Hemophagocytic Lymphohistiocytosis mimics many common conditions: case series and review of literature.

Introduction. Hemophagocytic lymphohistiocytosis (HLH), a rare but potentially fatal disease, is characterized by excessive immune activation and cytokine release which stimulates bone marrow macrophages to engulf hematopoietic cells. HLH could be secondary to infections: viral, fungal, and bacterial; malignancies and autoimmune diseases. The diagnosis of HLH is usually delayed due to the presence of non-specific symptoms at presentation. This delay contributes to increased mortality. Cases and review. We present the case of 4 patients who presented with subjective fevers and extreme fatigue. Patients all had systemic inflammatory response syndrome (SIRS). All patients were initially managed as in sepsis from an underlying infection. All unfortunately progressed to multiple organs dysfunction and died. The underlying causes for HLH in the patients were considered to be: HIV/AIDS, T cell lymphoma, histoplasmosis and juvenile rheumatoid arthritis. We have also included a brief review of the literature on HLH highlighting the treatment and outcomes of patients in case series; and the many conditions which can trigger HLH. Conclusion. Patients with HLH usually share various non-specific symptoms, such as fever and malaise, with patients across a wide spectrum of conditions: from bacterial sepsis to malignancies. Since early suspicion and diagnosis is critical to prompt therapy and improved mortality, including HLH as a possible cause of fever particularly in patients with prolonged fever of unknown origin and cytopenias will be crucial.

Overcoming Barriers to Experience Benefits: A Qualitative Analysis of Electronic Health Records and Health Information Exchange Implementation in Local Health Departments.

INTRODUCTION: Electronic Health Records (EHRs) and Health Information Exchanges (HIEs) are changing surveillance and analytic operations within local health departments (LHDs) across the United States. The objective of this study was to analyze the status, benefits, barriers, and ways of overcoming challenges in the implementation of EHRs and HIEs in LHDs. METHODS: This study employed a mixed methods approach, first using the 2013 National Profile of LHDs survey to ascertain the status of EHR and HIE implementation across the US, as well as to aid in selection of respondents for the second, interview-based part of project. Next, forty-nine key-informant interviews of local health department staff were conducted. Data were coded thematically and independently by two researchers. Coding was compared and re-coded using the consensus definitions. RESULTS: Twenty-three percent of LHDs nationwide are using EHRs and 14 percent are using HIEs. The most frequently mentioned benefits for implementation were identified as care coordination, retrieval or managing information, and the ability to track outcomes of care. A few mentioned barriers included financial resources, resistance to change, and IT related issues during implementation. DISCUSSION: Despite financial, technical capacity, and operational constraints, leaders interviewed as part of this project were optimistic about the future of EHRs in local health departments. Recent policy changes and accreditation have implications of improving processes to affect populations served. CONCLUSIONS: Overcoming the challenges in implementing EHRs can result in increased efficiencies in surveillance and higher quality patient care and tracking. However, significant opportunity cost does exist.

Multisector Health Policy Networks in 15 Large US Cities.

CONTEXT: Local health departments (LHDs) have historically not prioritized policy development, although it is one of the 3 core areas they address. One strategy that may influence policy in LHD jurisdictions is the formation of partnerships across sectors to work together on local public health policy. DESIGN: We used a network approach to examine LHD local health policy partnerships across 15 large cities from the Big Cities Health Coalition. SETTING/PARTICIPANTS: We surveyed the health departments and their partners about their working relationships in 5 policy areas: core local funding, tobacco control, obesity and chronic disease, violence and injury prevention, and infant mortality. OUTCOME MEASURES: Drawing on prior literature linking network structures with performance, we examined network density, transitivity, centralization and centrality, member diversity, and assortativity of ties. RESULTS: Networks included an average of 21.8 organizations. Nonprofits and government agencies made up the largest proportions of the networks, with 28.8% and 21.7% of network members, whereas for-profits and foundations made up the smallest proportions in all of the networks, with just 1.2% and 2.4% on average. Mean values of density, transitivity, diversity, assortativity, centralization, and centrality showed similarity across policy areas and most LHDs. The tobacco control and obesity/chronic disease networks were densest and most diverse, whereas the infant mortality policy networks were the most centralized and had the highest assortativity. Core local funding policy networks had lower scores than other policy area networks by most network measures. CONCLUSION: Urban LHDs partner with organizations from diverse sectors to conduct local public health policy work. Network structures are similar across policy areas jurisdictions. Obesity and chronic disease, tobacco control, and infant mortality networks had structures consistent with higher performing networks, whereas core local funding networks had structures consistent with lower performing networks.

The Double Disparity Facing Rural Local Health Departments.

Residents of rural jurisdictions face significant health challenges, including some of the highest rates of risky health behaviors and worst health outcomes of any group in the country. Rural communities are served by smaller local health departments (LHDs) that are more understaffed and underfunded than their suburban and urban peers. As a result of history and current need, rural LHDs are more likely than their urban peers to be providers of direct health services, leading to relatively lower levels of population-focused activities. This review examines the double disparity faced by rural LHDs and their constituents: pervasively poorer health behaviors and outcomes and a historical lack of investment by local, state, and federal public health entities.

Acceptability, feasibility and costs of universal offer of rapid point of care testing for HIV in an acute admissions unit: results of the RAPID project.

OBJECTIVES: UK guidance recommends that acute medical admissions are offered an HIV test. Our aim was to determine whether a dedicated staff member using a multimedia tool, a model found effective in the USA, is an acceptable, feasible, and cost-effective model when translated to a UK setting. METHODS: Over 4 months in 2010, a health advisor (HA) approached 19-65-year-olds at a central London acute medical admissions unit and offered a rapid HIV point of care test (POCT) with the aid of an educational video. Feasibility and acceptability were assessed through surveys and uptake rates. Costs per case of HIV infection identified were established. RESULTS: Of the 606 eligible people admitted during the pilot, 324 (53.5%) could not be approached or were individuals for whom testing was deemed inappropriate. In total, 23.0% of eligible admissions had an HIV POCT. Of the patients who watched the video and had not recently been tested for HIV, 93.6% (131 of 140) agreed to an HIV test; four further patients had an HIV test but did not watch the video. Three tests (2.2%; three of 135) were reactive and all were confirmed HIV positive on laboratory testing. HIV testing in this setting was felt to be appropriate by 97.5% of individuals. The cost per patient was £21, and the cost per case of HIV identified was £1083. CONCLUSIONS: Universal POCT HIV testing in an acute medical setting, facilitated by an educational video and dedicated staff, appears acceptable, feasible, effective, and low cost. These findings support the recommendation of HIV testing for all medical admissions in high-prevalence settings, although with this model a significant proportion remained untested.

Unsuspected swallowing of a partial denture.

We report a case of a swallowed partial denture in a 51-year-old man who presented with progressive dysphagia, odynophagia, and fevers. Imaging studies were initially interpreted as supraglottitis with laryngeal inflammation, which was confirmed by direct visualization with flexible endoscopy. Despite appropriate therapy, the patient's symptoms persisted and rigid laryngoscopy was performed, which revealed a partial denture in the hypopharynx and upper esophagus. The subtle imaging appearance of a swallowed denture is discussed.

Rehabilitation of patients with extended facial and craniofacial resection.

Surgery of benign and malignant disease of the nose and sinuses can result in disfigurement and disability. Many patients have speech, mastication, and swallowing problems, anosmia, and pain. If the orbit is retained, visual loss, dystopia, diplopia, and epiphora can occur. This study reviews the senior author's experience with 34 patients over the last 18 years. Group and case analyses demonstrate that in patients with cancer, the eye can be preserved if one anatomical boundary is retained beyond a negative frozen section margin. Dystopia can be prevented by reconstruction of the floor with skin and fascial grafts or flaps. Epiphora can be reduced by repair of the medial canthus and dacryocystorhinostomy. Evidence is presented for prosthetic management of speech and swallowing and restoration of cheek contour. Case examples are used to illustrate the surgical techniques.

The enlarged vestibular aqueduct syndrome (EVA syndrome).

The presentation to the Department of Pediatric Otolaryngology at the Children's Hospital of Michigan of a series of patients with sensorineural hearing loss and enlargement of the vestibular aqueduct prompted exploratory tympanotomy in three patients (two unilateral and one bilateral), for a total of four ears. These explorations were prompted by progression and/or fluctuation of hearing levels. The discovery of abnormal round windows in all four ears with a post-traumatic fistula present in one ear suggested the presence of a new association. A previously undescribed association of an enlarged vestibular aqueduct, sensorineural hearing loss and round window abnormality with potential fistula formation was identified. A review of the anatomy and physiology, literature review, and a prospective analysis with discussion of eight patients with enlarged vestibular aqueduct syndrome evaluated and treated at Children's Hospital of Michigan, is presented. We conclude that all children with sensorineural hearing loss should undergo extensive evaluation to determine etiology, including radiographic studies of the temporal bone. Further, the presence of an enlarged vestibular aqueduct should prompt the otolaryngologist to consider the presence of a round window abnormality and the potential for predisposition to perilymph fistula.

The effect of swallowing bolus and head position on eustachian tube function via sonotubometry.

Eustachian tube function was evaluated by sonotubometry in otologically normal young adults. The purpose of the research was to determine if the incidence or duration of eustachian tube opening would be altered with changes in swallowing bolus volume or changes in head rotation. The subject performed multiple swallows of 10 cc water bolus and dry swallows (saliva), with the head in the straight-forward, turned right, and turned left positions. Both ears were evaluated. The average incidence and duration of eustachian tube opening for all swallows was 74% (398 msec). No significant differences were found with any combination of bolus type or head position, suggesting that neither liquid bolus volume nor head rotation need be controlled when sonotubometry is performed.

The E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity.

In addition to members of the Orthomyxoviridae and Paramyxoviridae, several coronaviruses have been shown to possess receptor-destroying activities. Purified bovine coronavirus (BCV) preparations have an esterase activity which inactivates O-acetylsialic acid-containing receptors on erythrocytes. Diisopropyl fluorophosphate (DFP) completely inhibits this receptor-destroying activity of BCV, suggesting that the viral enzyme is a serine esterase. Treatment of purified BCV with [3H]DFP and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins revealed that the E3 protein was specifically phosphorylated. This finding suggests that the esterase/receptor-destroying activity of BCV is associated with the E3 protein. Furthermore, treatment of BCV with DFP dramatically reduced its infectivity in a plaque assay. It is assumed that the esterase activity of BCV is required in an early step of virus replication, possibly during virus entry or uncoating.

Determination of the mutation rate of a retrovirus.

The mutation rate of Rous sarcoma virus (RSV) was measured. Progeny descended from a single virion were collected after one replication cycle, and seven regions of the genome were analyzed for mutations by denaturing-gradient gel electrophoresis. In all, 65,250 nucleotides were screened, yielding nine mutations, and the RSV mutation rate was calculated as 1.4 x 10(-4) mutations per nucleotide per replication cycle. These results indicate that RSV is an extremely mutable virus. We speculate that the mutation rate of a virus may correlate inversely with the effectiveness of vaccination against a given virus and suggest that prevention of retrovirus-mediated disease via vaccination may prove difficult.

Measurement of the mutation rates of animal viruses: influenza A virus and poliovirus type 1.

Epidemiologic and genetic evidence suggests that influenza A viruses evolve more rapidly than other viruses in humans. Although the high mutation rate of the virus is often cited as the cause of the extensive variation, direct measurement of this parameter has not been obtained in vivo. In this study, the rate of mutation in tissue culture for the nonstructural (NS) gene of influenza A virus and for the VP1 gene in poliovirus type 1 was assayed by direct sequence analysis. Each gene was repeatedly sequenced in over 100 viral clones which were descended from a single virion in one plaque generation. A total of 108 NS genes of influenza virus were sequenced, and in the 91,708 nucleotides analyzed, seven point changes were observed. A total of 105 VP1 genes of poliovirus were sequenced, and in the 95,688 nucleotides analyzed, no mutations were observed. We then calculated mutation rates of 1.5 X 10(-5) and less than 2.1 X 10(-6) mutations per nucleotide per infectious cycle for influenza virus and poliovirus, respectively. We suggest that the higher mutation rate of influenza A virus may promote the rapid evolution of this virus in nature.

Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particle-bound ligands to specific receptors on the macrophage plasma membrane.

These experiments were designed to evaluate the role of macrophage plasma membrane receptors for the third component of complement (C) and for the Fc portion of IgG in the ingestion phase of phagocytosis. Sheep erythrocyte (E) were coated with anti-E IgG [E(IgG)]; these E(IgG) were then attached to cultivated monolayers of mouse peritoneal macrophages under conditions which reversibly inhibit ingestion of E(IgG). The E(IgG)-macrophage complexes were further incubated under similar conditions with an antimacrophage IgG fraction which blocks Fc receptor-mediated ingestion but has no effect upon ingestion mediated by other phagocytic receptors. When these cultures were subsequently incubated under conditions optimal for particle ingestion, phagocytosis of the IgG-coated erythrocytes did not occur; the erythrocytes remained bound to the Fc receptors of the macrophage plasma membrane. To determine whether ligands must cover the entire surface of an attached particle to permit ingestion of that particle, C-coated E [E(IgM)C] were bound to the C receptors of thioglycollate-induced (activated) macrophages at 4 degrees C. E(IgM)C-macrophage complexes were then trypsinized at 4 degrees C, a procedure which resulted in cleavage of erythrocyte-bound C3b molecules to a form of C3 not recognized by the macrophage receptors for C3b. Under the conditions used, trypsin did not affect the attachment of E(IgM)C to the macrophage surface or the macrophage receptors for C3b. When these trypsin treated E(IgM)C-macrophage complexes were incubated at 37 degrees C, the bound E(IgM)C were not ingested; the erythrocytes remained attached to the macrophage plasma membrane via the macrophage's C receptors. These results indicate that attachment of a particle to specific receptors on the macrophage plasma membrane is not sufficient to trigger ingestion of that particle. Rather, ingestion requires the sequential, circumferential interaction of particle-bound ligands with specific plasma membrane receptors not involved in the initial attachment process.

The effect of dried mussel extract on an induced polyarthritis in rats.

A polyarthritis was induced in a number of rats by the intradermal injection of a modified Freund's adjuvant into the right foot pad. Powered extract of New Zealand mussel fed to the rats did not have any beneficial effect on either the development or the severity of the arthritis.