its nationalist critics were briefly and paradoxically united in opposing these demands. The coercive extraction of funds for the imperial war effort as well as the British press's vituperative criticism contributed to a post-war, anti-colonial political upsurge. The procedure of creating a colonial ‘scandal’ out of a military disaster required a specific politics for assessing the regulated flows of information, which proved to be highly effective in shaping both the enquiry that followed and the politics of interwar colonial South Asia.
Perforations of the tympanic membrane are treated with various surgical techniques and materials. This study aimed to determine the efficacy of platelet-rich plasma during underlay myringoplasty.
The study included 40 patients. Autologous platelet-rich plasma was applied in-between temporalis fascia graft and tympanic membrane remnant during underlay myringoplasty in group 1 (n = 20). The outcome was evaluated after three months and compared with group 2 (n = 20), a control group that underwent routine underlay tympanoplasty.
After three months’ follow up, graft uptake was 95 per cent in group 1 and 85 per cent in group 2 (p < 0.03). Mean hearing threshold gain was 18.62 dB in group 1 and 13.15 dB in group 2. This difference was statistically significant (p < 0.01).
Platelet-rich plasma, with its ease of preparation technique, availability, low cost, autologous nature and good graft uptake rate, justifies its use in tympanoplasty type I procedures.
OBJECTIVES/SPECIFIC AIMS: Preliminary animal studies showed that low-intensity ultrasound (US) coincident with intravascularly administered microbubbles locally disrupts tumor vasculature. This study translates the novel therapy of antivascular ultrasound (AVUS) into an autochthonous model of hepatocellular carcinoma (HCC). The differential effects produced by AVUS at low and high doses are evaluated. METHODS/STUDY POPULATION: HCC was induced in 12 Wistar rats by ingestion of 0.01% diethylnitrosamine in drinking water for 12 weeks. Rats received AVUS treatment at low and high doses. Low dose group (n=6) received 1 W/cm2 US for 1 minute with 0.2 mL microbubbles injected IV. High dose group (n=6) received 2 W/cm2 for 2 minute with 0.7 mL microbubbles IV. Perfusion was measured before and after AVUS with contrast-enhanced ultrasound (CE-US) and power Doppler (PD-US). Peak enhancement (PE) and perfusion index (PI) were measured from each US mode. Histology after sacrifice or natural death was compared to pre/post US. Analysis of H&E and trichrome sections was evaluated for percent area of hemorrhage and findings of tissue injury and repair including inflammation, necrosis, and fibrosis. RESULTS/ANTICIPATED RESULTS: After high dose AVUS, PE, and PI of CE-US decreased from baseline by an average of 33.3% and 29.7%, respectively. Histology showed extensive tissue injury (hemorrhage, necrosis, fibrosis) in 58% of tumor cross-sectional area. Conversely, low dose AVUS increased PE and PI of CE-US by an average of 39.3% and 67.8%, respectively. Histology showed smaller areas of microhemorrhage Versus large pools of hemorrhage (only 17% area). PD-US changes were similar to CE-US. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, the opposing effects of AVUS observed at 2 doses allows for multiple roles in tumor therapy. Enhanced perfusion at a low dose may improve drug delivery or radiation therapy. Whereas, vascular disruption at high doses of AVUS may allow noninvasive ischemic therapy. Furthermore, AVUS is ripe for translation given the use its component parts clinically: low-intensity long-tone burst for physiotherapy and microbubbles as an US contrast agent. Thus, AVUS should be evaluated for translation of its differential effects into noninvasive therapies for HCC and other tumors.
The Institute of Medicine recommended the advance of innovation and entrepreneurship training programs within the Clinical & Translational Science Award (CTSA) program; however, there remains a gap in adoption by CTSA institutes. The University of Michigan’s Michigan Institute for Clinical & Health Research and Fast Forward Medical Innovation (FFMI) partnered to develop a pilot program designed to teach CTSA hubs how to implement innovation and entrepreneurship programs at their home institutions.
Materials and methods
The program provided a 2-day onsite training experience combined with observation of an ongoing course focused on providing biomedical innovation, commercialization and entrepreneurial training to a medical academician audience (FFMI fastPACE).
All 9 participating CTSA institutes reported a greater connection to biomedical research commercialization resources. Six launched their own version of the FFMI fastPACE course or modified existing programs. Two reported greater collaboration with their technology transfer offices.
The FFMI fastPACE course and training program may be suitable for CTSA hubs looking to enhance innovation and entrepreneurship within their institutions and across their innovation ecosystems.
OBJECTIVES/SPECIFIC AIMS: This study describes the design, operation, and evaluation of a community-based research (CBR) consult service within the setting of a Clinical and Translational Science Award (CTSA) institution. To our knowledge, there are no published evaluations of a CBR consult service at a CTSA hub. METHODS/STUDY POPULATION: A CBR consult service was created to support faculty, healthcare providers/research coordinators, trainees, community-based organizations, and community members. A framework was developed to assess the stages of client engagement and to foster clear articulation of client needs and challenges. A developmental evaluation system was integrated with the framework to track progress, store documents, continuously improve the consult service, and assess research outcomes. RESULTS/ANTICIPATED RESULTS: This framework provides information on client numbers, types, services used, and successful outreach methods. Tracking progress reveals reasons that prevent clients from completing projects and facilitates learning outcomes relevant to clients and funding agencies. Clients benefit from the expert knowledge, community connections, and project guidance provided by the consult service team, increasing the likelihood of study completion and achieving research outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: Our evaluation suggests that clients benefit by (1) gaining the collective knowledge of the experts comprising the team, (2) learning the process of doing CBR, including the required steps to reach completion, and (3) gaining a project management mentality promoting translational research outcomes. This study offers a framework by which CTSA institutions can expand their capacity to conduct and evaluate CBR while addressing challenges that inhibit community engagement.
Fetal growth restriction (FGR) and preterm birth are frequent co-morbidities, both are independent risks for brain injury. However, few studies have examined the mechanisms by which preterm FGR increases the risk of adverse neurological outcomes. We aimed to determine the effects of prematurity and mechanical ventilation (VENT) on the brain of FGR and appropriately grown (AG, control) lambs. We hypothesized that FGR preterm lambs are more vulnerable to ventilation-induced acute brain injury. FGR was surgically induced in fetal sheep (0.7 gestation) by ligation of a single umbilical artery. After 4 weeks, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Brains and cerebrospinal fluid (CSF) were collected for analysis of molecular and structural indices of early brain injury. FGRVENT lambs had increased oxidative cell damage and brain injury marker S100B levels compared with all other groups. Mechanical ventilation increased inflammatory marker IL-8 within the brain of FGRVENT and AGVENT lambs. Abnormalities in the neurovascular unit and increased blood–brain barrier permeability were observed in FGRVENT lambs, as well as an altered density of vascular tight junctions markers. FGR and AG preterm lambs have different responses to acute injurious mechanical ventilation, changes which appear to have been developmentally programmed in utero.
Changes in seroprevalence of cysticercosis diagnosed in Chandigarh, India between 1998 and 2014 were investigated by extraction and analysis of data from records held at the Postgraduate Institute of Medical Education and Research in Chandigarh. Among the total number of samples for which cysticercosis had been suspected during this period (N = 9650), 1716 (17·8%) were seropositive. Adults were more likely to be seropositive than children, and women were more likely to be seropositive than men. In addition to there being fewer patients with suspicion of cysticercosis over the data analysis period, the proportion of patients seropositive also reduced significantly. Despite these reductions, which are probably associated with improved infrastructure and sanitation within Chandigarh, and despite meat consumption being relatively rare in this area, the extent of cysticercosis in this population remains problematic. Further efforts should be made to reduce transmission of this infection, with particular emphasis on women. Such efforts should follow the One Health concept, and involve medical efforts (including diagnosis and treatment of T. solium tapeworm carriers), veterinary efforts directed towards meat inspection and prevention of infection of pigs, and environmental health and sanitation engineers (to minimize environmental contamination with human waste).
This study describes the design, operation, and evaluation of a community-based research (CBR) consult service within the setting of a Clinical and Translational Science Award (CTSA) institution. To our knowledge, there are no published evaluations of a CBR consult service at a CTSA hub.
A CBR consult service was created to support faculty, health-care providers/research coordinators, trainees, community-based organizations, and community members. A framework was developed to assess the stages of client engagement and to foster clear articulation of client needs and challenges. A developmental evaluation system was integrated with the framework to track progress, store documents, continuously improve the consult service, and assess research outcomes.
This framework provides information on client numbers, types, services used, and successful outreach methods. Tracking progress reveals reasons that prevent clients from completing projects and facilitates learning outcomes relevant to clients and funding agencies. Clients benefit from the expert knowledge, community connections, and project guidance provided by the consult service team, increasing the likelihood of study completion and achieving research outcomes.
This study offers a framework by which CTSA institutions can expand their capacity to conduct and evaluate CBR while addressing challenges that inhibit community engagement.
Intrauterine growth restriction has been noted to adversely impact morbidity and mortality in the neonatal period as well as cardiovascular well-being in adolescence and adulthood. Recent data based on a wide range of ultrasound parameters during fetal and neonatal life has noted early and persistent involvement of the cardiovascular system. Some of these measures are predictive of long-term morbidities. Assessment of vascular mechanics is a new and novel concept in this population, and opens up avenues for diagnosis, monitoring and evaluation of the likely effectiveness of interventions. Prevention of these adverse vascular and cardiac outcomes secondary to fetal growth restriction may be feasible and of clinical relevance. This review focuses on growth restriction in humans with respect to cardiovascular remodeling and dysfunction during fetal life, persistence of functional cardiac impairment during early childhood and adolescence, and possible preventive strategies.
Human lymphatic filariasis (LF) is a major cause of disability globally. The success of global elimination programmes for LF depends upon effectiveness of tools for diagnosis and treatment. In this study on stage-specific antigen detection in brugian filariasis, L3, adult worm (AW) and microfilarial antigenaemia were detected in around 90–95% of microfilariae carriers (MF group), 50–70% of adenolymphangitis (ADL) patients, 10–25% of chronic pathology (CP) patients and 10–15% of endemic normal (EN) controls. The sensitivity of the circulating filarial antigen (CFA) detection in serum samples from MF group was up to 95%. In sera from ADL patients, unexpectedly, less antigen reactivity was observed. In CP group all the CFA positive individuals were from CP grade I and II only and none from grade III or IV, suggesting that with chronicity the AWs lose fecundity and start to disintegrate and die. Amongst EN subject, 10–15% had CFA indicating that few of them harbour filarial AWs, thus they might not be truly immune as has been conventionally believed. The specificity for antigen detection was 100% when tested with sera from various other protozoan and non-filarial helminthic infections.
The coevolutionary relationships between avian malaria parasites and their hosts influence the host specificity, geographical distribution and pathogenicity of these parasites. However, to understand fine scale coevolutionary host–parasite relationships, robust and widespread sampling from closely related hosts is needed. We thus sought to explore the coevolutionary history of avian Plasmodium and the widespread African sunbirds, family Nectariniidae. These birds are distributed throughout Africa and occupy a variety of habitats. Considering the role that habitat plays in influencing host-specificity and the role that host-specificity plays in coevolutionary relationships, African sunbirds provide an exceptional model system to study the processes that govern the distribution and diversity of avian malaria. Here we evaluated the coevolutionary histories using a multi-gene phylogeny for Nectariniidae and avian Plasmodium found in Nectariniidae. We then assessed the host–parasite biogeography and the structuring of parasite assemblages. We recovered Plasmodium lineages concurrently in East, West, South and Island regions of Africa. However, several Plasmodium lineages were recovered exclusively within one respective region, despite being found in widely distributed hosts. In addition, we inferred the biogeographic history of these parasites and provide evidence supporting a model of biotic diversification in avian Plasmodium of African sunbirds.
To describe a relatively unknown clinical entity – inflammatory cast of the tympanic membrane after acute otitis media – and its simple out-patient treatment.
Retrospective review of case series.
Subspecialty practice at a tertiary hospital.
Seven patients diagnosed previously with acute otitis media with perforation or otitis externa, and with persistent ear discomfort.
Retrospective chart review.
The patients presented with weeks to months of persistent hearing loss after acute otitis media with perforation or acute otitis externa. Visits to their primary care physicians had been uninformative. After comparison of the affected and unaffected tympanic membranes, a thin, hard cast was identified and removed from the affected tympanic membrane. Improvement in hearing was documented in the three patients who underwent audiometric testing; the remainder had subjective improvement without audiometric evaluation.
Otolaryngologists should be aware of the possibility of an inflammatory cast of the tympanic membrane following acute otitis media with perforation or otitis externa, and should carefully compare the unaffected and affected ears in such cases. Treatment – removal of the rigid cast – is both simple and effective.
AN EXTREME STATE of skin irritation resulting in extensive erythema and/or scaling of the body in several skin disorders may ultimately culminate in erythroderma/exfoliative dermatitis. Largely, it is a secondary process; therefore, determining its cause is needed to facilitate precise management. Its clinical pattern is fascinating and has been the subject of detailed studies: Its changing scenario in various age groups, its presentation postoperatively, and its occurrence in human immunodeficiency virus (HIV)-positive individuals are vivid indicators. Several factors may be responsible for the causation of this extensive skin disorder. A detailed outline of a patient's history to elicit possible triggering events, namely, infection, drug ingestion, topical application of medicaments, and sun/ultraviolet light exposure, among other factors. It is also challenging to manage the condition, because the intricate process puts an extensive strain on an already compromised body system. In addition, the original dermatosis may be masked by extensive erythema/scaling, thus making it difficult to obtain a clear-cut diagnosis. Its intriguing clinical expression in neonates/infants and children poses a serious emergent challenge for its life-threatening overture.
Erythroderma and exfoliative dermatitis are largely synonymous; however, erythroderma is the preferred term and is currently in vogue. The former is characterized by extensive and pronounced erythema, coupled with perceptible scaling, whereas the latter is conspicuous by the presence of widespread erythema and marked scaling. Accordingly, 90% or more skin-surface involvement is considered as a salient prerequisite to make a clinical diagnosis of exfoliative dermatitis.
Ultrasound (US) consists of high-frequency sound waves that are above the range of human hearing, at frequencies higher than 20 kHz. Medical ultrasound imaging is performed at much higher frequencies, typically in the MHz range. Ultrasound differs from other conventional imaging methods in important ways. First, unlike electromagnetic radiation, ultrasound waves are non-ionizing pressure waves. Second, the ultrasound signal is recorded in the reflection mode rather than the transmission mode used for x-ray and CT imaging. In ultrasound imaging, the imaged structures are not the sources that emit radiation. Instead, the sample is imaged by applying external acoustic energy to it. A “pulse echo” technique is used to create an image from longitudinal mechanical waves that interact with tissues of the body. The applied energy is reflected to the source by tissue inhomogeneities. The resulting signals carry information about their source as well as about the sample. Decoding these signals into an image requires separating the detected signal components due to the external source from those due to the sample.
Medical ultrasound imaging systems typically incorporate a piezoelectric crystal as the external signal source. This crystal vibrates in response to an oscillating electric current, producing longitudinal mechanical waves. The ultrasound signal propagates linearly through various media, including water and soft tissue, at an average speed of 1540 m/s, but does not propagate satisfactorily through bone or air. As a result, ultrasound is most suited for imaging soft tissues.
Between February and March 1981 an epidemic of hepatitis occurred in Kolhapur City, Maharashtra State, India. Approximately 1200 cases of jaundice were reported; more than 300 patients were hospitalized and three died. The epidemiological investigations showed a distinct concentration of cases in municipal ward E of the city. Investigations of the ward E water supply system disclosed gross contamination of raw water with sewage at source. The serological studies revealed that the aetiological agent responsible for this epidemic was neither hepatitis A virus nor hepatitis B virus but was likely to have been due to a non-A, non-B hepatitis virus.
Habitat fragmentation and deforestation are thought to disrupt host–parasite interactions and increase the risk of epizootic outbreaks in wild vertebrates. A total of 220 individuals from three species of African rain-forest bird (Andropadus latirostris, Andropadus virens, Cyanomitra obscura), captured in two pristine and two agroforests in Cameroon, were screened for the presence of avian haemosporidian parasites (species of Plasmodium and Haemoproteus) to test whether habitat differences were associated with differences in the prevalence of infectious diseases in natural populations. Thirteen mitochondrial lineages, including 11 Plasmodium and two Haemoproteus lineages were identified. Whereas levels of Haemoproteus spp. infections were too low to permit analysis, the prevalence of infections with Plasmodium spp. reached significantly greater levels in undisturbed mature forests. Importantly however, the significant association between forest type and parasite prevalence was independent of host density effects, suggesting that the association did not reflect changes in host species composition and abundance between forest types. Our results illustrate how characterizing land-cover differences, and hence changes, may be a prerequisite to understanding and predicting patterns of parasite infections in natural populations of rain-forest birds.