bluuebunny/crossref_metadata_2025 huggingface dataset:
Progression of glomerular diseases
Authors: PETEN E. P. , STRIKER L. J.
Published: August 2009

Abstract. The nature and slope of progression of glomerular diseases is the subject of considerable discussion. The use of renal biopsies has been accompanied by considerable improvement in the classification of glomerular disease. However, the clinical and histological tools available to assess prognosis in individual patients lack accuracy, especially in slowly progressive glomerular diseases such as diabetes mellitus.

The development of molecular biology tools provides a new approach to the analysis of glomerulosclerosis. The accumulation of extracellular matrix in the glomerulus results from an exaggerated synthesis of collagens and other molecules forming the basement membranes, and is accompanied by an increase in the corresponding mRNAs. The measure of local glomerular gene activation can therefore provide a dynamic view of glomerular scarring. Utilizing a method combining microdissection of the glomeruli, reverse transcription in situ and a competitive polymerase‐chain‐reaction assay we were able to measure minute amounts of mRNAs in single mouse and human glomeruli. Both in mouse models and in human glomerulosclerosis we found upregulation of basement membrane collagen genes in the glomeruli. The increase appeared to be parallel to the slope of progression of glomerulosclerosis in experimental animals. This new approach may therefore provide a quantitative and sensitive method to define the propensity to sclerosis in human disease.
No effect of high‐dose inhaled steroids in pulmonary sarcoidosis: a double‐blind, placebo‐controlled study
Authors: MILMAN N. , GRAUDAL N. , GRODE G. , MUNCH E.
Published: August 2009

Abstract. Objective. To evaluate whether inhaled steroids in high doses might be of therapeutic value in pulmonary sarcoidosis.

Design. Randomized, double blind and placebo controlled parallel study.

Setting. The out‐patient clinic of the Department of Pulmonary Medicine, Gentofte Hospital, Copenhagen, Denmark.

Subjects. Twenty‐one untreated patients (17 males, 4 females, median age 33 years, range 21–65) and eight patients treated with systemic prednisolone. All patients had biopsy proven pulmonary sarcoidosis radiological stage I‐III.

Interventions. Treatment with either inhaled budesonide 1.2 mg day−1‐2.0 mg day−1 (n = 9) or placebo (n = 12) for 12 months.

Main outcome measures. Clinical (cough, chest pain, dyspnoea) and paraclinical variables (chest X‐ray, gallium scintigraphy, pulmonary function tests, and biochemical markers of disease activity: blood leukocytes, lymphocytes, serum (S‐) angiotensin converting enzyme (ACE), S‐1,25‐OH‐cholecalciferol, plasma (P‐) calcium, P‐immunoglobulins) were recorded before treatment, every three months during treatment, and 6 months after treatment had been discontinued.

Results. There were no significant differences between the recorded variables in the budesonide and placebo groups. In general, a regression of disease activity was observed in both groups. Two patients in the treatment group, treated with 2.0 mg budesonide/ day, and two in the placebo group had progression in disease and were put on systemic steroids.

Conclusion. Inhaled budesonide in doses of 1.2‐2.0 mg day−1 had no recognizable therapeutic effect on pulmonary sarcoidosis.
The relation of coronary and peripheral arterial disease to the severity of femoral atherosclerosis in hypercholesterolaemia
Authors: BERGSTRAND L. , OLSSON A. G. , ERIKSON U. , HOLME I. , JOHANSSON J. , KAIJSER L. , LASSVIK C. , MÖLGAARD J. , NILSSON S. , STENPORT G. , WALLDIUS G.
Published: August 2009

Abstract. Objectives. The extent of atherosclerosis in the superficial femoral artery and the severity of arterial disease in the aorto‐iliac and femoro‐popliteal arterial districts were related to clinical diagnosis of coronary and peripheral atherosclerosis in hypercholesterolaemic patients.

Design. The study constitutes baseline cross‐sectional data of a randomized double‐blind clinical trial on Probucol, using both computer based and visual estimations of angiographies as endpoints.

Subjects. Two hundred and ninety men and women (mean age 54 years) with hypercholesterolaemia.

Main outcome measures. Atherosclerosis was estimated with arteriographies. Lumen volume and edge roughness (vessel inner wall irregularity) of a 20 cm segment of the femoral artery were estimated by computer. A visual atherosclerosis score of the abdominal aorta to the popliteal arteries was made on both sides.

Results. Patients with peripheral arterial disease had significantly more advanced disease according to all three angiographic variables than those without symptoms of peripheral vascular disease. Both men and women with coronary artery disease had significantly lower femoral lumen volume and higher roughness values than patients without. Men with previous myocardial infarction had significantly higher mean visual scores of atherosclerosis than those without, while lumen volume and roughness did not differ in either sex.

Conclusions. Femoral atherosclerosis is an expression of a generalized disease, associated with clinical symptoms of coronary artery disease. Femoral atherosclerosis is often accompanied by atherosclerosis also in the coronary arteries.
Diagnostic approach to pulmonary lymphangioleiomyomatosis
Authors: DELGRANGE E. , DELGRANGE B. , WALLON J. , ROSOUX P.
Published: August 2009

Abstract. Pulmonary lymphangioleiomyomatosis is an interstitial lung disease with distinctive clinical, radio‐logic, physiological and pathological findings. We report an additional case of this rare condition, diagnosed on first medical evaluation by trans‐bronchial lung biopsy and discuss the diagnostic approach.
Warfarin resistance due to malabsorption
Authors: TALSTAD I. , GAMST O. N.
Published: August 2009

Abstract. A female patient developed warfarin resistance after 2 years of satisfactory therapy. Only a third of orally administered warfarin was absorbed, the clearance of warfarin was normal. The patient was also resistant for dicoumarol, while phenindione had satisfactory effect on the prothrombin time (PT).
Alteration of oxide reductive and haemostatic factors in type 2 diabetics
Authors: NERI S. , BRUNO C. M. , RACITI C. , D'ANGELO G. , D'AMICO R. , CRISTALDI R.
Published: August 2009

Abstract. Objective. To assess any pathogenic role of radical activity and haemostatic alteration in the early cardiovascular disease of microalbuminuric type 2 diabetics (non‐insulin dependent).

Design. A selected cohort of type 2 diabetics was identified, divided according to urinary albumin excretion and compared with a healthy control group depending on some haemostatic factors and radical activity.

Setting. All the subjects were studied as outpatients.

Subjects. Eighty diabetics and 84 healthy controls were interviewed and underwent blood tests to exclude standard cardiovascular risk factors before follow up.

Main outcome measures. The subjects were males, age range 43–55 years, and divided according to albumin excretion (microalbuminuria > 30–200 mg L−1; normoalbuminuria < 15 mg L−1). The mean duration of diabetes referred by the patients was 9.3 years in albuminuric and 11.1 years in normoalbuminuric patients with a good control of plasma glucose level. Neither the diabetics nor the control group showed clinical evidence of renal and cardiovascular diseases.

Results. Microalbuminuric patients presented elevated malondialdehyde concentration, glutathione peroxidase activity, phospholipidic fatty acid levels, fibrinogen, plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor compared with normoalbuminuric patients and controls.

More collagen was required in microalbuminuric diabetics than in normoalbuminurics and controls.

Conclusions. Our results confirm that both free radical activity and changes in haemostatic factors can be observed in type 2 diabetes and particularly in patients with albuminuria. Our very selected series with short duration, good control of diabetes and lack of clinical evidence of cardiovascular disease may suggest that these abnormalities develop earlier and may be associated with, and/or implicated in, the pathogenesis of microvascular complications which can be related to a higher and early cardiovascular morbidity and mortality rate in microalbuminuric diabetics.
Do clinicians accept the role of Helicobacter pylori in duodenal ulcer disease: a survey of European gastroenterologists and general practitioners
Authors: CHRISTENSEN A. H. , LOGAN R. P. H. , NOACH L. A. , GJøRUP T.
Published: August 2009

Abstract. Objectives. To examine to what extent clinicians in Europe accepted the theory of the casual role of Helicobacter pylori (H. pylori) in duodenal ulcer disease in the year 1992, and to what extent the theory had influenced their diagnostic and therapeutic habits in the management of duodenal ulcer patients at that time.

Design. Postal questionnaire.

Setting. Three European countries: the UK, the Netherlands, and Denmark.

Subjects. Three hundred and three gastroenterologists, 250 general practitioners, 83 junior hospital doctors.

Main outcome measures. Number of doctors believing H. pylori to be a significant cause of duodenal ulcer disease, use of diagnostic tests for detection of H. pylori and therapeutic regimens for eradicating H. pylori.

Results. Four hundred and forty‐two doctors replied. Eighty‐four per cent of the British doctors, 73% of the Dutch doctors, and 47% of the Danish doctors accepted the role of H. pylori in duodenal ulcer disease. The rates were higher among gastroenterologists than among general practitioners. Eighty‐four per cent of the British doctors, 80% of the Dutch doctors, and 48% of the Danish doctors used diagnostic tests for H. pylori, most frequently histological examination (64%). In patients with duodenal ulcer disease, H. pylori eradication was undertaken by 93% of the British doctors, 89% of the Dutch doctors, and 60% of the Danish doctors. A triple therapy (a bismuth salt, metronidazole, and either amoxicillin or tetracycline) was used by 57% (181/315) of the doctors.

Conclusions. H. pylori treatment is frequently used in some countries. However, the role of H. pylori in duodenal ulcer disease has not been accepted to the same extent in different European countries.
Relationship between visceral fat, steroid hormones and insulin sensitivity in premenopausal obese women
Authors: ZAMBONI M. , ARMELLINI F. , TURCATO E. , de PERGOLA G. , TODESCO T. , BISSOLI L. , ANDREIS I. A. BERGAMO , BOSELLO O.
Published: August 2009

Abstract: Objectives. The relationships between visceral fat distribution, steroid hormones and peripheral insulin sensitivity were studied.

Setting. All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona, Italy.

Subjects. Nineteen fertile obese women were studied with ages ranging from 18 to 53 years and body mass indexes ranging from 27.3 to 48.4.

Intervention. Body fat distribution was evaluated by waist‐to‐hip circumference ratio and by computed tomography. The insulin tolerance test was used to evaluate peripheral insulin sensitivity. Glucose, insulin and C‐peptide were measured in fasting conditions and during glucose load; total and free plasma testosterone and urinary cortisol excretion were also determined.

Results. Significant correlations emerged between visceral adipose tissue and fasting glucose, insulin, and C‐peptide. but not between visceral adipose tissue and total testosterone, free testosterone or urinary cortisol excretion. A negative correlation emerged between visceral adipose tissue and insulin sensitivity (r = −0.70; P < 0.01). No significant correlations were found between insulin sensitivity and age, body weight, body mass index, total adipose tissue, subcutaneous adipose tissue or waist‐to‐hip ratio. Total testosterone correlated with body weight, subcutaneous adipose tissue and total adipose tissue. Free testosterone and urinary cortisol excretion correlated positively with body weight, and negatively with age. No correlation was found between insulin sensitivity and total testosterone, free testosterone or urinary cortisol excretion. The correlation between visceral adipose tissue and insulin sensitivity remained significant even after adjusting for both age and the body mass index.

Conclusions. Our study shows that visceral fat is more closely associated with aberrations of insulin sensitivity than with obesity itself. Total testosterone, free testosterone and urinary cortisol excretion in our subjects do not seem to be associated with such aberrations.
Chronic idiopathic pure red cell aplasia: successful treatment during pregnancy and durable response to intravenous immunoglobulin
Authors: MANT M. J.
Published: August 2009

Abstract. A patient with chronic idiopathic pure red cell hypoplasia responded to intravenous immunoglobulin therapy. No other treatment was administered. During treatment, the patient was taken through two pregnancies without haematological problems. After 22 months of therapy, the intravenous immunoglobulin was discontinued; a durable remission was subsequently maintained. Intravenous immunoglobulin may be the treatment of choice for females of child‐bearing potential.
Homocysteine and cysteine: determinants of plasma levels in middle‐aged and elderly subjects
Authors: BRATTSTRÖM L. , LINDGREN A. , ISRAELSSON B. , ANDERSSON A. , HULTBERG B.
Published: August 2009

Abstract. Objectives. Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. We explored possible determinants of plasma homocysteine and cysteine concentrations amongst middle‐aged and elderly subjects.

Design and subjects. Of 501 35–95‐year‐old randomly selected residents of Lund and Malmö, Sweden, 244 (49%; 131 men, 113 women) were investigated.

Results. Total plasma homocysteine concentrations were higher in men than in women (mean ± SD: 13.9 ± 4.1 and 12.3 ± 4.1 μmol L−1; P < 0.001), increased markedly with age (Spearman's p = 0.488; P < 0.001), and were correlated (P < 0.001) to concentrations of blood folate, serum vitamin B12, and serum creatine (p = −0.366, −0.338, and 0.463). Users of multivitamins had lower homocysteine levels than nonusers [10.5 ± 3.3 μmol L−1 (n = 31) and 13.5 ± 4.2 μmol L−1 (n = 213), respectively; P < 0.001]. Total plasma cysteine concentrations also increased significantly with age and increasing serum creatinine, but were unrelated to gender, blood folate, serum vitamin B12 and use of multivitamins.

Conclusions. Age, gender, folate, serum vitamin B12, serum creatinine and multivitamin usage are all important determinants of the plasma homocysteine concentration, whereas only age and serum creatinine are determinants of the plasma cysteine concentration. The age‐related increase in homocysteine and cysteine may be linked to the age‐related impairment of renal function, whereas the sex difference in plasma homocysteine may be because of the fact that more homocysteine is formed in men than in women in conjunction with creatine‐creatinine synthesis.
The efficacy of multiple risk factor intervention in treated hypertensive men during long‐term follow up
Authors: AGEWALL S. , WIKSTRAND J. , SAMUELSSON O. , PERSSON B. , ANDERSSON O. K. , FAGERBERG B. ,   Risk Factor Intervention Study Groups
Published: August 2009

Abstract. Objective. To examine the feasibility and efficacy of a multifactorial intervention programme directed towards hypercholesterolaemia, smoking, and diabetes mellitus in treated hypertensive patients after more than 3 years' follow‐up and to describe the incidence of cardiovascular complications.

Design. Open, randomized, parallel‐group study with allocation either to a comprehensive multiple risk factor modification programme or to usual care.

Setting. Outpatient clinic in a city hospital.

Patients. A total of 508 male patients with treated hypertension, aged 50–72 years, with at least one of the following: serum cholesterol ≥ 6.5 μmol L−1 smoking or diabetes mellitus.

Intervention. Individually given advice and group meetings based on nutritional advice and behavioural treatment principles. Drug therapy could be instituted to achieve the treatment goals in the intervention group: serum total cholesterol below 6.0 μmol L−1, no smoking, and HbAl1c below 6.0%. Diastolic blood pressure below 90 mmHg was the treatment goal in both groups.

Main outcome measurements. Serum cholesterol, HbA1c, diastolic blood pressure, smoking. Cardiovascular end‐points were recorded.

Results. The net changes were (change intervention—change usual care): serum cholesterol − 5.0% (95% confidence interval, − 7.6 to − 2.3 %), 17.6% more stopped smoking (P = 0.04); diastolic blood pressure and HbA1c remained unchanged. The incidence of stroke was lower in the intervention group compared with the usual‐care group: 2.0 and 6.7%, respectively (P = 0.017).

Conclusion. The intervention programme was comparatively successful with regards to the effects on hypercholesterolaemia and smoking habits. An unexpected decrease in the stroke incidence was observed in the intervention group compared with the usual‐care group.
Pressure‐dependent, enhanced natriuretic response to low‐dose, atrial natriuretic peptide infusion in essential hypertension
Authors: EISKJÆR H. , NIELSEN C. B. , PEDERSEN E. B.
Published: August 2009

Abstract. Objective. To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent.

Design. Part 1. The renal effects of a low‐dose continuous infusion (10 ng kg−1 min−1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS).

Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP + placebo (Part 1).

Methods. Lithium clearance was used to estimate the proximal tubular reabsorption of sodium.

Results. Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+ 102 vs. + 38%; P < 0.05), fractional excretion of sodium (+ 80 vs. + 37%; P < 0.05), and urinary output (+ 56 vs. + 8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (CL1) increased and FEL1 tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5′‐phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups.

Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+ 51 vs. +99%; P <0.05). The relative changes in GFR, CL1, and FEL1 during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure.

Conclusions. Low‐dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH is secondary in some degree to the elevated systemic pressure.
Incidence of pheochromocytoma in South Galicia, Spain
Authors: FERNÁNDEZ‐CALVET L. , GARCÍA‐MAYOR R. V. G.
Published: August 2009

Abstract. Objectives. To estimate the incidence of pheochromocytoma in the population of South Galicia (Spain) during the period 1980–1992.

Design. A prospective study.

Setting. The General Hospital of Vigo, a tertiary referral centre.

Subjects. New cases of pheochromocytoma diagnosed in the population during the years 1980–1992. The average population size was 523934 inhabitants, (52% female, 48% male).

Main outcome measures. All data were obtained from the Medical Registry, which ensures virtually complete case ascertainment for diagnosed pheochromocytoma in the population. All cases were histologically confirmed. The average annual incidence rate of pheochromocytoma was calculated.

Results. For the study period, 14 new cases (eight female and six male) of pheochromocytoma were diagnosed in the population of South Galicia. The average annual incidence rate in the population was 2.06 (range 0.0–3.93) per million. This incidence rate was significantly higher in the female population (2.26 vs. 1.84; P < 0.05). The mean age at diagnosis was 43 ± 12 (range 21–65) years. Thirteen of the 14 cases were diagnosed in living patients (two discovered incidentally at operation) and one case was diagnosed at autopsy. One pheochromocytoma was located outside the adrenals. All but one tumour were benign. One patient had pheochromocytoma as part of the multiple endocrine neoplasia type IIa, and in four patients it was associated with neurofibromatosis (28.57%). Four of the 13 patients surgically treated had residual hypertension.

Conclusions. The incidence of pheochromocytoma in our population is similar to that reported from other European countries. Routine screening for this disease is not recommended, but postoperative follow‐up of the patients is needed. A wider study is necessary to confirm the high association with neurofibromatosis in our population.
Systemic polyarteritis nodosa as the initial manifestation of a gastric adenocarcinoma
Authors: POVEDA F. , GONZÁLEZ‐GARCÍA J. , PICAZO M. L. , GIMÉNEZ A. , CAMACHO J. , BARBADO F. J. , VÁZQUEZ‐RODRÍGUEZ J. J.
Published: August 2009

Abstract. We report a case of systemic polyarteritis nodosa (PAN) leading to the discovery of an as yet asymptomatic, surgically curable gastric adenocarcinoma.

PAN is rarely associated with malignancies and in such cases these are more often malignant haemato‐logical diseases than solid neoplasms. The immuno‐pathological findings, the temporal relationship between both conditions, and the spontaneous resolution of vasculitis after tumour removal suggest a paraneoplastic origin of the systemic angitis.
Management of corticosteroid‐induced osteoporosis
Authors: EASTELL RICHARD ,   UK Consensus Group Meeting on Osteoporosis
Published: August 2009

Abstract. Corticosteroid therapy results in osteoporosis. There is a doubling in the risk of fracture in patients taking more than the equivalent of 7.5 mg day−1. The bone loss is most rapid from the axial skeleton, particularly during the 1st year of therapy. The most important mechanism for the bone loss is a decrease in osteoblastic activity. Preventative strategies should be targeted to patients with low bone‐mineral density, especially if the dose of corticosteroids is likely to be high. Treatment strategies agreed on by the Consensus Panel included hormone replacement therapy and bisphosphonates, with monitoring of efficacy by bone densitometry.
Lipid intolerance in smokers
Authors: AXELSEN M. , ELIASSON B. , JOHEIM E. , LENNER R. A. , TASKINEN M.‐R. , SMITH U.
Published: August 2009

Abstract.Objectives.Smokers have recently been shown to be insulin resistant and to exhibit several characteristics of the insulin resistance syndrome (IRS). In this study, we assessed fasting and postprandial lipid levels in healthy, normolipidaemic, chronic smokers and a matched group of non‐smoking individuals.

Design.A standardized mixed meal (containing 3.78 MJ and 51 g of fat) was given in the morning after an overnight fast. The smokers were either abstinent from tobacco for 48 h or were allowed to smoke freely, including being allowed to smoke six cigarettes during the study.

Subjects.Twenty‐two middle‐aged, healthy male subjects, nine habitual smokers and 13 non‐smoking control subjects, were recruited to the study. The smokers had all been smoking at least 10 cigarettes per day for at least 10 years.

Results.The smokers exhibited a lipid intolerance in that their postprandial increase in triglyceride levels was more than 50% higher than in the non‐smokers' group. This lipid intolerance could not be discerned in the postabsorptive state because the fasting triglyceride levels were the same in both groups, whilst the smokers had significantly lower high‐density lipoprotein (HDL) cholesterol. The peak postprandial triglyceride level correlated closely and negatively with fasting HDL cholesterol, indicating an impaired lipolytic removal capacity in smokers.

Conclusions.Healthy, normotriglyceridaemic smokers exhibit an abnormal postprandial lipid metabolism consistent with lipid intolerance. It is suggested that postprandial hyperlipidaemia is a characteristic trait of the insulin resistance syndrome and that the defect in lipid removal is related to the low HDL cholesterol in this syndrome. The insulin resistance syndrome is likely to be an important reason for the increased propensity for cardiovascular disease in smokers.
Interrelation between risk factors for cardiovascular disease in men aged 33–42: A study from Habo in Skaraborg County, Sweden
Authors: PERSSON L.‐G. , LINDSTRÖM K. , LINGFORS H. , BENGTSSON C.
Published: August 2009

Abstract. Objectives. The main purpose was to study associations between different risk factors for coronary heart disease in order to find out whether such associations already exist during the fourth decade of life.

Setting. A study carried out by the primary healthcare staff in the community of Habo in Skaraborg County in south‐western Sweden.

Subjects. All men living in Habo aged 33–42 years who were willing to participate in the study ‐ in total 652 men (participation rate 86%).

Main outcome measures. Risk factors for coronary heart disease considered as markers of lifestyle: body‐mass index as a measure of general obesity, waist‐to‐hip circumference ratio as a measure of central obesity, arterial blood pressure, serum cholesterol concentration and serum triglyceride concentration.

Results. There were statistically significant correlations between all the factors analysed including anthropometric data, blood pressure and serum lipids.

Conclusions. The results indicate associations between different risk factors at an early age and emphasises the need for a multifactorial view on risk as early as at the ages which were the focus of this study.
Hyperinsulinaemia and decreased plasma levels of dehydroepiandrosterone sulfate in premenopausal women with coronary heart disease
Authors: SŁOWIŃSKA‐SRZEDNICKA J. , MALCZEWSKA B. , SRZEDNICKI M. , CHOTKOWSKA E. , BRZEZIŃSKA A. , ZGLICZYŃSKI W. , OSSOWSKI M. , JESKE W. , ZGLICZYŃSKI S. , SADOWSKI Z.
Published: August 2009

Abstract. Objectives. The purpose of the study was to establish plasma levels of insulin, ovarian sex hormones and dehydroepiandrosterone sulfate (DHEA‐S) and to evaluate their correlations with lipids in premenopausal women with angiographically demonstrated coronary stenosis.

Design. Differences in plasma levels of insulin, ovarian sex hormones, DHEA‐S and lipids between groups were compared by analysis of variance.

Setting. From January 1993 until December 1993 patients were diagnosed in the Outpatient Clinic of the Department of Endocrinology Medical Centre for Postgraduate Education, Warsaw.

Subjects. Premenopausal women with normal oral glucose tolerance test (OGTT) results, with and without coronary stenosis were studied: 21 women after acute myocardial infarction with angiographically demonstrated coronary stenosis (women with CHD), and 14 women with chest pain, a positive exercise test without significant changes of coronary arteries on coronarography (women with normal coronarography, NC). The control group consisted of nine, healthy women with no risk factors for CHD.

Main outcome measures. In premenopausal women with CHD, the decreased plasma level of DHEA‐S and hyperinsulinaemia were anticipated.

Results. In women with CHD, the plasma levels of DHEA‐S (926.5 ± 83 ng mL−1) were significantly lower than those in women with NC (1375.7 ± 181 ng mL−1) and in healthy controls (1984 ± 127 ng mL−1), P < 0.02 and P < 0.001, respectively. The fasting insulin and insulin response to an OGTT in women with CHD and with NC was higher than in healthy subjects. A significant decrease of high‐density lipoprotein (HDL) cholesterol, HDL‐2 cholesterol and apolipoprotein A‐I, and an increase of total cholesterol, low‐density lipoprotein cholesterol C and apolipoprotein B levels in women with CHD compared to healthy controls were observed. A negative correlation between fasting insulin and the plasma levels of DHEA‐S was established.

Conclusion. In premenopausal women, hyperinsulinaemia and decreased DHEA‐S levels may contribute to the development of coronary atherosclerosis.
The medical hierarchy and perceived influence on technical and ethical decisions
Authors: HOLM SØREN
Published: August 2009

Abstract.Objective.To investigate the influence of hierarchial position and perceived influence on ethical and technical decisions.

Design.The study was conducted as a postal questionnaire survey.

Subjects.A random sample of 329 Danish physicians working at departments of internal medicine and related subspecialties. Of these, 270 (82%) returned a completed questionnaire.

Main outcome measure.Self‐reported perceived influence in discussions about technical and ethical issues in connection with decisions to terminate treatment for patients with terminal malignant illness.

Results.The odds ratio for perceived influence between consultants and house officers is 14.9 for ethical issues, 44.9 for technical issues, and 652.3 for questions concerning departmental policy. Gender plays no role, when one controls for hierarchial position.

Conclusions.Hierarchial position is the major determinant of perceived influence on technical and ethical decisions. Position seem to play a larger role in technical than in ethical decisions.
Analysis of the MRFIT screenees: a methodological study
Authors: WERKÖ LARS
Published: August 2009

Abstract. Purpose. To review the methods used in the many publications on the MRFIT screenees.

Method. Medline was searched for articles mentioning MRFIT screenees. The articles were collected, abstracted, and the method section and some of the result section were scrutinized in detail. The statements in different articles regarding methods used and the presentation of results were compared.

Result. The analyses of the MRFIT screenees seem to be retrospective studies of mortality and risk factors, where the underlying data base has been far from complete. Similar data are presented in slightly different fashions in several papers published in different scientific journals at about the same time. The control of the quality of underlying data has been uneven and is not discussed at all in most of the papers published.

Conclusion. The often‐repeated statement that the MRFIT screenees constitute the largest and most exact data base regarding the relation of risk factors to mortality in the healthy male US population has no foundation.
Diminished vitamin B12 levels in patients with severe sickle cell disease
Authors: AL‐MOMEN A. K.
Published: August 2009

Abstract. Objective. The aim of this study was to estimate the levels of vitamin B12 in patients with severe sickle cell disease compared to normal controls. Complete blood count, iron studies and vitamin B12 levels were obtained in 85 consecutive patients with severe sickle cell disease (56 males, 29 females, aged 14–49 years) and 100 healthy blood donors (67 males, 33 females, aged 17–60 years) as a normal control group.

Results. Thirty‐seven of the 85 patients (43.5%) had serum vitamin B12 levels below normal values (mean 84.3 ± 28.7, range 7–145 pmol L−1) without macrocytosis or hypersegmented neutrophils. The mean level of vitamin B12 in the remaining 48 patients (56.5%) was normal (mean 233.3 ± 73.9, range 152–435 pmol L−1) which is below the mean of normal control levels (mean 327.7 ± 168.7, range 178–897 pmol L−1). Patients with low B12 achieved a significant symptomatic improvement when treated with vitamin B12, 1 mg intramuscularly weekly for 12 weeks when compared with patients with normal B12 levels.

Conclusion. We conclude that many patients with severe sickle cell disease may suffer from unrecognized vitamin B12 deficiency.
Impaired melatonin secretion in patients with Wernicke‐Korsakoff syndrome
Authors: WIKNER J. , ANDERSSON D. E. H. , WETTERBERG L. , RÖJDMARK S.
Published: August 2009

Abstract. Objectives. Melatonin (MT) undergoes circadian changes in response to external light conditions and has been implicated in the control of other circadian hormone variations. Alcohol inhibits MT secretion in healthy subjects. The purpose of the present investigation was to elucidate whether patients with Wernicke‐Korsakoff syndrome (WKS) also have impaired MT secretion after a period of prolonged alcohol abstention. If so, it would be of interest to find out whether this affects Cortisol rhythmicity.

Design. Seven patients with WKS and 8 healthy controls were included in the study. Venous blood was sampled every 2nd h between 18.00 and 08.00 hours, and urine collected between 22.00 and 07.00 hours.

Setting. Department of Internal Medicine, Endocrinology Section, Sódersjukhuset, Stockholm.

Main outcome measures. Peak serum MT values during the night, total nocturnal MT secretion (estimated by MT incremental areas), and urinary excretion of MT were determined in each participant. Serum Cortisol levels were determined in the patients at 18.00, 02.00 and 08.00 hours.

Results. Patients with WKS had a markedly reduced nocturnal secretion of MT compared to healthy volunteers (MT incremental areas 0.33 ± 0.21 vs. 1.60 ± 0.29 nmol L−1 h−1, mean ± SEM; P < 0.005). Amongst the patients, the serum Cortisol level was higher in the morning than in the afternoon (331 ± 46 vs. 240 ± 52 nmol L−1; P < 0.01), and showed a nadir during the night (138 ± 45 nmol L−1) as in normal individuals.

Conclusion. Patients with WKS have markedly reduced nocturnal secretion of MT. The exact mechanism behind this finding has to be further elucidated. However, it is of interest to note that despite the lack of clearcut circadian MT changes, WKS patients retain normal Cortisol secretion, thus suggesting that MT rhythm may not be obligatory for the proper control of circadian Cortisol rhythmicity.
Habitual diet, platelet function, fibrinogen and facto VII coagulant activity in young Finns
Authors: MUTANEN MARJA , KRUSIUS TOM , RÄSÄNEN LEENA , FREESE RIITTA , VAHTERA ELINA , VIIKARI JORMA S. A.
Published: August 2009

Abstract. Objectives. The objective of the study was to determine whether an association between diet and platelet function, plasma fibrinogen level and factor VII coagulant activity (VII:C) could be established in young subjects.

Design. Data on the habitual diet of the subjects were collected either by a questionnaire on food habits (n = 204) or by a 48‐h dietary recall interview (n = 53).

Subjects. The subjects were participants in the project ‘Cardiovascular Risk in Young Finns’ (age range 15–30 years). A total of 204 subjects having a questionnaire on food habits participated in the platelet function tests and 53 also participated in a 48‐h dietary recall interview. Plasma fibrinogen concentration and factor VII: C were measured from 79 subjects.

Main outcome measures. Platelet function was tested by turbidometric measurement of platelet aggregation using ADP and collagen as aggregation agents.

Results. Platelet aggregation with ADP (at up to 4.0 μmol L−1) and collagen (at up to 5.0 μg mL−1 platelet‐rich plasma PRP) showed that the diet characterized as ‘saturated’, i.e. containing high‐fat milk and saturated fat, was associated with platelets less sensitive to aggregating agents in vitro when compared to the unsaturated type of diet. Collagen‐but not ADP‐induced aggregation decreased with age of the subjects (P = 0.026–0.057, regression coefficient). An inverse regression coefficient between plasma factor VII:C (101%; range 64–145%) and serum trigycerides (P = 0.006) and the intake of rye (g 1000 kcal−1; P = 0.03) were found.

Conclusions. In this study we showed that platelet reactivity and factor VII: C already differ considerably between subjects at a young age, and diet may explain some of this variation.
Incidentally detected adrenal tumours (incidentalomas): histological heterogeneity and differentiated therapeutic approach
Authors: BENCSIK Zs. , SZABOLCS I. , GÓTH M. , VÖRÖS A. , KASZÁS I. , GÖNCZI J. , KOVÁCS L. , DOHÁN O. , SZILAAGYI G.
Published: August 2009

Abstract. Objectives. To find a differentiated therapeutical approach to incidentalomas.

Design. Prospective study of incidentalomas: their histology, hormonal activity, and growth if primarily non‐operated.

Setting. Admissions to an academic tertiary care centre because of incidentaloma.

Patients. Thirty‐eight female, 25 male, 27–85 years old.

Interventions. Ultrasound, computed tomography and adrenal scintigraphy when appropriate; investigations to exclude malignancy giving metastasis into the adrenal gland; ACTH, Cortisol, aldosterone, renin activity, androgene, catecholamine measurements; surgery or follow‐up.

Main outcome measures. Rate of malignancy; linkage of tumour size to probability of malignancy; prevalence of tumours with subtle hormone excess.

Results. Cortical adenomas occurred in 13/31, metastases in 7/31 of the histologically confirmed cases. In 10/31 cases, the computed tomography indicated a size that was smaller than the pathological size (mean = 20 mm). 20.6% of all incidentalomas and 61.5% of the 13 operated corticol adenomas showed subtle hormonal activity. Twenty‐seven incidentalomas < 30 mm were folio wed‐up (3–41 months; mean 18 months) and showed growth in only one case. Sensitivity, specificity, and predictive value (PV) of a tumour ≥ 30 mm to indicate malignancy were: 1.0, 0.56 and 0.27, respectively. The PV of a < 30 mm tumour to exclude malignancy was 1.0.

Conclusions. Oncological screening tests are necessary in all incidentalomas. Tumours ≥ 30 mm should be operated but smaller ones can be followed‐up, because they are usually benign and rarely show progressive growth. Cortical adenomas with subtle hormonal overproduction and hypertension, diabetes or osteoporosis should be operated, irrespective of their size, but in the absence of relevant clinical symptoms they can be followed‐up.
Membranous glomerulonephritis associated with testicular seminoma
Authors: SCHNEIDER B. F. , GLASS W. F. , BROOKS C. H. , KOENIG K. G.
Published: August 2009

Abstract. Proteinuria, often nephrotic in range, is a recognized paraneoplastic syndrome of solid tumours, with membranous glomerulonephritis (MGN) the most common histopathological lesion seen on renal biopsy. A 56‐year‐old male was found to have proteinuria on routine medical examination. History, physical and serological evaluation failed to reveal an aetiology and subsequent renal biopsy showed MGN, presumed to be idiopathic. Prednisone therapy was begun but this proteinuria did not resolve (> 1 g 24 h−1). Eleven months later the patient discovered a testicular mass which was found to be a stage I seminoma upon excision and metastatic evaluation. His proteinuria rapidly normalized after orchectomy and regional lymph node radiotherapy. This is the first known case of MGN associated with testicular seminoma.
Oral contraceptives and venous thromboembolism: a quantitative discussion of the uncertainties
Authors: KOSTER T. , SMALL R.‐A. , ROSENDAAL F. R. , HELMERHORST F. M.
Published: August 2009

Abstract. Objectives. The majority of post‐thrombotic women are barred from using oral contraceptives. We evaluated this policy for its clinical relevance.

Design. A meta‐analysis of controlled studies between 1960 and 1993.

Setting. A Medline computer search, from 1966 to 1993, in multiple languages, with the following index terms: thrombosis, thrombopheblitis, vein, venous, pulmonary embolism, contraceptives, oestrogen, oral.

Study selection. A total of 588 articles or abstracts were reviewed for controlled studies, in which an index group was compared with a control group. Included were one randomized trial, six follow‐up studies and eight case‐control studies.

Main outcome measures. Summary thrombosis risk for oral contraceptive users, number needed to discontinue oral contraceptives to prevent one (recurrent) thrombosis, comparison of additional unwanted pregnancies and postpartum thrombosis between alternative birth‐control methods.

Results. The studies proved highly heterogeneous with regard to size and direction of the risk estimate. The summary relative risk of first thrombosis during oral contraceptive use was 2.9 (95% CI, 0.5–17). Since the risk of thrombosis recurrence is not well known, we estimated alternatives, making various hypothetical assumptions, wherein women would continue to take oral contraceptives after a first episode of thrombosis, or stop and switch to use of an intra‐uterine device, condom or the progestogen‐ only pill. Depending on the assumptions with regard to recurrence risk and the existence of possible subgroups with genetic coagulation defects, the cost‐ benefit ratio of advising against the use of oral contraceptives after a first thrombosis varied tremendously.

Conclusions. Our analysis shows that we lack the necessary data for recurrence risk of venous thrombosis during continuing use of oral contraceptives, or after switching to other modes of contraception. This reflects the clinical uncertainties that result in highly contradictory advice to young women who have experienced a first thrombosis. Only follow‐up studies on recurrence risk will settle the issue.
Efficacy of sequential hormone replacement therapy in the treatment of hypercholesterolemia among postmenopausal women
Authors: TONSTAD S. , OSE L. , GØRBITZ C. , DJØSELAND O. , BARD J. M. , FRUCHART J. C.
Published: August 2009

Abstract. Objectives. To test the efficacy of hormone replacement therapy (HRT) and dietary therapy, compared to dietary therapy, in lowering LDL cholesterol levels among postmenopausal women.

Design. A prospective parallel randomized study of sequential 17β‐oestradiol and norethisterone acetate or placebo for 48 weeks.

Setting. A University outpatient lipid clinic.

Subjects. A total of 76 postmenopausal women, aged 43–60 years, with LDL cholesterol level ≥ 4.2 mmol I−1 treated with a lipid‐lowering diet.

Main outcome measures. Levels of lipids, lipoproteins, apolipoproteins, fibrinogen and glucose tolerance.

Results. Adherence to the diet was similar in both groups. Total and LDL cholesterol levels were reduced by 14% (95% CI, 11–17%) and 19% (95% CI, 14–23%), respectively, in the HRT group vs. 3% (95% CI. 0–7%) and 5% (95% CI, 0–11%) in the diet group. HRT reduced the levels of apolipoprotein B and lipoprotein(a). Levels of HDL cholesterol, HDL2, HDL3, triglycerides, lipoprotein populations and apolipoproteins. AI and AII remained unchanged. No adverse effects on glucose tolerance or on fibrinogen levels were observed. The reduction in LDL cholesterol was positively correlated with initial levels of LDL cholesterol and negatively correlated with body mass index.

Conclusions. HRT is effective in reducing elevated LDL cholesterol levels, and should be considered in the treatment of hyperlipidaemic postmenopausal women, in addition to dietary therapy.
Localized tuberculosis of the oesophagus: a rare condition
Authors: LEOTTA S. M. G. , ELSBORG L.
Published: August 2009

Abstract. This report describes the case of a male patient with progressive dysphagia, epigastric pain, odynophagia, generalized weakness and a mid‐oesophagus ulceration in which biopsies showed acid‐fast bacilli and histological evidence of tuberculosis. Culture of the biopsies and the sputum revealed mycobacterium tuberculosis. There were no respiratory symptoms, and radiographs did not reveal evidence of pulmonary tuberculosis. The patient responded well to antituberculous therapy and he is alive and well 7 years later, without any signs of relapse. The involvement of the oesophagus as the only demonstrable localization of tuberculosis is an extremely rare condition, which should always be considered as differential diagnosis in dyspepsia of unknown origin.
Plasma cholesteryl ester transfer protein and high‐density lipoproteins: new insights from molecular genetic studies
Authors: TALL A. R.
Published: August 2009

Abstract. Recent studies in transgenic mice provide strong evidence for a direct anti‐atherogenic role of high‐density lipoproteins (HDL) and highlight the importance of multiple gene interactions in the regulation of HDL levels. Plasma lipid transfer processes mediated by cholesteryl ester transfer protein (CETP) have a major impact on HDL levels, as revealed in studies of human genetic CETP deficiency and CETP transgenic mice. Subsequent to the discovery of an intron 14 CETP gene splicing defect, several new CETP gene mutations have been discovered recently in Japanese and other populations. One of these is an exon 15 missense mutation, changing amino acid 442 of CETP from aspartate to glycine. Population studies in Japan indicate that CETP gene mutations are sufficiently common to have a significant influence on HDL levels in the general population. Studies in transgenic mice show that CETP expression results in decreased levels of HDL cholesterol, but that the effects of CETP on HDL apolipoprotein A‐I (apoA‐I) content and size show important modulation by co‐expression with transgenes encoding human apoA‐I, apoC‐III and apoA‐II. In addition to the apparent antiatherogenic phenotype of human genetic CETP deficiency, high level expression of CETP in transgenic mice leads to accelerated atherosclerosis, illustrating the pro‐atherogenic potential of CETP expression.
The costs and effects of two different lipid intervention programmes in primary health care
Authors: TOMSON Y. , JOHANNESSON M. , ÅBERG H.
Published: August 2009

Abstract. Objective. To compare the costs and effects of two different intervention strategies for the nonpharmacological treatment of hypercholesterolaemia.

Design. Randomized, controlled trial. Subjects were randomly allocated to one of two intervention models and followed up for 1 year.

Setting. Vårby Health Centre, a primary care practice located in a suburb of Stockholm.

Subjects. Subjects with a total serum cholesterol in the range 7.0–7.8 mmol L−1 and no signs of ischaemic heart disease or diabetes mellitus, randomized to a low‐intensity (n = 35) or medium‐intensity (n = 41) intervention.

Intervention. Two strategies were used, one labelled medium‐intensity strategy which followed national current guidelines for nonpharmacological treatment of hypercholesterolaemia, the other was a low‐intensity strategy.

Main outcome measures. Total serum cholesterol and intervention costs.

Results. Both intervention strategies resulted in small (mean 3.5%) decreases in total cholesterol with no significant difference between the groups. The cost per subject in the low‐intensity group was SEK 753 and in the medium‐intensity group SEK 3614.

Conclusions. Because the effect of the two intervention programmes did not differ, the low‐intensity programme is to be preferred from a cost‐effectiveness point of view. If only one‐third of the population in Stockholm county with cholesterol levels ≥ 6.5 mmol L−1 are discovered by the primary health care system, and follow the treatment advice, the net savings in the low‐intensity model compared to the current guidelines here presented as the moderate‐intensity model, would be SEK 93 million.