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Biomedical subjects

A Ward

Publications and source records attributed to A Ward.

At least 37 records · Page 2Linked to original sources

Contribution of germline MLH1 and MSH2 mutations to lobular carcinoma in situ of the breast.

Lobular carcinoma in situ (LCIS) is an unusual histological pattern of non-invasive neoplastic disease of the breast occurring predominantly in women aged between 40 and 50 years. LCIS is frequently multicentric and bilateral suggesting a genetic basis to the disease. The high frequency of microsatellite instability in lobular breast cancers, coupled with increased risk of breast cancer associated with germline mismatch repair gene mutations raises the possibility that mutations MSH2 or MLH1 might confer susceptibility to LCIS. To explore this possibility we have examined a series of 71 LCIS patients for germline MSH2 and MLH1 mutations. No mutations were detected in MSH2. Two sequence variants were identified in MLH1. The first was a CTT-->CAT substitution, codon 607 (exon 16) changing leucine to histidine. The other mutation detected in MLH1 was a TAC-->TAA substitution codon 750 (exon 19) creating a stop codon, predicted to generate a truncated protein. These findings suggest that mutations in MLH1 may underlie a subset of LCIS cases.

Adaptor Proteins, Signal Transducing↗

Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review.

BACKGROUND: Anemia is common in cancer patients, although the prevalence is influenced both by the type of malignancy and the choice of treatment. Individual studies have compared the survival of patients with and without anemia and have shown reduced survival times in patients with various malignancies, including carcinoma of the lung, cervix, head and neck, prostate, lymphoma, and multiple myeloma. The objective of this study was to systematically review, to summarize, and to obtain an overall estimate of the effect of anemia on survival in patients with malignant disease. METHODS: A comprehensive literature review was carried out using the MEDLINE data base and reviewing the reference lists from published studies. Two hundred papers were identified. Of these, 60 papers that reported the survival of cancer patients according to either hemoglobin levels or the presence of anemia were included. Among these papers, 25% related to patients with lung carcinoma, 17% related to patients with head and neck carcinoma, 12% related to patients with multiple myeloma, 10% related to patients with prostate carcinoma, 8% related to patients with cervicouterine carcinoma, 7% related to patients with leukemia, 5% related to patients with lymphoma, and 16% related to patients with other types of malignancies. RESULTS: The relative risk of death increased by 19% (95% confidence interval, 10-29%) in anemic patients with lung carcinoma, by 75% (37-123%) in anemic patients with head and neck carcinoma, by 47% (21-78%) in anemic patients with prostate carcinoma, and by 67% (30-113%) in anemic patients with lymphoma. The overall estimate increase in risk was 65% (54-77%). CONCLUSIONS: Anemia is associated with shorter survival times for patients with lung carcinoma, cervicouterine carcinoma, head and neck carcinoma, prostate carcinoma, lymphoma, and multiple myeloma.

Anemia↗

Forbidden fruit: does thinking about a prohibited food lead to its consumption?

OBJECTIVE: The phenomenon of overeating the very foods that one is trying to resist is potentially consistent with both an ironic process account of overeating and a reactance account of the desire for "forbidden fruit." These two models are tested. METHOD: Participants in two studies were prohibited or not prohibited from eating a food, or they were encouraged to "choose" to avoid it. Food consumption, thoughts, and desire were assessed before and after the food was forbidden. RESULTS: Consistent with an ironic process account, participants' thoughts about the food increased, regardless of whether they were required to or chose to avoid it. Consistent with a reactance account, participants' desire for the food increased if they were required to avoid it, but not if they chose to avoid it. Participants did not, however, ultimately overeat the forbidden food. DISCUSSION: Neither increased thoughts nor enhanced desire for a food necessarily leads to overindulgence.

Adult↗

Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials.

BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS: A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Serum concentrations of vitamin D metabolites, vitamins A and E, and carotenoids in six canid and four ursid species at four zoos.

Nutritional status for six captive canid species (n=34) and four captive ursid species (n=18) were analyzed. The species analyzed included: African wild dog (Lycaon pictus), arctic fox (Alopex lagopus), gray wolf (Canis lupus), maned wolf (Chrysocyon brachyurus), Mexican wolf (Canis lupus baleiyi), red wolf (Canis rufus), brown bear (Ursus arctos), polar bear (Ursus maritimus), spectacled bear (Tremarctos ornatus), and sun bear (Ursus malayanus). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens, and North Carolina Zoological Park). The nutritional composition of the diet for each species at each institution met probable dietary requirements. Blood samples were collected from each animal and analyzed for vitamin D metabolites 25(OH)D and 1,25(OH)(2)D, vitamin A (retinol, retinyl stearate, retinyl palmitate), vitamin E (alpha-tocopherol and gamma-tocopherol) and selected carotenoids. Family differences were found for 25(OH)D, retinol, retinyl stearate, retinyl palmitate and gamma-tocopherol. Species differences were found for all detectable measurements. Carotenoids were not detected in any species. The large number of animals contributing to these data, provides a substantial base for comparing the nutritional status of healthy animals and the differences among them.

Animals↗

Pyrolysis mass spectrometry (PyMS) and 16S-23S rDNA spacer region fingerprinting suggests the presence of novel acinetobacters in activated sludge.

Screening of large numbers of Acinetobacter spp. from activated sludge systems with Pyrolysis Mass Spectrometry (PyMS) showed that many did not cluster tightly with the currently described genomic species which have been obtained mainly from clinical sources. Selected isolates were then genotypically fingerprinted using their 16S-23S rDNA spacer region, and again the data revealed considerable differences in the genomic fingerprints of many of these activated sludge isolates to the predominantly clinical genomic species. In fact, few could be identified from them. The possibility that the current speciation within this genus is not adequate to encompass all these environmental isolates is addressed in relation to the methods used to study the population dynamics of Acinetobacter in activated sludge.

Acinetobacter↗

Patient education provided to asthmatic children: a historical cohort study of the implementation of NIH recommendations.

NIH guidelines for treatment of childhood asthma emphasize educating both patients and family about avoiding triggers and providing information to support self-management of asthma. To determine the extent to which primary care providers had implemented these recommendations, we examined the patient education provided to a cohort of asthmatic children (n = 331) between January and December 1994. During 1994 education of any type was documented for less than half the children. Provision of education was associated with asthma severity: An action plan for exacerbations was discussed with the majority with moderate or severe asthma (61%). Avoiding triggers (aOR: 2.38, 95% CI: 1.37-4.12) and treatment goals (aOR: 3.14, 95% CI: 1.46-6.75), were more likely to be discussed with children who were prescribed inhaled anti-inflammatory medication, after adjustment for asthma severity and age. Limited implementation of the NIH recommendations by primary care providers in our study may have reduced their impact on the management of childhood asthma.

Administration, Inhalation↗

Asthmagenicity of coal mine roof-bolting resins: an assessment using inhalation provocation tests.

Inhalation provocation tests were used to assess whether the volatile products of an activated resin had caused occupational asthma in a non-random sample of six asthmatic coal miners. The resin system uses the polymerization of polyester and styrene under the influence of the cross-linking agent dibenzoyl peroxide to secure roof, wall and floor bolts in mine tunnels. The tests were conducted sequentially in a double-blind fashion over a 'dose' range which extended just beyond the maximum likely to have been experienced occupationally during a single day's work. The tests were monitored by symptoms, changes in the forced expiratory volume in 1 s (FEV1) and changes in airway responsiveness. All subjects completed the series of tests without any significant decrements in FEV1 or significant increases in airway responsiveness. We conclude that the use of this resin system is not likely to have been the cause of the asthma in the test subjects, nor in the larger group of miners of which they were a sample, but neither possibility is fully excluded and the participants may not have been adequately representative of other asthmatic coal miners.

Asthma↗

Radiotherapy equipment--purchase or lease?

Against a background of increasing demand for radiotherapy equipment, this study was undertaken to investigate options for equipment procurement, in particular to compare purchase with lease. The perceived advantages of lease are that equipment can be acquired within budget and cashflow constraints, with relatively low amounts of cash leaving the NHS in the first year, avoiding the necessity of capitalizing the equipment and providing protection against the risk of obsolescence associated with high technology equipment. The perceived disadvantages of leasing are that the Trust does not own the equipment, leasing can be more expensive in revenue terms, the tender process is extended and there may be lease conditions to be met, which may be costly and/or restrictive. There are also a number of technical considerations involved in the leasing of radiotherapy equipment that influence the financial analysis and practical operation of the radiotherapy service. The technical considerations include servicing and planned preventative maintenance, upgrades, spare parts, subsequent purchase of "add ons", modification of equipment, research and development work, commencement of the lease period, return of equipment at the end of the lease period and negotiations at the end of the lease period. A study from Raigmore Hospital, Inverness is described, which involves the procurement of new, state-of-the-art radiotherapy equipment. This provides an overview of the procurement process, including a summary of the advantages and disadvantages of leasing, with the figures from the financial analysis presented and explained. In addition, a detailed description is given of the technical considerations to be taken into account in the financial analysis and negotiation of any lease contract.

Hospital Costs↗

Attachment in anorexia nervosa: a transgenerational perspective.

Both clinical and empirical studies suggest that insecure attachment is common in eating disordered populations. Clinical studies have addressed mother-daughter interactions, but there has been little empirical research into the mother's own attachment patterns and whether there might be intergenerational transmission of these patterns. We aimed to examine the attachment status of patients with severe anorexia nervosa and their mothers, using the 'gold standard' Adult Attachment Interview (AAI). We predicted: (1) a high level of insecurity among the patients (women with anorexia nervosa with or without bulimic behaviours); (2) that the mothers would show a higher rate of insecurity than predicted by population norms; and (3) that there might be attachment style associations within mother-daughter pairs. Twenty consecutive in-patients with a DSM-IV diagnosis of anorexia nervosa were interviewed using the AAI, as were 12 of their mothers. The mental state of daughters was rated by experienced clinicians, and that of mothers by the Clinical Interview Schedule (Revised). AAIs were transcribed and rated by expert raters. Nineteen (95%) daughters and 10 (83%) mothers were rated insecure on the AAI. Of these, 15 (79%) daughters and seven (70%) mothers were dismissive in type. We did not find an association between mothers' and daughters' attachment style. The incidence of unresolved loss was high among the mothers (67%). Idealization scores were high and reflective functioning scores low in both mother and daughter groups. Women with anorexia nervosa and their mothers commonly have a dismissive attachment style. Low levels of reflective functioning and high idealization scores are found in both groups, and may be learned (or transmitted) from mother to daughter. A difficulty in emotional processing, exemplified by unresolved loss, may be transmitted to daughters, and act as a risk factor for the development of anorexia nervosa.

Adolescent↗

In vitro methylation of specific regions in recombinant DNA constructs by excision and religation.

The first imprinted genes were identified in the early 1990s (e.g., refs. 1,2) and there are now over 40 mammalian genes known to be regulated by genomic imprinting (for an up-to-date list, see ref. 3). The details of the mechanism that discriminates between the active and silent alleles of these genes, based on their parent of origin, may differ from one imprinted gene to the next, but must include some form of epigenetic mark that distinguishes alleles that have passed through the male or female germline (4-7). The addition of methyl groups to cytosine residues of CpG dinucleotides might provide such a mark, since regions of differential methylation have been identified in the vicinity of many of the known imprinted genes (8,9). Moreover, analysis of imprinted gene expression in a methyltransferase knockout (Dnmt1(-/-)) mouse has shown that the imprint is lost in a number of cases, resulting in either two silent alleles (Igf2, Igf2r and Kvlqt) or two expressed alleles (H19, p57(kip2), Snrpn, and Xist) (4,10-12). Although there may be exceptions (for instance, imprinted expression of Mash2 is maintained in Dmnt1(-/-) embryos; ref. 13), differential methylation is likely to be an important aspect of the imprinting mechanism that is relevant to most of the imprinted genes in mammals. There is accumulating evidence that methylation is also important for the imprinting of plant genes (reviewed in ref. 14).

Animals↗

Prokaryote multidrug efflux proteins of the major facilitator superfamily: amplified expression, purification and characterisation.

In bacterial genomes 3-12% of open reading frames are predicted to encode membrane transport proteins. These proteins can be vital for antibiotic efflux, protein/ toxin secretion, cell nutrition, environmental sensing, ATP synthesis, and other functions. Some, such as the multidrug efflux proteins, are potential targets for the development of new antibacterials and also for applications in biotechnology. In general membrane transport proteins are poorly understood, because of the technical difficulties involved in isolating sufficient protein for elucidation of their structure-activity relationships. We describe a general strategy for the amplified expression, purification and characterisation of prokaryotic multidrug efflux proteins of the 'Major facilitator superfamily' of transport proteins, using the Bacillus subtilis multidrug resistance protein, 'Bmr', as example.

Amino Acid Sequence↗

Fish shoal composition: mechanisms and constraints.

Observations were made on three fish species (banded killifish (Fundulus diaphanus), golden shiner (Notemigonus crysoleucas) and white sucker (Catostomus commersoni)) in a temperate lake (New Brunswick, Canada) in order to investigate the relationship between shoal choice behaviour of individual fishes and shoal composition. Encounters between shoals were observed to take place every 1.1 min per shoal and an encounter lasted 3.7 s on average. The duration of shoal encounters was influenced by shoal size but not by differences between shoals in either body length or species. Conversely, the outcome of shoal encounters (i.e. ences between shoals in either body length or species. Conversely, the outcome of shoal encounters (i.e. whether or not an individual changes shoal) was influenced by body length and species differences but not by shoal size. Together, these results suggest that encounter duration itself is unlikely to have an important influence on encounter outcome. The collection of ten entire fish shoals showed that they were assorted by species and body length. A simulation model demonstrated that individual shoal choice behaviour alone could account for the generation and maintenance of the observed levels of size assortedness of shoals without invoking the existence of other sorting mechanisms such as differential swimming speeds. However, the generation of species assortedness was not predicted by the model. Furthermore, our data suggest that fish density acts as a constraint on shoal choice, influencing both shoal size and composition. This work has implications for studies on information transfer and reciprocal altruism within populations.

Animals↗

Mental health. Picking up the pieces.

Research in Leeds had identified a group of mental health users whose lifestyles were often destructive and who appeared to be on an endless cycle of care between various statutory agencies. Oakwood Hall, a joint-funded, voluntary sector hostel has developed a holistic approach for 'difficult to place' individuals, enabling them to move back into mainstream support services. The objective of the service is to combine compassion with a nonjudgemental stance, encouraging social integration of clients, combined with boundaries for individual behaviour. The service offers respite care and a 24-hour telephone support system. The approach has led to a significant and positive change for many.

Crisis Intervention↗

Eating disorders: psyche or soma?

Speculation about the etiology of eating disorders has gone through different phases, variously favoring familial, organic, and psychosocial factors. Recent evidence has particularly contributed to our understanding of the organic view. We review the evidence for an organic contribution to the illness and present a series of cases in which organic factors were present. The cases illustrate the complex interaction between biological and psychological factors. In particular, a growth hormone-producing pituitary adenoma was discovered in a patient following successful treatment of her bulimia by psychological means alone. Etiological theories of eating disorders need to encompass both organic and psychosocial factors, allowed to interact in complex ways. Focusing exclusively on either aspect is a disservice to our patients.

Adenoma↗

Attachment patterns in eating disorders: past in the present.

OBJECTIVE: There is a wide literature suggesting abnormal mother-daughter and familial attachment patterns in individuals with eating disorders. We surmised that this insecurity would extend to adult attachment relationships. METHODS: The Reciprocal Attachment Questionnaire (RAQ) was administered to all inpatients and outpatients at a tertiary referral eating disorders unit over a given period of time, and to controls. The RAQ operationalizes the key components of reciprocal attachment, and is in close theoretical agreement with the Adult Attachment Interview. RESULTS: Patients scored significantly higher than controls on most scales of the RAQ, most notably on Compulsive Care-Seeking and Compulsive Self-Reliance. We did not find any associations between eating disorder diagnoses and particular attachment profiles. CONCLUSIONS: A basic "pull-push" dilemma was demonstrated in the reciprocal attachment relationships of eating-disordered subjects. This dilemma bedevils attempts at therapy and may illuminate the strong feelings elicited by these patients in their therapists. The association of attachment style with particular disorder subgroup diagnoses is complicated. Childhood attachment insecurity may provide a vulnerability whose symptomatic manifestation is colored by later events.

Adult↗

Don't mind if I do: disinhibited eating under cognitive load.

Past research has shown that strong emotional or motivational states can cause normally restrained eaters to overeat. In this article it is argued that simple cognitive load can also disinhibit eating by restrained eaters. Two studies examined this disinhibition effect. In Study 1, restrained and unrestrained eaters were given the opportunity to consume high-calorie food while performing either a high cognitive-load or low cognitive-load task. Restrained eaters consumed more food when under high cognitive load than when under low cognitive load; unrestrained eaters showed the opposite pattern. Study 2 replicated the disinhibition effect and ruled out stress, diminished awareness of food consumption, and ironic rebound as probable mediators. Results suggest that cognitive load may disinhibit consumption by preventing restrained eaters from monitoring the dietary consequences of their eating behavior. Implications for theories of self-regulation are discussed.

Adaptation, Psychological↗