Clinical experience with amikacin, a new aminoglycoside antibiotic

CITATION: Theron, F. P. & De Kock, M. A. 1977. Clinical experience with amikacin, a new aminoglycoside antibiotic. South African Medical Journal, 51(21):746-8.The original publication is available at http://www.samj.org.za[No abstract available]Publisher’s versio

Combined use of hyperthermia and radiation therapy for treating locally advanced cervical carcinoma (Withdrawn Paper, art. no. CD006377, 2010)

Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells. It was introduced into clinical oncology practice several decades ago. Positive clinical results, mostly obtained in single institutions, resulted in clinical implementation albeit in a limited number of cancer centres worldwide. Because large scale randomised clinical trials (RCTs) are lacking, firm conclusions cannot be drawn regarding its definitive role as an adjunct to radiotherapy in the treatment of locally advanced cervical carcinoma (LACC).To assess whether adding hyperthermia to standard radiotherapy for LACC has an impact on (1) local tumour control, (2) survival and (3) treatment related morbidity.The electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 1, 2009) and Cochrane Gynaecological Cancer Groups Specialised Register, MEDLINE, EMBASE, online databases for trial registration, handsearching of journals and conference abstracts, reviews, reference lists, and contacts with experts were used to identify potentially eligible trials, published and unpublished until January 2009.RCTs comparing radiotherapy alone (RT) versus combined hyperthermia and radiotherapy (RHT) in patients with LACC.Between 1987 and 2009 the results of six RCTs were published, these were used for the current analysis.74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 1 to 3). The pooled data analysis yielded a significantly higher complete response rate (relative risk (RR) 0.56; 95% confidence interval (CI) 0.39 to 0.79; p <0.001), a significantly reduced local recurrence rate at 3 years (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p <0.001) and a significanly better overall survival (OS) at three years following the combined treatment with RHT(HR 0.67; 95% CI 0.45 to 0.99; p = 0.05). No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30 to 3.31; p = 0.99) or late grade 3 to 4 toxicity (RR 1.01; CI 95% 0.44 to 2.30; p = 0.96) between both treatments.The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervical carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity

Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations.

Individuals harboring germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome or pleuropulmonary blastoma-familial tumor and dysplasia syndrome [online Mendelian inheritance in man (OMIM) #601200]. In addition, specific somatic mutations in the DICER1 RNase III catalytic domain have been identified in several DICER1-associated tumor types. Pituitary blastoma (PitB) was identified as a distinct entity in 2008, and is a very rare, potentially lethal early childhood tumor of the pituitary gland. Since the discovery by our team of an inherited mutation in DICER1 in a child with PitB in 2011, we have identified 12 additional PitB cases. We aimed to determine the contribution of germ-line and somatic DICER1 mutations to PitB. We hypothesized that PitB is a pathognomonic feature of a germ-line DICER1 mutation and that each PitB will harbor a second somatic mutation in DICER1. Lymphocyte or saliva DNA samples ascertained from ten infants with PitB were screened and nine were found to harbor a heterozygous germ-line DICER1 mutation. We identified additional DICER1 mutations in nine of ten tested PitB tumor samples, eight of which were confirmed to be somatic in origin. Seven of these mutations occurred within the RNase IIIb catalytic domain, a domain essential to the generation of 5p miRNAs from the 5' arm of miRNA-precursors. Germ-line DICER1 mutations are a major contributor to PitB. Second somatic DICER1 "hits" occurring within the RNase IIIb domain also appear to be critical in PitB pathogenesis

Monitoring stimulated darkening from UV-C light on different bean genotypes by NMR spectroscopy.

The use of UV-C cool white light on bean (Phaseolus vulgaris L.) seeds significantly increases the biochemical seed coat post-harvest darkening process, whilst preserving seed germination. The aim of this work consists in monitoring the effect caused by the incidence of UV-C light on different bean genotypes using NMR spectroscopy. The genotype samples named IAC Alvorada; TAA Dama; BRS Estilo and BRS Pérola from the Agronomic Institute (IAC; Campinas; SP; Brazil) were evaluated. The following two methodologies were used: a prolonged darkening, in which the grain is placed in a room at a controlled temperature (298 K) and humidity for 90 days, simulating the supermarket shelf; an accelerated darkening, where the grains are exposed to UV-C light (254 nm) for 96 h. The experiments were performed using the following innovative time-domain (TD) NMR approaches: the RK-ROSE pulse sequence; one- and two-dimensional high resolution (HR) NMR experiments ( 1H; 1H-1H COSY and 1H-13C HSQC); chemometrics tools, such as PLS-DA and heat plots. The results suggest that the observed darkening occurs on the tegument after prolonged (90 days) and accelerated (96 h) conditions. In addition, the results indicate that phenylalanine is the relevant metabolite within this context, being able to participate in the chemical reactions accounted for by the darkening processes. Additionally, it is possible to confirm that a UV-C lamp accelerates oxidative enzymatic reactions and that the NMR methods used were a trustworthy approach to monitor and understand the darkening in bean seeds at metabolite level

Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study

5-Fluorouracil (5-FU)-based chemotherapy is frequently associated with diarrhoea. We compared two 5-FU-based regimens and the effect of Lactobacillus and fibre supplementation on treatment tolerability. Patients diagnosed with colorectal cancer (n=150) were randomly allocated to receive monthly 5-FU and leucovorin bolus injections (the Mayo regimen) or a bimonthly 5-FU bolus plus continuous infusion (the simplified de Gramont regimen) for 24 weeks as postoperative adjuvant therapy. On the basis of random allocation, the study participants did or did not receive Lactobacillus rhamnosus GG supplementation (1–2 × 1010 per day) and fibre (11 g guar gum per day) during chemotherapy. Patients who received Lactobacillus had less grade 3 or 4 diarrhoea (22 vs 37%, P=0.027), reported less abdominal discomfort, needed less hospital care and had fewer chemotherapy dose reductions due to bowel toxicity. No Lactobacillus-related toxicity was detected. Guar gum supplementation had no influence on chemotherapy tolerability. The simplified de Gramont regimen was associated with fewer grade 3 or 4 adverse effects than the Mayo regimen (45 vs 89%), and with less diarrhoea. We conclude that Lactobacillus GG supplementation is well tolerated and may reduce the frequency of severe diarrhoea and abdominal discomfort related to 5-FU-based chemotherapy