bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated serum levels of methylmalonic acid and homocysteine in elderly people. A population‐based intervention study
Authors: Björkegren K. , Svärdsudd K.
Published: March 2003

Abstract. Björkegren K, Svärdsudd K (University Hospital Uppsala; Skutskär Primary Health Care Center, Skurskär, Sweden). Elevated serum levels of methylmalonic acid and homocysteine in elderly people. A population‐based intervention study. J Intern Med;246: 317–324.

Objectives.   There is uncertainty amongst clinicians about the definitions of cobalamin and folate deficiency and therefore about the indications for treatment. In this report we present the results of systematic cobalamin and folic acid treatment based upon serum cobalamin, total homocysteine (tHcy) and methylmalonic acid (MMA) analyses in a population‐based sample.

Subjects. A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey (n = 266). Sixty‐nine persons who had serum cobalamin < 300 pmol L–1 and serum MMA ≥0.37 µmol L–1 or serum tHcy ≥15 µmol L–1 and who had no cobalamin or folic acid substitution were selected for treatment.

Interventions. Initially all 69 patients were given cobalamin orally or intramuscularly. Those who remained high in tHcy were in addition given folic acid treatment.

Main outcome measures. Serum cobalamin, serum MMA and serum tHcy.

Results. After 6 months of cobalamin treatment, serum MMA became normal in 13 out of 15 persons. Mean serum tHcy decreased but was normalized in only 15 out of 56 persons. After 3 months of folic acid treatment added to those who still had an abnormal serum tHcy, serum tHcy had normalized in all but one person.

Conclusions. Cobalamin treatment normalizes increased MMA values and combined cobalamin and folic acid treatment normalizes tHcy, suggesting a pretreatment deficiency of tissue cobalamin and folate in spite of normal serum cobalamin and folate values in the majority of cases.
Relative importance of improved hospital treatment and primary prevention. Results from 20 years of the Myocardial Infarction Register, Göteborg, Sweden
Authors: Wilhelmsen L. , Rosengren A. , Lappas G.
Published: March 2003

Objective.  To analyse to what extent declines in incidence and mortality of coronary artery disease can be attributed to improved hospital and post‐hospital treatment in contrast to how much is due to primary prevention.

Design.  A register for non‐fatal and fatal myocardial infarction and sudden coronary death registered in in‐hospital as well as out‐of‐hospital events between 1975 and 1994.

Setting.  City of Göteborg, Sweden, with 450 000 inhabitants.

Results.  Seventy‐one per cent of the decline in attacks could be attributed to a decline in first infarctions. Of the decrease in coronary deaths, 63% was due to a decline in out‐of‐hospital mortality. Previous registrations for myocardial infarction were considerably more common amongst people who died in hospital (29%) than amongst those who died out‐of‐hospital (11–16%) or who survived an infarction (11–13%). Out‐of‐hospital resuscitation contributed to about half of the reduction in out‐of‐hospital mortality. Thus, most of the decline in incidence and about half of the decline in sudden coronary deaths was due to primary preventive measures. Population data on risk factors indicate a decline of 37% between 1963 and 1995 in coronary risk amongst consecutive cohorts of 50‐year‐old men in the community.

Conclusion.  Out‐of‐hospital resuscitation, treatment in coronary care units and post‐infarct treatment improved considerably, but changes in primary risk factors were also of major importance for the decline in incidence and mortality.
Fatal hepatitis and renal failure during treatment with nimesulide
Authors: Schattner A. , Sokolovskaya N. , Cohen J.
Published: March 2003

Abstract. Schattner A, Sokolovskaya N, Cohen J (Kaplan Medical Center, Rehovot, and the Hebrew University‐Hadassah School of Medicine, Jerusalem, Israel). Fatal hepatitis and renal failure during treatment with nimesulide (Case Report). J Intern Med 2000; 247: 153–155.

A healthy 70‐year‐old woman who took nimesulide for 5 days, presented 2 weeks later with jaundice for which no other cause was found. Laboratory evidence of coagulopathy, hypoalbuminaemia and hypoglycaemia were present on admission, and liver biopsy showed massive necrosis of hepatocytes and severe inflammatory infiltrate. Despite supportive and corticosteroid treatment, her jaundice deepened and progressive acute renal failure developed, characterized by a ‘prerenal’ profile changing into irreversible acute tubular necrosis pattern, coma, occult Gram‐negative sepsis and death. Although rare, nimesulide‐associated hepatotoxicity and nephrotoxicity may occur and should be recognized as early as possible, to ensure immediate drug withdrawal and treatment.
Mechanisms behind gender differences in circulating leptin levels
Authors: Hellström L. , Wahrenberg H. , Hruska K. , Reynisdottir S. , Arner P.
Published: March 2003

Abstract. Hellström L, Wahrenberg H, Hruska K, Wahrenberg H, Reynisdottir S, Arner P (Danderyd Hospital and Karolinska Institute, Stockholm, Sweden). Mechanisms behind gender differences in circulating leptin levels. J Intern Med 2000; 247: 457–462.

Objectives. To investigate gender differences in circulating leptin levels and adipose tissue production of leptin.

Design setting and subjects. Thirty‐two men and 63 women with a large interindividual variation in body mass index (BMI), but otherwise healthy, were investigated after an overnight fast. Body fat (bioimpedance), abdominal subcutaneous adipose tissue secretion of leptin in vitro and serum leptin were determined.

Results. Although there was no gender difference in mean BMI or fat cell size, mean percentage body fat was 49 in women and 36 in men (P < 0.001). At each level of BMI, serum leptin levels were about two times higher in women than in men (P < 0.001). Adipose tissue secretion rate of leptin in men was two‐thirds of that in women (P < 0.05). The gender differences in body fat content, serum leptin and leptin secretion were observed in obese (BMI > 27 kg m–2) as well as non‐obese subjects. Serum leptin levels (P < 0.001) and leptin secretion rate (P < 0.01) correlated positively with body fat content in either sex. However, the gender differences in serum leptin (P < 0.001) and leptin secretion rate (P < 0.01) remained statistically significantly different even when the values were adjusted for body fat.

Conclusion. The gender difference in circulating leptin concentrations can be due to at least two different mechanisms. A higher proportion of adipose tissue and increased production rate of leptin per unit mass of adipose tissue might explain why women have higher circulating leptin levels than men.
The role of habitual snoring and obesity in the development of diabetes: a 10‐year follow‐up study in a male population
Authors: Elmasry A. , Janson C. , Lindberg E. , Gislason T. , Tageldin M. A. , Boman G.
Published: March 2003

Abstract. Elmasry A, Janson C, Lindberg E, Gislason T, Tageldin MA, Boman G (Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden; Ain Shams University, Cairo, Egypt; and Viffilsstadir Hospital, Gardabær, Iceland). The role of habitual snoring and obesity in the development of diabetes: a 10‐year follow‐up study in a male population. J Intern Med 2000; 248: 13–20.

Objectives. There are many similarities between diabetes (mainly type 2) and sleep breathing disturbances regarding risk factors, anthropometric criteria and consequences of morbidity and mortality. The aim of this study was to investigate whether the association between habitual snoring and diabetes is entirely dependent on obesity.

Design. A population‐based prospective study.

Setting. The municipality of Uppsala, Sweden.

Subjects and methods. In 1984 and in 1994, 2668 men aged 30–69 years at baseline answered questionnaires concerning sleep breathing disturbances and somatic diseases.

Results. Of those with habitual snoring in 1984, 5.4% reported that they had developed diabetes during the 10‐year period compared with 2.4% of those without habitual snoring (P < 0.001). Amongst obese snorers, 13.5% developed diabetes compared with 8.6% of obese non‐snorers (P = 0.17). In a multiple logistic regression model, the odds ratio (95% confidence interval) for development of diabetes was higher in obese snorers [7.0 (2.9–16.9)] than in obese non‐snorers [5.1 (2.7–9.5)] after adjustment for age, weight gain, smoking, alcohol dependence and physical inactivity.

Conclusions. We conclude that, in males aged 30–69 years, habitual snoring is associated with an increased incidence of diabetes within 10 years. Although obesity is the main risk factor for developing diabetes, coexistent habitual snoring may add to this hazard.
Prospects for progress in diagnostic imaging
Authors: Potchen E. J.
Published: March 2003

Abstract. Potchen EJ (Michigan State University, Michigan, USA). Prospects for progress in diagnostic imaging (Internal Medicine in the 21st Century). J Intern Med 2000; 247: 411–424.

New fast‐imaging MRI systems designed specifically for cardiac magnetic resonance enable new applications of noninvasive vascular imaging. The use of functional MRI and diffusion tensor imaging to map brain function and structure offers a new dimension to an understanding of the human condition. Clinical applications of functional MRI will influence many specialties including surgery, education, and rehabilitation. Functional imaging has the potential to visualize the regional concentration of specific proteins. This imaging at the level of molecules may be possible by use of a contrast material whose signal is changed by local enzymatic activity.

The three‐dimensional digital data collected in modern imaging techniques allow for virtual endoscopy in the respiratory, alimentary, and cardiovascular systems. Virtual endoscopy may replace many of the more invasive diagnostic methods in the near future. The measurement of clinical decision‐making through observer performance studies better informs both the physician and the patient on how to improve upon the quality of clinical practice. These prospects for progress reinforce diagnostic imaging as a cornerstone in medical informatics. The history of creating images used in medicine reveals the invention of diagnostic tools which may provide new information but premature use can result in improper application of a poorly understood technology. Research into the use of new technology may be as important as the technology itself in improving the human condition.
Medical ethics in the 21st century
Authors: Parker M. , Hope T.
Published: March 2003

Abstract. Parker M, Hope T (Institute of Health Sciences, Headington, Oxford, UK). Medical ethics in the 21st century. J Intern Med 2000; 248: 1–6.

Objectives. To foresee how medical ethics may develop in the 21st century.

Design. We have looked into our crystal ball to see what factors are likely to drive medical ethics over the next few decades. We have given examples of how such factors might affect specific issues.

Results. Those factors that we identified as likely to shape the future of medical ethics are:

Globalization. Medical ethics is likely to have to grapple increasingly with ethical issues arising from the huge discrepancies in the level of health care available in different countries.

Increase in longevity. We predict that there will be, at least amongst the richer nations, a significant increase in life expectancy. This will result in issues of resource allocation becoming increasingly problematic within medicine.

Child enhancement. Developments in genetics combined with control of reproduction will make it possible to select our children for a broad range of characteristics. There are optimistic and pessimistic predictions as to how such power will be used. In either case, this area will be an important focus of concern in medical ethics.

The biological determination of behaviour. Genetic research will lead to an increasing sense that undesirable behaviour is genetically determined. This will lead to a re‐examination of such concepts as criminal responsibility.

Therapeutic research and clinical practice. We predict that an increasing amount of clinical practice will be within the setting of clinical trials. The ethics of therapeutic research and clinical practice will need to be brought within a coherent framework.
Infections as a major preventable cause of human cancer
Authors: Kuper H. , Adami H.‐O. , Trichopoulos D.
Published: March 2003

Abstract. Kuper H, Adami H‐O & Trichopoulos D (Harvard School of Public Health, Boston, MA, USA; Karolinska Institute, Stockholm, Sweden; University of Athens Medical School, Greece). Infections as a major preventable cause of human cancer (Internal Medicine in the 21st Century). J Intern Med 2000; 248: 171–183.

Infections may be responsible for over 15% of all malignancies worldwide. Important mechanisms by which infectious agents may induce carcinogenesis include the production of chronic inflammation, the transformation of cells by insertion of oncogenes and inhibition of tumour suppressors, and the induction of immunosuppression. Common characteristics shared by infectious agents linked to malignancies are that they are persistent in the host, often highly prevalent in the host population and induce cancer after a long latency. The associations between a selection of infectious agents and malignancies are covered in detail.
Biliary dysplasia, cell proliferation and nuclear  DNA‐fragmentation in primary sclerosing cholangitis with and without cholangiocarcinoma
Authors: Bergquist A. , Glaumann H. , Stål P. , Wang G.‐S. , Broomé U.
Published: March 2003

Abstract. Bergquist A, Glaumann H, Stål P, Wang G‐S, Broomé U (Huddinge University Hospital, Huddinge; and Karolinska Institute, Stockholm; Sweden). Biliary dysplasia, cell proliferation and nuclear DNA‐fragmentation in primary sclerosing cholangitis with and without cholangiocarcinoma. J Intern Med 2001; 249: 69–75.

Objectives. To study the extent of biliary dysplasia, and the degree of cell proliferation and apoptosis in bile duct cells (BDC) from patients with primary sclerosing cholangitis (PSC), with and without cholangiocarcinoma (CC).

Methods. Specimens of liver tissue from 16 patients suffering from PSC and CC, and 16 patients with end‐stage PSC without cancer, were investigated. Histological evaluation of presence of biliary dysplasia and bile duct proliferation was made. Immunohistochemistry, applying antibodies against Ki‐67, p53 and bcl‐2, was used. Nuclear DNA fragmentation was assessed by in situ DNA labelling (ApopTag). The numbers of positive cells expressed as a percentage of the total number of BDCs constituted the labelling index (LI).

Results. Bile duct dysplasia was significantly more frequent in nontumorous liver tissue from patients with PSC and CC than from patients having end‐stage PSC without cancer (P < 0.05). Patients with biliary dysplasia had a higher frequency of marked bile duct proliferation (P < 0.01) than patients without dysplasia. In tumour tissue, the LI for Ki‐67 positive nuclei was more than four times the LI of nuclear DNA fragmentation (P < 0.01). Ki‐67, bcl‐2, p53 or DNA fragmentation were not significantly different in nontumorous liver tissue from patients with and without CC. Immunohistochemical staining for p53 was positive in 75% of the tumours, whilst in nontumorous tissue no such overexpression was found.

Conclusion. PSC patients with CC more often display biliary dysplasia than those with end‐stage PSC, indicating that biliary dysplasia may be a precancerous stage in PSC. Additionally, p53 mutation seems to be a late event in tumour development, since no p53 expression was found in the premalignant areas with nontumorous BDC.
Serum cobalamin, folate, methylmalonic acid and total homocysteine as vitamin B12 and folate tissue deficiency markers amongst elderly Swedes – a population‐based study
Authors: Björkegren K. , Svärdsudd K.
Published: March 2003

Abstract. Björkegren K, Svärdsudd K (Uppsala University, University Hospital, Uppsala and Skutskär Primary Health Care Centre, Skutskär, Sweden). Serum cobalamin, folate, methylmalonic acid and total homocysteine as vitamin B12 and folate tissue deficiency markers amongst elderly Swedes. A population‐based study. J Intern Med 2001; 249: 423–432.

Objectives. The possibilities of detecting tissue cobalamin and folate deficiency are under debate. In this report the levels of serum cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) and their interrelations in a representative random population sample are presented.

Design. Cohort study.

Setting. A general mid‐Swedish population.

Subjects. A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey. A total of 235 (85%) persons responded, out of whom 224 had no interfering diseases.

Main outcome measures. Serum cobalamin, folate, MMA and tHcy.

Results. The serum levels of cobalamin, folate, MMA and tHcy were all correlated to cobalamin and folic acid treatment. They were also correlated to the intake of multivitamin preparations. In addition, serum cobalamin was higher in untreated women than in men but not correlated to age. Serum folate was correlated neither to sex nor age. Serum tHcy and MMA were both directly correlated to age but MMA not to sex. MMA was inversely correlated to serum cobalamin but not to serum folate, whereas serum tHcy was inversely correlated to serum cobalamin, folate and creatinine. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin, erythrocyte volume fraction (EVF) or mean red cell volume. Half of the study population had abnormal MMA or tHcy levels, suggesting a latent or overt tissue deficiency of cobalamin or folate.

Conclusions. A substantial proportion of the elderly general population had signs of low tissue levels of cobalamin or folate. Amongst those who took multivitamin preparations this proportion was much lower.
Chronic myelogenous leukaemia – new therapeutic principles
Authors: O'Dwyer Michael E. , Druker Brian J.
Published: March 2003

O’Dwyer ME, Druker BJ (Oregon Health Sciences University, Portland, USA). Chronic myelogenous leukaemia – new therapeutic principles. J. Intern Med 2001; 250: 3–9

The deregulated tyrosine kinase activity of the BCR‐ABL fusion protein is the cause of malignant transformation in almost all cases of chronic myelogenous leukaemia (CML), making BCR‐ABL an ideal target for pharmacological inhibition. Signal transduction inhibitor (STI571) (formerly CGP57 148B), is an ABL specific, tyrosine kinase inhibitor. In preclinical studies, it has been shown to selectively kill BCR‐ABL expressing cells, both in‐vitro and in vivo. The results of clinical studies to date are highly encourageing and STI571 promises to be an important addition to the therapy of CML.
Lack of association between polymorphisms of catalase, copper–zinc superoxide dismutase (SOD), extracellular SOD and endothelial nitric oxide synthase genes and macroangiopathy in patients with type 2 diabetes mellitus
Authors: Ukkola O. , Erkkilä P. H. , Savolainen M. J. , Kesäniemi Y. A.
Published: March 2003

Abstract. Ukkola O, Erkkilä PH, Savolainen MJ, Kesäniemi YA (University of Oulu, Oulu, Finland). Lack of association between polymorphisms of catalase, copper–zinc superoxide dismutase (SOD), extracellular SOD and endothelial nitric oxide synthase genes and macroangiopathy in patients with type 2 diabetes mellitus. J Intern Med 2001; 249: 451–459.

Objectives. The association between the polymorphisms of three different antioxidative enzyme – catalase, copper–zinc superoxide dismutase (Cu/ Zn‐SOD) and extracellular superoxide dismutase (EC‐SOD) – genes and macroangiopathy was examined in patients with type 2 diabetes mellitus. The prevalence of the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and its association with macroangiopathy were also determined.

Design. Cross‐sectional study.

Setting. District around Oulu University Hospital, North Finland.

Subjects and methods.  A total of 239 patients with type 2 diabetes mellitus and 245 control subjects were screened. Genotypes were determined by polymerase chain reaction (PCR) technique. The diagnosis of coronary heart disease (CHD) was based on clinical and ECG criteria. The prevalences of cerebrovascular (CVD) and peripheral vascular diseases (PVD) were assessed on the basis of clinical criteria. Laboratory analyses were carried out in the hospital laboratory.

Results. No differences in the genotype distributions and allele frequencies of the antioxidative enzymes were found between type 2 diabetes mellitus patients and controls. The eNOS genotypes and allele frequencies were also similar in the diabetic patients and controls being close to that reported earlier in the British population. None of the polymorphisms were associated with macro‐ or microangiopathy or hypertension. However, male diabetic patients with eNOS Asp298Asp genotype had higher plasma very‐low density lipoprotein (VLDL) cholesterol and VLDL‐triglyceride concentrations than those with the genotypes Glu298Glu or Glu298Asp (P < 0.01 for trend).

Conclusions. The polymorphism of catalase, Cu/Zn SOD and EC‐SOD genes were not related to cardiovascular disease in type 2 diabetes mellitus patients. The eNOS Glu298Asp variant was associated with plasma VLDL‐containing lipoproteins but not with macroangiopathy in diabetic male patients. The findings do not support the notion that the polymorphisms of the key antioxidative enzymes could be amongst the factors that explain the high prevalence of macroangiopathy in patients with type 2 diabetes mellitus.
Treatment of benign nodular goitre with mildly suppressive doses of L‐thyroxine: effects on bone mineral density and on nodule size
Authors: BALDINI M. , GALLAZZI M. , ORSATTI A. , FOSSATI S. , LEONARDI P. , CANTALAMESSA L.
Published: March 2003

Abstract. Baldini M, Gallazzi M, Orsatti A, Fossati S, Leonardi P, Cantalamessa L (Department of Internal Medicine, University of Milan, IRCCS Ospedale Maggiore and Istituto Ortopedico G. Pini, Milan, Italy). Treatment of benign nodular goitre with mildly suppressive doses of L‐thyroxine: effects on bone mineral density and on nodule size. J Intern Med 2002; 251: 407–414.

Objectives. To evaluate (i) the demineralizing effect of L‐thyroxine (LT4) therapy at doses mildly inhibiting serum thyroid stimulating hormone (TSH) in patients with benign nodular goitre; (ii) the efficacy of treatment on nodule size.

Design. Cross‐sectional study comparing euthyroid women with nodular goitre treated with LT4 for ≥ 2 years (52 ± 32 months, range 24–138, median 42) and a matched group with untreated goitre.

Subjects. A total of 89 female outpatients (53.3 ± 9 years; 36 pre‐ and 53 postmenopausal), 43 treated and 46 untreated.

Main outcome measures. Bone mineralization was measured with total body and regional mineralometry [dual energy X‐ray absorptiometry (DEXA)], and indirectly evaluated with biochemical parameters (alkaline phosphatase, osteocalcin). Efficacy of LT4 therapy was assessed by measuring the nodule size during ultrasonography. The adequacy of the treatment was evaluated on the basis of serum TSH levels.

Results. No significant differences were found at DEXA for total body and regional mineralization (P > 0.05 for all comparisons) in treated and untreated patients, both in pre‐ and postmenopausal states. Evaluation of the nodule size during the ultrasound scan showed a reduction of ≥ 30% in 11 of 43 treated patients (26%) versus none of the untreated, an unchanged size in 29 treated patients (67%) versus 18 untreated, an increase of nodules and/or new nodule development in three treated patients (7%) versus 28 untreated (61%).

Conclusions. L‐thyroxine (LT4) treatment at doses slightly suppressing TSH does not significantly affect bone mineralization, nor does it represent a risk factor for osteoporosis, even in postmenopausal patients. The efficacy of this therapeutic schedule on goitre size is comparable with the effects previously reported with suppressive doses.
Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review
Authors: Ernst E.
Published: March 2003

Abstract. Ernst E. (University of Exeter, Exeter, UK). Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review (Review Article). J Intern Med 2002; 252: 107–113.

The popularity of Chinese herbal medicines (CHMs) demands a critical analysis of safety issues. The aim of this systematic review is to summarize data regarding adulterations of CHMs with conventional drugs. Literature searches were carried out in six databases. Articles containing original data on adulterations were considered without language restrictions. Eighteen case reports, two case series and four analytical investigations were identified. The list of adulterants contains drugs associated with serious adverse effects like corticosteroids. In several instances, patients were seriously harmed. One report from Taiwan suggests that 24% of all samples were contaminated with at least one conventional pharmacological compound. It is concluded that adulteration of CHMs with synthetic drugs is a potentially serious problem which needs to be addressed by adequate regulatory measures.
Atypical attack of acute intermittent porphyria – paresis but no abdominal pain
Authors: Andersson C. , Nilsson A. , Bäckström T.
Published: March 2003

Abstract. Andersson C, Nilsson A, Bäckström T (University Hospital, Umeå, Sweden; and Primary Health Care Centre, Arvidsjaur). Atypical attack of acute intermittent porphyria – paresis but no abdominal pain (Case report). J Intern Med 2002; 252: 265–270.

We report a case of acute intermittent porphyria (AIP) in a 45‐year‐old woman. Her first attack occurred at the age of 38. Because of escalating cyclical premenstrual attacks, the following 2 years, depletion of the endogenous sex hormone was considered as haeme arginate treatment proved insufficient. Gonadotropin releasing hormone agonist treatment with low‐dose oestradiol add back was quite successful initially but was abandoned after 18 months when progesterone add back precipitated a severe attack. Following hysterectomy and oophorectomy at age 42 and oestradiol add back, a remarkable monthly regularity of attacks ensured periodically but with milder symptoms. Two years after surgery, preceded by six attack‐free months, a puzzling symptom‐shift occurred, from abdominal pain, back and thigh pain during the attacks, to solely severe distal extensor paresis in the arms. Haeme arginate treatment interrupted the progress of the paresis almost immediately and motor function improved considerably up to the 9‐month follow‐up. Electrophysiological examination revealed only motor neuropathy, consistent with axonal degeneration. Subsequently the symptoms changed yet again, to sensory disturbances with numbness and dysesthesia as the primary expression followed by rather mild abdominal pain. However, cyclical attacks occurred, despite absence of endogenous ovarial hormone production, possibly attributable to impaired oestrogen metabolism in the liver, or adrenal oestrogen production. Treatment comprising oophorectomy, low‐dose oestradiol add back and haeme arginate infusion for 2 days on the appearance of early AIP symptoms is now quite successful affording improvement in life quality.
A case of POEMS syndrome associated with reactive amyloidosis and Waldenström's macroglobulinaemia
Authors: Kihara Y. , Hori H. , Murakami H. , Hatakeyama Y. , Yoshikawa I. , Hamada T. , Otsuki M.
Published: March 2003

Abstract. Kihara Y, Hori H, Murakami H, Hatakeyama Y, Yoshikawa I, Hamada T, Otsuki M (University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan). A case of POEMS syndrome associated withreactive amyloidosis and Waldenström's macroglobulinaemia (Case report). J Intern Med 2002; 252: 255–258.

A72‐year‐old Japanese man presented with a 5‐year history of fatigue, night sweats, oedema of dorsum of foot, muscle weakness, and paresthesia of the lower extremities. On examination, the patient fulfilled the diagnostic criteria for POEMS syndrome, but was unusual in that he also had underling Waldenström's macroglobulinaemia with IgM κ. The M protein of POEMS syndrome is usually IgG and IgA with λ light chains. To our knowledge, there are only three cases of POEMS syndrome with IgM κ including our case. Autopsy findings revealed that small lymphocytes were more prominent than plasma cells in the bone marrow. These plasma cells were stained with IgM κ. Amyloid deposits identified by Congo red stain were detected predominantly in the vascular walls of the gastrointestinal tract, pancreas and kidney. This amyloid protein was classified as amyloid associated protein. This is the first case of POEMS syndrome associated with reactive amyloidosis and Waldenström's macroglobulinaemiae.
Circulating oxidized low‐density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58‐year‐old men (AIR study)
Authors: Sigurdardottir V. , Fagerberg B. , Hulthe J.
Published: March 2003

Abstract. Sigurdardottir V, Fagerberg B, Hulthe J (Sahlgrenska University Hospital, Göteborg University, Gothenburg, Sweden). Circulating oxidized low‐density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58‐year‐old men (AIR study). J Intern Med 2002; 252: 440–447.

Objectives. Hypothetically the atherogenic effect of the metabolic syndrome may be mediated through the increased occurrence of small LDL‐particles which are easily modified to atherogenic oxidized LDL (ox‐LDL). The aim of this study was to test this concept by examining the association between circulating ox‐LDL, LDL‐particle size, and the metabolic syndrome.

Design and results. A population‐based sample of clinically healthy 58‐year‐old men (n = 391) was recruited. Ox‐LDL was measured by ELISA (specific monoclonal antibody, mAb‐4E6) and LDL‐particle size by gradient gel electrophoresis. The results showed that ox‐LDL significantly correlated to factors constituting the metabolic syndrome; triglycerides (r = 0.43), plasma insulin (r = 0.20), body mass index (r = 0.20), waist‐to‐hip ratio (r = 0.21) and HDL (r = −0.24); (P < 0.001). Ox‐LDL correlated also to LDL‐particle size (r = −0.42), Apo‐B (r = 0.70), LDL (r = 0.65); (P < 0.001) and, furthermore, with Apo A‐1 (r = −0.13) and heart rate (r = 0.13); (P < 0.01).

Conclusion. The metabolic syndrome was accompanied by high plasma ox‐LDL concentrations compared with those without the syndrome. Ox‐LDL levels were associated with most of the risk factors constituting the metabolic syndrome and was, in addition related to small LDL‐particle size. To our knowledge the present study is the first one to demonstrate that circulating ox‐LDL levels are associated with small LDL‐particle size in a population representative sample of clinically healthy middle‐aged men. The high degree of intercorrelation amongst several factors makes it difficult to clarify the independent role of any specific factor.
Nosocomial enterococcal endocarditis: a serious hazard for hospitalized patients with enterococcal bacteraemia
Authors: Fernández‐Guerrero M. L. , Herrero L. , Bellver M. , Gadea I. , Roblas R. F. , De Górgolas M.
Published: March 2003

Abstract.  Fernández‐Guerrero ML, Herrero L, Bellver M, Gadea I, Roblas RF, de Górgolas M (Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Spain). Nosocomial enterococcal endocarditis: a serious hazard for hospitalized patients with enterococcal bacteraemia. J Intern Med 2002; 252: 510–515.

Objectives.  Enterococci are a major leading cause of infectious endocarditis and also a common cause of hospital‐acquired bacteraemia, which is not believed to represent a serious hazard for the endocarditis. The incidence and risk factors for infectious endocarditis in patients with hospital‐acquired enterococcal bacteraemia is determined.

Methods.  Prospective analysis of 116 patients with enterococcal bacteraemia admitted to medical or surgical wards of a tertiary‐care, university affiliated hospital during a period of 5 years. Echocardiography was performed when indicated by clinical criteria.

Results.  Seventy‐five (61.4%) episodes were hospital‐acquired and 47 (38.5%) were community‐acquired. Most patients had one or more underlying chronic diseases and major abdominal (58.6%) or genitourinary (38.6%) surgery. Seventeen patients (14.6%) developed enterococcal endocarditis. By univariate analysis the risk factors associated with endocarditis were community‐acquired infection (P 0.012); monomicrobial bacteraemia (P 0.006); three or more positive blood cultures (P < 0.001); underlying valvulopathy (P < 0.001); presence of a prosthetic valve (P < 0.001) and age (P 0.012). Six patients (8%) developed nosocomial endocarditis. In this group of patients, three or more positive blood cultures (P < 0.01), bacteraemia as a result of Enterococcus faecalis (P 0.007); underlying valvulopathy (P < 0.001) and presence of a prosthetic valve (P < 0.001) were associated with endocarditis. By logistic regression, the presence of underlying valvulopathy and three or more positive blood cultures were associated with endocarditis (OR 21.0; CI 95% 1.65–26.9; P 0.019).

Conclusions.  The risk of developing infectious endocarditis in patients with hospital‐acquired enterococcal bacteraemia is significant. Patients with underlying valvulopathy and three or more positive blood cultures with E. faecalis are prone to nosocomial enterococcal endocarditis.
Obesity and myocardial infarction – vulnerability related to occupational level and marital status. A 23‐year follow‐up of an urban male Swedish population
Authors: Hedblad B. , Jonsson S. , Nilsson P. , Engström G. , Berglund G. , Janzon L.
Published: March 2003

Abstract.  Hedblad B, Jonsson S, Nilsson P, Engström G, Berglund G, Janzon L (Lund University, Malmö University Hospital, Malmö, Sweden). Obesity and myocardial infarction – vulnerability related to occupational level and marital status. A 23‐year follow‐up of an urban male Swedish population. J Intern Med 2002; 252: 542–550.

Background.  People, who are single, have a blue‐collar job or low income have an increased cardiovascular risk. This study on myocardial infarction sought to explore whether the socio‐economic pattern of disease has any relationship with obesity.

Methods.  In the cohort are 20 099 middle‐aged men of whom 9150 were manual and 9190 nonmanual workers and 1759 were self‐employed. A total of 4081 were single, 16 018 cohabiting. The body mass index (BMI) cut‐off values for overweight and obesity were 25–30 and ≥30 kg m−2, respectively. Local and national registers were used to monitor incidence of events over 18 years.

Results.  Obesity was associated with an increased incidence of coronary events and deaths in each occupational group. Being single significantly increased the risk associated with obesity. After stratification for civil status the risk associated with obesity was limited to those who were single and who either had a blue‐collar job or were self‐employed. The multivariate‐adjusted relative risk (RR) of coronary events and deaths in obese manual workers who were single was 1.91 (95% confidence interval: 1.21–3.02) and 2.54 (1.74–3.69), respectively, times higher than it was amongst those who were cohabiting. Amongst those who were self‐employed, the corresponding age‐adjusted RRs were 4.79 (1.69–13.57) and 3.80 (1.62–8.93).

Conclusions.  Adjusted for lifestyle and biological risk factors, the increased risk of coronary events and death for obese men with manual jobs was applicable only to those who were single. It is concluded that being single significantly increases the cardiovascular risk associated with obesity.
Paracetamol‐induced hepatotoxicity at recommended dosage
Authors: Kurtovic J. , Riordan S. M.
Published: March 2003

Abstract. Kurtovic J, Riordan SM (The Prince of Wales Hospital and University of New South Wales, Sydney, Australia). Paracetamol‐induced hepatotoxicity at recommended dosage (Case report). J Intern Med 2003; 253: 240–243.

In patients who develop liver damage following moderate paracetamol overdose in the order of 5–10 g daily, recent fasting and nutritional impairment have been identified as key precipitants. Hepatotoxicity caused by paracetamol at recommended dosage, in the absence of exposure to enzyme‐inducing drugs, has recently been described as an idiosyncratic phenomenon. The possible importance of fasting and malnutrition in this setting is uncertain. We report a severely malnourished 53‐year‐old woman who developed severe hepatotoxicity whilst receiving paracetamol at recommended dosage (4 g daily) following a period of fasting, in the absence of enzyme‐inducing agents. Subsequent paracetamol exposure up to 2.6 g daily thrice weekly, in the setting of ongoing malnutrition and fasting as before, did not lead to recurrent liver damage. These findings indicate that paracetamol‐related liver damage occurring within recommended dosage guidelines can be a dose‐dependent rather than necessarily idiosyncratic phenomenon, at least in the setting of recent fasting and severe malnutrition.
Decreasing serum concentrations of all‐trans, 13‐cis retinoic acids and retinol during fasting and caloric restriction
Authors: Berggren Söderlund M. , Fex G. , Nilsson‐Ehle P.
Published: March 2003

Abstract. Berggren Söderlund M, Fex G, Nilsson‐Ehle P (Institute of Laboratory Medicine, Lund University, Lund, Sweden). Decreasing serum concentrations of all‐trans, 13‐cis retinoic acids and retinol during fasting and caloric restriction. J Intern Med 2003; 253: 375–380.

Objectives.  To investigate the effects of caloric restriction on the serum concentrations of retinoids in man.

Design.  Samples were drawn before and during caloric restriction by fasting or 4–6 weeks after gastric surgery.

Subjects.  The fasting group included 17 healthy subjects (11 women and six men) and 16 obese patients (10 women and six men) who underwent bariatric surgery (vertical banded gastroplasty).

Main outcome measures.  Serum concentrations of all‐trans, 13‐cis, 4‐oxo‐13‐cis retinoic acids and retinol.

Results.  The serum concentrations of retinol, all‐trans and 13‐cis retinoic acids decreased by about 20% after 5 days of fasting. After gastroplasty, the serum concentration of retinol, all‐trans, 13‐cis retinoic acids, retinol‐binding protein and transthyretin also decreased to a similar extent after 1 month. In both groups we found a correlation between the delta values of 13‐cis retinoic acid and its metabolite 4‐oxo‐13‐cis retinoic acid. In all subjects there were also correlations between the delta values of the retinoids. However, these correlations were comparatively weak (e.g. r2 = 0.36 for retinol – all‐trans retinoic acid). The change in retinoid concentrations did not correlate to the change of weight or body mass index.

Conclusion.  Our results support the hypothesis that serum retinol is one of the determinants of serum concentrations of all‐trans and 13‐cis retinoic acid and that the catabolism of 13‐cis retinoic acid is not affected by fasting. However, in the individual case, S‐Retinol is a poor predictor of S‐All‐trans retinoic acid.
Energy‐filtered cryotransmission electron microscopy of liposomes prepared from human stratum corneum lipids
Authors: Schmidtgen  , Drechsler  , Lasch  , Schubert
Published: March 2003

We used cryo‐TEM to examine the morphology of vesicles formed from lipids of the human stratum corneum (hSC). Human stratum corneum lipid liposomes (hSCLLs) were prepared in buffer at various pH values, using different preparation methods (film method, extrusion, ultrasonication, detergent dialysis). The morphology of hSCLLs at pH 7.4 differed markedly from that of liposomes formed by phospholipids, showing folds, stacks and membrane thickening. At pH 5.0, corresponding to natural conditions at the skin surface, membrane structures are essentially the same as those prepared at pH 7.4. Sharp edges in hSCLLs, branching membranes and stable membrane stacks were explained by the presence of ceramides, the major components and structural elements of human stratum corneum lipids (hSCLs). Thickened areas in the membranes may be caused by the local accumulation of triacylglycerols and cholesterol esters in the hydrophobic interior of the bilayer.
Neurofilament‐L homopolymers are less mechanically stable than native neurofilaments
Authors: Brown  , Troncoso  , Hoh
Published: March 2003

Neurofilaments are cytoskeletal components of neurones that are thought to play an important structural role in the axon. Specific functions of neurofilaments are not yet well defined; however, other intermediate filaments are known to have structural and mechanical functions in different cell types. The atomic force microscope (AFM) can be used to visualize and manipulate biological structures through direct physical contact. This allows the AFM to be used to probe the mechanical properties of these structures. In this paper we present AFM images of native neurofilaments isolated from bovine spinal cord, composed of NF‐L, NF‐M and NF‐H, and filaments polymerized in vitro from purified NF‐L. Morphologically these structures, in solution and under ambient conditions, are in agreement with previous data from electron microscopy. However, repeated scanning of NF‐L homopolymers (in solution) produced significant disruptions of segments of filaments, both within and at the ends of the filaments. This disruption resulted in complete loss of portions of the filaments and in breaks in the continuity of the filaments. Repeated scanning of isolated native neurofilaments under similar conditions produced no detectable structural changes. Under extremely high applied forces the native neurofilaments were bent and distorted by the action of the AFM tip, but were never broken. These data suggest that purified NF‐L is not sufficient to confer complete mechanical stability to neurofilaments.
A quantitative method for analysing AFM images of the outer surfaces of human hair
Authors: Smith
Published: March 2003

Cuticle step height is an important parameter for the quantitative assessment of human hair. This paper describes a novel, computational method for the rapid calculation of step heights from atomic force microscope images obtained from large numbers of specimens. Such an approach is necessary to allow a statistical analysis of the inherently wide distribution of cuticle step heights characteristic of a single hair sample. The method described will be of use to cosmetic formulation chemists and forensic scientists and also to dermatologists in the field of disease diagnosis.
Three dimensional image restoration in fluorescence lifetime imaging microscopy
Authors: Squire A. , Bastiaens P. I. H.
Published: March 2003

A microscope set‐up and numerical methods are described which enable the measurement and reconstruction of three‐dimensional nanosecond fluorescence lifetime images in every voxel. The frequency domain fluorescence lifetime imaging microscope (FLIM) utilizes phase detection of high‐frequency modulated light by homodyne mixing on a microchannel plate image intensifier. The output signal at the image intensifier's phosphor screen is integrated on a charge coupled device camera. A scanning stage is employed to obtain a series of phase‐dependent intensity images at equally separated depths in a specimen. The Fourier transform of phase‐dependent data gives three‐dimensional (3D) images of the Fourier coefficients. These images are deblurred using an Iterative Constrained Tikhonov–Miller (ICTM) algorithm in conjunction with a measured point spread function. The 3D reconstruction of fluorescence lifetimes are calculated from the deblurred images of the Fourier coefficients. An improved spatial and temporal resolution of fluorescence lifetimes was obtained using this approach to the reconstruction of simulated 3D FLIM data. The technique was applied to restore 3D FLIM data of a live cell specimen expressing two green fluorescent protein fusion constructs having distinct fluorescence lifetimes which localized to separate cellular compartments.
Stereological estimation using vertical sections in a complex tissue
Authors: Dorph‐Petersen
Published: March 2003

A method designed for stereological estimation in a very complex tissue using vertical sections is presented. In some tissues, the random rotation of the tissue for vertical sections may obscure recognition of the anatomical structures of interest. The present method overcomes this problem by generating sections with both a particular orientation, ‘mapping sections’, and ordinary random vertical sections usable for the required observations. A map describing the positions of the vertical sections is produced to make the complex reference space recognizable. The method is illustrated by estimating the number and size of neurones in the dorsal raphe nucleus of the human brainstem with its dense packing of roughly 100 nuclei within a volume less than 50 cm3.
Quantitative electron spectroscopic diffraction analyses of the crystal formation in dentine
Authors: Arnold  , Plate  , Wiesmann  , Stratmann  , Kohl  , Höhling
Published: March 2003

Newly formed apatitic crystallites of different hard tissues consist, according to our investigations, of chains composed of nanometre‐sized particles (islands, dots) arising at nucleating sites of the collagenous and noncollagenous matrix macromolecules. In dentine these islands coalesce rapidly in longitudinal direction to form needle‐like crystallites which further coalesce to ribbon‐like crystallites. We have concluded that the centre‐to‐centre distances between these islands represent the distances between the nucleating sites of the matrix macromolecules. We have applied energy‐filtering transmission electron microscopy in the selected area electron diffraction mode at different stages of crystal formation in dentine and have obtained quantitative information of the degree of crystal disorder on the basis of the paracrystal theory. The fluctuation of the lattice plane distances in c‐axis direction decreases, proceeding from the region near the dentine/predentine border to the dentine/enamel border.
Polarization contrast in reflection near‐field optical microscopy with uncoated fibre tips
Authors: Bozhevolnyi S. I. , Langbein W. , Hvam J. M.
Published: March 2003

Using cross‐hatched, patterned semiconductor surfaces and round 20‐nm‐thick gold pads on semiconductor wafers, we investigate the imaging characteristics of a reflection near‐field optical microscope with an uncoated fibre tip for different polarization configurations and light wavelengths. It is shown that cross‐polarized detection allows one to effectively suppress far‐field components in the detected signal and to realize imaging of optical contrast on the sub‐wavelength scale. The sensitivity window of our microscope, i.e. the scale on which near‐field optical images represent mainly optical contrast, is found to be ≈100 nm for light wavelengths in the visible region. We demonstrate imaging of near‐field components of a dipole field and purely dielectric contrast (related to well‐width fluctuations in a semiconductor quantum well) with a spatial resolution of ≈100 nm. The results obtained show that such a near‐field technique can be used for polarization‐sensitive imaging with reasonably high spatial resolution and suggest a number of applications for this technique.