Psychosis in paratyphoid fever - a case report from Australia.

OBJECTIVE: Neuropsychiatric presentation in paratyphoid fever is not a well-known entity. In countries such as Australia, where the prevalence of enteric fever is one of the lowest, this presentation seems to be unlikely. METHOD: We present a case that demonstrates the importance of considering this possibility in Australian context in returned travellers. RESULTS: A young male, who recently returned to Australia from his home country in South East Asia, presented with abnormal behaviour in the context of febrile illness. His behaviour was characterised by grandiosity, aggression, hallucinatory behaviour and paranoia, along with disturbed biological functions. Detailed inpatient assessment revealed him to be suffering from Salmonella Paratyphi A infection and psychotic illness because of his general medical condition. Although his fever and inflammatory markers responded to antibiotics, antipsychotics were required for treatment of his mental health problems. CONCLUSION: This case demonstrates that paratyphoid fever, which is considered to be a less common variant of enteric fever, can present with neuropsychiatric manifestations.

Vision-Related Quality of Life and Ocular Parameters in End-Stage Renal Disease Patients Undergoing Hemodialysis.

Purpose: To evaluate the vision-related quality of life (VRQoL) of patients receiving hemodialysis through the assessment of the impact of vision impairment (IVI) questionnaire and ocular parameters, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), and refraction as calculated by spherical equivalent (SE) of each eye. Methods: Fifty-one patients with end-stage renal disease undergoing hemodialysis at a single center were recruited, and a total of 77 eyes were evaluated. BCVA, IOP, and SE were evaluated before and after hemodialysis (within 30 min). Results: Of the 51 patients recruited, 13 (25%) were female, 37 (73%) were male, and one (2%) chose not to specify gender. The mean age was 61.85 ± 32 years. The mobility IVI score was correlated significantly with the presence of hypertension (P = 0.01), eye drop usage (P = 0.04), and gender (P = 0.04). Emotional IVI scores were correlated significantly with diabetes (P = 0.03) and hypertension (P < 0.01). IOP significantly correlated with the IVI overall score (P = 0.02), including the reading IVI subscale and the emotional IVI subscale. Several factors were associated with posthemodialysis ocular parameters, including predialysis ocular parameters, age, and hypertension (P < 0.05 for all). Conclusions: IOP significantly correlated with VRQoL in hemodialysis patients. Demographic variables such as diabetes status, hypertension, eye drop usage, and gender also significantly correlated with subsections of the IVI questionnaire. This study investigated the relationship between ocular parameters and VRQoL in hemodialysis patients, and future longitudinal research is needed to further elucidate the mechanisms.

Right ventricular pneumatosis and extensive multi-territory air emboli in an intravenous drug user: a case report.

Background: Air emboli are a life-threatening diagnosis, which may form through a range of mechanisms. In this case, we describe the case of extensive multi-territory air emboli in a patient with a history of intravenous drug abuse. Case summary: This case describes a 41-year-old male who presented with confusion following fall with long lie. He was diagnosed with hyperkalaemia, renal failure, rhabdomyolysis, and compartment syndrome, and he developed extensive multi-territory air emboli. Air embolism was identified in arterial, venous, subcutaneous, and mediastinal territories. Echocardiography demonstrated right ventricular dilation and dysfunction, consistent with air visualized in the right coronary artery on computed tomography. The patient was transferred to the intensive care unit for close cardiac and neurological monitoring and supportive organ care, and ultimately made an uneventful recovery by 6 weeks without apparent complications from the air emboli. Discussion: The presence of multi-territory air emboli has previously been described in the setting of surgery, manipulation of intravascular catheters, pulmonary barotrauma, and in sepsis with gas-forming organisms. It has not previously been reported in intravenous drug use or sterile rhabdomyolysis. Computed tomography imaging and echocardiography are useful to diagnose air emboli and their haemodynamic impact. Our patient's case provides a novel example of multi-territory air emboli in a unique scenario.

A CD46CD[55-46] chimeric receptor, eight short consensus repeats long, acts as an inhibitor of both CD46 (MCP)- and CD150 (SLAM)-mediated cell-cell fusion induced by CD46-using measles virus.

According to their cellular receptor use, measles virus (MV) strains can be separated into two phenotypes, CD46-using and CD46-non-using. A long chimeric receptor, CD46CD[55-46], was generated from the CD46 backbone, encompassing the four short consensus repeat (SCR) domains of CD46 linked via a flexible glycine hinge to SCR1 and SCR2 of CD55, SCR3 and SCR4 of CD46 and the STP, transmembrane and cytoplasmic tail of CD46. This chimeric receptor was proficient for MV binding but deficient in mediating MV-induced cell-to-cell fusion and virus replication, possibly due to the extended distance between the MV haemagglutinin (H) binding site (CD46 SCR1-SCR2) and the cell membrane. When coexpressed with either wild-type CD46 or CD150, this fusion-incompetent receptor exerted a dominant negative effect and inhibited both cell-to-cell fusion and entry of MV with CD46-using, but not CD46-non-using, phenotype. A soluble octameric CD46-C4bpalpha exhibited similar CD46- and CD150-mediated fusion inhibition properties only against CD46-using MV. This suggests that the long CD46CD[55-46] receptor acts by sequestering incoming MV prior to its binding to the shorter functional CD46 or CD150 receptor.

Ligand binding determines whether CD46 is internalized by clathrin-coated pits or macropinocytosis.

CD46 is a ubiquitous human cell surface receptor for the complement components C3b and C4b and for various pathogens, including the measles virus and human herpes virus 6. Ligand binding to CD46 affects (i) protection of autologous cells from complement attack by breakdown of complement components, (ii) intracellular signals that affect the regulation of immune cell function, (iii) antigen presentation, and (iv) down-regulation of cell surface CD46. Recent evidence indicates that CD46 signaling can link innate and acquired immune function. The molecular mechanisms for these processes and the importance of intracellular trafficking of the receptor have not yet been elucidated. We demonstrate here that, in nonlymphoid cells, CD46 is constitutively internalized via clathrin-coated pits, traffics to multivesicular bodies, and is recycled to the cell surface. However, cross-linking of CD46 at the cell surface, by either multivalent antibody or by measles virus, induces pseudopodia that engulf the ligand in a process similar to macropinocytosis, and leads to the degradation of cell surface CD46. Thus, we have elucidated two pathways for CD46 internalization, which are regulated by the valence of cross-linking of CD46 and which utilize either clathrin-coated pits or pseudopodial extension. This has important implications for CD46 signaling, antigen presentation, CD46 down-regulation, and engulfment of pathogens.

Characterization of a CD46 transgenic pig and protection of transgenic kidneys against hyperacute rejection in non-immunosuppressed baboons.

Human membrane cofactor protein (CD46) controls complement activation and when expressed sufficiently as a transgene protects xenografts against complement-mediated rejection, as shown here using non-immunosuppressed baboons and heterotopic CD46 transgenic pig kidney xenografts. This report is of a carefully engineered transgene that enables high-level CD46 expression. A novel CD46 minigene was validated by transfection and production of a transgenic pig line. Pig lymphocytes were tested for resistance to antibody and complement-mediated lysis, transgenic tissues were characterized for CD46 expression, and kidneys were transplanted to baboons without immunosuppression. Absorption of anti-Galalpha(1,3)Gal epitope (anti-GAL) serum antibodies was measured. Transgenic pigs expressed high levels of CD46 in all tissues, especially vascular endothelium, with stable expression through three generations that was readily monitored by flow cytometry of transgenic peripheral blood mononuclear cells (PBMC). Transgenic PBMC pre-sensitized with antibody were highly resistant to human complement-mediated lysis which readily lysed normal pig PBMC. Normal pig kidneys transplanted without cold ischemia into non-immunosuppressed adult baboons survived a median of 3.5 h (n = 7) whereas transgenic grafts (n = 9), harvested at approximately 24-h intervals, were either macroscopically normal (at 29, 48 and 68 h) or showed limited macroscopic damage (median > 50 h). Microscopic assessment of transplanted transgenic kidneys showed only focal tubular infarcts with viable renal tissue elsewhere, no endothelial swelling or polymorph adherence and infiltration by lymphocytes beginning at 3 days. Coagulopathy was not a feature of the histology in four kidneys not rejected and assessed at 48 h or later after transplantation. Baboon anti-GAL serum antibody titers were high before transplantation and, in one extensively analyzed recipient, reduced approximately 8-fold within 5.5 h. The data demonstrate that a single CD46 transgene controls hyperacute kidney graft rejection in untreated baboons despite the presence of antibody and complement deposition. The expression levels, tissue distribution and in vitro functional tests indicate highly efficient CD46 function, controlling both classical and alternative pathway complement activation, which suggests it might be the complement regulator of choice to protect xenografts.