Cutaneous clues to Cronkhite-Canada syndrome: a case report.
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Biomedical subjects
Publications and source records attributed to A Bruce.
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BACKGROUND: Animal studies suggest that monounsaturated and polyunsaturated fat may have opposite effects on the risk of breast cancer. METHODS: We performed a population-based prospective cohort study, including 61,471 women aged 40 to 76 years from 2 counties in central Sweden who did not have any previous diagnosis of cancer; 674 cases of invasive breast cancer occurred during an average follow-up of 4.2 years. All subjects answered a validated 67-item food frequency questionnaire at baseline. Cox proportional hazards models were used to obtain adjusted rate ratio (RR) estimates with 95% confidence intervals (CIs). RESULTS: After mutual adjustment of different types of fat, an inverse association with monounsaturated fat and a positive association with polyunsaturated fat were found. The RR for each 10-g increment in daily intake of monounsaturated fat was 0.45 (95% CI, 0.22-0.95), whereas the RR for a 5-g increment of polyunsaturated fat was 1.69 (95% CI, 1.02-2.78); the increments correspond to approximately 2 SDs of intake in the population. Comparing the highest quartile of intake with the lowest, we found an RR of 0.8 (95% CI, 0.5-1.2) for monounsaturated fat and 1.2 (95% CI, 0.9-1.6) for polyunsaturated fat. Saturated fat was not associated with the risk of breast cancer. CONCLUSIONS: Our results indicate that various types of fat may have specific opposite effects on the risk of breast cancer that closely resemble the corresponding effects in experimental animals. Research investigations and health policy considerations should take into account the emerging evidence that monounsaturated fat might be protective for risk of breast cancer.
PURPOSE: To compare intraoperative anaesthetic and haemodynamic effects of clonidine-bupivacaine, morphine-bupivacaine and placebo-bupivacaine combinations during continuous spinal anaesthesia. METHODS: Thirty six geriatric patients, undergoing knee replacement using continuous spinal anaesthesia were randomly assigned to: Placebo (n = 12), clonidine (n = 12) and morphine (n = 12), where 1 ml saline, 0.15 mg clonidine or 0.15 mg morphine were mixed with 10 mg bupivacaine 0.5%. Anaesthetic variables studied were maximal sensory level and degree of motor block, duration of surgical analgesia and duration of anaesthesia. Changes in systolic arterial pressure and vasopressor requirements were evaluated. RESULTS: Maximal sensory level and degree of motor block were comparable among the groups. Before surgery two patients in the placebo group, three in the clonidine and one in the morphine group received one additional ml bupivacaine 0.5% because of inadequate anaesthesia and were not considered for determination of duration of surgical analgesia. In the remainder, 1/9 in the clonidine group, 8/10 in placebo and 8/11 in morphine (P < 0.05) received reinjection of bupivacaine for surgical pain. These injections were given about 2 1/2 hr after the initial intrathecal injection, the duration of anaesthesia being about four hours. During the first 30 min after the initial injection the decrease in systolic pressure was greater in the clonidine and morphine than in the placebo group (P < 0.05). Thereafter, vasopressor requirements were higher only in the clonidine group (P < 0.05). CONCLUSION: In elderly patients 0.15 mg clonidine but not 0.15 mg morphine prolonged surgical analgesia when added to 10 mg plain bupivacaine.
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OBJECTIVE: To examine the effectiveness of dementia programmes and report factors related to programme outcomes. To describe the characteristics which placed hostel residents at risk for nursing home placement and to measure changes in dependencies and impairments over 2 years. DESIGN: Longitudinal, quasi-experimental using in situ resident groups matched on resident and facility characteristics. SETTING: Australian hostels for the elderly. SUBJECTS: 587 residents (programme group N = 184, comparison group N = 162, frail groups N = 241). MEASURES: Mini-Mental State Examination, Geriatric Depression Scale and staff-rated indices of functioning, including activities of daily living, problem behaviours, psychiatric symptomology and health status, were used to monitor changes in resident characteristics. Time to nursing home placement was another outcome measure. RESULTS: Residents in hostel dementia programmes remained significantly longer than those in the comparison group (2.5 months over 2 years) before exit to a nursing home. Quality of life for residents in dementia programmes was enhanced through higher levels of social contact with relatives and lower reported levels of depressive symptoms. CONCLUSIONS: Dementia programmes worked, but the reasons why were more difficult to establish. The programmes did not appear to modify the capacities of residents by slowing rates of decline. Dementia programmes provided specialist (non-personal care) staff focusing on the social and emotional needs of residents. These staff provided appropriate, targeted activities for residents with dementia, had a clearly defined role directed exclusively to these residents and felt directly responsible for them. Dementia programmes produced a system effect. They increased the capacity of hostels to care for residents with dementia for longer periods, before admission to a nursing home.
The p53 tumor suppressor gene encodes a cell cycle regulatory protein that is induced by DNA damage and has been implicated in apoptosis. To investigate whether excitotoxic cell death due to kainic acid (KA) and cell death due to N-methyl-D-aspartate (NMDA) share similar molecular mechanisms, we studied p53 expression and DNA fragmentation in organotypic hippocampal slice cultures following excitotoxin treatment. Cellular analyses showed that both p53 induction and DNA fragmentation occurred only in injured neurons following exposure to either excitotoxin. The temporal profiles of these changes demonstrated that p53 induction preceded DNA fragmentation. The extent of regional alterations in p53 expression and DNA fragmentation correlated with drug-related toxicity (i.e., NMDA > KA). These results support the hypothesis that p53 is a marker of neuronal death in the CNS and suggest the possibility that excitotoxin-mediated neuronal death may occur through a p53-dependent pathway.
Dietary reference values for food energy for population groups are set at the level of average energy requirement without a safety margin to avoid any risk of inadequate energy intake. Average energy requirements and hence reference values for energy can be determined from either energy intake data or energy expenditure. In this article, the present reference values for energy of 12 countries, the FAO/WHO/UNU and the Scientific Committee on Food (SCF/EC) are compared regarding the level of their standards and underlying concepts. Methods for estimating energy requirements of different population groups and data sources for reference values for energy are summarized. Furthermore, reference values for energy for males and females of all ages are presented in separate graphs. The comparison of national standards illustrates that the level of reference values for energy for individual countries is dependent on variables such as methodology, data sources, allowances for physical activity, reference body weight, and age range. Standards for adolescents and elderly persons reveal that differences in reference values are most apparent in population groups for which only limited data on energy requirements are available. Although it is not possible to evaluate the adequacy of reference values for energy by comparing data of different countries, many differences in the level of reference values can be explained on the basis of underlying concepts.
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OBJECTIVES: The iron fortification of food in Sweden, the highest in the world, was withdrawn 1st January 1995, because the effect upon target groups was considered to be uncertain. We wanted to study the effect of such a dietary experiment. DESIGN: Comparative cross over study. SETTING: Out patient service and Blood Bank. SUBJECTS: Sixteen men aged 24-73 y on maintenance phlebotomy after treatment for iron overload. One was excluded because of inflammatory disease. INTERVENTIONS: Quantitative phlebotomy with serial measurements of Hb conc., % transferrin saturation and serum ferritin concentration. MAIN OUTCOME MEASURES: Iron absorption was measured by phlebotomy during two periods, with and without iron fortification. 1 g Hb = 3.4 mg Fe. RESULTS: Iron absorption was significantly reduced (P < 0.001) when iron fortification was withdrawn from a mean of 4.27 +/- 1.2 to 3.63 +/- 1.1 mg/d. The difference of 0.65 mg/d (95% c.i. 0.32-0.97) corresponds to the fraction of iron derived from fortification. Intervals between donations had to be extended from 59 +/- 15 to 69 +/- 17 d (P < 0.01) to avoid induction of iron deficiency anemia. The iron content of the fortified diet averaged 15.4 mg/d, of which the fortified fraction constituted 4.1 mg/d (27%). The relative bioavailability of carbonyl iron used as fortificant was 38%. CONCLUSIONS: The relative bioavailability of carbonyl iron used as fortificant was higher than previously reported. Target groups such as menstruating females will probably be affected by a higher prevalence of iron deficiency when food is no longer fortified. People with genetic hemochromatosis will accelerate into clinical disease at a slower rate.
BACKGROUND: In retrospective studies of dietary habits and breast cancer risk, recall bias is a concern since diet has been publicized as a cause of breast cancer. METHODS: In a case-control study of diet and breast cancer risk nested within a cohort of women screened with mammography, we contrasted answers to a retrospective dietary interview with answers to a dietary questionnaire which was filled out before any diagnostic procedures for breast cancer were undertaken. The source population was all women aged 40-74 in two counties in Sweden invited to mammographic screening and asked to fill out a questionnaire before the screening. Cases and controls were subsequently defined -- matched on age, county of residence, and time of mammography -- and approached for an interview. RESULTS: In all, 265 cases and 431 controls participated in the study. Means of frequencies differed between the agreement in the questionnaire's and the interview's classifications of study subjects into quartiles of monthly intake varied between 31 percent and 57 percent. Kappa statistics in all food groups were below 0.41. In a regression analysis, case subjects with low responses on the questionnaire about intake of meat, snacks, and coffee and tea gave higher responses on interview than did controls who had low questionnaire responses for these food groups. The reverse was also true: cases' responses that were high on the questionnaire were lower on interview for these food groups than were controls' responses. CONCLUSIONS: We found few signs of recall bias, and the few indications of a differential misclassification that we found were not in food groups that have been publicly discussed as causes of breast cancer.
PURPOSE: Knowledge about the mobility of organs relative to the bony anatomy is of great importance when preparing and verifying conformal radiotherapy. The conventional technique for measuring the motion of an organ is to locate landmarks on the organ and the bony anatomy and to compare the distance between these landmarks on subsequent computerized tomography (CT) scans. The first purpose of this study is to investigate the use of a three dimensional (3D) image registration method based on chamfer matching for measurement of the location and orientation of the whole organ relative to the bony anatomy. The second purpose is to quantify organ motion during conformal therapy of the prostate. METHODS AND MATERIALS: Four CT scans were made during the course of conformal treatment of 11 patients with prostate cancer. With the use of a 3D treatment planning system, the prostate and seminal vesicles were contoured interactively. In addition, bladder and rectum were contoured and the volume computed. Next, the bony anatomy of subsequent scans was segmented and matched automatically on the first scan. The femora and the pelvic bone were matched separately to quantify motion of the legs. Prostate (and seminal vesicle) contours from the subsequent scans were matched on the corresponding contours of the first scan, resulting in the 3D rotations and translations that describe the motion of the prostate and seminal vesicles relative to the pelvic bone. RESULTS: Bone matching of two scans with about 50 slices of 256 x 256 pixels takes about 2 min on a workstation and achieves subpixel registration accuracy. Matching of the organ contours takes about 30 s. The accuracy in determining the relative movement of the prostate is 0.5 to 0.9 mm for translations (depending on the axis) and 1 degree for rotations (standard deviations). Because all organ contours are used for matching, small differences in delineation of the prostate, missing slices, or differences in slice distance have only a limited influence on the accuracy. Rotations of the femora and the pelvic bone are quantified with about 0.4 degree accuracy. A strong correlation was found between rectal volume and anterior-posterior translation and rotation around the left-right axis of the prostate. Consequently, these parameters had the largest standard deviations of 2.7 mm and 4.0 degrees. Bladder filling had much less influence. Less significant correlations were found between various leg rotations and pelvic and prostate motion. Standard deviations of the rotation angles of the pelvic bone were less than 1 degree in all directions. CONCLUSIONS: Using 3D image registration, the motion of organs relative to bony anatomy has been quantified accurately. Uncertainties in contouring and visual interpretation of the scans have a much smaller influence on the measurement of organ displacement with our new method than with conventional methods. We have quantified correlations between rectal filling, leg motions, and prostate motion.
Acid beta-glucosidase (beta Glc) is a housekeeping enzyme whose expression is ubiquitous, but differs greatly according to tissue of origin. Expression of a reporter gene under the control of a 622 bp fragment of the beta Glc promoter correlated roughly with the relative amount of beta Glc mRNA detected in five different cell lines, suggesting that elements within this region play a role in determining differential expression of the beta Glc gene. Experiments using deletion mutants revealed that differential expression of beta Glc is not due to the presence of promoter elements that are active in only certain cell types, but rather due to subtle changes in the magnitude of the effect of the different elements. Strikingly, regulatory elements located upstream of the TATA box are dispensible in several cell types, whereas elements located within exon 1 of the beta Glc gene are essential for reporter gene expression in cultured cells. At least two exon 1 elements regulate mRNA levels, and one double stranded probe containing exon 1 sequences binds a factor present in extracts from HeLa and glioblastoma cells. Additionally, at least two of the exon 1 elements act in an orientation-independent fashion. Thus, it is likely that at least a subset of the exon 1 elements act as transcriptional enhancers.
BACKGROUND: We describe an epidemiologic analytical study of the relationship between current diet and breast cancer risk. METHOD: The study design is a case-control analysis. Cases were recruited from a mammography screening program used within the national health care system; the control subjects were selected from subjects free of breast cancer in the same population. A total of 380 cases and 525 control subjects, frequency-matched for age, month of mammography, and county of residence, were identified. Of these, 265 cases and 432 control subjects were included in this analysis. Odds ratios for breast cancer in relation to food and nutrient intake were the main outcome measures. RESULTS: Exposure in the highest quartile of beta-carotene intake gave an odds ratio of 0.6 (95% confidence interval, 0.4 to 1.0). No increased risk was noted with high fat intake. Breast cancer risk was associated with alcohol intake only when alcohol was analyzed in quartiles: odds ratio, 1.6 (95% confidence interval, 1.0 to 2.4) for the highest quartile of intake vs the lowest. Stratified analyses showed that a high fat intake might decrease the protective effect of beta-carotene intake. Risks did not change appreciably with adjustment for total energy intake or known breast cancer risk factors. CONCLUSIONS: As in most other studies, no strong risk factors for breast cancer have been identified in the current diet. The negative association between breast cancer risk and beta-carotene intake may be supported by a plausible mechanism, but our finding concerning alcohol should be interpreted cautiously since there was no dose-response relationship and the biological mechanism for a threshold effect at very low levels of consumption is unclear.
The p53 tumor-suppressor gene encodes a growth-regulatory protein that has been implicated in programmed cell death. To investigate the possible role of p53 in neuronal death, we studied p53 expression associated with excitotoxicity in the adult rat brain. Within hours of systemic administration of the glutamate analogue kainic acid, p53 mRNA levels were increased in neurons exhibiting morphological features of damage within kainate-vulnerable brain regions. A similar distribution was found for neurons exhibiting DNA damage as evidenced by in situ end-labeling of fragmented DNA. Pretreatment with the protein synthesis inhibitor cycloheximide prevented both kainate-mediated p53 induction and neuronal damage. The distinctive pattern of excitotoxin-mediated p53 expression suggests that p53 induction is a marker of irreversible injury in postmitotic cells of the central nervous system and could have functional significance in determining selective neuronal vulnerability.
Rat liver and kidney were investigated for the presence of sigma (sigma) receptor subtypes by radioligand binding with three highly selective sigma probes and by photoaffinity labeling using [3H]azido-di-o-tolylguanidine ([3H]azido-DTG). [3H](+)-Pentazocine, a highly selective sigma 1 probe, bound to sites in liver membranes with Kd = 7.5 nM and Bmax3 = 2929 fmol/mg protein. [3H](+)-Pentazocine binding sites in kidney had Kd = 23.3 nM and Bmax = 229 fmol/mg protein. [3H]1,3-Di-o-tolylguanidine ([3H]DTG) and [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([3H](+)-3-PPP) label both sigma 1 and sigma 2 receptors. Parameters for [3H]DTG in the liver were Kd = 17.9 nM and Bmax = 11,895 fmol/mg protein. Similar parameters were observed for [3H](+)-3-PPP, Kd = 51.9 nM and Bmax = 11,070 fmol/mg protein. [3H]DTG bound to rat kidney with Kd = 45.8 nM and Bmax = 1190 fmol/mg protein. The observation that either [3H]DTG or [3H](+)-3-PPP and [3H](+)-3-PPP labeled a higher number of sites relative to [3H](+)-pentazocine suggested that liver and kidney contain both subtypes of sigma receptor. This was confirmed by competition studies vs. [3H](+)-pentazocine and [3H]DTG (in the presence of dextrallorphan to mask sigma 1 sites). In both tissues, [3H](+)-pentazocine labeled sites with high affinity for haloperidol and enantioselectivity for (+)-benzomorphans over (-)-benzomorphans. [3H]DTG + dextrallorphan labeled sites in both tissues which also had high affinity for haloperidol, but which had the characteristic sigma 2 property of low affinity for (+)-benzomorphans and enantioselectivity for (-)-benzomorphans over the corresponding (+)-isomer. Similar results were obtained with [3H](+)-3-PPP + dextrallorphan. Several novel aryl diamines, such as 1S,2R-cis-N-[2-(3,4-dichlorophenylethyl]-N-methyl-2- (1-pyrrolidinyl)cyclohexylamine (BD737) and N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD1008), bound to both sites with high affinity. Photoaffinity labeling with 10 nM [3H]azido-DTG resulted in specific labeling of polypeptides of 25 kDa and 21.5 kDa. Dextrallorphan (100 nM or 500 nM) completely blocked labeling of the 25 kDa polypeptide, but had no effect on labeling of the lower molecular weight protein. (+)-10,11-Dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10- imine((+)-MK-801) had no effect on labeling of either polypeptide. These data are consistent with the notion that the 25 kDa and 21.5 kDa proteins represent sigma 1 and sigma 2 receptors, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
The impact of long-term, heavy exercise on recently established cardiovascular/thromboembolic risk factors of the fibrinolytic system, tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in relation to food composition was studied. Twenty healthy men, aged 18-55 years participated in a 14-day skiing tour through the Swedish mountains, carrying a pack load of 30 kg, and spending each night in self-dug igloos (ambient temp -10 degrees to -25 degrees C), and were randomized to 2 food regimens having 30 or 40 energy percent of fat. Individual records were kept of all consumed food. Citrated plasma was obtained before and after 1 and 2 weeks of exercise: tPA release was assessed by a 10 min venous occlusion (VO) test. At baseline, daily dietary fiber intake correlated negatively with PAI-1 activity. Already after the first week of the skiing tour there were significant drops in PAI-1 activities, cholesterol and triglycerides. The tPA mass concentrations also dropped, both before and after VO, but tPA activities were unchanged, as were von Willebrand factor (vWF) levels. These changes were related mainly to the expenditure of energy, calculated from the food consumption, and appeared to be mediated through changed insulin sensitivity and decreased body fat mass. The energy percent of fat in the food had no differential impact. The effects receded a few weeks after cessation of the endurance exercise. Thus, endurance physical activity improves the fibrinolytic risk factor profile by reducing PAI-1 while leaving tPA activity unaffected, independently of food composition. A low dietary fiber intake appears to be associated with higher PAI-1 activities at baseline.
Anoxia produces deleterious effects on synaptic transmission in the hippocampal slice preparation. A proposed source of damage is the superoxide radical (.O2-) produced during the earlier period of reoxygenation. The present study tested the effects of a synthetic, catalytic superoxide radical scavenger (EUK-8) on CA1 pyramidal cell responses elicited by electrical stimulation of the Schaffer-commissural pathway after severe anoxic episodes. Following reoxygenation, slices incubated with EUK-8 (50 microM) exhibited significantly better recovery of excitatory postsynaptic potentials (EPSPs) than control slices. In addition, repeated episodes of anoxia produced irreversible loss of synaptic transmission in the majority of control slices (93 +/- 7%, n = 15), compared to a small fraction in EUK-8-incubated slices (27 +/- 12%, n = 15). A thiobarbituric acid (TBA) test was used to assess the effect of EUK-8 on lipid peroxidation elicited in hippocampal slices by acidosis and lactic acid (pH 5.0 and 30 mM lactic acid). Incubation in the presence of EUK-8 totally prevented the increase in lipid peroxidation produced by acidosis and lactic acid in both the incubation medium and the slice homogenates. These results indicate that a superoxide scavenger like EUK-8 prevents damage produced by acidosis and anoxia in hippocampal slices and suggest the possibility of using this type of molecule under various pathological conditions.
BACKGROUND: Our objective was to determine the possible influence that different designs of a food frequency questionnaire might have on food, energy and nutrient intake estimates. METHODS: A population-based survey included 6783 women, 40-70 years old, living in central Sweden. Using a factorial study design, we compared eight different types of questionnaire covering combinations of three factors: increasing/decreasing frequency categories; addition of portion sizes; and addition of non-dietary questions. All questionnaires included the same list of 60 food items. One of the eight questionnaires was mailed to each subject according to a random assignment. The overall response rate was 77%. RESULTS: Compared with increasing frequencies, decreasing order of frequency categories entailed 3-11% higher estimates of mean intake for 7 of 14 food groups, 4% higher estimates for energy and 3-6% higher estimates for 13 of 18 nutrients. Addition of portion sizes had heterogeneous effects, both on dietary items (e.g. from -30% decrease for eggs to +76% increase for coffee) and on calculated nutrients (from -7% for beta-carotene to +19% for vitamin C). The inclusion of some additional non-dietary questions did not influence the estimated mean intake of any food or nutrient. CONCLUSIONS: The results of this study have implications for the design of questionnaires and for pooled analyses in nutritional epidemiology, when different food questionnaires are used.