bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute renal failure due to carnitine palmitoyltransferase deficiency
Authors: BERKMAN N. , MEIROW D. , KATZIR Z. , BAR‐ON H.
Published: August 2009

Abstract. A young, apparently healthy, soldier developed acute muscle weakness and rhabdomyolysis following prolonged exercise. The resultant myoglobinuria caused severe acute renal failure. Further investigation revealed the presence of carnitine palmitoyltransferase deficiency as the cause of the rhabdomyolysis. Renal function subsequently returned to normal. This rare metabolic disorder should be considered in cases of unexplained myoglobinuria and renal failure.
Acute phase reactants and severity of homozygous sickle cell disease
Authors: HEDO C. C. , AKEN'OVA Y. A. , OKPALA I. E. , DUROJAIYE A. O. , SALIMONU L. S.
Published: August 2009

Abstract. Serum concentrations of seven acute‐phase reactants: albumin, transferrin (Tf), alpha‐1‐antitrypsin (AIAT), caeruloplasmin (Cp), α2‐macroglobulin (α2‐MG), haptoglobin (hp) and C‐reactive protein (CRP) were determined in 73 subjects with varying severities of homozygous sickle cell (HbSS) disease. Fifty healthy subjects of comparable sex, age and socio‐economic class distributions as the HbSS subjects served as controls. Albumin and α2‐MG were comparable in all the subject groups. Tf and hp levels were significantly reduced in the HbSS groups relative to the control group. Conversely, AIAT, CRP and CP were significantly elevated. However only Tf and CRP manifested significant correlations with any of the indices of disease severity employed. Transferrin and CRP are suggested as plasma proteins worthy of further evaluation as indicators of severity in homozygous sickle cell disease.
Effects of alcohol intake and obesity on serum liver enzyme activity in obese men with mild hypertension
Authors: FAGERBERG B. , LINDSTEDT G. , BERGLUND G.
Published: August 2009

Abstract. Objectives. To examine the relationships between alcohol intake, obesity, plasma insulin concentration and serum activities of three liver enzymes in obese men with mild hypertension.

Design. A 6‐week run‐in period followed by randomization to either diet treatment or antihypertensive drug treatment, lasting for 1 year. Alcohol intake was estimated using questionnaires. Plasma insulin concentration, serum activities of gamma‐glutamyl transferase, and aspartate and alanine aminotransferase, respectively, were measured at entry and after 1 year.

Setting. Out‐patient clinic, city hospital.

Patients. Sixty‐four men aged 40–69 years with a body mass index > 26 kg m−1 and with mild untreated hypertension. Exclusion criteria were alcoholism and diabetes mellitus. Sixty‐one patients completed the study.

Interventions. Dietary treatment was based upon weight reduction and recommendations about a low alcohol intake. Drug treatment used a stepped‐care approach with atenolol as the first‐choice drug.

Main outcome measures. Serum activities of the liver enzymes, body weight, body mass index, alcohol intake, plasma insulin concentration.

Results. Body weight decreased by 7.8 kg in the diet group and increased by 1.0 kg in the drug‐treated group. Alcohol intake did not differ between the groups before or after 1 year. Serum gamma‐glutamyl transferase activity correlated with alcohol consumption; it showed no significant change after weight loss. At entry, serum activities of aspartate and alanine aminotransferases correlated to plasma insulin concentration independent of body mass index. Weight reduction significantly lowered serum activities of these liver enzymes as well as plasma insulin concentrations and normalized elevated serum activity of alanine aminotransferase in a majority of the cases.

Conclusion. Alcohol intake was an important determinant for elevated serum gamma‐glutamyl transferase activity. The degree of obesity was a contributing factor for elevations of serum alanine aminotransferase activity. We speculate that insulin may play a role in this relationship.
Long‐term prognosis for diabetic patients with foot ulcers
Authors: APELQVIST J. , LARSSON J. , AGARDH C.‐D.
Published: August 2009

Abstract. Objective. To evaluate the recurrence of foot ulcers as well as the cumulative amputation and mortality rates in diabetic patients with previous foot ulcers.

Design. A prospective study of consecutively presenting diabetic patients admitted to the Department of Internal Medicine because of foot ulcer with a median follow‐up of 4 years.

Setting. A multidisciplinary foot‐care team.

Population. Five‐hundred‐and‐fifty‐eight consecutive diabetic patients with foot ulcers treated between 1 July 1983 and 31 December 1990 were followed to final outcome. Out of these patients, 468 healed either primarily (n = 345) or after minor or major amputations (n = 123) and 90 died before healing had occurred. Those 468 patients who healed were included in this prospective study from the time of healing.

Main outcome measures. Patients were followed according to a standardized protocol with registration of foot lesions, amputation, morbidity and mortality. Clinical examination was performed twice yearly.

Results. After 1, 3 and 5 years of observation 34%, 61% and 70% of the patients, respectively, had developed a new foot ulcer. The recurrence rate of foot lesions was slightly higher among patients who previously had had an amputation (P < 0.05, P < 0.01 and non‐significant, respectively). Among patients with previous primary healing the cumulative amputation rates were 3%, 10% and 12% after 1, 3 and 5 years of follow‐up compared with 13%, 35% and 48% among those who previously healed after amputation, irrespective of previous amputation level (P < 0.001 at all time‐points). All amputations except three were initiated by a foot ulcer deteriorating to deep infection or progressive gangrene. The long‐term survival ratio was lower among patients healed after previous amputation (80%, 59%, 27%) compared with patients with previously primary healing (92%, 73%, 58%) after 1, 3 and 5 years of observation, respectively (P < 0.001. P < 0.01 and P < 0.001 respectively). The mortality rate was twice as high among primarily healed and four times as high among patients with amputation compared to an age‐ and sex‐matched Swedish population.

Conclusion. These findings stress the need for life‐long surveillance of the diabetic foot at risk and the necessity of preventive foot care among diabetic patients with previous foot lesions, and particularly among those who had had a previous amputation.
Intraplaque haemorrhage at carotid artery surgery ‐ a predictor of cardiovascular mortality
Authors: FALKE P. , MÄTZSCH T. , STERNBY N. H. , BERGQVIST D. , STAVENOW L.
Published: August 2009

Abstract. Objective. To ascertain whether carotid intraplaque haemorrhage (IH) in patients undergoing carotid artery surgery is a predictor of increased cardiac mortality over a 5.5 year follow‐up.

Design and subjects. Carotid artery plaques were obtained at surgery from 47 consecutive patients (41 men. six women), median age 67 (range 48–81) years, with symptoms of carotid transient ischaemic attacks (TIAs) or carotid territory minor stroke. As determined at preoperative angiography, the degree of stenosis was 50–99%. Specimens were classified histologically as manifesting severe atherosclerosis, fibrous plaque, IH, or residual IH debris.

Setting. Medical Angiology and Vascular Surgery Units, Malmö General Hospital.

Intervention. Carotid endarterectomy.

Main outcome measure. Correlation between mortality and IH.

Results. At follow‐up after 5.5 years, mortality was 28% (13/47) overall, 92% (12/13) in the IH subgroup [of stroke (n = 1) or myocardial infarction (n = 11)], but only 3% (1/34), of pancreatic cancer, in the non‐IH subgroup (P = 0.0001). Mortality was also significantly higher in the severe atherosclerosis than in the fibrous plaque subgroup, 39% (12/31) vs. 6% (1/16) (P = 0.044), but not significantly increased in any other subgroup (fibrous plaque, residual IH, TIA, minor stroke, or acetylsalicylic acid or anticoagulant treatment). No correlation existed between IH or death and haemoglobin value or platelet count.

Conclusions. Evidence of recent IH seen at carotid artery surgery may be a marker of cardiovascular mortality. As IH was also found in a post‐mortem control subgroup, the difference may be due to abnormality in blood components (e.g., coagulation factors) or impaired vessel‐wall healing capacity (e.g. endothelial dysfunction).
Short‐term treatment of Graves' disease with methimazole in high versus low doses
Authors: JORDE R. , YTRE‐ARNE K. , STØRMER J. , SUNDSFJORD J.
Published: August 2009

Abstract. Objectives. To compare the relapse rates in Graves' disease the first 2 years after methimazole 60 mg day−1 combined with thyroxine versus a titration regimen with methimazole alone, and to look for possible prognostic factors.

Design. A randomized, open, prospective study. Methimazole was given for 6 months in both groups, and thyroid status evaluated every 3rd month during the first year, and every 6th month during the second year.

Setting. The study was performed at our outpatient clinic with patients referred from primary care.

Subjects. Fifty‐six patients were included. One became pregnant and one dropped out during the treatment period. Furthermore, nine patients in the high‐dose and four in the low‐dose group stopped the treatment because of side‐effects. Thus, 19 patients in the high‐ and 22 in the low‐dose group completed 6 months with methimazole.

Results. In those tolerating the treatment, the relapse rates in the high‐ and low‐dose groups were 26.3 vs. 59.1% (P < 0.05), 42.1 vs. 77.3% (P < 0.02); and 57.9 vs. 77.3% (NS) after 3, 12 and 24 months, respectively. The corresponding relapse rates calculated on an ‘intention to treat’ basis were: 51.7 vs. 66.7%; 62.1 vs. 81.5%; 72.4 vs. 81.5% (NS). The thyroid volume was significantly (P < 0.05) larger in those that relapsed (17.8 ± 2.9 vs. 11.6 ± 1.2 mL; mean ± SEM).

Conclusions. In those tolerating the treatment, methimazole significantly reduced the relapse rate the 1st year when given in a high dose. However, the relapse rates in both groups, and the number of side‐effects in the high‐dose group, were unacceptably high.
Disturbed energy balance in skeletal muscle of patients with untreated primary hypertension
Authors: RONQUIST G. , SOUSSI B. , FRITHZ G. , SCHERSTÉN T. , WALDENSTRÖM A.
Published: August 2009

Abstract. Objective. It has been shown that the distribution of Na+ and Ca2+ in various cells is abnormal in patients with untreated primary hypertension, indicating an altered membrane permeability in these cells. This would activate certain ion pumps and thereby enhance ATP turnover. We investigated possible alterations in energy economy of skeletal muscle tissue.

Design. Skeletal muscle energetics were studied in vitro and in vivo in patients with untreated primary hypertension. Phosphocreatine (PCr), energy charge (EC) and total adenylate values were assessed.

Setting. The study was performed at the outpatient clinic of a general hospital and at a university clinical chemistry department and at a specialized bioenergetic laboratory.

Subjects. Altogether, 17 patients with untreated primary hypertension were examined together with matched, healthy and normotensive controls with normal body‐mass index.

Main outcome measures. Skeletal muscle biopsies were obtained from 10 patients and 10 controls for analysis of high energy phosphate compounds. Another seven patients were enrolled for in vivo NMR spectroscopy.

Results. We found a decrease of 30% (P < 0.01) of PCr content in the patients, whilst EC and total adenylates were unchanged. Nuclear magnetic resonance spectroscopy showed an abnormal decrease of PCr during exercise followed by a markedly slower regeneration of PCr during post‐exercise recovery parallelled by a slower recovery of pH. This phenomenon was mirrored by a more pronounced decrease of ATP/Pi in patients during exercise and a slower recovery of ATP/Pi.

Conclusion. The data are compatible with an increased ATP turnover in skeletal muscle cells of patients with untreated primary hypertension although ATP was favoured and kept at a normal resting level at the expense of the PCr store.
Primary antiphospholipid syndrome associated with postoperative primary adrenal failure
Authors: PAPADOPOULOS K. I. , JÖNSSON A. , BERNTORP E. , TÖRNQUIST C. , HULTHÉN U. L.
Published: August 2009

Abstract. A 51‐year‐old Caucasian male without previous history of thromboembolic disease developed Coomb's positive haemolytic anaemia, thrombocytopenia, transient paranoid psychosis and bilateral adrenal haemorrhage with primary adrenal failure after surgery for inguinal hernia. The activated partial thromboplastin time was spontaneously prolonged, and lupus anticoagulant and anticardiolipin antibodies were detected. In the absence of criteria for classification of systemic lupus erythematosus (SLE), the entity was classified as a primary antiphospholipid syndrome. Despite the persistence of the serological abnormalities, the patient remains well after substitution with cortisone. Primary adrenal failure due to adrenal haemorrhage can be associated with the primary antiphospholipid syndrome.
Angio‐oedema induced by enalapril
Authors: FORSLUND T. , TOHMO H. , WECKSTRÖM G. , STENBORG M. , JÄRVINEN S.
Published: August 2009

Abstract. We report the case of a patient who, 9 months after initiation of enalapril and hydrochlorothiazide combination treatment for hypertension, developed angio‐oedema with near fatal outcome. Our patient was successfully intubated using a flexible broncho‐fiberoscope. This case demonstrates that patients given an angiotensin‐converting enzyme (ACE) inhibitor may develop serious facial and laryngeal swelling even several months after the initiation of treatment. The occurrence of even mild swelling should lead to prompt cessation of the drug. Patients with incipient ACE inhibitor‐related angio‐oedema should, without any delay, be referred to hospital for emergency treatment.
Body iron stores, dietary iron intake and coronary heart disease mortality
Authors: REUNANEN A. , TAKKUNEN H. , KNEKT P. , SEPPÄNEN R. , AROMAA A.
Published: August 2009

Abstract. Objectives. To assess whether increased body iron stores and dietary iron intake are associated with an increased risk of coronary heart disease mortality.

Design. A prospective population study with a mean mortality follow‐up time of 14 years.

Setting. Participants attending a health screening examination carried out in several localities in Finland.

Subjects. All 6086 men and 6102 women aged from 45 to 64 years at the baseline examination without known heart disease, who had had serum iron and total iron binding capacity (TIBC) assessed. In a random fifth of these people, dietary iron intake was assessed by a dietary history.

Interventions. The study was observational without any interventions.

Main outcome measures. Mortality from coronary heart disease.

Results. Altogether, 739 of the men and 245 of the women died from coronary heart disease. No relationship between TIBC and coronary mortality was observed in the men; in the women, an inverse although not significant association was found. Transferrin saturation was inversely but not significantly associated with coronary mortality in men; in women, the relationship was U‐formed with a higher mortality at both the lower and higher ends of the distribution. Adjustment for other risk factors did not alter the results. No association was found with dietary iron intake and coronary mortality.

Conclusions. The results do not corroborate earlier findings that excess body iron stores and increased iron intake are associated with an elevated risk of coronary heart disease.
Candidate genes for multiple endocrine neoplasia type 1
Authors: LAGERCRANTZ J. , LARSSON C. , GRIMMOND S. , SKOGSEID B. , GOBL A. , FRIEDMAN E. , CARSON E. , PHELAN C. , ÖBERG K. , NORDENSKJÖLD M. , HAYWARD N. K. , WEBER G.
Published: August 2009

Abstract. The aim of this study was to isolate and characterize candidates for the multiple endocrine neoplasia type 1 (MEN1) gene. The development of tumours related to MEN1 is associated with somatic deletions involving the MEN1 locus, suggesting inactivation of a tumour‐suppressor gene in this region. We have isolated five cDNA candidates located within the 900 kb remaining for the MEN1 gene, determined their sequence, and characterized their expression in normal tissues and several endocrine tumours. One of the candidates, encoding for phospholipase C‐β3, showed properties consistent with the idea of a tumour‐suppressor gene.
Experience with multiple endocrine neoplasia type 1 screening
Authors: SKOGSEID B. , ÖBERG K.
Published: August 2009

Abstract. Screening for multiple endocrine neoplasia type 1 (MEN1) may be conducted for a variety of reasons. The principal aims may be more or less scientific, such as early identification of the trait. Other reasons for screening comprise attempts to avoid endocrine morbidity and possibly forthcoming problems from malignant transformation, as well as attempts to identify and treat gene carriers with a clinically overt disease. Several reports have substantiated the diagnostic yield from screening efforts among MEN1 kindreds. Such increases in detection of the disease ideally should be accompanied by enhanced rates of survival in order to fully justify an unlimited search for the trait. However, studies are lacking a clearly verifying reduction of mortality from the detection of presymptomatic MEN1 individuals. While waiting for the results of survival studies in progress, the generally prevailing opinion favours widespread screening because of the evidently decreased morbidity resulting from early diagnosis of the MEN1 trait, which apparently persists even during decades of follow‐up. This paper presents the clinical features of the disease and experience derived from a prospective screening programme for MEN1 detection.
Multiple endocrine neoplasia type 1 in France: clinical and genetic studies
Authors: CALENDER A. , GIRAUD S. , COUGARD P. , CHANSON P. , LENOIR G. , MURAT A. , HAMON P. , PROYE C.
Published: August 2009

Abstract. Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by the involvement of several endocrine glands, including the parathyroid glands, the pancreatic islet cells, the anterior pituitary gland and other neuroendocrine tissues. In order to build up a French MEN1 register, a collaborative network was developed through the ‘Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1’ or GENEM 1. A 2‐year follow‐up in 40 medical and surgical units allowed the identification of more than 150 individual patients and 45 MEN1 families, and defined the major clinical features of the disease in our series. Multiple endocrine neoplasia type 1 is inherited as an autosomal dominant trait. The gene causing this syndrome has been localized to chromosome 11, band 11q13, and molecular genetic markers flanking the MEN1 locus are of use in identifying disease gene carriers in predisposed families. Selected data were presented in order to discuss the management of patients by combined clinical, biochemical and genetic screening. The set‐up of a national register by a multi‐disciplinary and collaborative medical and surgical network will facilitate further research on the clinical management of MEN1 patients and the basic physio‐pathology of the disease.
Operative tumour yield obviates preoperative pancreatic tumour localization in multiple endocrine neoplasia type 1
Authors: SKOGSEID B. , GRAMA D. , RASTAD J. , ERIKSSON B. , LINDGREN P.‐G. , AHLSTRÖM H. , LÖRELIUS L.‐E. , WILANDER E. , ÅKERSTRÖM G. , ÖBERG K.
Published: August 2009

Abstract. The efficiency of pancreatic tumour localization was prospectively evaluated in 12 consecutive patients with multiple endocrine neoplasia type 1 (MEN1), who were subjected to extirpation of 56 islet cell neoplasms of 0.2–4 cm in diameter (mean 0.8 cm) during pancreatic resection and enucleation. Computed tomography, angiography of the coeliac trunc and superior mesenteric artery, and percutaneous ultrasound correctly localized 7–12% of the tumours and 21–37% of the 19 lesions measuring at least one centimetre in diameter. Transhepatic portal vein sampling correctly located tumour sites in the proximal or distal portions of the pancreas in four out of six patients, but demonstrated unsatisfactory specificity. Intra‐operative ultrasound and bidigital palpation of the pancreas had overall sensitivities of 86 and 45%, respectively, and eight lesions below 0.3 cm in diameter remained undetected with intraoperative ultrasound. It is concluded that diagnosis of endocrine pancreatic neoplasms is biochemical in MEN1 and that broad screening of tumour markers efficiently reveals pancreatic involvement decades before the development of a clinically overt disease. Intra‐operative ultrasound is a requisite for pancreatic endocrine surgery in MEN1, and it obviates the need for conventional pancreatic imaging unless a pre‐operative search for metastatic disease and anatomical aberrations is considered important.
The RET proto‐oncogene and cancer
Authors: DONIS‐KELLER H.
Published: August 2009

Abstract. The RET proto‐oncogene, a receptor tyrosine kinase, has been evaluated as a candidate gene for multiple endocrine neoplasia type 2A and type 2B (MEN 2A and MEN 2B), for familial medullary thyroid carcinoma (FMTC), and for sporadic cases of medullary thyroid carcinoma (MTC) and pheochromocytomas. We determined the genomic structure of RET and used single‐strand conformational polymorphism (SSCP) analysis to identify sequence variants in genomic DNA from families segregating MEN 2 and FMTC. In addition, we examined paired tumour and lymphocyte genomic DNAs from individuals with sporadic cases of MTC and pheochromocytoma. Altogether, we and others found 21 missense mutations in five cysteines clustered in the extra cellular domain of RET (exons 10 and 11) associated with 111 MEN 2 A and FMTC families. In contrast, a single point mutation that results in the substitution of threonine for methionine within the catalytic core of the tyrosine kinase domain (codon 918, exon 16) is responsible for all 66 reported cases of MEN 2B. Two missense mutations and a six base‐pair deletion were identified in MTC tumour DNA, but no mutations were identified from pheochromocytoma tumour DNAs. A predictive DNA test for MEN 2A‐associated mutations in RET has been developed that is based on detection of missense mutations by polymerase chain reaction (PCR) amplification and restriction endonuclease cleavage. A dominant oncogene model for the action of the RET gene product is proposed as a mechanism of action in MEN 2A, MEN 2B, FMTC and for at least some cases of sporadic MTC.
Genotype‐phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium
Authors: Mulligan Lois M. , MARSH D. J. , ROBINSON B. G. , SCHUFFENECKER I. , ZEDENIUS J. , LIPS C. J. M. , GAGEL R. F. , TAKAI S.‐I. , NOLL W. W. , FINK M. , RAUE F. , LACROIX A. , THIBODEAU S. N. , FRILLING A. , PONDER B. A. J. , ENG C. ,   FOR THE INTERNATIONAL RET MUTATION CONSORTIUM
Published: August 2009

Abstract. The International RET Mutation Consortium was first convened as part of the Fifth International Workshop on Multiple Endocrine Neoplasia, Stockholm, Sweden, in an attempt to analyse the relationship of RET mutation and disease phenotype in the autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN 2) syndromes. Out of 361 families studied, 41% had MEN 2A, 17.7% MEN 2B, 6.4% FMTC and the remaining subjects were unclassified. RET mutations were detected in 87.3% of families overall. Over 93% of MEN 2B families had the RET 918 ATG → ACG mutation, while the most frequent mutation detected in MEN 2A families was cysteine codon 634 (87% of all mutations).
From medical history and biochemical tests to presymptomatic treatment in a large MEN 2A family*
Authors: LIPS C. J. M. , LANDSVATER R. M. , HÖPPENER J. W. M. , GEERDINK R. A. , BLIJHAM G. H. , VAN VEEN J. M. JANSEN‐SCHILLHORN , FELDBERG M. A. M. , VAN GILS A. P. G. , HOOGENBOOM H. , BERENDS M. J. H. , BEEMER F. A. , VAN AMSTEL H.‐K. PLOOS , VAN VROONHOVEN T. J. M. V. , VROOM T. M.
Published: August 2009

Abstract. An extensive study was published in 1959 in the Netherlands on a large family, which initially attracted attention because of a family history of attacks of shaking. Clinical investigation revealed phaeochromocytomas in four family members. In 1975, the family was identified to be a MEN 2A family, and since then, the members were examined annually using measurement of catecholamine metabolites in 24‐h excreted urine and C‐cell stimulation tests. In 1993, the RET proto‐oncogene on chromosome 10q11 was found to be associated with MEN 2A and a specific mutation in this gene was identified in the family. In this family, 32 MEN 2A patients were detected. Since screening started in 1975, no patient died of phaeochromocytoma; however, two patients died of metastasized medullary thyroid carcinoma (MTC) (mean age 46 years). Twelve patients were operated on for phaeochromocytoma, and 13 for MTC. The results of DNA‐analysis revealed the failures of the biochemical tests to identify affected family members. Six disease gene carriers with normal C‐cell stimulation test results appeared to have small multifocal MTCs. Two carriers with normal excretion levels of catecholamines had a small phaeochromocytoma. DNA‐analysis enables the unambiguous diagnosis of MEN 2A gene carriership, allowing presymptomatic surgery for MTC.
Euthyroid Graves' disease showing no thyroid abnormalities except positive thyroid‐stimulating antibody (TSAb): two case reports
Authors: WATANABE MIKIO , IWATANL YOSHINORI , KASHIWAI TAKU , IIJIMA TAKASHI , FUJIKADO TAKASHI , AMINO NOBUYUKI
Published: August 2009

Abstract. We report two cases of euthyroid Graves' disease in women who had ophthalmopathy without previous history of hyperthyroidism. Enlargement of extraocular muscles was observed by magnetic resonance imaging (MRI). The patients had no thyroid enlargement and their serum concentrations of free T4, free T3, and TSH were normal. The sera were negative for antithyroid microsomal and thyrogobulin antibodies, and anti‐TSH receptor antibodies measured by radioreceptor assay. T3 suppression test results were normal. Only thyroid‐stimulating antibody (TSAb) measured by sensitive bioassay was positive. These findings indicate that sensitive TSAb is the most useful laboratory test in the diagnosis of euthyroid Graves' disease.
Neuroendocrine ageing
Authors: Björntorp Per
Published: August 2009

Abstract. Ageing is followed by an involution of neuroendocrine functions, resulting in a decreased secretion of sex steroids and growth hormone. In addition, Cortisol secretion may be inadequately elevated upon stress challenges, due to deficient braking functions by central glucocorticoid receptors. In combination, these endocrine perturbations will probably result in changes in psychological factors such as energy and well‐being, altered body composition, and insulin resistance, as well as other risk factors for diseases characteristic of the ageing human, such as cardiovascular disease, non‐insulin‐dependent diabetes mellitus and stroke. This cluster of phenomena is frequently seen before the period of normal ageing, indicating premature ageing processes. The background factors in these conditions probably include psychosocial stressors, which are perceived differently depending on individual coping abilities. Socio‐economic and other environmental factors, such as smoking and alcohol abuse, may well be responsible for the expression of this syndrome of premature ageing. Preventive and therapeutic trials with hormonal substitution therapy to treat these aberrations have been promising, and encourage further studies aimed at elucidating potential risks in relation to potential improvement of quality of life and, perhaps, longevity.
Effect of gemfibrozil on the regulation of HDL subfractions in hypertriglyceridaemic patients
Authors: Kahri Juhani , SANE T. , VAN TOL A. , TASKINEN M.‐R.
Published: August 2009

Abstract. Objectives. To study changes of HDL subfractions and their regulation during gemfibrozil treatment in hypertriglyceridaemia.

Design. Twenty patients with hypertriglyceridaemia were randomized to receive either 1200 mg day‐1gemfibrozil or placebo for 3 months. After a 6‐week, single‐blind placebo period, the patients were randomized to receive either gemfibrozil or placebo for 3 months in a double‐blind study.

Setting. The patients were studied as outpatients in the Third Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.

Main outcome measures. Ultracentrifugally isolated HDL subclasses; concentrations of apoA‐I, apoA‐II, LpA‐I and LpA‐I: A‐II particles; post‐heparin plasma lipoprotein lipase (LPL), hepatic lipase (HL) and plasma cholesteryl ester transfer protein (CETP) activities; phospholipid transfer protein (PLTP) and lecithine cholesteryl acyltransferase (LCAT) activities were measured in plasma from six patients from both groups.

Results. Gemfibrozil increased the concentration of HDL cholesterol (+ 11.1%) because of the rise of HDL3 cholesterol (34.5%, P < 0.01). The concentration of LpA‐I particles was reduced during gemfibrozil treatment (–12.4%, P < 0.05), while that of apoA‐II increased (+ 12.3%, P < 0.01). The LpA‐I to LpA‐I:A‐II ratio decreased significantly in the gemfibrozil group (–18.9%, P < 0.01). Gemfibrozil increased LPL and HL activities by 18.2% (P < 0.05) and by 19.6%, respectively. Plasma CETP activity was also increased during gemfibrozil treatment (+15.8%, P < 0.05).

Conclusion. The gemfibrozil‐induced elevation of HDL3 and apoA‐II may reflect the combined action of LPL, HL and CETP on plasma HDL metabolism.
Propafenone in a usual dose produces severe side‐effects: the impact of genetically determined metabolic status on drug therapy
Authors: Mörike Klaus , MAGADUM S. , METTANG T. , GRIESE E.‐U. , MACHLEIDT C. , KUHLMANN U.
Published: August 2009

Abstract.We report the case of an elderly lady presenting with dizziness, a head injury resulting from a fall and bradycardia. Propafenone 150 mg t.i.d. had been prescribed for atrial fibrillation with tachyarrhythmia, induced by hyperthyroidism, 18 months earlier. A toxic concentration of parent propafenone, and no 5‐hydroxy metabolite, was detected in a plasma sample. Symptoms disappeared after the discontinuation of propafenone. The poor metaboliser (PM) phenotype of sparteine/debrisoquine was assumed and subsequently confirmed by phenotyping (sparteine test) and genotyping (allele‐specific polymerase chain reaction). The PM phenotype is common in European populations, with a prevalence of about 7%. If drugs with narrow therapeutic ranges undergo genetically polymorphic metabolism, toxicity may arise even with recommended doses. Individualization of doses is required to avoid adverse effects.
Prorenin and renal function in NIDDM patients with normo‐ and microalbuminuria
Authors: Nielsen Søren , SCHMITZ A. , DERKX F. H. M. , MOGENSEN C. E.
Published: August 2009

Abstract. Objectives. To assess whether prorenin is elevated and perhaps a predictor of deteriorations in albuminuria and/or renal function in NIDDM patients with normo‐ and microalbuminuria.

Design. A cross‐sectional and a longitudinal study.

Setting. Outpatient diabetic clinic.

Subjects. Twenty‐eight NIDDM patients (16 with normoalbuminuria, 12 with microalbuminuric) and 16 healthy subjects, matched for sex, age and BMI. Fifteen patients were reinvestigated after (mean [range]) 3.1 (2.1–4.3) years.

Main outcome measures. Serum prorenin and renin, urinary albumin excretion rate, and glomerular filtration rate.

Results. Serum prorenin was similar in both normoalbuminuric (116 × / ÷ 1.9 μU ml‐1(geometric mean × / ÷ antilog SD) and microalbuminuric (124 × / ÷ 1.7 μU ml‐1) as well as in healthy control subjects (90 × / ÷ 1.7 μU ml‐1). Prorenin did not correlate to either urinary albumin excretion rate or glomerular filtration rate. No difference between baseline and follow‐up levels of albuminuria, glomerular filtration rate or prorenin were observed. The annual changes in albuminuria, glomerular filtration rate and prorenin were not correlated, and no correlation was found between baseline prorenin levels and annual changes in albuminuria or glomerular filtration rate.

Conclusions. Serum prorenin levels are not elevated in either normoalbuminuric or microalbuminuric NIDDM patients, and serum prorenin is not a valid predictor of long‐term changes in albuminuria in this patient group.
The hospital: battleground or meeting place? Ethical considerations regarding a fair distribution of new medical technologies
Authors: VAN DER KLOOT MEIJBURG H. H.
Published: August 2009

Abstract. Here, the notion of distributive justice is explored in relation to the introduction and the application of new medical technologies within the clinical setting. The point of departure is that, in the decision making process on what is necessary and fair in patient care, participants will mobilize different ethical models to justify their outlooks and interests. The history of the introduction of Taxol (paclitaxel) is used as an illustration. In the hospital, it is important to make a clear distinction between the moral obligations of the physician and those of the chief executive officer (medical director). Finally, a model is proposed that could help to develop a better moral understanding on the meso‐level about what is necessary and fair in distributing the results of medical innovations, without turning the clinic into a battleground of moral interests.
Nitric oxide modulates the discharge rate of basal forebrain neurones: a study in freely moving rats
Authors: KOSTIN ANDREY , STENBERG DAG , PORKKA‐HEISKANEN TARJA
Published: August 2009

In urethane‐anaesthetized rats the infusion of a nitric oxide (NO)‐donor [NOC‐18, 1 mM (DETA/NO); 2,2’‐(hydroxynitrosohydrazino)bis‐ethanamine)] into the basal forebrain (BF) inhibited the discharge rate of most neurones, suggesting that NO may promote sleep via inhibition of wake‐promoting neurones in the BF. However, this hypothesis still needs to be confirmed in freely moving rats. The objective of this study was to examine whether NO modulates the discharge rate of BF neurones in freely moving rats in a similar manner to anaesthetized rats. We measured the discharge rates of BF neurones in freely moving rats during microdialysis infusion of a NO‐donor (1 mm; NOC‐18) in different vigilance states. Neurones were characterized as wake (W)‐on (51.8%), W‐off (28.6%) and W/non‐rapid eye movement (REM)‐independent (21.4%) based on their discharge profiles during wakefulness (W) and non‐REM sleep. The NO‐donor affected the discharge rate of most BF neurones during quiet wakefulness (QW; 55%) and non‐REM sleep (64%). The most prominent response in all neuronal groups was a decrease in the discharge rate during QW and non‐REM sleep. A small subpopulation of neurones increased the discharge rate. The increase in NO in the BF during prolonged wakefulness may facilitate sleep via inhibition of wake‐promoting neurones.
Cannabinoid signalling in the enteric nervous system
Authors: Galligan J. J.
Published: August 2009

Abstract  Cannabinoid signalling is an important mechanism of synaptic modulation in the nervous system. Endogenous cannabinoids (anandamide and 2‐arachidonyl‐glycerol) are synthesized and released via calcium‐activated biosynthetic pathways. Exogenous cannabinoids and endocannabinoids act on CB1 and CB2 receptors. CB1 receptors are neuronal receptors which couple via G‐proteins to inhibition of adenylate cyclase or to activation or inhibition of ion channels. CB2 receptors are expressed by immune cells and cannabinoids can suppress immune function. In the central nervous system, the endocannabinoids may function as retrograde signals released by the postsynaptic neuron to inhibit neurotransmitter release from presynaptic nerve terminals. Enteric neurons also express CB receptors. Exogenously applied CB receptor agonists inhibit enteric neuronal activity but it is not clear if endocannabinoids released by enteric neurons can produce similar responses in the enteric nervous system (ENS). In this issue of Neurogastroenterology and Motility, Boesmans et al. show that CB1 receptor activation on myenteric neurons maintained in primary culture can suppress neuronal activity, inhibit synaptic transmission and mitochondrial transport along axons. They also provide initial evidence that myenteric neurons (or other cell types present in the cultures) release endocannabinoids and which activate CB1 receptors constitutively. These data provide new information about targets for cannabinoid signalling in the ENS and highlight the potential importance of CB receptors as drug targets. It is necessary that future work extends these interesting findings to intact tissues and ideally to the in vivo setting.
Factors influencing the incidence and prevalence of food allergy
Authors: Cochrane S. , Beyer K. , Clausen M. , Wjst M. , Hiller R. , Nicoletti C. , Szepfalusi Z. , Savelkoul H. , Breiteneder H. , Manios Y. , Crittenden R. , Burney P.
Published: August 2009

Food allergy is an increasing problem in Europe and elsewhere and severe reactions to food are also becoming more common. As food allergy is usually associated with other forms of allergic sensitisation it is likely that many risk factors are common to all forms of allergy. However the potential severity of the disease and the specific public heath measures required for food allergy make it important to identify the specific risk factors for this condition. Food allergy is unusual in that it often manifests itself very early in life and commonly remits with the development of tolerance. Hypotheses that explain the distribution of food allergy include specific genetic polymorphisms, the nature of the allergens involved and the unique exposure to large quantities of allergen through the gut. Progress has been made in developing more specific and testable hypotheses but the evidence for any of these is still only preliminary. Further collaborative research is required to develop an appropriate public health response to this growing problem.
Cross‐talk between L‐type Ca2+ channels and mitochondria
Authors: Viola Helena M , Hool Livia C
Published: August 2009

1. Calcium is necessary for myocardial function, including contraction and maintenance of cardiac output. Calcium is also necessary for myocardial energetics and production of ATP by mitochondria, but the mechanisms for calcium regulation by mitochondria are still not fully resolved.

2. The cytoskeleton plays an important role in maintaining a cell’s integrity. It is now recognized that cytoskeletal proteins can also assist in the transmission of signals from the plasma membrane to intracellular organelles. Cytoskeletal proteins can regulate the function of the L‐type Ca2+ channel and alter intracellular calcium homeostasis.

3. Recent evidence suggests that calcium influx through the L‐type Ca2+ channel is sufficient to alter a number of mitochondrial functional parameters, including superoxide production, NADH production and metabolic activity, assessed as the formation of formazan from tetrazolium salt. This occurs in a calcium‐dependent manner.

4. Activation of the L‐type Ca2+ channel also alters mitochondrial membrane potential in a calcium‐independent manner and this is assisted by movement of the auxiliary β2‐subunit through F‐actin filaments.

5. Because the L‐type Ca2+ channel is the initiator of contraction, a functional coupling between the channels and mitochondria may assist in meeting myocardial energy demand on a beat‐to‐beat basis.
The effect of micro‐incision and small‐incision coaxial phaco‐emulsification on corneal astigmatism
Authors: Wang Jun , Zhang En‐Kui , Fan Wen‐Ying , Ma Jian‐Xin , Zhao Peng‐Fei
Published: August 2009

Abstract

Purpose:  To evaluate the effect of micro‐incision (2.2 mm) and small‐incision (2.6 mm or 3.0 mm) coaxial phaco‐emulsification on surgically induced astigmatism (SIA).

Methods:  Cataract patients (n = 83, 129 eyes) were randomized into three groups: 43 eyes in the 2.2‐mm incision group, 42 eyes in the 2.6‐mm group and 44 eyes in the 3.0‐mm group. Torsional phaco‐emulsification was followed by intraocular lens implantation via the Monarch II injector with the C cartridge (Alcon Laboratories Inc., Fort Worth, TX, USA). Corneal astigmatism, SIA and uncorrected distance visual acuity were assessed 30 and 90 days after cataract surgery.

Results:  At 30 and 90 days postoperative, SIA of the 3.0‐mm group was greater than SIA of the 2.2‐mm and 2.6‐mm groups (P ≤ 0.015), but SIA was similar between the 2.2‐mm group and the 2.6‐mm group. Timewise, mean SIA at 30 days was greater than SIA at 90 days in the 3.0‐mm group (P = 0.04), while SIA did not change with time for the 2.2‐mm and 2.6‐mm groups. Postoperative uncorrected distance visual acuity tended to be better with the smaller incisions, but this trend did not reach stastical significance (P ≥ 0.07).

Conclusion:  Incision size contributed to postoperative corneal astigmatism. When incision size was reduced from 3.0 mm to 2.6 mm, SIA was reduced and refractive stabilization was faster. Reduction of incision size from 2.6 mm to 2.2 mm offered no greater reduction of SIA when using the C cartridge; however, the D cartridge (designed for 2.2‐mm incisions) should be evaluated.
Laryngeal mask airways – to inflate or to deflate after insertion?
Authors: Von UNGERN‐STERNBERG BRITTA S. , ERB THOMAS O. , CHAMBERS NEIL A. , HEANEY MAIREAD
Published: August 2009

Background:  Hyperinflation of the laryngeal mask airway (LMA) cuff is known to be a risk factor for airway morbidity and increased leakage around the LMA. While the manufacturers’ recommendation is to inflate the cuff with the maximum recommended volumes and/or to adjust the cuff pressure to <60 cmH2O, cuff pressures below 40 cmH2O have been shown to be associated with a minimal rate of sore throat and minimal leakage. However, it remains to be determined whether inflation or deflation is needed to achieve favorable pressures. Therefore, we assessed the need for cuff‐volume adjustment following insertion of the LMA unchanged straight from the sterile packaging in a prospective audit.

Methods:  One thousand children (0–16 years) undergoing elective surgery were consecutively included in this quality of care audit. After taking the LMA from its sterile packaging, the LMA cuff was emptied and the amount of air recorded. Then, the same amount of air was returned into the LMA, the LMA was inserted into the patient, and the cuff pressure was measured using a calibrated cuff manometer.

Results:  Following insertion of the LMA (without further inflation or deflation of the cuff), 20.5% of children had cuff pressures ≥60 cmH2, while 55.7% had LMA cuff pressures <40 cmH2O. Cuff pressures were also significantly higher in size 1 LMAs (66.6% had cuff pressures ≥60 cmH2O and 2% <40 cmH2O) compared with all other sizes (P < 0.05). Furthermore, cuff pressures in LMAs with a poly vinyl chloride (PVC) surface were higher compared to LMAs with a silicone surface (65.2%≥60 cmH2O and 9.3% <40 cmH2O vs 9%≥60 cmH2O and 67.6% <40 cmH2O, respectively).

Conclusions:  This study demonstrates that LMAs, particularly when using small‐sized LMAs or LMAs with a more rigid PVC surface, need to be deflated following insertion of the device rather than inflated to avoid cuff hyperinflation. Hence, cuff pressures should be measured routinely using a manometer to minimize potential pressure‐related airway complications.
Hemostatic consequences of a non‐fresh or reconstituted whole blood small volume cardiopulmonary bypass prime in neonates and infants
Authors: HORNYKEWYCZ STEPHAN , ODEGARD KIRSTEN C. , CASTRO ROBERT A. , ZURAKOWSKI DAVID , PIGULA FRANK , DINARDO JAMES A.
Published: August 2009

Objectives:  Despite aggressive measures to miniaturize the cardiopulmonary bypass (CPB) circuit in neonates and infants, the CPB prime volume is often at least as large as the patients’ blood volume. We conducted an observational study to characterize the hemostatic consequences of a CPB prime consisting of either non‐fresh or reconstituted whole blood.

Methods:  Hematocrit, fibrinogen, platelet count, plasminogen, anti‐thrombin III (AT‐III), and factors (F) II, V, VII, IX, and X of 30 neonates and infants undergoing cardiac surgery with CPB utilizing either a non‐fresh or reconstituted whole blood prime were prospectively evaluated at eight time points. Following protamine administration, microvascular bleeding was treated by protocol.

Results:  The hemostatic composition of the CPB prime was the same following the use of either non‐fresh or reconstituted whole blood. The CPB prime platelet count (mean ± sd) was 5.87 ± 2.84 × 103 μl−1 when compared to a preoperative platelet count of 298 ± 142 × 103 μl−1 (P < 0.0001). Twenty patients received 17.3 ± 9.2 ml·kg−1 (0.86 ± 0.46 units·kg−1) of platelets with significant improvement in platelet count. Nine patients received 16.7 ± 13.4 ml·kg−1 (0.84 ± 0.67 units·kg−1) of cryoprecipitate with significant improvements in FVIII and fibrinogen.

Conclusions:  Non‐fresh or reconstituted whole blood as a component of a small volume CPB prime in neonates and infants induces clinically significant dilutional thrombocytopenia in conjunction with less significant reductions in fibrinogen, FII, FV, FVII, FVIII, FIX, FX, plasminogen, and AT‐III.
O‐acetyltransferase gene neuO is segregated according to phylogenetic background and contributes to environmental desiccation resistance in Escherichia coli K1
Authors: Mordhorst Ines L. , Claus Heike , Ewers Christa , Lappann Martin , Schoen Christoph , Elias Johannes , Batzilla Julia , Dobrindt Ulrich , Wieler Lothar H. , Bergfeld Anne K. , Mühlenhoff Martina , Vogel Ulrich
Published: August 2009

Escherichia coli K1 causes disease in humans and birds. Its polysialic acid capsule can be O‐acetylated via phase‐variable expression of the acetyltransferase NeuO encoded by prophage CUS‐3. The role of capsule O‐acetylation in ecological adaptation or pathogenic invasion of E. coli K1 is largely unclear. A population genetics approach was performed to study the distribution of neuO among E. coli K1 isolates from human and avian sources. Multilocus sequence typing revealed 39 different sequence types (STs) among 183 E. coli K1 strains. The proportion of the ST95 complex (STC95) was 44%. NeuO was found in 98% of the STC95 strains, but only in 24% of other STs. Grouping of STs and prophage genotypes revealed a segregation of prophage types according to STs, suggesting coevolution of CUS‐3 and the E. coli K1 host. Within the STC95, which is known to harbour both human and avian pathogenic isolates, CUS‐3 genotypes were shared irrespective of the host species. Functional analysis of a variety of strain pairs revealed that NeuO‐mediated K1 capsule O‐acetylation enhanced desiccation resistance. In contrast, NeuO expression led to a reduced biofilm formation in biofilm positive E. coli K1 isolates. These findings suggest a delicate ecological balance of neuO‘on’/‘off’ switching.