bluuebunny/crossref_metadata_2025 huggingface dataset:
Offenders with intellectual disability: the size of the problem and therapeutic outcomes
Authors: Barron P. , Hassiotis A. , Banes J.
Published: March 2003

Background

People with intellectual disability (ID) who offend may be subject to a variety of disposals within the criminal justice system, or via diversion to health and social services in inpatient units or in community ID teams. Offenders with ID are a group with complex needs who may pose a recurrent risk to the public. Despite the significant number of offenders with ID, there is limited evidence on treatment effectiveness and outcomes.

Methods

A literature search of all electronic databases was undertaken, and journals were hand‐searched for clinical trials or case studies of interventions for offenders with ID. The main outcome was recidivism rates.

ResultsThere were no published clinical trials of offenders with ID. A series of small‐scale group cognitive‐behavioural treatments for sex offenders offers the most persuasive evidence of success in reducing recidivism.

Conclusion

Offenders with ID often receive inadequate services as a result of poor identification through the criminal justice system and research into effective treatments is rudimentary. Further studies are necessary in order to improve treatment efficacy and service provision for a complex group of individuals.
Different presentations of late‐detected phenylketonuria in two brothers with the same R408W/R111X genotype in the PAH gene
Authors: Giz·ewska M. , Cabalska B. , Cyrytowski L. , Nowacki P. , Z·ekanowski C. , Walczak M. , Józ´wiak I. , Koziarska D.
Published: March 2003

Although the clinical heterogeneity of phenylketonuria (PKU) is well established, some questions about this condition remain. Subjects from the same family who share the same mutations in the phenylalanine hydroxylase (PAH) gene are expected to display similar disease courses, and therefore, when blood phenylalanine (Phe) levels, genotype and dietary treatment are all similar, differences in patient outcomes require additional explanations. The present authors describe two entirely different courses of late‐detected PKU in two brothers with the same R408W/R111X genotype in the PAH gene. The older sibling was diagnosed with PKU at the age of 4 years and given treatment. His IQ was 97 at 26 years of age and moderate involvement of periventricular white matter was detected. The younger brother was diagnosed with PKU at the age of 11 months and given treatment. His IQ was < 25 at 22 years of age and severe dysmyelination changes were found by magnetic resonance imaging. The differences in the courses of the disease between these two brothers appear to be related to variations in their blood–brain barriers.
Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease
Authors: Valdemarsson  , Lindergård  , Tibblin  , Bergenfelz
Published: March 2003

Valdemarsson S, Lindergård B, Tibblin S, Bergenfelz A (Lund University Hospital, Sweden). Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease. J Intern Med 1998; 243: 115–22.

Objectives

.To evaluate the impact on bone turnover of primary hyperparathyroidism (pHPT) with special reference to patients with mild pHPT, using biochemical markers of bone formation and resorption.

Design

.A longitudinal study of patients with pHPT before and one year after surgical treatment.

Setting

.The Departments of Internal Medicine and Surgery, Lund University Hospital.

Subjects

.Forty consecutive patients with pHPT. Thirty of these patients had mild pHPT and are reported separately. Data on bone mineral was also compared to a reference population.

Intervention

All patients were operated upon and restudied one year later.

Main outcome measures

.Bone resorption and formation was studied by means of the serum concentrations of the telopeptide of the carboxyterminal region of type 1 collagen (ICTP) and of alkaline phosphatase (ALP), osteocalcin and the carboxyterminal propeptide of type 1 procollagen (PICP), respectively. Bone density was measured at the distal radius by single photon absorptiometry (SPA).

Results

.Bone formation markers consistenly decreased after parathyroid surgery: ALP from 3.51 ± 0.23 to 2.94 ± 0.21 µkat L−1 (P < 0.05), osteocalcin from 6.15 ± 0.53 to 2.89 ± 0.23 µg L−1 (P < 0.001) and PICP from 126.4 ± 10.9 to 96.0 ± 6.5 µg L−1 (P < 0.001). In parallel, the ICTP concentration, reflecting bone resorption, decreased from 5.10 ± 0.54 to 3.94 ± 0.34 µg L−1 (P < 0.001). There was not any significant change in distal radius bone mineral 1 one year after surgery. In the subgroup of patients classified as mild pHPT, a significant decrease was noted for osteocalcin, PICP and for ICTP but not for ALP, without significant changes in variables reflecting distal radius bone mineral content. Glomerular filtration rate was inversely correlated to serum levels of intact PTH, ionized calcium, alkaline phosphatase, osteocalcin and ICTP and directly correlated to the 1.25‐dihydroxy‐vitamin D concentrations.

Conclusions

.pHPT is associated with substantial changes in circulating levels of biochemical markers of bone formation and resorption. These findings are also present in patients with mild pHPT. Renal function should be considered in the evaluation of the impact of pHPT on bone turnover.
Factors modifying the prognosis in men with asymptomatic carotid artery disease
Authors: Hedblad  , Janzon  , Jungquist  , Ögren
Published: March 2003

Hedblad B, Janzon L, Jungquist G, Ögren M (Malmö University Hospital, Lund University, Malmö, Sweden). Factors modifying the prognosis in men with asymptomatic carotid artery disease.J Intern Med1998;243: 57–64.

Objectives.

Carotid artery stenosis is associated with an increased prevalence and incidence of ischaemic heart disease (IHD). The aim of this study has been to assess whether, in men with carotid artery stenosis, survival and incidence of stroke and myocardial infarction is different in men with and men free from IHD; and to characterize probands with incident cerebrovascular (CBV) event in terms of smoking, hypertension and leg artery disease.

Design

Population‐based cohort study, ‘Men born 1914’.

Setting

Malmö, a city in southern Sweden.

Subjects

A total of 478 of 621 men born in 1914, who in 1982 participated in ultrasound examination of the carotid arteries.

Main outcome measures

Morbidity and mortality during 10 years of followup.

Results.

Asymptomatic carotid artery stenosis was, in men free from IHD, associated with reduced survival and an increased incidence of serious CBV events that occurred, on average, 3.6 years after the examination.

In men with prevalent IHD, there was no relationship between carotid artery stenosis and incidence of CBV events. The main explanation to the lack of association seems to be the high vascular mortality rate in that group.

Conclusions.

It's our conclusion that in patients with asymptomatic carotid artery stenosis there is a great heterogeneity with regard to severity of disease and prognosis. Survival and incidence of stroke and myocardial infarction depends on whether patients have concomitant IHD.
Clostridium difficile colitis associated with a ‘triple’ regimen, containing clarithromycin and metronidazole, to eradicate Helicobacter pylori
Authors: Archimandritis  , Souyioultzis  , Katsorida  , Tzivras
Published: March 2003

Archimandritis A, Souyioultzis S, Katsorida M, Tzivras M (University of Athens Medical School, Laiko General Hospital, Athens, Greece). Clostridium difficile colitis associated with a ‘triple’ regimen, containing clarithromycin and metronidazole, to eradicate Helicobacter pylori (Case Report). J Intern Med 1998; 243: 251–53.

We describe a 54‐year‐old man with Helicobacter pylori (+) duodenal ulcer who developed Clostridium difficile associated colitis, 5 days after commencing a ‘triple’ regimen consisting of omeprazole 20 mg b.d., metronidazole 500 mg b.d. and clarithromycin 500 mg b.d., to eradicate H. pylori. Despite the fact that oral metronidazole did not prevent the disease, the patient did well after treatment with oral metronidazole plus a yeast preparation (Saccharomyces bulardii). No relapse occurred.
Secular trends in social patterning of cardiovascular risk factor levels in Sweden. The Northern Sweden MONICA Study 1986–1994
Authors: Peltonen  , Huhtasaari  , Stegmayr  , Lundberg  , Asplund
Published: March 2003

Peltonen M, Huhtasaari F, Stegmayr B, Lundberg V, Asplund K (Umeå University Hospital, Luleå‐Boden Hospital, Kalix Hospital, Sweden). Secular trends in social patterning of cardiovascular risk factor levels in Sweden. The North Sweden MONICA Study 1986–1994. J Intern Med 1998; 244: 1–9.

Objectives

In the Northern Sweden MONICA Study, levels of cardiovascular risk factors were determined in 1986, 1990 and 1994. The aim of this study was to assess the trends in cardiovascular risk factors, and to analyse the relationship between levels of risk factors and level of education.

Design

Cardiovascular risk factors were determined in cross‐sectional population studies of randomly selected 25–64 year old men and women in 1986, 1990 and 1994 (a total of 4742 individuals).

Results

Throughout the years 1986 to 1994, cardiovascular risk factor levels showed a marked social pattern, generally being more favourable among people with a university education. Serum cholesterol levels declined in all educational groups, but blood pressure declined significantly only in women with a university education. Body mass index increased, most markedly in men with university and in women with a secondary school education. Prevalence of cigarette smoking decreased significantly in young men. It increased markedly in low‐educated women so that the social gaps in smoking widened substantially over time. The improved level of education in the population at large was calculated to explain only a little of the risk factor changes between 1986 and 1994.

Conclusions

Trends in risk factor levels in different educational groups have been more diverging for women than for men. The most marked change in risk factor levels has been the decline in total serum cholesterol for both men and women in all educational groups.
Septic arthritis with Listeria monocytogenes during low‐dose methotrexate
Authors: Jansen T. L. Th. A. , Van Heereveld H. A. E. M. , Laan R. F. L. M. , Barrera P. , Van De Putte L. B. A.
Published: March 2003

Jansen TLThA, van Heereveld HAEM, Laan RFLM, Barrera P, van de Putte LBA (University Hospital Nijmegen, Nijmegen, The Netherlands). Septic arthritis with Listeria monocytogenes during low‐dose methotrexate (Case Report). J Intern Med 1998; 244: 87–90.

We describe a 22‐year‐old female with systemic lupus erythematosus and lymphopenia, who developed septic arthritis of the right knee with Listeria monocytogenes type 1/2 A, whilst on low‐dose methotrexate (MTX). So far, septic arthritis due to this microorganism has been reported in two other patients treated with low‐dose MTX, one having rheumatoid arthritis and the other psoriatic arthritis. No reports exist on patients treated with other cytotoxic antirheumatic therapies.
Clinical, biochemical and immunological characteristics of relapsers and non‐relapsers of thyrotoxicosis treated with anti‐thyroid drugs
Authors: Chowdhury T. A. , Dyer P. H.
Published: March 2003

Chowdhury TA, Dyer PH (Birmingham Heartlands Hospital, Birmingham, UK). Clinical, biochemical and immunological characteristics of relapsers and non‐relapsers of thyrotoxicosis treated with anti‐thyroid drugs. J Intern Med 1998; 244: 293–297.

Objectives

This study aims to correlate clinical, biochemical and immunological factors seen at diagnosis of thyrotoxicosis with subsequent relapse within 5 years.

Design

Retrospective review of case notes, and biochemical assessment at least 5 years after cessation of treatment.

Setting

A large general hospital endocrine clinic.

Subjects

Patients presenting with a first episode of thyrotoxicosis between 1988 and 1991 who were treated with antithyroid drugs for at least 18 months.

Main outcome measures. Relapse was determined by examination of hospital records, general practice records, patient questionnaire and thyroid function tests.

Results

A total of 216 subjects presented for the first time with thyrotoxicosis, of whom 89 (41.2%) suffered a relapse of the disease. On univariate analysis, clinical factors associated with increased relapse include younger age at diagnosis, goitre, marked tachycardia, requirement for higher maintenance dose of carbimazole, higher FT4 levels at diagnosis and smoking. Factors not predictive of relapse include presence of thyroid eye signs, positive family history, atrial fibrillation or congestive cardiac failure, acropachy or pretibial myxoedema, and presence or absence of thyroid autoantibodies. Logistic regression analysis showed relapse was predominantly determined by an FT4 > 56.2 nmol L−1, pulse rate > 110, presence of goitre and a positive smoking history (R2= 0.36, P < 0.001). Presence of these four factors predicted relapse in 76 (85.4%) of the 89 patients who relapsed.

Conclusions

Increased ‘toxicity’ of thyrotoxicosis, goitre and smoking are associated with relapse of thyrotoxicosis, and this may be helpful in determining which patients may be better managed with early ablative therapy.
The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia
Authors: Hoogerbrugge  , Jansen  , De Heide  , Zillikens  , Deckers  , BirkenhÄger
Published: March 2003

Hoogerbrugge N, Jansen H, de Heide L, Zillikens MC, Deckers JW, Birkenhäger JC (University Hospital Dijkzigt, Rotterdam, The Netherlands). The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia. J Intern Med 1997; 241: 151–56.

Objectives

Nicotinic acid, an effective drug for treatment of combined hyperlipidaemia, is often not tolerated because of side‐effects. Acipimox is a nicotinic acid like lipid lowering drug with less side‐effects. We studied whether the addition of acipimox to simvastatin improves the lipid profile in patients with a combined hyperlipidaemia.

Design

Randomized double‐blind placebo controlled crossover trial.

Setting

Outpatient lipid clinic of a tertiary referral centre.

Subjects

Eighteen patients with combined hyper‐ lipidaemia treated with diet and 20–40 mg simvastatin for at least 3 months.

Intervention.<

> Acipimox in a daily dose of 3 × 250 mg for 12 weeks.

Main outcome measures

Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as well as on LDL‐size and LDL‐resistance to oxidative modification.

Results

Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not statistically significant change in TG (−32%) and HDLc (+6%) levels was seen. All patients were found to have small dense LDL, with a size of 229 ± 4 Å. LDL size and the resistance to oxidation, reflected in the lag phase during in vitro oxidation, were not affected by the addition of acipimox. In a subgroup of 8 patients with the most severe hypertriglyceridaemia (baseline TG > 4 mmol L‐ [1]), acipimox induced a significant increase in HDLc (+15%, P < 0.01). The effects on TG (−41%), LDLc (−10%) and lag phase (+17%) were also more pronounced than in the group with a lower baseline TG, but none of these changes reached the level of significance.

Conclusions. Adding acipimox to simvastatin reduced Lp(a) and substantially but not significantly lowered TG. However, in patients with the highest TG levels, HDLc was also significantly improved.
Prevalence of APC resistance and its relationship to arterial and venous thromboembolism in a general population sample of elderly Swedish men: The Study of Men Born in 1913
Authors: Hansson P.‐O. , Eriksson E. , Welin L. , Eriksson H.
Published: March 2003

Abstract. Hansson P‐O, Eriksson E, Welin L, Eriksson H (Sahlgrenska University Hospital‐ÖSTRA, Göteborg, Sweden). Prevalence of APC resistance and its relationship to arterial and venous thromboembolism in a general population sample of elderly Swedish men: The Study of Men Born in 1913. J Intern Med 1999; 245: 593–600.

Background. Most studies of hereditary resistance to activated protein C (APC resistance) as a risk factor for venous thromboembolism are derived from case–control studies of hospitalized patients, whilst the importance of this condition in the general population has been only sparsely investigated.

Objective. To study the prevalence of APC resistance and its relationship to morbidity and mortality in a general population sample of elderly men.

Design. Cross‐sectional and prospective follow‐up study.

Setting. General community: The Study of Men Born in 1913.

Subjects. A random population sample of 404 men, all 75 years of age.

Main outcome measures. Four hundred and four men participated in a screening examination in 1988. The APC ratio was analysed in 382 of them. All the men were followed up for 5 years. Medical records were reviewed for all the men with a history of deep vein thrombosis, pulmonary embolism, myocardial infarction or stroke.

Results. Twenty‐five men (6.5%) were found to have APC resistance. The incidence of venous thromboembolism, myocardial infarction or stroke did not differ between men with or without APC resistance, either retrospectively or during follow‐up. Only two men experienced a deep vein thrombosis before the age of 80 and there was no case of pulmonary embolism. Mortality during 5 years of follow‐up did not differ between men with and without APC resistance.

Conclusion. The prevalence of APC resistance was 6.5% in this study of Swedish men. Although the size of the population sample is somewhat small, the study shows that, amongst elderly men, the association between APC resistance and venous thromboembolic disease was weak and men with this hereditary condition did not have any increase in morbidity or mortality compared with men without APC resistance.
Alarmingly high occurrence and case fatality of acute coronary heart disease events in Estonia: results from the Tallinn AMI register 1991–94
Authors: Laks T. , Tuomilehto J. , Jõeste E. , Mäeots E. , Salomaa V. , Palomäki P. , Pullisaar O. , Karu K. , Torppa J.
Published: March 2003

Objective. The purpose of this study was to produce stable estimates for the incidence, attack and mortality rates and case fatality of acute myocardial infarction (AMI) in Tallinn, the capital of Estonia.

Research design and methods. The Tallinn AMI register covers the population aged 25–64 years and official residents of Tallinn. The register follows the WHO MONICA project protocols in the data collection and diagnostic evaluation of the suspected AMI events and CHD death.

Results. Age‐standardized annual incidence, attack rate and mortality in men aged 35–64 years were high, varying from (per 100 000 per year) 352, 499 and 208, respectively, in 1991 to 438, 628 and 317, respectively, in 1993. In addition, in women, annual incidence, attack rate and mortality were high, varying from (per 100 000 per year) 82, 100 and 31, respectively, in 1991 to 110 and 142 in 1993 for the incidence and attack rate, and to 61 in 1992 for mortality. The percentage of out‐of‐hospital coronary death (sudden death) increased in men from 33 to 52% and in women from 24 to 42% during 1991–94, and the 28‐day case fatality increased in men from 42 to 58% and in women from 32 to 50%. In Tallinn, women with AMI were treated as actively as men with invasive treatment (thrombolysis, angioplasty, bypass surgery) during the acute phase of MI.

Conclusions. The incidence, attack rate and mortality of AMI were high in both men and women in Tallinn. The high 28‐day case fatality observed was primarily due to the high proportion of out‐of‐hospital deaths.
Plasma thrombopoietin levels in liver cirrhosis and kidney failure
Authors: Stockelberg D. , Andersson P.‐O. , Björnsson E. , Björk S. , Wadenvik H.
Published: March 2003

Abstract. Stockelberg D, Andersson P‐O, Björnsson E, Björk S, Wadenvik H (Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden) Plasma thrombopoietin levels in liver cirrhosis and kidney failure (Review). J Intern Med 1999; 246: 471–475.

Background. Recently, c‐Mpl ligand (thrombopoietin, TPO) has been cloned by several groups and found to be a primary regulator of thrombopoiesis. Its mRNA expression has been detected in several organs including kidneys, bone marrow stroma cells, muscles, and is very strongly expressed in the liver.

Objective. To clarify thrombopoiesis and the regulation of TPO in severe liver and renal failure.

Design. We analysed plasma TPO levels in patients with biopsy verified liver cirrhosis (n = 18; mean platelet count 115 ± 54 × 109 L–1), in patients on chronic haemodialysis as a result of end‐stage renal failure (n = 20; mean platelet count 295 ± 94 × 109 L–1), and in healthy individuals (n = 20; mean platelet count 250 ± 40 × 109 L–1). Plasma was prepared from EDTA‐anticoagulated whole blood and a commercially available ELISA kit was used for the analysis.

Results. The mean plasma TPO concentration amongst the normal individuals was 50 ± 14 pg mL–1. In the patients with liver cirrhosis and in patients on haemodialysis the mean TPO levels were 62 ± 19 pg mL–1 and 46 ± 17 pg mL–1, respectively. The mean plasma TPO concentration for the cirrhotic patients was significantly higher than the mean recorded for the healthy volunteers (P = 0.031), whereas no statistically significant differences in plasma TPO were seen between the group of end‐stage renal failure and normals.

Conclusion. Our results suggest that TPO production is maintained in liver cirrhosis and in renal failure, and that the thrombocytopenia in liver cirrhosis is not due to an impaired TPO production.
Beneficial effects of exercise training in heart failure patients with low cardiac output response to exercise – a comparison of two training models
Authors: Gordon A. , Tyni‐Lenné R. , Jansson E. , Jensen‐Urstad M. , Kaijser L.
Published: March 2003

Abstract.Gordon A, Tyni‐Lenné R, Jansson E, Jensen‐Urstad M, Kaijser L (Karolinska Institute at the Huddinge University Hospital, SE‐141 86 Huddinge, Sweden) Beneficial effects of exercise training in heart failure patients with low cardiac output response to exercise – a comparison of two training models.J Intern Med1999;246: 175–182.

Background.Exercise capacity of patients with chronic heart failure (CHF) correlates poorly with estimates of cardiac function. Yet, it has been suggested that only patients without severely impaired cardiac output (CO) benefit from exercise training. Comparisons of different training models have not been made in the same study.

Aims.To evaluate whether the response to different training models diverges according to the cardiac output response to exercise in patients with chronic heart failure.

Methods.Sixteen CHF patients (63 ± 11 years) with an ejection fraction of 30 ± 11% underwent a baseline cardiopulmonary exercise test, right heart catheterization and leg muscle biopsy. Cardiac output (CO) response to exercise was defined as the ratio between CO increase and the increase in oxygen uptake (CO response index) during exercise. Patients were randomized into two training regimens, differing with regard to active muscle mass, i.e. whole body and one‐legged exercise.

Results.Baseline exercise capacity expressed as W kg–1correlated with the CO response index (r = 0.51,P < 0.05). Exercise capacity on the cycle ergometer increased in both groups but more in the one‐legged than in the two‐legged training group (P < 0.05). The improvement in exercise capacity did not correlate with base‐line exercise capacity. It correlated with CO response index in the one‐legged (r = 0.75,P < 0.01) but not in the two‐legged training group. CO response index correlated negatively with the pulmonary capillary wedge pressure at peak exercise (r = – 0.60,P < 0.05). The increase in leg muscle citrate synthase activity after training correlated negatively with the baseline CO response index (r = – 0.50,P < 0.05).

Conclusions.The improvement of exercise capacity after one‐legged training correlates with the CO increase in relation to the O2uptake before training. In patients with low CO response, individualization of the exercise regimen is needed and the benefits of training a limited muscle mass at a time deserve further study.
A case of neurofibromatosis type 1 with an aldosterone‐producing adenoma of the adrenal
Authors: Biagi P. , Alessandri M. , Campanella G. , Castro R. , Totteri A. , Fanciullacci M.
Published: March 2003

Abstract. Biagi P Alessandri M, Campanella G, Castro R, Totteri A, Fanciullacci M (Abbadia San Salvatore Hospital, Abbadia San Salvatore; Misericordia Hospital, Grosseto; University of Florence, Florence, Italy). A case of neurofibromatosis type 1 with an aldosterone‐producing adenoma of the adrenal (Case Report). J Intern Med 1999; 246: 509–512.

Neurofibromatosis type 1 is a phacomatosis. Neurofibromas are the most common tumours associated with the disease, and along with other tumours, make neurofibromatosis type 1 the most common tumour predisposing syndrome in humans. Hypertension may be coincidental, but at least two specific neurofibromatosis related causes must be considered, namely neurofibromatous involvement of the renal artery and pheochromocytoma. We have described the first known case of a patient with neurofibromatosis type 1 who developed hypertension due to an aldosterone‐producing adenoma of the adrenal. The question of whether this association was coincidental or due to the tumour predisposition of neurofibromatosis type 1 was debated.
Bone mineral density and blood pressure in patients with asymptomatic hyperparathyroidism. The Tromsø Study
Authors: Jorde R. , Sundsfjord J.
Published: March 2003

Abstract. Jorde R, Sundsfjord J (University Hospital of Tromsø, Tromsø, Norway). Bone mineral density and blood pressure in patients with asymptomatic hyperparathyroidism. The Tromsø Study. J Intern Med 2000; 247: 325–330.

Objective. To evaluate bone mineral density and blood pressure in asymptomatic hyperparathyroidism.

Design. A case‐control study.

Setting. The participants obtained from an epidemiological survey in Tromsø 1994–95, that included more than 27 000 subjects. The re‐examination in 1998 was performed at the University Hospital of Tromsø, Norway.

Participants. Thirty‐nine subjects with hyperparathyroidism and 72 control subjects were studied.

Main outcome measures. Bone mineral density measurements of the lumbar spine and the proximal femur (femoral neck, Ward’s triangle, and trochanter). Systolic and diastolic blood pressure.

Results. In the hyperparathyroidism group bone mineral density was significantly lower measured at the lumbar spine (1.000 ± 0.181 vs. 1.079 ± 0.194 g cm–2, mean ± SD, P < 0.01) and at the femoral neck (0.806 ± 0.121 vs. 0.852 ± 0.141 g cm–2, P < 0.05). In the females, but not in the males, blood pressure was significantly higher in the hyperparathyroidism group than in the control group [systolic blood pressure 146.7 ± 18.6 vs. 137.4 ± 23.0 mmHg (P < 0.05) and diastolic blood pressure 88.1 ± 11.8 vs. 82.2 ± 10.6 mmHg (P < 0.05)]. In the females the number of subjects on antihypertensive medication was significantly higher in the hyperparathyroidism group than in the control group (32.1% and 16.6%, respectively, P < 0.01).

Conclusions. Subjects with asymptomatic hyperparathyroidism have moderately reduced bone mineral density. In females with hyperparathyroidism there is an increase in blood pressure.
Physicians’ use of plasma methylmalonic acid as a diagnostic tool
Authors: Hvas A.‐M. , Vestergaard H. , Gerdes L. U. , Nexø E.
Published: March 2003

Abstract. Hvas A‐M, Vestergaard H, Gerdes LU, Nexø E (Randers Hospital, Randers, and Aarhus University Hospital, Aarhus, Denmark). Physicians’ use of plasma methylmalonic acid as a diagnostic tool. J Intern Med 2000; 247: 311–317.

Objectives. To investigate physicians’ reasons for requesting plasma methylmalonic acid and their reactions to an increased concentration of plasma methylmalonic acid.

Design. Study of medical records.

Setting. Three somatic district hospitals in Denmark.

Subjects. Medical records of 198 patients with a plasma methylmalonic acid measurement above the reference interval. Information on diagnostic decisions was available for 177 patients.

Main outcome measures. Reasons for requesting plasma methylmalonic acid and the reactions to the finding of elevated plasma methylmalonic acid.

Results. An explicit reason for requesting plasma methylmalonic acid was stated in 57% of 198 examined medical records, known or suspected anaemia being the most frequent reason. No further action was taken in 109 (62%) of the 177 cases available for follow‐up. Amongst the remaining 68 patients, the finding of an increased plasma methylmalonic acid led to diagnosis of cobalamin deficiency in 46 patients. Six patients with a markedly increased plasma methylmalonic acid (above 0.99 µmol L–1) and clearly decreased plasma cobalamins (below 200 pmol L–1) were not recognized as having cobalamin deficiency.

Conclusions. This lack of response to an increased plasma methylmalonic acid raises an important question. Is the clinical response inadequate, or is the connection between an increased level of plasma methylmalonic acid and signs of clinical significant cobalamin deficiency less clear?
Associations of leptin, insulin resistance and thyroid function with long‐term weight loss in dieting obese men
Authors: Näslund E. , Andersson I. , Degerblad M. , Kogner P. , Kral J. G. , Rössner S. , Hellström P. M.
Published: March 2003

Abstract. Näslund E, Andersson I, Degerblad M, Kogner P, Kral JG, Rössner S, Hellström PM (Danderyd Hospital, Huddinge University Hospital and Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; and the Health Science Center at Brooklyn, New York, USA). Associations of leptin, insulin resistance and thyroid function with long‐term weight loss in dieting obese men. J Intern Med 2000; 248: 299–308.

Objective. The aim of the present study was to identify predictors of weight loss in obese men participating in a 2‐year behaviour modification programme.

Design. Longitudinal, clinical intervention study of a behaviour modifying weight loss program.

Setting. University Hospital, Stockholm, Sweden

Subjects. Forty‐four obese men (age, 42.7 ± 1.1 years; BMI, 37.1 ± 0.6 kg m–2, mean ± SEM) followed for 2 years.

Interventions. Behaviour modification weight loss programme.

Main outcome measures. Associations between plasma leptin and thyroid function tests, insulin resistance by homeostatic model assessment (HOMA), dietary recall and anthropometrically determined body composition.

Results. At baseline, there were significant correlations between plasma leptin and body mass index (BMI), fat‐free mass (FFM) and insulin resistance. Median weight loss over 2 years was 4.9 kg (range, – 27.2 to + 11.9). Baseline serum leptin concentrations adjusted for BMI (leptin/BMI ratio) were significantly correlated with 2‐year weight change (r = 0.34, P = 0.04). A subset of seven of the 44 men gained weight over the 2 years. These ‘gainers’ differed significantly in initial leptin/BMI ratio (0.62 ± 0.07) compared with the 37 ‘losers’ (0.42 ± 0.03, P < 0.05). In a multiple regression model, baseline leptin, insulin and age predicted 22% of the variance in weight change with no additional significant contribution from BMI, FFM, waist:hip ratio, thyroid function tests or energy intake. There was a strong correlation between the change in leptin concentrations and the change in insulin resistance from baseline to 2‐year follow‐up (r = 0.54; P < 0.001).

Conclusion. Baseline plasma leptin concentrations predicted long‐term weight loss. Inappropriate leptin secretion or disposal, corrected for BMI, was associated with failure to maintain weight loss in obese men in a behaviour modification weight loss programme.
Ageing and medicine
Authors: Grimley Evans J.
Published: March 2003

Abstract. Grimley Evans J (University of Oxford, Oxford, UK). Ageing and medicine (Review). J Intern Med 2000; 247: 159–167.

Throughout the world, populations are ageing. The response of the health services needs to be based on a knowledge of the nature of human ageing and the principles of rational health care for older people. Ageing comes about from interactions between intrinsic (genetic) and extrinsic (environment and lifestyle) factors. Health care has to be responsive to the general needs of older people, but also to recognize the heterogeneity produced by different rates and patterns of individual ageing. There are now real possibilities of improving the course of human ageing through modulation of both intrinsic and extrinsic processes. There is also a need to adapt social institutions to what is a permanent change in demography.
Medical education in the new millennium
Authors: Rees L. H.
Published: March 2003

Abstract. Rees LH (Royal College of Physicians, London, UK). Medical education in the new millennium (Internal Medicine in the 21st Century). J Intern Med 2000; 248: 95–101.

This article reviews current trends in undergraduate and postgraduate medical education and speculates on the future in the new millennium.
Carotid and femoral atherosclerosis, cardiovascular risk factors and C‐reactive protein in relation to smokeless tobacco use or smoking in 58‐year‐old men
Authors: Wallenfeldt K. , Hulthe J. , Bokemark L. , Wikstrand J. , Fagerberg B.
Published: March 2003

Abstract. Wallenfeldt K, Hulthe J, Bokemark L, Wikstrand J, Fagerberg B (Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden). Carotid and femoral atherosclerosis, cardiovascular risk factors and C‐reactive protein in relation to smokeless tobacco use or smoking in 58‐year‐old men. J Intern Med 2001; 250: 492–501.

Objectives. To examine the associations between smokeless tobacco use, smoking, cardiovascular risk factors, inflammation and ultrasound‐assessed measures of atherosclerosis in the carotid and femoral arteries.

Subjects. The study was performed in a population‐based sample of clinically healthy men (n=391) all 58 years old. Exclusion criteria were cardiovascular or other clinically overt diseases or continuous medication with cardiovascular drugs.

Methods. The habits of smoking and oral moist snuff use were assessed by questionnaires. C‐reactive protein (CRP) was assessed by high sensitive enzyme‐linked immunosorbent assay (ELISA). Intima‐media thickness (IMT) in the carotid bulb, the common carotid artery and the common femoral artery and plaque occurrence were measured by ultrasound.

Results. The use of oral moist snuff was associated with serum triglycerides and waist–hip ratio (WHR), but not with CRP or ultrasound‐assessed measures of subclinical atherosclerosis. Smoking, on the other hand, was associated with CRP, the components in the metabolic syndrome and IMT as well as plaques in the carotid and femoral arteries. In comparison to never‐smokers the current smokers had higher values of WHR, triglycerides, C‐reactive protein and IMT in carotid bulb and femoral artery. Ex‐smokers were in general more obese and had a femoral IMT that was in‐between that of never‐smokers and current smokers.

Conclusions. Tobacco smoking, but not oral moist snuff use, was associated with carotid and femoral artery IMT, and increased levels of CRP. Current smoking was also associated with abdominal obesity. Ex‐smokers though, are generally more obese. Smoking was also associated with hyperinsulinaemia, dyslipidaemia and high blood pressure, i.e. the metabolic syndrome. The inhaled smoke from the combustion of tobacco seems to be an important aetiological factor in the atherosclerotic process.
Diabetes and advanced glycation endproducts
Authors: Vlassara H. , Palace M.R.
Published: March 2003

Abstract. Vlassara H, Palace MR (Department of Geriatrics, Division of Experimental Diabetes and Ageing, Mount Sinai School of Medicine, and Department of Medicine, Division of Endocrinology, Mount Sinai School of Medicine, NY, USA). Diabetes and Advanced Glycation Endproducts. J Intern Med 2002; 251: 87–101.

Bio‐reactive advanced glycation endproducts (AGE) alter the structure and function of molecules in biological systems and increase oxidative stress. These adverse effects of both exogenous and endogenously derived AGE have been implicated in the pathogenesis of diabetic complications and changes associated with ageing including atherosclerosis, renal, eye and neurological disease. Specific AGE receptors and nonreceptor mechanisms contribute to these processes but also assist in the removal and degradation of AGE. The final disposal of AGE depends on renal clearance. Promising pharmacologic strategies to prevent AGE formation, reduce AGE toxicity, and/or inactivate AGE are under investigation.
Is there a role for microorganisms in the pathogenesis of sarcoidosis?
Authors: Du Bois R. M. , Goh N. , McGrath D. , Cullinan P.
Published: March 2003

du Bois RM, Goh N, McGrath D, Cullinan P (Royal Brompton Hospital and Imperial College, London, UK). Is there a role for microorganisms in the pathogenesis of sarcoidosis (Minisymposium)?J Intern Med2003;253:4–17.

Sarcoidosis is a granulomatous disease that has the immunopathological features of being antigen‐driven. It is a complex disease that appears to arise from the interaction of one or more triggers with an immunologically predisposed host. Previous reports of familial clustering and varying prevalence of sarcoidosis in different populations could reflect differences in ethnic predisposition or differences in local environmental exposures. This review focuses specifically on these areas that have been the subjects of intensive investigation recently. Specific focus is provided on the issue of an infective trigger and highlights popular candidates. It is concluded that microbes are a likely trigger (but not as an infection) in a genetically predisposed individual and that this initial event culminates in the sarcoidosis granulomatous response.
The fracture‐flip technique reveals new structural features of the Escherichia coli cell wall
Authors: Risco  , Pinto da Silva
Published: March 2003

With few exceptions, all bacteria possess a wall which protects them and controls their communication with the environment. In Gram‐negative bacteria the cell wall exhibits a complex and unique multilayered organization. We have applied a modification of the freeze‐fracture technique known as ‘fracture‐flip’ to visualize the real surfaces of the different wall layers in a Gram‐negative bacterium, Escherichia coli. In combination with treatments to weaken the interlayer connections, this technique has provided new insights into the structure of the bacterial wall. Large areas of an intermediate layer (most probably the peptidoglycan‐containing matrix) have been visualized for the first time between the plasma membrane and the outer membrane of the wall. Extensive regions corresponding to the cytoplasmic face of the plasma membrane have also been obtained. These images provide new three‐dimensional views of the bacterial cell wall and provide the structural framework for the analysis of the molecular relationships between the different cell wall components.
A light efficient optically sectioning microscope
Authors: Neil  , Wilson  , JUŠkaitis
Published: March 2003

We describe a simple method by which optically sectioned images may be obtained. The system geometry is similar to that of a tandem scanning microscope but a one‐dimensional grid pattern is used rather than an array of pinholes. This produces a composite image consisting of an optically sectioned image superimposed on a conventional image. A blank sector on the disc is used to provide a wide‐field image. Image subtraction yields the optically sectioned image in real time.
HREM and STEM of intergranular films at zinc oxide varistor grain boundaries
Authors: Chiang  , Wang  , Lee
Published: March 2003

Grain boundaries in model ZnO–Bi2O3 and ZnO–Bi2O3–CoO varistors and a commercial multicomponent varistor have been characterized by high‐resolution electron microscopy (HREM) and scanning transmission electron microscopy (STEM), in order to determine the relationship between Bi grain boundary segregation and formation of thin intergranular films. By controlling Bi2O3 content, applied pressure and temperature, the grain boundary Bi excess has been systematically varied from nearly zero to ΓBi = 1 × 1015 cm−2 (≈ 1 monolayer), as measured by HB 603 STEM using an area‐scan method. HREM shows that intergranular amorphous films are clearly distinguishable in samples with ΓBi > 8 × 1014 cm−2. These films range in thickness, depending on the Bi excess, from 0.6 to 1.5 nm. Similar films of ≈ 1 nm thickness are widely observed in the commercial varistor. The composition of the films is a ZnO–Bi2O3 solid solution, which is in all cases more enriched in ZnO than the bulk eutectic liquid. The Bi‐doped grain boundaries in ZnO varistors therefore contain an intergranular amorphous film which has not only an equilibrium thickness, but also a distinct equilibrium composition.
Cryo‐TEM liquid nitrogen splash guard
Authors: Gowen  , Burger
Published: March 2003

A simple aluminium splash guard provides protection for both microscopes and operators during cryo‐transfer procedures.
Structural changes in samples cryofixed by contact with a cold metal block
Authors: Bennett
Published: March 2003

A common method of cryofixation is to bring a specimen rapidly in contact with a cold metal block. It is usually thought that during this process the surface of the specimen suffers little distortion since it freezes rapidly. Whether this is likely depends on the rate at which samples freeze compared with the speed at which the sample hits the cold block. There is some discrepancy between the published experimentally and theoretically determined freezing rates. As a contribution to this debate the distortion in cryofixed, freeze‐substituted, striated muscle fibres has been investigated. In transverse sections, compression can be detected by deviations of the filament lattice from the hexagonal and used to estimate the time of freezing. Some specimens were frozen using a Gatan Cryosnapper, which freezes by catching the specimen between two nitrogen‐cooled copper jaws. In addition, the speed with which the jaws close has also been determined. The results suggest that freezing of the well‐preserved areas occurs in substantially less than 1 ms. This conclusion is supported by results obtained using metal‐mirror apparatus in which the cushioned specimen was dropped onto a nitrogen‐ or helium‐cooled copper block. All the specimens frozen against a cold block have a flat edge whereas muscle fibres are round. At the very edge there is evidence of structural damage as well as the more general lattice distortion.
Electron and light microscopy studies on particulate EPR spin probes lithium phthalocyanine, fusinite and synthetic chars
Authors: Norby  , Swartz  , Clarkson
Published: March 2003

This is the first detailed study on the morphology of the widely used particulate electron paramagnetic resonance (EPR) probes lithium phthalocyanine (LiPc), methyl‐LiPc, methoxy‐LiPc, fusinite and synthetic carbon‐based chars, by means of both light and electronmicroscopy (LM and EM). The importance of these EPR probes for the measurement of O2/NO has been reported previously. Under LM, LiPc with its distinct crystalline structure differs significantly from the noncrystalline black flakes of both LiPc derivatives, methyl‐LiPc and methoxy‐LiPc. Unlike the shiny carbon‐based synthetic chars, which have no characteristic morphology, fusinite, a fraction of fossilized coal maceral, displays distinctive fine, parallel channels. SEM studies reveal a striated surface and interlocking multilayered structure of LiPc that is markedly different from either the multilayered stacked methyl‐LiPc or botryoidal methoxy‐LiPc. The regularly spaced pores and channels of fusinite, a reflection of its plant origin, contrast sharply with the randomly distributed pores of all sizes of the various synthetic chars. Furthermore, the combined results of both LM and EM studies strongly suggest the nonperturbing nature of fusinite and LiPc when they were used as EPR probes to measure oxygen in cells or tissues. We hope that this study, in conjunction with the numerous EPR functional studies of probes reported earlier, provides valuable information for the future development of new particulate EPR spin probes.
Extended confocal microscopy of myocardial laminae and collagen network
Authors: Young  , Legrice  , Young  , Smaill
Published: March 2003

Ventricular myocardium has a complex three‐dimensional structure which has previously been inferred from two‐dimensional images. We describe a technique for imaging the 3D organization of myocytes in conjunction with the collagen network in extended blocks of myocardium. Rat hearts were fixed with Bouin's solution and perfusion‐stained with picrosirius red. Transmural blocks from the left ventricular free wall were embedded in Agar 100 resin and mounted securely in an ultramicrotome chuck. Confocal fluorescence laser scanning microscopy was used to obtain 3D images to a depth of 60 μm in a contiguous mosaic across the surface. Approximately 50 μm was then cut off the surface of the block with an ultramicrotome. This sequence was repeated 20 times. Images were assembled and registered in 3D to form an extended volume 3800 × 800 × 800 μm3 spanning the heart wall from epicardium to endocardium. Examples are given of how digital reslicing and volume rendering methods can be applied to the resulting dataset to provide quantitative structural information about the 3D organization of myocytes, extracellular collagen matrix and blood vessel network of the heart.
Composition mapping at high resolution
Authors: Schwander P. , Rau W‐D. , Ourmazd A.
Published: March 2003

HRTEM images are traditionally interpreted by comparing experiment and simulation. However, quantitative agreement between experimental and simulated images is rarely achieved. It is thus highly desirable to extract quantitative information from HRTEM lattice images directly, without recourse to simulated images. Such ‘direct’ methods have been used to obtain high‐resolution composition maps from the local information content of HRTEM images. We review the real‐space techniques QUANTITEM and chemical mapping and delineate their application range. Finally, we demonstrate that both methods can be regarded as limiting cases of a more general approach.
High angle [001] twist boundaries in platelet colonies of BiSrCaCuO (2223) superconductor
Authors: DIKO P. , HANIC F.
Published: March 2003

The microstructure of BiPbSrCaCuO (2223) ceramic was studied by polarised light microscopy and the etch‐pits technique. The high‐angle twist grain boundaries in the platelet colonies were confirmed to be [001] coincidence type twisted boundaries or rotation twin boundaries with the (001) twinning plane.
Determination of the inelastic mean free path of electrons in vitrified ice layers for on‐line thickness measurements by zero‐loss imaging
Authors: FEJA B. , AEBI U.
Published: March 2003

The inelastic mean free path of 120 keV electrons in vitrified ice layers has been determined in an energy‐filtering TEM. From the ratio of the unfiltered and zero‐loss‐filtered image intensities recorded with a slow‐scan CCD camera, the relative sample thickness t/Λ can be calculated. For calibration, the geometric ice thickness was measured by imaging a tilted view of a cylindrical hole which had been burnt into the ice layer. The total inelastic mean free path was found to be 161 nm, and the partial inelastic mean free path for an acceptance angle of 4.2 mrad was 232 nm. These results were built into a standard protocol for use in cryo‐electron microscopy allowing on‐line measurements of local ice‐layer thicknesses by zero‐loss‐filtered/unfiltered imaging.