bluuebunny/crossref_metadata_2025 huggingface dataset:
Unintentional weight loss: diagnosis and prognosis. The first prospective follow‐up study from a secondary referral centre
Authors: Lankisch P. G. , Gerzmann M. , Gerzmann J.‐F. , Lehnick D.
Published: March 2003

Abstract. Lankisch PG, Gerzmann M, Gerzmann J‐F, Lehnick D (Municipal Clinic of Lüneburg, Lüneburg, and University of Göttingen, Göttingen, Germany). Unintentional weight loss: diagnosis and prognosis. The first prospective follow‐up study from a secondary referral centre. J Intern Med 2001; 249: 41–46.

Objectives. To establish the incidence and causes of unintentional weight loss and to compare prognoses.

Design. Prospective.

Setting. Secondary referral centre.

Subjects. 158 patients (89 female, 56%; 69 male, 44%) referred by general physicians for unexplained weight loss or for other reasons. In the latter case, weight loss was established after admission to hospital. Follow‐up lasted for up to 3 years.

Main outcome measure. Determining the course of weight loss in patients with diagnosed and undiagnosed causes.

Results. The cause of weight loss was established in 132 (84%) patients and remained unclear in 26 (16%). Reasons were non‐malignant (60% of patients) and malignant (24%) diseases. Psychological disorders represented 11% of the non‐malignant group. A gastrointestinal disease caused weight loss in 50 (30%) patients. Of malignant disorders, 53% (20 of 38 patients) were gastrointestinal. Amongst the non‐malignant group, 39% (30 of 77 patients) had somatic disorders. The prognosis for unknown causes of weight loss was the same as for non‐malignant causes.

Conclusion. Contrary to common belief, weight loss is not usually due to a malignant disease. A gastrointestinal tract disorder accounts for weight loss in every third patient. If minimal diagnostic procedures cannot establish a diagnosis, then endoscopic investigation of the upper and lower gastrointestinal tract and function tests should be performed to exclude malabsorption.
Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population
Authors: Rolandsson O. , Hägg E. , Nilsson M. , Hallmans G. , Mincheva‐Nilsson L. , Lernmark Å.
Published: March 2003

Abstract. Rolandsson O, Hägg E, Nilsson M, Hallmans G, Mincheva‐Nilsson L, Lernmark Å (Umeå University, Sweden; and University of Washington, Seattle, WA, USA). Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population. J Intern Med 2001; 249: 279–288.

Objective. Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA‐2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population.

Design. A population‐based follow‐up cohort study.

Setting. Participants visited the primary health care centre in Lycksele, Sweden in 1988–92.

Participants. A cohort of 2278 subjects (M/F 1149/1129) who were studied at follow‐up in 1998. At base line there were 2314 subjects (M/F 1167/1147) who participated in the Västerbotten Intervention Program on their birthday when turning either 30, 40, 50 or 60 years of age.

Main outcome measurements. A clinically diagnosed diabetes at follow‐up when the medical records were reviewed for diagnosis of diabetes. At base line, the participants were subjected to a standard OGTT and their BMI determined along with the autoantibodies.

Results. At follow‐up, 42/2278 (1.8%, 95% CI 1.2–2.3) (M/F 23/19) had developed diabetes: 41 subjects were clinically classified with Type 2 and one with Type 1 diabetes. There was no significant relation between autoantibody levels at base line and diabetes at follow‐up. Stepwise multiple logistic regression showed that the odds ratio for developing diabetes was 10.8 (95% CI 6.3–18.9) in subjects in the fourth quartile of BMI (BMI > 27) compared with 7.8 (95% CI 4.8–12.6) in the fourth quartile of 2‐h plasma glucose (>7.5 mmol L−1) and 7.2 (95% CI 4.8–11.4) in the fourth quartile of the fasting plasma glucose (>5.6 mmol L−1).

Conclusion. Islet cell autoantibodies did not predict diabetes at follow‐up. BMI measured at base line was as effective as 2‐h plasma glucose and fasting plasma glucose to predict diabetes in this adult population.
Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy
Authors: Ingelman‐Sundberg M.
Published: March 2003

Abstract. Ingelman‐Sundberg M ( IMM, Karolinska Institutet, Stockholm, Sweden). Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J Intern Med 2001; 250: 186–200.

Drug treatment is in many cases ineffective. Besides patients who do not respond to the treatment despite receiving expensive drugs, adverse drug reactions (ADRs) as a consequence of the treatment, is estimated to cost the US society 100 billion USD and over 100 000 deaths per year. Pharmacogenetics is the discipline which takes the patient’s genetic information of drug transporters, drug metabolizing enzymes and drug receptors into account to allow for an individualized drug therapy leading to optimal choice and dose of the drugs in question. It is believed that much cost for the society can be saved in this manner. Many drug transporters are polymorphic. In addition, the majority of phase I and phase II dependent drug metabolism is carried out by polymorphic enzymes which can cause abolished, quantitatively or qualitatively altered or enhanced drug metabolism. Stable duplication, multiduplication or amplification of active genes, most likely in response to dietary components that have resulted in a selection of alleles with multiple noninducible genes, has been described. Several examples exist where subjects carrying certain alleles suffer from a lack of drug efficacy because of ultrarapid metabolism caused by multiple genes or by induction of gene expression, or, alternatively, adverse effects from the drug treatment as a result of the presence of defective alleles. The information about the role of polymorphic drug receptors for efficiency of drug therapy is more scarce, although promising examples are seen in drug treatment of asthma where the efficiency can be severely enhanced by predictive genotyping of the drug targets. In addition, certain polymorphic genes can be used as markers for optimization of the drug therapy. It is likely that predictive genotyping is of benefit in 10–20% of drug treatment and thereby allows for prevention of causalities as a cause of ADRs and thus improves the health for a significant fraction of the patients. In 15–40% of the cases, the penetrance of genetic polymorphism is of less importance because of the polygenic influence on the outcome of drug treatment and in 50% of the cases, pharmacogenetics would be without influence because of other more important physiological and environmental factors. In the present contribution an overview about our present knowledge how polymorphic genes can influence the drug efficacy is presented. Some emphasis will be given to different forms of cytochrome P450 which are of importance for drug metabolism.
Low risk of contrast‐medium‐induced nephropathy with modern angiographic technique
Authors: Sterner G. , Nyman U. , Valdes T.
Published: March 2003

Abstract. Sterner G, Nyman U, Valdes T (Malmö University Hospital, Malmö, Sweden). Low risk of contrast‐medium‐induced nephropathy with modern angiographic technique. J Intern Med 2001; 250: 429–434.

Objective and design. A retrospective study of the incidence of contrast‐medium‐induced nephropathy (CMN) in patients with renal insufficiency.

Subjects. All angiographies with and without endovascular therapeutic procedures (n=2400) performed at the hospital during 1 year were evaluated. A total of 139 patients were found to have a preangiographic serum‐creatinine (s‐Cr) of 150 μmol L–1 or above. Postprocedural serial s‐Cr values were present in 118 patients and these were included in the study.

Results. Amongst patients receiving only iodinated contrast media (CM) 8% demonstrated a 25% rise in s‐Cr. The corresponding figure was 11 and 12.5% amongst patients who were given either iodinated CM together with carbon dioxide (CO2) or CO2 as sole contrast medium. After exclusion of other explanations of impaired renal function all together only seven of 114 patients (6%) were considered to have developed CMN. Four of the seven patients restituted renal function completely, whilst it remained decreased in three. No patient required dialysis. The percentage of diabetic patients were not found to be different in patients with and without signs of CMN.

Conclusions. The present retrospective study indicate that the risk of CMN in connection with angiography is low when modern low‐osmolality CM and contrast saving angiographic technique including CO2 is used combined with proper hydration. Patients with diabetes mellitus were not found more frequently in the groups with CMN.
Sleep complaints predict coronary artery disease mortality in males: a 12‐year follow‐up study of a middle‐aged Swedish population
Authors: Mallon L. , Broman J.‐E. , Hetta J.
Published: March 2003

Abstract. Mallon L, Broman J‐E, Hetta J (University Hospital, Uppsala, and Falun Hospital, Falun; and Institute of Clinical Neuroscience, Göteborg; Sweden). Sleep complaints predict coronary artery disease mortality in males: a 12‐year follow‐up study of a middle‐aged Swedish population. J Intern Med 2002; 251: 207–216.

Objectives. Only a few prospective surveys have been performed to investigate the relationship between sleep complaints and coronary artery disease (CAD) mortality. This study was conducted to determine whether sleep complaints in a middle‐aged population predicted total mortality and CAD mortality.

Design. A population‐based prospective study.

Setting. The County of Dalarna, Sweden.

Subjects and methods. In 1983, a random sample of 1870 subjects aged 45–65 years responded to a postal questionnaire (response rate 70.2%) including questions about sleep complaints and various diseases. Mortality data for the period 1983–95 were collected, and Cox proportional hazard analyses were used to examine the mortality risks.

Results. At 12‐year follow‐up 165 males (18.2%) and 101 females (10.5%) had died. After adjustment for a wide range of important putative risk factors, difficulties initiating sleep (DIS) were related to CAD death in males [relative risk (RR), 3.1; 95% confidence interval (CI), 1.5–6.3; P < 0.01], but not in females. Short or long sleep duration did not influence risk of CAD mortality or total mortality for either gender. Depression in males increased the risk of death attributed to CAD (RR, 3.0; 95% CI, 1.1–8.4; P < 0.05) and total mortality (RR, 2.2; 95% CI, 1.1–4.5; P < 0.05).

Conclusion. These results provide evidence that there is an association between difficulties falling asleep and CAD mortality in males.
Quality of life in patients with familial hypercholesterolaemia
Authors: HOLLMAN G. , GULLBERG M. , EK A.‐C. , ERIKSSON M. , OLSSON A. G.
Published: March 2003

Abstract. Hollman G, Gullberg M, Ek A.‐C, Eriksson M, Olsson AG (University of Linköping, Linköping; Huddinge University Hospital, Stockholm, Sweden). Quality of life in patients with familial hypercholesterolaemia. J Intern Med 2002; 251: 331–337.

Objectives. The primary aim of this study was to analyse quality of life in adult patients with familial hypercholesterolaemia (FH), a genetic disorder with increased risk of coronary heart disease (CHD). Secondary aims were to find explanatory factors for quality of life and anxiety.

Design. A descriptive cross‐sectional design was used.

Setting. Outpatients from lipid clinics at two university hospitals in Sweden were included. Patients with heterozygous FH and a randomly selected control group participated by filling out questionnaires.

Subjects. Two hundred and eighty patients with heterozygous FH above 18 years of age were asked, and 212 of whom 185 were free of overt CHD, participated. Of a control group of 2980 persons 1485 were included for comparison.

Methods. We used Likert‐type questionnaires: the Quality of Life Index (QLI) consisting of four subscales, the Hospital Anxiety and Depression Scale (HAD), the Mastery Scale measuring coping and a questionnaire on health and lipids constructed for FH patients.

Results. Patients with FH were significantly more satisfied with overall quality of life 21.8 ± 0.3 (SEM) vs. controls 21.1 ± 0.1 and this was also the case in three of four subscales, all differences P < 0.05. Anxiety about getting CHD was expressed amongst 86% of the patients with FH.

Conclusions. Quality of life amongst patients with FH was at least as good as in controls but they were worried about getting CHD.
Left ventricular diastolic function is related to glucose in a middle‐aged population
Authors: HOLZMANN M. , OLSSON A. , JOHANSSON J. , JENSEN‐URSTAD M.
Published: March 2003

Abstract. Holzmann M, Olsson A, Johansson J, Jensen‐Urstad M (Karolinska Institute, Karolinska Hospital, Stockholm, Sweden). Left ventricular diastolic function is related to glucose in a middle‐aged population. J Intern Med 2002; 251: 415–420.

Objectives. To examine the relation between left ventricular (LV) diastolic function and glucose metabolism in individuals without previously diagnosed diabetes mellitus.

Design. A cross‐sectional population‐based study.

Setting. A university hospital.

Subjects. Thirty‐five men and women 56–58 years of age without previously diagnosed diabetes or heart disease.

Main outcome measures. Left ventricular diastolic function assessed by pulsed Doppler tissue imaging and its relation to fasting plasma glucose, glucose postload and glycated haemoglobin. LV diastolic function was determined by measuring early diastolic filling peak velocity (Em wave cm s−1), late diastolic filling peak velocity (Am wave cm s−1) and their ratio Em/Am.

Results. Peak Em velocity, peak Am velocity and their ratio Em/Am correlated with fasting plasma glucose (r=–0.42, P=0.01; r=0.47, P=0.04 and r=−0.53, P=0.001, respectively). There was a correlation between peak Em velocity, the ratio of Em/Am and glycated haemoglobin. LV diastolic function was also related to glucose postload.

Conclusions. Left ventricular diastolic function is related to concentrations of fasting plasma glucose, glucose postload and glycated haemoglobin even below the threshold of diabetes. This indicates that glucose concentrations already in the upper end of the normal range has negative impact on cardiac function.
Effects of micronized fenofibrate versus atorvastatin in the treatment of dyslipidaemic patients with low plasma HDL‐cholesterol levels: a 12‐week randomized trial
Authors: Després J.‐P. , Lemieux I. , Salomon H. , Delaval D.
Published: March 2003

Abstract. Després J‐P, Lemieux I, Salomon H, Delaval D (CHUL Research Center, Ste‐Foy, Québec, Laval Hospital Research Center, Ste‐Foy, Québec, Canada and Laboratoires Fournier, Garches, France). Effects of micronized fenofibrate versus atorvastatin in the treatment of dyslipidaemic patients with low plasma HDL‐cholesterol levels: a 12‐week randomized trial. J Intern Med 2002; 251: 490–499.

Background. Studies have suggested that raising low levels of high‐density lipoprotein cholesterol (HDL‐C) may be an important target for the prevention of coronary heart disease.

Objective. To compare the ability of micronized fenofibrate and atorvastatin to increase plasma HDL‐C levels.

Design. Multicentre, randomized open‐label study.

Settings. The study was conducted in 19 centres across the UK and Canada.

Subjects. One hundred and eighty‐one patients were randomized and the full analysis set included 165 nondiabetic patients with low HDL‐C (women <46 mg dL−1, i.e. 1.2 mmol L−1 and men <43 mg dL−1, i.e. 1.1 mmol L−1): 86 patients in the atorvastatin group and 79 patients in the micronized fenofibrate group.

Interventions. Micronized fenofibrate (200 mg day−1, 87 patients) or atorvastatin (10 mg day−1, 94 patients) for a period of 12 weeks.

Main outcome measures. Percent change in HDL‐C levels.

Results. After 12 weeks of treatment, the mean percent change from baseline in HDL‐C was significantly higher in the micronized fenofibrate group (13.3%) compared with the atorvastatin group (5.3%, P=0.0003). The magnitude of such relative change was inversely related to the baseline HDL‐C levels only in the micronized fenofibrate group. Furthermore, in the fenofibrate treatment group, 50.9% of the patients (29 of 57 patients) with a baseline HDL‐C <40 mg dL−1 achieved a plasma HDL‐C level above 40 mg dL−1 after 12 weeks of treatment versus 27.9% of the patients (19 of 68 patients) in the atorvastatin group (P=0.01).

Conclusions. On the basis of (1) the greater impact of fenofibrate than atorvastatin on HDL‐C levels and (2) the greater proportion of dyslipidemic patients achieving HDL‐C levels above 40 mg dL−1 with fenofibrate than atorvastatin, it is suggested that micronized fenofibrate should be considered as a good therapeutic option to treat dyslipidemic patients with low HDL‐C and moderately elevated LDL‐C concentrations.
Atrial fibrillation or flutter and stroke: a Danish population‐based study of the effectiveness of oral anticoagulation in clinical practice
Authors: FROST L. , JOHNSEN S. P. , PEDERSEN L. , TOFT E. , HUSTED S. , SØRENSEN H. T.
Published: March 2003

Abstract. Frost L, Johnsen SP, Pedersen L, Toft E, Husted S, Sørensen HT (Aarhus University Hospital and Aarhus University, Aarhus, Denmark).J Intern Med2002;252:64–69.

Objectives. A pooled analysis of randomized trials has shown that oral anticoagulation therapy reduces the risk of ischaemic stroke with 68% in patients with atrial fibrillation. We examined the effectiveness of oral anticoagulation on risk of stroke of any nature (fatal and nonfatal ischaemic and/or haemorrhagic stroke) in patients with nonvalvular atrial fibrillation or flutter living in the County of North Jutland, Denmark.

Design. Cohort study.

Subjects and methods. We used the Hospital Discharge Registry covering the county (490 000 inhabitants) from 1991 to 1998 to identify 2699 men and 2425 women with atrial fibrillation or flutter, aged 60–89 years. Data on prescriptions of anticoagulation were obtained from the National Health Service. We defined use of oral anticoagulation as date of prescription or reiteration plus 90 days. Patients were followed in the County Hospital Discharge Registry until a diagnosis of stroke (fatal and nonfatal ischaemic and/or haemorrhagic stroke), emigration, death or the end of 1998. We used Cox regression analyses to estimate the relative risk of stroke associated with use of oral anticoagulation compared with no use, adjusted for age, diabetes and underlying cardiovascular diseases.

Results. Eight hundred and thirty‐eight of 2699 men (31%) and 552 of 2425 women (23%) with atrial fibrillation had one or more recorded prescriptions of oral anticoagulation. The incidence rates of stroke were 31 per 1000 person‐years of follow‐up in men, and 30 per 1000 person‐years of follow‐up in women. The adjusted relative risks of stroke during anticoagulation were 0.6 [95% confidence interval (CI) 0.4–1.0] in men, and 1.0 (95% CI 0.7–1.6) in women compared with nonuse periods.

Conclusions. The effectiveness of oral anticoagulation in clinical practice may be lesser than the efficacy of oral anticoagulation reported from randomized trials.
Individual variations of platelet inhibition after loading doses of clopidogrel
Authors: Järemo P. , Lindahl T. L. , Fransson S. G. , Richter A.
Published: March 2003

Abstract. Järemo P, Lindahl TL, Fransson SG, Richter A (Linköping University Hospital, Linköping, Sweden). Individual variations of platelet inhibition after loading doses of clopidogrel. J Intern Med 2002; 252: 233–238.

Objective.  To investigate individual variations of platelet inhibition after clopidogrel‐loading doses.

Setting.  Department of Cardiology, Linköping University Hospital, Linköping, Sweden.

Subjects.  Individuals with stable angina pectoris (n = 18) subject to percutaneous coronary interventions (PCI) and subsequent stenting were investigated.

Methods and experimental protocol.  A 300‐mg clopidogrel loading dose was administrated immediately after stenting (day 1) followed by an additional 75 mg clopidogrel after 24 h (day 2). The ADP‐evoked platelet fibrinogen binding was analysed to estimate platelet reactivity immediately before angiography and on day 2. A flow cytometry technique was used with two ADP solutions (final concentrations 0.6 and 1.7 μmol L−1) employed as platelet activating agents. Soluble P‐selectin was used as a marker of platelet activity.

Results.  When using 1.7 μmol L−1 ADP to activate platelets four individuals had a strong inhibition (i.e. platelet reactivity <10% of the day 1‐value day 2). In contrast, five patients demonstrated a weak inhibition (i.e. platelet reactivity >60% of the day 1‐value day 2). Similar results were obtained when using 0.6 μmol L−1 ADP as a platelet‐activating agent. Clopidogrel, however, fails to suppress platelet activity as estimated from soluble P‐selectin.

Conclusions.  Clopidogrel evoked platelet inhibition exhibits a considerable individual heterogeneity. Some individuals only had weak responses whereas others displayed strong platelet inhibition. The present flow cytometry technique appears suitable for identifying patients with abnormal reactions after clopidogrel exposure.
Heritability of death from coronary heart disease: a 36‐year follow‐up of 20 966 Swedish twins
Authors: Zdravkovic S. , Wienke A. , Pedersen N. L. , Marenberg M. E. , Yashin A. I. , De Faire U.
Published: March 2003

Abstract. Zdravkovic S, Wienke A, Pedersen NL, Marenberg ME, Yashin AI, de Faire U (Karolinska Institutet, Stockholm, Sweden; Max‐Planck Institute for Demographic Research, Rostock, Germany; University of Pennsylvania School of Medicine, Philadelphia, PA, USA). Heritability of death from coronary heart disease: a 36‐year follow‐up of 20 966 Swedish twins.J Intern Med2002;252:247–254.

Objective. The aim of the present study was to evaluate and distinguish between environmental and genetic effects for death from coronary heart disease (CHD) as well as to determine whether the importance of genetic influences is changing with age.

Design. A cohort study with a follow‐up time of 36 years.

Subjects. The cohort drawn for the present study includes 20 966 twins born in Sweden between 1886 and 1925 where both twins within a pair still lived within the country in 1961.

Methods. Concordances and correlated γ‐frailty model were used to assess and distinguish between genetic and environmental influences as well as to evaluateage‐relatedchanges in genetic influences.

Results. A total number of 4007 CHD‐deaths (2208 males, and 1799 females) was observed. The probability of dying from CHD given that one's twin partner already has died from CHD decreased with increasing age, particularly amongst males. The genetic variation in susceptibility to death from CHD was moderately large, and decreased slightly across time, particularly amongst males. The heritability was 0.57 (95% CI, 0.45–0.69) amongst male twins, and 0.38 (0.26–0.50) amongst female twins.

Conclusions. The genetic contribution to the variation in CHD‐mortality was moderate both in females and males. Furthermore, although genetic effects appeared to be greater at younger ages of death, our findings clearly suggest that genetic factors are in operation throughout the entire life span.
The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies
Authors: Lichtenstein P. , De faire U. , Floderus B. , Svartengren M. , Svedberg P. , Pedersen N. L.
Published: March 2003

Abstract.  Lichtenstein P, de Faire U, Floderus B, Svartengren M, Svedberg P, Pedersen NL (Karolinska Institutet; Karolinska Hospital; Institute of Environmental Medicine, Karolinska Institutet, National Institute for Working life, Stockholm, Sweden; and University of Southern California, CA, USA) The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies (Review). J Intern Med 2002; 252: 184–205.

The Swedish Twin Registry (STR), which today hasdeveloped into a unique resource, was first established in the late 1950s to study the importance of smoking and alcohol consumption on cancer and cardiovascular diseases whilst controlling for genetic propensity to disease. Since that time, the Registry has been expanded and updated on several occasions, and the focus has similarly broadened to most common complex diseases. In the following, we will summarize the content of the database, describe for the first time recent data collection efforts and review some of the principal findings that have come from the Registry.
Phospholipid and cholesteryl ester transfer are increased in lipoprotein lipase deficiency
Authors: Kaser S. , Sandhofer A. , Hölzl B. , Gander R. , Ebenbichler C. F. , Paulweber B. , Patsch J. R.
Published: March 2003

Abstract.  Kaser S, Sandhofer A, Hölzl B, Gander R, Ebenbichler CF, Paulweber B, Patsch JR (University Hospital Innsbruck, Innsbruck; and General Hospital Salzburg, Salzburg, Austria). Phospholipid and cholesteryl ester transfer are increased in lipoprotein lipase deficiency. J Intern Med 2003; 253: 208–216.

Objectives.  Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism by mediating the transfer and exchange of phospholipids (PL) and neutral lipids between lipoproteins. Lipoprotein lipase (LPL) deficiency is associated with low HDL‐cholesterol (HDL‐C) levels in both, the homozygous and heterozygous state. In the present study we set out to investigate the role of lipid transfer proteins, which are known to strongly determine HDL‐C levels, in LPL deficiency.

Design/subjects.  Phospholipid acceptor and donor properties of lipoproteins, PLTP activity, CETP mass, activity and cholesteryl ester (CE) transfer were determined in two homozygous and six heterozygous LPL‐deficient subjects and in 10 healthy, normolipidaemic controls, respectively.

Results.  The HDL isolated from LPL‐deficient subjects showed strongly increased PL‐acceptance when compared with controls (homozygotes versus heterozygotes versus control: 26.46 ± 15.26 vs. 3.41 ± 1.61 vs. 1.89 ± 0.33 μmol mL−1 h−1/μmol mL−1 PL; all P < 0.05). Phospholipid transfer from apolipoprotein B containing lipoproteins was increased in heterozygotes when compared with controls (46.66 ± 23.3 vs. 28.91 ± 18.05 μmol mL−1 h−1/μmol mL−1 PL, P = 0.05). PLTP activity, however, was similar in LPL‐deficient subjects and controls. CETP mass was highest in homozygotes, whilst enzyme activity was similar in LPL‐deficient subjects and controls. CE transfer was highest in homozygotes (72.5 ± 8.8%) and lowest in controls (28.7 ± 5.2%, P < 0.01).

Conclusions.  In conclusion, PL and CE transfer are increased in LPL deficiency and thus, partly explain low HDL‐levels in LPL‐deficient subjects. Enhanced transfer seems rather to be the result of altered lipoprotein composition and concentration than altered enzyme activity. Our findings on mechanisms leading to low HDL‐C levels might show another aspect in atherogenesis in LPL deficiency.
Association of alcohol consumption with white blood cell count: a study of Japanese male office workers
Authors: Nakanishi N. , Yoshida H. , Okamoto M. , Matsuo Y. , Suzuki K. , Tatara K.
Published: March 2003

Abstract.  Nakanishi N, Yoshida H, Okamoto M, Matsuo Y, Suzuki K, Tatara K (Course of Social Medicine, Osaka University Graduate School of Medicine F2, Osaka, Japan; Japan Labor and Welfare Association, Tokyo, Japan). Association of alcohol consumption with white blood cell count; a study of Japanese male office workers. J Intern Med 2003; 253: 367–374.

Objectives.  To investigate the association of alcohol consumption with white blood cell (WBC) count.

Design.  Cross‐sectional study.

Setting.  A work site in Japan.

Subjects.  A total of 5218 Japanese male office workers aged 23–59 years who participated in annual health examinations.

Main outcome measures.  Subjects were classified as nondrinkers, or current drinkers who averaged <12, 12–22, 23–34, 35–45, 46–68 or ≥ 69 g day−1 of ethanol. The association between alcohol consumption and WBC count was examined by smoking status.

Results.  After controlling for age, body mass index, systolic blood pressure, and levels of total cholesterol, high‐density lipoprotein (HDL) cholesterol and fasting plasma glucose, WBC count showed a negative dose–response relation with alcohol consumption in each smoking status. The WBC count increment per category of alcohol intake (×109 cells L‐1) was −0.07 [95% confidence interval (CI), −0.11 to −0.04] for never smokers, −0.11 (95% CI, −0.15 to −0.06) for ex‐smokers, and −0.04 (−0.08 to −0.00) for current smokers. For current smokers, additional adjustment for cigarettes smoked per day heightened the magnitude of these associations [the respective WBC count increment (×109 cells L‐1), −0.07 (95% CI, −0.11 to −0.03)]. The risk for high WBC count (fifth quintile) also showed a negative linear trend related to alcohol intake in each smoking status.

Conclusions.  The WBC count was inversely associated with alcohol consumption in both nonsmokers and smokers. In view of the firm association of WBC count with the increased risk of coronary heart disease, alcohol consumption seems to have a favourable impact on the link between WBC count and the risk of cardiovascular disease.
Reconstruction of off‐axis electron holograms using a neural net
Authors: Meyer  , Heindl
Published: March 2003

In off‐axis electron holography, the information about the specimen contained in amplitude and phase of the image wave is recorded by superimposing a reference wave to the image wave and recording the resulting interference pattern, called a hologram. The image wave is usually retrieved from this hologram by a filtering process in Fourier space. An alternative approach is to calculate the image wave pixel by pixel from the intensities in the hologram. In this paper, we describe a neural network that performs this step. As neural networks can represent nonlinear relations between the input and output data, this reconstruction process can use the nonlinear part of the information contained in the hologram and is thus less sensitive to noise.
Global spatial sampling with isotropic virtual planes: estimators of length density and total length in thick, arbitrarily orientated sections
Authors: Larsen  , Gundersen  , Nielsen
Published: March 2003

Existing design‐based direct length estimators require random rotation around at least one axis of the tissue specimen prior to sectioning to ensure isotropy of test probes. In some tissue it is, however, difficult or even impossible to define the region of interest, unless the tissue is sectioned in a specific, nonrandom orientation. Spatial uniform sampling with isotropic virtual planes circumvents the use of physically isotropic or vertical sections. The structure that is contained in a thick physical section is investigated with software‐randomized isotropic virtual planes in volume probes in systematically sampled microscope fields using computer‐assisted stereological analysis. A fixed volume of 3D space in each uniformly sampled field is probed with systematic random, isotropic virtual planes by a line that moves across the computer screen showing live video images of the microscope field when the test volume is scanned with a focal plane. The intersections between the linear structure and the virtual probes are counted with columns of two dimensional disectors.

Global spatial sampling with sets of isotropic uniform random virtual planes provides a basis for length density estimates from a set of parallel physical sections of any orientation preferred by the investigator, i.e. the simplest sampling scheme in stereology. Additional virtues include optimal conditions for reducing the estimator variance, the possibility to estimate total length directly using a fractionator design and the potential to estimate efficiently the distribution of directions from a set of parallel physical sections with arbitrary orientation.

Other implementations of the basic idea, systematic uniform sampling using probes that have total 3D × 4π freedom inside the section, and therefore independent of the position and the orientation of the physical section, are briefly discussed.
Towards automatic cell identification in DIC microscopy
Authors: Young  , Glasbey  , Gray  , Martin
Published: March 2003

A general method is proposed for constructing templates of cells in differential interference contrast (DIC) microscopy. This takes account of the optics which generate DIC images, and is applicable to both transparent and semi‐transparent cells of simple and complex shapes. Then, a template matching methodology is presented, which uses fast Fourier transforms to fit templates of a range of sizes and orientations to images. For illustration, this is used to automatically identify and measure individual Candida yeast cells in clusters.
Probabilistic data analysis: an introductory guide
Authors: Skilling J.
Published: March 2003

Quantitative science requires the assessment of uncertainty, and this means that measurements and inferences should be described as probability distributions. This is done by building data into a probabilistic likelihood function which produces a posterior ‘answer’ by modulating a prior ‘question’.

Probability calculus is the only way of doing this consistently, so that data can be included gradually or all at once while the answer remains the same. However, probability calculus is only a language; it does not restrict the questions one can ask by setting one's prior. We discuss how to set sensible priors, in particular for a large problem like image reconstruction.

We also introduce practical modern algorithms (Gibbs sampling, Metropolis algorithm, genetic algorithms, and simulated annealing) for computing probabilistic inference.
A coherence function approach to image simulation
Authors: Müller H. , Rose H. , Schorsch P.
Published: March 2003

A quantitatively correct theory of the simulation of electron micrographs is proposed which considers the partially coherent process of image formation within the electron microscope. The new approach is based on the propagation of the mutual coherence function of the partially coherent electron wave field. Our method leads to the formulation of a generalized multislice algorithm. Applications to imaging with zero‐loss electrons and inelastically scattered electrons are presented. In addition the effect of thermal diffuse scattering is investigated in detail.
Brighter near‐field optical probes by means of improving the optical destruction threshold
Authors: Stöckle R. M. , Schaller N. , Deckert V. , Fokas C. , Zenobi R.
Published: March 2003

The optical destruction thresholds of conventionally etched and tube‐etched near‐field optical probes were measured. One of the main advantages of tube‐etched tips is their smooth glass surface after taper formation. Presumably for this reason, a destruction limit of over 120 μJ was obtained, almost twice as large as that of the rougher, conventionally etched fibre probes. The use of additional adhesion layers (Ti, Cr, Co and Ni) between the glass surface and the aluminium coating produced, especially for tube‐etched tips, a significant increase in the optical destruction threshold. With increasingly thin metal coatings, the use of a protection coating that prevents corrosion during aging is recommended. An additional increase in optical stability was achieved by applying mixed‐metal coatings: alternating thin titanium and thick aluminium layers yielded fibre probes with superior properties that achieved average optical destruction thresholds of > 270 μJ. This is an increase in stability of > 400% compared with conventionally fabricated near‐field optical tips.
The tuning fork as sensor for dynamic force distance control in scanning near‐field optical microscopy
Authors: Naber A.
Published: March 2003

The dynamic force distance control for scanning near‐field optical microscopy on the basis of a tuning fork as piezoelectric force sensor is remarkably sensitive. In order to gain a better understanding of this sensitivity the vibrational properties of the tuning fork are modelled within the framework of two coupled harmonic oscillators. As a result, the effective force constant of the tuning fork at resonance frequency is determined. Furthermore, the influence of the additional mass by the attachment of the near‐field probe is investigated.
Second‐order stereology and ultrastructural examination of the spatial arrangements of tissue compartments within glomeruli of normal and diabetic kidneys
Authors: Mayhew
Published: March 2003

The present study explores 3D spatial arrangements of compartments within the rat renal glomerulus and tests for differences after chemically‐induced diabetes. In particular, the arrangements of capillaries, podocytes, mesangium and urinary space are quantified and compared between (a) kidneys within groups and (b) kidneys from streptozotocin‐diabetic rats and age‐matched controls. The stereological tool employed is the pair correlation function which is estimated by counting linear dipole probes of different sizes superimposed on ultrathin sections so as to be random in position and orientation. Unbiased estimates of the volume density of each glomerular component were estimated by point counting. Thereafter, estimates of the covariance and pair correlation function were determined from corresponding dipole counts. Plots of covariance and pair correlation functions against dipole length were almost identical in control and diabetic groups, indicating that diabetes did not disturb the normal spatial arrangements within glomeruli. However, differences were detected between compartments within groups. Whilst volume elements within all compartments were clustered at distances below about 8 μm (the approximate size of the basic cellular or other structural unit), the cluster size varied between compartments. The pattern was one of progressively smaller clusters in the sequence capillaries, podocytes, urinary space, mesangium. Beyond a distance of 8 μm, all glomerular components (in both control and diabetic groups) were arranged as expected for a ‘random’ (meaning neither clustered nor repulsed) volume process. These studies re‐emphasize the relative invariance of biological organization and the value and limitations of covariance analysis for quantifying different levels of organization in different tissues and experimental groups.
Flat‐bed scanning as a tool for quantitative neuroimaging
Authors: Schmitt  , Eggers
Published: March 2003

The aim of this study was to compare three different imaging techniques which are used to provide data on the laminar structure of the human cerebral cortex. Region V1 of Brodmann's area 17 stained with cresyl violet was investigated, and a conventional semi‐automatic morphometric evaluation, the videomicroscropic procedure and a new transparent flat‐bed scanning technique were compared. The results of each digitizing method were converted into normalized profiles which allow the laminae in the striate cortex to be displayed. It was found that major laminar patterns can be detected by the scanning technique, but that subsidiary laminations are more clearly displayed by morphometry and videomicroscopy. For magnifications up to × 400 a high resolution transparent flat‐bed scanner may be used in place of the videomicroscopy technique.
Scanning and transmission electron microscopy study of the microstructural changes occurring in aluminium matrix composites reinforced with SiC particles during casting and welding: interface reactions
Authors: Ureña  , Gómez De Salazar  , Gil  , Escalera  , Baldonedo
Published: March 2003

Processing of aluminium matrix composites (AMCs), especially those constituted by a reactive system such as Al–SiC, presents great difficulties which limit their potential applications. The interface reactivity between SiC and molten Al generates an aluminium carbide which degrades the composite properties. Scanning and transmission electron microscopes equipped with energy‐dispersive X‐ray spectroscopes are essential tools for determining the structure and chemistry of the Al–SiC interfaces in AMCs and changes occurring during casting and arc welding. In the present work, an aluminium–copper alloy (AA2014) reinforced with three different percentages of SiC particles was subjected to controlled remelting tests, at temperatures in the range 750–900 °C for 10 and 30 min. Arc welding tests using a tungsten intert gas with power inputs in the range 850–2000 W were also carried out. The results of these studies showed that during remelting there is preferential SiC particle consumption with formation of Al4C3 by interface reaction between the solid SiC particle and the molten aluminium matrix. The formation of Al4C3 by the same mechanism has also been detected in molten pools of arc welded composites. However, in this case there was formation of an almost continuous layer of Al4C3, which protects the particle against further consumption, and formation of aciculate aluminium carbide on the top weld. Both are formed by fusion and dissolution of the SiC in molten aluminium followed by reaction and precipitation of the Al4C3 during cooling.
An integral‐geometric approach for the Euler–Poincaré characteristic of spatial images
Authors: Nagel  , Ohser  , Pischang
Published: March 2003

The determination of the Euler–Poincaré characteristic of a set can be based on observations of a digitized image of that set. In the present paper the correctness of the method is proved due to a strict integral‐geometric approach. Our result also provides a link to the methods which are used in image analysis and are based on graph theory.
An investigation of segmentation methods and texture analysis applied to tomographic images of human vertebral cancellous bone
Authors: Cendre  , Kaftandjian  , Peix  , Jourlin  , Mitton  , Babot
Published: March 2003

The goal of this study is to determine architectural and textural parameters on computed tomographic (CT) images, allowing us to explain the mechanical compressive properties of bone. Although the resolution (150 μm) is of the same order of magnitude as the trabecular thickness, this method enables the possibility of perfecting an in vivo peripheral CT system with an acceptable radiation dose for the patient. This study was performed on L2 vertebrae cancellous bone specimens taken after necropsy in 22 subjects aged 47–95 years (mean: 79 years). The segmentation process is a crucial point in the determination of accurate architectural parameters. In this paper the use of two different segmentation methods is investigated, based on an edge enhancement and a region growing approach. The images are compared and the architectural parameters extracted from the images segmented by both methods lead to a quantitative evaluation. The parameters are found to be globally robust towards the segmentation process, although some of them are much more sensitive to the approach used. Highly significant correlations (P < 0.0005) have been obtained between the two segmentation methods for all the parameters, with ρ ranging from 0.70 to 0.93. In order to improve the assessment of bone architecture, texture analysis (run length method) was investigated. New features are obtained from an image reduced to 16 grey‐levels. Textural parameters in addition to architectural parameters in a multivariate regression model increase significantly (P = 0.01) the prediction of the maximum compressive strength (variation of r2 from 0.75 up to 0.89).
The behaviour of the plasma membrane during plasmolysis: a study by UV microscopy
Authors: Lang‐Pauluzzi I.
Published: March 2003

A high resolution ultraviolet (UV) bright‐field microscope was used to analyse the formation of Hechtian strands and the Hechtian reticulation that remain attached to the cell wall after plasmolysis and deplasmolysis of onion inner epidermal cells. In real time video images, UV microscopy allowed a detailed investigation of the dynamic behaviour of the plasma membrane during the processes of osmotic water loss and uptake. Furthermore, the role of cytoskeletal elements as possible linkers of the plasma membrane to the cell wall was probed by application of cytoskeletal drugs during plasmolysis. Microtubules were depolymerized in oryzalin, and latrunculin B was used to destabilize actin microfilaments. The results showed no visible changes in the formation of the Hechtian reticulation or strands. Plasmolysis forms appeared to be normal, indicating stong membrane‐to‐wall attachments independent of cytoskeletal elements. During re‐expansion of the protoplast in deplasmolysis, the plasma membrane incorporated Hechtian strands and subprotoplasts, fused with the Hechtian reticulation and finally realigned at the cell wall.
Using the Hilbert transform for 3D visualization of differential interference contrast microscope images
Authors: Arnison M. R. , Cogswell C. J. , Smith N. I. , Fekete P. W. , Larkin K. G.
Published: March 2003

Differential interference contrast (DIC) is frequently used in conventional 2D biological microscopy. Our recent investigations into producing a 3D DIC microscope (in both conventional and confocal modes) have uncovered a fundamental difficulty: namely that the phase gradient images of DIC microscopy cannot be visualized using standard digital image processing and reconstruction techniques, as commonly used elsewhere in microscopy. We discuss two approaches to the problem of preparing gradient images for 3D visualization: integration and the Hilbert transform. After applying the Hilbert transform, the dataset can then be visualized in 3D using standard techniques. We find that the Hilbert transform provides a rapid qualitative pre‐processing technique for 3D visualization for a wide range of biological specimens in DIC microscopy, including chromosomes, which we use in this study.
Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy
Authors: Gustafsson M. G. L.
Published: March 2003

Lateral resolution that exceeds the classical diffraction limit by a factor of two is achieved by using spatially structured illumination in a wide‐field fluorescence microscope. The sample is illuminated with a series of excitation light patterns, which cause normally inaccessible high‐resolution information to be encoded into the observed image. The recorded images are linearly processed to extract the new information and produce a reconstruction with twice the normal resolution. Unlike confocal microscopy, the resolution improvement is achieved with no need to discard any of the emission light. The method produces images of strikingly increased clarity compared to both conventional and confocal microscopes.
Cathodoluminescence microscopy characterization of chrome‐free refractories for copper smelting and converting furnaces
Authors: Karakus M. , Crites M. D. , Schlesinger M. E.
Published: March 2003

The results of an experimental program assessing the potential of several chrome‐free refractory materials as potential replacements for the mag‐chrome brick currently used in copper production furnaces are presented. Several commercial chrome‐free bricks were subjected to the standard dip test in a high‐copper calcium ferrite slag. The mineralogical changes in the bricks resulting from their interaction with the molten slag are described. The use of optical cathodoluminescence microscopy as an analytical tool is highlighted, along with reflected light microscopy and scanning electron microscopy–energy dispersive spectroscopy. Using the three tools together provides a description of the experimental results not achievable using one or two alone. The penetration resistance of the potential replacement refractories is comparable to that of mag‐chrome, but the substitution of Fe2+ for Mg2+ in the periclase and spinel crystalline structures of the replacements reduces their corrosion resistance compared with mag‐chrome, diminishing the likelihood that they will serve as reliable alternatives.