First case of ivermectin-induced severe hepatitis

Loiasis, caused by the filarial parasite Loa loa, is endemic in West and Central Africa. Ivermectin has been shown to be an effective treatment of loiasis. We report the case of a 20-year-old woman originally from Cameroon who was infected by the L. loa parasite and developed severe hepatitis, identified 1 month after a single dose of ivermectin. Liver biopsy showed intralobular inflammatory infiltrates, confluent necrosis and apoptosis, compatible with drug-induced liver disease. To our knowledge, this is the first case of ivermectin-induced severe liver disease published in the literatur

End expiratory oxygen concentrations to predict central venous oxygen saturation: an observational pilot study

BACKGROUND: A non-invasive surrogate measurement for central venous oxygen saturation (ScVO2) would be useful in the ED for assessing therapeutic interventions in critically ill patients. We hypothesized that either linear or nonlinear mathematical manipulation of the partial pressure of oxygen in breath at end expiration (EtO2) would accurately predict ScVO2. METHODS: Prospective observational study of a convenience sample of hemodialysis patients age > 17 years with existing upper extremity central venous catheters were enrolled. Using a portable respiratory device, we collected both tidal breathing and end expiratory oxygen and carbon dioxide concentrations, volume and flow on each patient. Simultaneous ScVO2 measurements were obtained via blood samples collected from the hemodialysis catheter. Two models were used to predict ScVO2: 1) Best-fit multivariate linear regression equation incorporating all respiratory variables; 2) MathCAD to model the decay curve of EtO2 versus expiratory volume using the least squares method to estimate the pO2 that would occur at <20% of total lung capacity. RESULTS: From 21 patients, the correlation between EtO2 and measured ScVO2 yielded R(2 )= 0.11. The best fit multivariate equation included EtCO2 and EtO2 and when solved for ScVO2, the equation yielded a mean absolute difference from the measured ScVO2 of 8 ± 6% (range -18 to +17%). The predicted ScVO2 value was within 10% of the actual value for 57% of the patients. Modeling of the EtO2 curve did not accurately predict ScVO2 at any lung volume. CONCLUSION: We found no significant correlation between EtO2 and ScVO2. A linear equation incorporating EtCO2 and EtO2 had at best modest predictive accuracy for ScVO2

One year mortality of patients treated with an emergency department based early goal directed therapy protocol for severe sepsis and septic shock: a before and after study

Abstract Introduction Early structured resuscitation of severe sepsis has been suggested to improve short term mortality; however, no previous study has examined the long-term effect of this therapy. We sought to determine one year outcomes associated with implementation of early goal directed therapy (EGDT) in the emergency department (ED) care of sepsis. Methods We performed a longitudinal analysis of a prospective before and after study conducted at a large urban ED. Adult patients were enrolled if they had suspected infection, 2 or more systemic inflammatory response criteria, and either systolic blood pressure (SBP) 4 mM. Exclusion criteria were: age <18 years, no aggressive care desired, or need for immediate surgery. Clinical and outcomes data were prospectively collected on consecutive eligible patients for 1 year before and 2 years after implementing EGDT. Patients in the pre-implementation phase received non-protocolized care at attending physician discretion. The primary outcome was mortality at one year. Results 285 subjects, 79 in the pre- and 206 in the post-implementation phases, were enrolled. Compared to pre-implementation, post-implementation subjects had a significantly lower ED SBP (72 vs. 85 mm Hg, P < 0.001) and higher sequential organ failure assessment score (7 vs. 5, P = 0.0004). The primary outcome of 1 year mortality was observed in 39/79 (49%) pre-implementation subjects and 77/206 (37%) post-implementation subjects (difference 12%; P = 0.04). Conclusions Implementation of EGDT for the treatment of ED patients with severe sepsis and septic shock was associated with significantly lower mortality at one year

Neonatal screening: identification of children with 11β-hydroxylase deficiency by second-tier testing

21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adrenal hyperplasia (CAH). We describe the additional detection of patients suffering from 11β-hydroxylase deficiency (11-OHD) by second-tier testing.Over a period of 5 years, screening for CAH was done in a total of 986,098 newborns by time-resolved immunoassay (DELFIA®) for 17α-hydroxyprogesterone (17-OHP). Positive samples were subsequently analyzed in an LC-MS/MS second-tier test including 17-OHP, cortisol, 11-deoxycortisol, 4-androstenedione and 21-deoxycortisol.In addition to 78 cases of 21-OHD, 5 patients with 11-OHD were identified. Diagnostic parameters were a markedly elevated concentration of 11-deoxycortisol in the presence of a low level of cortisol. Androstenedione was also increased. In contrast to 21-OHD, concentrations of 21-deoxycortisol were normal.Steroid profiling in newborn blood samples showing positive results in immunoassays for 17-OHP allows for differentiating 21-OHD from 11-OHD. This procedure may not detect all cases of 11-OHD in the newborn population because there may be samples of affected newborns with negative results for 17-OHP in the immunoassay

Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF)

We recently reported evidence suggesting associations between urine cadmium concentrations, reflecting long-term exposure, measured in 25 female patients (relative risk = 1.41, P = 0.412) and 15 of their male partners (relative risk = 0.19, P = 0.097) and oocyte fertilization in vitro. Blood cadmium concentrations reflect more recent exposure. We here incorporate those measures into our prior data set and employ multivariable log-binomial regression models to generate hypotheses concerning the relative effects of long-term and recent cadmium exposure on oocyte fertilization in vitro. No association is indicated for blood cadmium from women and oocyte fertilization, adjusted for urine cadmium and creatinine, blood lead and mercury, age, race/ethnicity and cigarette smoking (relative risk = 0.88, P = 0.828). However, we suggest an inverse adjusted association between blood cadmium from men and oocyte fertilization (relative risk = 0.66, P = 0.143). These results suggest that consideration of long-term and recent exposures are both important for assessing the effect of partner cadmium levels on oocyte fertilization in vitro

The Role of Gastrointestinal Bacterial Ecology in Inflammatory Bowel Disease (IBD)

The pathogenesis of inflammatory bowel disease (IBD) is not yet fully understood. A genetic predisposition, some environmental factors and microbial flora of the gut are the key factors. The presence of bacteria in the intestinal lumen is a prerequisite for the development of IBD. In animal models, mice incapable of expressing IL2 or IL10 invariably develop a colitis- or Crohn-like inflammation. No inflammation occurs if they grow up in a pathogen-free environment or if they are fed with Lactobacillus sp when exposed to environmental bacteria. Thus, the absence of luminal bacteria or a different make-up there of prevents the development of inflammatory bowel disease in this model. Patients with IBD have been found to have a decreased stool excretion of Lactobacillus and/or Bifidobacteria. Furthermore, an increased number of bacteria adherents to the mucosa and within the epithelium has been demonstrated in quantitative studies. It appears that these bacteria trigger a strong abnormal mucosal immunological response, leading to intestinal epithelial cell injury mediated by activated T-cells, mononuclear cells and macrophages. If this response can not be down regulated by regulatory T-cells, numerous inflammatory cytokines are activated by stimulation of the intracellular transcription factor NF-kB. Recently it was shown that bacterial lipopolysaccharides can activate NF-kB by binding to two specific receptors on the cell membrane (Toll-like receptors [TLR’s]) or intracellular receptors (NOD’s). New insights of the role of bacteria in IBD became available by identifying susceptibility genes for IBD. Several IBD susceptibility loci were recently identified. The IBD-1 locus on chromosome 16 shows positive evidence for linkage in Crohn’s disease and IBD-2 locus on chromosome 12 for ulcerative colitis. The evidence for an association with Crohn’s disease at the IBD-1 locus have been shown to be attributed to mutations in the CARD15/NOD2 gene. This gene is expressed in peripheral blood monocytes and in intestinal epithelial cells and serves as a key factor of innate mucosal response to luminal bacteria as an antibacterial factor. The intact intercellular NOD2 protein binds LPS and activates NF-kB. This activation of the NF-kB signalling pathway in response to bacterial components plays a protective role in the mucosal epithelial cells for the host against inviting pathogens and an increased apoptosis of infected cells. There is evidence, that the defective NOD2 protein variants increase the susceptibility to pathogen invasion and a decrease in cellular apoptosis. NF-kB plays a dual role in IBD. On the mucosal epithelial cells, bacterial components bind on NOD2 proteins and protect bacterial invasion. If this barrier mechanism is not intact, the bacterial invasion stimulates via TLR- and NOD2 receptors in immune-active cells (macrophages, T-cells and monocytes) NF-kB and triggers an aberrant inflammatory response leading to tissue damage. These new insights in the pathogenesis in IBD have led to new treatment possibilities including pre- and probiotics. These therapies are aimed at directly modulating the host immune system to suppress intestinal inflammation. This has prompted considerable interest in manipulating the enteric microenvironment as a novel therapeutic strategy. Several clinical studies showed promising results using pre- and probiotics in patients with ulcerative colitis, pouchitis and Crohn’s disease. The introduction of genetically engineered probiotic organism to produce and deliver anti- inflammatory cytokines or other biological relevant molecules to the mucosa offers further new potential for the treatment of IBD. Keywords : Inflammatory Bowel Disease, inflammatory cytokine