Interregional foodborne salmonellosis outbreak due to powdered infant formula contaminated with lactose-fermenting Salmonella virchow

Spain's Salmonella surveillance system backed by regionally-based epidemiologists around the country made it possible to detect and halt the spread of a foodborne salmonellosis outbreak due to powdered infant formula contaminated with a lactose-fermenting strain of Salmonella virchow. Forty-eight cases involving children, mostly under 7 months old, were detected in 14 out of Spain's 17 Regions. The outbreak started in January and ended in June 1994. All cases were microbiologically confirmed. The implicated strain had a 3.6 kb plasmid, was susceptible to all antimicrobials tested except nitrofurantoin and was phagetype 4a. Isolates from 8 of 24 Brand A milk samples tested had the same characteristics as case isolates. All affected/suspect batches of Brand A milk were destroyed and the product withdrawn from sale, which led to the end of the outbreak. This incident underscores the importance of maintaining surveillance systems able to detect and prevent foodborne outbreaks and alert to the possibility of isolating unusual lactose-fermenting Salmonella serotypes in especially sensitive food products.     

Intra-and inter-individual heterogeneity in exon 2 of the MDR1 gene in primary breast carcinoma and healthy individuals

Increased expression of P-glycoprotein, encoded by the MDR1 gene, is considered to be responsible for chemotherapy failure in a number of human cancers. Although it is clear that mutations in the MDR1 gene affect substrate specificity of the transporter in multidrug-resistant cell lines, scant interest has been directed at whether mutations have a unique clinical presentation. To address this question, we studied exon 2 of the MDR1 gene in 9 patients with primary breast carcinoma and 9 healthy controls using PCR and DNA sequence analysis. In order to reduce the possibility of nucleotide misincorporations introduced by Tag polymerase, sequencing of six subclones of each DNA specimen was performed. A mutation was seen as a substitution from G to A at position -1 in two patients and one control. An A to G nucleotide substitution giving rise to an amino acid substitution (Asn-->Asp) in codon 21 at the first potential N-glycosylation site of the P-glycoprotein was seen in primary tumors from four patients and in an axillar lymph node metastases from one of these patients. This mutation was also seen in two healthy individuals, which similar to the patients, both seem to be heterozygous for this MDR1 exon 2 allele. Three other mutations were also found in the patients; a substitution of A to G at position 23 and A to G at position 52 in the same patient and in another patient, G at position 42 was changed to A. However, the last three mutations were not confirmed by repeating analysis of the original genomic sample. The results revealed different distribution of a point mutation between various parts of the same primary tumor and between a lymph node metastasis and the primary tumor tissue. Thus, demonstrating both intra-and inter-tumor heterogeneity. The results also emphasized constitutional allelic variation in the MDR1 gene. Whether this might affect sensitivity to chemotherapy has to be further evaluated.     

Glutathione administration against cisplatin-induced nephrotoxicity does not modify its cytotoxic activity

Glutathione (GSH) is an intracellular thiol compound which has been shown to protect against cisplatin-induced nephrotoxicity, in animal models and clinical trials. In order to determine whether GSH interferes with cisplatin activity, the lymphoma L5178Y was implanted in 50 DBA/2 mice, and then they were treated with cisplatin with or without previous GSH. Two similar experiments were carried out with three different groups: Group 1: Control group without cisplatin; Group 2: Treatment with cisplatin without GSH, and Group 3: GSH administration prior to cisplatin. Tumor area and survival have been considered as parameters to measure the activity of cisplatin. The average Values of tumor areas in the mice pretreated with GSH were not significantly different from those corresponding to the group treated with cisplatin alone. Sixty days survival was 55% and 73% in the groups pretreated with GSH and with cisplatin alone respectively, the difference was not statistically significant. In conclusion, GSH administration prior to cisplatin does not modify its cytotoxic activity.     

Pharmacotherapeutic Considerations for Individuals with Down Syndrome

Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some individuals. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight literature focused on pharmacotherapy for individuals with DS. We discuss reports of altered drug disposition or response in patients with DS and explore social factors that may impact medication adherence in the DS setting. Enhanced monitoring during drug therapy in individuals with DS is justified based on reports of altered drug disposition, drug response, and other characteristics present in this population.     

Administración de medios de contraste. ¿Existe riesgo de daño renal agudo?

ObjectiveTo determine whether the intravenous administration of iodinated contrast material for computed tomography (CT) is associated with an increase in creatinine levels and acute kidney injury.Material and methodsThis retrospective cohort study included all patients who presented at the emergency department between 2010 and 2015 with baseline creatinine measurement (C1) and follow-up creatinine measurement (C2) between 24 and 72 hours later. The clinical research ethics committee approved the study. The exclusion criteria were age < 18 years, creatinine ≤ 0.4 mg/dl or ≥4.0 mg/dl, and the administration of contrast media within the previous 6 months. The mean number of patients presenting at the emergency department was 105,435.6 per year. Patients who met the inclusion criteria were classified into three groups: those who underwent contrast-enhanced CT (n = 6,642), those who underwent noncontrast CT (n = 6,193), and those who did not undergo CT (n = 33,802). We used the Acute Kidney Injury Network's (AKIN) and the Contrast-induced Nephropathy Consensus Working Panel's (CIN) criteria. Statistical analyses included bivariate statistics and logistic regression. Stata 15 was used for all statistical analyses.ResultsWe analyzed 52,411 patients; after data cleansing: 46,637; mean age: 67.95 years; C1: mean 1.16 mg/dl (SD: 0.61); C2: 1.14 mg/dl (SD: 0.66). With AKIN and CIN criteria: contrast-enhanced CT was not associated with a greater probability of developing nephropathy (odds ratio [OR: 0.90; 95% CI: 0.83–0.99] and [OR 0.89, 95% CI: 0.81–0.98], respectively). The propensity score matching study using both sets of criteria (AKIN + CIN) yielded OR 0.80 [95% CI: 0.77–0.84]. Glomerular filtration rates less than 30 ml/min were not associated with increased kidney damage [OR: 0.66, 95% CI: 0.47–0.91].ConclusionThe administration of intravenous contrast material in the patients studied is not associated with increased acute kidney injury.