bluuebunny/crossref_metadata_2025 huggingface dataset:
C‐peptide revisited – new physiological effects and therapeutic implications
Authors: WAHREN J. , JOHANSSON B‐L. , WALLBERG‐HENRIKSSON H. , LINDE B. , FERNQVIST‐FORBES E. , ZIERATH J. R.
Published: November 2003

Recent studies have demonstrated that replacement of C‐peptide to normal physiological concentrations in insulin‐dependent diabetic (IDDM) patients on a short‐term basis (1–3 h) results in decreased glomerular hyperfiltration, augmented glucose utilization and improved autonomic nervous function. More prolonged administration (1–3 months) of C‐peptide to IDDM patients is accompanied by improvements in both renal and autonomic nervous function. Moreover, both in‐vitro and in‐vivo studies indicate that C‐peptide may have a role in the regulation of insulin secretion. The effects of C‐peptide may in part be explained by its ability to stimulate Na+,K+‐ATPase activity. In conclusion, the combined findings indicate that C‐peptide is a biologically active hormone. The possibility that C‐peptide therapy in IDDM patients may be beneficial should be considered.
Improved carbohydrate metabolism after physical training and dietary intervention in individuals with the ‘atherothrombogenic syndrome’. Oslo Diet and Exercise Study (ODES). A randomized trial
Authors: ANDERSSEN S. A. , HJERMANN I. , URDAL P. , TORJESEN P. A. , HOLME I.
Published: November 2003

Objectives. To compare the single and joint effect of 1‐year diet and exercise intervention on carbohydrate metabolism and associated coronary risk variables.

Design. Unmasked, randomized, 2×2 factorial intervention trial with 1‐year duration for each participant.

Setting. The participants were recruited from a screening examination of 40‐year‐old persons in Oslo, Norway.

Subjects. Two hundred and nineteen sedentary men and women, with diastolic blood pressure 86–99 mmHg, HDL cholesterol <1.20 mmol L‐1, triglycerides >1.4 mmol L‐1, total cholesterol 5.20–7.74 mmol L‐1 and BMI>24. Participants were randomly allocated to control (n=43), diet (n= 55), exercise (n=54) and diet+exercise (n=67).

Interventions. Exercise: supervised endurance exercise three times a week. Diet: reduce weight, increase the intake of fish and reduce total fat intake.

Main outcome measures. One‐year changes in insulin and glucose before and after a standardized glucose load.

Results. As compared with controls fasting insulin in pmol L‐1 decreased significantly in the combined diet and exercise group (3.9±6.2 versus ‐22.6±4.7 respectively, P=0.003). Insulin in pmol L‐1 after glucose load decreased significantly in all intervention groups compared to controls (diet: ‐82.2± 49.9 P=0.02; exercise: ‐92.4±60.1 P=0.03; diet+exercise: ‐179.6±45.1 P=0.0004). Fasting glucose in mmol L‐1 decreased significantly in the diet alone group (0.21±0.07 P=0.006) and in the diet+exercise group (‐0.26±0.08 P=0.005). In a subgroup analysis of the good responders, the observed changes with respect to total cholesterol (‐0.76 mmol L‐1), HDL cholesterol (0.16 mmol L‐1), triglycerides (‐0.72 mmol L‐1), systolic and diastolic blood pressure (‐8.5/‐6.8 mmHg) were all statistically significant compared to the control with P<0.001.

Conclusions. Exercise and diet intervention and in particular the combination of the two, were effective in improving carbohydrate metabolism. Associated risk factors were also affected in a beneficial direction.
Glutamic Acid Decarboxylase – Gene to Antigen to Disease
Authors: LERNMARK Å.
Published: November 2003

Glutamic acid decarboxylase (GAD) enzymes catalyse the formation of gamma‐aminobuturic acid (GABA), which is a major transmittor in the central nervous system but also exerts functions in peripheral organs. Recent molecular analyses have revealed surprising new roles for the GAD isoforms in human diseases of autoimmune character including neurological disorders and insulin‐dependent diabetes. In the 1995 Frontiers in Medicine Symposium, the coauthors of this review discussed the genetics, cell biology, molecular immunology and the role of GAD as autoantigens in human autoimmunity. Studies on disease diagnosis, prediction, and prognosis have revealed unique patterns of reactivities in both cellular and humoral immune responses. Further work will be needed to establish whether the GAD molecules can be used to treat autoimmune diseases.
Rising erythrocyte sedimentation rate during several years before diagnosis can be a predictive factor in 70% of renal cell carcinoma patients. The benefit of knowing subject‐based reference values
Authors: IVERSEN O. H. , RØGER M. , SOLBERG H. E. , WETTELAND P.
Published: November 2003

Objectives. A diagnosis of renal cell carcinoma (RCC) early enough for potentially curative surgery is difficult. We wanted to establish whether the erythrocyte sedimentation rate (ESR) in RCC patients had begun to rise before the appearance of any symptoms or signs and, if so, when.

Design. A retrospective study of the evolution of the ESR in 236 randomly selected RCC patients during several years before diagnosis, comparing the results with previously obtained population‐based control values.

Results. It is generally held that RCC patients have a high ESR at diagnosis. In our material, however, 29.7% of the RCC cases had an ESR that at this time was at or below the population‐based upper reference limit; it had not increased significantly, neither with time before diagnosis, nor with age. In 70.3% of RCC patients the ESR was increased and had been significantly rising for up to 6 years or more before diagnosis. This had not been adequately responded to, probably because the physicians lacked knowledge of the patients' baseline ESR, and because none of the prediagnostic readings had been above the population‐based reference limit.

Conclusions. Systematic ESR graphic recordings over time will enable a physician to determine each individual's baseline value, and hence note any continuously rising trend, which should lead to further investigations, e.g. an ultrasound kidney examination. This may provide an early clue to many otherwise non‐symptomatic RCC cases. It is time for a reappraisal of the predictive value of the ESR to discover early RCC, and possibly other diseases as well.
Population‐based erythrocyte sedimentation rates in 3910 subjectively healthy Norwegian adults. A statistical study based on men and women from the Oslo area
Authors: WETTELAND P. , RØGER M. , SOLBERG H. E. , IVERSEN O. H.
Published: November 2003

Objectives. To establish age‐ and sex‐specific reference limits for the erythrocyte sedimentation rate (ESR) in asymptomatic Norwegian adults.

Design. Single ESR recordings were obtained by the classical or a modified Westergren method from 2145 men and 1765 women (93% being blood donors) with age range 20–90 years, and analysed statistically.

Results. There was a significant positive association between ESR level and age, consistent with a parabolic pattern in men but a linear one in women. The mean values for men were about 3 mm h‐1 at 20 years, 6 mm h‐1 at 55 years, and 10 mm h‐1 at 90 years, and 6, 9, and 11 mm h‐1 respectively for women. These averages (predicted by regression lines) were significantly higher in women up to the age of 75 years, after which the estimated sex‐specific 95% confidence limits for mean values were found to overlap.

Conclusions. The upper reference levels expected to be exceeded only by chance in 5% of single individual recordings at the ages of 20, 55 or 90 years, respectively, were estimated to be 12, 14 and 19 mm h‐1 for men, and 18, 21 and 23 mm h‐1 for women. Higher values should be controlled and, if confirmed, lead to a clinical check‐up. However, about 76% of our overall material had ESR values lower than 9 mm h‐1. Knowledge of each person's baseline ESR value might increase the disease‐predictive ability of the test. If several measurements over years reveal a steeper rise with age than depicted in our population‐based curves, it should be taken seriously, even when each reading is below the population‐based reference limits.
Atrial fibrillation – new aspects on mechanism and treatment
Authors: BERTIL OLSSON S.
Published: November 2003

During recent years, the exploration of different aspects of atrial fibrillation (AF) has become increasingly interesting. Thus, knowledge about basic underlying mechanisms, consequences and different modes of treatment has rapidly expanded. At a meeting in Lund, Sweden, in 1993, scientists within different fields of AF research gathered for the exchange of information. This paper is a short summary of some topics discussed at the Lund meeting and some suggestions as to how further research in this field may help to improve our understanding of this arrhythmia and the treatment of patients suffering from it.

Underlying pathoelectrophysiological mechanisms in AF have been explored in experimental models in animals and by direct recordings of different atrial myocardial electrophysiological variables both in the catheter laboratory and during open heart surgery in man. Some findings illustrate possible generalized atrial myocardial mechanisms, whilst other findings clearly indicate the possibility of localized pathoelectrophysiological mechanisms. The generally accepted hypothesis that AF is perpetuated by multiple re‐entry mechanisms is, thus, both verified and modified by recent studies.

In addition to subjective symptoms and well identified thromboembolic consequences, accumulating evidence tells us that AF may precipitate a myocardial dysfunction which may be misinterpreted as an underlying factor initiating the arrhythmia.

Today's treatment of AF includes several newer antiarrhythmic drugs, different ablation techniques, the application of different electrical devices as well as different surgical methods. New, improved and simplified methods are expected.

Atrial fibrillation is the single most important supraventricular arrhythmia needing substantial further exploration of mechanisms, consequences and treatment. The Lund symposium contributed to this process by defining the state of knowledge in 1993 and outlining the need for the years to come.
Diabetes mellitus and impaired pancreatic β‐cell proliferation
Authors: SJÖHOLM Å.
Published: November 2003

The factors that normally regulate the proliferation of the insulin‐producing pancreatic β‐cell largely remain elusive although several factors have been identified that influence β‐cell growth in vitro. The adult β‐cell is normally virtually quiescent, but its replicatory activity can be enhanced in vitro by certain nutrients and growth factors, and long‐term alterations in β‐cell mass constitute an important means to accommodate an increased demand for insulin. Likewise, expansion of the β‐cell mass by recruitment of β‐cells to proliferate may constitute a means by which the organism can compensate for the loss or dysfunction of β‐cells occurring in diabetes. However, neither in human or animal models for type‐1 diabetes, nor in type‐2 diabetes, is β‐cell regeneration a noteworthy feature. Thus, if β‐cells could be induced to replicate at a higher rate, this may prove beneficial in maintaining normoglycaemia, since the β‐cell mass is a major determinant of the total amount of insulin that can be secreted by the pancreas. The present review will focus on the normal regulation of β‐cell mitogenesis and hormones production in vitro and in vivo, and furthermore, will present evidence for an insufficient extent of β‐cell regeneration in different forms of diabetes mellitus. Additionally, the possibility of manipulating β‐cell proliferation by peptides and genetic engineering, and the significance of β‐cell mitogenesis in islet transplantation will be discussed in relation to treatments of diabetes mellitus.
Stroke management in Europe
Authors: ABODERIN ISABELLA , VENABLES GRAHAM
Published: November 2003

Stroke is a leading cause of death and disability in Europe. Standards of care vary widely, and the introduction of simple standards will improve mortality and morbidity. It has been shown, in the absence of any medical treatment for acute stroke, that improving the organization of care for people with stroke significantly improves outcome. Recommendations are made for simple changes to the organization of care. Preventative measures after first stroke reduce incidence of subsequent stroke; these could be made widely available. Rehabilitation for those with persisting disability should be patient centred and commence immediately after the patient is alert and medically stable. Urgent research is required to find out which components of rehabilitation are important, and measures should be in place to ensure that all who require rehabilitation receive it from appropriately trained professionals. Population‐based monitoring systems covering incidence, case fatality, mortality and disability should be put in place in all European Member States by the year 2005.
Tumour‐induced hypoglycaemia in a patient with insulin‐dependent diabetes mellitus
Authors: SVARTBERG J. , STRIDSBERG M. , WILANDER E. , ANDERSSON D. E. H. , ERIKSSON B.
Published: November 2003

We report on a case of malignant insulinoma occurring in a patient with genuine insulin‐dependent diabetes mellitus (IDDM). A review of cases concerning patients with diabetes mellitus and insulinomas is presented, and reveals only patients with non‐insulin‐dependent diabetes mellitus (NIDDM). Our case appears to be the first in showing the combination of IDDM and a functioning malignant insulinoma.
Recovery from severe osteoporosis following cure from ectopic ACTH syndrome caused by an appendix carcinoid
Authors: DOBNIG H. , STEPAN V. , LEB G. , WOLF G. , BUCHFELDER M. , KREJS G. J.
Published: November 2003

Dobnig H et al. (Department of Internal Medicine, Karl Franzens University, Graz, Austria). Recovery from severe osteoporosis following cure from ectopic ACTH syndrome caused by an appendix carcinoid (Case report). J Intern Med 1996; 239: 365–9.

It is well established that endogenous overproduction of glucocorticoids may cause osteoporosis. However, knowledge about potential recovery of the skeleton after cessation of corticosteroid excess is limited. We describe a 34‐year‐old female patient and discuss the complex diagnostic workup that led to the rare diagnosis of carcinoid of the appendix as the cause of Cushing's syndrome. The patient experienced multiple spontaneous rip fractures, and at that time, the bone mineral density of the lumbar spine was 4.3 SD below values for age‐matched healthy controls. After removal of the tumour, the patient completely recovered. Measurements at the lumbar spine showed an increase in area bone density of 79% equivalent to 4 SD over a subsequent 3‐year observation period. This first case of documented bone mass recovery in a patient cured of ectopic ACTH syndrome suggests a potential for excellent reversibility of steroid‐induced osteoporosis and should be considered in the management of such patients.
Hereditary angio‐oedema: new clinical observations and autoimmune screening, complement and kallikrein‐kinin analyses
Authors: NIELSEN E. W. , GRAN J. T. , STRAUME B. , MELLBYE O. J. , JOHANSEN H. T. , MOLLNES T. E.
Published: November 2003

Objectives. To study clinical and laboratory manifestations of hereditary angio‐oedema (HAE).

Subjects. Thirty‐three affected members of a kindred of 63.

Results. Oedematous attacks in the skin, mucous membranes and gastrointestinal tract with fluid displacement were elicited by mental and physical stress, minor traumas, dental and surgical procedures, eruption of teeth, tonsillitis, pregnancies, and use of oestrogen‐containing pills including menopausal substitution. Every adult woman with symptomatic HAE (n=11) showed symptoms of urinary tract infections in conjunction with the attacks (P= 0.010), and also experienced more spontaneous abortions or premature labours (P=0.037) than healthy relatives. Patients with HAE of both sexes more frequently reported heartburn or peptic ulcers (P=0.002). Rheumatic complaints were reported by 53% of HAE patients and 12% of their unaffected relatives (P=0.013), but biochemical screening for 18 autoantibodies and quantitation of immunoglobulins did not reveal statistically significant differences between the two groups. C3, prekallikrein, total kininogen, high molecular weight kininogen (HK), alpha‐2‐macroglobulin and factor XII were not significantly different in HAE patients. In contrast, levels of C1‐INH and C4 were depressed and cleaved HK increased in patients compared to unaffected relatives.

Conclusions. HAE manifests in a variety of ways, and may influence risk of spontaneous abortions and premature labour.
Relationships between vitamin D, parathyroid hormone and bone mineral density in inflammatory bowel disease
Authors: SILVENNOINEN J.
Published: November 2003

Objectives. To explore the relationships between vitamin D intake, serum parathyroid hormone (PTH) and 25‐hydroxyvitamin D (250HD) concentrations, and bone mineral density (BMD) in inflammatory bowel disease (IBD).

Setting. A university hospital clinic in Finland.

Subjects. One hundred and fifty randomly selected patients with IBD from the hospital register and 73 healthy controls.

Measurements. BMD of the lumbar spine and the proximal femur was measured with dual energy X‐ray absorptiometry. Vitamin D intake and serum levels of 250HD and PTH were determined.

Results. The IBD patients had a lower serum 250HD concentration (28.4 [SD 12.0] nmol L‐1) than the controls (36.1 [16.7] nmol L‐1; P=0.001), whereas no differences in the vitamin D intake or the serum PTH levels were found. The serum 250HD concentrations and the vitamin D intake of the patients with ulcerative colitis (n=67) were similar to those of the Crohn's disease patients (n=76). The patients with Crohn's disease of the small bowel had slightly, but not significantly, lower serum 250HD concentrations (25.6 [11.0] nmol L‐1) than the other Crohn's disease patients (31.4 [14.3] nmol L‐1; P=0.061). In the IBD patients, the vitamin D intake and the serum 250HD and PTH concentrations were not associated with BMD.

Conclusions. Patients with IBD have lower serum levels of 250HD than healthy controls, but similar serum PTH concentrations and vitamin D intake. Vitamin D intake, and the serum levels of 250HD and PTH are not associated with BMD, and malabsorption is unlikely to be a major factor in the aetiology of bone loss in unselected IBD patients.
Neurofibromatosis complicated with XXX syndrome and renovascular hypertension
Authors: WATANO K. , OKAMOTO H. , TAKAGI C. , MATSUO H. , HIRAO N. , KITABATAKE A.
Published: November 2003

A 25‐year‐old woman with neurofibromatosis was admitted to our hospital for evaluation of hypertension. When she was 6 years old, she was diagnosed as having neurofibromatosis and XXX syndrome because of multiple café‐au‐lait spots, neurofibromas of the skin and mental retardation. Chromosome analysis revealed that her karyotype was 46, XX/47, XXX. Renal arteriography disclosed aneurysmal change and stenosis of the right renal artery. After right‐side nephrectomy and aneurysmectomy, the kidney was autotransplanted in the left iliac fossa. Surgical procedure resulted in marked amelioration of the hypertension without medical treatment. Thus, aortorenal bypass and renal autotransplantation have emerged as the preferred revascularization operations. This is the first report of a chromosomal linkage between neurofibromatosis which is thought to be an autosomal dominant disease and the XXX syndrome.
Predictors of enhanced well‐being after coronary artery bypass surgery
Authors: STEINE S. , LÆRUM E. , ERITSLAND J. , ARNESEN H.
Published: November 2003

Objectives. To assess patients' perception of the therapeutic outcome after coronary artery bypass surgery, and to find predictors for increased well‐being.

Design. Self‐administered questionnaires (Family APGAR and GHQ‐30) were completed on admission and at the follow‐up after 12 months, together with functional classification according to the NYHA index.

Setting. Ullevål University Hospital, Oslo, Norway, 1990–1992.

Subjects. Two hundred and thirteen patients with stable angina admitted for elective coronary artery bypass surgery.

Intervention. Elective coronary artery bypass surgery.

Main outcome measures. Improved physical and psychosocial functioning after one year.

Results. One hundred and ninety‐seven (92%) patients improved their NYHA class, while it remained stable or declined in 16 (8%) patients. Significantly fewer patients with mental distress were found at the follow‐up than at the baseline examination (49 patients [23%] versus 80 patients [38%], respectively, P<0.0001). One hundred and forty‐six patients (69%) reported enhanced psychosocial well‐being, while it was reduced (n=60) or unchanged (n=7) in 67 patients (31%). Predictors for improved psychosocial well‐being following coronary artery bypass surgery were mental distress before surgery (odds ratio 2.8) and being a male patient (odds ratio 2.8).

Conclusions. The majority of the patients reported significant improvement in their physical and psychosocial functioning one year after coronary artery bypass surgery. Mental distress and male sex were significant predictors of enhanced well‐being. Questionnaires on psychosocial well‐being such as the GHQ‐30 may, in addition to health status measurements, offer additional useful information when coronary artery bypass surgery is considered.
Advances in osteoporosis: better identification of risk factors can reduce morbidity and mortality
Authors: JOHNELL O.
Published: November 2003

Johnell O (Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden). Advances in osteoporosis: better identification of risk factors can reduce morbidity and mortality (Review). J Intern Med 1996; 239: 299–304.

Osteoporosis is a common disease of postmenopausal women and the elderly. Low bone mass results from genetic, nutritional and lifestyle factors, decreased oestrogen levels, certain medical conditions, and the use of certain drugs. The overall incidence and age‐and sex‐related incidences of osteoporosis are increasing worldwide. Osteoporotic fractures can cause considerable pain, disability, loss of independence and deterioration in quality of life. Many patients lose the ability to perform the activities of daily living. Mortality and morbidity after hip fracture increase with age. Prevention of osteoporosis and osteoporotic fractures is an urgent priority to reduce the burden placed on health care and social welfare systems.
How to evaluate interaction between causes: a review of practices in cardiovascular epidemiology
Authors: HALLQVIST J. , AHLBOM A. , DIDERICHSEN F. , REUTERWALL C.
Published: November 2003

Hallqvist J et al. (Institute of Environmental Medicine and Department of International Health and Social Medicine, Karolinska Institute, Stockholm, Sweden). How to evaluate interaction between causes: a review of practices in cardiovascular epidemiology (Review). J Intern Med 1996; 239: 377–82.

To increase the knowledge of interaction or synergy between risk factors is an important task in medical research. Still, current literature in cardiovascular epidemiology reflects major misconceptions as how to evaluate interaction. This paper presents Rothman's model of causation from which strict empirical criteria of interaction can be derived. In principle, the method to apply consists of comparing risk differences for one risk factor of interest across strata of the other. Commonly used but incorrect approaches are exemplified and discussed. These include reporting risk of disease among those with combined exposure, comparing relative risks for one exposure after stratification by level of the other, and including an interaction term in the regression model and drawing conclusions from its P‐value.
Severe hyperkalaemia induced by trimethoprim in combination with an angiotensin‐converting enzyme inhibitor in a patient with transplanted lungs
Authors: BUGGE JAN F.
Published: November 2003

A 40‐year‐old woman with transplanted lungs developed life threatening hyperkalaemia (6.8 mmol L‐1) during high dose treatment with trimethoprim‐sulfamethoxazole for Pneumocystis carinii pneumonia. Trimethoprim has an amiloride‐like effect on the distal nephron and may thus induce hyperkalaemia, particularly if other contributing factors coexist. The present patient was also treated with the angiotensin‐converting enzyme (ACE) inhibitor enalapril, and the combination of ACE‐inhibition and potassium‐sparing diuretics is known to induce hyperkalaemia. Hyperkalaemia was probably induced by the combination of ACE‐inhibitor and trimethoprim, and this combination may be as dangerous as the combination of ACE‐inhibitors with other potassium‐sparing diuretics.
Relationship between sodium–lithium countertransport and insulin sensitivity in mild hypertension
Authors: HERLITZ H. , LANDIN K. , WIDGREN B.
Published: November 2003

Objectives. To study the relationship between insulin sensitivity and sodium‐lithium countertransport (Na+‐Li+ CT) in mild, essential hypertension, and to investigate the effect of metformin and metoprolol, respectively.

Design. A double‐blind, triple cross‐over, placebo‐controlled study over a total period of 18 weeks.

Setting. A hypertension out‐patient clinic and research laboratory at Sahlgrenska University Hospital.

Subjects. Seventeen non‐obese men with mild essential hypertension and 17 weight‐matched, healthy controls.

Interventions. Metformin 850 mg b.i.d., metoprolol CR 100 mg once daily and placebo were given during 18 weeks. Each treatment period was 6 weeks. A euglycaemic clamp was performed and erythrocyte Na+‐Li+ CT measured after each 6‐week treatment period.

Main outcome measures. Insulin sensitivity, erythrocyte Na+‐Li+ CT, their interrelation, and the effect of metformin and metoprolol CR on both variables, respectively.

Results. The hypertensive men tended to have an elevated Na+‐Li+ CT compared with the control subjects (0.34±0.03 versus 0.26±0.02 mmol L‐1  h‐1, P<0.1). Glucose disposal rate was similar, but plasma insulin levels higher (P<0.05) among the hypertensives than the controls. Na+‐Li+ CT exhibited a positive relationship to BMI (r=0.53, P=0.03) and a negative correlation to glucose disposal rate (r=‐0.66, P=0.008) in the hypertensive subjects. In multiple regression analysis, Na+‐Li+ CT showed a significant correlation to glucose disposal rate only. In the control subjects, there was no relation between glucose metabolism and Na+‐Li+ CT. Neither metformin nor metoprolol influenced Na+‐Li+ CT, glucose disposal rate or plasma insulin.

Conclusion. Erythrocyte Na+‐Li+ CT seemed to be closely related to insulin‐glucose metabolism in mild hypertension, but was not influenced by metformin or metoprolol.
Idiopathic CD4+ lymphocytopenia and systemic vasculitis
Authors: BORDIN G. , BALLARÉ M. , PAGLINO S. , RAVANINI P. , DULIO D. , MALOSSO M. C. , BOLDORINI R. , MONTEVERDE A.
Published: November 2003

The syndrome defined as ‘idiopathic CD4 lymphocytopenia’ (ICL) is a rare disease of unknown aetiology, often associated with severe depression of immune defences and the occurrence of opportunistic infections. A case is reported wherein a severe immunodeficiency syndrome with persistent idiopathic CD4+ lymphopenia developed in a woman suffering from systemic microscopic polyarteritis; no signs of HIV 1/2 or HTLV I/II infection were evident. The patient died of widespread opportunistic infections. The association of ICL with vasculitis has never been reported until now. A link between the two diseases cannot be ruled out.
Insulin sensitivity in cardiological syndrome X
Authors: QUIÑONES GALVAN A. , NATALI A. , MUSCELLI E. , CIOCIARO D. , PECORI N. , CAMICI P. G. , FERRANNINI E.
Published: November 2003

Objectives. To test whether cardiological syndrome X is an insulin‐resistant state.

Setting, design and subjects. The coronary care unit of a referral centre for angina pectoris in Pisa, Italy. A case‐control study, involving 10 patients with unequivocal (angiographycally proven) cardiological syndrome X, but normal glucose tolerance, blood pressure and lipid levels, and 13 matched healthy subjects.

Main outcome measures. Insulin sensitivity and pattern of substrate oxidation (assessed by the euglycaemic insulin clamp technique in combination with indirect calorimetry).

Results. Fasting plasma glucose and insulin levels were 5.05±0.11 versus 4.88±0.11 mmol l‐1 and 68±10 versus 56±6 pmol l‐1, respectively (controls versus patients, ns). During the insulin clamp, glucose disposal rate was nearly identical in patients and controls (25.9±1.8 and 27.2±1.8 μmol kg‐1 min‐1, respectively, P=0.88). Non‐oxidative glucose disposal accounted for similar proportions of total glucose uptake (59 versus 53%, patients versus controls, ns). Resting energy expenditure (13.7±0.6 versus 13.8±0.8 cal kg‐1 min‐1, ns) and insulin‐induced thermogenesis were similar in the two groups. Fasting plasma NEFA concentrations (0.64±0.09 and 0.64±0.06 mmol l‐1, patients and controls, ns) fell in a similar time‐course and to virtually identical nadirs (0.13±0.02 and 0.14±0.02 mmol l‐1) after insulin infusion. Fasting plasma potassium was similar in patients and controls (3.99±0.10 and 4.16±0.04 mmol l‐1, ns), and insulin induced equivalent hypokalaemia (‐14 versus ‐19%).

Conclusions. None of the in vivo actions of insulin were impaired in patients with when compared to matched controls. Therefore, we conclude that cardiological syndrome X is not an insulin resistant state per se, and that any decrease in insulin sensitivity found in this condition is likely to be secondary.
New concepts in the pathophysiology of heart failure: beneficial and deleterious interaction of endogenous haemodynamic and neurohormonal mechanisms
Authors: PACKER M.
Published: November 2003

Packer, M (Division of Circulatory Physiology, Columbia University, College of Physicians and Surgeons, New York, USA). New concepts in the pathophysiology of heart failure: beneficial and deleterious interaction of endogenous haemodynamic and neurohormonal mechanisms (Minisymposium: Heart failure). J Intern Med 1996; 239: 327–33.

During most of the last 50 years, physicians have viewed heart failure primarily as an oedematous disorder, in which fluid retention occurs because the heart cannot pump adequate quantities of blood to the kidneys. This conceptual model led to the successful utilization of diuretics for heart failure, but it failed to permit physicians to recognize that heart failure is a chronic progressive disorder that impairs both the quality and quantity of life, even when oedema is adequately controlled.

To accommodate this new understanding, a new model has been developed, in which the development and progression of heart failure is viewed as resulting from the interplay of haemodynamic and neurohormonal mechanisms. Both mechanisms support the inotropic state of the heart following an injury to the myocardium, but when sustained for long periods, their ability to augment cardiac contractility wanes, and, instead, these same mechanisms act to enhance ventricular wall stress, thereby impairing ventricular performance. As the heart‐failure state evolves, endogenous mechanisms that are normally activated to control wall stress become exhausted, and peripheral vasoconstriction and sodium retention develop. Unopposed activation of haemodynamic stresses and neurohormonal systems leads to further destruction of the myocardium and progression of the underlying disease.

The acceptance of this haemodynamic– neurohormonal model has led to the development of vasodilators and neurohormonal antagonists that have been shown to be useful alone, or when added to diuretics, in the treatment of heart failure.
Cardiovascular risk groups and mortality in an urban Swedish male population: the Malmö Preventive Project
Authors: BERGLUND G. , ERIKSSON K. F. , ISRAELSSON B. , KJELLSTRÖM T. , LINDGÄRDE F. , MATTIASSON I. , NILSSON J. Å. , STAVENOW L.
Published: November 2003

Objectives. To describe the size, overlap and mortality of four cardiovascular risk groups, in order to give a scientific background for the prevention of cardiovascular disease in a representative urban population.

Setting. Section of Preventive Medicine, Department of Medicine, Malmö University Hospital, Malmö, Sweden.

Subjects. Between 1974 and 1984 22444 men born between 1949 and 1921, constituting 75% of the total male population in these age groups, took part in a comprehensive screening examination aimed at detecting risk factors for cardiovascular disease.

Interventions. Those at high‐risk of developing cardiovascular disease were referred to their general practitioner or to special clinics for hypertension, hyperlipidaemia and diabetes. The follow‐up, which lasted until the end of 1991, averaged 12.2 years.

Main outcome measures. Total death (n=1450) and death from ischaemic heart disease (IHD) (n=471).

Results. Hypertension was found in 13%, hypercholesterolaemia in 19% and diabetes mellitus in 2.6% of the subjects; 49% of the subjects smoked. Multiple risk factors were found in over 17% of the total cohort.

Despite the intervention, all‐cause mortality during follow‐up was increased three‐fold in smokers and in men with hypercholesterolaemia, four‐fold in hypertensive men and five‐fold in men with diabetes, compared to men with no risk factors. The vast majority of deaths (81%) occurred in men who smoked, had hypertension or had high serum cholesterol. Ischaemic heart disease (IHD) was increased five‐fold in smokers, seven‐fold in men with hypercholesterolaemia, nine‐fold in hypertensive men and 12‐fold in men with diabetes. Again, the vast majority of IHD deaths (86%) occurred in the first three categories. Combinations of risk factors substantially increased total mortality as well as IHD mortality.

Conclusions. The large proportion (64%) of the population with risk factors for cardiovascular disease and the substantially (5–12‐fold) increased IHD mortality in those risk groups, calls for actions aimed at preventing premature IHD deaths. Such action should include measures directed towards the whole population and comprehensive treatment programmes for high‐risk individuals, including intervention to stop smoking. The substantial overlap between risk factors calls for one high‐risk clinic caring for all risk groups.
Urolithiasis and distal renal tubular acidosis preceding primary Sjögren's syndrome: a retrospective study 5–53 years after the presentation of urolithiasis
Authors: ERIKSSON PER , DENNEBERG TORSTEN , ENESTRÖM SVERKER , JOHANSSON BJÖRN , LINDSTRÖM FOLKE , SKOGH THOMAS
Published: November 2003

Objectives. Distal renal tubular acidosis (dRTA) can be associated with autoimmune diseases such as primary Sjögren's syndrome (SS). Our objective was to study SS‐associated symptoms, autoantibodies and renal histopathology in patients with urolithiasis and dRTA.

Setting. The patients were from the Departments of Nephrology and Rheumatology, University Hospital of Linköping, which is a tertiary referral hospital, as well as a secondary referral centre for the immediate area around the city of Linköping.

Subjects. Ten female patients with dRTA, who presented with urolithiasis and not with subjective sicca symptoms, were from the Department of Nephrology, University Hospital, Linköping. Autoantibodies were detected in eight of these patients, and they were studied with respect to clinical and laboratory evidence of SS (urolithiasis group). Fifteen women with SS, who presented with sicca symptoms and not with urolithiasis or dRTA, served as the reference group.

Results. In the urolithiasis group, all of the eight patients had anti‐SS‐A antibodies, and SS (or possible SS) developed in seven of the eight patients 1–48 (mean 15) years after the onset of urolithiasis. Histological features of tubulointerstitial nephritis were found in four of five biopsied patients in the urolithiasis group, and in two of four patients (with dRTA) in the reference group.

Conclusions. Urolithiasis and dRTA can precede subjective sicca symptoms, and patients with dRTA may have SS in the absence of subjective sicca symptoms. Anti‐SS‐A antibodies are common in patients with urolithiasis and dRTA. Therefore, we hypothesize the possibility of a Sjögren‐related renal disease in these patients.
Comparison of standardized initial doses of two antithyroid drugs in the treatment of Graves' disease
Authors: KALLNER G. , VITOLS S. , LJUNGGREN J. G.
Published: November 2003

Objectives. To obtain a simple standard regimen, suitable for general practice, and based upon the addition of antithyroid drug plus thyroxine for attaining euthyroidism in patients with Graves' disease.

Design. Prospective, randomized trial of patients with Graves' disease followed for 3 months after the initiation of therapy with an antithyroid drug and combined with the later addition of triiodothyronine to keep the patient euthyroid. The patients were randomized, according to birth date, between methimazole and propylthiouracil. Three dose schemes were tested for each antithyroid drug.

Setting. The study was performed at the thyroid outpatient units of two general hospitals, with the patients having been referred from primary care.

Subjects. Ninety‐four patients with Graves' disease who were suitable for treatment with antithyroid drugs.

Interventions. The patients were allocated into six groups. Three groups received methimazole (10 mg every 6th, 8th or 12th h) and three received propylthiouracil (100 mg every 6th, 8th or 12th h). Twenty micrograms of triiodothyronine was added when the patients were euthyroid to avoid hypothyroidism.

Main outcome measures. The lowest serum free thyroxine level within 3 months of the initiation of the antithyroid treatment.

Results. Fourteen per cent of the patients on methimazole 10 mg every 12th h and 29% on propylthiouracil 100 mg every 12th h did not achieve euthyroidism within the 3‐month observation period. All but one patient on methimazole 10 mg every 8th h or propylthiouracil 100 mg every 8th h reduced the free serum thyroxine levels to the normal or hypothyroid range within the observation period. All of the patients on methimazole 10 mg every 6th h and 56% on propylthiouracil 100 mg every 6th h reduced the serum T4 values into the hypothyroid range within the period.

Conclusion. A standard regimen, based upon the addition of methimazole 10 mg every 8th or 6th h or propylthiouracil 100 mg every 8th or 6th h and followed by the addition of thyroxine or triiodothyronine when euthyroid to avoid hypothyroidism, seems to be suitable for attaining euthyroidism within 3 months in patients with Graves' disease. A dose scheme based on methimazole 10 mg every 12th h or propylthiouracil 100 mg every 12th h were found to be unsuitable due to an unacceptably high incidence of failure to attain euthyroidism or hypothyroidism within 3 months.
Low molecular weight heparins
Authors: BERGQVIST DAVID
Published: November 2003

Low molecular weight heparins (LMWHs) differ from unfractionated heparin (UFH) in a number of characteristics, which is probably due to differences in molecular weight distribution. From a clinical point of view the better subcutaneous bioavailability and longer biological half‐life are important, making it sufficient to inject LMWHs once‐daily only. For practical purposes it is also important that LMWHs be used without monitoring. They are effective as prophylaxis against postoperative venous thromboembolism after all types of surgery; in most studies, more effective than UFH. In most studies, this effect can be obtained safely and with less bleeding than with UFH. LMWHs compare favourably with UFH for starting treatment of deep vein thrombosis, as well as an anticoagulant during haemodialysis. Adverse effects such as thrombocytopenia and osteoporosis are more common with UFH than with LMWHs. Studies evaluating whether or not LMWHs can replace UFH in arterial diseases are still few with small sample sizes. Thus further systematic research is needed.
POEMS syndrome, arterial thrombosis and thrombocythaemia
Authors: ZENONE T. , BASTION Y. , SALLES G. , RIEUX C. , MOREL D. , FELMAN P. , ESPINOUSE D. , BRYON P. A. , COIFFIER B.
Published: November 2003

The case of a 22‐year‐old man with polyneuropathy, endocrinopathy, skin change and monoclonal gammopathy of IgG‐lambda type is described. There was no solitary plasmocytoma, osteosclerotic myeloma or Castleman's disease. However, significant thrombocytosis occurred and the patient developed arterial thrombosis, these were attributed to essential thrombocythaemia in the absence of other aetiological factors.
Glomerular lipid deposition and proteinuria in a patient with familial dysbetalipoproteinaemia
Authors: BALSON K. R. , NIALL J. F. , BEST J. D.
Published: November 2003

This report describes a male patient who was found to have proteinuria at age 31. Renal biopsy showed glomerular hypercellularity with enlarged, lipid‐filled endocapillary cells. On subsequent lipid analysis there was elevation of cholesterol and triglyceride, with apolipoprotein E genotype E2/E2. The clinical course was complicated by pancreatitis and onset of diabetes. After treatment with gemfibrozil and some improvement of the lipid profile, a second renal biopsy showed marked reduction of the glomerular foam cells, despite an increased level of proteinuria. This case emphasizes the potential role that lipid abnormalities may play in renal dysfunction.
Aluminium‐containing agents may be toxic in predialysis chronic renal insufficiency patients
Authors: LIN JA‐LIANG , LEU MEI‐LING
Published: November 2003

Objective. To investigate the possible toxic effects of long‐term low dose aluminium (Al) exposure in predialysis chronic renal insufficiency (CRI) patients (serum creatinine >1.4 mg dL‐1).

Design. An open, random, and prospective clinical study.

Setting. The study was carried out at Chang Gung Memorial Hospital, a medical centre of Chang Gung Medical College.

Subjects. Seventy CRI patients who have regularly attended a nephrology out‐patient department participated in this study. After a 3‐month wash‐out period 50 were given an Al loading test and 20 received no Al‐containing agents.

Interventions. We used a low dose of Al(OH)3 (one tablet three times day‐1, about 302 mg aluminium day‐1) for 3 months as an Al loading test.

Main outcome measures. The study was divided into two phases: phase 1, a basal study to measure serum Al, iron, ferritin, daily urinary Al excretion and renal function status; and phase 2, in which an Al loading test was performed. The phase 1 parameters were measured again after the Al loading test to compare the differences between pre‐ and post‐study in the two groups.

Results. We found significant increments of serum Al and daily urinary Al excretion in all study group patients afterthe Al loading test. The increments of serum Al correlated with basal creatinine clearance (Ccr: r=–0.352, P<0.05) and basal serum ferritin (r=–0.302, P<0.05). Serum ferritin was significantly reduced after the Al loading tests, and the reduction (r=0.357, P<0.05) positively correlated with the increments of daily urinary Al excretion in the study group patients. However, no significant changes of serum Al, ferritin, and daily urinary Al excretion were noted in the control group patients.

Conclusions. A long‐term low dose Al exposure can cause significant Al accumulation and iron store depletion in CRI patients. Therefore, Al‐containing agents should be used with caution in patients with CRI.
Helicobacter pylori–can the mechanisms of pathogenesis guide us towards novel strategies for treatment and prevention?
Authors: FALK PER
Published: November 2003

Falk P (Gastrointestinal Research Laboratory, Department of Medicine, the Karolinska Institute, Stockholm, Sweden and the Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, USA). Helicobacter pylori—Can the mechanism of pathogenesis guide us towards novel strategies for treatment and prevention? (Review). J Intern Med 1996; 240: 319–32.

Helicobacter pylori establishes a chronic infection in the stomach of humans. The infection is associated with a low grade inflammatory response in the epithelium that can develop into chronic active gastritis, peptic ulcer disease or neoplasia. Antibiotics have dramatically decreased the rate of recurrence of peptic ulcers. However, antibiotic resistance is already evident, casting doubts on the future efficacy of these strategies. The link between childhood infection and severe health problems, including increased risk for gastric tumours motivate efforts to develop vaccines. Characterization of the molecular mechanisms of pathogenesis will pave the way for novel strategies for treatment and prevention of H. pylori infection.
Relations between vasoactive hormones and diastolic function in hypertensive uraemic patients
Authors: NAPOLI C. , LIGUORI A. , SORICE P. , DI BENEDETTO A. , CIAFRE S. , POSCA T. , DI IESO N. , D'ARMIENTO F. P.
Published: November 2003

Background. Arterial hypertension is a significant risk factor for the high rate of cardiovascular disease in chronic uraemic (CU) patients. Any role that hypertension may play in CU patient outcomes assumes added significance. The elevation of some hormonal factors in early clinical stage could represent a valuable marker of cardiac disease in CU.

Aim. This study first investigated the role of several hormones on cardiac diastolic properties in CU patients. Moreover, the study investigated the association of hypertension with both diastolic function and release of vasoactive hormones in CU patients.

Results. We have reported that the early impairment of diastolic function is correlated with the elevation of both circulating plasma atrial natriuretic factor and endothelin‐1 (ET‐1) in hypertensive CU patients. Since the effect of ET‐1 on diastolic function is still poorly understood, we have investigated also this issue. In eight additional patients with reduced E/A ratio, but without uraemia, hypertension or chronic heart failure, we have showed a high inverse correlation between the values of E/A ratio and ET‐1 plasma concentrations.

Conclusions. These results strongly suggest that the elevation in ET‐1 levels was correlated with diastolic dysfunction in man. This phenomenon may have important pathophysiological implications suggesting the possibility of an early therapeutic approach in these patients.