Almost a tragedy: severe methotrexate toxicity in a hemodialysis patient treated for ectopic pregnancy

Background

Methotrexate (MTX), an antimetabolite of folic acid, is the drug of choice for the nonsurgical management of ectopic pregnancy. MTX-related toxicity may include leukopenia, thrombocytopenia, pancytopenia, nausea, vomiting, stomatitis, mucositis, and liver and lung toxicity, depending primarily on the dosage of the drug and patients' renal function. Currently, the use of MTX in hemodialysis patients, even at a low dosage, is controversial, and no clear-cut guidelines are available.

Case report

We report here a rare case of a life-threatening complication characterized by severe pancytopenia and skin and mucosal injury, which developed in a young patient on hemodialysis after oral treatment with MTX for ectopic pregnancy.

Conclusion

We conclude that even low-dose MTX administration is not to be used in patients with renal insufficiency, and when no other therapeutic options are available we suggest taking several clinical measures to prevent or treat myelosuppression.     

Effect of Different Surface Treatments of Lithium Disilicate on the Adhesive Properties of Resin Cements

The aim of the current study was to evaluate the influence of hydrofluoric (HF) acid concentration and conditioning time on the shear bond strength (SBS) of dual cure resin cement to pressed lithium disilicate ceramic compared to treatment with an Etch and Prime self-etching glass-ceramic primer (EP). A total of 100 samples of pressed lithium disilicate (IPS e.max Press, Ivoclar Vivadent) were randomly divided into five groups (n = 20) according to surface treatment: two different concentrations of HF (5% or 9%), for different durations (20 or 90 s), or treatment with EP. Adhesion of light-cured resin cement to the treated surface was tested by the SBS test. The substrate surfaces of the specimen after failures were examined by SEM. Data were analyzed using Weibull distribution. The highest cumulative failure probability of 63.2% of the shear bond strength (η parameter) values was in the 9% HF −90 s group (17.71 MPa), while the lowest values were observed in the 5% HF −20 s group (7.94 MPa). SBS values were not affected significantly by the conditioning time (20 s or 90 s). However, compared to treatment with 5% HF, surface treatment with 9% HF showed a significantly higher η (MPa) as well as β (reliability parameter). Moreover, while compared to 9% HF for 20 s, EP treatment did not differ significantly in SBS values. Examination of the failure mode revealed a mixed mode of failure in all the groups. Within the limits of this study, it is possible to assume that IPS e.max Press surface treatment with 9% HF acid for only 20 s will provide a better bonding strength with resin cement than using 5% HF acid.     

Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin

Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication.     

What is and isn’t working: Factors involved in sustaining community‐based health and participation initiatives for people ageing with intellectual and developmental disabilities

As people with intellectual and developmental disabilities (I/DD) age, it is important that I/DD agencies are prepared to support healthy ageing in homes and in communities. This study explored supports and barriers to sustaining community‐based health and participation initiatives (CBHPI) for people ageing with I/DD living in group homes managed by agencies. The study utilized interviews and photovoice with 70 participants—35 individuals with I/DD and 35 management/direct support agency staff. Data were analysed through content analysis and triangulation of data where five themes emerged: Agency values and policies related to healthy ageing; resources and staff competencies; communication between management and staff; community/university partnerships; and peer relations. Findings show that I/DD agencies and people with I/DD value CBHPI, but they find them difficult to sustain due to limited resources and lack of training specific to ageing with I/DD. Conducting system‐level research within I/DD agencies to include first‐person accounts of people with I/DD, staff and management provides insight on how to effectively support the needs of people with I/DD to improve their health and community participation as they age.     

The use of corticosteroids does not influence CD4+ lymphocyte recovery in HIV-infected patients with advanced immunodeficiency

ABSTRACT

Corticosteroids inhibit HIV-related immune activation and seem to have a mild favorable effect on immunological recovery in patients with CD4⁺ counts ≥200?cells/mm³. Data in patients with advanced immunodeficiency are lacking. We analyzed whether corticosteroids negatively influence the short-term CD4⁺ lymphocyte recovery in patients with CD4⁺ cell counts <200?cells/mm³ started on combination antiretroviral therapy (cART). We performed a retrospective cohort analysis including all HIV-infected patients under follow-up in our hospital with a documented episode of Pneumocystis Jirovecii Pneumonia (PJP) in the cART era. CD4⁺ lymphocyte recovery was assessed at three months after the episode of PJP and subsequent start of cART, comparing patients that received adjunctive corticosteroids (AC) versus patients that did not receive corticosteroids (standard care (SC)). In total, 66 patients with an episode of PJP were identified with 38 patients in the AC-group versus 28 patients in the SC-group. Almost all baseline characteristics were similar, including mean CD4⁺ lymphocyte counts. After three months, the mean CD4⁺ cell count did not differ; 222?cells/mm³ for the SC-group versus 259?cells/mm³ for the AC-group (p?=?.29). The use of corticosteroids does not alter CD4⁺ lymphocyte recovery in HIV-infected patients with advanced immunodeficiency in the first months of antiretroviral therapy.     

Antipsychotics and the risk of sudden cardiac death

BACKGROUND: Antipsychotics have been associated with prolongation of the corrected QT interval and sudden cardiac death. Only a few epidemiological studies have investigated this association. We performed a case-control study to investigate the association between use of antipsychotics and sudden cardiac death in a well-defined community-dwelling population. METHODS: We performed a population-based case-control study in the Integrated Primary Care Information (IPCI) project, a longitudinal observational database with complete medical records from 150 general practitioners. All instances of death between January 1, 1995, and April 1, 2001, were reviewed. Sudden cardiac death was classified based on time between onset of cardiovascular symptoms and death. For each case, up to 10 random controls were matched for age, sex, date of sudden death, and practice. Exposure at the index date was categorized as 3 mutually exclusive groups of current use, past use, and nonuse. RESULTS: The study population comprised 554 cases of sudden cardiac death. Current use of antipsychotics was associated with a 3-fold increase in risk of sudden cardiac death. The risk of sudden cardiac death was highest among those using butyrophenone antipsychotics, those with a defined daily dose equivalent of more than 0.5 and short-term (相似文献   

Increased risk of achilles tendon rupture with quinolone antibacterial use,especially in elderly patients taking oral corticosteroids

BACKGROUND: In several case reports, the occurrence of Achilles tendon rupture has been attributed to the use of quinolones, but the epidemiologic evidence for this association is scanty. METHODS: We conducted a population-based case-control study in the General Practice Research Database in the United Kingdom during the period 1988 through 1998. Cases were defined as all persons who had a first-time recording of an Achilles tendon rupture, and who had at least 18 months of valid history before the index date. As a control group, we randomly sampled 50 000 patients with at least 18 months of valid history who were assigned a random date as index date. RESULTS: We identified 1367 cases that met the inclusion criteria. The adjusted odds ratio (OR) for Achilles tendon rupture was 4.3 (95% confidence interval [CI], 2.4-7.8) for current exposure to quinolones, 2.4 (95% CI, 1.5-3.7) for recent exposure, and 1.4 (95% CI, 0.9-2.1) for past exposure. The OR of Achilles tendon rupture was 6.4 (95% CI, 3.0-13.7) in patients aged 60 to 79 years and 20.4 (95% CI, 4.6-90.1) in patients aged 80 years or older. In persons aged 60 years and older, the OR was 28.4 (95% CI, 7.0-115.3) for current exposure to ofloxacin, while the ORs were 3.6 (95% CI, 1.4-9.1) and 14.2 (95% CI, 1.6-128.6) for ciprofloxacin and norfloxacin, respectively. Approximately 2% to 6% of all Achilles tendon ruptures in people older than 60 years can be attributed to quinolones. CONCLUSIONS: Current exposure to quinolones increased the risk of Achilles tendon rupture. The risk is highest among elderly patients who were concomitantly treated with corticosteroids.     

Delays to Care in Pediatric Lupus Patients: Data From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry

Objective

Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist.

Methods

We analyzed data from 598 CARRA Legacy Registry participants for differences between those who presented early (within <1 month of symptom onset), between 1–3 months (typical presentation), with moderate delays (3–12 months), and with severe delays (≥1 year). Factors associated with early presentation, moderate delay, and severe delay were determined by multinomial logistic regression.

Results

Forty‐four percent of patients presented early, while 23% had moderate delays and 9% had severe delays. Family history of lupus, absence of discoid rash, and location in a state with a higher density of pediatric rheumatologists were associated with earlier presentation. Younger age, low household income (<$25,000 per year), and a family history of lupus were associated with severe delay.

Conclusion

Delays to care ≥1 year exist in a notable minority of pediatric lupus patients from the CARRA Legacy Registry. In this large and diverse sample of patients, access to care and family resources played an important role in predicting time to presentation to a pediatric rheumatologist.

     

Characterization of the Inducer Required for the Development of Macrophage and Granulocyte Colonies

A substance produced by various types of cells can induce from single hematopoietic cells the formation of colonies of normal macrophages and granulocytes. This inducer has been purified 600-fold from serum-free conditioned medium from a tissue culture line of mouse cells. It is shown that the inducer is a protein, with a molecular weight of 65-70,000, whose inducing activity was about 1 ng per colony. Acrylamide gel electrophoresis of this material gave four bands, only one of which contained inducing activity. The purified protein was inactive. Activity was regained by the addition of a low molecular weight cofactor that is present in conditioned medium. Under certain conditions, activity was also regained by the addition of adenosine 3':5'-cyclic monophosphate (cyclic AMP).     

Salmonella Subtypes with Increased MICs for Azithromycin in Travelers Returned to the Netherlands

Antimicrobial susceptibility was analyzed for 354 typhoidal Salmonella isolates collected during 1999–2012 in the Netherlands. In 16.1% of all isolates and in 23.8% of all isolates that showed increased MICs for ciprofloxacin, the MIC for azithromycin was increased. This resistance may complicate empirical treatment of enteric fever.