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Biomedical subjects

S Gray

Publications and source records attributed to S Gray.

At least 73 records · Page 4Linked to original sources
PubMed1999

Influence of high and low glycemic index meals on endurance running capacity.

PURPOSE: The purpose of this study was to examine the effect of high and low glycemic index (GI) carbohydrate (CHO) pre-exercise meals on endurance running capacity. METHODS: Eight active subjects (five male and three female) ran on a treadmill at approximately 70% VO2max to exhaustion on two occasions separated by 7 d. Three hours before the run after an overnight fast, each subject was given in a single-blind, random order, isoenergetic meal of 850+/-21 kcal (mean+/-SEM; 67% carbohydrate, 30% protein, and 3% fat) containing either high (HGI) or low (LGI) GI carbohydrate foods providing 2.0 g CHO.kg(-1) body weight. RESULTS: Ingestion of the HGI meal resulted in a 580% and 330% greater incremental area under the 3-h blood glucose and serum insulin response curves, respectively. Performance times were not different between the HGI and LGI trials (113+/-4 min and 111+/-5 min, respectively). During the first 80 min of exercise in the LGI trial, CHO oxidation was 12% lower and fat oxidation was 118% higher than in the HGI trial. Although serum insulin concentrations did not differ between trials, blood glucose at 20 min into exercise in the HGI trial was lower than that during the LGI trial at the same time (3.6+/-0.3 mmol.L(-1) vs 4.3+/-0.3 mmol.L(-1); P < 0.05). During exercise, plasma glycerol and serum free fatty acid concentrations were lower in the HGI trial than in the LGI trial. CONCLUSIONS: This results demonstrate that although there is a relative shift in substrate utilization from CHO to fat when a low GI meal is ingested before exercise compared with that for a high GI meal, there is no difference in endurance running capacity.

Adult↗
PubMed1999

The Bristol Shared Care Glaucoma Study: reliability of community optometric and hospital eye service test measures.

BACKGROUND/AIMS: Primary open angle glaucoma patients and glaucoma suspects make up a considerable proportion of outpatient ophthalmological attendances and require lifelong review. Community optometrists can be suitably trained for assessment of glaucoma. This randomised controlled trial aims to assess the ability of community optometrists in the monitoring of this group of patients. METHODS: Measures of cup to disc ratio, visual field score, and intraocular pressure were taken by community optometrists, the hospital eye service and a research clinic reference "gold" standard in 405 stable glaucoma patients and ocular hypertensives. Agreement between and within the three centres was assessed using mean differences and intraclass correlation coefficients. Tolerance limits for a change in status at the level of individual pairs of measurements were also calculated. RESULTS: Compared with a research clinic reference standard, measurements made by community optometrists and those made in the routine hospital eye service were similar. Mean measurement differences and variability were similar across all three groups compared for each of the test variables (IOP, cup to disc ratio, and visual field). Overall, the visual field was found to be the most reliable measurement and the cup to disc ratio the least. CONCLUSIONS: Trained community optometrists are able to make reliable measurements of the factors important in the assessment of glaucoma patients and glaucoma suspects. This clinical ability should allow those optometrists with appropriate training to play a role in the monitoring of suitable patients.

Community Health Services↗
PubMed1999

Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair.

BACKGROUND: Despite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments. AIMS: To assess the feasibility of using immunohistochemistry to detect replication error (RER) positive CRCs and determine the incidence of RER positivity within distinct patient subgroups. METHODS: 502 CRCs were analysed for RER positivity (at least two markers affected) and/or expression of hMSH2 and hMLH1. RESULTS: There were 15/30 (50%) patients with metachronous CRCs, 16/51 (31%) with synchronous CRCs, 14/45 (31%) with a proximal colon carcinoma, and 4/23 (17%) who developed a CRC under the age of 50 showed RER positivity. However, 0/54 patients who developed a solitary carcinoma of the rectum/left colon over the age of 50 showed RER positivity. Immunohistochemical analysis revealed that 66/66 (100%) RER positive carcinomas were associated with complete lack of expression of either hMSH2 or hMLH1. This correlation was confirmed using a further 101 proximal colon carcinomas. Patients with a mismatch repair defective carcinoma showed improved survival but a 5.54 times relative risk of developing a metachronous CRC. A prospective immunohistochemical study revealed 13/117 (11%) patients had a mismatch repair defective carcinoma. A fivefold excess of hMLH1 defective cases was noted. CONCLUSIONS: All RER positive carcinomas were identified by the immunohistochemical test. This is the first simple laboratory test which can be performed routinely on all CRCs. It will provide a method for selecting patients who should be investigated for HNPCC, offered long term follow up, and who may not respond to standard chemotherapy regimens.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Expression of the 17-1A antigen in gastric and gastro-oesophageal junction adenocarcinomas: a potential immunotherapeutic target?

BACKGROUND: A murine monoclonal antibody against the 17-1A epithelial antigen has been shown to be a useful adjuvant therapy in colorectal cancer. Its clinical use could be extended to patients with upper gastrointestinal adenocarcinoma. AIM: To determine the distribution of the antigen in gastric and oesophageal adenocarcinoma. METHODS: The activity of two monoclonal antibodies active against 17-1A epithelial antigen was studied in gastric and gastro-oesophageal junction adenocarcinomas: fresh frozen tissue from both the carcinoma and adjacent mucosa was stained using immunocytochemistry with a murine monoclonal antibody (17-1A edrecolomab, Glaxo Wellcome); paraffin embedded tissue was stained using the humanised monoclonal antibody 3622W94 (Glaxo Wellcome). RESULTS: 29 of 33 cancers (88%) stained with the murine antibody and 39 of 40 (98%) with the humanised antibody. The degree of staining was greater in well differentiated and moderately differentiated tumours. There was no staining of the normal background gastric or oesophageal mucosa, but areas of intestinal metaplasia stained intensely. The humanised monoclonal 3622W94 antibody produced more intense staining than the murine antibody. CONCLUSIONS: The high incidence of expression of the 17-1A antigen in patients with gastric and gastro-oesophageal junction adenocarcinomas suggests a potential role for these antibodies as an adjuvant treatment for these common cancers.

Adenocarcinoma↗
PubMed1999

Systolic blood pressure within an intermediate range may reduce memory loss in an elderly hypertensive cohort.

The objective of this study was to determine if maintenance of systolic blood pressure (BP) within a high range or low range among treated hypertensive patients increases the risk of memory decline. Biennial neuropsychological evaluations were performed on 158 hypertensive subjects. Decline/year was measured on the Cued Selective Reminding test (total free recall and delayed recall) in three systolic BP groups (low-i.e., mean systolic BP during the follow-up period < 135 mm Hg; intermediate-i.e., 135 mm Hg < or = mean systolic BP < or = 150 mm Hg; high-i.e., mean systolic BP > 150 mm Hg). In total free recall, the three systolic BP groups had significantly different declines per year (P = .02), with patients in the high subgroup showing the greatest decline. In delayed recall, the three systolic BP groups also showed significantly different declines per year (P = .04), with patients in the low subgroup having the greatest decline. Chronically elevated systolic BP > 150 mm Hg is associated with accelerated memory decline compared to older treated hypertensive patients with systolic BP in an intermediate range. Chronically maintained systolic BP within a low normal range < 135 mm Hg in older treated hypertensive subjects may be associated with accelerated memory decline, specifically in a test of delayed memory recall, compared to patients with systolic BP in an intermediate range. Optimal regulation of systolic BP may be a potential modifiable risk factor to prevent or minimize memory loss in older hypertensive patients.

Aged↗
PubMed1999

Genotyping of adrenocortical tumors: very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16.

To identify chromosomal regions that may contain loci for tumor suppressor genes involved in adrenocortical tumor development, a panel of 60 tumors (39 carcinomas and 21 adenomas) were screened for loss of heterozygosity. Although the vast majority of loss of heterozygosity (LOH) were detected in the carcinomas and involved chromosomes 2, 4, 11, and 18, only few were found in the adenomas. Therefore, 2 loci that harbor the familial cancer syndromes Carney complex in 2p16 and the multiple endocrine neoplasia type 1 gene in 11q13 were further studied in 27 (13 carcinomas and 14 adenomas) of the 60 tumors. Detailed analysis of the 2p16 region mapped a minimal area of overlapping deletions to a 1-centimorgan region, which is separate from the Carney complex locus. LOH for a microsatellite marker (PYGM), very close to the MEN1 gene, was detected in all 8 informative carcinomas (100%) and in 2 of 14 adenomas. Of the 27 cases analyzed in detail, 13 cases (11 carcinomas and 2 adenomas) showed LOH on chromosome 11 and was therefore selected for MEN1 gene mutation analysis. In 6 cases a common polymorphism (Asp418Asp) was found, but no mutation was detected. In conclusion, our data indicate the existence of tumor suppressor genes at multiple chromosomal locations, whose inactivations are involved in the development of adrenocortical carcinomas. Loss of genetic material from 2p16 was strongly associated with the malignant phenotype, as it was seen in almost all carcinomas but not in any of the adenomas. LOH in 11q13 also occurred frequently in the carcinomas, but was not associated with a MEN1 mutation, suggesting the involvement of a different tumor suppressor gene on this chromosome.

Adenoma↗
PubMed1999

Deposition and disposition of [11C]zanamivir following administration as an intranasal spray. Evaluation with positron emission tomography.

OBJECTIVE: This study used positron emission tomography (PET) to investigate the deposition and disposition of zanamivir administered as a nasal spray. DESIGN: This was an open-label single-dose study in healthy volunteers. STUDY PARTICIPANTS: Six healthy male volunteers, aged 19 to 33 years (mean age 25 years) with a bodyweight of 65 to 94 kg (mean bodyweight 76 kg), took part in the study. INTERVENTIONS: Each participant received by nasal spray zanamivir 6.4 mg mixed with, on average, 2.5 MBq of [11C]zanamivir. The amount of radioactivity was recorded sequentially in 5 different sectors of the body, starting with a short dynamic sequence over the nasal passage. Each of the regions was examined 1 to 4 times at different times after inhalation. The duration of the examination was 90 minutes. During this time, multiple blood samples were taken for analysis of radioactivity in whole blood. Serum samples for pharmacokinetic determinations were collected for 8 hours after administration. RESULTS: Immediately after administration, about 90% of the drug was deposited in the nasal passage, decreasing to 48% at 90 minutes after administration. Less than 2% was detected in the lower respiratory tract. The major elimination route was via the oesophagus to the stomach. Approximately 2% of the dose was absorbed; the median maximum drug concentration in serum was 15 micrograms/L, and occurred around 1.75 hours after inhalation. CONCLUSIONS: The major deposition site for zanamivir administered by nasal inhalation is the nasal passage; half of the drug remains there for at least 1.5 hours after administration. PET seems to be an excellent tool for this type of kinetic study, allowing imaging and measurements of inhaled drugs with high quantitative accuracy and good spacial resolution.

Administration, Intranasal↗
PubMed1999

General practitioners' use of guidelines in the consultation and their attitudes to them.

BACKGROUND: There is concern about the apparent lack of uptake of management and referral guideline information by general practitioners (GPs) in their day-to-day consultations with patients. Little is understood about the barriers to the uptake of guidelines as perceived by GPs. AIMS: To explore how GPs gain access to and use guidelines, including computer-based guidelines, in day-to-day consultations with their patients; and to identify the perceived problems and barriers to the use of guidelines in such situations. METHOD: Postal questionnaires enquiring about the practices and attitudes towards the use of guidelines in general practice were completed by 391 of 600 randomly selected GPs in the South and West NHS region. RESULTS: GPs found guidelines a useful method of accessing expert information. Key factors in their uptake were brevity, an authoritative and unbiased source of evidence, and resonance with the GP's usual practices; they also needed to be flexible enough to incorporate individual viewpoints. Guidelines were perceived as being valuable to enable safe delegation of care to other health professionals and for sharing decision-making with patients. Dissemination of guidelines through the medium of computers was acceptable to the majority of GPs. Virtually all (93%) responders reported adapting guidelines to the needs of individual patients. Older GPs from non-fundholding practices were least likely to show a positive attitude towards guidelines. CONCLUSION: In principle, there is a very positive attitude towards the use of guidelines in general practice. However, those developing guidelines for use by GPs in the consulting room need to be aware of the factors that facilitate their use in practice. Educational strategies aimed at increasing the use of guidelines need to take into account the significant proportion who show negative attitudes towards guidelines, whose characteristics have been identified in this study.

Attitude of Health Personnel↗
PubMed1999

General practitioners' use of computers during the consultation.

This study documents the extent of reported computer use by general practitioners (GPs) in consultations with patients, and identifies barriers to their use. There was a 65% response rate from a random sample of 600 GPs in the South and West National Health Service (NHS) region who were sent a questionnaire. Ninety-one per cent (357) had a desktop computer terminal in their consulting rooms. Of these, 98% used the computer to look up information or prescribe medication, 75% entered details about selected problems presented by patients, and 36% entered information about the patient's presenting problem at every consultation. Only 18% used computers to access reference information. Use of the computer for anything other than looking up patient information or prescribing was positively associated with fundholding status and use of a personal computer at home, and was independent of number of years in practice. Sixty-five per cent of responders had positive attitudes to the inclusion of management guidelines on the computer software, and 45% of responders held positive views towards the idea of integrating management guidelines with the patient's personal computerized medical record. Consideration should be given to targeting training at those GPs who appear to be reluctant to use computers during the consultation.

Attitude to Computers↗
PubMed1998

Stability of reconstituted indomethacin sodium trihydrate in original vials and polypropylene syringes.

The stability of reconstituted indomethacin sodium trihydrate 0.5 mg/mL in sterile water for injection for 14 days at either 2-6 degrees C or room temperature (21-25 degrees C) in the drug's original vial and in polypropylene syringes was studied. Twenty 1-mg vials of indomethacin sodium trihydrate were reconstituted with 2 mL of Sterile Water for Injection, USP. Solution from 10 vials was drawn into 20 1-mL disposable polypropylene syringes. Five vials and 10 syringes were stored at 21-25 degrees C, and the other 5 vials and 10 syringes were stored at 2-6 degrees C. Samples were taken on days 0, 1, 2, 4, 5, 7, 9, 12, and 14 and analyzed by liquid chromatography. Physical inspections and pH determinations were made as well. Throughout the study period, all solutions stored at 2-6 degrees C retained more than 95% of the initial indomethacin concentration. At room temperature, solutions stored in syringes retained more than 95% of the initial indomethacin concentration. Solutions stored in glass vials contained only 89.7% of the initial concentration on day 14. Solutions stored at room temperature in either syringes or vials had greater amounts of degradation products than solutions stored at 2-6 degrees C. Reconstituted indomethacin sodium trihydrate 0.5 mg/mL was stable for 14 days when stored in polypropylene syringes at 2-6 or 21-25 degrees C and in its original glass vials at 2-6 degrees C. When stored in the glass vials at 21-25 degrees C, the reconstituted drug was stable for 12 days.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Assessment of intratumoral vascularization (angiogenesis) in breast cancer prognosis.

The search for prognostic markers is important both to identify those patients with occult metastases and also to spare chemotherapy in those patients whose tumors have not developed the capacity for distant spread. Angiogenesis, the formation of new blood vessels, is necessary for breast cancer growth and metastasis. Good correlation has been demonstrated between intratumoral vascularization and outcome in patients with breast cancer. Intratumoral vascularization in human breast cancer can be measured by using standard immunohistochemical methods. Strict guidelines for scoring need to be followed. Although attempts are being made to automate the reading, visual scoring remains superior. We studied a population of women with small node-negative breast cancer who received no adjuvant therapy and have a median follow-up of 15 years. We have found intratumoral vascularization, as measured by microvessel count, to be an independent prognostic factor for disease-free survival. Low microvessel count identifies a group of patients with a 20 year disease free survival of 93%. The proportion of women with low microvessel count decreases with increase in tumor size and increases with patient age. But even in mammographically detected nonpalpable breast cancer, that is, the smallest breast cancer we currently detect, the majority already have high microvessel count. Intratumoral vascularization appears to be an early event that is necessary but not sufficient for metastatic progression. Microvessel count seems to be an excellent marker to identify patients with good prognosis because those with low microvessel count have a 93% disease-free survival irrespective of size, grade, or estrogen receptor status, but is less good at predicting those at high risk since the 20-year disease-free survival is still 67-70% in those with high microvessel count. Thus, the higher risk group needs to be further stratified using additional prognostic factors.

Breast Neoplasms↗
PubMed1998

Containment of herbicide resistance through genetic engineering of the chloroplast genome.

Glyphosate is a potent herbicide. It works by competitive inhibition of the enzyme 5-enol-pyruvyl shikimate-3-phosphate synthase (EPSPS), which catalyzes an essential step in the aromatic amino acid biosynthetic pathway. We report the genetic engineering of herbicide resistance by stable integration of the petunia EPSPS gene into the tobacco chloroplast genome using the tobacco or universal vector. Southern blot analysis confirms stable integration of the EPSPS gene into all of the chloroplast genomes (5000-10,000 copies per cell) of transgenic plants. Seeds obtained after the first self-cross of transgenic plants germinated and grew normally in the presence of the selectable marker, whereas the control seedlings were bleached. While control plants were extremely sensitive to glyphosate, transgenic plants survived sprays of high concentrations of glyphosate. Chloroplast transformation provides containment of foreign genes because plastid transgenes are not transmitted by pollen. The escape of foreign genes via pollen is a serious environmental concern in nuclear transgenic plants because of the high rates of gene flow from crops to wild weedy relatives.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1998

Word learning in a supported-learning context by preschool children with specific language impairment.

Word learning in a supported-learning context is described for 30 preschoolers with SLI and 30 age- and sex-matched children without SLI. Daily production probes assessed number of words learned to criterion, and daily posttests assessed comprehension of the words. Number of words produced to criterion differed between groups; however, the majority of children with SLI performed within the range of the children without SLI. Children typically comprehended words they did not produce to criterion. The relation between vocabulary-test and word-learning findings was not significant (p < .05). Findings for children with SLI indicate that (a) comprehension does not ensure same-word production, (b) word-learning potential cannot be inferred from test scores, and (c) a clinically significant variability in word-learning skills characterizes the disorder.

Child, Preschool↗
PubMed1998

First stage labor management: An examination of patterned breathing and fatigue.

BACKGROUND: Patterned breathing is one way that women cope with labor. Fatigue is a frequently reported symptom over which women and caregivers have little control. The purpose of this study was to examine the relationship between the use of patterned breathing, a traditional intervention, and the level of fatigue reported during the first stage of labor. METHOD: A secondary analysis was conducted on a subset (n = 56) of a prospective longitudinal study of fatigue during the intrapartum period. The sample comprised primiparous women in labor whose fatigue was measured every two hours for six hours after admission. At each data point the investigator evaluated the method of breathing that participants used. RESULTS: During the latent phase of labor, women using patterned breathing exhibited significantly more fatigue. In the active phase, differences between groups were not significant. Controlling for age, education, and marital status of participants did not change the results. CONCLUSIONS: It is appropriate for nurses, midwives, physicians, and doulas to encourage the use of patterned breathing as an intervention in active labor; however, patterned breathing may increase the mother's fatigue level if begun too early.

Adaptation, Psychological↗
PubMed1998

Use of guidelines in primary care--practitioners' perspectives.

BACKGROUND AND OBJECTIVES: Concern about the inadequate take-up of guidelines in general practice has concentrated on problems arising from the process of their development and implementation. However, these perspectives fail to take account of the needs, attitudes and problems of GPs themselves. In this study we aimed to identify barriers to the use of guidelines and opportunities for tackling them, from the point of view of the GP, so that future guideline development and policy could be more sensitive to the needs of GPs in the environment in which they work. METHOD: Twenty in-depth semi-structured interviews were audiotaped with GPs from within the Avon Health Authority area, representing GPs with different backgrounds and working environments. The transcribed data collected were analysed using a grounded theory approach. RESULTS: Utilization of guideline information is complex. GPs' appraisals of the value of guidelines interact with prior knowledge and beliefs, practicalities of existing information storage and retrieval systems, and individual working practices. Conditions where guidelines are most likely to be referred to may be those either very rarely or very commonly presenting in general practice. Key issues for the uptake of guidelines in the consultation are: general preference for certain formats of presentation; reputability and ownership; use of guidelines in shared decision-making; scope for computer-based systems; and GPs' attitudes to time pressures on information-seeking in relation to tolerance of uncertainty. CONCLUSION: Local initiatives might usefully explore the possibilities of supporting development of guideline-retrieval systems customized for individual GPs or practices. Novel means of stimulating 'ownership' and demonstrating reputability should be sought. The analysis provides a framework for understanding the complexities of the processes of GPs' use of guidelines in practice which can be useful in explaining the results of trials of guideline effectiveness. Guideline implementation occurs in the context of conflicting pressures for clinical autonomy and professional standardization and quality improvement.

Attitude of Health Personnel↗
PubMed1998

The Direct Assessment of Functional Abilities (DAFA): a comparison to an indirect measure of instrumental activities of daily living.

The Direct Assessment of Functional Abilities (DAFA) was designed as a direct measure of instrumental activities of daily living (IADLs) that could be compared with an indirect assessment of IADLs by the Pfeffer Functional Activities Questionnaire (PFAQ). The DAFA (28 demented and 15 control subjects) and PFAQ (subjects and informants) were administered twice, together with a brief cognitive battery. Demented subjects performed significantly worse on direct assessment (DAFA) than predicted by self-report (PFAQ), and overestimation of abilities increased with severity of dementia. In contrast, informants tended to underestimate abilities of demented subjects, but not to a significant degree. Control (nondemented) subjects had comparable results with the two methods. The DAFA may provide a more objective measure of functional status in demented subjects than do indirect methods of assessment.

Activities of Daily Living↗
PubMed1998

Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset.

OBJECTIVES: The goal of this study was to project the future prevalence and incidence of Alzheimer's disease in the United States and the potential impact of interventions to delay disease onset. METHODS: The numbers of individuals in the United States with Alzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections. RESULTS: in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: 1.09 to 4.58 million); of these individuals, 68% were female. It is projected that the prevalence will nearly quadruple in the next 50 years, by which time approximately 1 in 45 Americans will be afflicted with the disease. Currently, the annual number of new incident cases in 360,000. If interventions could delay onset of the disease by 2 years, after 50 years there would be nearly 2 million fewer cases than projected; if onset could be delayed by 1 year, there would be nearly 800,000 fewer prevalent cases. CONCLUSIONS: As the US population ages, Alzheimer's disease will become an enormous public health problem. interventions that could delay disease onset even modestly would have a major public health impact.

Age Distribution↗