bluuebunny/crossref_metadata_2025 huggingface dataset:
Audit and comprehensive health assessment programme in the primary healthcare of adults with intellectual disability: a pilot study
Authors: Lennox N. G. , Green M. , Diggens J. , Ugoni A.
Published: March 2003

International research has demonstrated significant shortcomings in the health of adults with intellectual disability (ID). Because general practitioners (GPs) are the main providers of primary healthcare for this population, strategies to improve general practice care are an important aspect of rectifying these shortcomings. The present pilot study aimed to determine the effect of various interventions on health maintenance activities and to assess their acceptability to GPs, with a view to informing larger scale studies. The GPs were recruited through an earlier questionnaire‐based postal survey. The GPs identified all their adult patients with ID, then obtained consent for participation from three patients randomly selected by the investigators. The GPs completed two self‐evaluation forms and case note audits 12 months apart, read a synopsis of the relevant literature provided by the researchers, and completed a comprehensive health assessment (CHA) of their three patients. Forty‐five GPs agreed to participate in the CHA programme (CHAP), and 15 completed the project. Thirty‐eight patients completed the project. The number of patient–GP dyads who completed the project was too small to demonstrate statistically significant changes in health issues over time. The GPs found that the synopsis of the literature was the best intervention for increasing knowledge and was also the most practical to use in general practice. The CHAP was the intervention that prompted the most action from the GP which would not have been undertaken otherwise. The CHAP appeared to provide a superior review process compared to the other interventions used in the present study. The numbers of health maintenance activities found to be overdue and the number of health issues detected as a result of the process were considerable. The CHAP served as a communication tool and an educative instrument, providing a basis for future studies and strategies to improve the general practice care of adults with ID.
Utilization of medical care among children with Down’s syndrome
Authors: Frid C. , Annerén G. , Rasmussen F. , Sundelin C. , Drott P.
Published: March 2003

Background The present authors have previously found an increased mortality rate in children with Down’s syndrome (DS) and a congenital heart defect (CHD). The aim of the present study was to investigate the utilization of medical care in relation to congenital malformations in DS.

Method Retrospectively, 211 children with DS born between 1973 and 1980 in the northern part of Sweden were followed up for at least 17 years (1973–1997). The duration of neonatal care was compared with that of children with DS born between 1995 and 1998 in the same region.

Results Neonatal care was reduced over time. Almost 50% of the children had CHD, and before 10 years of age, these subjects were admitted for inpatient care twice as often as children with DS who did not have malformations, and had more than 12 times as many inpatient days per month. The existence of a gastrointestinal or other malformation increased inpatient days per month four and two times, respectively, compared to healthy children with DS. During the first 10 years of life, children with DS and a CHD accounted for 71% of all inpatient days caused by infections. No gender differences were observed.

Conclusions At a group level, the presence of a CHD was the most important congenital abnormality in determining utilization of medical care and the burden of infections in the population of children with DS.
Low prevalence of abnormal cervical cytology in an institutionalized population with intellectual disability
Authors: Jaffe J. S. , Timell A. M. , Eisenberg M. S. , Chambers J. T.
Published: March 2003

Background

The present study was designed to determine the prevalence of abnormal cervical cytology in an institutionalized population with intellectual disability.

Method

A retrospective review of charts for 162 women at a large state‐owned facility was performed. Slides from 310 cervical Papanicolau smears were re‐screened by a cytotechnologist and then reviewed by a pathologist.

Results

The prevalence of abnormal cytology (three out of 162 participants) and biopsy confirmed that the prevalence cervical dysplasia (one out of 310 smears) was low.

Conclusion

The present preliminary study suggests that further investigation of the optimal interval for cervical cancer screening is warranted in this population.
Thyroid hormone treatment aiming at reduced, but not suppressed, serum thyroid‐stimulating hormone levels in nontoxic goitre: effects on bone metabolism amongst premenopausal women
Authors: Knudsen  , Faber  , SierbÆk‐nielsen  , Badstrup  , SØrensen  , HegedÜs
Published: March 2003

Knudsen N, Faber J, Siersbæk‐Nielsen K, Vadstrup S, Sørensen HA, Hegedüs L.(Frederiksberg Hospital; Herlev University Hospital; Copenhagen Municipal Hospital; Denmark). Thyroid hormone treatment aiming at reduced, but not suppressed, serum TSH levels in nontoxic goitre: effects on bone metabolism among premenopausal women. J Intern Med 1998; 243: 149‐54.

Objectives

To study the effects of six months' treatment with either T4 or T3, aiming at reduced but not totally suppressed serum TSH levels, as measured by a third generation TSH assay, on biochemical bone turnover parameters as well as bone mass in patients with nontoxic goitre.

Design

Prospective randomized study with a matched control group, not blinded.

Setting

Two University Hospital Clinics in Copenhagen.

Subjects and Intervention

Twenty‐four consecutive premenopausal women with moderate sized non‐toxic goitre. Fourteen patients randomized to T4 or T3 treatment for six months with monthly titration of the dose, aiming at TSH values between 0.005 and 0.2 mUL−1. Ten controls.

Main outcome measures

Serum parathyroid hormone (PTH), serum procollagen I C‐terminal propeptide (PICP), serum alkaline phosphatase, serum osteocalcin, u‐pyridinoline, u‐deoxypyridinoline, u‐hydroxyproline. Bone mass (BMD) at the lumbar spine and at both femoral necks.

Results

Serum TSH was generally kept within the desired interval. There was no difference in any marker of bone metabolism between the effects of T4 and T3. Consequently, these groups were combined in order to evaluate the effect of thyroid hormones on the bone and mineral metabolism. Thyroid hormone treatment resulted in increased levels of serum ionized calcium (Ca) (P=0.02), serum alkaline phosphatase (P=0.007), serum‐PICP (P=0.003), serum osteocalcin (P=0.02) and urinary excretion of deoxypridinoline (P=0.03) compared to untreated controls. Bone mass did not change.

Conclusion

Six months treatment with either T4 or T3 of premenopausal women with nontoxic goitre, aiming at reduced but not totally suppressed TSH values, resulted in biochemical signs of increased bone turnover, whereas bone mass remained unaltered. No differences were found between the effects of T4 or T3 treatment.
Gemfibrozil decreases autoantibodies against oxidized low‐density lipoprotein in men with combined hyperlipidaemia
Authors: Hoogerbrugge  , Kerkhofs  , Jansen
Published: March 2003

Hoogerbrugge N, Kerkhofs LGN, Jansen H (University Hospital Dijkzigt, Rotterdam, The Netherlands). Gemfibrozil decreases autoantibodies against oxidized low‐density lipoprotein in men with combined hyperlipidaemia. J Intern Med 1998; 243: 355–59.

Objectives

Gemfibrozil is the most widely used fibric acid for the management of combined hyperlipidaemia. It has beneficial effects in the prevention of coronary heart disease (CHD). The mechanisms by which it exerts this effect are not completely resolved. We studied whether gemfibrozil affects low‐density lipoprotein (LDL) size and LDL oxidation parameters in males with a moderate combined hyperlipidaemia at high risk for progressive atherosclerosis.

Design

Open treatment with 2 × 600 mg gemfibrozil daily for 12 weeks.

Setting

Outpatient lipid clinic of a tertiary referral centre.

Subjects

Twenty‐three patients with combined hyperlipidaemia and CHD or a positive family history for both CHD and hyperlipidaemia.

Main outcome measures

Effects on triglyceride (TG), autoantibodies to oxidized LDL, LDL pattern and resistance to oxidative modification.

Results

During treatment with gemfibrozil, plasma TG concentration decreased from 2.83 ± 0.85 to 2.02 ± 0.89 mmol L−1 (P < 0.001). All but one patient were shown to have LDL pattern B. The LDL pattern did not change upon treatment with gemfibrozil. The resistance to oxidation, reflected in the lagtime during in‐vitro oxidation slightly decreased from 105 ± 22 to 99 ± 18 min (P= 0.01). The concentration of autoantibodies against oxidized LDL indicates the rate of LDL oxidation in vivo. This concentration significantly decreased from 14.2 ± 9.9 to 13.1 ± 9.2 mg L−1 (P < 0.01).

Conclusions

The beneficial effect of gemfibrozil in reducing CHD may at least in part depend on a decrease of the rate of LDL oxidation in vivo.
Thymic carcinoids in multiple endocrine neoplasia type 1
Authors: Teh
Published: March 2003

Teh BT (Karolinska Hospital, Stockholm, Sweden). Thymic carcinoids in multiple endocrine neoplasia type 1 (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 501–4.

Thymic carcinoid is a rare malignancy with about 150 cases reported to date. It is associated with multiple endocrine neoplasia type 1 (MEN‐1), but compared with other MEN‐1‐related neoplasia little is known about it. We have recently described and studied 20 MEN‐1‐related cases and found that up to 25% of all reported thymic carcinoids are MEN‐1 related. It is an insidious tumour not associated with Cushing's syndrome or carcinoid syndrome. Local invasion, recurrence and distant metastasis are common with no known effective treatment. Its male predominance, the absence of loss of heterozygosity (LOH) in the MEN1 region, clustering in some MEN‐1 families and the findings of different MEN1 mutations in these clustered families suggest the involvement of additional aetiological factors. We propose that computed tomography (CT) or magnetic resonance imaging (MRI) of the chest should be included as part of the clinical workup for all MEN‐1 patients. Prophylactic thymectomy should be considered during subtotal or total parathyroidectomy on MEN‐1 patients to reduce the risk of this malignancy.
Effect of folic acid and betaine on fasting and postmethionine‐loading plasma homocysteine and methionine levels in chronic haemodialysis patients
Authors: Guldener C. , Janssen M. J. F. M. , Meer K. , Donker A. J. M. , Stehouwer C. D. A.
Published: March 2003

Objectives. To study fasting and postmethionine‐loading (increment and decrement) plasma homocysteine levels in end‐stage renal disease (ESRD) patients in relation to B‐vitamin status and after folic acid treatment without or with betaine.

Design. Plasma total homocysteine (tHcy) and methionine levels were measured in chronic haemodialysis patients after an overnight fast, and 6 and 24 h after an oral methionine load (0.1 g kg−1). The patients were subsequently randomized to treatment with folic acid 5 mg daily with or without betaine 4 g daily, and the loading test was repeated after 12 weeks. The patients were then re‐randomized to treatment with 1 or 5 mg folic acid daily for 40 weeks, after which a third loading test was performed.

Setting. Haemodialysis unit of university hospital and centre for haemodialysis.

Subjects. Twenty‐nine consecutive maintenance (> 3 months) haemodialysis patients, not on folic acid supplementation, 26 of whom completed the study.

Results. At baseline, the mean fasting, the 6 h postload and the 6 h postload increment plasma tHcy levels were increased as compared with those in healthy controls (46.8 ± 6.9 (SEM), 92.8 ± 9.1 and 46.0 ± 4.2 μmol L−1, respectively) and correlated with serum folate (r = −0.42, P = 0.02; r = −0.61, P = 0.001 and r = −0.54, P = 0.003, respectively), but not with vitamin B6 or vitamin B12. At week 12, these variables had all decreased significantly. Betaine did not have additional homocysteine‐lowering effects. At week 52, fasting and postload tHcy levels did not differ significantly between patients on 1 or 5 mg folic acid daily. Plasma tHcy half‐life and plasma methionine levels after methionine loading were not altered by folic acid treatment.

Conclusions. In chronic haemodialysis patients, fasting as well as postmethionine‐loading plasma tHcy levels depend on folate status and decrease after folic acid therapy. Increased postload homocysteine levels in these patients therefore do not necessarily indicate an impaired transsulphuration capacity only; alternatively, folate may indirectly influence transsulphuration. The elucidation of the complex pathogenesis of hyperhomocysteinaemia in chronic renal failure requires further investigation.
Oral anticoagulation in nonvalvular atrial fibrillation
Authors: Koefoed B. G. , Petersen P.
Published: March 2003

Chronic nonvalvular atrial fibrillation is associated with an overall risk of thromboembolic complications of 4.5% per year. Advancing age, prior stroke or transient cerebral ischaemia, diabetes, hypertension, and impaired function of the left ventricle are known risk factors. Placebo‐controlled trials have demonstrated that oral anticoagulant therapy with warfarin is effective for primary and secondary prevention of ischaemic stroke, reducing the risk by 68%. The effect of aspirin is still controversial, reducing the risk by 18–44%. Recent clinical trials have investigated the effect of warfarin given at a very low intensity alone or combined with aspirin. The results from the SPAF III study demonstrated that a combination of mini‐intensity warfarin plus aspirin was insufficient for stroke prevention in atrial fibrillation. More trials have now confirmed that oral anticoagulation at INR‐values below 2.0 is not effective for prevention of thromboembolic events in these patients. It is currently recommended that patients at a high risk of stroke are treated with warfarin at an intensity of INR 2.0–3.0. Patients younger than 65 years without other risk factors can be given aspirin 325 mg day–1.
The prevalence and prognosis of third‐degree atrioventricular conduction block: the Reykjavik Study
Authors: Kojic E. M. , Hardarson T. , Sigfusson N. , Sigvaldason H.
Published: March 2003

Objectives. The objectives of this study were to find the prevalence of third‐degree atrioventricular block in representative population sample and to estimate its prognostic significance. Most earlier studies have been performed on hospital patients and some professional groups.

Setting and subjects. In the Reykjavik Study, a prospective cardiovascular population study, 9139 men and 9773 women aged 33–79 years were examined in 1967–91. Electrocardiograms were taken and coded according to the Minnesota code. Third‐degree atrioventricular block was found in 11 persons, seven male and four female, an overall prevalence of 0.04%. All of these individuals had signs of dysrhythmia on electrocardiograms taken later, and in addition some other heart disease. The heart block was temporary in seven individuals (64%); six (55%) needed a pacemaker.

Conclusions. The prevalence of third‐degree atrioventricular block in this general population was low. The block was temporary in the majority of subjects. All had some underlying heart disease, which may affect the prognosis more than the heart block. Fewer subjects than expected were found to need a pacemaker.
Do ACE‐inhibitors suppress tumour necrosis factor‐α production in advanced chronic renal failure?
Authors: Stenvinkel P. , Andersson P. , Wang T. , Lindholm B. , Bergström J. , Palmblad J. , Heimbürger O. , Cederholm T.
Published: March 2003

Abstract. Stenvinkel P, Andersson P, Wang T, Lindholm B, Bergström J, Palmblad J, Heimbürger O, Cederholm T (Huddinge University Hospital and Karolinska Institute, Stockholm; Sweden). Do ACE‐inhibitors suppress tumour necrosis factor‐α production in advanced chronic renal failure? J Intern Med 1999; 246: 503–507.

Objectives. The serum levels of the catabolic cytokine TNF‐α are often raised in malnourished chronic heart failure patients as well as in chronic renal failure (CRF) patients. Angiotensin‐converting enzyme (ACE) inhibitors are often used in these patients and may decrease TNF‐α and IL‐1β levels in vitro and in vivo. The aim of this study was to find out whether CRF patients with ongoing ACE‐inhibitor treatment have lower TNF‐α levels.

Design. Cross‐sectional study.

Setting. Tertiary Referral Center and University Hospital.

Subjects. Ninety‐six predialysis patients (mean age 52 ± 1 years) with advanced CRF (glomerular filtration rate 7 ± 1 mL min–1).

Main outcome measures. Plasma levels of TNF‐α, subjective global assessment of nutritional status and data on ongoing antihypertensive treatment (ACE‐inhibitors, beta blockers, calcium channel blockers and angiotensin II (AII) receptor blockers).

Results. Patients treated with ACE‐inhibitors (n = 44) had significantly lower plasma TNF‐α levels (18.5 ± 1.2 vs. 26.6 ± 2.2 pg mL–1; P < 0.01) and were less frequently malnourished, relative to 52 patients not treated with ACE‐inhibitors. No significant difference in TNF‐α levels were observed when comparing patients with or without treatment with beta, calcium channel, or AII receptor blockers, respectively.

Conclusions. The present data suggest that the use of ACE‐inhibitors is associated with lower plasma TNF‐α and CRP levels as well as a lower prevalence of malnutrition in patients with advanced CRF. Further studies are needed to establish if there is a casual relationship between these findings and, if so, the molecular mechanism(s).
Gallstone ileus: endoscopic removal of a gallstone obstructing the upper jejunum
Authors: Lübbers H. , Mahlke R. , Lankisch P. G.
Published: March 2003

Abstract. Lübbers H, Mahlke R, Lankisch PG (Department of Internal Medicine, Municipal Clinic, Lüneburg, Germany). Gallstone ileus: endoscopic removal of a gallstone obstructing the upper jejunum (Case Report). J Intern Med 1999; 246: 593–597.

In a 91‐year‐old female patient admitted with an ileus, ultrasound and computed tomography demonstrated the obstruction of the upper jejunum by a large gallstone. Due to concurrent diseases the patient was unfit for surgery. An attempt was made to remove the impacted stone endoscopically. After successful mobilization and fragmentation by mechanical lithotripsy the obstruction was cleared away. Since the patient improved considerably after this procedure, the gallbladder and the cholecystoduodenal fistula were left in place.
The risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg
Authors: Lindmarker P. , Schulman S. ,   THE DURAC TRIAL STUDY GROUP
Published: March 2003

Abstract. Lindmarker P, Schulman S, the DURAC Trial Study Group (Karolinska Hospital, Karolinska Institute, Stockholm, Sweden) The risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg. J Intern Med 2000; 247: 601–606.

Objectives. To investigate the risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg.

Design. An open prospective long term follow‐up multicentre trial. Patients were followed by frequent outpatient visits at each centre during the first 12 months after inclusion and thereafter annually.

Setting. Sixteen hospitals in central Sweden.

Subjects. A total of 790 consecutive patients with objectively verified first episode of acute deep vein thrombosis and without diagnosed malignant disease were recruited from a randomized study comparing 6 weeks with 6 months of oral antivitamin K therapy as secondary thromboprophylaxis.

Main outcome measures. Deep vein thrombosis in the contralateral leg was confirmed by venography or ultrasound. With regard to the ipsilateral leg, venography was required.

Results. A recurrent episode of venous thromboembolism was documented in 192 patients after a mean (±SD) period of 31(±29) months. In 26 additional patients with ipsilateral symptoms the diagnostic critera were not fulfilled. One hundred and eleven patients have deceased and 69 patients withdrew from the study. The 392 patients without recurrent episodes were followed for a median of 96 months with 90% for at least 48 months. An objectively verified recurrent contralateral and ipsilateral deep vein thrombosis occurred in 95 and 54 cases, respectively, and in 41 patients pulmonary embolism was documented. In two patients thromboses with unusual locations were registered. The risk of contralateral versus ipsilateral recurrence was significantly increased with a risk ratio of 1.6 (95% confidence interval 1.4–1.9) in a time to event model. In a multivariate analysis none of the investigated variables were significantly associated with the side of recurrent thrombosis.

Conclusions. The risk of a recurrent deep vein thrombosis is increased in the contralateral leg. This brings into question the importance of an impaired venous flow for recurrent episodes of thrombosis.
Early postoperative growth hormone levels: high predictive value for long‐term outcome after surgery for acromegaly
Authors: Valdemarsson S. , Ljunggren S. , Bramnert M. , Norrhamn O. , Nordström C. H.
Published: March 2003

Abstract. Valdemarsson S, Ljunggren S, Bramnert M, Norrhamn O, Nordström CH (Lund University Hospital, Lund, and Malmö University Hospital, Malmö, Sweden). Early postoperative growth hormone levels: high predictive value for long‐term outcome after surgery for acromegaly. J Intern Med 2000; 247: 640–650.

Objectives. To explore the prognostic value of early – within 1 week – postoperative growth hormone (GH) measurements with regard to outcome after surgery for acromegaly in a short‐ and a long‐term perspective.

Design. Retrospective study of patients operated on between 1987 and 1998, including follow‐up for up to 60 months.

Setting. University hospital.

Subjects. Sixty‐eight patients with acromegaly.

Intervention. Pituitary surgery aiming at adenomectomy with preservation of pituitary function.

Main outcome measures. The effect of the operation was evaluated after 3 months, mostly by means of an oral glucose load or by insulin‐like growth factor 1 (IGF‐1). The specificity, sensitivity and the predictive values of an early postoperative mean GH concentration ≤ 4.8 mU L–1, as well as of the GH response to thyrotropin‐releasing hormone (TRH) 3 months after surgery, were calculated with regard to outcome of the operation in both 3‐month and long‐term perspectives.

Results. Fifty patients (73.5%) showed a satisfactory effect at the evaluation 3 months postoperatively; 45 of these were followed between 12 and 60 months. Relapse was registered in five cases: 12, 12, 24, 24 and 48 months after surgery.

In the long‐term perspective, the predictive value of an early mean GH ≤ 4.8 mU L–1 was 93.6% with regard to a satisfactory effect of surgery, compared with 90.2% for a normalized somatomedin C (SmC)/IGF‐1 and 90.0% for an absent GH response after TRH. An early mean GH > 4.8 mU L–1 had a 77.8% predictive value for persistent or recurrent disease, compared with 85.7% for persistently increased SmC/IGF‐1 and 68.8% for an abnormal GH release after TRH 3 months after surgery.

In the short‐term perspective, the specificity and the predictive value of an early GH ≤ 4.8 mU L–1 were 77.3 and 97.1%, respectively. Early GH > 4.8 mU L–1 had a 94.4% sensitivity but a predicative value of only 63.0% for an unsatisfactory effect.

Conclusion. Measurement of GH within 1 week after surgery is highly predictive for outcome of surgery for acromegaly. Specifically, an early mean GH ≤ 4.8 mU L–1 is as predictive for a satisfactory effect of treatment as a normalized IGF‐1 3 months after surgery. Early postoperative GH values > 4.8 mU L–1 have a high sensitivity for persistent or recurrent disease in both the short‐ and long‐term perspectives, but lower predictive value. The usefulness of the TRH test can be questioned.
Insulin resistance and intima–media thickness in the carotid and femoral arteries of clinically healthy 58‐year‐old men. The Atherosclerosis and Insulin Resistance Study (AIR)
Authors: Bokemark L. , Wikstrand J. , Attvall S. , Hulthe J. , Wedel H. , Fagerberg B.
Published: March 2003

Abstract. Bokemark L, Wikstrand J, Attvall S, Hulthe J, Wedel H, Fagerberg B (Sahlgrenska University Hospital, and the Nordic School of Public Health, Göteborg, Sweden). Insulin resistance and intima–media thickness in the carotid and femoral arteries of clinically healthy 58‐year‐old men. The Atherosclerosis and Insulin Resistance Study (AIR). J Intern Med 2001; 249: 59–67.

Objective. To examine whether insulin resistance was associated with ultrasound‐assessed measures of atherosclerosis in men with varying degrees of obesity.

Design. A random selection of subjects from the general population were divided into quintiles of a body mass index/blood glucose score that was shown to be a valid and reproducible index of the degree of insulin sensitivity as assessed by the clamp technique. Every fourth man in quintiles 1 and 5 and every 20th man in quintiles 2–4 (in total, 104 men) were selected for an ultrasound examination of the carotid and femoral arteries and a euglycaemic hyperinsulinaemic clamp examination, adjusted for fat‐free mass.

Setting. A university hospital.

Subjects. A total of 104 clinically healthy 58‐year‐old men of Swedish ancestry.

Results. The mean common carotid artery intima–media thickness (IMT), but not the common femoral IMT, correlated significantly with glucose infusion rate (GIR) (r = − 0.20, P < 0.05), systolic blood pressure (r = 0.20, P < 0.05), pulse pressure (r = 0.23 P < 0.01), heart rate (r = 0.20, P < 0.05), HDL cholesterol (r = − 0.18, P < 0.05), log triglycerides (r = 0.28, P < 0.01), apoA1 (r = − 0.20, P < 0.05), apoB (r = 0.21, P < 0.05), LDL particle size (r = − 0.22, P < 0.05) and plasma insulin (r = 0.20, P < 0.05). In a multiple regression, common carotid IMT was independently associated with log triglycerides (β = 0.25, P = 0.012) and pulse pressure (β = 0.21, P = 0.031) (R2 = 8.7%, P = 0.005)

Conclusions. Insulin sensitivity, measured with the gold standard euglycaemic hyperinsulinaemic clamp method, showed similar associations with ultrasound‐assessed measures of atherosclerosis in the carotid arteries as established cardiovascular risk factors, but only triglycerides and pulse pressure contributed independently to the variability in the common carotid intima–media thickness.
Almost all institutionalized women are osteoporotic, when measured by heel and finger ultrasound
Authors: Ekman A. , Michaëlsson K. , Ljunghall S. , Mallmin H.
Published: March 2003

Abstract. Ekman A, Michaëlsson K, Ljunghall S, Mallmin H (University Hospital, Uppsala, Sweden). Almost all institutionalized women are osteoporotic, when measured by heel and finger ultrasound. J Intern Med 2001; 249: 173–180.

Objectives. Since there is a need for simple methods to identify individuals with osteoporosis, we investigated bone status (heel and finger) with ultrasound in an institutionalized elderly population and studied the association between these measures, risk factors for osteoporosis and prevalent osteoporotic fractures.

Design. Cross‐sectional study.

Subjects. Nursing home residents, 237 women and 84 men, mean age 84 years.

Results. Altogether 82% of those eligible could undergo heel ultrasound, 65% finger ultrasound and 41% measurements at both sites. Using a transcription of the WHO criterion of osteoporosis, 95% of the women who underwent heel ultrasound were classified as osteoporotic (mean T‐score =–4.8) and 92% had Z‐scores below zero (mean Z‐score=–1.6), whereas 51% of the men were osteoporotic (mean T‐score=–2.6) and 77% had Z‐scores below zero (mean Z‐score=–1.3). Based on finger ultrasound measurements, 99% of the women were classified as osteoporotic (mean T‐score=–5.0) and 93% had Z‐scores below zero (mean –1.6). The variations in ultrasound values were only moderately explained by age, current weight and walking ability. Amongst women, the association with a prevalent osteoporotic fracture decreased by 43% (95% CI=10–63%) for every SD increase in speed of sound (SOS) of the heel, but no such relationship was found for finger SOS.

Conclusions. Our results from ultrasound measurements at two different anatomical sites indicate that virtually all institutionalized elderly women could be classified as osteoporotic, when measured by these techniques.
Bioinformatic and experimental tools for identification of single‐nucleotide polymorphisms in genes with a potential role for the development of the insulin resistance syndrome
Authors: Bennet A. M. , Näslund T. I. , Morgenstern R. , De Faire U.
Published: March 2003

Abstract. Bennet AM, Näslund TI, Morgenstern R & De Faire U (Divisions of Cardiovascular Epidemiology and Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institute and Department of Medicine, Karolinska Hospital, Stockholm, Sweden). Bioinformatic and experimental tools for identification of single nucleotide polymorphisms in genes with a potential role for the development of the insulin resistance syndrome. J Intern Med 2001; 249: 127–136.

Objectives. Genes with a possible role for the development of the insulin resistance syndrome (IRS) were scanned for novel single‐nucleotide polymorphisms (SNPs) using bioinformatics.

Methods. GenBank mRNA sequences were compared to the human EST database using gapped BLAST, software that is available on the internet. Mismatches between the search and the EST sequences indicated potential SNPs. Thirty‐two SNPs in 13 genes were randomly chosen for experimental verification. PCR and direct sequencing were used to determine the ‘true’ SNPs. A random sample of 30 Swedish men with slightly elevated diastolic blood pressure (85–94 mmHg) obtained from a population‐based study was selected for the sequencing. After completion of these stages, the potential SNPs were checked against the large and rapidly expanding SNP databases HGBASE and NCBI.

Results. EST searches of 146 genes revealed 106 potential SNPs in 44 genes. Experimental analysis of 32 of these potential SNPs verified two SNPs; endothelin receptor A 1471 G/C (3′ UTR) and PAI‐1 Trp514Arg from a T/C exchange. These two SNPs were also identified in the NCBI and HGBASE databases together with two polymorphisms that were not experimentally identified in our homogenous Swedish population. Overall, the HGBASE and NCBI databases contained entries of 22% (23 out of 106) of the SNPs identified through our EST searches.

Conclusions. In the search for genetic variations causing complex diseases like IRS in homogenous populations (such as the Swedish one used here), important information can be obtained through bioinformatic searches of human genome databases and experimental verification.
Geographical pattern of female deaths from myocardial infarction in an urban population: fatal outcome out‐of‐hospital related to socio‐economic deprivation
Authors: Tydén P. , Engström G. , Hansen O. , Hedblad B. , Janzon L.
Published: March 2003

Abstract. Tydén P, Engström G, Hansen O, Hedblad B, Janzon L (Malmö University Hospital, Lund University, Malmö, Sweden). Geographical pattern of female deaths from myocardial infarction in an urban population: fatal outcome out‐of‐hospital related to socio‐economic deprivation. J Intern Med 2001; 250: 201–207.

Objective. This study of myocardial infarction (MI) amongst urban women has sought to assess whether there are differences in fatal outcome, in‐hospital respectively out‐of‐hospital, between residential areas defined in terms of socio‐economic circumstances.

Design. Register‐based surveillance study 1986–95.

Setting. Seventeen residential areas in the city of Malmö, Sweden.

Subjects. Women 20–74 years of age.

Main outcome measures. Differences in fatal outcome, in‐hospital respectively out‐of‐hospital, between residential areas were expressed in terms of age‐adjusted odds ratios (ORs), calculated by means of logistic regression. Socio‐economic circumstances in the areas were expressed in terms of a composite score.

Results. Between residential areas there were marked and statistically significant differences in incidence (range 124–328/105, P < 0.001, d.f.=16) and mortality (range 38–132/105, P < 0.005, d.f.=16). Area rates of mortality covaried with incidence (r=0.85, P < 0.001) and with odds ratios of fatal outcome out‐of‐hospital (r=0.52, P=0.031) but not in‐hospital. The odds ratios of fatal outcome out‐of‐hospital decreased in a statistically significant stepwise fashion from areas in the lowest socio‐economic quintile (reference) to areas in the highest socio‐economic quintile (OR: 0.67, 95% CI: 0.48–0.94). There was no corresponding association with the odds ratios of fatal outcome in‐hospital.

Conclusions. The high rate of mortality from MI amongst women in areas with deprived socio‐economic circumstances was related to deaths occurring out‐of‐hospital. In order to assess the preventive potential there is a need for further studies that may clarify to what extent the association with socio‐economic circumstances can be explained by other factors and conditions known to influence the probability of survival.
The NciI polymorphism in the cyclin D1 gene and sporadic primary hyperparathyroidism
Authors: Correa P. , Lundgren E. , Rastad J. , Åkerström G. , Westin G. , Carling T.
Published: March 2003

Abstract. Correa P, Lundgren E, Rastad J, Åkerström G, Westin G, Carling T (Uppsala University Hospital, Uppsala, Sweden). The NciI polymorphism in the cyclin D1 gene and sporadic primary hyperparathyroidism. J Intern Med 2001; 250: 516–520.

Objectives. The cell cycle regulator cyclin D1 plays an important role in parathyroid tumourigenesis. The NciI polymorphism in exon 4 has recently been associated with early onset of hereditary nonpolyposis colorectal cancer and is a prognostic indicator of nonsmall cell lung cancer and squamous cell carcinomas. Furthermore, a limited study of 28 primary hyperparathyroidism (pHPT) patients displayed a tendency of NciI influence on HPT development. We hypothesized that the NciI polymorphism may relate to a risk of developing pHPT.

Design, setting and subjects. We genotyped 182 patients with sporadic pHPT and matched controls for the cyclin D1 polymorphism. A total of 88 pHPT patients and controls were recruited via a health‐screening.

Results. The frequency distribution of the NciI genotypes NN, Ni, and ii were in pHPT patients and controls 22, 44 and 34%, and 26, 49 and 25%, respectively. The calculated allele frequencies were A=0.56; G=0.44 in cases and A=0.49; G=0.51 in controls. The frequency distributions did not differ comparing cases and controls when subgrouped after age and menopausal status. The NciI genotypes were not significantly associated with age of the individuals, serum (s)‐calcium, s‐parathyroid hormone (PTH), bone mineral density (BMD) or parathyroid tumour weight in any of the groups of pHPT patients or controls.

Conclusions. No significant differences in distribution of the genotypes could be detected between the groups, suggesting that the polymorphism has minor or no pathogenic importance in the development of pHPT. Our results suggest that determination of the NciI polymorphism in the cyclin D1 gene is not a clinically useful tool for prediction of pHPT.
Oral oestradiol/trimegestone replacement reduces procarboxypeptidase U (TAFI): a randomized, placebo‐ controlled, 12‐week study in early postmenopausal women
Authors: Post M. S. , Hendriks D. F. , Van Der Mooren M. J. , Van Baal W. M. , Leurs J. R. , Emeis J. J. , Kenemans P. , Stehouwer C. D. A.
Published: March 2003

Abstract. Post MS, Hendriks DF, van der Mooren MJ, van Baal WM, Leurs JR, Emeis JJ, Kenemans P, Stehouwer CDA (VU university medical center, Amsterdam, The Netherlands; University of Antwerp, Wilrijk, Belgium; and Gaubius Laboratory, TNO‐PG, Leiden, The Netherlands). Oral oestradiol/trimegestone replacement reduces procarboxypeptidase U (TAFI): a randomized, placebo‐controlled, 12‐week study in early postmenopausal women. J Intern Med 2002; 251: 245–251.

Objective. To investigate the effects of short‐term postmenopausal oral hormone administration on plasma levels of procarboxypeptidase U (proCPU, thrombin‐activatable fibrinolysis inhibitor, EC 3.4.17.20), an inhibitor of fibrinolysis, in healthy early postmenopausal women.

Design. A prospective, randomized, placebo‐controlled study.

Setting. Outpatient clinic of the Department of Obstetrics and Gynaecology.

Subjects. Seventy‐seven healthy early postmenopausal women were screened of whom 65 were randomized. Analyses were based on 60 participants.

Interventions. The women received oral micronized oestradiol 2 mg either alone (E2 group, n=16), or sequentially combined with dydrogesterone 10 mg (E2 + D group, n=14) or trimegestone 0.5 mg (E2 + T, n=14), or placebo (n=16) for 12 weeks.

Main outcome measure. ProCPU concentrations at baseline, and at 4 and 12 weeks of treatment.

Results. Four weeks of E2 + T was associated with a significant decrease in the fasting proCPU concentration, which was sustained after 12 weeks [t=0: 636 ± 57 U L–1 (mean ± SD); t=4: 583 ± 63 U L–1; t=12: 589 ± 48 U L–1; ANCOVA versus placebo: P=0.011]. The percentage change from baseline versus placebo in this group was –8.4% [95% confidence interval (CI) –15.7 to –1.1] after 4 weeks and –5.9% (95% CI –11.7 to –0.1) after 12 weeks. There were no significant changes versus placebo in the E2 group nor in the E2 + D group.

Conclusion. Short‐term treatment with E2 + T, but not E2 alone or E2 + D, lowers proCPU concentration. These findings add to accumulating evidence suggesting that different progestagens added to oestrogen replacement may differentially affect the risk of arterial and venous disease.
Primary and secondary prevention in cardiovascular disease: an old‐fashioned concept?
Authors: VAN VENROOIJ F. V. , STOLK R. P. , BANGA J. D. , ERKELENS D. W. , GROBBEE D. E.
Published: March 2003

Abstract. van Venrooij FV, Stolk RP, Banga JD, Erkelens DW, Grobbee DE (Julius Centre for General Practice and Patient Oriented Research, University Medical Center, Utrecht, The Netherlands). Primary and secondary prevention in cardiovascular disease: an old‐fashioned concept? (Review). J. Intern Med 2002; 251: 301–306.

Objective. Is the concept of primary and secondary cardiovascular prevention an old‐fashioned concept that needs to be re‐defined?

Design. Discussion paper.

Results. Cardiovascular prevention means reduction of absolute risk for cardiovascular disease (CVD), irrespective of clinical stage.

Conclusion. For the calculation of an individual probability to develop CVD all factors that contribute to the risk must be taken into account, including previous CVD events.
Effect of medroxyprogesterone on pulmonary arterial pressure, exhaled nitric oxide, ECG and arterial blood gases
Authors: SAARESRANTA T. , UOTILA P. , SARASTE M. , IRJALA K. , HARTIALA J. , POLO O.
Published: March 2003

ABG arterial blood gases BE base excess BP blood pressure COPD chronic obstructive pulmonary disease ECG electrocardiogram FSH follicle stimulating hormone MPA medroxyprogesterone acetate NO nitric oxide INOS inducible nitric oxide synthase PAP pulmonary arterial pressure
Lipoprotein lipase polymorphisms and responses to long‐term overfeeding
Authors: UKKOLA O. , TREMBLAY A. , BOUCHARD C.
Published: March 2003

Abstract. Ukkola O, Tremblay A, Bouchard C (Louisiana State University, Baton Rouge, LA, USA; University of Oulu, Oulu, Finland; and Laval University, Ste‐Foy, Quebec, Canada). Lipoprotein lipase polymorphisms and responses to long‐term overfeeding. J Intern Med 2002; 251: 429–436.

Objectives. The role of the lipoprotein lipase (LPL) gene Hind III, S447X, Bam HI and Pvu II polymorphisms on body composition and lipid and lipoprotein changes in response to long‐term overfeeding was studied.

Subjects. Twelve pairs of male monozygotic twins ate a 4.2 MJ day−1 energy surplus, 6 days a week, during a period of 100 days.

Results. Overfeeding induced a decrease in high‐density lipoprotein 2 cholesterol (HDL2‐C) and HDL2‐C to HDL3‐C ratio in the H2H2 (n = 12) subjects of the LPL Hind III polymorphism. In contrast, the H1H1/H1H2 (n = 12) subjects experienced increases both in the HDL2‐C and HDL2‐C to HDL3‐C ratio (P = 0.009 and 0.007, respectively, for differences in percentage changes between H2H2 and H1H1/H1H2). In addition, the H2H2 genotype was associated with higher levels of very‐low‐density lipoprotein triglyceride (VLDL‐TG) (P < 0.03) and VLDL‐C (P < 0.05) before and after overfeeding and higher HDL‐TG levels (P < 0.003) after overfeeding. Postheparin lipoprotein lipase (PH‐LPL) activity tended to increase in H1H1/H1H2 and decrease in H2H2 subjects. The H2H2 subjects had lower total HDL‐C than those with the genotype H1H1/H1H2 4 months and 5 years after overfeeding (P = 0.04 and 0.10, respectively). The plasma lipid differences were similar amongst subjects with the S447S (n = 4) genotype of the S447X and H2H2 genotype of the Hind III polymorphisms. Body composition changes in response to overfeeding were not different between the Hind III genotypes. LPL Pvu II and Hind III polymorphisms were associated weakly with body weight gain (P = 0.015–0.039) but strongly with adipose tissue LPL activity (P < 0.01) after the caloric surplus.

Conclusions. We conclude that the H2H2 subjects of the LPL gene Hind III polymorphism experience a decrease in the concentration of antiaterogenic lipoproteins when they are exposed to long‐term positive energy balance. This may have been partly caused by a diminished catabolism of TG‐rich particles in H2H2 subjects. LPL Pvu II and Bam HI polymorphisms were associated with body weight gain and adipose tissue LPL activity. Genetic variation at the LPL locus could thus be one of the factors responsible for the inter‐individual differences observed in plasma lipid and lipoprotein responses to chronic positive energy balance. It must be kept in mind that the sample size for this study was small. Nonetheless, it provides useful information on the genes and pathways that should be further explored.
Inhibitory effects of N‐acetylcysteine on scavenger receptor class A expression in human macrophages
Authors: SVENSSON L. , NORÉN K. , WIKLUND O. , LINDMARK H. , OHLSSON B. , HULTÉN L. Mattsson
Published: March 2003

Abstract. Svensson L, Norén K, Wiklund O, Lindmark H, Ohlsson B, Mattsson Hultén L (Wallenberg Laboratory for Cardiovascular Research, The Sahlgrenska Academy at Göteborg University, Göteborg; and AstraZeneca, Mölndal, Sweden). Inhibitory effects of N‐acetylcysteine on scavenger receptor class A expression in human macrophages. J Intern Med 2002; 251:.

Objective. The formation of foam cells from monocyte‐derived macrophages involves the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit lipoprotein oxidation and may also modulate gene expression. We investigated the effect of the antioxidant N‐acetylcysteine on the expression of the class A scavenger receptor (SR‐A) types I and II in human macrophages.

Design. Monocytes and macrophages from healthy blood donors and plaque‐derived macrophages from patients undergoing carotid endartherectomy were used for experiments. SR‐A mRNA was analysed with quantitative and semiquantitative reverse transcription‐polymerase chain reaction, and ligand binding and uptake were assessed with 125I‐labelled acetylated low‐density lipoprotein (LDL).

Results. Incubation of monocytes and monocyte‐derived macrophages with N‐acetylcysteine decreased both SR‐A I and II mRNA expression. N‐Acetylcysteine also reduced SR‐A mRNA in lesion‐derived cells. Binding and uptake of 125I‐acetylated LDL was decreased after brief incubation with N‐acetylcysteine. After longer periods of incubation with N‐acetylcysteine we observed an increased degradation of lipoproteins.

Conclusions. Our results imply that N‐acetylcysteine leads to a decrease in SR‐A mRNA and initially also to an attenuated uptake of modified lipoproteins. This adds more to the knowledge about the cellular actions of this drug.
The enigma of increased non‐cancer mortality after weight loss in healthy men who are overweight or obese
Authors: NILSSON P. M. , NILSSON J.‐Å. , HEDBLAD B. , BERGLUND G. , LINDGäRDE F.
Published: March 2003

Abstract. Nilsson PM, Nilsson J‐A, Hedblad B, Berglund G, Lindgärde F. (University Hospital, Malmö, Sweden). The enigma of increased non‐cancer mortality after weight loss in healthy men who are overweight or obese. J Intern Med 2002; 252: 70−78.

Objective. To study effects on non‐cancer mortality of observational weight loss in middle‐aged men stratified for body mass index (BMI), taking a wide range of possible confounders into account.

Design. Prospective, population based study.

Setting. Male population of Malmö, Sweden.

Participants. In all 5722 men were screened twice with a mean time interval of 6 years in Malmö, southern Sweden. They were classified according to BMI category at baseline (<21, 22−25, overweight: 26−30, and obesity: 30+ kg m−2) and weight change category until second screening (weight stable men defined as having a baseline BMI ± 0.1 kg m−2 year−1 at follow‐up re‐screening).

Main outcome measures. Non‐cancer mortality calculated from national registers during 16 years of follow‐up after the second screening. Data from the first year of follow‐up were excluded to avoid bias by mortality caused by subclinical disease at re‐screening.

Results. The relative risk (RR; 95% CI) for non‐cancer mortality during follow‐up was higher in men with decreasing BMI in all subgroups: RR 2.64 (1.46−4.71, baseline BMI <21 kg m−2), 1.39 (0.98−1.95, baseline BMI 22−25 kg m−2), and 1.71 (1.18−2.47, baseline BMI 26+ kg m−2), using BMI‐stable men as reference group. Correspondingly, the non‐cancer mortality was also higher in men with increasing BMI, but only in the obese group (baseline BMI 26+ kg m−2) with RR 1.86 (1.31−2.65). In a subanalysis, nonsmoking obese (30+ kg m−2) men with decreased BMI had an increased non‐cancer mortality compared with BMI‐stable obese men (Fischer's test: P=0.001). The mortality risk for nonsmoking overweight men who increased their BMI compared with BMI‐stable men was also significant (P=0.006), but not in corresponding obese men (P=0.094).

Conclusions. Weight loss in self‐reported healthy but overweight middle‐aged men, without serious disease, is associated with an increased non‐cancer mortality, which seems even more pronounced in obese, nonsmoking men, as compared with corresponding but weight‐stable men. The explanation for these observational findings is still enigmatic but could hypothetically be because of premature ageing effects causing so‐called weight loss of involution.