bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries
Authors: HOLM JOHAN , ZÖLLER BENGT , BERNTORP ERIK , ERHARDT LEIF , DAHLBÄCK BJÖRN
Published: November 2003

Objective. Haemostatic imbalance may be an aetiological factor in the development of acute coronary syndromes. Inherited resistance to activated protein C (APC) is a common disorder associated with hypercoagulability and lifelong risk of venous thrombosis. APC resistance is due to a single mutation in the gene coding for coagulation factor V (FV:Q506). To test the importance of the FV:Q506 mutation in premature myocardial infarction (MI), its prevalence was investigated in Swedish patients with MI before the age of 50 years.

Design, setting and subjects. In a retrospective case‐control study, the FV:Q506 mutation was investigated in 101 survivors of MI (79 men, 22 women) and in 101 healthy sex‐ and age‐matched controls.

Main outcome measure. The prevalence of FV:Q506 mutation.

Results. The FV:Q506 mutation was found in 18% of patients versus 11% of controls (P=0.16). The mutation was significantly more frequent amongst male patients than amongst controls (23 vs. 10%; P=0.03), the calculated odds ratio being 2.6 (95% CI, 1.1–6.4).

Conclusion. The high prevalence of the FV:Q506 mutation found amongst Swedish MI patients, especially amongst men, is noteworthy, and calls for further studies on the outcome of MI in APC‐resistant patients. The prevalence of the FV:Q506 mutation in controls is higher than figures reported from other countries, suggesting that at least 10% of the Swedish population are carriers of a congenital prothrombotic disorder.
Sarcoidosis causes abnormal seasonal variation in 1,25‐dihydroxy‐cholecalciferol
Authors: BONNEMA S. J. , MØLLE R J. , MARVING J. , KVETNY J.
Published: November 2003

Bonnema SJ, Møller J, Marving J, Kvetny J (Departments of Internal Medicine and Clinical Physiology and Nuclear Medicine, Esbjerg Centralsygehus, Esbjerg, Denmark). Sarcoidosis causes abnormal seasonal variation in 1,25‐dihydroxy‐cholecalciferol. J Intern Med 1996; 239: 393–98.

Objectives. The spontaneous seasonal variations in the calcium regulating hormones 1,25‐dihydroxy‐cholecalciferol (1,25‐DHCC) and parathyroid hormone (PTH) were investigated in patients with sarcoidosis.

Design. Controlled, prospective observational study with measurements in the winter and summer seasons, respectively.

Subjects. Twelve patients (age: median 33, range 21–54 years) with biopsy‐verified (n=8) sarcoidosis were included as well as 11 age‐matched healthy control subjects.

Main outcome measures. Serum values of calcium, ionized calcium, phosphate, chloride, bicarbonate, creatinine, albumin, angiotensin‐converting enzyme, alkaline phosphatase, 1,25‐DHCC, and PTH. Also, 24‐h whole‐body retention of 99mTc methylene‐diphosphonate was assessed.

Results. The patient group showed an increased level of 1,25‐DHCC in the summer season (w:146±67, s:198±73 pmol L‐1; P<0.01) in contrast to the opposite finding among controls (w:161±34, s:144±43 pmol L‐1; P<0.05). Comparing the individual seasonal changes between the two groups, the difference was marked (P<0.001). Compared with controls, total serum calcium was elevated in the summer season in the patient group (P<0.05), in which the same parameter correlated positively with 1,25‐DHCC (r=0.658; P<0.01). PTH was increased two to three times above the control values throughout the year (patients: w:0.37±0.13, s:0.24±0.08 μg L‐1; controls: w:0.14±0.09, s:0.10±0.04 μg L‐1; P<0.001); although, the level of this hormone was still found within the reference interval. 24‐h whole body bone scintigraphy failed to show any seasonal variation in bone metabolism. In contrast, serum alkaline phosphatase was found to be increased during the summer season compared with the control group (P<0.001). Angiotensin‐converting enzyme showed no seasonal variation.

Conclusions. In sarcoidosis, 1,25‐DHCC is abnormally regulated throughout the year, with a significantly higher serum level in the summer season. Uncontrolled production of 1,25‐DHCC in sarcoid pulmonary alveolary macrophages is possibly responsible for hypercalcaemic episodes, and this parameter should be used as a marker of disease activity.
Daytime sleepiness in an adult, Finnish population
Authors: HUBLIN C. , KAPRIO J. , PARTINEN M. , HEIKKILÄ K. , KOSKENVUO M.
Published: November 2003

Hublin C, Kaprio J, Partinen M, Heikkilä K, Koskenvuo M (Departments of Psychiatry and Neurology and the Department of Public Health (The Finnish Twin Cohort), University of Helsinki, Helsinki; and the Department of Public Health, University of Turku, Turku; Finland). Daytime sleepiness in an adult, Finnish population. J Intern Med 1996; 239: 417–23.

Objectives. To investigate the prevalence of and the factors associated with daytime sleepiness occurring every or almost every day.

Design. A cross‐sectional, questionnaire survey.

Subjects. A total of 11354 adults (aged 33–60 years) representative of the Finnish population.

Main outcome measures. Frequency of daytime sleepiness, naps and sleep attacks; occurrence of emotion‐associated muscle weakness, sleep debt, insomnia, sleep apnoeas and type of snoring; Beck Depression Inventory score; and the use of hypnotics and tranquillisers.

Results. A total of 11.0% of women and 6.7% of men suffered from daytime sleepiness every or almost every day. Amongst those with sleepiness (n= 1026) 19.5% of women and 42.3% of men reported snoring 3 nights per week, 25% had scores suggesting moderate to severe depression, 11% used hypnotics or tranquilizers on more than 180 days per year, and 9% reported insufficient sleep. Insomnia at least every other day was reported by 20.7% of women and by 28.6% of men. Amongst those with sleepiness, narcolepsy was found in 0.3%, with the diagnosis confirmed in a sleep laboratory evaluation.

Conclusions. Daytime sleepiness occurring daily or almost daily is most often associated with depression, insomnia and sleep‐disordered breathing. In most cases, indications of the cause of sleepiness can be obtained by using simple screening questions.
Primary Sjögren's syndrome: the challenge for classification of disease manifestations
Authors: OXHOLM P. , ASMUSSEN K.
Published: November 2003

A new model for classifying the clinical disease manifestations of primary Sjögren's syndrome is introduced. Three ‘exocrine’ and four ‘nonexocrine’ subgroups of disease manifestations are defined. Accordingly, ‘surface exocrine disease' includes the diagnostic features from eyes, mouth, and the manifestations from the upper airways, skin and genital tract. Involvement of the excretory parenchyma of the lungs, hepatobiliary system, pancreas, gastrointestinal tract and kidneys is designated ‘internal organ exocrine disease’. We suggest ‘monoclonal B lymphocyte disease’ to be an exocrine disease manifestation because it originates mostly from the immunoinflammatory foci of the autoimmune exocrinopathy. The nonexocrine manifestations are subgrouped into ‘inflammatory vascular disease’, ‘noninflammatory vascular disease’, ‘mediator‐induced disease’ and ‘autoimmune endocrine disease’.
Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil
Authors: VAN PUIJENBROEK E. P. , DU BUF‐VEREIJKEN P. W. G. , SPOOREN P. F. M. J. , VAN DOORMAAL J. J.
Published: November 2003

The occurrence of rhabdomyolysis is one of the rare side‐effects of the cholesterol‐lowering agent simvastatin. During the use of lovastatin, an agent related to simvastatin, the risk of this side‐effect might be increased when cyclosporin or gemfibrozil are used concomitantly. It is possible that this also applies for simvastatin. We present two patients who developed rhabdomyolysis during the concomitant use of simvastatin and gemfibrozil.
Systemic amyloidosis in a patient with hypogammaglobulinaemia
Authors: KOTILAINEN P. , VUORI K. , KAINULAINEN L. , AHO H. , SAARIO R. , ASOLA M. , NIKOSKELAINEN J.
Published: November 2003

A 49‐year‐old patient with an 18‐year history of hypogammaglobulinaemia presented with nephrotic syndrome due to systemic amyloidosis. Recurrent infections as a consequence of an inadequate gamma‐globulin substitution therapy were regarded as the main reason for the development of amyloidosis. When a high‐dose intravenous immunoglobulin therapy was started, the clinical symptoms declined and the patient felt moderately well. Later the patient developed symmetrical polyarthritis clinically suggestive of rheumatoid arthritis. Although the incidence of arthritis is increased in hypogammaglobulinaemia, arthritis has not been reported in any of the few previously described patients with hypogammaglobulinaemia‐associated amyloidosis. Moreover, this case provides further evidence that, in these patients, the amyloid fibrils may be of the AA type.
Hodgkin's disease associated with IgA and IgG subclass deficiency
Authors: ZENONE T. , SOUQUET P. J. , CUNNINGHAM‐RUNDLES C. , BERNARD J. P.
Published: November 2003

Cases of cancer have been reported in patients with primary humoral immunodeficiency syndromes, mainly non‐Hodgkin's lymphoma and gastric adenocarcinoma. Two cases of Hodgkin's disease complicating IgA and IgG subclass deficiency are reported. This association is probably more than mere coincidence. A review of the literature is presented.
Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis
Authors: WÅLLBERG‐JONSSON SOLVEIG , DAHLÉN GÖSTA , JOHNSON OWE , OLIVECRONA GUNILLA , RANTAPÄÄ‐DAHLQVIST SOLBRITT
Published: November 2003

Objective. To evaluate the impact of chronic inflammation on lipoprotein lipase (LPL) levels and triglyceride metabolism in patients with rheumatoid arthritis (RA).

Design. Plasma levels of LPL activity and mass before and after heparin were determined in post‐menopausal women with active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with triglyceride levels were also measured before and 6 h after an oral fat load.

Setting. The study was performed on in‐ and out‐patients at a University Rheumatology clinic. The controls came from the same reference area.

Subjects. Altogether 17 consecutive post‐menopausal female patients with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the fat load. Of these, one patient and one control were excluded.

Main outcome measures. LPL determination: basal levels and post‐heparin levels of LPL activity and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides), lipoprotein levels (high density lipoprotein, HDL; low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor α, TNF‐α; interleukin 1β, IL‐1β; and interleukin‐6, IL‐6). Fat tolerance test: LPL activity, mass and triglyceride levels before and 6 h after a per oral fat load.

Results. Pre‐heparin LPL mass (P<0.01) and activity (P<0.01) were significantly lower in the rheumatoid patients. Pre‐heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters; it was significant for orosomucoid (rs=−0.63, P<0.05) and C‐reactive protein (CRP) (rs=−0.54, P<0.05) and close to significant for haptoglobin (rs=−0.48, P=0.087) and IL‐6 (rs=−0.52, P=0.061). Six hours after a lipid load the LPL activity and mass were significantly lower in RA (P<0.05 and P<0.01, respectively) but the triglyceride level was not significantly different compared to controls.

Conclusion. An inverse relationship exists between inflammatory status and pre‐heparin LPL mass. Pre‐heparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor‐related protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of the level of monomeric LPL in plasma may thus be beneficial for remnant catabolism. The same mechanism may on the other hand increase macrophage uptake of lipids. This may not affect global lipid metabolism but may be important in driving the atherosclerotic process in the vessel wall.
Use of low molecular weight heparin (dalteparin), once daily, for the treatment of deep vein thrombosis A feasibility and health economic study in an outpatient setting
Authors: LINDMARKER P. , HOLMSTRÖM M. ,   Swedish Venous Thrombosis Dalteparin Trial Group
Published: November 2003

Objectives. To test the safety and feasibility of treating deep vein thrombosis (DVT) in an outpatient setting, using the low molecular weight heparin dalteparin, to calculate the potential and actual cost reductions achievable as a result of such a treatment regimen.

Design. An open, nonrandomized, multicentre trial.

Setting. Fourteen hospitals in central Sweden.

Subjects. Ambulant patients, aged 18 years or older, with symptomatic DVT in the leg, diagnosed using phlebography or ultrasound (Duplex‐Doppler).

Interventions. Dalteparin (Fragmin®) at a fixed dose of 200 IU kg‐1 body weight, was administered once daily subcutaneously for at least 4 consecutive days. Treatment with warfarin was initiated from the first day of dalteparin administration. Outpatient treatment was encouraged whenever possible. Financial calculations were performed independently at two hospitals, giving an average cost for all actions.

Outcome measures. Increasing severity of symptoms (or thromboembolic recurrences during the 3‐month follow‐up period), pulmonary embolism (PE), bleeding events, and death during the initial phase and follow‐up period.

Results. Of 434 patients, 35% and 64% were treated in hospital within 24 and 72 h, respectively, and thereafter as outpatients. The overall frequency of serious complications was 0.92% (exact 95% confidence interval, 0.25–2.35%) during the initial phase and one patient suffered a PE and three patients had a recurrent DVT during the follow‐up period. A cost reduction of 2705529 Swedish crowns (34.5%) was achieved in this study compared with traditional in‐patient treatment.

Conclusions. Dalteparin, administered subcutaneously, once daily, for the initial treatment of DVT yields large cost reductions and is well tolerated and effective in an outpatient setting.
Aplastic anaemia with a trilineage response to erythropoietin therapy
Authors: BERNELL P.
Published: November 2003

An 89‐year‐old man with a severe aplastic anaemia is described. The patient was proven to be corticosteroid and cyclosporin resistant, but had a trilineage response during subsequent treatment with recombinant human erythropoietin.
The interaction between age and comorbidity contributes to predicting the mortality of geriatric patients in the acute‐care hospital
Authors: INCALZI R. A. , CAPPARELLA O. , GEMMA A. , LANDI F. , BRUNO E. , DI MEO F. , CARBONIN P.
Published: November 2003

Incalzi RA, Capparella O, Gemma A, Landi F, Bruno E, Di Meo F, Carbonin P (Instituto di Medicina Interna e Geriatria dell'Universita' Cattolica del Sacro Cuore, Rome, and the Teaching Nursing Home ‘Cittadella della Carita’, Taranto, Italy. The interaction between age and comorbidity contributes to predicting the mortality of geriatric patients in the acute‐care hospital. J Intern Med 1997; 242: 291–8.

Objective

To test the predictive power of comorbidity and of the interaction between age and comorbidity in geriatric patients with acute medical illness.

Design

Prospective observational study.

Setting

Medical and geriatric wards of an acute‐care hospital.

Subjects

Three hundred and seventy patients over 70 years of age consecutively admitted in an 18‐month period.

Main outcome measure

In‐hospital mortality.

Method

On admission a multidimensional assessment was performed, and a comorbidity index and an age–comorbidity index developed on a comparable training population were calculated. The comorbidity index is based upon a scoring system that quantifies the prognostic weight of individual diseases, while the age–comorbidity index corrects the former for the age‐related increase of the risk of death. The predictive power of variables univariately correlated with the outcome was tested by logistic regression.

Results

Death was independently predicted by clinical diagnosis of malnutrition (odds ratio = 1.87, confidence limits CL = 1.20–2.86), age–comorbidity index > 7 (odds ratio = 1.77, CL = 1.15–2.72), preadmission impairment in activities of daily living (odds ratio = 1.74, CL = 1.13–2.69), lymphocytopenia (odds ratio = 1.74, CL = 1.15–2.61). A weaker predictive model was obtained by substituting the comorbidity index for the index of age–comorbidity. Excluding comorbidity from the logistic regression greatly weakened the predictive model.
The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective
Authors: BOONEN S. , BROOS P. , DEQUEKER J. , BOUILLON R.
Published: November 2003

Boonen S, Broos P, Dequeker J, Bouillon R (Department of Internal Medicine, Division of Geriatric Medicine, the Arthritis and Metabolic Bone Disease Research Unit, the Department of Traumatology and Emergency Surgery and the Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium). The prevention or treatment of age‐related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF‐I or rhTGFβ): a perspective (Review). J Intern Med 1997; 242: 285–90.

Both insulin‐like growth factor‐I (IGF‐I) and transforming growth factor β (TGFβ) have powerful modulatory effects in a variety of tissues. A major target of action is the skeletal system, where they enhance bone formation and decrease matrix degradation, thus playing a part in the maintenance of bone mass. Because of the potent mitogenic effect of these agents on osteoblasts, recombinant IGF‐I (rhIGF‐I) and recombinant TGFβ (rhTGFβ) have potential as drugs to stimulate bone formation in the prevention and treatment of osteoporosis. Using biochemical markers, subcutaneous rhIGF‐I therapy has been shown to increase bone turnover and bone formation in nonosteoporotic older people. However, a corresponding increase in bone mass has not yet been documented nor have there been reports yet on the effects of systemically administered rhTGFβ in humans. Further investigation is required to define the clinical potential of rhIGF‐I and rhTGFβ as therapeutic agents in age‐related osteoporosis.
Efficacy and safety of human leucocyte interferon‐α treatment in patients younger than 60 years of age with polycythaemia vera
Authors: STASI R. , BRUNETTI M. , BUSSA S. , VENDITTI A. , DEL POETA G. , CONFORTI M. , SCIMÒ M. T. , CUDILLO L. , ADORNO G. , CECCONI M. , AMADORI S. , PAGANO A.
Published: November 2003

Stasi R, Brunetti M, Bussa S, Venditti A, Del Poeta G, Conforti M, Scimò MT, Cudillo L, Adorno G, Cecconi M, Amadori S, Pagano A (Department of Medical Sciences, Regina Apostolorum Hospital, Albano Laziale, and Chair of Haematology, University of Rome ‘Tor Vergata’, S. Eugenio Hospital, Rome, Italy). Efficacy and safety of human leucocyte interferon‐α treatment in patients younger than 60 years of age with polycythaemia vera. J Intern Med 1997; 242: 143–7.

Objectives

To evaluate the therapeutic activity and toxicity of human leucocyte interferon‐α (lIFN‐α) in patients with polycythaemia vera (PV) aged less than 60 years.

Design

An open clinical study.

Setting

Department of Medical Sciences, Regina Apostolorum Hospital, Albano Laziale, and Chair of Haematology, University of Rome ‘Tor Vergata’, S. Eugenio Hospital, Rome, Italy.

Subjects

Fourteen patients with PV and aged <60 years who had active disease as indicated by the need for phlebotomy and/or cytoreductive therapy.

Interventions

lIFN‐α was administered subcutaneously at the starting dose of 3 MU thrice weekly. The interferon dose could be escalated to six MU thrice weekly if it was well tolerated and disease was not controlled after three months of treatment at the lower dose.

Main outcome measures

Change in phlebotomy requirements, spleen size, pruritus score and haematological parameters after 6 months of treatment. Evaluation of lIFN‐α side effects.

Results

Complete or partial disease control was achieved in 13 patients. Six patients achieved a complete response (CR) and four a partial response (PR) after 3 months of therapy. Dose escalation in partial or nonresponders resulted in two patients switching from a status of PR to CR, and three other patients achieving a partial response after being unresponsive to the lower dosage. Human leucocyte interferon‐α therapy significantly improved (P < 01) phlebotomy requirements, the degree of splenomegaly, pruritus scores, iron stores and MCV values, and platelet and leucocyte counts. A mild flu‐like syndrome (low‐grade fever, nausea and myalgias) appeared during the early phase of therapy in the majority of patients, but no patient had to discontinue lIFN‐α because of intolerance.

Conclusions

Subcutaneous human leucocyte interferon‐α appears an effective and well tolerated therapy in the management of PV‐associated myeloproliferation and pruritus in patients aged less than 60 years.
Risk factors for cardiovascular disease during the period 1985–1995 in Göteborg, Sweden. The GOT‐MONICA Project
Authors: WILHELMSEN L. , JOHANSSON S. , ROSENGREN A. , WALLIN I. , DOTEVALL A. , LAPPAS G.
Published: November 2003

Wilhelmsen L, Johansson S, Rosengren A, Wallin I, Dotevall A, Lappas G (Sahlgrenska University Hospital at Östra, Göteborg University; and Astra Hässle AB, Mölndal; Sweden). Risk factors for cardiovascular disease during the period 1985–1995 in Göteborg, Sweden. The GOT‐MONICA Project. J Intern Med 1997; 242: 199–211.

Aims

To report levels of cardiovascular risk factors in 1985, 1990 and 1995 in three population samples in Göteborg, Sweden, and to compare with previous population risk factor levels.

Population

The study was performed within the framework of the WHO MONICA Project which compares risk factor levels as well as the incidence of coronary heart disease and stroke in 38 populations.

Methods

Three random samples of men and women aged 25–34, 35–44, 45–54 and 55–64 comprising 152–218 subjects in each age group who responded to the invitation for screening procedures which included questionnaires, physical and laboratory investigations in 1985, 1990 and 1995.

Results

More men than women had smoked, except for those aged 35–44 where there was no difference between men and women. The proportion of men who had smoked decreased strongly between the first and third investigations (P < 0.0001), particularly amongst the younger age‐groups, with a similar tendency amongst women. In the 25–44‐years age group there was a tendency towards more women than men to be smokers in 1995. Snuff was used by 27% and 19% of men aged 25–34 and 35–44 years, respectively, in 1995. Up to 5% of women used snuff; higher in the younger age groups. More young men than women reported regular physical activity during leisure time with a tendency towards an increase from 1985 to 1995. The proportion of men reporting psychological stress varied little over the study period, but women aged 25–34 reported increased stress from 1985 to 1995. Body weight increased whereas height remained stable and consequently body mass index increased in men and women (P= 0.0001). Similarly, waist:hip ratio (measured in 1990 and 1995 only) also increased (P= 0.0001). Mean systolic and diastolic blood pressure increased with age and there was also a small increase between 1985 and 1995. Systolic blood pressure increased by a mean of 1.24 mmHg per 5‐year period independent of sex and age (P= 0.0001). Antihypertensive treatment increased with age, but was stable between 1985 and 1995. Serum total and LDL cholesterol concentrations increased with age, and there was a nonsignificant tendency also to higher HDL cholesterol concentrations at older ages. Serum total cholesterol concentration declined between 1985 and 1995, and HDL cholesterol declined significantly between 1985 and 1995 in all age groups for men and women only when all age groups were analysed together. Similar to total cholesterol, levels of LDL cholesterol declined between 1985 and 1995 for all ages. Serum triglyceride levels increased for men and women between 1985 and 1995.
Nephrotic syndrome and fibrillary glomerulonephritis
Authors: LAUFER J. , AUGARTEN A. , SZEINBERG A. , RAPOPORT J. , KATZENELSON D. , YAHAV Y.
Published: November 2003

Laufer J, Augarten A, Szeinberg A, Rapoport J, Katzenelson D, Yahav Y (The Chaim Sheba Medical Center, Tel Hashomer, Affiliated to the Sackler School of Medicine, Tel Aviv, Israel). Nephrotic syndrome and fibrillary glomerulonephritis (Case Report). J Intern Med 1997; 242: 83–6.

A 28‐year‐old female with cystic fibrosis presented with nephrotic syndrome and progressive renal failure. In addition, she complained of blurred vision and there was a purpuric skin eruption localized to her legs. A renal biopsy revealed fibrillary glomerulonephritis. Skin biopsy demonstrated swelling of capillary endothelium, thickening of arteriolar walls and deposition of IgA, C3 and fibrinogen by immunofluorescence. Opthalmoscopy and fluorescein angiography disclosed cotton wool spots with intraretinal haemorrhages and ischaemia of the macula. Albumin infusions resulted in worsening of eye symptoms and signs. The presence of these three clinicopathologic entities in a patient with CF may indicate the possibility of systemic involvement related to continued exposure to chronic bacterial lower lung infection.
Hyaluronan: its nature, distribution, functions and turnover
Authors: Fraser J. R. E. , Laurent T. C. , Laurent U. B. G.
Published: November 2003

Fraser JRE, Laurent TC, Laurent UBG (Monash University, Clayton, Victoria, Australia; and University of Uppsala, Uppsala, Sweden). Hyaluronan: its nature, distribution, functions and turnover (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 27–33.

Hyaluronan is a polysaccharide found in all tissues and body fluids of vertebrates as well as in some bacteria. It is a linear polymer of exceptional molecular weight, especially abundant in loose connective tissue. Hyaluronan is synthesized in the cellular plasma membrane. It exists as a pool associated with the cell surface, another bound to other matrix components, and a largely mobile pool. A number of proteins, the hyaladherins, specifically recognize the hyaluronan structure. Interactions of this kind bind hyaluronan with proteoglycans to stabilize the structure of the matrix, and with cell surfaces to modify cell behaviour. Because of the striking physicochemical properties of hyaluronan solutions, various physiological functions have been assigned to it, including lubrication, water homeostasis, filtering effects and regulation of plasma protein distribution. In animals and man, the half‐life of hyaluronan in tissues ranges from less than 1 to several days. It is catabolized by receptor‐mediated endocytosis and lysosomal degradation either locally or after transport by lymph to lymph nodes which degrade much of it. The remainder enters the general circulation and is removed from blood, with a half‐life of 2–5 min, mainly by the endothelial cells of the liver sinuoids.
Hyaluronan in morphogenesis
Authors: Toole B. P.
Published: November 2003

Toole BP (Tufts University School of Medicine, Boston, MA, USA). Hyaluronan in morphogenesis (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 35–40.

Pericellular matrices surrounding migrating and proliferating cells in the developing embryo, in regenerating tissues and in other dynamic cellular events, such as tumour cell invasion, are enriched in hyaluronan. In addition to contributing to the unique structure of the pericellular matrix, hyaluronan interacts with cell surface receptors, such as RHAMM and CD44. During morphogenesis, these interactions of hyaluronan with the cell surface are important in several ways. First, hyaluronan–CD44 interactions have been shown to mediate endocytic removal of hyaluronan at critical stages of embryonic development. Secondly, hyaluronan provides an appropriately hydrated, pericellular milieu that facilitates cellular invasion. Thirdly, in‐vitro studies suggest strongly that interactions of hyaluronan with RHAMM or CD44 are involved in cell movement and proliferation, which are critical events in morphogenesis.
Hyaluronan: fundamental principles and applications in cancer
Authors: DELPECH B. , GIRARD N. , BERTRAND P. , COUREL M.‐N. , CHAUZY C. , DELPECH A.
Published: November 2003

Delpech B, Girard N, Bertrand P, Courel M‐N, Chauzy C, Delpech A (Centre Henri‐Becquerel, Rouen, France). Hyaluronan: fundamental principles and applications in cancer (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 41–8.

Hyaluronan (HYA) plays a particular role in cancer cell microenvironment. A component of the desmoplasia, HYA is associated to other macromolecules and contributes to the net structure of the matrix. Cancer cells exhibit binding sites (CD44, RHAMM) for HYA. The cell adhesion to HYA can influence the cell motility and different factors could interplay to facilitate cell detachment from HYA. HYA protects cancer cells against immune cell attack. Serum HYA is often increased in metastatic patients.
Is serum hyaluronan a helpful tool in the management of patients with liver diseases?
Authors: Lindqvist U.
Published: November 2003

Lindqvist U (University Hospital, Uppsala, Sweden). Is serum hyaluronan a helpful tool in the management of patients with liver diseases? (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 67–71.

The results of serial determinations of serum hyaluronan indicate a prognostic value in progressive liver damage. In primary biliary cirrhosis and in cirrhotic alcoholic liver diseases serum hyaluronan level discriminates between early and advanced disease. In alcoholic liver disease serum hyaluronan can be applied as assessment of haemodynamic changes. Serum hyaluronan is of use as a non‐invasive index of liver fibrosis in chronic viral hepatitis. A reversible defect in the hyaluronan receptor of the hepatic endothelial cells was suggested following studies on paracetamol‐induced acute liver damage. In liver transplantation, graft function can be predicted by determination of the venous effluent of hyaluronan.
Declining autopsy rate in Sweden: a study of causes and consequences in Malmö, Sweden
Authors: LINDSTRÖM P. , JANZON L. , STERNBY N. H.
Published: November 2003

Lindström P, Janzon L, Sternby NH (Helsingborg Hospital; the Division of Epidemiology, Department of Community Medicine; and the Department of Pathology, Lund University, Malmö University Hospital, Sweden). Declining autopsy rate in Sweden: a study of causes and consequences in Malmö, Sweden. J Intern Med 1997; 242: 157–65.

Objective

In Sweden there has been a continuous decrease in the autopsy rate during the last 15–20 years. The autopsy rate in the city of Malmö has declined from 81% in 1984 to 34% in 1993. The intention of this study was to improve our understanding of the causes of the decline, and to assess its consequences with regard to cause of death surveillance and case retrieval in epidemiological and clinical research.

Design

A retrospective study.

Setting

The University Hospital in Malmö, a city in southern Sweden with 230 000 inhabitants.

Subjects

All deceased in 1984 (2900) and 1993 (3198). Cancer incidence 1984 and 1993.

Main outcome measures

Changes in autopsy rate in relation to age, sex, place of death and cause of death 1984 and 1993. Changes in the distribution of underlying causes of death in cases submitted and not submitted for a post mortem 1984 and 1993. Changes in cancer incidence and the number of incidentally‐detected new tumours 1984 and 1993.

Results

Patients who died in nursing homes were less often sent for a post mortem than were patients who died at the hospital. From 1984 to 1993 the percentage of people dying in nursing homes increased from 1 to 29%. Care of the elderly has been reorganized, and the number of terminally ill patients who die in nursing homes has increased during the last 20 years in Sweden. This shift in place of death seems to be the single major explanation of the declining autopsy rate in Malmö. The overall autopsy rate in 1993 remained, however, lower than it was in 1984 when a shift in place of death was taken into account. During the period of study there was a decline in the autopsy rate at all departments within the hospital. The distribution of underlying causes of death according to the death certificates was similar in 1984 and in 1993. However, in cases not submitted for autopsy in 1993 there were greater proportions dying from pulmonary and circulatory diseases, respectively, than there were in 1984. The lower autopsy rate in 1993 was for several cancer sites also associated with a reduced number of new cancer cases. The percentage of tumours incidentally detected at autopsy went down in men from 40 to 19% and in women from 39 to 17%.

Conclusion

Patients submitted for autopsy represented, with regard to age, sex, cause and place of death, a selected group of all deceased. The declining autopsy rate was associated with a difference in the distribution of underlying cause of death and of the incidence of cancer. It is concluded that the changes in the autopsy rate have to be taken into account in studies dealing with time trends of causes of death and incidence of cancer.
Acute intermittent porphyria: prevalence of mutations in the porphobilinogen deaminase gene in blood donors in France
Authors: Nordmann Y. , Puy H. , Da Silva V. , Simonin S. , Robreau A. M. , Bonaiti C. , Phung L. N. , Deybach J. C.
Published: November 2003

Nordmann Y, Puy H, Da Silva V, Simonin S, Robreau AM, Bonaiti C, Phung LN, Deybach JC (Centre Français des Porphyries, Hopital Louis Mourier, Colombes Cedex, France, and the Institut Gustave Roussy, Cedex, France). Acute intermittent porphyria: prevalence of mutations in the porphobilinogen deaminase gene in blood donors in France. J Intern Med 1997; 242: 213–217.

Objectives

Acute intermittent porphyria (AIP) is an autosomal dominant disorder resulting from a 50% deficiency in porphobilinogen deaminase (PBG deaminase). The true prevalence in the general population of mutations in the PBG deaminase gene capable of causing AIP is unknown. However, it is important to identify asymptomatic carriers of AIP mutations because all are at risk to have an acute attack.

Design

We measured erythrocyte PBG deaminase from 3350 healthy blood donors. When a clear cut deficiency (< mean minus 2.5 SD) was found, the PBG deaminase gene was analysed by molecular biology technics.

Subjects

Four subjects with PBG deaminase deficiency were identified. Two had mutations in the PBG deaminase gene which are known to cause AIP.

Conclusion

We conclude that, in France, the mutations of the PBG deaminase gene show a high prevalence in the healthy population. If only these two confirmed latent cases are used for the calculation, in France the minimal prevalence of the AIP gene is 1:1675.
A superfemale with primary Sjögren's syndrome which involved systemic organs
Authors: MIYAKAWA H. , IYONAGA K. , ARIMA S. , YONEKAWA Y. , SUGA M. , ANDO M.
Published: November 2003

Miyakawa H, Iyonaga K, Arima S, Yonekawa Y, Suga M, Ando M (First and Third Departments of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan). A superfemale with primary Sjögren's syndrome which involved systemic organs (Case report). J Intern Med 1997; 242: 261–5.

A 52‐year‐old Japanese woman complicated by a sex chromosomal anomaly as a superfemale, a mosaic of XXXXX/XXXX/XXX/XX/XO, with mild mental retardation, was hospitalized for dry mouth, dry eyes, and proteinuria. The sialography of the right parotid gland showed a globular‐type gland enlargement. A definite diagnosis of primary Sjögren's syndrome (SS) was made, and further examinations revealed not only typical sicca syndrome but also systemic extraglandular lymphocytic infiltration; interstitial pneumonitis, glomerular‐ and interstitial nephritis, superficial gastritis, thyroiditis, and a severe excitation conductive impairment of heart. We report a very rare case of superfemale with primary SS which involved systemic organs.
IgA nephropathy: 30 years on
Authors: Pettersson E.
Published: November 2003

Pettersson E (Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden). IgA nephropathy: 30 years on (Review). J Intern Med 1997; 242: 349–53.

Thirty years since its discovery, IgA nephropathy (IgAN) has turned out to be the commonest primary glomerulonephritis around the world. The major presenting symptom is haematuria, with or without proteinuria. IgAN was initially considered a benign disease, but long‐term follow‐up studies have shown the course to be slowly progressive with up to 50% of the patients developing terminal renal failure after several decades. The aetiology and pathogenesis are still unclear, but IgAN seems to be associated with a dysregulation of the immune response which is not very well understood. There is today no specific treatment. Effective blood pressure control is the cornerstone of therapy.
Moderate beer consumption and positive biochemical changes in patients with coronary atherosclerosis
Authors: GORINSTEIN S. , ZEMSER M. , BERLINER M. , GOLDSTEIN R. , LIBMAN I. , TRAKHTENBERG S. , CASPI A.
Published: November 2003

Gorinstein S, Zemser M, Berliner M, Goldstein R, Libman I, Trakhtenberg S, Caspi A (School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel). Moderate beer consumption and positive biochemical changes in patients with coronary atherosclerosis. J Intern Med 1997; 242: 219–24.

Objectives

The aim of this study was to evaluate the influence of moderate beer consumption on lipid metabolism and antioxidant activity in patients (pts) with coronary artery disease (CAD).

Subjects

Forty‐eight male pts with CAD not alcohol beverages consumers were randomly divided into experimental (EG) and control (CG) groups, 24 pts each.

Setting

Rehovot University Hospital, Israel.

Intervention

Every patient of the EG during a period of 30 consecutive days consumed 330 ml of Maccabee beer (>20 g of alcohol). The pts of the CG did not consume alcohol during the trial period.

Methods

A wide range of tests including total cholesterol, LDL–C, HDL–C, total tocopherol and α–tocopherol.

Results

Only in the pts of the EG were found a tendency to an increase of the level of HDL–C and a statistically significant rise in the level of total tocopherol (P < 0.025) and α–tocopherol (P < 0.025).

Conclusions

Even a short period of moderate beer consumption leads to some favourable biochemical changes in blood of pts with CAD which are widely regarded as indicators of CAD prevention.
The emergence of mouse models of atherosclerosis and their relevance to clinical research
Authors: Smith J. D. , Breslow J. L.
Published: November 2003

Smith JD, Breslow JL (Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY, USA). The emergence of mouse models of atherosclerosis and their relevance to clinical research (Review). J Intern Med 1997; 242: 99–109.

Due to the ability to introduce or mutate genes, the mouse has become the most common experimental animal model for atherosclerosis research. Wildtype mice on a chow diet do not get atherosclerosis. Three ways to induce atherosclerosis in mice are discussed: diet‐induced, apoE deficiency‐induced, and LDL receptor‐deficiency induced. The atherosclerotic lesions in apoE‐deficient mice have been well characterized, and they resemble human lesions in their sites of predilection and progression to the fibroproliferative stage. These mouse models of atherosclerosis are being used to identify genes which modify atherosclerosis susceptibility and in the development of antiatherogenic therapies.
The clinical course and outcome in patients with acute ischaemic stroke and transient ischaemic attack in relation to severe carotid disease
Authors: RÖDÉN‐JÜLLIG Å.
Published: November 2003

Rödén‐Jüllig Å (Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden). The clinical course and outcome in patients with acute ischaemic stroke and transient ischaemic attack in relation to severe carotid disease. J Intern Med 1997; 242: 355–60.

Objectives

To determine whether a severe ipsilateral carotid lesion influences the patient's clinical course and outcome in the acute phase of an ischaemic stroke or transient ischaemic attack (TIA).

Design

An evaluation of prospectively‐ collected and recorded clinical information and sonographic findings in patients treated in a stroke unit.

Subjects

Two hundred and sixty‐six consecutive patients with acute ischaemic stroke or TIA in the carotid territory.

Main outcome variables

A sonography of the carotid arteries was performed in all cases. Stroke symptoms were continuously monitored and progression and recurrence particularly looked for. Patient outcome at discharge was also recorded.

Results

An ipsilateral carotid stenosis of ≥ 70% was found in 11%, and 4% had an occlusion. These patients had no statistically significant increase in the rate of progression or recurrence of stroke during the acute phase. Furthermore, they did not become more disabled or in need of extended institutional care.

Conclusions

Severe ipsilateral carotid disease does not significantly influence the acute clinical course or outcome in ischaemic stroke patients and there seems to be no need for urgent sonography and treatment.
Myelodysplastic syndrome with vasculitic manifestations
Authors: Pirayesh A. , Verbunt R. J. A. M. , Kluin PH. M. , Meinders A. E. , de Meijer P. H. E. M.
Published: November 2003

Pirayesh A, Verbunt RJAM, Kluin PHM, Meinders AE, De Meijer PHEM (Leiden University Hospital, Leiden, The Netherlands). Myelodysplastic syndrome with vasculitic manifestations (Case Report). J Intern Med 1997; 242: 425–31.

Vasculitis in patients with the myelodysplastic syndrome (MDS) is a rare phenomenon. We describe a patient who presented with necrotic lesions of his toes, which proved to be the result of immune complex mediated vasculitis. This unusual combination of vasculitis and MDS prompted us to review the literature. Forty‐four cases of vasculitis in association with MDS were found. The pathogenesis of the vasculitis in MDS remains speculative, although several reports suggest an immunological mechanism. The temporal relationship could not be determined in 20 (45%) of reported cases. The prognosis of these patients appears to be worse than in patients with MDS without vasculitis. Steroids were used in 41 (93%) of the reported cases. Our patient did not receive any drug therapy, nevertheless his necrotic lesions improved within a few weeks.
Limited Wegener's granulomatosis with central nervous system involvement and fatal outcome
Authors: NORDMARK G. , BOQUIST L. , RÖNNBLOM L.
Published: November 2003

Nordmark G, Boquist L, Rönnblom L (Boden Hospital and University Hospital, Umeå, Sweden). Limited Wegener's granulomatosis with central nervous system involvement and fatal outcome (Case Report). J Intern Med 1997; 242: 433–36.

A 74‐year‐old woman was admitted to the medical department with vertigo and confusion, and suffered seizures three days later. Clinical, radiological and histopathological examination revealed limited Wegener's granulomatosis (WG) with central nervous system (CNS) involvement. Initially she was treated successfully with prednisolone and cyclophosphamide, but she relapsed after 25 months and died four weeks later. Autopsy showed widespread granulomas with vasculitis in the cerebrum. These findings emphasize the importance of considering WG in CNS disease of unclear origin, and demonstrate the aggressive nature of the disease.
Colonic endocrine cells in inflammatory bowel disease
Authors: El‐Salhy M. , Danielsson Å. , Stenling R. , Grimelius L.
Published: November 2003

El‐Salhy M, Danielsson Å, Stenling R, Grimelius L (University Hospital, Umeå; and University Hospital, Uppsala; Sweden). Colonic endocrine cells in inflammatory bowel disease. J Intern Med 1997; 242: 413–19.

Objectives

To study colonic endocrine cell types in patients with ulcerative colitis (UC) and Crohn's disease (CD).

Setting

Departments of Medicine and Pathology, University Hospitals, Umeå and Uppsala, Sweden.

Subjects

Seventeen patients with UC (seven females and 10 males) and 11 patients with CD (five females and six males). Twenty‐two patients (eight females and 14 males) operated on for colon carcinoma and without signs of inflammatory bowel disease were used as controls.

Measurements

The colonic endocrine cell types were identified by immunohistochemical methods and quantified by computed image analysis.

Results

The areas of the argyrophil cells as well as those immunoreactive to chromogranin A and serotonin were significantly increased in patients with both UC and CD, compared with those in the controls. In patients with CD, the areas of polypeptide YY(PYY)‐ and pancreatic polypeptide (PP)‐immunoreactive cells were significantly reduced, whilst the area of enteroglucagon‐immunoreactive cells was increased. There was no statistical difference in endocrine cell area between specimens with slight versus severe inflammation, except for PYY and enteroglucagon cell areas in patients with CD. Whilst the former cell area decreased, the latter increased in specimens with severe inflammation. The mean cellular area for each endocrine cell type did not differ between the controls and patients with UC or CD.

Conclusions

The increase in the serotonin‐immunoreactive cell area in patients with both UC and CD might be one of the factors causing reduced colonic contraction and increased intraluminal pressure observed in patients with inflammatory bowel disease. Furthermore, in patients with CD, the decreased PYY‐immunoreactive cell area may explain the decreased absorption and increased secretion found in these patients.
Abnormal ambulatory electrocardiographic findings in patients with the Marfan syndrome
Authors: SAVOLAINEN A. , KUPARI M. , TOIVONEN L. , KAITILA I. , VIITASALO M.
Published: November 2003

Objectives. The aim of this study was to assess the prevalence of cardiac dysrhythmias and abnormalities of conduction and repolarization in the Marfan syndrome (MFS).

Subjects and methods. Forty‐five adult MFS patients (25 men) and healthy age and sex matched controls. A 24‐h ambulatory electrocardiogram was recorded.

Results. There was no difference in heart rates between the two groups. Two MFS patients had atrial fibrillation. The median number of premature atrial beats was 12/24 h in the MFS group vs. 6/24 h in the controls (P<0.05), and the respective medians of premature ventricular beats were 17/24 h vs. 1/24 h (P<0.001). Five patients but no healthy person had salvos of 3 premature ventricular complexes (P<0.05). Ventricular premature beats with R on T configuration were recorded in nine patients but in none of the control subjects (P<0.05). Both PQ and QT intervals at heart rates of 60, 80 and 100 beats min−1 were longer in the MFS group compared with healthy persons (P<0.005). Also ST segment depression was seen more often in the MFS group (17/43 vs. 6/45; P<0.05). In patients with MFS, the findings at ambulatory electrocardiography showed no association with echocardiographically determined aortic root diameter, left atrial diameter or left ventricular diameters, wall thickness and systolic function. Nor did the electrocardiographic findings correlate with the presence of mitral or tricuspid valve prolapse.

Conclusions. Patients with MFS have a higher prevalence of cardiac dysrhythmias than healthy persons. Likewise they have prolonged atrio‐ventricular conduction time and disturbed depolarization as suggested by longer QT intervals and more common ST segment depression.