bluuebunny/crossref_metadata_2025 huggingface dataset:
What Do You Expect? A Reconfiguration of the Audit Expectations Gap
Authors: Dennis Ian
Published: August 2009

This paper undertakes a conceptual enquiry into the idea of the expectations gap. This method of enquiry is explained as a philosophical investigation into the concepts used in the literature relating to the expectations gap. A descriptive conceptual enquiry is undertaken into the current use of the expression ‘expectations gap’ and the related terms ‘expectation’ and ‘expects’. It is argued that vagueness and misunderstandings of the uses of these expressions undermines a grasp of the issues involved and of how they are to be resolved. The paper looks at the various explanations of these expressions in the literature and suggests that more clarity in discussions of the issues would be achieved by characterizing expectations as beliefs about what auditors do or desires for them to perform certain procedures with certain qualities in audits. The grounds for the beliefs are considered. The belief that the auditor will do something because of a belief that it is a duty is examined. The way in which the auditor's beliefs that something is a duty determines what they do is explained through the idea of practical reasoning. The paper goes on to explore the suggestion that an expectation might also be some kind of desire that auditors perform certain actions in the context of an audit. These desires are related to a consideration of the objectives of auditing. The idea of the reasonableness of these desires is examined. The reasons for wanting auditors to undertake particular procedures can also underlie the acceptance of particular meanings of ‘audit’ and ‘auditing’. The audit expectations gap is reconfigured in terms of the beliefs and desires identified in the paper.
Transfusion‐related acute lung injury (TRALI): a clinical review with emphasis on the critically ill
Authors: Benson Alexander B. , Moss Marc , Silliman Christopher C.
Published: August 2009

Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related morbidity and mortality world‐wide. Although first described in 1983, it took two decades to develop consensus definitions, which remain controversial. The pathogenesis of TRALI is related to the infusion of donor antibodies that recognize leucocyte antigens in the transfused host or the infusion of lipids and other biological response modifiers that accumulate during the storage or processing of blood components. TRALI appears to be the result of at least two sequential events and treatment is supportive. This review demonstrates that critically ill patients are more susceptible to TRALI and require special attention by critical care specialists, haematologists and transfusion medicine experts. Further research is required into TRALI and its pathogenesis so that transfusions are safer and administered appropriately. Avoidance including male‐only transfusion practises, the use of leucoreduced components, fresher blood/blood components and solvent detergent plasma are also discussed.
A qualitative study of teacher's perceptions of an intervention to prevent conduct problems in Jamaican pre‐schools
Authors: Baker‐Henningham H. , Walker S.
Published: August 2009

Background  There is a growing evidence base showing the efficacy of school‐based interventions to prevent conduct problems but few evaluations have addressed teachers' perceptions of these programmes. Teachers' views on the acceptability, feasibility and usefulness of an intervention will influence implementation fidelity and programme sustainability and can help further our understanding of how the intervention works and how it may be improved.

Methods  A pilot study of the Incredible Years Teacher Training Programme supplemented by a curriculum unit on social and emotional skills was conducted in inner‐city pre‐schools in Kingston, Jamaica. Three pre‐schools comprising 15 classrooms participated in the intervention which involved seven monthly teacher workshops and 14 weekly child lessons in each class. At the end of the intervention in‐depth individual interviews were conducted with each intervention teacher.

Results  Teachers reported benefits to their own teaching skills and professional development, to their relationships with children and to the behaviour, social‐emotional competence and school readiness skills of the children in their class. Teachers also reported benefits to teacher–parent relationships and to children's behaviour at home. A hypothesis representing the teachers' perceptions of how the intervention achieved these benefits was developed. The hypothesis suggests that intervention effects were due to teachers' gains in skills and knowledge in three main areas: (1) a deeper understanding of young children's needs and abilities; (2) increased use of positive and proactive strategies; and (3) explicitly teaching social and emotional skills. These changes then led to the variety of benefits reported for teachers, children and parents. Teachers reported few difficulties in implementing the majority of strategies and strongly recommended wider dissemination of the intervention.

Conclusions  The intervention was valued by Jamaican pre‐school teachers and teachers felt they were able to successfully integrate the strategies learned into their regular practice.
Pyomyositis in a patient with myeloma responding to antibiotics alone
Authors: HOYLE C. , GOLDMAN J. M.
Published: August 2009

Abstract. Pyomyositis is a rare purulent infection of skeletal muscle with striking clinical features. It usually occurs in patients living in the tropics but is increasingly being reported in immunosuppressed patients. The traditional approach to management has been surgical with drainage and debridement of the multiple muscle abscesses. We report a patient with myeloma who developed multiple muscle and lung abscesses associated with a Staphylococcus aureus septicaemia. The case was successfully managed with intravenous antibiotics alone with no recurrence of the abscesses during a later episode of neutropenia. The advantages of avoiding surgical intervention in immunosuppressed and thrombocytopenic patients are obvious.
Plasma growth factor activity and cardiac wall thickness
Authors: LEMNE C. , VOLK‐JOVINGE S. , NILSSON J. , VESTERQVIST O. , DE FAIRE U.
Published: August 2009

Abstract. Objectives. The aim of this study was to investigate the growth factor activity in plasma (GFAP) in hypertension, and the correlation of GFAP to blood pressure levels, cardiac structural changes and platelet activation at rest and during exercise.

Subjects. Fifteen untreated hypertensive subjects and 15 normotensive controls were recruited from a blood pressure screening programme.

Interventions. GFAP before and after 30 min of strenuous exercise was analysed as the ability of patient or control plasma to stimulate incorporation of 3H‐thymidine in cultured human smooth muscle cells. M‐mode echocardiography was performed and platelet activity was measured by the excretion of the urinary metabolite of thromboxane A2.

Results. There were no significant differences in GFAP or platelet activation at rest or after exercise between the groups. The fractions of labelled cells were 52.6% vs. 56.6% (HT vs. NT) at rest. Septum and posterior wall end‐diastolic thicknesses (PWT[D]) were significantly increased in the HT group (10.4 ± 0.3 vs. 9.2 ± 0.3 mm and 11.4 ± 0.5 vs. 10.0 ± 0.4 mm, respectively, P < 0.05). PWT(D) was significantly correlated to GFAP (r = 0.40, P = 0.04) and to blood pressure (r = 0.53, P < 0.005) but there was no correlation between blood pressure and GFAP.

Conclusion. The data suggest that GFAP could play a role in the early development of cardiac hypertrophy in hypertension, but that this effect does not seem to be directly linked to blood pressure levels alone.
Correlation between blood pressure and plasma insulin in acromegaly
Authors: IKEDA T. , TERASAWA H. , ISHIMURA M. , OCHI H. , OHTANI I. , FUJIYAMA K. , HOSHINO T. , TANAKA Y. , MASHIBA H.
Published: August 2009

Abstract. Objectives. The aims of this study were to determine the possible role of hyperinsulinaemia in the increase in blood pressure in acromegalic patients.

Design. After an overnight fast, blood samples were obtained at 0, 30, 60, 120 and 180 min after 75 g glucose ingestion, and plasma growth hormone (GH) and plasma insulin (IRI) were measured by radioimmunoassay. The blood pressure was measured at 10.00 hours for 3 days in a supine position.

Subjects. Nineteen (nine women and 10 men) untreated acromegalic patients, aged 25–69 years.

Results. There were no significant correlations between mean blood pressure (MBP; diastolic + one‐third pulse pressure) and basal GH, sum of plasma GH at 0, 30, 60, 120 and 180 min or basal IRI. However, significant correlation was observed between MBP and IRI at 120 min (r = 0.57, P < 0.02) or sum of plasma IRI at 0, 30, 60, 120 and 180 min) (r = 0.58, P < 0.02).

Conclusions. We conclude that hyperinsulinaemia may be involved in an increase in blood pressure in active acromegalics.
Individual utilization of anti‐asthma medication by young adults: a prescription database analysis
Authors: HALLAS J. , HANSEN N.‐C. G.
Published: August 2009

Abstract. Objectives. To analyse and evaluate current practice of asthma therapy by use of computerized prescription data.

Design. Descriptive, non‐interventive.

Setting. A pharmacoepidemiological database on computerized refund claims from pharmacies in the Odense region in Denmark.

Subjects. Persons aged 20–44, presenting prescriptions for asthma drugs during the period 1 October 1990 to 30 September 1991.

Main outcome measures. Prevalence of asthma drug use, the regimes chosen, relationship between β‐agonist and steroid use by the individual patient.

Results. In all, 3020 persons used anti‐asthma drugs, corresponding to a crude 1‐year prevalence of 3.6%. Sixty per cent were women. The subjects had an average anti‐asthma drug consumption corresponding to 86% of the population's average. The four most common regimes were inhaled β‐agonist monotherapy, inhaled β‐agonist and corticosteroid, oral β‐agonist monotherapy and inhaled corticosteroid monotherapy, altogether accounting for 79% of users. The proportion of corticosteroid users increased with increasing individual use of β‐agonists. With an annual β‐agonist purchase of 100–200 defined daily doses, still less than half also used steroids.

Conclusion. The majority of patients use a regime agreeing with current guidelines, except that more patients should be prescribed corticosteroids. The observed large increase in asthma drug use is likely to be explained by an intensified treatment of individual patients, rather than an increased prevalence.
Presenting features of monoclonal gammopathies: an analysis of 684 newly diagnosed cases
Authors: UCCI G. , RICCARDI A. , LUONI R. , ASCARI E. ,   For the Cooperative Group for the Study and Treatment of Multiple Myeloma
Published: August 2009

Abstract. Objectives. The clinical, laboratory and radiologic features at diagnosis of 684 newly diagnosed patients with monoclonal gammopathy were revised in order to underline the differences between monoclonal gammopathies of undetermined significance (MGUS) and stage I multiple myeloma (MM).

Design. Patients were screened for inclusion in a prospective controlled protocol for treatment of MM. Those having serum or urine monoclonal component (MC) were diagnosed as MM when they demonstrated osteolysis and/or bone marrow plasma cells (BMPC) > 20%; patients not fulfilling these criteria were considered MGUS.

Setting. Patients were recruited from 24 general or university hospitals from the departments of internal medicine, haematology and medical oncology.

Subjects. Seven‐hundred‐and‐fifty were enrolled between January 1986 and March 1990; 684 (343 MGUS and 341 MM) were able to be evaluated for this study and 78 were stage I MM.

Interventions. Complete clinical, radiologic and laboratory work‐up was carried out at the referral centres.

Main outcome measures. The main outcome expected was the confirmation that BMPC > 20% could reliably differentiate stage I MM from MGUS.

Results. At a median follow‐up of 36 months (minimum follow‐up: 18 months), MGUS had a lower progression rate to overt MM, longer overall survival and different causes of death than stage I MM. Further differences concerned erythrocyte sedimentation rate (28 vs. 47, P < 0.001), per cent reduction of normal immunoglobulin (86 vs. 60%, P < 0.001), serum MC (1.6 vs. 2.2 g dl−1, P < 0.001) and thymidine kinase level (3.3 vs. 4.5 mU ml−1, P < 0.05).

Conclusions. The study suggests that 20% BMPC can be taken as a safe cut‐off point at which to differentiate MGUS from early MM and outlines a few simple parameters which can be of diagnostic aid.
Diurnal blood pressure variations in normoalbuminuric type 1 diabetic patients
Authors: HANSEN K. W. , PEDERSEN M. M. , CHRISTIANSEN J. S. , MOGENSEN C. E.
Published: August 2009

Abstract. Objective. To test the hypothesis that normoal‐buminuric type 1 diabetic patients segregate into groups with normal and elevated ambulatory blood pressure. To evaluate diurnal variation of blood pressure assessed by individual or fixed night‐time periods.

Design. Cross‐sectional study.

Setting. Tertiary referral centre.

Subjects. Inclusion criteria for type 1 diabetic patients (n = 33): normal urinary albumin excretion (UAE age < 45 < 20 μg min−1), diabetes duration ≤ 20 years, age 45 years. Healthy controls (n = 33) were matched for sex and age.

Main outcome measure. Twenty‐four hour, day‐time, night‐time and night/day ratio of ambulatory blood pressure.

Results. Twenty‐four‐hour blood pressure in diabetic patients did not differ significantly from a normal distribution. The 24‐h systolic blood pressure was higher in diabetic patients than in healthy controls (difference: 6 mmHg, 95% confidence interval (CI) from 1 to 10 mmHg, P < 0.05), while no significant differences were found for diastolic values. The 24‐h systolic blood pressure in diabetic patients with UAE above the median value (5.8 μg min−1) was higher than for those with lower UAE (difference: 7 mmHg, 95% CI from 0.5 to 13 mmHg, P < 0.05). The night/day ratio of diastolic blood pressure based on individual informations of the night period was (mean ± SD) 80 ± 6% in diabetic patients and 78 ± 8% in controls (difference: 2%, 95% CI from −1 to 5%, not significant [NS]). This ratio increase significantly (P < 0.00001) to 90 ± 5% in diabetes and to 84 ± 7% in controls if a fixed night period from 22.30 hours to 06.30 hours was assumed.

Conclusions. It was not possible to identify a well‐separated group of normoalbuminuric type 1 diabetic patients with elevated ambulatory blood pressure. Values of UAE above the median in diabetic patients are associated with higher ambulatory blood pressure. Assessment of the night/day variation from fixed time‐points should be abandoned because this leads to a serious underestimation of the nocturnal reduction in blood pressure.
Effects of age, sex, season and diet on serum ionized calcium, parathyroid hormone and vitamin D in a random population
Authors: RUDNICKI M. , THODE J. , JØRGENSEN T. , HEITMANN B. L. , SØRENSEN O. H.
Published: August 2009

Abstract. Objectives. To study the influence of age, sex, season and diet on calcium status in normal subjects.

Design. A random population study.

Setting. Institutional clinic for large population studies.

Subjects. The subjects were drawn randomly from the Danish Civil Registration System and represented a random sample of the background population in the area. The sample comprised 127 subjects (54 men and 73 women, aged 35–65 years).

Main outcome measures. The effects of age, sex, season and diet on parathyroid hormone (PTH), 1,25‐ dihydroxyvitamin D (1,25(OH)2D) and 25‐hydroxy‐vitamin D (25‐OHD).

Results. There was no statistical significant difference for the serum concentrations of ionized calcium, PTH, 1,25(OH)2D and 25‐OHD between the two sexes, nor any influence by age in either sex, in contrast to serum phosphate, which declined significantly in men (P < 0.05), but tended to increase in women. Serum PTH (P < 0.009) showed seasonal fluctuations, whereas serum concentrations of 1,25(OH)2D, 25‐OHD, ionized calcium, phosphate and magnesium remained stable throughout the year. Dietary intake of calcium and vitamin D were not related to any serum variables.

Conclusions. In healthy subjects differences between the two sexes exist regarding phosphate metabolism. Serum PTH shows seasonal fluctuations.
Long QT syndrome with insulin‐dependent diabetes mellitus: contiguous gene syndrome on chromosome 11p
Authors: OHZEKI T. , TAMURA A. , HANAKI K. , KOHNO Y. , URASHIMA H. , OKUDA H. , OGIHARA Y. , SHIRAKI K. , UTSUNOMIYA Y. , YAZAKI Y.
Published: August 2009

Abstract. Long QT syndrome (Romano‐Ward syndrome) and insulin‐dependent diabetes mellitus (IDDM) have been documented as being linked with gene(s) on chromosome 11p although concurrence of the two disorders has not been reported. Our case is a 13‐year‐old boy with Romano‐Ward syndrome accompanied by IDDM. The long QT syndrome seemed to be transmitted in an autosomal‐dominant mode because the Q‐T intervals of his father and paternal grandfather were longer than normal. There was no family member with an abnormally high level of blood glucose except the patient. The human leucocyte antigen (HLA) haplotypes of the patient and the father were DR4/DR9 and DR2/DR9, respectively. This study suggests that in our patient IDDM, as well as Romano‐Ward syndrome, is linked with chromosome 11p in the presence of HLA‐DR4. The results support the previous study that chromosome 11p encodes a gene implicated in HLA‐DR4‐dependent diabetes susceptibility.
High serum insulin, insulin resistance and their associations with cardiovascular risk factors The Northern Sweden MONICA population study
Authors: LINDAHL B. , ASPLUND K. , HALLMANS G.
Published: August 2009

Abstract. Objectives. To estimate the prevalence of insulin resistance and high serum insulin levels and to investigate their relationship to other cardiovascular risk factors.

Design. Cross‐sectional cardiovascular risk factor survey.

Setting. Northern Sweden.

Subjects. A subsample of the population‐based Northern Sweden MONICA Study. This subsample underwent an oral glucose tolerance test after an overnight fast, and consisted of 354 men and 404 women in the 25–64‐year age range.

Main outcome measures. Delineation of low insulin sensitivity and high serum insulin by the diagnostic test technique, prevalence of these variables and their associations with cardiovascular risk factors.

Results. The participants were classified into four subgroups by an insulin sensitivity index and fasting serum insulin. The combination of low insulin sensitivity and high serum insulin was present in 17% of the male and in 18% of the female 25–64‐year‐old population. In both sexes this combination was closely associated (P < 0.001) with body mass index, waist‐hip ratio, blood pressure and serum triglycerides, and correlated inversely with serum HDL cholesterol (P < 0.001). When high serum insulin was present as an isolated entity it was as closely associated with other cardiovascular risk factors such as isolated low insulin sensitivity, except that impaired glucose tolerance occurred exclusively in the group with isolated low insulin sensitivity.

Conclusions. The combination of insulin resistance and high insulin levels is associated with a marked clustering of cardiovascular risk factors and is present in one‐sixth of the middle‐aged population in the north of Sweden.
Very early risk stratification by electrocardiogram at rest in men with suspected unstable coronary heart disease
Authors: NYMAN I. , ARESKOG M. , ARESKOG N.‐H. , SWAHN E. , WALLENTIN L. ,   RISC STUDY GROUP
Published: August 2009

Abstract. Objectives. To determine the possibility of very early prognostic stratification based on electrocardiograms (ECGs) at rest and/or cardiac enzyme levels after an episode of suspected unstable coronary heart disease.

Design and setting. Men with suspected unstable angina or non‐Q‐wave myocardial infarction were studied in the coronary care units of eight hospitals. The ECGs at rest and creatinine kinase were followed.

Subjects. In total 911 men were followed for 12 months. Of 8136 consecutively admitted, 3365 fulfilled the inclusion criteria. Excluded were 2454 patients, mainly because of a larger myocardial damage, signs of myocardial dysfunction, other serious cardiac or non‐cardiac disease or an ECG not possible to interprete regarding ST‐T‐segment changes in the precordial leads.

Main outcome measures. End‐points at follow‐up were cardiac death, myocardial infarction and severe (class III or IV) angina.

Results. Compared to patients with normal a ECG who had an 8% 1‐year risk of myocardial infarction or death, the risk with isolated negative T waves was 14% (P < 0.05), ST elevation 16% (P < 0.05), ST depression 18% (P < 0.01) and the combination of ST elevation and ST depression 26% (P < 0.001). The only finding related to future severe angina was ST depression. The risk of cardiac events was comparably elevated in patients with anterior or inferior site of ECG changes. Cardiac enzyme levels had no predictive value regarding future events.

Conclusions. Electrocardiograms at rest obtained during the initial days of hospitalization provide very early and valuble prognostic information in men admitted with suspected unstable coronary heart disease.
Low‐dose warfarin decreases coagulability without affecting prothrombin complex activity
Authors: HOLM J. , BERNTORP E. , CARLSSON R. , ERHARDT L.
Published: August 2009

Abstract. Objectives. To asses the efficacy of a fixed, low dose of warfarin in lowering factor VII coagulant activity (FVII: C) and to investigate the effects on the plasma coagulation cascade.

Design. An open pilot study with two dose levels of warfarin: 1.25 and 2.5 mg day−1 during two consecutive 4‐week periods. All subjects received aspirin 75 mg day−1. Prothrombin fragment 1 + 2 (F(1 + 2)), protein C, protein S, FVII:C, factor X and P‐prothrombin complex activity (P‐PT) were measured at baseline, at 2‐week intervals and 4 weeks after end of treatment. Coagulation activation peptide F(1 + 2) was used as a marker of thrombin formation [13].

Subjects. Twelve male patients with a history of myocardial infarction. Inclusion was made through a written questionnaire.

Results. Warfarin 1.25 mg day−1 lowered FVII:C from 113 U dl−1 to 107 U dl−1 (P = 0.025) and F(1 + 2) from 1.60 nmol l−1 to 1.27 nmol l−1 (P = 0.013) but had no effect on protein C or P‐PT. A dose of 2.5 mg day−1 induced further lowering of FVII:C (91 U dl−1, P = 0.0042), and also of protein C from 116% to 99% (P = 0.034) and P‐PT from 107% to 81% (P = 0.0096) mean values.

Conclusion. Warfarin 1.25 mg day−1 seems to exert an anticoagulant effect without reduction in PT or the natural anticoagulant protein C and is suggested, in combination with aspirin, to be a safe and simple therapy against arterial thrombotic disease, making regular PT controls unnecessary.
The cost‐effectiveness of treating hypertension in elderly people—an analysis of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension)
Authors: JOHANNESSON M. , DAHLÖF B. , LINDHOLM L. H. , EKBOM T. , HANSSON L. , ODÉN A. , SCHERSTÉN B. , WESTER P.‐O. , JÖNSSON B.
Published: August 2009

Abstract. Objectives. The aim of this study was to estimate the cost‐effectiveness of antihypertensive treatment in elderly people based on the results of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension).

Design. The STOP Hypertension study was a randomized trial comparing active antihypertensive treatment with a placebo. The risk of stroke, cardiovascular disease and total mortality was significantly reduced in the actively treated group compared to placebo.

Setting. One hundred and sixteen primary health care centres in Sweden.

Subjects. A total of 1627 hypertensive patients aged 70–84. No patient was lost to follow‐up.

Interventions. Antihypertensive treatment with beta blockers and diuretics for a mean follow‐up of 25 months.

Main outcome measure. The cost‐effectiveness ratio estimated as the net cost (the treatment cost minus saved costs of reduced cardiovascular morbidity) divided by the number of life‐years gained (the increase in life expectancy from treatment).

Results. The cost per life‐year gained was estimated as SEK 5000 for men and SEK 15000 for women ($1 = SEK6; £1 = SEK10). The cost per life‐year gained did not exceed SEK100000 in any of the sensitivity analyses.

Conclusions. It is concluded that treatment of elderly hypertensive patients with beta blockers and/or diuretics is cost‐effective according to the results of the STOP Hypertension study.
Non‐paroxysmal arterioventricular junctional tachycardia during postprandial hypoglycaemia in an obese non‐diabetic patient
Authors: PEZZAROSSA A. , BAGGI V. , MANCA C. , BOLOGNESI R.
Published: August 2009

Abstract. We have observed the simultaneous occurrence of postprandial hypoglycaemia and a rare cardiac arrhythmia: non‐paroxysmal arteriovenous junctional tachycardia (NPJT) in a patient with suspected coronary heart disease (CHD) submitted to oral glucose tolerance testing (OGTT). To our knowledge the association between hypoglycaemia and NPJT has not been previously described. The pathogenesis of NPJT might involve a myocellular Ca2+ overloading determined by a hypoglycaemia‐induced catecholamine discharge in a transiently ischaemic myocardium.
Low‐dose interferon alpha combined with zidovudine in patients with AIDS‐associated Kaposi's sarcoma
Authors: PODZAMCZER D. , BOLAO F. , CLOTET B. , GARCIA P. , CASANOVA A. , PAGEROLS X. , GUDIOL F.
Published: August 2009

Abstract. Forty patients with AIDS‐associated Kaposi's sarcoma (KS) treated with the combination of interferon alpha‐2b (IFN‐α) 10–20 MU day−1 and zidovudine (ZDV), 500–800 mg day−1, were evaluated for safety and efficacy. Eighteen patients (45%) had an overall response (CR + PR) at 3 months and a response persisting for a median of 14 (3–27) months. Patients with a CD4 count of less than 300 mm−3, prior to opportunistic infections or constitutional symptoms, were less likely to respond. However, between 28.5% and 36% of patients with a low CD4 count did respond to combined therapy. This is higher than would be predicted from single agent IFN‐α therapy. Twelve of 28 patients (42.8%) receiving 10 MU day−1 of IFN‐α (low dose) had an overall response. In addition, patients tolerated this dose of IFN‐α better, presenting fewer flu‐like symptoms and displayed a trend toward less anaemia, p24 antigen decreased in six out of nine evaluable cases, four of whom were treated with low‐dose IFN‐α. Low‐dose IFN‐α plus ZDV seems to be a useful and well‐tolerated therapy for KS with antitumoral and antiviral activity. Patients without ‘bad prognostic markers’ are most likely to show improvement.
Sporadic distal renal tubular acidosis and periodic hypokalaemic paralysis in Kashmir
Authors: KOUL P. A. , SALEEM S. M. , BHAT D.
Published: August 2009

Abstract. Twenty‐one cases of renal tubular acidosis presenting with periodic hypokalaemic muscular weakness, that were seen over an 8‐year period, are presented. The biochemical features suggested a diagnosis of distal renal tubular acidosis and absence of family history with negative screening of eighteen families pointed towards the primary sporadic nature of the disorder in nineteen of the cases. Alkali and replacement potassium therapy resulted in immediate and sustained clinical recovery in all the cases.
Deficiency of erythropoietin is not responsible for the anaemia associated with cyclosporin treatment of insulin‐dependent diabetes mellitus
Authors: NIELSEN O. J. , MANDRUP‐POULSEN T. , NERUP J. ,   CANADIAN‐EUR0PEAN RANDOMIZED CONTROL TRIAL GROUP
Published: August 2009

Abstract. Objectives. To explore the possible pathogenetic role of erythropoietin (EPO) in the anaemia associated with cyclosporin (Cs) in newly diagnosed patients with insulin‐dependent diabetes mellitus (IDDM).

Design. A multicentre randomized placebo controlled prospective trial of Cs immunosuppression for 12 months in IDDM patients.

Setting. Patients were recruited from the out‐patient clinics of diabetes centres in Europe and Canada.

Subjects. Patients 9–35 years old with a clinical diagnosis of ketonuric IDDM entering less than 6 weeks after diagnosis. 188 patients were originally recruited; 105 patients completed the investigation, 52 patients being treated with Cs, and 53 patients receiving placebo.

Interventions. Random allocation to receive either Cs or placebo. The initial dose of Cs was 10 mg kg−1 BW day−1. Therapy was maintained for 12 months.

Main outcome measures. B‐Haemoglobin, s‐creatinine, and s‐EPO concentrations were monitored before, during and after therapy with either Cs or placebo.

Results. Blood‐haemoglobin (Hgb) fell from 8.5 ± 0.8 to a nadir of 7.8 ± 0.9 mmol l−1 at 6 months (P < 0.0001) in IDDM patients treated with Cs but not in the placebo patients (8.5 ± 0.8 to 8.8 ± 0.9 mmol l−1, NS). The mean serum EPO levels remained unaltered throughout the 6‐month period of Cs and placebo therapy. No significant differences in serum EPO levels between Cs and placebo‐treated diabetic patients were found after 6 months of treatment.

Conclusions. The light anaemia associated with Cs therapy in IDDM patients is not related to an insufficient production of EPO, but is caused by other, as yet unknown mechanisms, unrelated to the nephrotoxic action of this drug.
Reversal of apparent AIDS dementia complex following treatment with vitamin B12
Authors: HERZLICH B. C. , SCHIANO T. D.
Published: August 2009

Abstract. The human immunodeficiency virus (HIV)‐associated dementia complex is characterized by difficulties in concentration and memory followed by apathy, social withdrawal and motor dysfunction. Decreased serum vitamin B12 levels occur in up to 20% of patients with acquired immune deficiency syndrome (AIDS) and may adversely contribute to the haematologic and neurologic dysfunction which is frequently attributed to the human immunodeficiency virus. We describe a patient with AIDS who presented with an apparent advanced AIDS dementia complex. There was an associated low serum vitamin B12 resulting from malabsorption due to low gastric intrinsic factor secretion. Following treatment with vitamin B12 the symptoms resolved over a 2‐month period. We believe that the AIDS dementia complex represented a reversible adverse synergistic interaction between the human immunodeficiency virus and vitamin B12 deficiency.
GM‐CSF in the treatment of a patient with severe methotrexate intoxication
Authors: STEGER G. G. , MADER R. M. , GNANT M. F. X. , MAROSI C. , LENZ K. , JAKESZ R.
Published: August 2009

Abstract. This case report describes the successful treatment of severe methotrexate intoxication in a 72‐year‐old female patient. Following two prior uneventful courses of a polychemotherapy regimen including low‐dose intravenous (i.v.) methotrexate, the patient presented with fever, polymucositis, incipient pyodermia, acute renal failure and pancytopenia 9 days after the third application. Severe methotrexate overdose was confirmed by serum levels. Using a polypragmatic treatment approach focusing on renal function and including granulocyte‐macrophage‐colony‐stimulating factor (GM‐CSF) this life threatening and nearly fatal intoxication was successfully treated. This case report demonstrates that GM‐CSF might contribute to rapid reconstitution of leukopoiesis once methotrexate serum levels are in the subtoxic range.
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease
Authors: SØRENSEN JENS B. , ANDERSEN METTE K. , HANSEN HEINE H.
Published: August 2009

Abstract. The first clinical case of a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was presented by Schwartz et al. in 1957 (Am J Med 1957; 23: 529–42), describing two patients with lung cancer who developed hypo‐natraemia associated with continued urinary sodium loss. They postulated that the tumours led to the inappropriate release of antidiuretic hormone (ADH), later discovered to consist of arginine‐vasopressin (AVP). This suggestion was later confirmed in several studies. The clinical description of the syndrome has changed little since the original observation, and the cardinal findings of SIADH are as follows: (i) hyponatremia with corresponding hypo‐osmolality of the serum and extracellular fluid, (ii) continued renal excretion of sodium, (iii) absence of clinical evidence of fluid volume depletion, (iv) osmolality of the urine greater than that appropriate for the concomittant osmolality of the plasma, i.e. urine less than maximal diluted, and (v) normal function of kidneys, suprarenal glands and thyroid glands. Measurement of AVP in plasma is not a part of the definition of SIADH. SIADH may be caused by a variety of malignant tumours, but may also be caused by various other conditions, such as disorders involving the central nervous system, intrathoratic disorders such as infections, positive pressure ventilation and conditions with decrease in left atrial pressure. Also, a large number of pharmaceutical agents have been shown to produce SIADH, including a number of cytotoxic drugs such as vincristine, vinblastine, cisplatin, cyclophosphamide, and melphalan.

A broad spectrum of malignant tumours has been reported to cause SIADH; however, most of these observations have been in case reports including very few patients. This includes a number of primary brain tumours, haematologic malignancies, intrathoracic non‐pulmonary cancers, skin tumours, gastrointestinal cancers, gynaecological cancer, breast‐and prostatic cancer, and sarcomas. Larger series of patients have revealed that SIADH occurs in 3% of patients with head and neck cancer (47 cases out of 1696 patients), in 0.7% of patients with non‐small‐cell lung cancer (three cases out of 427 patients), and in 15% of cases of small‐cell lung cancer (214 cases out of 1473 patients). The optimal therapy for SIADH is to treat the underlying malignant disease. If this is not possible, or if the disease has become refractory, other treatment methods are available such as water restriction, demeclocycline therapy, or, in severe cases, infusion of hypertonic saline together with furosemide during careful monitoring.
Lecithin‐cholesterol acyltransferase deficiency presenting with acute pancreatitis: effect of infusion of normal plasma on triglyceride‐rich lipoproteins
Authors: WATTS G. F. , MITROPOULOS K. A. , AL‐BAHRANI A. , REEVES B. E. A. , OWEN J. S.
Published: August 2009

Abstract. A 38‐year‐old Asian man presented with acute pancreatitis, marked hypertriglyceridaemia and macroproteinuria, 20 years after the diagnosis of lecithin‐cholesterol acyltransferase (LCAT) deficiency. After recovery, he exhibited macroproteinuria and chylomicronaemia despite treatment with a very‐low‐fat diet. Infusion of normal plasma significantly increased the proportion of cholesterol esters in the patient's plasma and significantly lowered chylomicron‐triglyceride levels, but not proteinuria. We conclude that renal dysfunction may be a late manifestation of LCAT deficiency and that it may lead to severe chylomicronaemia and acute pancreatitis. Infusion of normal plasma corrects the dyslipidaemia in LCAT deficiency, but in the short term does not improve renal function.
Reported treatment of hypertension by family physicians in Sweden and Minnesota: a physician survey of practice habits
Authors: TROEIN M. , ARNESON T. , RÅSTAM L. , PIRIE P. L. , SELANDER S. , LUEPKER R. V.
Published: August 2009

Abstract. Objectives. To compare family physicians' reported practice habits on hypertension in Sweden and Minnesota, and to assess to what extent different national guidelines account for differences.

Design. Random samples of family physicians were selected for telephone interviews on their practice of hypertension.

Setting. Primary care in southern Sweden and in Minnesota.

Subjects. Family medicine specialists. Participation rates were 236/264 (89%) in Sweden and 183/209 (88%) in Minnesota.

Main outcome measures. Cut‐off levels, and non‐pharmacological and pharmacological treatment of hypertension, related to three case scenarios: a 48‐year‐old man, a 65‐year‐old man and a 65‐year‐old woman.

Results. Swedish physicians reported significantly higher levels of diastolic blood pressure than Minnesota physicians for the institution of treatment of hypertension for all case scenarios. In both countries, physicians adhered to the cut‐off levels of their national guidelines in the case of the 48‐year‐old man. Minnesota physicians did not use age as a modifying factor for treatment cut‐off levels, as did Swedish physicians. Swedish physicians emphasized alcohol, fat and stress reduction, and Minnesota physicians weight and salt reduction as non‐pharmacological treatment. While Swedish physicians generally preferred beta‐blockers, Minnesota physicians chose ACE inhibitors or calcium channel blockers as the first choice drug.

Conclusion. Swedish and US guidelines on hypertension were identical except for higher cut‐off level for drug treatment in Sweden. Minnesota physicians reported cut‐off levels close to national guidelines. For 65‐year‐old patients, Swedish physicians reported applying a higher cut‐off level than indicated by guidelines. Swedish physicians also reported preferring less expensive drugs. As a consequence of the differing national guidelines and the identified physicians' practice habits in the two medical communities, it is likely that the segments of the populations treated and the drug costs differ substantially.
Genetic mapping of the multiple endocrine neoplasia type 1 locus at 11q13
Authors: TEH B. T. , CARDINAL J. , SHEPHERD J. , HAYWARD N. K. , WEBER G. , CAMERON D. , LARSSON C.
Published: August 2009

Abstract. Oncogenesis of tumours related to multiple endocrine neoplasia type 1 (MEN1) is associated with somatic deletions involving the MEN1 locus at chromosomal region 11q13, suggesting inactivation of a tumour‐suppressor gene in this region. Here we describe the localization of the MEN1 gene to a 900‐kb region, based on linkage analysis in affected families and deletion mapping of MEN1‐associated tumours. In addition, a set of microsatellite markers mapped to the 11q11–13 region were used for linkage analysis in a large Tasmanian MEN1 pedigree, demonstrating the usefulness of these markers for presymptomatic testing in affected families.
The surgical management of hyperparathyroidism and endocrine disease of the pancreas in the multiple endocrine neoplasia type 1 patient
Authors: THOMPSON N. W.
Published: August 2009

Abstract. The surgical management of multiple endocrine neoplasia type 1 (MEN1) parathyroid disease and involvement of the endocrine pancreas remains controversial. Hyperparathyroidism, usually the first clinical manifestation of the syndrome, requires surgical treatment in nearly all patients. We favour a subtotal parathyroidectomy and cervical thymectomy rather than a total parathyroidectomy and autotransplant because of good long‐term results and the absence of permanent hypoparathyroidism. The results of treating 34 MEN1 patients during a 20‐year period are reported. The most common functional pancreatic or duodenal tumours in MEN1 patients are gastrinomas and insulinomas. In addition to the management of functional syndromes, another major concern is the malignant potential of the neuroendocrine tumours that frequently develop. Our surgical management of gastrinomas and the ZES has evolved over a period of 15 years. We have found that distal pancreatectomy, enucleation of any neoplasms in the head, and duodenotomy and excision of any neuroendocrine tumours (gastrinomas) combined with a regional node dissection are effective in the majority of patients. The results of treating 21 MEN1 patients with ZES are reported.
Differences in utilization of asthma drugs between two neighbouring Swedish provinces: relation to treatment in individuals with airway disease
Authors: LARSSON L. , BOËTHIUS G.
Published: August 2009

Abstract. Objective. To assess the extent to which drugs were used by individuals found to have asthma in a population survey. To assess the relative influence of the proportion of patients treated and doses reported on the sales of drugs. To study if observed differences in sales of asthma drugs between the county of Jämtland (with high sales) and Gävleborg (with lower sales) correlated to a difference in the control of the disease.

Design. A cross‐sectional population study with a postal questionnaire followed by an interview and examination of symptomatic individuals. Asthma was diagnosed in subjects reporting a typical history of asthma or repeated episodes of dyspnoea and wheezing, or dry cough combined with reversibility in FEV1. PEF‐variability or PC20 ≤ 4 mg ml‐1.

Setting. The county of Jämtland, and Gästrikland, a southern part of the county of Gävleborg in central Sweden.

Subjects. All 16 year olds, and 13% (randomly selected) of 30–39 and of 60–69 year olds (totalling 12732 individuals). Subjects reporting airway symptoms in the questionnaire (n = 2100) and 450 asymptomatic controls were further investigated.

Main outcome measures. Drug use and symptoms reported by individuals found to have asthma or chronic obstructive pulmonary disease (COPD).

Results. Inhaled β2 agonists and inhaled steroids were used more often by individuals with asthma and COPD in Jämtland. However, regular use was more common in Gävleborg. Most of the asthmatics did not use any medication in spite of the fact that symptoms were commonly reported. The drug combinations most often used were inhaled β2 agonists alone or in combination with inhaled steroids. There were only minor differences in the prevalence of symptoms reported by individuals with asthma treated in different ways.

Conclusion. Differences in the way anti‐asthma drugs were used contributed to the observed difference in the sales of drugs. However, this difference was mainly caused by differences in the prevalence of asthma. The goals of asthma management plans were fulfilled only in a minority of patients despite the sales of asthma drugs being high.
RET‐deficient mice: an animal model for Hirschsprung's disease and renal agenesis
Authors: SCHUCHARDT A. , D'AGATI V. , LARSSON‐BLOMBERG L. , COSTANTINI F. , PACHNIS V.
Published: August 2009

Abstract. Receptor tyrosine kinases play a critical role in transducing signals involved in cell growth and differentiation. The c‐ret proto‐oncogene is a member of the receptor tyrosine kinase gene superfamily originally identified by its transforming ability. Somatic mutations of c‐ret are responsible for a large proportion of thyroid papillary carcinomas, while germ‐line mutations are responsible for multiple endocrine neoplasia types 2A and 2B, dominantly inherited cancer syndromes characterized by multiple tumours of neuroectodermal origin. In addition to its role in tumour formation, c‐ret is thought to have a developmental role since mutations of the gene have been implicated in the aetiology of Hirschsprung's syndrome (congenital megacolon). A targeted mutation in the murine c‐ret locus shows that the ret receptor is required for normal development of two lineally unrelated systems, the excretory system and the enteric nervous system.
The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study
Authors: Dralle H. , SCHEUMANN G. F. W. , PROYE C. , BACOURT F. , FRILLING A. , LIMBERT F. , GHERI G. , HENRY J. F. , BERNER M. , NIEDERLE B. , VASEN H. F. A.
Published: August 2009

Abstract. Clinical data of 139 patients with hereditary medullary thyroid carcinoma (HMTC) from nine european centres surgically treated from 1980 to 1991 were reviewed retrospectively to analyse the value of systematic versus selective lymphadenectomy (LA). Biochemical cure rate was significantly higher in patients who underwent LA compared to patients who did not. In nodal‐positive HMTC, systematic LA compared to selective LA improved biochemical cure in small but not large tumours. In nodal‐negative HMTC, systematic LA compared to selective LA could not improve biochemical cure in either small or large primary tumours. To prevent local recurrences with the risk of increased surgical and tumour‐related morbidity, systematic LA should be performed in all HMTC patients regardless of the primary tumour stage. However, an improvement of biochemical cure by systematic LA seems to be possible only in nodal‐positive small primary tumours without distant metastases.
Primary hyperparathyroidism in multiple endocrine neoplasia type 2A
Authors: Raue F. , KRAIMPS J. L. , DRALLE H. , COUGARD P. , PROYE C. , FRILLING A. , LIMBERT E. , LLENAS L. F. , NIEDERLE B.
Published: August 2009

Abstract. The rarity of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) led us to study clinical findings, surgical therapy and outcome in 67 patients in order to evaluate our therapeutic strategy. The retrospective study was based on cases registered by the EUROMEN study group (nine participating centres) from 1972 to 1993. Characteristics of PHPT in 67 patients (41 females, 26 males) with MEN 2A were reviewed. All patients underwent exploratory neck surgery; PHPT was confirmed histologically and/or biochemically. The median age at diagnosis of PHPT was 38 years. In 75% of the patients, PHPT and medullary thyroid carcinoma were diagnosed synchronously, while in 4%, PHPT was diagnosed earlier. In 18% of the patients, PHPT was diagnosed after thyroidectomy, and in 3%, after discovery of pheochromocytoma. Primary hyperparathyroidism was asymptomatic in 84% of the patients; 15% suffered from renal stones. Serum calcium was slightly elevated in 69% (2.9 ± 0.2 mmol‐1) and normal in 16% of subjects. A single adenomectomy was performed in 42% of the patients, subtotal parathyroidectomy in 31% and total parathyroidectomy with autotransplantation in 16%. Independent from the extent of resection, cure was achieved in 94% of the patients, including 13% with hypoparathyroidism; hypercalcaemia persisted in 3% and no information was available in 3%. In an 8‐year follow‐up, hypercalcaemia recurred in 12% of the patients, although half had undergone parathyroidectomy totally or subtotally.

Conclusion. MEN 2A‐related PHPT is characterized by a mild hypercalcemia which is mostly asymptomatic and can be cured by simple resection of an enlarged parathyroid gland in most cases.
Walking exercise and improved neuropsychological functioning in elderly patients with cardiac disease
Authors: Satoh Tsunehisa , SAKURAI I. , MIYAGI K. , HOHSHAKU Y.
Published: August 2009

Abstract. Objectives. The present study examines the effects of exercise by walking on demented elderly patients with cardiac diseases.

Design. Walking exercise, mental activity and brain atrophy were assessed by using the number of steps, Hasegawa's dementia score and computed tomography, respectively.

Setting/subjects. Forty‐six elderly patients with cardiac disease who were living in a metropolitan city.

Interventions. The Hasegawa dementia score was determined for each patient. The memory scores were used to divide the patients into four groups: normal, > 30.0; subnormal, 30.0 ∽ 22.0; pre‐dementia, 21.5 ˜ 10.5; and dementia, < 10.0. The walking exercises were performed every day. We also studied the ratio of the fullness of the brain (S1) to head size (S), represented as a percentage (S1/S × 100). We screened our patients for depression by means of a self‐rating depression test.

Main outcome measures. Walking exercise and improved mental activities.

Results. The mean numbers of the steps per day for the groups were 3386 ± 676 (normal), 1008 ± 193 (subnormal), 1597 ± 661 (pre‐dementia) and almost no walking (dementia). The mean values of the S1/S ratio for the first three groups were as follows: normal, 84.8 ± 3.2; subnormal, 79.2 ± 4.3; and pre‐dementia, 76.8 ± 4.9. Only one patient was positive with regard to the depression test.

Conclusions. The mental activity of elderly cardiac patients with dementia and/or brain atrophy improved with exercise from walking.