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Objective: This report described the first Escherichia coli (E. coli) isolates harbouring mcr-1 in Uruguay., Methods: Three E. coli isolates were obtained from blood, urine and rectal swabs from different patients in two hospitals. Extended-spectrum β-lactamases (ESBL), plasmid-encoded (pAmpC) β-lactamases, plasmid-mediated quinolone resistance (PMQR) genes, class 1 integrons, and mcr-1, mcr-2 and mcr-3 were sought and characterised in three E. coli isolates. Transfer of resistance determinants was assessed by conjugation. Clonality was analysed by multilocus sequence typing., Results: All isolates were categorised as being colistin-resistant and the mcr-1 gene was detected. Two isolates were also resistant to oxyimino cephalosporins: one on account of bla CMY-2 and the other due to bla CTX-M-15 , the latter also harbouring transferable quinolone-resistance genes (aac(6')Ib-cr and qnrB). All mcr-1 genes were transferred by conjugation to recipient strains. The mcr-1-bearing isolates belonged to sequence types ST10, ST93 and ST5442., Conclusions: ST10 is considered as a high-risk clone worldwide. This type of mcr-1-harbouring clone is a major concern for human and animal health and must be under close surveillance. This study detected the presence of mcr-1 for the first time in Uruguay, albeit in an allodemic manner, associated with different antibiotic-resistance genes and from diverse clinical contexts. Considering that colistin is often the last therapeutic option available for multidrug-resistant Gram-negative bacilli infections, it is important to maximise precautions to avoid dissemination of isolates carrying mcr-1., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.) more...

This corrects the article DOI: 10.1038/ncomms15805.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74g <-0.55) and blood pressure (-0.35g <-0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization. more...

A novel, methicillin-resistant [corrected] Staphylococcus aureus clone (Uruguay clone) with a non-multidrug-resistant phenotype caused a large outbreak, including 7 deaths, in Montevideo, Uruguay. The clone was distinct from the highly virulent community clone represented by strain MW2, although both clones carried Panton-Valentine leukocidin gene and cna gene. more...

In an attempt to create uniform nationwide guidelines for the management of all stages of endometrial carcinoma, and to limit the use of adjuvant radiation therapy in stage I disease to high-risk patients only, a protocol was developed by the Danish Endometrial Cancer group (DEMCA). From September 1986 through August 1988, 1214 women in Denmark with newly diagnosed carcinoma of the endometrium have been treated according to this protocol. This figure represents all endometrial carcinomas diagnosed in Denmark during this two-year period. The primary treatment was total abdominal hysterectomy and bilateral salpingo-oophorectomy, no preoperative radiation therapy was delivered. In 1039 cases no macroscopic residual tumour and/or microscopic tumor tissue in the resection margins was found following surgery. Based on surgery and histopathology, these patients were classified as: P-stage I low risk (n = 641), P-stage I high risk (n = 235), P-stage II (n = 105) and P-stage III, Group 1 (n = 58). No postoperative radiation therapy was given to P-I low risk cases. P-I high risk, P-II, and P-III (Group 1) cases received external radiation therapy. Recurrence rate at 68-92 months follow-up was 45/641 (7%) in P-I low risk, 36/235 (15%) in P-I high risk, 30/105 (29%) in P-II, and 27/58 (47%) in P-III (Group 1) cases. Fifteen of 17 vaginal recurrences in P-I low risk cases were salvaged (mean observation time 61 months). In this population-based investigation it has been shown that P-stage low-risk patients are adequately treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy, and that no pre- or postoperative radiation therapy is necessary. more...

The current status of cervical cancer treatment in Denmark is discussed. Diagnostic aspects and problems of classification are presented briefly supplemented with a comment on new prognostic parameters based on a semiquantitative score system and flow cytometry. Surgery is the treatment of election for the early stages whereas radiotherapy is the treatment of choice in advanced stages. Chemotherapy should only be employed in the framework of clinical trials. It is concluded that centralised treatment should be maintained. more...

The treatment of 10 patients having neoplastic disease with exogenous i.m. interferon therapy is described. The interferon given is partially purified interferon produced from human leukocytes. Sendai virus is used as interferon inductor. The patients reported in this paper have been on treatment for periods of 2-28 months. Apart from initial periods of fever, no side-effects have been recorded. Patients suffering from bladder papillomas have shown partial regression after a few months of therapy. The other cases treated are too few to warrant any conclusions, but the therapy does seem to have been beneficial. more...

Since July 1976, 19 patients with carcinoma of the bladder have been treated with adriamycin, 5-fluorouracil, and levamisole combined with radiotherapy (60 Gy [6000 radsA1/24 fractions/6 weeks). Chemotherapy and radiotherapy were initiated simultaneously, with the entire treatment lasting 7--8 months. Three months after the completion of radiotherapy, 14 of the 18 patients in whom cystoscopy was performed were found to be in complete remission. Overall, 17 of the 19 patients have responded to the treatment and 15 patients have at some time shown complete remission. The toxic effects seen were myelosuppression, nausea, vomiting, diarrhea, loss of weight, and alopecia. Thirteen patients received the entire treatment as outpatients while six patients had to be hospitalized for a period of 8--14 days because of severe side effects, especially in Weeks 3--8. Serious complications such as bowel perforation were not seen, but one patient died with septicemia as a result of agranulocytosis, which was attributed to the treatment with levamisole. more...

Carcinoma in situ in the contralateral testis was diagnosed in 27 of 500 patients (5.4%) with unilateral testicular germ cell cancer. Eight of the 27 patients received intensive chemotherapy for spread of their initial testicular cancer. Follow up biopsy studies did not detect changes of carcinoma in situ in any of these patients, and none developed a contralateral testicular tumour (observation time 12-88 months). Of the remaining 19 patients with carcinoma in situ, seven developed contralateral testicular cancer. The estimated risk of developing invasive growth was 40% within three years and 50% within five years. None of the 473 patients without carcinoma in situ detected by screening biopsy developed contralateral testicular cancer (observation time 12-96 months). No serious complications arose from the biopsy procedures. All patients with unilateral testicular germ cell cancer should be offered biopsy of the contralateral testis. more...

A total of 64 consecutive patients with noninvasive bladder tumors (stage Ta) between 1977 and 1983 underwent treatment with intravesical instillation of doxorubicin. The total response rate was 85 per cent and 57 per cent of the patients had a complete response after 16 weekly instillations. Half of the patients with a complete response had recurrences within 12 to 16 months. Ten per cent of all patients had an invasive tumor during the observation period. We conclude that doxorubicin can render some patients with noninvasive bladder tumors (stage Ta) free of disease but there currently is nothing to indicate that the same results could not be obtained by transurethral resection. more...

Seven patients with recurrent renal carcinoma, who had previously been treated with progesterone and vinblastine for progressive disease, were treated with human leukocyte interferon (HuIFN alpha). Five patients received daily escalating i.m. IFN doses from 4 X 10 up to 16 X 10(6) U during a minimum of 4 weeks, while two patients received intralesional IFN, 20 X 10(6) U/dose. No serious side-effects were observed. No tumor response was found in any of these patients. more...