Enzyme Defects in the Porphyrias and their Relevance to the Biochemical Abnormalities in these Disorders

Defects in enzymes of the heme biosynthesis pathway underlie the biochemical abnormalities which occur in the porphyrias. Porphyrins and porphyrin precursors are accumulated and excreted in excessive amounts because of the enzyme defects. This is illustrated by studies in protoporphyria and variegate porphyria, disorders in which the biochemical abnormalities indicate a defect(s) in the terminal part of the heme biosynthesis pathway. The activity of heme synthease (ferrochelatase), which catalyzes the chelation of ferrous iron to protoporphyrin, is deficient in tissues of patients with protoporphyria. This causes protoporphyrin to be accumulated and excreted excessively. In variegate porphyria protoporphyrinogen oxidase, which catalyzes the oxidation of protoporphyrinogen to protoporphyrin, appears to be defective. As a result, protoporphyrinogen may be excreted in increased amounts in bile, where it is subsequently auto-oxidized to protoporphyrin. The following questions have arisen as a result of the demonstrations of enzyme defects in tissues of patients with porphyria: (1) Will different defects in the same enzyme be found among patients who fulfill the clinical and biochemical criteria for diagnosis of a specific porphyria? That is, does genetic heterogeneity exist in each of the porphyrias? (2) Why do some patients with an enzyme defect not have biochemical abnormalities? (3) Why is one type of tissue, usually the liver, the major site of expression of the biochemical abnormality, when the enzyme defect can be demonstrated in all tissues

Preliminary Altitude Performance Characteristics of the J57-P-1 Turbojet Engine with Fixed-area Exhaust Nozzle

An investigation to determine the altitude performance of the J57-P-1 turbojet engine and components was conducted at the NACA Lewis altitude wind tunnel. Data were obtained over a corrected inboard rotor speed range from 56 to 106 percent of rated speed, with intercompressor bleeds both open and closed, at altitudes from 15,000 to 50,000 feet and at a flight Mach number of 0.81. The corresponding range of Reynolds number indices was from 0.858 to 0.213. All data presented were obtained with a fixed-area exhaust nozzle sized according to the manufacturer's specification. Over-all engine performance parameters are presented as functions of inboard rotor speed corrected on the basis of engine inlet temperature. Component parameters are presented as functions of their respective corrected rotor speeds. A tabulation of all performance data is included in addition to the graphical presentation. Corrected net thrust is unusually sensitive to changes in corrected inboard rotor speed in the high speed region. A change of 1 percent in speed, at sated speed, produced a change of 6 percent in corrected net thrust . At rated engine speed, increasing the altitude from 15,000 to 50,000 feet at a constant flight Mach number of 0.81 increased the specific fuel consumption 13 percent but did not affect corrected net thrust

Metagenomic deep sequencing of aqueous fluid detects intraocular lymphomas.

IntroductionCurrently, the detection of pathogens or mutations associated with intraocular lymphomas heavily relies on prespecified, directed PCRs. With metagenomic deep sequencing (MDS), an unbiased high-throughput sequencing approach, all pathogens as well as all mutations present in the host's genome can be detected in the same small amount of ocular fluid.MethodsIn this cross-sectional case series, aqueous fluid samples from two patients were submitted to MDS to identify pathogens as well as common and rare cancer mutations.ResultsMDS of aqueous fluid from the first patient with vitreal lymphoma revealed the presence of both Epstein-Barr virus (HHV-4/EBV) and human herpes virus 8 (HHV-8) RNA. Aqueous fluid from the second patient with intraocular B-cell lymphoma demonstrated a less common mutation in the MYD88 gene associated with B-cell lymphoma.ConclusionMDS detects pathogens that, in some instances, may drive the development of intraocular lymphomas. Moreover, MDS is able to identify both common and rare mutations associated with lymphomas

Family centred care before and during life-sustaining treatment withdrawal in intensive care: A survey of information provided to families by Australasian critical care nurses

publisher: Elsevier articletitle: Family centred care before and during life-sustaining treatment withdrawal in intensive care: A survey of information provided to families by Australasian critical care nurses journaltitle: Australian Critical Care articlelink: http://dx.doi.org/10.1016/j.aucc.2016.08.006 content_type: article copyright: © 2016 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved

An integrative review of how families are prepared for, and supported during withdrawal of life-sustaining treatment in intensive care

AIM: To conduct an integrative review on how nurses prepare families for and support families during withdrawal of life-sustaining treatments in intensive care. BACKGROUND: End-of-life care is widely acknowledged as integral to the practice of intensive care. However, little is known about what happens after the decision to withdraw life-sustaining treatments has been made and how families are prepared for death and the dying process. DESIGN: Integrative literature review. DATA SOURCES: MEDLINE, CINAHL Plus, PsychINFO, PUBMED, Scopus, EMBASE and Web of Knowledge were searched for papers published between 2000 - May 2015. REVIEW METHODS: A five stage review process, informed by Whittemore and Knafl\u27s methodology was conducted. All papers were reviewed and quality assessment performed. Data were extracted, organised and analysed. Convergent qualitative thematic synthesis was used. RESULTS: From an identified 479 papers, 24 papers were included in this review with a range of research approaches: qualitative (n=15); quantitative (n=4); mixed methods (n=2); case study (n=2); and discourse analysis (n=1). Thematic analysis revealed the nurses: equipped families for end of life through information provision and communication; managed the withdrawal of life-sustaining treatments to meet family need; and continued care to build memories. CONCLUSION: Greater understanding is needed of the language that can be used with families to describe death and dying in intensive care. Clearer conceptualisation of the relationship between the medically focussed withdrawal of life-sustaining treatments and patient/family centred end-of-life care is required making the nursing contribution at this time more visible

Cryptococcal choroiditis in advanced AIDS with clinicopathologic correlation.

PurposeTo describe a case of disseminated cryptococcal meningitis with multifocal choroiditis and provide optical coherence tomography (OCT) findings correlated with described histopathology in a patient with advanced acquired immunodeficiency syndrome (AIDS).ObservationsThe patient was a 54-year-old man with AIDS who presented with dyspnea and headache followed by acute vision loss. OCT demonstrated a lesion with a small area of fluid that was limited by a more prominent and irregular external limiting membrane with underlying nodular choroidal thickening, mild RPE disorganization, and hyperreflectivity of the overlying photoreceptor layer. Patient was found to have disseminated cryptococcal infection and passed away despite aggressive therapy. Autopsy was performed including bilateral enucleation and a Cryptococcus lesion was confirmed on histopathology.Conclusion and importanceThis case highlights the clinical, imaging, and histopathologic findings of cryptococcal choroiditis and provides a review of the updated treatment recommendations for disseminated infection in a patient with advanced AIDS. Although currently fundoscopy has proven most useful in directing the diagnostic algorithm in choroiditis in the setting of advanced immunosuppression, OCT may provide insight into the spread of Cryptococcus within the eye