Amygdalar kindling is associated with elevated zinc concentration in the cortex and hippocampus of rats

The reported convulsant properties of zinc and its association with hippocampal function prompted investigation of zinc levels during the induction and maintenance of kindling. Rats were fed zinc adequate diets during kindling, incited by daily amygdalar stimulation. The concentration of zinc in hippocampus was unperturbed during 3 stages of kindling induction when compared to either naive, sham surgery, or electroshock controls. In contrast, cortical zinc increased during kindling induction but returned to control levels in fully kindled animals. Two weeks after full kindling was established, the concentration of zinc in the hippocampus and overlying cortex increased significantly, in the absence of further electrical stimulation. The effect was restricted to the central nervous system inasmuch as zinc levels were unaffected in liver and other extracerebral tissues. Moreover, the zinc concentration was relatively unchanged during the 24 h period following a single electroconvulsive seizure, implying that the observed changes were not simply a postictal phenomenon. The results of this study suggest that long-lasting elevations in zinc are present after kindling is established. Whether this finding is related to the perpetuation of abnormal neuronal excitability or represents a compensatory response remains to be elucidated.     

Comparison of three oral sip-feed supplements in patients with cancer

This study set out to compare the long-term palatability of three oral sip-feed supplements. Sixty patients with various malignancies were randomized to receive one of three products—Build-Up, Fortimel and Fortisip. Participants were encouraged to take as much of the supplements each day for as long as they could manage. At the initial tasting, palatability and acceptability of the products was recorded and this was repeated throughout the trial period. Patients' reasons for discontinuing the trial were noted.
Build-Up was found to be the best-tolerated product of the three. It was taken for a significantly longer time than either Fortimel or Fortisip. There was an indication that Build-Up was more acceptable at the initial tasting than Fortisip but not Fortimel. A smaller proportion of patients stopped taking Build-Up due to flavour-related reasons compared to Fortisip but there was no significant difference between Build-Up and Fortimel. In all, 54% of the patients discontinued the trial for flavour-related reasons. Thirty-five per cent found that the sip-feeds they had been allotted unpalatable at the initial tasting, while 19% stopped the trial due to 'flavour fatigue'. Only 10% of the sample continued taking their allotted product for 90 days or more.     

Adult nephroblastoma--five cases treated by surgery, radiotherapy and chemotherapy

Nephroblastoma in adults is rare; consequently very little experience of treatment for adult cases has been reported. We report five cases of adult nephroblastoma managed by nephrectomy, radiotherapy and combination chemotherapy. The treatment schedules were derived from childhood nephroblastoma regimens. However, four of the five patients were dead within 12 months of nephrectomy and all five had progression of disease whilst on combination chemotherapy. A good prognosis should not be anticipated for adult nephroblastoma. The chemotherapy schedules which are so successful in childhood nephroblastoma may require modification to improve prognosis in adults.     

Mapping the Von Hippel -- Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis

Von Hlppel—Lindau (VHL) disease is a dominantly Inheritedfamillal cancer syndrome In which affected individuals havea greatly increased predisposition to the development of haemangloblastomasof the central nervous system and retina, renal cell carcinomaand phaeochromocytoma. The VHL gene has been mapped to chromosome3p25 -p26 by genetic linkage studies and we have previouslydemonstrated that the VHL gene is tightly linked to the D3S601locus (Zmax = 18.86 at     

An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype

Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth disorder involving the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5. In sporadic BWS cases the majority of patients have epimutations in this region. Loss of imprinting of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1. The causes of epimutations are unknown, although recently an association with assisted reproductive technologies has been described. To date the only genetic mutations described in BWS are in the CDKN1C gene. In order to screen for other genetic predispositions to BWS, the conserved sequences between human and mouse differentially methylated regions (DMRs) of the IGF2 gene were analyzed for variants. Four single nucleotide polymorphisms (SNPs) were found in DMR0 (T123C, G358A, T382G and A402G) which occurred in three out of 16 possible haplotypes: TGTA, CATG and CAGA. DNA samples from a cohort of sporadic BWS patients and healthy controls were genotyped for the DMR0 SNPs. There was a significant increase in the frequency of the CAGA haplotype and a significant decrease in the frequency of the CATG haplotype in the patient cohort compared to controls. These associations were still significant in a BWS subgroup with KvDMR1 LOM, suggesting that the G allele at T382G SNP (CAGA haplotype) is associated with LOM at KvDMR1. This indicates either a genetic predisposition to LOM or interactions between genotype and epigenotype that impinge on the disease phenotype.     

Molecular analysis of de novo germline mutations in the von Hippel-Lindau disease gene

VHL disease is a dominantly inherited familial cancer syndromewith variable expression and age-dependent penetrance. The diagnosisof isolated cases is often delayed compared with familial cases,and estimates of the new mutation rate have varied more than20-fold. To investigate the frequency and origin of de novoVHL gene mutations we have analysed: (i) families with identicalmutations to determine if there is a common haplotype, and (ii)apparent new mutation cases to determine whether the clinicaldiagnosis of such cases is reliable and to define the parentalorigin of de novo VHL gene mutations. Haplotyping of 12 VHLmutations occurring in two or more families (total 42 kindreds)revealed that for most mutations there was no evidence of afounder effect. A marked bias for a paternal origin of new mutationshas been reported in other familial cancer syndromes such asneurofibromatosis type 1 (NF1), multiple endocrine neoplasia(MEN) 2B and bilateral retinoblastoma, but it is unclear whetherthis bias results from a greater susceptibility for mutagenesisduring male gametogenesis because of the larger number of celldivisions compared with that in oogenesis, or from genomic imprintingeffects. Analysis of 13 de novo VHL mutations in which the parentof origin could be established, showed no evidence for a biasfor a paternal origin (seven paternal, six maternal), and differedsignificantly from that reported in NF1, MEN2B and bilateralretinoblastoma. This result demonstrates that an increased susceptibilityto paternal allele mutation is not a universal finding in autosomalgenetic diseases and that the origin of new mutations may beinfluenced by both genomic imprinting effects and the increasednumber of cell divisions in spermatogenesis compared with oogenesis.     

Does salivary gland scintigraphy predict response to pilocarpine in patients with post-radiotherapy xerostomia?

This study was undertaken to determine whether standard salivary gland scintigraphy may be used for the objective assessment of salivary gland sialogogues, in particular oral pilocarpine, in the treatment of post-radiotherapy xerostomia. Nine patients, with xerostomia following radiotherapy to the head and neck region underwent salivary gland scintigraphy with technetium-99m pertechnetate (40 MBq) both before and following 1 month of oral pilocarpine (5 mg tds). For each scan, the percentage uptake in the first 14 min, the peak uptake, time to peak uptake and the percentage of activity excreted following lemon juice stimulation were calculated. The results were correlated with the subjective response as assessed by questionnaire and visual analogue scale. We found no correlation between subjective response and any of the four scan parameters analysed. We could not identify any parameter that predicted those patients who would respond to pilocarpine. In addition, only one parameter, the percentage of activity excreted following stimulation, correlated with previous dose of radiotherapy to the gland. In conclusion, in this study salivary gland scintigraphy did not appear to correlate with or predict response to oral pilocarpine. However, future studies might consider performing salivary gland scintigraphy prior to radiotherapy as well as at differing time points following the commencement of pilocarpine.     

The ganglioside GM(3) is raised in the sera and tissue of patients with bladder tumours

An extraction procedure was developed which allowed the quantification of gangliosides from small volumes of sera (0.5 cm(3)) and samples of tissue (10 mg wet weight) from subjects with bladder cancer and from controls. The gangliosides were identified by high performance thin layer chromatography and mass spectrometry. In all samples the major ganglioside was GM(3) and amounts were elevated in both tissue and sera derived from tumour patients. The total lipid-bound sialic acid was greater in tumour tissue than in healthy bladder but was below the level of detection in all sera. We suggest that serum GM(3) may be of prognostic value in bladder cancer.