A case report of transfusion-related acute lung injury during plasma exchange therapy for thrombotic thrombocytopenia purpura

Transfusion-related acute lung injury (TRALI) is a transfusion reaction that is often under recognized and underreported. Implications for diagnosis not only influence treatment considerations but also extend to donor selection, donor deferral and ultimately the safety of the final blood product. We report a case of a previously well 19-year-old female who presented a one week history of flu-like symptoms and mucosal bleeding. Laboratory results confirmed the diagnosis of thrombotic thrombocytopaenia purpura (TTP) and she was commenced on plasma exchange. During her second day of plasma exchange, she developed dyspnoea and rigors. Examination and investigation findings were consistent with a clinical diagnosis of TRALI. Granulocytes immunofluorescent test (GIFT - flow cytometry) was performed and cross reactivity was demonstrated between the patient's granulocytes and plasma from one of the nine donor fresh frozen plasma (FFP) packs. She made a full recovery. TRALIa accounts for 7% of all adverse events reported in the Serious Hazards of Transfusion (SHOT) database and has a mortality rate between 5-25%. Apheresis patients are a particularly vulnerable group of patients where clinical recognition and rapid laboratory confirmation of TRALI is imperative to minimize the risk of further patient exposure to donor granulocyte or human leukocyte antigen (HLA) antibodies. The provision of plasma from male donors may additionally reduce exposure. On a wider scale, rapid donor identification and deferral maintains the safety of the national blood supply.     

Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients

It has been suggested that the retinoid X receptor beta (RXRB) gene is a risk factor for Wegener's granulomatosis. We addressed if there is a functional difference in the response to retinoic acid (RA) and vitamin D in Antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis (AASV) patients and if this was associated with RXRB genotypes. TNFα and IL-10 production were measured in whole blood assay from AASV patients (n = 51) and healthy controls (HC, n = 67). One micromolar of 1,25-(OH)₂ D3, 9-cis RA (9c-RA) or all-trans RA (ATRA) was added to the assay. Genotyping was performed for exons 7 and 2 of the RXRB gene and for a microsatellite in vicinity of the RXRB gene. Lipopolysaccharide (LPS) mediated TNFα production and IL-10 were significantly lower in patients. Addition of 1,25-(OH)₂ D3, ATRA or 9c-RA, blunted TNFα production, more pronounced in patients. Although all three compounds inhibited IL-10 production significantly in HC, only 1,25-(OH)₂ D3 was found to be effective in patients. Allele distribution of the RXRB microsatellite differed significantly between patients and HC. This was not found for the SNP in exons 2 and 7. Genotype of the latter correlated with the ability of 1,25-(OH)₂ D3 and ATRA to inhibit IL-10 production. We provide immunological evidence for a functional difference in vitamins D and A responsiveness in AASV patients. Since the inhibition of TNFα was more effective in patients, vitamin D supplementation might be an additional therapeutical approach.     

Detecting EGFR alterations in clinical specimens—pitfalls and necessities

We investigated the epidermal growth factor receptor (EGFR) status in early stage lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell lung cancers, adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas were analyzed using a combination of techniques for the analysis of protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific antibodies. High expression of total EGFR protein was correlated to high gene copy numbers but did not reflect the mutational status of the tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific antibodies, and we also raise some other issues regarding the use of the mutation-specific antibodies, for example concerning heterogeneous expression of the mutated protein, optimal antibody dilution, and discrepancies between staining results and PCR.     

Long-term treatment costs and cost-effectiveness of restoration repair versus replacement

ObjectivesWhen managing partially defective restorations, dentists can choose between repair and replacement. We aimed to assess the long-term treatment costs of repairs and replacements.MethodsPartially defective anterior and posterior composite restorations in permanent teeth had been repaired or replaced in a German university hospital and were retrospectively followed until censoring or one of the following events: (1) Extraction, (2) Major complications including placement of indirect restorations, endodontic treatments and extractions, or (3) Any complications including major complications and further direct restorations. Costs were estimated from a German mixed public-private-payer perspective. Cost-effectiveness differences were described using median-based incremental-cost-effectiveness ratios (ICER_MEDIAN). Statistical analysis was performed using generalized linear mixed modeling (GLM), Chi²-test, and Wilcoxon rank-sum test (p < 0.05).ResultsA total of 616 repairs in 468 patients (follow-up: 4.9 ± 4.1 years) and 264 replacements in 218 patients (follow-up: 4.8 ± 4.3) were included. While replacements were associated with higher initial treatment costs, median annualized treatment costs did not significantly differ between repair (47.58 Euro [IQR: 24.41–107.04]) and replacement (50.64 Euro [IQR: 26.30–118.78]; p > 0.05), but were higher for molars (75.53 Euro [IQR: 24.41–92.18]) than incisors (45.03 Euro [IQR: 28.19–168.50]; p = 0.011). The difference in the % of extractions, major and any complications were minimal between both groups. The mean ICER_MEDIAN of replacement vs. repair was -146.8 Euro/% when extractions were considered as outcomes. Regarding major and any complications, mean ICER_MEDIAN amounted to 67.6 Euro/% and 23.9 Euro/%, respectively.SignificanceRepairs and replacements of partially defective restorations showed similar long-term costs and cost-effectiveness.     

A combined clinical,neuropsychological, and neuroanatomical study of adults with high functioning autism

Introduction. Three hypotheses concerning associations between neuroanatomical abnormalities, neuropsychological impairments, and the behavioural manifestations of autism were investigated. The primary hypothesis was that the social interaction impairments diagnostic of autism are associated with deficits of socioemotional perception and abnormalities of the amygdala. One subsidiary hypothesis was that the learning and language impairments that occur in less able individuals with autism are associated with impaired memory, and with abnormalities of hippocampal regions. A second subsidiary hypothesis was that the repetitive behaviour diagnostic of autism is associated with executive deficits and with abnormalities of the prefrontal cortex. Associations between the neuroanatomical regions investigated were also examined.Methods. Ten adult males with high functioning autism (HFA) were compared with 10 healthy controls matched for age, sex, verbal and nonverbal ability. Hypothesis-driven structural MRI and neuropsychological tests were used to collect neuroanatomical and neuropsychological data on all subjects. A version of the Wing Autism Diagnostic Interview Checklist was used to collect clinical data on the HFA subjects.Results. Strong convergent evidence in support of the amygdala hypothesis was obtained, and preliminary support for the hippocampal/parahippocampal hypothesis. No clear evidence was obtained in support of the prefrontal hypothesis. Patterns of associations amongst volume measures within and between medial temporal and prefrontal regions suggest stronger within-region and weaker between-region associations in the HFA group compared with controls.Conclusions. These findings are discussed in terms of a model of autism in which selective abnormalities of the amygdala and hippocampus (in all cases) and of the parahippocampal gyrus (in lower functioning cases) are implicated, and in which a disruption of coordinated limbic and prefrontal activity may be critical.     

Stalking as paranoid attachment: A typological and dynamic model

Abstract

Stalking encompasses a wide range of behavioral patterns, risk factors, interpersonal dynamics, and dangerousness. To account for these diverse phenomena, we propose that stalking behavior is best conceptualized by a dynamic interaction of attachment styles and psychodynamic phenomena. This paper articulates a model that explains stalking behavior within the framework of attachment theory. Four prototypical configurations of stalkers and their victims are developed. Each configuration is discussed in terms of a pattern of internal representations, affective constellations, combinations of aggression and narcissism, and potential for future violence. The four configurations proposed here are maintained through stalkers' over ideational linkage fantasies and projective identifications, which range from shame-prone and needy idealization to malevolent torment of the victim. Our model arrays erotomanic, jealous, and persecutory attachments along a continuum of increasingly paranoid and pathological identifications. We argue that these prototypical attachment configurations provide a theoretically driven means of differentiating phases of stalking, and as such provide useful leads in the empirical study and clinical assessment, treatment, and management of stalkers.     

Two cases of brand-specific albumin sensitivity in patients receiving regular therapeutic plasma exchange

Therapeutic plasma exchange (PLEX) involves the removal of detrimental substances, commonly pathogenic antibodies or toxins, from a patient’s blood by exchanging their plasma with a replacement fluid. While a variety of replacement fluids are available, human albumin (4–5 %) is the most commonly used, as it is widely available, easily stored, and generally well tolerated. Despite its excellent safety profile, adverse reactions to albumin are well documented, ranging in severity from mild allergic symptoms to severe anaphylaxis. This report describes two cases of patients receiving frequent PLEX who developed sensitivities to human albumin. These patients differed substantially in the manifestations of their symptoms, the duration of their treatment, and their medical indication for PLEX. In both cases, symptom onset occurred shortly after completion of plasma exchange procedures and lasted for several hours. Symptoms disappeared when the patients were switched to albumin from a different manufacturer, suggesting that the reaction was specific to that formulation of albumin and not to the albumin itself. These cases highlight the possibility of manufacturer-specific acquired albumin sensitivities and provide a simple framework for the initial approach to the management of such reactions.