bluuebunny/crossref_metadata_2025 huggingface dataset:
Relapsing pneumonia due to a migrating intrathoracic foreign body in a World War II veteran shot 53 years ago
Authors: Langer D. , Petermann C. , Lübbers H. , Lankisch P. G.
Published: March 2003

In the great majority of cases of long‐standing intrathoracic foreign bodies, patients are asymptomatic. However, symptoms may occur years later from the migration of the foreign body. We report on a 70‐year‐old patient who developed relapsing pneumonia due to obstruction of a bronchial branch of the left apical group by a migrating infantry bullet impacting 53 years ago. This was not diagnosed until the second attack of pneumonia in 1998. The bullet remains were removed bronchoscopically and the pneumonia resolved completely without further complications.
Bronchoalveolar lavage cells from sarcoidosis patients and healthy controls can efficiently present antigens
Authors: Grunewald J. , Eklund A. , Wigzell H. , Van Meijgaarden K. E. , Ottenhoff T. H. M.
Published: March 2003

Objectives. The interaction between antigen‐presenting cells (APC) and T lymphocytes, that recognize the antigen‐HLA complex using its T cell‐receptor for antigen, is of crucial importance for a subsequent specific immune response. In patients with pulmonary sarcoidosis, the local antigen‐ presenting capacity in the lungs has been suggested to be abnormally enhanced, and implicated in the immunopathogenesis of the disease. This study was aimed at increasing the understanding of the capacity to present antigens by APC in the lung compartment.

Design and subjects. We used bronchoalveolar lavage (BAL) cells and paired peripheral blood mononuclear cells (PBMC) of six sarcoidosis patients and two healthy controls to stimulate in total eight well characterized T‐cell clones with known HLA and antigen specificities. All subjects were HLA typed.

Results.  BAL cells of sarcoidosis patients as well as of healthy controls efficiently induced proliferation of the relevant T‐cell clone in an HLA‐restricted manner when adding either intact antigen or antigenic peptides.

Conclusions.  BAL cells have the capacity to process and present antigens adequately, irrespective of whether they are derived from healthy individuals or from patients with sarcoidosis, implying the alveolar space as an important location for active immune reactions.
Urinary albumin excretion rate is independently related to autonomic neuropathy in type 2 diabetes mellitus
Authors: Wirta O. R. , Pasternack A. I. , Mustonen J. T. , Laippala P. J. , Reinikainen P. M.
Published: March 2003

Objective.  To evaluate if urinary albumin excretion rate (UAER) is independently related to subclinical autonomic neuropathy in type 2 diabetes.

Design.  A controlled cross‐sectional study.

Setting.  Primary health care centre.

Subjects.  Consecutive recently diagnosed (<1 year) type 2 diabetic patients (group A, n = 150) and patients with long‐standing (median 11 years) type 2 diabetes (group B, n = 146) chosen at random. A nondiabetic control group (group C, n = 150) matched for age and gender to group A.

Main outcome measures.  Neuropathy by cardiovascular reflex tests and UAER by nephelometry.

Methods.  Univariate statistics in group A + B (t‐test χ2– or McNemars test) with Valsalva and breathing ratios as categorical grouping variables and the independent variables gender, smoking, systolic and diastolic blood pressure, fasting serum cholesterol, HDL cholesterol, triglycerides, haemoglobin A1c, glucagon stimulated C‐peptide, fasting and postload 1 and 2 h blood glucose and serum insulin, UAER, coronary heart disease and congestive heart failure. Logistic regression analyses in group A + B with Valsalva and breathing ratios as dependent categorical variables and age, systolic blood pressure, congestive heart failure, coronary heart disease, fasting blood glucose, serum triglycerides and UAER as independent variables.

Results.  Compared to nondiabetic subjects the diabetic patients of both groups were at increased risk of neuropathy as judged by the Valsalva ratio (P < 0.01). In known diabetic patients with a UAER ≥30 mg 24–1 h neuropathy was more common than amongst their normoalbuminuric counterparts (Valsalva test P = 0.007, breathing test P = 0.02). In logistic regression analysis UAER independently explained abnormal Valsalva (P = 0.015) and breathing tests (P = 0.04) in the group A + B.

Conclusions.  UAER is independently related to subclinical autonomic neuropathy in type 2 diabetes.
Chronic fatigue syndrome: new insights and old ignorance
Authors: Evengård B. , Schacterle R. S. , Komaroff A. L.
Published: March 2003

Abstract. Evengård B, Schacterle RS, Komaroff AL (Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden; and Brigham and Women’s Hospital, Harvard Medical School, Boston, USA). Chronic fatigue syndrome: new insights and old ignorance. J Intern Med 1999; 246: 455–469.

Chronic fatigue syndrome (CFS) is a condition characterized by impairment of neurocognitive functions and quality of sleep and of somatic symptoms such as recurrent sore throat, muscle aches, arthralgias, headache, and postexertional malaise. A majority of patients describe an infectious onset but the link between infections and CFS remains uncertain. Findings show an activation of the immune system, abberations in several hypothalamic‐pituitary axes and involvement of other parts of the central nervous system. The origin is bound to be complex and it may well be that the solution will come together with a more generally altered view about mind–body dualism, and the concept of illness and disease.
High prevalence of Hypophosphataemia amongst patients with infectious diseases. A retrospective study
Authors: Håglin L. , Burman L. ‐A. , Nilsson M.
Published: March 2003

Objectives  To describe the prevalence of hypophosphataemia amongst all patients treated during 1993 for infectious diseases. The associations between serum C‐reactive protein, serum albumin and white blood cells in blood were studied amongst hypophosphataemic patients. Comparisons were made according to the severity of infection.

Design.  A retrospective study of the prevalence of hypophosphataemia, and a case‐control study amongst a subgroup of patients.

Setting   The Department of Infectious Diseases, University Hospital, Umeå, Sweden.

Subjects  For the prevalence study all 967 patients (449 women and 518 men) treated during 1993 were included. In the case‐control study, 108 cases, with serum phosphate ≤ 0.64 mmol L–1, 216 age‐ and sex‐matched controls with serum phosphate > 0.82 mmol L–1 (men) and > 0.86 mmol L–1 (women), respectively, were included.

Results  In 402 of 967 patients (42%) at least one serum phosphate value was below the reference level. Hypophosphataemia was found in 573 of 1966 blood samples (29%). Severe hypophosphataemia (< 0.30 mmol L–1) was seen in 1.2% of the patients (0.9% of blood samples). The prevalence of hypophosphataemia was higher amongst women than amongst men. In the case‐control study, the serum C‐reactive protein and the number of white blood cells was higher amongst the cases compared with the controls (124 vs. 94 mg L–1 and 11.4 vs. 9.3 cells/L × 109, respectively). The multiple logistic regression showed a 4‐fold higher risk of having low serum phosphate in patients with severe infection, compared with mild infections. None of the other variables (albumin, days of hospital stay or white blood cells in blood) increased the risk for hypophosphataemia.

Conclusions  The high prevalence of low serum phosphate levels and the increased risk of having low levels in severe infections shown in this study needs further attention.
Low‐dose vasopressin restores diuresis both in patients with hepatorenal syndrome and in anuric patients with end‐stage heart failure
Authors: Eisenman A. , Armali Z. , Enat R. , Bankir L. , Baruch Y.
Published: March 2003

Abstract. Eisenman A, Armali Z, Enat R, Bankir L, Baruch Y (Rambam Medical Center and Technion‐Israel Institute of Technology, Haifa, Israel; and INSERM, Necker Hospital, Paris, France). Low‐dose vasopressin restores diuresis both in patients with hepatorenal syndrome and in anuric patients with end‐stage heart failure. J Intern Med 1999; 246: 183–190.

Objectives. The purpose of this study was to confirm earlier reports that low‐dose vasopressin (LDVP) analogues promote urine output in patients with hepatorenal syndrome (HRS) and to check whether this mode of therapy could also be effective in renal shutdown due to nonhepatic conditions.

Design. A prospective, open, interventional study.

Setting. An intermediate‐level (step‐down) medical intensive care unit within a general medical ward of a large university‐affiliated hospital.

Subjects. Eighteen successive hospitalized patients with HRS (mean age 65 ± 13 years) and 11 patients with end‐stage congestive heart failure (CHF) (mean age 81 ± 5 years) who failed to restore urine output with conventional treatment (fluids, dopamine, and diuretics) given for at least 24 h.

Interventions. The patients received LDVP (1 IU h−1) continuously in addition to the conventional treatment.

Main outcome measures. Urine output and creatinine clearance every 24 h.

Results. In the HRS group, before treatment the urine output was 155 ± 9 mL 24 –1h (mean ± SD). After treatment with LDVP for 24, 48, and 72 h, urine output improved to 1067 ± 87, 1020 ± 501, and 1311 ± 988 mL 24 –1h, respectively (P < 0.0001 for all measures; two‐tailed paired t‐test). In the CHF group, before treatment the urine output was 99 ± 99 mL 24 –1h. After treatment with LDVP for 24, 48, and 72 h, this improved to 1125 ± 994 mL 24 –1h (P = 0.0028), 1821 ± 1300 mL 24 –1h (P = 0.004), and 2920 ± 2423 mL 24 –1h (P = 0.0012), respectively. The improvement in urine output was not accompanied by a parallel improvement in creatinine clearance. The overall outcome did not change, and all patients except two in each group succumbed to their end‐stage disease, due to nonrenal causes.

Conclusions. LDVP is effective in restoring urine output both in HRS and in CHF. This suggests that LDVP affects mechanisms not specifically related to liver disease. LDVP may be useful in critical patients with renal shutdown whilst awaiting liver or heart transplantation.
Chronic intoxication by doxycycline use for more than 12 years
Authors: Westermann G. W. , Böhm M. , Bonsmann G. , Rahn K. H. , Kisters K.
Published: March 2003

Abstract.   Westermann GW, Böhm M, Bonsmann G, Rahn KH, Kisters K (Westfälische Wilhelms‐University, Münster, Germany). Chronic intoxication by doxycycline use for more than 12 years (Case Report). J Intern Med 1999; 246: 591–592.

We report the clinical case of a 12‐years’ intoxication by doxycycline. A patient with a depersonalization and derealization syndrome took 1 g doxycycline per day. In addition to hepatocellular necrosis with cholestasis, nephrotoxicity, leukopenia, anaemia and skin hyperpigmentation he suffered from hitherto unreported adverse cardiac events as intermittent supraventricular tachycardia and sporadic Wenckebach heart block. Despite a long period of self‐medication these side‐effects were reversible.
Hyperhomocysteinaemia is not associated with isolated crural arterial occlusive disease: The Hoorn Study
Authors: Hoogeveen E. K. , Kostense P. J. , Jakobs C. , Rauwerda J. A. , Dekker J. M. , Nijpels G. , Bouter L. M. , Heine R. J. , Stehouwer C. D. A.
Published: March 2003

Abstract.  Hoogeveen EK, Kostense PJ, Jakobs C, Rauwerda JA, Dekker JM, Nijpels G, Bouter LM, Heine RJ, Stehouwer CDA (University Hospital Vrije Universiteit, Amsterdam). Hyperhomocysteinaemia is not associated with isolated crural arterial occlusive disease: the Hoorn Study. J Intern Med 2000; 247: 442–448.

Objectives.  Hyperhomocysteinaemia is an independent risk factor for peripheral arterial disease (PAD). The localization of peripheral arterial disease is clinically relevant, because proximal (aortoiliac and femoropopliteal) disease is associated with a particularly poor overall prognosis, whereas isolated distal (i.e. crural) disease is associated with a better overall prognosis. The aim of the study was to investigate whether the strength of the association between hyperhomocysteinaemia and peripheral arterial disease differs according to the localization of the anatomical obstruction.

Design.  Fasting serum total homocysteine (tHcy) was measured in an age‐, sex‐ and glucose‐tolerance stratified random sample (n = 631) of a 50‐ to 75‐year‐old general Caucasian population. History of a peripheral arterial reconstruction was recorded. Aortoiliac, femoropopliteal and crural arterial obstructions were registered by means of Doppler flow velocity curves.

Results.  The median serum tHcy level was 12.2 µmol L–1 (interquartile range: 10.0–15.3) in men and 10.7 µmol L–1 (interquartile range: 9.0–13.3) in women. The prevalences of aortoiliac, femoropopliteal and crural obstructions were 2.1%, 2.7% and 11.9%, respectively. After adjustment for age, sex, systolic blood pressure, current smoking, serum cholesterol and diabetes mellitus, the odds ratios (95% confidence interval) per 5 µmol L–1 tHcy increment were 1.41 (1.05–1.89) for aortoiliac, 1.03 (0.70–1.52) for femoropopliteal and 0.82 (0.59–1.15) for crural obstructions. Finally, diabetes mellitus, HbA1c and current smoking were significantly associated with crural and femoropopliteal disease, whereas systolic blood pressure was significantly associated with aortoiliac obstructions.

Conclusions.  The present study indicates that hyperhomocysteinaemia is associated with aortoiliac but not with isolated crural arterial occlusive disease.
Modified LDL – trigger of atherosclerosis and inflammation in the arterial intima
Authors: Pentikäinen M. O. , Öörni K. , Ala‐Korpela M. , Kovanen P. T.
Published: March 2003

Abstract. Pentikäinen MO, Öörni K, Ala‐Korpela M, Kovanen PT (Wihuri Research Institute, Helsinki, Finland). Modified LDL – trigger of atherosclerosis and inflammation in the arterial intima (Minisymposium). J Intern Med 2000; 247: 359–370.

Atherosclerosis is characterized by chronic inflammation of an injured intima. The pathological processes are initiated by accumulation of morphologically distinct, modified forms of LDL, and followed by cellular infiltration and foam cell formation. Activated intimal cells secrete enzymes and agents capable of modifying LDL, and the modified lipids of LDL, in turn, are able to activate intimal cells and to trigger various inflammatory signals. These processes can initiate and maintain a vicious circle in the intima and lead to lesion progression. In this review, we focus on the LDL modifications relevant to the initial lipid accumulation and discuss their pro‐inflammatory effects.
Plasma total homocysteine concentration and the risk of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Studytpdel
Authors: Voutilainen S. , Lakka T. A. , Hämelahti P. , Lehtimäki T. , Poulsen H. E. , Salonen J. T.
Published: March 2003

Abstract. Voutilainen S, Lakka TA, Hämelahti P, Lehtimäki T, Poulsen HE, Salonen JT (University of Kuopio, Kuopio, Finland; Tampere University Medical School, Tampere, Finland; University of Copenhagen, Copenhagen, Denmark). Plasma total homocysteine concentration and the risk of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. J Intern Med 2000; 248: 217–222.

Objectives. Results from prospective studies concerning the association between plasma total homocysteine (tHcy) concentration and coronary heart disease (CHD) are conflicting. The purpose of this study was to test the hypothesis that plasma tHcy is associated with an increased risk of acute coronary events in middle‐aged men.

Design and subjects. We investigated this association in a prospective nested case–control study among Eastern Finnish men aged 42–60 years. Plasma tHcy measurements were carried out for 163 men who had an acute coronary event during an average 8 years and 11 months follow‐up of the whole cohort and for 163 control subjects. Both the cases and the controls were from a cohort of 2005 men who had no clinical CHD at the Kuopio Ischaemic Heart Disease (KIHD) baseline.

Results. Men in the highest plasma tHcy concentration quarter had no increase in the risk of coronary events compared with men with lower tHcy concentrations (odds ratio = 0.88, 95% confidence interval 0.44–1.76). Average follow‐up time before the first coronary event was 4.9 years (SD 3.2) in men in the highest plasma tHcy quarter and 5.5 years (SD 3.1) in men in the three lowest quarters (P = 0.368).

Conclusion. We conclude that plasma tHcy is not associated with an increased risk of coronary events in the middle‐aged male population in eastern Finland.
A case of toxic shock‐like syndrome presenting with serious hypoproteinaemia because of a protein‐losing gastroenteropathy
Authors: Tasaki K. , Sasaki M. , Bamba M. , Shintani Y. , Andoh A. , Tsujikawa T. , Koyama S. , Fujiyama Y. , Bamba T.
Published: March 2003

Abstract. Tasaki K, Sasaki M, Bamba M, Shintani Y, Andoh A, Tsujikawa T, Koyama S, Fujiyama Y, Bamba T (Shiga University of Medical Science, Shiga, Japan). A case of toxic shock‐like syndrome presenting with serious hypoproteinaemia because of a protein‐losing gastroenteropathy (Case report). J Intern Med 2001; 250: 174–179.

A 37‐year‐old man was admitted to our hospital because of toxic shock‐like syndrome (TSLS) induced by Streptococcus pyogenes. After the pathogenic bacteria had been eradicated, serious diarrhoea appeared and a protein‐losing gastroenteropathy developed. An immunohistochemical study of the biopsy specimens of both small and large intestines revealed the infiltration of T‐lymphocytes, predominantly CD8+ cells, into the lamina propria of affected mucosa, villus atrophy and crypt hyperplasia. Considering these histological findings, some immunological mechanism which lead the activation of cytotoxic T‐lymphocytes may play an important role in the pathogenesis of this rare intestinal manifestation of TSLS.
Visceral fat and psychosocial stress in identical twins discordant for obesity
Authors: MARNIEMI J. , KRONHOLM E. , AUNOLA S. , TOIKKA T. , MATTLAR C.‐E. , KOSKENVUO M. , RÖNNEMAA T.
Published: March 2003

Abstract. Marniemi J, Kronholm E, Aunola S, Toikka T, Mattlar C.‐E., Koskenvuo M, Rönnemaa T (Social Insurance Institution, Turku, Finland). Visceral fat and psychosocial stress in identical twins discordant for obesity. J Intern Med 2002; 251: 35–43.

Objectives. Accumulation of intra‐abdominal fat has been suggested, but not yet proved, to be basically as a result of chronic psychosocial stress causing arousal of hypothalamic‐pituitary‐adrenal cortex axis. Our objectives were to study the association between psychosocial stress, obesity and body fat distribution when genetic factors are identical.

Design. Monozygotic twins discordant for obesity were examined in an in‐patient setting.

Subjects. Adult monozygotic twin pairs (12 female, 8 male) with an average intrapair difference of 17 kg in body weight. They were divided into two groups: in group A the visceral fat area of the obese cotwin was higher and, in group B, lower than the gender‐specific median value.

Main measures. Hormonal, physiological and psychological distress indicators, and sleep measures.

Results. Daily urinary cortisol and noradrenaline excretion were higher in the obese cotwins when compared with the nonobese cotwins in group A but not in group B (P=0.026 and 0.020 when intrapair differences were compared between groups A and B, respectively). In serum cortisol, ACTH and CBG concentrations a similar trend was not statistically significant. In group A, the obese cotwins consumed almost 2.5 times as much alcohol as their lean cotwins, whilst in group B the situation was the opposite. The mean amount of active sleep was significantly higher and that of quiet sleep significantly lower in the obese than the lean cotwins only in group A. Intrapair differences in emotional reactions indicating distress and lack of subjective energy were seen only in group A.

Conclusion. When genetic factors are identical, visceral fat accumulation, rather than obesity in general, is associated with increased psychosocial stress and concomitant hormonal changes.
Cerebrotendinous xanthomatosis: molecular characterization of two Scandinavian sisters
Authors: Rystedt E. , Olin M. , Seyama Y. , Buchmann M. , Berstad A. , Eggertsen G. , Björkhem I.
Published: March 2003

Abstract. Rystedt E, Olin M, Seyama Y, Buchmann M, Berstad A, Eggertsen G, Björkhem I (Karolinska Institutet, Stockholm, Sweden; OchanomizuUniversity, Tokyo, Japan; Medisinsk avdeling, Haukeland sykehus, Bergen). Cerebrotendinous xanthomatosis: molecular characterization of two Scandinavian sisters (Case report). Journal of Internal Medicine 2002; 252: 259–264.

Cerebrotendinous xanthomatosis (CTX) is a hereditary disorder, which is inherited as an autosomally recessive disease, causing production of cholesterol and cholestanol xanthomas and mental retardation. The disease is caused by mutations in the gene for sterol 27‐hydroxylase (CYP27A1). The only CTX patients diagnosed in Scandinavia are two Norwegian sisters from a consanguineous marriage. Here we have characterized the mutation and its functional consequences for the enzyme. Analysis of genomic DNA from cultured fibroblasts identified a base exchange C > T in position 1441, causing arginine at amino acid position 441 to be replaced by tryptophan. The same mutation was introduced by mutagenesis in the complimentary DNA (cDNA) for CYP27, ligated into the expression vector pcDNA4/HisMax and transfected into HEK293 cells. The mutated enzyme had less than 5% of the enzyme activity compared with the native enzyme. No abnormal catalytic products could be identified in the cell culture medium. Probably the mutation affects the haem binding within the holoenzyme. The mutation has also previously been reported in a Japanese family. This is the second example of a CTX‐causing mutation that has been recognized in more than one population.
Traffic hypoglycaemias and accidents in patients with diabetes mellitus treated with different antidiabetic regimens
Authors: Harsch I. A. , Stocker S. , Radespiel‐Tröger M. , Hahn E. G. , Konturek P. C. , Ficker J. H. , Lohmann T.
Published: March 2003

Objectives.  Insulin‐treated patients with diabetes are at a higher risk than the general population in causing traffic accidents due to hypoglycaemias. Preceeding investigations focused on insulin‐treated patients and hypoglycaemia‐induced accidents as ‘end‐points’. We studied the incidence of symptomatic hypoglycaemia and hypoglycaemia‐induced accidents during driving and put it in relation to the different treatment modes of insulin therapy (Conventional Insulin Treatment = CT, Intensified Conventional Insulin Treatment = ICT, Continuous Subcutaneous Insulin Infusion = CSII) as well as to patients treated with oral hypoglycaemia‐inducing agents and the two main types of diabetes mellitus.

Design.  Subjects and setting: We investigated 450 patients (122 treated with sulphonylureas, 151 with CT, 143 with ICT and 34 with CSII) by an anonymous questionnaire at different locations to avoid bias. A total of 176 persons had type 1 diabetes, 243 persons had type 2 diabetes, 31 subjects could not be classified.

Results.  Symptomatic hypoglycaemias during driving were rare events with an occurrence of 0.19–8.26 (minimal and maximal mean, depending on the mode of treatment), if given as hypoglycaemias per 100 000 km on one treatment regimen, or 0.02–0.63, if given as events per year driven. Their incidence increased significantly with the degree of ‘strictness’ between the treatment groups, except between the patients treated with ICT and CSII. Hypoglycaemia‐induced accidents are rare with 0.01–0.49, if given as events per 100 000 km and 0.007–0.01, if given as events per year driven. These differences were not significant. Significant confounders influencing the traffic safety of the patients were age, duration of diabetes and concomitant antihypertensive medication. Analysing the data in accordance with the type of diabetes revealed a significantly higher rate of hypoglycaemic events in patients with type 1 diabetes. The number of hypoglycaemia‐induced accidents was considerably higher in this group, but failed slightly to reach statistical significance.

Conclusions.  Hypoglycaemias during driving are rare events, their occurrence is significantly influenced by the treatment regimen and type of diabetes. Hypoglycaemia‐induced accidents are extremely rare, presumably as a positive effect of patient education in our group.
Validation of a glucose–insulin–potassium infusion algorithm in hospitalized diabetic patients
Authors: Bonnier M. , Lönnroth P. , Gudbjörnsdottir S. , Attvall S. , Jansson P.‐A.
Published: March 2003

Abstract.  Bonnier M, Lönnroth P, Gudbjörnsdottir S, Attvall S, Jansson P‐A (Sahlgrenska University Hospital, Gothenburg, Sweden). Validation of a glucose–insulin–potassium infusion algorithm in hospitalized diabetic patients. J Intern Med 2003; 253: 189–193.

Background.  The short and long time prognoses of acute internal medicine diseases in diabetic patients are dependent on the level of diabetes control.

Objectives.  Validation of a novel glucose–insulin–potassium (GIK) infusion algorithm to optimize metabolic control in hospitalized diabetic patients.

Subjects.  We randomized 33 diabetic patients admitted to Sahlgrenska University Hospital with acute internal medicine diseases to either GIK infusion or multiple injection therapy (MIT). The GIK infusion rate and the MIT were controlled according to special algorithms. The treatment efficacy was evaluated through comparisons of capillary blood glucose eight times on day 2 of the study.

Results.  The GIK infusion led to significantly lower mean blood glucose when compared with MIT [10.1 (9.0–11.2) vs. 12.3 (9.3–14.4) mmol L−1, median and interquartile range, P < 0.01]. Four episodes of hypoglycaemia without loss of consciousness were recorded in the GIK group whereas no hypoglycaemic event occurred in the MIT group. A mean of 1 (1–3) episodes of blood glucose levels above 12.0 mmol L−1 were recorded in the GIK group compared with 3.5 (1.5–5.0) in the MIT group, P < 0.01.

Conclusions.  The algorithm used for the GIK infusion gave an acceptable level of metabolic control and this insulin infusion protocol is safe enough to be used by the nursing staff on a general internal medicine ward.
Physical activity in relation to indices of endothelial function and angiogenesis factors in hypertension: a substudy of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT)
Authors: Felmeden D. C. , Spencer C. G. C. , Blann A. D. , Beevers D. G. , Lip G. Y. H.
Published: March 2003

Abstract.  Felmeden DC, Spencer CGC, Blann AD, Beevers DG, Lip GYH (University Department of Medicine, City Hospital, Birmingham, UK). Physical activity in relation to indices of endothelial function and angiogenesis factors in hypertension: a substudy of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT). J Intern Med 2003; 253: 81–91.

Background.  Hypertension is an important risk factor for cardiovascular disease. The latest guidelines recommend regular physical exercise as initial step or adjunct in the treatment of hypertension. We investigated the association between physical activity and the degree of hypertension, as well as the relation to indices of endothelial damage/dysfunction and angiogenesis.

Methods.  We studied 234 patients with hypertension (198 males; mean age 64 years; mean blood pressure 166/90 mmHg), who were compared with 60 age and sex‐matched healthy normotensive controls. We assessed the patient's physical activity using the validated Baecke physical activity questionnaire and measured flow‐mediated dilatation (FMD) of the brachial artery and von Willebrand factor (vWf) as indices of endothelial damage/dysfunction, whilst angiogenesis was assessed by measurement of plasma vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt‐1) both by ELISA.

Results.  When hypertensive patients were compared with the controls, there was no statistically significant difference in total physical activity score using the Baecke questionnaire although plasma VEGF and vWf levels were higher, but sFlt‐1 levels and FMD lower (all P < 0.001). Patients with high physical activity were younger, and had lower mean diastolic blood pressure and 10‐year Framingham stroke risk, when compared with those with low physical activity; but indices of endothelial damage/dysfunction and angiogenesis were not significantly different.

Conclusion.  Physical activity scores in hypertensive patients are not significantly different from healthy normotensive controls, and there appears to be no relation to the abnormal processes of endothelial damage/dysfunction and angiogenesis seen in hypertensives.
Overview of the clinical efficacy of investigational anticancer drugs
Authors: Nygren P. , Larsson R.
Published: March 2003

Nygren P, Larsson R (Section of Oncology and Section of Clinical Pharmacology, University Hospital, Uppsala, Sweden). Overview of the clinical efficacy of investigational anticancer drugs (Review). J Intern Med 2003; 253: 46–75.

The purpose of this overview was to make a broad inventory of investigational drugs for medicinal cancer treatment and, specifically, to indicate the evidence of clinical efficacy. Information was retrieved from electronic database searches in Medline and CANCERLIT and relevant published reviews. As the most recent findings are first reported as conference abstracts, an important basis for identification of new drugs and clinical results was a hand search of 13 392 abstracts from five major recent cancer conferences. A total of 209 investigational approaches or drugs were identified and classified into one of eight groups according to proposed mechanism of action. For 28 drugs/approaches survival data were available from randomized controlled trials. Statistically significant benefit was observed for only 12. In earlier phases no or modest anticancer activity was reported. It is speculated that the expanding knowledge in tumour biology might not easily translate into new substantially better anticancer drugs.
High‐pressure freezing of plant cells cultured in cellulose microcapillaries
Authors: Tiedemann  , Hohenberg  , Kollmann
Published: March 2003

A new microculturing technique for plant cells was used to meet the requirements of high‐pressure freezing (HPF). The plant cells were cultured inside cellulose microcapillaries, providing an easy‐to‐handle method for a real in situ fixation. The high viability of the cells was demonstrated by regenerating shoots from microcalluses cultivated by this method. In general, the freezing quality of the high‐pressure frozen samples was excellent across the whole diameter of the capillaries, as shown with ultrathin sectioned cells after freeze‐substitution and embedding in Spurr's resin. In comparison with conventional chemically fixed cells, cultured under identical conditions, all membranous compartments and organelles were more turgid and smoother after HPF. The cytoplasm and the matrix of the organelles were more homogeneous and dense. Thus, high‐pressure freezing in combination with the microculture method described here appears to preserve the ultrastructure of chemically untreated plant cells close to the native state.
Near‐field optical excitation as a dipole–dipole energy transfer process
Authors: Sekatskii S. K. , Dietler G.
Published: March 2003

The process of fluorescence excitation in the scanning near‐field optical microscope (SNOM) is considered as a dipole–dipole resonance energy transfer process between a molecule under study and a SNOM aperture, which can be treated as a magnetic‐type point dipole. It is shown that such an approach satisfactorily describes the conditions of the usual SNOM fluorescence experiments. Fluorescence excitation dependence on the polarization of the incident light and medium refraction index have been obtained. The equation to calculate the resonance dipole–dipole energy transfer radius (which is a natural unit of a SNOM's longitudinal resolution) is derived. Those cases where such a radius is of the order of the SNOM aperture, and thus single dipole, can strongly influence the radiation conditions are discussed briefly.
Near‐field optical microscopy of localized excitations on rough surfaces: influence of a probe
Authors: Bozhevolnyi S. I.
Published: March 2003

Starting from the general principles of near‐field optical microscopy, I consider the influence of a probe when being used to image localized dipolar excitations and suggest a way of evaluating the perturbation thus introduced. Using the rigorous microscopic (electric) point–dipole description, I calculate the self‐consistent field intensity at the site of a probe dipole scanning over resonantly interacting object dipoles and show that the intensity distribution deviates from that existing in the absence of a probe. I demonstrate that this difference increases with an increase in the polarizability of the probe dipole, resulting eventually in a completely different intensity distribution. The calculations also show that the perturbation of the intensity distribution due to the presence of a probe decreases with an increase in the probe–sample distance. In order to evaluate the degree of perturbation, I suggest comparing the images obtained at different probe–sample distances. Finally, I formulate a simple rule of thumb that allows one to roughly estimate the probe–sample coupling when imaging localized excitations.
Fluorescence resonance energy transfer detected by scanning near‐field optical microscopy
Authors: Kirsch A. K. , Subramaniam V. , Jenei A. , Jovin T. M.
Published: March 2003

Fluorescence resonance energy transfer (FRET) between excited fluorescent donor and acceptor molecules occurs via the Förster mechanism over a range of 1–10 nm. Because of the strong (sixth power) distance dependence of the signal, FRET has been used to assess the proximity of molecules in biological systems. We used a scanning near‐field optical microscope (SNOM) operated in the shared‐aperture mode using uncoated glass fibre tips to detect FRET between dye molecules embedded in polyvinyl alcohol films and bound to cell surfaces. FRET was detected by selective photobleaching of donor and acceptor fluorophores. We also present preliminary results on pixel‐by‐pixel energy transfer efficiency measurements using SNOM.
Reflection mode scanning near‐field optical microscopy analyses of integrated devices
Authors: Cramer R. M. , Chin R. , Balk L. J.
Published: March 2003

Ultra‐large‐scale integrated devices have been investigated by a reflection mode scanning near‐field optical microscope designed for semiconductor analyses. Although it could be found that imaging the reflectivity of metal structures buried underneath thin, optically transparent passivation layers is practicable, shading of the reflected light by the SNOM probe complicated the interpretability of the achieved results. This issue has been overcome by using the SNOM probe as both illumination source and detector, simultaneously. The application of focused ion beam milling to the probes has allowed the increase of the transmittivity of the probes to such an extent that coated fibres could be utilized and the interpretability of the results could be enhanced. Furthermore, the investigated structures are of great interest for an investigation of z‐motion artefacts, as the presence of the polished passivation layers allows topographical influences to be distinguished from pure optical contrast.
Detection of an infrared near‐field optical signal by attaching an infrared‐excitable phosphor to the end of a photocantilever
Authors: Tanaka Y. , Fukuzawa K. , Ohwaki J.
Published: March 2003

To improve the signal‐to‐noise ratio of near‐field scanning optical microscopy, we propose attaching an infrared‐excitable phosphor (IEP) to a photocantilever. One source of noise is the light scattered from locations on the sample surface other than that of the probe tip. By detecting only the light scattered from the tip, we can obtain a near‐field optical signal without noise. We attached an IEP particle to a photocantilever to convert infrared light to visible light and we used 1550‐nm infrared illumination, so the light scattered from the sample was only infrared. The silicon photodiode of the photocantilever is 106 times less sensitive to infrared light than to visible light. As a result, only the converted visible light from the IEP particle, i.e. the signal containing the near‐field optical information from the tip, was detected. We verified that the photocantilever detected the signal in the evanescent light produced by infrared illumination and that the detected signal was the light converted by the IEP. The experimental results show the feasibility of detecting infrared light and not the background light through the use of the IEP.
Optical characterization of probes for photon scanning tunnelling microscopy
Authors: Vohnsen B. , Bozhevolnyi S. I.
Published: March 2003

The photon scanning tunnelling microscope is a well‐established member of the family of scanning near‐field optical microscopes used for optical imaging at the sub‐wavelength scale. The quality of the probes, typically pointed uncoated optical fibres, used is however, difficult to evaluate in a direct manner and has most often been inferred from the apparent quality of recorded optical images. Complicated near‐field optical imaging characteristics, together with the possibility of topographically induced artefacts, however, has increased demands for a more reliable probe characterization technique. Here we present experimental results obtained for optical characterization of two different probes by imaging of a well‐specified near‐field intensity distribution at various spatial frequencies. In particular, we observe that a sharply pointed dielectric probe can be highly suitable for imaging when using p‐polarized light for the illumination. We conclude that the proposed scheme can be used directly for probe characterization and, subsequently, for determination of an optical transfer function, which would allow one to deduce from an experimentally obtained image of a weakly scattering sample the field distribution existing near the sample surface in the absence of the probe.
Laser scanning gradient index optics microscope: submicrometre scale spectroscopy and imaging at cryogenic temperatures
Authors: Vacha M. , Hashizume K. , Tani T.
Published: March 2003

A laser scanning far‐field optical microscope for low‐temperature imaging and spectroscopy based on gradient index optics is presented. A rod‐shaped gradient index microlens is used as a zero‐working‐distance solid immersion objective lens. The obtained lateral resolution is 310 nm of the FWHM at a wavelength of 545 nm. A laser scanning mechanism located outside an optical cryostat enables one to achieve large scanning ranges independent of temperature. The use of the microscope for submicrometre‐scale spectroscopy and low‐temperature photochemistry performed on molecular J aggregates in thin polymer films is presented.
Near‐field mapping of the emission distribution in semiconductor microdiscs
Authors: Zhu X. , Zhang Y. , Xin Y. , Wang G. , Wang R. , Ling Y. , Zhou H. , Yin Y. , Zhang B. , Dai L. , Zhang G. , Gan Z.
Published: March 2003

We have used a scanning near‐field optical microscope to study the fluorescent light distribution in the near‐ and far‐fields with two types of microdiscs, InGaP and GaN, fabricated in our laboratory. The InGaP microdisc has a radius of 2.5–5.0 μm, a thickness of 0.15–0.2 μm and a circular shape and the GaN disc has a radius of 5–8 μm with a thickness of 0.5–2 μm. Spontaneous emission enhancement in these microdiscs has been observed with emitting wavelengths of 650 and 550 nm respectively. In both types of microdisc, the whispering‐gallery mode (WGM) has been observed on the top surface using near‐field optical and far‐field microscopic methods. However, due to the different disc structures and optical confinements, the light distributions of the type types of disc are quite different. In the case of the InGaP disc, WGM is the dominant mode with a mixture of other modes. Interference‐like ring intensities have been observed both inside the disc surface and outside, with a period ratio of 1:2. In addition, the propagating waves emitted from the side of the disc have been collected for the first time by using near‐field optical microscopy. A theoretical calculation based on the theory of optical modes in microdisc lasers confirmed this observation. It also predicted the behaviour of the electric field distribution (transverse electric) inside and outside the disc, as well as the period of the wave propagation. In contrast, the near‐field mapping of the GaN fluorescence showed not only a ring‐like emission intensity along the circumference of the disc, an indication of WGM, but also an even intensity distribution inside the disc. This can be explained as the combination of the WGM with the Fabry–Perot mode of multi‐reflection between the GaN layer and the substrate. The results also demonstrate the potential application of near‐field optics to explore the light emission mode of a microdisc on a nanometre scale.
Spectroscopic study of the image formation in near‐field microscopy, near an evanescent–homogeneous switching
Authors: Vial A. , Barchiesi D. , Parent G.
Published: March 2003

Near‐field optical microscopes provide highly resolved images of various samples. However, images are difficult to interpret owing to their sensitivity to illumination conditions. Moreover, by contrast with classical microscopy, the near‐field signal combines the contributions of evanescent and propagative modes. In this study, we present results of a spectroscopic study in near‐field. Our purpose is to explain how a switching of one diffracted mode from homogeneous to evanescent can modify image formation. The main point is to establish a relation between the evanescence of one diffracted mode and the fringes that are often observed in near‐field experimental images. Moreover, on a metallic sample, the possible occurrence of plasmon resonance contributes to image distortion in a mainly different way. We use a Fourier series Rayleigh 3D method to explain image formation.
Evaluation of nano‐optical probe from scanning near‐field optical microscope images
Authors: Hosaka S. , Shintani T. , Kikukawa A. , Itoh K.
Published: March 2003

We studied a nanometre‐sized optical probe in a scanning near‐field optical microscope. The probe profile is determined by using a knife‐edge method and a modulated transfer function evaluation method which uses nanometre‐sized line‐and‐space tungsten patterns (with spaces 1 μm to 50 nm apart) on SiO2 substrates. The aluminium‐covered, pipette‐pulled fibre probe used here has two optical probes: one with a large diameter (350 nm) and the other with a small diameter (10 nm). The small‐diameter probe has an optical intensity ≈63 times larger than that of the large‐diameter probe, but the power is about 1/25 of that of the large probe.
Time‐resolved near‐field optics: exciton transport in semiconductor nanostructures
Authors: Richter A. , Süptitz M. , Lienau CH. , Elsaesser T. , Ramsteiner M. , Nötzel R. , Ploog K. H.
Published: March 2003

We present a systematic, temperature‐dependent study of excitonic real‐space transfer into single GaAs quantum wires using time‐resolved low‐temperature near‐field luminescence spectroscopy. Excitons generated by local short pulse optical excitation in a 250 nm spot undergo diffusive transport over a length of several micrometres and are subsequently trapped into the quantum wire by optical phonon emission. The effect of local energy barriers in the vicinity of the quantum wire on the real‐space transfer dynamics is monitored directly by mapping the time‐resolved quantum wire luminescence. Experiments at variable temperatures are compared to numerical simulations based on drift‐diffusive model calculations, and the spatio‐temporal evolution of the two‐dimensional exciton distribution within the nanostructure is visualized.
The height regulation of a near‐field scanning optical microscope probe tip
Authors: Wang K. , Wang X. , Jin N. , Huang W. , Xu J.
Published: March 2003

A nonoptical detection of the optical fibre tip has been developed. By detecting the output signal from a tiny piezoelectric detector attached to the vibrating fibre tip, the distance between the fibre tip and the sample has been successfully controlled. The frequency responses of the system composed of tip, the dither and the detector have been studied. The difference between the shear‐force detection and the tapping‐mode detection is discussed. It is found that the shear force exerted on the tip reduces the vibration amplitude with an unvaried resonance frequency. However, in the tapping mode, the resonance frequency varies with the tip–sample distance as the force is exerted on the fibre tip only within a half period. This requires better adjustments for the tapping‐mode detection.
Thickness measurement of thin dielectric films by evanescent total reflection fluorescence
Authors: Benešová M. , Tománek P.
Published: March 2003

The electric field of an evanescent wave generates fluorescence in the interface between a dielectric surface and an adjacent, fluorescing, medium of lower refractive index. The difference between the fluorescing signals from covered and noncovered surfaces enables nondestructive measurement of the film thickness to be made in the range 1–15 nm.
Studies of a magnetically focused electrostatic mirror. II. Aberration corrections
Authors: Tsai
Published: March 2003

A magnetically focused electrostatic mirror is shown to be able to correct the spherical and chromatic aberrations of a probe forming system simultaneously. The probe forming system comprises a uniform magnetic lens and a uniform electrostatic mirror. Previous theoretical investigations showed that the spherical and chromatic aberration coefficients of these two components are the same values but with opposite sign, whose combination will therefore be free from aberrations. The experimental arrangement used a solenoid to produce a uniform magnetic field, and a series of plate electrodes to produce a uniform electrostatic field. These fields are shown to satisfy the experimental requirements. By deliberately changing the extraction voltage to defocus the electron beam, the author is able to observe correction of chromatic aberration by one order of magnitude. By deliberately changing the lens field and the mirror field, the author is able to observe the reduction of the asymmetry caused by the spherical aberration, which the author believes also indicates correction by one order of magnitude.