Breast and cervical cancer survival: making sense of ‘league tables’

During 1998, the Department of Health proposed to use survival rates of cervical and breast cancer in the 1989/90 incidence cohort as indicators of care. Valid interpretation was of concern within Trent and the Trent Cancer Registry responded by performing additional analyses. Trent Cancer Registry registrations for 1989/90 were re-analysed and the stability of districts' ranks for that cohort was investigated using random simulation techniques. Stability of ranks across more recent cohorts was investigated and attempts made to use all available information.The Department of Health's analyses were confirmed by our re-analysis of the 1989/90 cohort: Rotherham residents appeared to have the "worst" survival for cervical cancer, and Sheffield residents for breast cancer, although not statistically significantly so. Random simulations indicated that ranks based on a single cohort are not stable: for example Sheffield (ranked tenth for 1-y breast cancer survival) was ranked third or better in 6% of randomisations. Ranks were also unstable across cohorts: for example Rotherham 1-y cervical cancer survival was ranked tenth for 1989/90, fifth for 1991/92 and tenth for 1993/94. Analysis of 3-y running averages provided better information than the league table approach. Most districts improved over time, to different degrees, and similar sized gaps remained between the "best" and the "worst" districts. This analysis illustrates the need to be circumspect when interpreting "league tables" based on a single year or cohort analysis. League tables are based on ranks: clearly a large difference in rank may reflect only trivial (ie medically unimportant) differences in actual outcome. Lack of a statistically significant difference in survival between two districts does not mean their survival is equivalent. Even for a common cancer, like breast cancer, rankings were unstable from cohort to cohort. At the Registry we propose to perform these trend analyses routinely in future, adjusting, when possible, for the effects of deprivation and stage at diagnosis.     

The role of humic fractions from soil and compost in controlling the growth in vitro of phytopathogenic and antagonistic soil-borne fungi

The regulation capacity of four humic substance (HS) samples, a soil humic acid (HA) and two HAs and one fulvic acid (FA) isolated from a composting substrate, was evaluated at two concentrations on the growth in vitro of one plant pathogenic, Sclerotinia sclerotiorum, and two antagonistic, Trichoderma viride and T. harzianum, soil-borne fungi. The presence of any HS sample in the growing medium, especially those from the composting substrate, caused a relevant inhibition of the mycelial growth of S. sclerotiorum and a marked stimulation of sclerotial formation that was exhibited as early appearance and numerical increase. On the contrary, the same HS treatments generally did not inhibit the growth of the two Trichoderma species. In particular, T. viride was significantly stimulated by any HS sample at any concentration, with the only exception of HA from fresh-composting substrate, whereas T. harzianum appeared to be stimulated only slightly or not significantly influenced. Only S. sclerotiorum showed evident high correlations of both the extent of the inhibitory action on mycelial growth and the final number of sclerotia with some chemical and functional properties of HS, such as total acidity, COOH group content, and elemental composition.     

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

Dissecting the neurological phenotype in children with callosal agenesis,interhemispheric cysts and malformations of cortical development

Journal of Neurology - To describe the neurological phenotype of children with prenatal diagnosis of agenesis of corpus callosum (ACC) and interhemispheric cysts associated with malformations of...     

Kidney Transplantation in Alström Syndrome: Case Report

The Alström syndrome is a rare genetic disorder, inherited in an autosomal recessive manner. It has recently been classified as a ciliopathic disorder. Alström syndrome is a multiorgan pathology characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, short stature in adulthood, hypothyroidism, hypogonadism, dilated or restrictive cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. End-stage renal disease can occur as early as the late teens and is the leading cause of death. More than 900 people with Alström syndrome have been reported worldwide. We present a case of a 42-year-old man affected by this syndrome with end-stage renal disease, type 2 diabetes mellitus, and loss of visual function and hearing who received a kidney transplant from a cadaveric donor. Basiliximab and steroid were used as induction therapy. Tacrolimus, mycophenolate mofetil, and steroid were used as maintenance therapy. No complications were reported during the recovery. In selected patients affected by Alström syndrome, renal transplantation can be a successful treatment for chronic kidney disease.     

Antioxidant effect of short-term hormonal treatment in postmenopausal women

OBJECTIVES: Recent studies have shown that estrogens alone or in association with progestins can exert an antioxidant effect on Low-Density Lipoprotein (LDL) and lipids of platelet membranes. It has been demonstrated that the oxidative modification of LDLs also involving the formation of lipid peroxides, exerts several biological effects that may contribute to the onset and progression of cardiovascular diseases. Therefore, the aim of our study was to evaluate the effect of short-term treatment with oral estrogens alone and estrogens plus progestin on endogenous and copper-induced serum levels of lipid peroxides in postmenopausal women. METHODS: Thirty-nine postmenopausal women were randomly divided into three groups: group I was treated with oral conjugated equine estrogens (CEE) for 21 days; group II received oral CEE for 21 days and, after 14 days of this treatment, 5 mg/day of medrogestone was added for 7 days; group III did not receive any therapy (controls). Endogenous and copper-induced serum levels of lipid peroxides were determined before and after 21 days of treatment in the two treated groups and in the control group. RESULTS: The serum endogenous levels of lipid peroxides in postmenopausal women did not change after short-term treatment with hormone replacement therapy. Moreover, copper-induced serum levels of lipid peroxides significantly decreased after therapy in both groups I and II. CONCLUSIONS: Our data show that hormone replacement therapy (HRT) inhibits lipid peroxidation and may play a role in preventing cardiovascular diseases.