bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep‐disordered breathing and glucose metabolism in hypertensive men: a population‐based study
Authors: Elmasry A. , Lindberg E. , Berne C. , Janson C. , Gislason T. , Tageldin M. Awad , Boman G.
Published: March 2003

Abstract. Elmasry A, Lindberg E, Berne C, Janson C, Gislason T, Awad Tageldin M, Boman G (Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden; Ain Shams University, Cairo, Egypt; and Vifilsstadir Hospital, Gardabaer, Iceland). Sleep‐disordered breathing and glucose metabolism in hypertensive men: a population‐based study. J Intern Med 2001; 249: 153–161.

Objectives. Diabetes mellitus and obstructive sleep apnoea (OSA) are two prevalent medical problems. Both are strongly associated with obesity and hypertension. The aim of this study was to investigate whether the association between OSA and diabetes is entirely dependent on obesity in hypertensive men.

Design. A population‐based study.

Setting. The municipality of Uppsala, Sweden.

Subjects and methods. In 1994, 2668 men aged 40–79 years answered a questionnaire regarding snoring, sleep disturbances and somatic diseases. An age‐stratified sample of 116 hypertensive men was selected for a whole‐night sleep study. Twenty‐five of them had diabetes, defined as reporting regular medical controls for diabetes or having a fasting blood glucose ≥6.1 mmol L−1.

Results. The prevalence of severe OSA, defined as apnoea‐hypopnoea index (AHI) ≥20 h−1 was significantly higher in diabetic patients than in normoglycaemic subjects (36 vs. 14.5%, P < 0.05). The sample was divided into four groups based on the presence or absence of severe OSA and the presence or absence of central obesity, defined as waist‐to‐hip ratio (WHR) ≥1.0. In a logistic regression model with the non‐OSA, WHR <1.0 as the reference group, the adjusted odds ratio (95% confidence interval) for diabetes was 11.8 (2.0–69.8) in the OSA, WHR ≥1.0 group, whilst it was 3.6 (0.9–14.8) in the non‐OSA, WHR ≥1.0 group and 5.7 (0.3–112) in the OSA, WHR <1.0 group. In a linear regression model, after adjustment for WHR, there was a significant relationship between variables of sleep‐disordered breathing and fasting insulin, glucose and haemoglobin A1c.

Conclusions. We conclude that, in hypertensive men, although obesity is the main risk factor for diabetes, coexistent severe OSA may add to this risk. Sleep breathing disorders, independent of central obesity, may influence plasma insulin and glycaemia.
The role of gene–environment interaction in the aetiology of human cancer: examples from cancers of the large bowel, lung and breast
Authors: Mucci L. A. , Wedren S. , Tamimi R. M. , Trichopoulos D. , Adami H.‐O.
Published: March 2003

Abstract. Mucci LA, Wedren S, Tamimi RM, Trichopoulos D, Adami H.‐O. (Harvard School of Public Health, Boston, MA, USA; and Karolinska Institutet, Stockholm, Sweden) The role of gene–environment interaction in the aetiology of human cancer: examples from cancers of the large bowel, lung and breast. J Intern Med 2001; 249: 477–493.

It has become increasingly clear that cancer can be considered neither purely genetic nor purely environmental. A relatively new area of cancer research has focused on the interaction between genes and environment in the same causal mechanism. Primary candidates for gene‐environment interaction studies have been genes that encode enzymes involved in the metabolism of established cancer risk factors. There are common variant forms of these genes (polymorphisms), which may alter metabolism and increase or decrease exposure to carcinogens, thus impacting the risk of cancer. We present an overview of enzymes involved in carcinogen metabolism, present epidemiological tools to evaluate gene‐environment interactions, and provide examples from cancers of the breast, lung and large bowel.
Gender difference in age‐related changes in vascular function
Authors: Jensen‐Urstad K. , Johansson J.
Published: March 2003

Jensen‐Urstad K, Johansson J (Karolinska Hospital, Stockholm, Sweden) Gender difference in age‐related changes in vascular function. J Intern Med 2001; 250: 29–36.

Purpose. We investigated whether, in a randomly selected population of 55‐year‐old men and women, there is a relationship between vascular function measured as flow‐mediated (endothelium‐dependent) and nitroglycerine‐mediated (nonendotheliumdependent) dilatation of the brachial artery and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood‐lipids and high blood pressure. The results are compared with those in a young healthy population of 35‐year‐olds.

Subjects. A total of 57 men (73% of the invited males) living in the community and 47 women (62% of the invited females) participated and were compared with a previously studied 35‐year‐old population (52 men and 56 women).

Methods. Basal brachial artery diameter was measured by high‐frequency ultrasound methods. Endothelial function was measured as flow‐mediated dilatation (FMD) in response to reactive hyperaemia. The nonendothelium‐dependent vasodilatation was measured after administering sublingual nitroglycerine (NTG).

Results. Flow‐mediated endothelium‐dependent dilatation was similar in men and women being 3.1 ± 2.5% (mean ± SD) in men vs. 2.6 ± 2.3% in women. FMD of the brachial artery was negatively correlated with vessel size in both men and women (P < 0.001). Men had larger brachial artery diameter than women (4.6 ± 0.7 vs. 3.6 ± 0.4 mm, P < 0.001). There was no difference in FMD or in NTG‐induced dilatation in the women receiving oral oestrogen replacement therapy compared with those that did not. The women taking oral oestrogen had lower cholesterol than those not taking oral oestrogen (P=0.04). FMD was not correlated with any of the risk factors. NTG‐induced vasodilatation was correlated with the body mass index (BMI) in men (P=0.01) and a combined risk factor score in women (P=0.04). There was a large increase in the number of subjects with cardiovascular risk factors in the 55‐year‐old men and women compared with the 35‐year‐olds. The distribution of risk factors was fairly equal amongst men and women.

Conclusion. There are no correlations between any of the conventional cardiovascular risk factors and FMD in a population of 55‐year‐olds, but there is a high prevalence of risk factors in the 55‐year‐old age group. NTG‐induced vasodilatation correlated with the BMI in men and a combined risk‐factor score in women. FMD‐induced vasodilatation is smaller in women at 55 years of age than at 35 years of age. FMD was similar in men at 35 and 55 years of age and in men and women at 55 years of age. The smaller FMD in women at 55 years of age, compared with at 35, could be due to postmenopausal hormonal changes.
The yield of a diagnostic hospital dyspnoea clinic for the primary health care section
Authors: Nielsen L. Svendstrup , Svanegaard J. , Wiggers P. , Egeblad H.
Published: March 2003

Abstract. Svendstrup Nielsen L, Svanegaard J, Wiggers P, Egeblad H (Haderslev Hospital; Aarhus University Hospital, Skejby, Denmark). The yield of a diagnostic hospital dyspnoea clinic for the primary health care section. J Intern Med 2001; 250: 422–428.

Objective. To investigate the impact of a combined examination programme with treatment advice on with dyspnoea.

Design. Prospective study with 6 months follow‐up.

Setting. Regional hospital offering care for patients from 74 general practitioners.

Subjects. A total of 284 consecutive patients referred from general practice with dyspnoea.

Interventions. Patients were subjected to a combined examination programme including physical examination, ECG, chest X‐ray, lung spirometry, echocardiography and routine laboratory tests.

Main outcome measures. (i) Relationship between a diagnosis made by the referring general practitioner and the diagnosis based on the combined examination programme. (ii) The impact of the investigation programme and resulting therapeutic advice on dyspnoea after 6 months.

Results. Only in 39% of the patients there was concordance of the diagnoses on referral and the diagnosis based on the examination programme. Heart failure and lung disease was suspected in 126 and 79 patients, respectively, but these diagnoses were confirmed in only one‐third to half of the patients. Conversely heart failure was revealed in 13 of 107 patients not suspected of heart failure (12%) and lung disease in 45 of 154 patients not suspected of pulmonary disease (29%). A change of treatment was suggested in 64% of all patients. After 6 months, improvement of dyspnoea was seen in more than half of the patients. In patients in whom the changes of medical treatment were completed, 61% expressed improvement in dyspnoea, whereas improvement of dyspnoea was recorded in only 34% of patients in whom the recommended treatment advice was not taken (P < 0.01).

Conclusion. (i) In most patients it seems to be too difficult to establish the background of dyspnoea in general practice. (ii) There appears to be a substantial chance of improvement in patients with dyspnoea, in particular for patients who act on treatment advice based on an integrated examination programme; the chance of improvement is almost twice as good as in patients who are not capable to do so.
Reduction of free radical activity in amyloid deposits following liver transplantation for familial amyloidotic polyneuropathy
Authors: Nyhlin N. , Anan I. , El Salhy M. , Ando Y. , Suhr O. B.
Published: March 2003

Abstract. Nyhlin N, Anan I, el Salhy M, Ando Y, Suhr OB (Umeå University Hospital, Umeå, Sweden and Kumamoto University Hospital, Kumamoto, Japan). Reduction of free radical activity in amyloid deposits following liver transplantation for familial amyloidotic polyneuropathy. J Intern Med 2002; 251: 136–141.

Objectives. Liver transplantation halt the progress of familial amyloidotic polyneuropathy (FAP). Oxidative stress has been implicated in amyloid toxicity and formation. The objective of this study was to establish whether markers for oxidant stress and antioxidant capacity change following liver transplantation in patients with FAP.

Design. Morphometric and biochemical study.

Setting. Tertiary referral centre.

Subjects. Duodenal biopsy samples from 16 patients, taken before and after liver transplantation were used for morphometry. Serum samples from 14 patients, seven of whom had received transplants, were analysed regarding antioxidant capacity.

Intervention. Liver transplantation.

Main outcome measures. Immunohistochemistry was used to stain for the lipid peroxidation product 4‐hydroxynonenal (HNE), and Congo red staining was used for amyloid detection. Positive areas were quantified by point counting. Total antioxidant capacity (TAC) was measured with a colourimetric assay.

Results. In tissue, a decrease of HNE was noted after liver transplantation, whereas no significant changes were detected for amyloid deposits. No difference between transplanted and not transplanted patients was noted for total antioxidant capacity measured in serum.

Conclusion. To our knowledge, this is the first description of a reduction of markers for free radical activity after cessation of amyloid formation. The findings implicate that amyloid formation in transthyretin (TTR) amyloidosis generates oxidative stress, whereas amyloid deposits as such are less toxic to sourroundig tissues.
Attitudes towards clinical research amongst participants and nonparticipants
Authors: Madsen S. M. , Mirza M. R. , Holm S. , Hilsted K. L. , Kampmann K. , Riis P.
Published: March 2003

Abstract. Madsen SM, Mirza MR, Holm S, Hilsted KL, Kampmann K, Riis P (Copenhagen University Hospital in Herlev, Herlev, Denmark; Odense University Hospital in Odense, Odense C, Denmark; University of Manchester, Manchester, UK; Copenhagen University Hospital in Herlev, Herlev, Denmark; and Odense University Hospital in Odense, Odense C, Denmark). Attitudes towards clinical research amongst participants and nonparticipants. J Intern Med 2002; 251: 156–168.

Objectives. To investigate attitudes to clinical research amongst cancer trial participants and nonparticipants, and to compare results with those from previous studies amongst participants in noncancer trials.

Design. Trial participating respondents were given three questionnaires during the clinical trials. Respondents amongst patients declining randomization answered a single questionnaire.

Setting. Participants and nonparticipants in randomized clinical cancer trials.

Subjects. Forty‐one participants and 47 nonparticipants in cancer trials.

Results. Altruistic motives of physicians to conduct medical research were highly rated. Attitudes towards clinical research were positive in all groups, with nonparticipant respondents being the least positive. Eight to nine tenths found scientific testing necessary before general health service implementation. Trial participants were, as compared with nonparticipating respondents, more positive towards both participation of self and others. Both personal and altruistic motives for participation were highly rated. Primary reasons for nonparticipation were fear of ‘the unknown’ and/or unease with randomization. Only a minority felt a moral problem created by declining trial participation. Respondents amongst noncancer participants were more satisfied with the information given than both cancer participants and cancer nonparticipants. Negative experiences in cancer participants generally dealt with frustration related to seeing too many physicians at check‐up appointments.

Conclusion. Attitudes towards clinical research are generally positive even in cancer nonparticipants. Both personal and altruistic motives for participation were highly rated. A fear of ‘the unknown’ and resentments towards randomization were primary reasons to renounce participation. Seeing too many physicians at check‐up appointments seems to be an important factor for negative experiences in cancer trial participants.
A C‐1291G polymorphism in the α2A‐adrenergic receptor gene (ADRA2A) promoter is associated with cortisol escape from dexamethasone and elevated glucose levels
Authors: Rosmond R. , Bouchard C. , Björntorp P.
Published: March 2003

Abstract. Rosmond R, Bouchard C, Björntorp P (Sahlgrenska University Hospital, Göteborg, Sweden; Pennington Biomedical Research Center, LA, USA). A C‐1291G polymorphism in the α2A‐adrenergic receptor gene (ADRA2A) promoter is associated with cortisol escape from dexamethasone and elevated glucose levels. J Intern Med 2002; 251: 252–257.

Objectives. The objective of the current study was to examine the potential impact of a C → G substitution at position −1291 of the α2A‐adrenergic receptor gene (ADRA2A) promoter on obesity and estimates of insulin, glucose, and lipid metabolism as well as circulating hormones, including salivary cortisol in 284 unrelated Swedish men born in 1944.

Main outcome measures. The subjects were genotyped by using PCR amplification of the promoter region of the ADRA2A gene followed by digestion with the restriction enzyme MspI.

Results. The frequencies were 0.23 for allele C and 0.77 for allele G. The observed genotype frequencies were 45.8 and 54.2% for C/G and G/G, respectively. Heterozygotes (n=121) had significantly (P=0.009) higher salivary cortisol levels after 0.5 mg dexamethasone compared with G/G homozygotes (n=143). Fasting glucose was found to be significantly (P=0.017) higher in heterozygotes than in G/G homozygotes. The latter group had also a borderline significantly (P=0.080) higher mean diastolic blood pressure. These results were all adjusted for the potential confounding effect of body mass index (BMI) and waist‐to‐hip ratio (WHR). Other measurements such as BMI, WHR, abdominal sagittal diameter, total testosterone, insulin‐like growth factor I, serum leptin, fasting insulin and serum lipids were not different across the ADRA2A genotype groups.

Conclusions. In conclusion, we have shown that an C → G polymorphism at position −1291 of the ADRA2A gene is associated with a subnormal cortisol response to dexamethasone, elevated glucose levels and perhaps increased diastolic blood pressure. The pathophysiology could involve an altered density of the α2A‐AR that destabilizes the sympathetic–hypothalamic–pituitary–adrenal systems in those with genetic vulnerability in the α2A‐adrenergic receptor gene promoter.
Prospects for chemoprevention of cancer
Authors: TAMIMI R. M. , LAGIOU P. , ADAMI H.‐O. , TRICHOPOULOS D.
Published: March 2003

Tamimi RM, Lagiou P, Adami H‐O, Trichopoulos D (Harvard School of Public Health, Boston, MA, USA; University of Athens Medical School, Goudi, Athens, Greece; and Karolinska Institute, University of Stockholm, Stockholm, Sweden). Prospects for chemoprevention of cancer (Review). J Intern Med 2002; 251: 286–300.

The recent progress in molecular biology and pharmacology has increased the likelihood that cancer prevention will rely increasingly on interventions collectively termed `chemoprevention'. Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis. A number of potential targets for chemoprevention have recently been identified. Many classes of agents including antioestrogens, anti‐inflammatories, antioxidants and other diet‐derived agents have shown a great deal of promise. In this review, we will begin by describing the general classes of chemopreventive agents and the mechanisms by which these agents act. We will then describe the opportunities that presently exist for chemoprevention of specific cancers.
Is lipoprotein(a) a predictor for survival in patients with established coronary artery disease? Results from a prospective patient cohort study in northern Sweden
Authors: GLADER C. AHLBECK , BIRGANDER L. SLUNGA , STENLUND H. , DAHLÉN G. H.
Published: March 2003

Abstract.  Ahlbeck Glader C, Slunga Birgander L, Stenlund H, Dahlén GH (Umeå University, Umeå, Sweden). Is lipoprotein(a) a predictor for survival in patients with established coronary artery disease? Results from a prospective patient cohort study in northern Sweden. J Intern Med 2002; 252: 27–35.

Objectives. Lipoprotein(a) [Lp(a)] is a known risk factor for the development of atherosclerosis. The aim of the present study was to test the importance of Lp(a) as a predictor for the further prognosis in patients with established coronary artery disease.

Design.  A prospective patient cohort study was carried out.

Setting and subjects.  The cohort consists of 1216 patients who were examined with coronary angiography at the University Hospital in Umeå, Sweden, because of stable effort angina.

Main outcome measures.  Lipids, Lp(a), fibrinogen, antithrombin III (AT III), sedimentation rate and clinical data were registered at angiography. After a mean follow‐up time of 6.7 years information on survival was collected from the municipal census lists and death certificates were examined. Total mortality and mortality because of cardiovascular disease were both used as outcome variables in the survival analyses.

Results.  The total mortality in the patient cohort was 16.4%. An Lp(a) level of 300 mg L−1 or more was found in 30% of the study population and was found to be an independent predictor for death. A high fibrinogen, a low AT III level, a depressed left ventricular function and a high coronary obstruction score were other significant independent predictors of death. Total cholesterol, HDL‐ and LDL‐cholesterol were not related to survival in this study, but a substantial proportion of the population probably received lipid‐lowering agents during the study period.

Conclusions.  An Lp(a) level exceeding 300 mg L−1 indicates a poor further prognosis and may help to identify patients who probably need powerful secondary prevention programmes to improve their prognosis.
The association between leptin and proinsulin is lost with central obesity
Authors: Söderberg S. , AhrÉn B. , Eliasson M. , Dinesen B. , Olsson T.
Published: March 2003

Abstract. Söderberg S, Ahrén B, Eliasson M, DinesenB, Olsson T (Umeå University, Umeå, Lund University and Luleå Hospital, Lund, Sweden; and Steno Diabetes Center, Gentofte, Denmark). The association between leptin and proinsulin is lost with central obesity. J Intern Med 2002; 252: 140–148.

Objective.  Hyperproinsulinaemia and hyperleptinaemia are interrelated features of the insulin resistance syndrome that are linked to the prospective risk of cardiovascular diseases. Whether the association between leptin and proinsulin is different between groups displaying different degrees of risk for cardiovascular diseases is not known. We therefore examined this association in men versus women and in pre‐ versus postmenopausal women from a population‐based sample.

Design and subjects.  Healthy subjects (n = 158; 85 men and 73 pre‐ and postmenopausal women) from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease population were studied with a cross‐sectional design.

Methods.  Anthropometric measurements (body mass index and waist circumference) and oral glucose tolerance tests were performed. Enzyme‐linked immunosorbent assays were used for the analyses of specific insulin and proinsulin, and radioimmunoassay for leptin. Insulin resistance and β‐cell function were calculated according to the homeostasis assessment model. Partial correlation coefficients adjusted for age and measures of adiposity were calculated and multiple linear regression analyses were performed with leptin as dependent variable.

Results.  In nonobese men and premenopausal women and in obese postmenopausal women, leptin was significantly associated with proinsulin after stratification for waist circumference. Furthermore, a multivariate analyses taking age and measures of adiposity into account, showed that high fasting proinsulin was a significant predictor of high leptin in these groups. In contrast, this association was lost with increasing central obesity in men and premenopausal women.

Conclusions.  This study shows that both the degree of adiposity and the hormonal milieu influence the association between circulating leptin and proinsulin in a normal population. Therefore, the insulin resistance syndrome seems to be characterized by lost association between leptin and proinsulin, which may be explained by dysfunction in the adipoinsular axis.
Tobacco use and cancer causation: association by tumour type
Authors: Kuper H. , Boffetta P. , Adami H.‐O.
Published: March 2003

Abstract.  Kuper H, Boffetta P, Adami H‐O (London School of Hygiene and Tropical Medicine, London, UK; Karolinska Institutet, Stockholm, Sweden; and International Agency for Research on Cancer, Lyon, France). Tobacco use and cancer causation: association by tumour type (Review). J Intern Med 2002; 252: 206–224.

In the second part of our review we describe the association between tobacco use and risk of specific cancer types. There is evidence for an established association of tobacco use with cancer of the lung and larynx, head and neck, bladder, oesophagus, pancreas, stomach and kidney. In contrast, endometrial cancer is less common in women who smoke cigarettes. There are some data suggesting that tobacco use increases the risk for myeloid leukaemia, squamous cell sinonasal cancer, liver cancer, cervical cancer, colorectal cancer after an extended latency, childhood cancers and cancer of the gall bladder, adrenal gland and small intestine. Other forms of cancer, including breast, ovarian and prostate cancer, are unlikely to be linked to tobacco use.
Major bleeding complications after cardiopulmonary resuscitation: impact of thrombolytic treatment
Authors: Kurkciyan I. , Meron G. , Sterz F. , Müllner M. , Tobler K. , Domanovits H. , Schreiber W. , Bankl H. C. , Laggner A. N.
Published: March 2003

Abstract.  Kurkciyan I, Meron G, Sterz F, Müllner M, Tobler K, Domanovits H, Schreiber W, Bankl HC, Laggner AN (General Hospital of Vienna, University of Vienna, Vienna, Austria). Major bleeding complications after cardiopulmonary resuscitation: impact of thrombolytic treatment. J Intern Med 2003; 253: 128–135.

Objective.  The risk of bleeding complications caused by thrombolysis in patients with cardiac arrest and prolonged cardiopulmonary resuscitation is unclear. We evaluate the complication rate of systemic thrombolysis in patients with out‐of‐hospital cardiac arrest caused by acute myocardial infarction, especially in relation to duration of cardiopulmonary resuscitation.

Design.  The study was designed as retrospective cohort study, the risk factor being systemic thrombolysis and the end‐point major haemorrhage, defined as life‐threatening and/or need for transfusion. Over 10.5 years, emergency cardiac care data, therapy, major haemorrhage and outcome of 265 patients with acute myocardial infarction admitted to an emergency department after successful cardiopulmonary resuscitation were registered.

Results.  We observed major haemorrhage in 13 of 132 patients who received thrombolysis (10%, 95% confidence interval 5–15%), five of these survived to discharge, none died because of this complication. Major haemorrhage occurred in seven of 133 patients in whom no thrombolytic treatment had been given (5%, 95% confidence interval 1–9%), two of these survived to discharge. Taking into account baseline imbalances between the groups, the risk of bleeding was slightly increased if thrombolytics were used (odds ratio 2.5, 95% confidence interval 0.9–7.4) but this was not significant (P = 0.09). There was no clear association between duration of resuscitation and bleeding complications (z for trend = 1.52, P = 0.12). Survival was not significantly better in patients receiving thrombolysis (odds ratio 1.6, 0.9–3.0, P = 0.12).

Conclusions.  Bleeding complications after cardiopulmonary resuscitation are frequent, particularly in patients with thrombolytic treatment, but do not appear to be related to the duration of resuscitation. In the light of possible benefits on outcome, thrombolytic treatment should not be withheld in carefully selected patients.
Exercise stress testing, myocardial perfusion imaging and stress echocardiography for detecting restenosis after successful percutaneous transluminal coronary angioplasty: a review of performance
Authors: Dori G. , Denekamp Y. , Fishman S. , Bitterman H.
Published: March 2003

Abstract.  Dori G, Denekamp Y, Fishman S, Bitterman H (Carmel Medical Center, Haifa, Israel; Israel Institute of Technology, Israel). Exercise stress testing, myocardial perfusion imaging and stress echocardiography for detecting restenosis after successful percutaneous transluminal coronary angioplasty: a review of performance (Review). J Intern Med 2003; 253: 253–262.

When chest symptoms recur in a patient who underwent percutaneous transluminal coronary angioplasty (PTCA), it is necessary to rule out restenosis (R). Three main noninvasive tests suggest the presence of R: exercise stress test (XT), myocardial perfusion imaging (MPI) and stress echocardiography (s‐echo). The objectives of this review were: (1) to estimate the pretest probability of R as a function of time after PTCA in symptomatic patients and (2) to obtain an approximation of the diagnostic parameters of the XT, MPI and s‐echo for detecting R. A MEDLINE search (English‐language, years: 1980–2001) was conducted to identify studies examining post‐PTCA functional testing for diagnosing R. Data from the studies were pooled. Comparing studies was often difficult due to varying methodology in the studies.

Pretest probability of R in symptomatic patients increases in a nonlinear fashion from 20% or less at 1 month, to nearly 90% at 1‐year postangioplasty. The approximated accuracy of the XT, MPI, and s‐echo for detecting R was 62, 82 and 84%, respectively. During the first month after PTCA, none of the noninvasive modalities is able to accurately detect R. Late (7–9 months) after PTCA, the pretest probability of R is high and therefore the noninvasive measure may be spared. Our analysis suggests that MPI and s‐echo should be preferred over the XT for diagnosing R.
Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes
Authors: Becker A. , Kostense P. J. , Bos G. , Heine R. J. , Dekker J. M. , Nijpels G. , Bouter L. M. , Stehouwer C. D. A.
Published: March 2003

Abstract.  Becker A, Kostense PJ, Bos G, Heine RJ, Dekker JM, Nijpels G, Bouter LM, Stehouwer CDA (VU University Medical Center, Amsterdam, the Netherlands). Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes. J Intern Med 2003; 253: 293–300.

Objectives.  Amongst nondiabetic individuals, a high serum homocysteine concentration is an independent but relatively weak risk factor for coronary events. However, it is not known whether homocysteine increases risk of coronary events in type 2 diabetes. Therefore, we examined the combined effect of homocysteine and type 2 diabetes on risk of fatal and nonfatal coronary events.

Subjects.  We assessed the 10‐year risk of coronary events associated with homocysteine amongst diabetic (n = 140) and nondiabetic (n = 361) individuals.

Design.  We did this in the Hoorn Study, a population‐based study of glucose tolerance and related complications in Caucasian men and women aged 50–75 years.

Results.  The incidence rate for coronary events was 2.63 (29 of 140) per 100 person‐years amongst diabetic and 1.29 (42 of 361) amongst nondiabetic individuals. Amongst diabetic individuals, risk of coronary events increased 28% for each 5‐μmol L−1 increment of homocysteine (hazard ratio, 1.28; 95% CI, 1.02–1.58). This risk was independent of age, sex, hypertension, total cholesterol, HDL‐cholesterol, cigarette smoking, body mass index and glomerular filtration rate. In nondiabetic participants, homocysteine was not associated with an increased risk of coronary events (hazard ratio for each 5‐μmol L−1 increment of homocysteine, 0.86; 0.52–1.41).

Conclusions.  These data suggest that homocysteine is significantly associated with coronary events in individuals with type 2 diabetes, independent of traditional cardiovascular risk factors. Investigation of the effect of treatment with vitamin B on prognosis of individuals with type 2 diabetes is warranted.
High‐precision distance measurements and volume‐conserving segmentation of objects near and below the resolution limit in three‐dimensional confocal fluorescence microscopy
Authors: Bornfleth  , Sätzler  , Eils  , Cremer
Published: March 2003

This study presents a method for high‐precision distance measurements and for the volume‐conserving segmentation of fluorescent objects with a size of the order of the microscopic observation volume. The segmentation was performed via a model‐based approach, using an algorithm that was calibrated by the microscopic point spread function. Its performance was evaluated for three different fluorochromes using model images and fluorescent microspheres as test targets. The fundamental limits which the microscopic imaging process imposes on the accuracy of volume and distance measurements were evaluated in detail. A method for the calibration of the axial stepwidth of a confocal microscope is presented. The results suggest that in biological applications, 3D distances and radii of objects in cell nuclei can be determined with an accuracy of ≤ 60 nm. Using objects of different spectral signature, 3D distance measurements substantially below the lateral half width of the confocal point spread function are feasible. This is shown both theoretically and experimentally.
Fluorescence microscopy of rat embryo sections stained with haematoxylin–eosin and Masson's trichrome method
Authors: Apgar  , Juarranz  , Espada  , Villanueva  , CAÑete  , Stockert
Published: March 2003

The fluorescence pattern induced by haematoxylin–eosin (HE) and Masson's trichrome (MT) staining methods on paraffin sections of rat embryos (from 13 to 18 days old) has been studied. Using optimal excitation (green light, 545 nm), HE‐ or MT‐stained sections showed a selective red emission of the acidophilic tissue components, which was due to eosin Y in the case of HE and to acid fuchsin and/or xylidine ponceau in the case of MT. The fluorescence intensity induced by these anionic dyes was variable and related to the substrate nature and the embryo age. Whereas in young embryos only the immature red blood cells showed a noticeable fluorescence, in the oldest embryos there were also other tissue components that selectively fluoresced with these dyes, in particular fibre lens cells, elastic fibres, zymogen granules and muscle cells. Spectrofluorometric studies on free dyes and densitometric analysis of protein blots confirmed microscopical observations. Our results indicate that the standard HE and MT staining methods can be used in recognizing the appearance of specific protein structures in embryonic tissues by means of fluorescence microscopy.
A numerical study of resolution and contrast in soft X‐ray contact microscopy
Authors: Wang Y. , Jacobsen
Published: March 2003

We consider the case of soft X‐ray contact microscopy using a laser‐produced plasma. We model the effects of sample and resist absorption and diffraction as well as the process of isotropic development of the photoresist. Our results indicate that the micrograph resolution depends heavily on the exposure and the sample‐to‐resist distance. In addition, the contrast of small features depends crucially on the development procedure to the point where information on such features may be destroyed by excessive development. These issues must be kept in mind when interpreting contact microradiographs of high resolution, low contrast objects such as biological structures.
Dispersion pre‐compensation of 15 femtosecond optical pulses for high‐numerical‐aperture objectives
Authors: Müller  , Squier  , Wolleschensky  , Simon  , Brakenhoff
Published: March 2003

The excitation efficiency in two‐photon absorption (TPA) microscopy depends strongly — owing to the square dependence of the TPA fluorescence on the excitation intensity — on the temporal width of the excitation pulse. Because of their inherently large frequency bandwidth, ultrashort optical pulses tend to broaden substantially because of dispersion from propagation through the dispersive elements in the microscope. In this paper, the dispersion characteristics of a wide range of microscope objectives are investigated. It is shown that the induced dispersion can be pre‐compensated in all cases for pulses as short as 15 fs. Because of the excellent agreement between the results from theoretical modelling and the experimental data, predictions of the possibility of dispersion control for microscope objectives in general, as well as for even shorter pulses, can be inferred. Since for TPA imaging the background due to single photon absorption processes and scattering is independent of the pulse width, proper dispersion pre‐compensation — which minimizes the pulse duration at the focal point and hence maximizes the excitation efficiency — provides optimal image contrast in TPA microscopy.
Crystallographic analysis of freeze‐fracture electron micrographs: application to the structure determination of cubic lipid–water phases
Authors: Delacroix
Published: March 2003

An original approach combining freeze‐fracture electron microscopy and quantitative image processing has been developed as an alternative to X‐ray analysis. It has been applied to the crystallographic study of different lipid–water cubic phases [bicontinuous or micellar and of type I (oil‐in‐water) or type II (water‐in‐oil)] and has enabled significant advances in the study of these phases. Freeze‐fracture electron microscopy has revealed that the cubic phases fracture preferentially along a few crystallographic directions which appeared on the images as noisy planar fracture surfaces containing periodic information. The visibility of the corresponding unit cells has been considerably improved by image‐filtering techniques based on correlation averaging, allowing a quantitative analysis of the fracture images to be made. This analysis yielded faithful information on the symmetries of the cubic structure (rotation axes and mirror planes) as well as on the structure of the cubic phase itself. Eventually, the different parameters that determine the most favourable fracture pathways within the structures were established. This novel approach constitutes a powerful tool of general interest, complementary to X‐ray diffraction, for solving complex ordered macromolecular structures at low resolution.
A new cryostage design for cryomicroscopy
Authors: Namperumal  , Coger
Published: March 2003

The use of cryomicroscopes for the study of cryopreservation of biological samples has been well established. This paper describes a new cryostage design for a cryomicroscopic system able to yield cooling and warming rates up to 18 000 °C min−1. This directional solidification cryostage incorporates design features that enable it to span large temperature gradients and high cooling rates. Each copper base of the new design is a three‐piece construction containing a sandwiched thermofoil heater and an internal zigzag flow channel for the refrigerant. Consequently, the temperature of each base can be independently varied between −150 °C and +150 °C. In addition, the new design includes an adjustable gap between the bases that can be adjusted from 0.5 mm to 2.5 mm using attached micrometer heads. The visible gradations on each micrometer enable symmetry of the copper bases to be maintained after each adjustment. In addition to the specifics of the design, this work discusses the surface and thermal characterization results of the stage. Then to demonstrate the performance of the instrument, experimental results with saline solution and the subsequent quantitative analysis are presented.
A cryoclamp for the rapid cryofixation of the isolated blood‐perfused rabbit cardiac papillary muscle preparation at predefined times during the contraction cycle
Authors: Shattock  , Miller  , Marchant  , Foreman  , Ford  , Bray  , Waldron  , Chambers  , Warley
Published: March 2003

There is increasing evidence that the distribution of monovalent cations in cardiac cells may be non‐uniform, particularly in the region immediately beneath the sarcolemma, and we have proposed that a build‐up of sodium in this region could be an important factor in the development of ischaemia‐reperfusion injury. Electron probe X‐ray microanalysis is ideal for the study of such changes in distribution but the application of the technique to this problem imposes severe requirements on the specimen and on the method for cryofixation. The specimen must be perfused through its vasculature so that it can be made truly ischaemic and be successfully reperfused. It is necessary to be able to cryofix the specimen without disturbance of its blood supply, electrical stimulation or temperature. It is also important to know the time in the contraction cycle when cryofixation occurs. Here we describe the design of an automated cryofixation device which can be used to cryofix a blood perfused papillary muscle preparation at predetermined time points in the contraction cycle. Preliminary data obtained from the analysis of rabbit papillary muscles subjected to varying periods of ischaemia are included as an example of the use of the cryoclamp.
Multivariate statistical methods for the analysis of microscope image series: applications in materials science
Authors: Bonnet N.
Published: March 2003

Multivariate data sets are now produced in several types of microscopy. Multivariate statistical methods are necessary in order to extract the useful information contained in such (image or spectrum) series. In this review, linear and nonlinear multivariate methods are described and illustrated with examples related both to the segmentation of microanalytical maps and to the study of variability in the images of unit cells in high‐resolution transmission electron microscopy. Concerning linear multivariate statistical analysis, emphasis is put on the need to go beyond the classical orthogonal decomposition already routinely performed through principal components analysis or correspondence analysis. It is shown that oblique analysis is often necessary when quantitative results are expected. Concerning nonlinear multivariate analysis, several methods are first described for performing the mapping of data from a high‐dimensional space to a space of lower dimensionality. Then, automatic classification methods are described. These methods, which range from classical methods (hard and fuzzy C‐means) to neural networks through clustering methods which do not make assumptions concerning the shape of classes, can be used for multivariate image segmentation and image classification and averaging.
High‐precision assessment of interface lattice offset by quantitative HRTEM
Authors: SCHWEINFEST  , ERNST  , WAGNER  , RÜHLE
Published: March 2003

We introduce a new method to determine the ‘lattice offset’ or ‘rigid‐body shift’ between two crystals forming an interface. Our method relies on quantitative evaluation of high‐resolution transmission electron microscopy images. Employing the (001)‐orientated interface between Al and MgAl2O4 in parallel orientation as a model system we demonstrate that we can assess the interface lattice offset with a precision in the picometre range.
Photocurrent near‐field microscopy of Schottky barriers
Authors: Coluzza C. , Di Claudio G. , Davy S. , Spajer M. , Courjon D. , Cricenti A. , Generosi R. , Faini G. , Almeida J. , Conforto E. , Margaritondo G.
Published: March 2003

We used a combination of internal photoemission and of near‐field optical microscopy (SNOM) to study the lateral variations in solid interface properties such as energy barriers and electron–hole recombination. In particular we investigated the fully formed Pt–GaP, Au–GaAs, Au–SiNx–GaAs and PtSi–Si Schottky barriers. Our approach enabled us to measure large lateral variations in the photocurrent with spatial resolution on the nanometric scale. Due to the ability of SNOM to supply parallel topographic information, we observed photocurrent variations from zone to zone that only correlated in a few cases with local variations in surface morphology. We assigned the uncorrelated fluctuations to local variations in the interface stoichiometry, the presence of interface states induced by the metallic overlayer and to defect states at the junction. Furthermore, by tuning the photon energy and applied bias we were able to measure the surface distribution of the diffusion length.
Problems in determining the misorientation axes, for small angular misorientations, using electron backscatter diffraction in the SEM
Authors: PRIOR D. J.
Published: March 2003

The errors associated with calculating misorientation axes from electron backscatter diffraction (EBSD) data have been assessed experimentally. EBSD measurements were made on the same grains after imposed rotations of 2°, 5°, 7°, 10°, 12°, 17°, 27° and 180° around the normal to the specimen surface. The misorientation magnitudes and the misorientation axes associated with the imposed rotations have been calculated from the EBSD data. Individual measurements of misorientation axes are precise for misorientation magnitudes greater than ≈ 20°. The errors must be appreciated when assessing misorientation data at lower misorientation magnitudes and particularly at magnitudes less than 5°. Where misorientation axes can be characterized by the distribution of axes from a number of individual measurements, current EBSD techniques are satisfactory, for data sets of 30 measurements, as long as misorientation magnitudes are 10° or more. With larger data sets it may be possible to extend this approach to smaller misorientation magnitudes. For characterization of individual misorientations less than 5°, new EBSD techniques need to be developed.
Microstructural investigations in Cf–SiC composites in as‐sintered state and after creep experiments
Authors: Vicens  , Boitier  , Chermant
Published: March 2003

The high interest in ceramic matrix composites during the last decade has led to a considerable number of studies devoted to their thermomechanical properties and damage processes. Despite their sensitivity to oxygen partial pressure, carbon fibres appear to possess higher stability and better mechanical properties if they are treated under protective atmospheres than other ceramic fibres (especially classical silicon carbide fibres). The aim of this investigation is to characterize at the nanoscale the main microstructural parameters of Cf–SiC composites provided by the SEP (Division of SNECMA, Bordeaux, France). This material was fabricated from a 2.5D preform made of high strength polyacrylonitrile (PAN)‐based carbon fibres densified according to the chemical vapour infiltration process. A pyrocarbon (PyC) interphase was deposited on the fibre prior to the β‐SiC matrix infiltration. A careful high resolution electron microscopy (HREM) microstructural investigation focused on the fibre microstructure as well as on the different interfaces in the material: pyrocarbon/fibre and matrix/pyrocarbon interfaces. All these observations have been realized in longitudinal and transverse sections of the specimen. These observations are found in good agreement with Guigon's model for high strength ex‐PAN carbon fibres. The PyC interphase texture was strongly anisotropic at the fibre/interphase and interphase/matrix interfaces over a mean thickness of 8–15 nm. Tensile creep tests were performed under partial pressure of argon between 1273 and 1673 K for stress levels ranging from 110 to 220 MPa. Scanning electron microscopy and high resolution electron microscopy were used to study the microstructural modifications inside the fibres and at the different interfaces. A discussion of the possible creep mechanisms based on the microstructural investigation and the creep results is presented.
Optimizing the window size for multiple least squares fitting of electron energy loss spectra
Authors: Ho  , Feng  , Somlyo  , Shao
Published: March 2003

The purpose of this study was to determine the effect of the fitting window size used with the linear least squares fit method when quantitating trace elements with electron energy loss spectroscopy. Theory and computer simulation with a simple model of two ‘signals’ show that, when the background underlying the signal is slowly varying and the signal is localized, there exists a minimum window optimal for fitting raw spectra. The width of the minimum fitting window can be determined directly from the reference standard spectrum of the signal alone and the estimates of signal and background are related. Use of narrower than the minimum window will increase the fitting uncertainty of the signal and yield less reliable results. More complicated experimental spectra must be fitted to more than two standards and a simple analytical expression of the minimum fitting window cannot be derived, but can be determined empirically. Our study shows that the empirical value obtained from experimental spectra is only slightly larger than the theoretical value derived from the simple model, indicating that this conclusion is still valid. When fitting difference spectra with a slowly varying background, the estimates of signal and background are independent and windows wider than the size of the signal will yield the same fitting uncertainty. In the presence of a non‐slowly varying background, common in difference spectra, the minimum window size depends on the fine structure of the signal and the background.