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R Walker

Publications and source records attributed to R Walker.

At least 37 records · Page 2Linked to original sources
PubMed2004

Best Practice No 176: Updated recommendations for HER2 testing in the UK.

This paper serves to update previously published guidance on rationale and methodology for HER2 laboratory testing following the recommendation for the use of HER2 targeted treatment in the management of advanced breast cancer in the UK. Emphasis is placed on the standardisation of methodology and assessment and strategies to achieve high quality performance. A two phase testing algorithm based on first line immunocytochemistry evaluation and second line fluorescence in situ hybridisation assessment of borderline cases is recommended. To ensure maintenance of expertise, an annual caseload volume of at least 250 cases is recommended for laboratories providing a testing service.

Algorithms↗
PubMed2003

Cultural differences in emotions: a context for interpreting emotional experiences.

In this article, it is suggested that cross-cultural assessment of emotional disturbances would benefit from the consideration of cultural differences in the modal, and normative emotions. A summary of the research literature on cultural differences in emotions, in particular in antecedent events, subjective feeling, appraisal, and behavior is provided. Cultural differences in emotions are understood functionally, such that the most prevalent emotional phenomena in a culture are those that fit and reinforce the distinct cultural models (i.e. goals and practices) of self and relationship. It is argued that a culture-sensitive approach to emotional disturbances would entail the assessment of emotional phenomena that are dysfunctional to the cultural models of self and relationship.

Affective Symptoms↗
PubMed2003

Reduced and standard target concentration tacrolimus with sirolimus in renal allograft recipients.

We report 6-month results of renal allograft recipients enrolled in seven Australian centers as part of a worldwide, multicenter, randomized, open-label, concentration-controlled trial comparing standard tacrolimus (sTAC) with reduced tacrolimus (rTAC) both with sirolimus (SRL) and steroids. Patients were randomized 1:1 to either rTAC (n = 33) with a target maintenance concentration of SRL of 8 to 15 ng/mL and TAC of 3 to 7 ng/mL, or sTAC (n = 31) with SRL target of 5 to 10 ng/mL and TAC of 8 to 12 ng/mL. Antibody induction was prohibited. Adult recipients of a first or second cadaveric or non-HLA-identical living donor renal graft were eligible for enrollment. Recipients with a panel-reactive antibody level of >50% and recipients of regrafts who had lost their first graft from rejection within the first 6 months were ineligible. The groups were compared for graft function, incidence of rejection, and patient and graft survival at 6 months. There were no differences in demographics. There were 30% and 29% discontinuations in the rTAC and sTAC groups mainly due to adverse events in the first month. The 6-month patient and graft survival by intention-to-treat analysis was 94% and 91% for rTAC and 100% and 97% for sTAC (P = NS), respectively. Incidence and severity of biopsy-proven acute rejection was not different between the two groups, being 21% for rTAC and 19% for sTAC. The mean serum creatinine was 121 micromol/L and 148 micromol/L for rTAC and sTAC groups (P =.09), respectively. Glomerular filtration rate (GFR) was 68 mL/min and 62 mL/min (P =.23), respectively. Adverse events, infections, and antihypertensive and antilipidemic agent usage were similar. Of interest is that the overall incidence of thrombotic microangiopathy was 14%. These results support the safety and efficacy of SRL + TAC. Reduced TAC is associated with a trend toward improved renal function.

Adult↗
PubMed2003

Sirolimus: a single center experience in combination with calcineurin inhibitors.

A retrospective survey was performed to establish patient and graft outcome for all 41 patients at our centre receiving sirolimus (SRL) in combination with calcineurin inhibition (CNI) as primary therapy for the 6 years prior to March 2002. Patient mortality [12%; n = 5 (TTP, lymphoma, mucormycosis, and small bowel perforation] was significantly higher at 3 months compared with those not receiving SRL, but not thereafter. 12.8% had delayed graft function and 33% had one or more episodes of rejection in the first 6 months. Mean GFR at 12 months was significantly lower (47.3 mL/min) in the SRL group compared with those not receiving SRL (51.3 mL/min). Twenty-two patients had a 12-month protocol biopsy; CNI toxicity was present in 36%. SRL was associated with significant hyperlipidaemia (serum cholesterol, 5.2 +/- 1.4 at baseline vs 7.3 +/- 1.7 mmol/L at 3 months, P <.001; triglycerides, 2.3 +/- 1.4 at baseline vs 2.7 +/- 1.1 mmol/L at 3 months, P <.05). Mild thrombocytopenia occurred in 23% but was not associated with haemorrhagic events. LDH increased by 62%, remaining elevated out to 2 years post engraftment. Seven patients developed insulin requiring diabetes mellitus, similar to the rate observed in our general transplant population.Thus, in this early experience, SRL in combination with CNI was associated with significant mortality and morbidity including CNI toxicity, presumably a reflection of a heavy burden of immunosuppression. However, 1-year graft survival on SRL was similar to the mean Australia-wide graft survival regardless of immunosuppression. The future use of SRL may center around CNI sparing and avoidance type protocols.

Adrenal Cortex Hormones↗
PubMed2003

Guidance for the safety assessment of botanicals and botanical preparations for use in food and food supplements.

There is a growing interest by both consumers and industry for the development of food products with 'functional' properties, or health benefits. These products may take the form of dietary supplements or of foods. The health benefits are given by particular ingredients, and in many cases these are derived from botanicals. The variety of plants providing these functions is large, ranging from staple food sources such as cereals, fruits and vegetables, to herbals as used in traditional medicine. The food or ingredient conferring health properties may consist of the plants themselves, extracts thereof, or more purified components. The scientific literature is abundant with articles not only on the beneficial properties, but also on possible adverse health effects of plants and their components. The present report discusses the data required to determine the safe use of these types of ingredients, and provides advice on the development of risk assessment strategies consistent with due diligence under existing food regulations. Product specifications, composition and characterisation of standardised and authentic materials, documented history of use and comparison to existing products (taking into account the effect of industrial processing), description of the intended use and consequent exposure are highlighted as key background information on which to base a risk evaluation. The extent of experimental investigation required, such as in vitro, animal, and/or human studies, depends on the adequacy of this information. A decision tree is presented as an aid to determine the extent of data requirements based on product comparison. The ultimate safety in use depends on the establishment of an adequate safety margin between expected exposure and identified potential hazards. Health hazards may arise from inherent toxicities or contaminants of the plant materials, including the mechanism of the intended beneficial effect. A lower safety margin may therefore be expected than for food ingredients or additives where no physiological effects are intended. In rare cases, post launch monitoring programmes may be envisaged to confirm expected exposures and adequacy of the safety margin. This guidance document was elaborated by an expert group of the Natural Toxin Task Force of the European Branch of the International Life Sciences Institute--ILSI Europe and discussed with a wider audience of scientists at a workshop held on 13-15 May 2002 in Marseille, France.

Animals↗
PubMed2003

[Comparison of utilization of cardiovascular drugs in the Czech Republic and in Wales].

AIM: To compare and describe the trends in the consumption of selected groups of cardiovascular drugs in several districts of the Czech Republic and counties of Wales in the period of 1997-2000. METHODS: A retrospective analysis of prescription data from General Medical Insurance Company (three districts in the Czech Republic) and data from the Health Solutions Wales (3 counties of Wales). The data were analyzed during seven half-year intervals from January 1997 till June 2000. The authors investigated the consumption of antihypertensives, diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, hypolipidemic drugs, digoxin and acetylsalicylic acid classified according to ATC classification. The drug consumption was expressed at defined daily doses (DDD) and standardized per 1,000 insured individuals and day for the Czech districts and per 1,000 inhabitants and day for the Welsh counties (DID). RESULTS: The total consumption of the cardiovascular drugs under study in the last half-year of the investigated period of time (1/00) proved to be highest in CZ2 (40.2 DID), the value being by 40% higher than in CZ1 (348.6 DID) and by 11% higher than in CZ3 (386.9% DID). The rates of consumption in the Welsh counties during this period of time were 338.8 DID (W1), 307.9 DID (W2) and 298.0 DID (W3), respectively. Diuretics proved to be used at the highest rate in both countries. The consumption of thiazides and loop diuretics in the Czech districts during 1/00 represented 67.6% and 16.7% of the all diuretic consumption on the average, whereas the corresponding values in Wales were 42.3% for thiazide preparations and 46.7% for the loop diuretics. An increase in the consumption of new drugs such as ACE inhibitors, calcium channel blockers of 2nd generation and statins was noted in both countries. The statins represented 33.5% of total prescription of hypolipidemic drugs in the Czech districts, whereas their consumption in the Welsh districts represented 88.1% consumption of these drugs. CONCLUSION: The most significant differences were found in the consumption of diuretics and hypolipidemic drugs. The results of consumption studies could highlight the differences in drug utilization and thereby stimulate discussion on optimization of drug selection.

Cardiovascular Agents↗
PubMed2002

The symbiosis of Bacillus subtilis L-forms with Chinese cabbage seedlings inhibits conidial germination of Botrytis cinerea.

AIMS: To establish whether germination of Botrytis cinerea was affected by the symbiosis of Bacillus subtilis L-form bacteria with Chinese cabbage. METHODS AND RESULTS: Germinating seeds of Chinese cabbage were co-cultivated with either L-forms of Bacillus subtilis or 5% (w/v) mannitol by soaking for 3 h. Seeds were then washed in sterile water, sown on a minimal medium and incubated in controlled conditions. L-form symbiosis was detected over a time course by ELISA. Conidial germination of Botrytis cinerea was significantly reduced on cotyledonous leaves of L-form-treated plants compared with controls. CONCLUSIONS: Symbiosis of B. subtilis L-form bacteria during seed germination of Chinese cabbage inhibits conidial germination in plants on subsequent exposure to Botrytis cinerea. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first account of plant symbiosis with L-form bacteria showing antagonism to a fungal plant pathogen. This has promising implications for the use of this L-form as a biocontrol agent.

Bacillus subtilis↗
PubMed2002

[Theoretical and physical aspects of excimer laser trabeculotomy (ELT) ab interno with the AIDA laser with a wave length of 308 mm].

Ablation of tissue structures containing and surrounded by water differs from tissue ablation at a surface, not only theoretically, but also in terms of outcome. In contrast to the situation often observed with surface ablation, it is shown that the trabecular meshwork in the anterior chamber of the eye can be ablated cleanly and accurately with the 308 nm Excimer laser without causing collateral thermal damage. The reason for this is that in the trabecular meshwork, the ratio of radiation-absorbing tissue to water--which absorbs very little energy--is very small. A marked cooling effect thus results, which permits the development of only a very small amount of collateral thermal damage at the boundaries of the ablation zone.

Biophysical Phenomena↗
PubMed2001

Unfocused ergonomics?

Ergonomics is now fairly routinely used in industry. Managers often initiate contact with ergonomists. The paper argues that many ergonomists have abandoned some fundamental ergonomics principles and have unwittingly succumbed to 'sitting complacently in the manager's toolbox'. It is also argued that through its inherent diversity, ergonomics is in danger of becoming fragmented and losing its identity.

Ergonomics↗
PubMed2001

Sentinel practice-based survey of the management and health of horses in northern Britain.

Details of the management, feeding, level of activity and routine health care of horses in Scotland and the five northernmost counties in England were recorded through a stratified random sample of horse owners who had responded to a previous survey. Sixty-eight per cent of the horses were kept where their owners resided, and 32 per cent were kept away from the owner's home. More than 99 per cent were turned out to grazing for at least part of the year and 81 per cent were stabled for at least part of the time, most commonly bedded on straw (50 per cent) or shavings (34 per cent). Hay was fed to 87 per cent, sugar beet pulp to 64 per cent and commercially prepared concentrate mixes to 60 per cent of the horses. Hacking was the most popular activity (52 per cent of horses) followed by riding/pony club events (28 per cent) and showing (21 per cent). The majority of the horses were involved in more than one activity. There were an estimated 0.88 veterinary visits per horse per year and 29 per cent of the horses were reported to suffer from at least one permanent or recurrent health disorder. The median annual numbers of administrations of vaccines (influenza and tetanus) and anthelmintics were one and seven respectively per horse, and each horse was shod a median seven times. There were significant differences in the management of horses kept in different types of premises and in areas of different human population density.

Animal Feed↗
PubMed2001

Risk of thyroid carcinoma in a female population after radiotherapy for breast carcinoma.

BACKGROUND: There is increasing concern regarding the risk of developing a second primary tumor in adjacent organs as a result of scattered radiation among patients who have undergone radiotherapy (RT) for breast carcinoma. Previous studies have focused mainly on the possible increase in the incidence of contralateral breast carcinoma. To the authors' knowledge, the risk of thyroid carcinoma among these women has not been explored to date. METHODS: In this population-based, retrospective cohort study, the authors identified 194,798 women who were diagnosed with invasive breast carcinoma (exclusive of those with distant metastasis) between 1973 and 1993, and ascertained subsequent cases of thyroid carcinoma utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National Cancer Institute. Poisson regression was used to calculate the age-standardized incidence ratio (SIR) of thyroid carcinoma and to model the influence of RT on the relative risk (RR) between the RT cohort (48,495 women) and the non-RT cohort (146,303 women). RESULTS: A total of 28 women in the RT cohort and 112 women in the non-RT cohort subsequently developed thyroid carcinoma. The distribution of thyroid carcinoma histologies in both the RT cohort and the non-RT cohort was similar to that in the female general population. Overall, there was no significant increase in the risk of thyroid carcinoma in either the RT cohort or the non-RT cohort compared with the general population; the SIR was 1.1 (95% confidence interval [95% CI], 0.8-1.6) for the RT cohort and 1.2 (95% CI, 1.0-1.4) for the non-RT cohort. When the RT cohort was compared with the non-RT cohort, the RR of thyroid carcinoma was 1.0 (95%CI, 0.7-1.5). CONCLUSIONS: The risk of radiation-associated thyroid carcinoma after initial RT for breast carcinoma was so low as to be undetectable in the current large population-based study. Continued monitoring of these women will be required to document that these findings are maintained with even longer follow-up periods. However, with 10,895 women having been followed for > 10 years at the time of last follow-up in the current study, these findings should be reassuring to women considering RT for their breast carcinoma. Therefore, women who have received RT for breast carcinoma require no special surveillance for their thyroid gland. Furthermore, previous breast radiation need not be a factor in determining the optimal management of thyroid nodules arising in women who received RT for breast carcinoma.

Adenocarcinoma, Follicular↗
PubMed2001

The metabolism and bioactivation of agaritine and of other mushroom hydrazines by whole mushroom homogenate and by mushroom tyrosinase.

Whole homogenates of Agaricus bisporus metabolised the mushroom hydrazine agaritine [beta-N-(gamma-L(+)glutamyl)-4-(hydroxymethyl) phenylhydrazine] to generate at least three metabolites. None of these metabolites, however, was the free hydrazine [4-(hydroxymethyl)phenylhydrazine], the postulated metabolite of agaritine believed to be formed as a result of the loss of the gamma-glutamyl group, the reaction being catalysed by gamma-glutamyltransferase. The three metabolites of agaritine displayed weak mutagenic activity towards Salmonella typhimurium strain TA104. 4-(Hydroxymethyl)phenylhydrazine, as the N'-acetyl derivative, was metabolised by mushroom tyrosinase to yield a number of metabolites that induced a mutagenic response in S. typhimurium TA104. Similar to N'-acetyl-4-(hydroxymethyl)phenylhydrazine, agaritine was extensively metabolised by the mushroom tyrosinase but, in contrast, the structurally related N'-acetyl-4-hydrazinobenzoic acid did not serve as substrate of this enzyme, implying a critical role for the hydroxymethyl group at the para-position. In conclusion, the current studies have demonstrated for the first time that: (a) whole mushroom homogenates readily metabolise agaritine but not to the postulated 4-(hydroxymethyl)phenylhydrazine; and (b) mushroom tyrosinase metabolises agaritine and N'-acetyl-4-(hydroxymethyl)phenylhydrazine, in the latter case forming genotoxic metabolites.

Agaricales↗
PubMed2001

Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours.

Previously we analysed overlapping homozygous deletions in lung and breast tumours/tumour lines and defined a small region of 120 kb (part of LCTSGR1) at 3p21.3 that contained putative lung and breast cancer tumour suppressor gene(s) (TSG). Eight genes including RASSF1 were isolated from the minimal region. However, extensive mutation analysis in lung tumours and tumour lines revealed only rare inactivating mutations. Recently, de novo methylation at a CpG island associated with isoform A of RASSF1 (RASSF1A) was reported in lung tumours and tumour lines. To investigate RASSF1A as a candidate TSG for various cancers, we investigated: (a) RASSF1A methylation status in a large series of primary tumour and tumour lines; (b) chromosome 3p allele loss in lung tumours and (c) RASSF1 mutation analysis in breast tumours. RASSF1A promoter region CpG island methylation was detected in 72% of SCLC, 34% of NSCLC, 9% of breast, 10% of ovarian and 0% of primary cervical tumours and in 72% SCLC, 36% NSCLC, 80% of breast and 40% of ovarian tumour lines. In view of the lower frequency of RASSF1 methylation in primary breast cancers we proceeded to RASSF1 mutation analysis in 40 breast cancers. No mutations were detected, but six single nucleotide polymorphisms were identified. Twenty of 26 SCLC tumours with 3p21.3 allelic loss had RASSF1A methylation, while only six out of 22 NSCLC with 3p21.3 allele loss had RASSF1A methylation (P=0.0012), one out of five ovarian and none out of six cervical tumours with 3p21.3 loss had RASSF1A methylation. These results suggest that (a) RASSF1A inactivation by two hits (methylation and loss) is a critical step in SCLC tumourigenesis and (b) RASSF1A inactivation is of lesser importance in NSCLC, breast, ovarian and cervical cancers in which other genes within LCTSGR1 are likely to be implicated.

Amino Acid Sequence↗