bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic features of acute myocardial infarction – changes over time from 1983 to 1990: results from the FINMONICA AMI register study
Authors: SALOMAA V. , MIETTINEN H. , PALOMÄKI P. , ARSTILA M. , MUSTANIEMI H. , KUULASMAA K. , TUOMILEHTO J. ,   FINMONICA AMI Register Study Group
Published: August 2009

Abstract. Objectives. To examine, whether the acute myocardial infarctions (AMIs) are becoming smaller.

Design. Analysis of electrocardiogram (ECG) and enzyme findings of community‐based AMI registers in three geographical areas of Finland during the 8‐year period 1983–90.

Setting. In the FINMONICA AMI Register, all suspected coronary events in persons aged 25–64 years have been registered since 1983 according to the protocol of the WHO MONICA project in the provinces of North Karelia and Kuopio in eastern Finland and Turku/Loimaa area in south‐western Finland.

Subjects. Each consecutive case of suspected AMI originating from the monitored populations. During the study period, 11487 definite or possible AMIs were registered.

Main outcome measures. Trends in ECG findings classified as definite or probable, and trends in enzyme findings classified as abnormal or equivocal.

Results. Of the registered AMIs, 8439 (73.5%) reached the hospital alive and survived ≥ 24 h from the beginning of the symptoms. They were included in the analyses of this report and divided further, to first ever AMIs (n = 5392) and to recurrent AMIs (3047). During the study period, the proportion of ECG findings classified as definite on the basis of the serial Minnesota coding declined in men 3.1% year−1 (P < 0.0001) on average for first AMIs and 1.9% year−1 (P = 0.004) for recurrent AMIs. In women, the corresponding declines were 1.9% year−1 (P = 0.007) and 1.6% year−1 (P = 0.02), respectively. Also, the proportion of enzymes classified as abnormal declined amongst men 2.2% year (P < 0.0001) for first AMIs and 2.8% year−1 (P < 0.0001) for recurrent AMIs. In women, the corresponding declines for abnormal enzymes was 1.3% year−1 (P = 0.13) and 3.0% year−1 (P = 0.02). These findings were consistent in all three areas with different registration teams and different laboratories. The proportion of definite ECG findings amongst patients hospitalized for AMI declined almost by half and the proportion of abnormal enzyme findings declined almost by one‐third during the study period.

Conclusions. Our findings are compatible with the clinical observation that the hospitalized AMIs are becoming smaller. The timing and magnitude of the changes suggest that they are mainly caused by decreased risk‐factor levels in the population. Improved treatment of coronary heart disease and changed hospital admission policy are likely to be contributing factors.
Body fat as a predictor of the antihypertensive effect of nifedipine
Authors: STØA‐BIRKETVEDT G. , THOM E. , AARBAKKE J. , FLORHOLMEN J.
Published: August 2009

Abstract. Objective. The aim of this study was to investigate the relationship between the blood pressure response and body fat in patients treated with the calcium entry blocker nifedipine.

Subjects. Forty untreated subjects with moderate hypertension completed the study.

Interventions. Height, weight, body mass index (BMI) and body fat (measured by near infrared spectrophotometry using Futrex 5000) were measured before the start of the study. Based on blood pressure measurements before and 30 min after one capsule of 10 mg nifedipine, the patients were allocated to treatment with 10 mg nifedipine daily in the re‐sponder group (reduction in diastolic blood pressure ≥ 10 mmHg) and with 20 mg nifedipine daily in the non‐responder group. Finally, the blood pressure was measured after 1 week.

Results. Twelve patients were classified as responders and 28 patients as non‐responders. The responder/non‐responder groups were comparable with respect to the blood pressure readings initially and to age, whereas the non‐responders had higher weight (P < 0.01) and BMI (P < 0.01), more body fat (P < 0.01) and were smaller in height (P < 0.01). After 1 week no additional antihypertensive effect was observed in either group. The blood pressure reduction was negatively correlated to the body fat mass in kilogrammes (P < 0.05 for systolic and P < 0.01 for diastolic blood pressure) in the responder group but not in the non‐responder group, whereas no significant correlations were found to BMI in either group.

Conclusion. Our data indicate that the body fat can be used to predict the antihypertensive effect of nifedipine.
Imaging of the sella in the syndrome of inappropriate secretion of antidiuretic hormone
Authors: PAPAPOSTOLOU C. , MANTZOROS C. S. , EVAGELOPOULOU C. , MOSES A. C. , KLEEFIELD J.
Published: August 2009

Abstract. Objective. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) results either from ectopic production or inappropriate release of antidiuretic hormone from the neurohypophysis. Although magnetic resonance imaging (MRI) has provided new insights into the morphological changes of the hypophysis in health and disease, no previous studies have evaluated its use in SIADH. The aim of this study was to evaluate the MRI appearance of the neurohypophysis in patients with SIADH.

Design. Retrospective case‐control study.

Setting. Tertiary care teaching hospital.

Subjects. We studied retrospectively eight patients with SIADH who had been hospitalized in Boston's Beth Israel between 1984 and 1994 and who had MRI scans including the sella turcica. We also evaluated prospectively the MRIs of the heads of 23 consecutive control patients who had no pituitary pathology and no serum osmolality or electrolyte abnormalities.

Interventions. Clinical evaluation as well as sagittal and axial T1‐MR images.

Main outcome measures. Presence or absence of the high intensity signal of the neurohypophysis.

Results. In seven out of eight patients (87.5%) the normal high intensity signal of the neurohypophysis was not present. In one patient (12.5%), two interpreting radiologists disagreed about its presence. The high intensity signal was present in the neurohypophysis of 20 out of 23 controls (87.5%).

Conclusions. Our data indicate an association of SIADH with the absence of the normal hyperintense signal of the neurohypophysis, confirming the usefulness of MRI as a tool to visualize ADH processing. These data also raise the possibility that the absence of the high intensity signal may be a useful diagnostic tool in cases of SIADH that are difficult to diagnose clinically. Additional studies to correlate this signal with various forms of SIADH will be needed.
Microalbuminuria, insulin sensitivity and haemostatic factors in non‐diabetic treated hypertensive men
Authors: AGEWALL S. , FAGERBERG B. , ATTVALL S. , LJUNGMAN S. , URBANAVICIUS V. , TENGBORN L. , WIKSTRAND J. ,   Risk factor Intervention Study Group
Published: August 2009

Abstract. Objective. To examine whether microalbuminuria in non‐diabetic, treated hypertensive men is associated with insulin resistance and measures of endothelial function, thrombogenesis and fibrinolysis.

Design. Cross‐sectional study.

Setting. Outpatient clinic in city hospital.

Patients. Ninety‐two treated hypertensive men, aged 57–77 years, either with a serum cholesterol of ≥ 6.5 mmol L−1 or smokers, or both. Patients with diabetes mellitus or overnight urinary albumin excretion of > 100 mg 12 h−1 were excluded.

Main outcome measures. Overnight urinary albumin excretion, insulin‐mediated glucose disposal (hyper‐insulinaemic euglycaemic clamp), blood glucose and plasma insulin during oral glucose tolerance test, fibrinogen, von Willebrand factor and plasminogen activator inhibitor activity.

Results. Microalbuminuric patients had increased blood glucose concentrations during the oral glucose tolerance test and higher plasma fibrinogen levels compared with the normoalbuminuric patients. In a randomly selected subgroup (n = 36), insulin‐mediated glucose disposal was lower in microalbuminuric than in normoalbuminuric patients, and an inverse relationship between insulin sensitivity and albuminuria (r = –0.37; P = 0.028) was found. This relationship was not significant after adjustment for body‐mass index (P = 0.098). In the univariate analyses including all patients, albuminuria was associated with blood glucose, serum creatinine, body‐mass index, systolic blood pressure, fibrinogen, von Willebrand factor and cholesterol (negatively). In a multiple regression analysis, only the body‐mass index was independently related to urinary albumin excretion.

Conclusions. Microalbuminuria was associated with insulin resistance but obesity was a confounding factor. Relationships between microalbuminuria and fibrinogen as well as von Willebrand factor were found, but only in univariate analysis.
Refractory oedema in congestive heart failure: a contributory role of loop diuretics?
Authors: HALLER C. , SALBACH P. , KATUS H. , KÜBLER W.
Published: August 2009

Abstract. We report a patient with congestive heart failure (CHF) who presented with massive oedema resistant to therapy with maximal doses of loop diuretics, despite an adequate renal function. After a diuretic pause and dietary salt restriction, a conventional dose of furosemide in combination with distally active diuretics induced a prompt weight loss exceeding 30 kg with stable renal function. We suggest that the ‘refractory’ oedema in this patient was due to a combination of CHF and inappropriate (loop) diuretic therapy in conjunction with a high dietary sodium intake. We conclude that in the absence of hyponatraemia and renal failure, even severe oedema may not represent a negative prognostic indicator. The recognition of diuretic‐associated mechanisms complicating cardiac oedema is essential to avoid the vicious circle of worsening oedema whilst escalating therapy with loop diuretics.
Factor V gene mutation causing inherited resistance to activated protein C as a basis for venous thromboembolism
Authors: DahlbäCK B.
Published: August 2009

Abstract. Venous thromboembolism is often familial, suggesting that genetic risk factors are involved. Until recently, genetic defects known to predispose for thrombosis (deficiencies of antithrombin III, protein C, and protein S) had not been shown to account for more than 5–10% of the cases. Inherited resistance to the anticoagulant function of activated protein C (APC) in the last year has been identified as a major basis for familial thrombosis. Unlike other genetic risk factors for thrombosis, APC resistance is highly prevalent in the general population (2–5%). In more than 90% of cases, the APC‐resistance phenotype is associated with a point mutation in the factor V gene, which predicts replacement of arginine at position 506 with a glutamine. As APC inhibits factor Va by cleavage at arginine 506, mutated factor V is resistant to APC. In its heterozygous state, the mutation is associated with a 5–10‐fold increased risk of thrombosis. Homozygocity is associated with more severe APC resistance, and with a higher risk of thrombosis. Because of its high prevalence in the population, individuals with deficiencies of other anticoagulant proteins occasionally carry the factor V gene mutation. People with such combinations of mutations have a higher risk of thrombosis than those with the single mutations. In conclusion, in the majority of familial thrombosis cases it is now possible to identify an underlying genetic risk factor. APC resistance caused by a single, factor V gene mutation, is the most frequent risk factor and it is at least ten times more common than any of the other genetic defects associated with thrombosis.
Human somatic gene therapy: progress and problems
Authors: BRENNER M. K.
Published: August 2009

Abstract. Whilst the potential of gene therapy is considerable, current applications have been restricted by the limitations of available vectors. As yet, no vector is able to produce the desired safe, targeted and efficient transfer of genetic material with regulation of the new gene in the targeted cell. Notwithstanding these limitations, more than 65 clinical gene transfer protocols have been approved in the US. The majority of these are open to patients with malignant disease, in whom the risk: benefit ratio is most appropriate. Current progress and problems in gene transfer are illustrated by reference to gene transfer into haemopoietic stem cells (HSC), an area that has attracted particular attention, both because of the logistic advantages of these cells and because of the wide range of pathologies that may be corrected in the HSC itself or in its progeny. Because of the low efficiency of transfer into HSC, initial studies have involved transfer of marker genes to determine the origin of relapse after autologous bone marrow transplantation and to learn more about the conditions that enhance gene transfer and expression in haemopoietic tissue. Information gained from these studies is already guiding the practice of autologous and allogeneic marrow transplantation and has contributed to the development of gene therapy protocols for the treatment of malignant disease, immune deficiency syndromes and lysosomal storage disorders. Over the next decade, as the technology of gene transfer advances, many further clinical applications of the approach will become evident.
Improvement of serum lipids and blood pressure during intervention with n‐3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia
Authors: GRUNDT H. , NILSEN D. W. T. , HETLAND Ø. , AARSLAND T. , BAKSAAS I. , GRANDE T. , WOIE L.
Published: August 2009

Abstract. Objectives. To investigate the effect of an omega‐3 fatty acid concentrate K85 on serum lipids, lipoproteins, insulin metabolism and blood pressure in subjects with combined hyperlipidaemia.

Design. After a run‐in dietary period of 10 weeks, subjects were randomly allocated to receive either encapsulated K85 (n = 28) or corn oil (n = 29). The intervention was double‐blind.

Setting. An outpatient centre in Stavanger, Norway.

Subjects. Fifty‐seven of 141 individuals, who, after the run‐in period continued to meet the inclusion criteria: serum triglycerides of ≥ 2.0 mmol L−1 and total serum cholesterol of ≥ 6.0 mmol L−1.

Intervention. Encapsulated K85, containing 85% eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), or corn oil, both administered in a daily dose of 4 g for 12 weeks.

Main outcome measures. Change in metabolic and haemodynamic parameters related to intervention. Results. Serum EPA and DHA increased significantly in the K85 group during the treatment period. The body‐mass index remained unchanged. A 28% reduction in serum triglycerides was noted in the K85 group from the first 4 weeks. Total serum cholesterol was significantly reduced with both regimens. Serum high‐density lipoprotein cholesterol increased significantly during the first 8 weeks in the K85 group. Significant reductions in systolic and diastolic blood pressures were noted in subjects on K85. The treatment did not affect serum glucose, plasma insulin and proinsulin levels. Insulin: glucose and proinsulin: glucose ratios remained unchanged.

Conclusions. The atherogenic risk profile was improved with K85 in subjects with combined hyperlipidaemia, but n‐3 fatty acids supplementation did not affect glucose/insulin homeostasis.
Daytime sleepiness, snoring and gastro‐oesophageal reflux amongst young adults in three European countries
Authors: JANSON C. , GISLASON T. , DE BACKER W. , PLASCHKE P. , BJÖRNSSON E. , HETTA J. , KRISTBJARNASON H. , VERMEIRE P. , BOMAN G.
Published: August 2009

Abstract. Objectives. To study the geographical variation in daytime sleepiness, snoring and disrupted breathing during sleep and to identify and compare risk factors using the same method in four European cities.

Design. A cross‐sectional, multicentre epidemiological survey.

Setting. Reykjavik in Iceland, Uppsala and Göteborg in Sweden and Antwerp in Belgium.

Participants. A random population sample of 2202 subjects who participated in the European Community Respiratory Health Survey.

Main outcome measures. Sleep disturbances and daytime symptoms.

Results. At all the centres, 5% of the men and 2–3% of the women reported snoring every night. Daytime sleepiness (DS) was more often reported in Uppsala [odds ratio (OR) and 95% confidence interval: 1.6 (1.2–2.1)] than in the other centres, whilst daytime tiredness (DT) was most common in Reykjavik [OR 1.8 (1.4–2.1)]. Snoring was positively correlated with age, male gender and body‐mass index in all areas. Symptoms of gastro‐oesophageal reflux were associated with DS: OR 2.6 (1.5–4.4) and DT: OR 4.5 (2.7–7.6) and disrupted breathing: OR 3.8 (1.4–10). DS and DT were reported more often by women than by men.

Conclusion. The prevalence of snoring was about the same in all four areas, whilst there was a geographical variation in daytime sleepiness and tiredness. As complaints of DS and DT and disrupted breathing were more common in subjects who reported symptoms of gastro‐oesophageal reflux, we suggest that polysomnographic studies comparing sleep patterns in adult patients with and without reflux should be conducted.
Effects of smoking and physical activity on body weight: developments in Sweden between 1980 and 1989
Authors: WOLK A. , RÖSSNER S.
Published: August 2009

Abstract. Objectives. To study the effects of changes in smoking and exercise habits on body weight in Sweden.

Design. Analysis of factors affecting relative body weight by construction of regression equations using two models: one adjusted for age, education, socioeconomic group, geographical region and nationality, the other further adjusted for cigarette smoking and leisure‐time physical activity.

Setting. Cross‐sectional interview data derived from the ‘Undersökning om LevnadsFörhållanden’ (Living Conditions) survey 1980–81 and 1989–89.

Subjects. Nationally representative samples of Swedish men and women aged 16–84.

Main outcome measures. Changes in body‐mass index (BMI) in Sweden during the 1980s.

Results. Using the first model, an increase in the BMI of 0.23 kg/m2 in men and 0.17 kg/m2 in women, from 1980 to 1989, was found. When controlling for smoking and physical activity, these values were 0.20 and 0.18 kg/m2, respectively, (P at least < 0.003).

Conclusions. These findings indicate that the reported decrease in smoking and changes in physical activity during the 1980s only marginally explain the BMI increase in the adult Swedish population. The health programmes launched during the 1980s seem to have little beneficial effects on body‐weight development, in particular in younger generations of both sexes.
Chronic mesenteric ischaemia: diagnostic challenges and treatment options
Authors: HOOGENBERG K. , VAN ESSEN L. H. , VAN DEN DUNGEN J. J. A. M. , LIMBURG A. J. , BOEVE W. J. , KLEIBEUKER J. H.
Published: August 2009

Abstract. Objectives. A description of the clinical presentation, diagnostic procedure and mode of therapy in three patients suffering from chronic mesenteric ischaemia.

Design and interventions. In all cases, the diagnosis was made on the basis of abdominal complaints in combination with angiographic findings. The primary treatment objective was restoration of blood flow via a revascularization procedure, for the patient in whom this could not be accomplished an enteral feeding programme was undertaken.

Results. One patient had a panmalabsorption syndrome which was treated with an aortomesenteric bypass operation, the second one presented with multiple gastric ulcerations which only improved after a percutaneous transluminal angioplasty. In the third patient, neither surgery or angioplasty were feasible and a tentative enteral feeding programme was given, after which the ability to consume a normal oral diet without abdominal distress was regained.

Conclusions. These three cases illustrate the diverse clinical pictures by which chronic mesenteric ischaemia may present itself. This diagnosis should be kept in mind when other more common causes of a patient's abdominal complaints cannot be found, hence giving consideration to abdominal angiography as the next diagnostic procedure. With respect to therapy, restoring blood flow through surgery or angioplasty is the primary form of treatment. However, if neither of these therapeutic options is feasible, it is suggested that such patients may benefit from a nutritional training programme.
Erythrocyte porphobilinogen deaminase activity and primary liver cancer
Authors: KACZYNSKI J. , HANSSON G. , THUNELL S. , WETTERBERG L. , WALLERSTEDT S.
Published: August 2009

Abstract. Objectives. To study whether primary liver cancer (PLC) could be associated with acute intermittent porphyria (AIP) carriership and whether the activity of erythrocyte porphobilinogen deaminase (PBGD) could be used as a tumour marker for PLC.

Design. Prospective study.

Setting. Medical and surgical wards in two general hospitals in Göteborg, Sweden.

Subjects. All patients with a strong suspicion of PLC (n = 109) who came to the authors' attention.

Main outcome measures. Measurement of PBGD activity in erythrocytes. Comparison of the PBGD activity in groups with various final diagnoses – hepatocellular carcinoma (n = 58), cholangio‐cellular carcinoma (n = 2), malignancy other than PLC (n = 18), benign liver disorders (n = 11) – and according to presence of cirrhosis.

Results. None of the patients had a clinical or family history of AIP. Four cases with low PBGD activity, suggesting AIP gene carriership, were found, which is more than expected. However, the cases were evenly distributed amongst the groups. The mean activity of PBGD was higher in cirrhotic patients, irrespective of the presence of PLC, than in others.

Conclusions. (i) Acute intermittent porphyria gene carriership might be associated with an increased risk not only for PLC but also for secondary malignancies and benign tumours in the liver, (ii) High activity of PBGD is not unusual in liver cirrhosis and the reason for this needs to be elucidated, but it seems to be of no clinical value as a tumour marker for PLC.
Frequency of diabetes in family members of probands with non‐insulin‐dependent diabetes mellitus
Authors: SIMMONS D. , GATLAND B. A. , LEAKEHE L. , FLEMING C.
Published: August 2009

Abstract. Objectives. To describe the prevalence of known diabetes in a multi‐ethnic community in South Auckland, New Zealand, in relation to family history of diabetes and past history of diabetes in pregnancy.

Design. A cross‐sectional, household survey comparing ascertainment with local general practice diabetes registers where they existed.

Setting. An inner‐city community with a high proportion of Maori, Pacific Islands people and Europeans.

Subjects. A total of 55518 residents (91% response). Comparison with diabetes registers showed 91% ascertainment of known diabetic residents. More detailed interviews with 176/214 (82%) Europeans, 286/336 (85%) Maori and 495/585 (85%) Pacific Islands people with known diabetes. Fifty subjects had insulin‐dependent diabetes mellitus on clinical criteria and were excluded from analyses.

Main outcome measures. Prevalence of diabetes.

Results. Those with non‐insulin‐dependent diabetes mellitus were more likely to have a diabetic mother than father (Europeans, 21.7% vs. 9.9%; Maori, 17.6 vs. 11.4%; Pacific Islands, 15.7 vs. 5.3%). Diabetic women had a similar likelihood of having a diabetic father as diabetic men but were 1.84 times as likely to have a diabetic mother (95% CI, 1.27–2.69). Diabetic women with past diabetes in pregnancy had 2.05 (95% CI, 1.01–4.15) times the chance of a diabetic offspring as women who had not had past diabetes in pregnancy, who in turn had 2.69 (95% CI, 1.17–6.18) times the likelihood of having a diabetic offspring as diabetic men.

Conclusions. The mother is a more important conduit for inheritance of diabetes than the father in these three ethnic groups. A history of diabetes in pregnancy confers an extra risk to the offspring above this usual maternal excess.
Long‐term anticoagulant therapy in cerebrovascular disease: does bleeding outweigh the benefit?
Authors: DAHL T. , ABILDGAARD U. , SANDSET P. M.
Published: August 2009

Abstract. Objective. The aim of the present study was to determine the risk of major haemorrhagic complications, stroke and other cardiovascular events, and mortality during long‐term anticoagulant therapy (ACT) in patients with cerebrovascular disease not included in any prospective trials.

Design. The data were collected retrospectively.

Setting. All patients with symptomatic cerebrovascular disease discharged from the Stroke Unit, Aker University Hospital, Oslo, with ACT (warfarin) during 1983 through to 1986 were included.

Subjects. The material consists of 161 patients with a mean age of 67.8 (range 40–90) years. The reason for initiating ACT was frequent transient ischaemic attacks (TIAs) in 52 patients, stroke in progression (SIP) in 33 patients, and probable embolic stroke in 76 patients. International normalized ratio (INR) of 4.2–2.8 was aimed at.

Main outcome measures. Major haemorrhagic complications, recurrent stroke and survival was determined for the total material, and in the subgroups non‐valvular atrial fibrillation (NVAF, n = 49), TIAs, and SIP.

Results. The mean duration of ACT was 21.1 (range 0.5–60.2) months with a total of 282.9 patient‐years. The rate of major (including fatal) haemorrhagic complications was 4.6% per year, and the rate of fatal haemorrhagic complications was 1.4% per year. The complication rates in the subgroups of patients did not differ significantly from that in the total material. Only two out of the 13 major haemorrhagic complications occurred during the initial 6 months of ACT. No strokes occurred in the TIA subgroup. The rate of recurrent stroke (excluding intracranial haemorrhage) was 3.9% per year for all patients, 4.7% per year for the patients with NVAF, and 4.2% per year for the patients with SIP.

Conclusions. The total results suggest a positive net effect of ACT in patients with NVAF and TIAs. Without comparable data, no definite conclusions concerning the effect of ACT on patients with SIP can be drawn. The rate of bleeding complications was similar to that in other studied materials and is not negligible. In patients with SIP and TIAs, ACT beyond 6 months should probably only be continued if aspirin is not tolerated or has proven ineffective in the particular patient.
The role of lipoprotein(a) in the vascular complications of diabetes mellitus
Authors: JENKINS A. J. , BEST J. D.
Published: August 2009

Abstract. Lipoprotein(a) has been identified as an independent risk factor for atherosclerotic vascular disease in non‐diabetic populations. Because of its potential role in the pathogenesis of both microvascular and macrovascular complications in diabetes, there have recently been many reports on lipoprotein(a) in diabetic populations. Some studies indicate an association between elevated lipoprotein(a) and macro‐vascular disease in non‐insulin‐dependent diabetes mellitus (NIDDM), but this link has not been found with insulin‐dependent diabetes mellitus (IDDM). In IDDM, elevated lipoprotein(a) has been found in groups with diabetic nephropathy and retinopathy, raising the possibility that it plays a causative role. The relationship between glycaemic control and the lipoprotein(a) level has not been fully resolved. Most studies have not found any connection in NIDDM, but some found higher lipoprotein(a) levels in hyper‐glycaemic IDDM patients. Potentially, lipoprotein(a) is an important factor linking the microvascular and macrovascular complications of diabetes.
Albumin excretion rate and its relation to kidney disease in non‐insulin‐dependent diabetes mellitus
Authors: WIRTA O. , PASTERNACK A. , MUSTONEN J. , OKSA H. , KOIVULA T. , HELIN H.
Published: August 2009

Abstract. Objective. To estimate the occurrence of increased albumin excretion rate (AER) and its significance as a marker of diabetic kidney disease in non‐insulin‐dependent diabetic subjects.

Design. Population‐based, controlled cross‐sectional study.

Setting. A primary health care centre in the city of Tampere, south‐west Finland.

Subjects. Consecutive, recently diagnosed (n = 150) and long‐term (n = 146) middle‐aged non‐insulin‐dependent diabetic subjects. Matched non‐diabetic control subjects (n = 150).

Main outcome measures. Albumin excretion rate, fractional AER, microalbuminuria (AER 30–300 mg 24 h−1), clinical nephropathy (AER exceeding 300 mg 24 h−1) and kidney biopsy in diabetic subjects with an AER exceeding 100 mg 24 h−1.

Results. Mean (± standard deviation [SD]) 24‐h AER was increased in recently diagnosed diabetic subjects, 54 (111) mg, and long‐term diabetic subjects, 134 (479) mg, compared to non‐diabetic control subjects, 16 (19) mg. The fractional AER was 7.5 (18.3) × 10−6 in recent diabetic subjects, 53.1 (306.9) × 10−6 in long‐term diabetic subjects and 2.8 (3.7) × 10−6 in non‐diabetic control subjects. Microalbuminuria was found in 8% of non‐diabetic subjects, in 29% of recent and in 27% of long‐term diabetic subjects. The prevalence of clinical nephropathy was 7% in long‐term and 4% in recent diabetic subjects, whilst no non‐diabetic subject had nephropathy. In 12 of 16 eligible kidney biopsies, diabetic glomerulosclerosis was found, in four subjects the finding was normal.

Conclusions. The AER is clearly increased in recent non‐insulin‐dependent diabetic subjects and further increased in diabetic subjects with a mean disease duration of 10 years. An increased AER in non‐insulin‐dependent diabetic subjects suggests diabetic kidney disease.
Plasma homocysteine in acute myocardial infarction: homocysteine‐lowering effect of folic acid
Authors: LANDGREN F. , ISRAELSSON B. , LINDGREN A. , HULTBERG B. , ANDERSSON A. , Brattström Lars
Published: August 2009

Abstract. Objectives. Moderate hyperhomocysteinaemia is an independent risk factor for cardiovascular disease which may be causal. We investigated whether the concentration of plasma homocysteine changes between the acute phase of myocardial infarction and follow‐up, and whether treatment with oral folic acid was effective in lowering homocysteine levels in patients with myocardial infarction.

Design and subjects. Plasma total homocysteine levels 24–36 h (baseline) after onset of acute myocardial infarction were compared with the levels obtained at 6 weeks' follow‐up and with the levels in the controls. In the same patients, we studied the effect on plasma homocysteine of 6 weeks' treatment with daily oral folic acid doses of 2.5 or 10 mg compared to no treatment.

Results. At baseline, 12 of 68 patients (18%) had moderate hyperhomocysteinaemia (>17.3 μmol L−1; P < 0.05). Between baseline and follow‐up, plasma homocysteine levels increased from 13.1 ± 4.6 to 14.8 ± 4.8 μmol L−1 (mean ± SD; P < 0.001). Treatment with nitroglycerin, streptokinase, beta blockers, or acetylsalicylic acid seemed not to have caused this change. Folic acid lowered plasma homocysteine in all but two of 33 treated patients with a mean decrease of 4.4 μmol L−1 (–27%; P < 0.001). There was no difference between the effect of 2.5 and 10 mg of folic acid. In the untreated group (n = 20), plasma homocysteine increased with a mean increase of 0.6 μmol L−1 (+ 4%; P < 0.05).

Conclusions. Plasma homocysteine seems to increase in the post myocardial infarction period, the cause of which warrants further study. Folic acid appears to be an effective treatment for the reduction of both normal and increased plasma homocysteine concentrations in patients with myocardial infarction. This suggests that folic acid should be used for intervention when studying the effect of homocysteine‐lowering therapy on the risk on myocardial infarction.
Gastrointestinal motility disorders in patients with diabetes mellitus
Authors: Abrahamsson Hasse
Published: August 2009

Abstract. Disturbed gastric and small intestinal motility is an often overlooked clinical problem. Delayed gastric emptying of liquid and/or solid food in patients with type 1 and type 2 diabetes (gastroparesis diabeticorum) occurs in approximately 50% of the patients. Also, the interdigestive gastric and small intestinal motility is often affected. There is only a weak correlation between symptoms and objectively measurable motor disturbances. Patients with severe upper gastrointestinal symptoms usually have disturbed motility, but most patients with impaired motility are asymptomatic. Recent studies have clearly shown that, in addition to autonomic neuropathy, acute metabolic derangements are likely to contribute to disturbed motility. Elevated glucose levels impair gastric and small intestinal motility during fasting and after food intake. Hyperinsulinemia per se has effects similar to hyperglycaemia on the stomach and small bowel, and may be a mediator of the effects of hyperglycaemia in healthy subjects. The impact of insulin on motility in diabetic patients is still unclear. Treatment of the gastric motility disorder should include a stabilization of gastric emptying. Different therapeutic modes may be useful, e.g. application of prokinetic drugs and optimizing the metabolic situation.
Chronic Stress Alters Glucocorticoid Receptor and Mineralocorticoid Receptor mRNA Expression in the European Starling (Sturnus vulgaris) Brain
Authors: Dickens M. , Romero L. M. , Cyr N. E. , Dunn I. C. , Meddle S. L.
Published: August 2009

Although the glucocorticoid response to acute short‐term stress is an adaptive physiological mechanism that aids in the response to and survival of noxious stimuli, chronic stress is associated with a negative impact on health. In wild‐caught European starlings (Sturnus vulgaris), chronic stress alters the responsiveness of hypothalamic‐pituitary‐adrenal (HPA) axis as measured by the acute corticosterone response. In the present study, we investigated potential underlying neuroendocrine mechanisms by comparing glucocorticoid receptor and mineralocorticoid receptor mRNA expression in the brains of chronically and nonchronically‐stressed starlings. Hypothalamic paraventricular nucleus, but not hippocampal, glucocorticoid receptor mRNA expression in chronically‐stressed birds was significantly lower compared to controls, suggesting changes in the efficacy of corticosterone negative feedback. In addition, chronically‐stressed birds showed a significant decrease in hippocampal MR mRNA expression. Together, these results suggest that chronic stress changes the brain physiology of wild birds and provides important information for the understanding of the underlying mechanisms that result in dysregulation of the HPA axis in wild animals by chronic stress.
Positive and negative feedback regulatory loops of thiol‐oxidative stress response mediated by an unstable isoform of σRin actinomycetes
Authors: Kim Min‐Sik , Hahn Mi‐Young , Cho Yoobok , Cho Sang‐Nae , Roe Jung‐Hye
Published: August 2009

Alternate sigma factors provide an effective way of diversifying bacterial gene expression in response to environmental changes. InStreptomyces coelicolorwhere more than 65 sigma factors are predicted, σRis the major regulator for response to thiol‐oxidative stresses. σRbecomes available when its bound anti‐sigma factor RsrA is oxidized at sensitive cysteine thiols to form disulphide bonds. σRregulon includes genes for itself and multiple thiol‐reducing systems, which constitute positive and negative feedback loops respectively. We found that the positive amplification loop involves an isoform of σR(σR′) with an N‐terminal extension of 55 amino acids, produced from an upstream start codon. A major difference between constitutive σRand inducible σR′is that the latter is markedly unstable (t1/2 ∼ 10 min) compared with the former (> 70 min). The rapid turnover of σR′is partly due to induced ClpP1/P2 proteases from the σRregulon. This represents a novel way of elaborating positive and negative feedback loops in a control circuit. Similar phenomenon may occur in other actinomycetes that harbour multiple start codons in thesigRhomologous gene. We observed thatsigHgene, thesigRorthologue inMycobacterium smegmatis, produces an unstable larger isoform of σHupon induction by thiol‐oxidative stress.
The transcriptionally active regions in the genome of Bacillus subtilis
Authors: Rasmussen Simon , Nielsen Henrik Bjørn , Jarmer Hanne
Published: August 2009

The majority of all genes have so far been identified and annotated systematically through in silico gene finding. Here we report the finding of 3662 strand‐specific transcriptionally active regions (TARs) in the genome of Bacillus subtilis by the use of tiling arrays. We have measured the genome‐wide expression during mid‐exponential growth on rich (LB) and minimal (M9) medium. The identified TARs account for 77.3% of the genes as they are currently annotated and additionally we find 84 putative non‐coding RNAs (ncRNAs) and 127 antisense transcripts. One ncRNA, ncr22, is predicted to act as a translational control on cstA and an antisense transcript was observed opposite the housekeeping sigma factor sigA. Through this work we have discovered a long conserved 3′ untranslated region (UTR) in a group of membrane‐associated genes that is predicted to fold into a large and highly stable secondary structure. One of the genes having this tail is efeN, which encodes a target of the twin‐arginine translocase (Tat) protein translocation system.
A mechanism of transposon‐mediated directed mutation
Authors: Zhang Zhongge , Saier Milton H.
Published: August 2009

Directed mutation is a proposed process that allows mutations to occur at higher frequencies when they are beneficial. Until now, the existence of such a process has been controversial. Here we describe a novel mechanism of directed mutation mediated by the transposon, IS5 in Escherichia coli. crp deletion mutants mutate specifically to glycerol utilization (Glp+) at rates that are enhanced by glycerol or the loss of the glycerol repressor (GlpR), depressed by glucose or glpR overexpression, and RecA‐independent. Of the four tandem GlpR binding sites (O1–O4) upstream of the glpFK operon, O4 specifically controls glpFK expression while O1 primarily controls mutation rate in a process mediated by IS5 hopping to a specific site on the E. coli chromosome upstream of the glpFK promoter. IS5 insertion into other gene activation sites is unaffected by the presence of glycerol or the loss of GlpR. The results establish an example of transposon‐mediated directed mutation, identify the protein responsible and define the mechanism involved.
Co‐ordinated regulation of two divergent promoters through higher‐order complex formation by the LysR‐type regulator ThnR
Authors: López‐Sánchez Aroa , Rivas‐Marín Elena , Martínez‐Pérez Olga , Floriano Belén , Santero Eduardo
Published: August 2009

The genes required for tetralin biodegradation by Sphingomonas macrogolitabida strain TFA are clustered in two divergent and closely linked operons. ThnR, a LysR‐type regulator, activates transcription from each operon in response to tetralin. The regulatory thnR gene is co‐transcribed with the catabolic genes thnC, thnA3 and thnA4, resulting in positive autoregulation. ThnR binds with different affinity to two primary binding sites, designated B and C, in the intervening region between the two operons and makes additional contact with secondary sites that extend towards the promoters. In addition, ThnR may interact with itself when bound to each site via the formation of a DNA loop, as evidenced by the distortion of the DNA between the primary binding sites and the elimination of the higher‐order complexes following the introduction of a half‐turn of the DNA helix between the primary binding sites. Transcription from each promoter is not fully independent since mutations in each binding site affected transcription from both promoters. Based on these results, we propose a model of transcription activation that involves the formation of a complex structure by interactions between ThnR molecules bound to distant binding sites and favours transcription from one promoter to the detriment of the other.
An alternative to the glyoxylate shunt
Authors: Schink Bernhard
Published: August 2009

A cycle remains a cycle only as long as the spokes of the wheel are not stolen. To keep the citric acid cycle going requires anaplerotic reactions such as the glyoxylate shunt to restore the cycle intermediates that are withdrawn for the biosynthesis of cell constituents, e.g. amino acids and haemin precursors. The article by Erb et al. in this issue of Molecular Microbiology documents an alternative path that replenishes four‐carbon intermediates during growth on acetate in the absence of the glyoxylate shunt. The reaction sequence forms malate and succinyl‐CoA from three acetyl‐CoA, one CO2 and one HCO3 in a linear pathway. This new pathway was discovered in phototrophic anoxygenic bacteria and in few aerobic bacteria, but it is probably widespread among many metabolic groups of bacteria.
Does Alzheimer's disease begin in the brainstem?
Authors: Simic G. , Stanic G. , Mladinov M. , Jovanov‐Milosevic N. , Kostovic I. , Hof P. R.
Published: August 2009

Although substantial evidence indicates that the progression of pathological changes of the neuronal cytoskeleton is crucial in determining the severity of dementia in Alzheimer's disease (AD), the exact causes and evolution of these changes, the initial site at which they begin, and the neuronal susceptibility levels for their development are poorly understood. The current clinical criteria for diagnosis of AD are focused mostly on cognitive deficits produced by dysfunction of hippocampal and high‐order neocortical areas, whereas noncognitive, behavioural and psychological symptoms of dementia such as disturbances in mood, emotion, appetite, and wake–sleep cycle, confusion, agitation and depression have been less considered. The early occurrence of these symptoms suggests brainstem involvement, and more specifically of the serotonergic nuclei. In spite of the fact that the Braak and Braak staging system and National Institutes of Aging – Reagan Institute (NIA‐RI) criteria do not include their evaluation, several recent reports drew attention to the possibility of selective and early involvement of raphe nuclei, particularly the dorsal raphe nucleus (DRN), in the pathogenesis of AD. Based on these findings of differential susceptibility and anatomical connectivity, a novel pathogenetic scheme of AD progression was proposed. Although the precise mechanisms of neurofibrillary degeneration still await elucidation, we speculated that cumulative oxidative damage may be the main cause of DRN alterations, as the age is the main risk factor for sporadic AD. Within such a framework, β‐amyloid production is considered only as one of the factors (although a significant one in familial cases) that promotes molecular series of events underlying AD‐related neuropathological changes.
Impact of genetic polymorphisms of the renin–angiotensin system and of non‐genetic factors on kidney transplant function – a single‐center experience
Authors: Siekierka‐Harreis Magdalena , Kuhr Nicola , Willers Rainhart , Ivens Katrin , Grabensee B. , Mondry Adrian , Loh Marie C.S. , Rump Lars Christian , Blume Cornelia
Published: August 2009

Abstract:  Renin–angiotensin–aldosterone system (RAAS) polymorphisms such as the angiotensinogen‐gene‐M235T‐, the angiotensin‐conversion enzyme (ACE)‐gene I/D‐ and the angiotensin‐II‐type 1‐receptor‐(AT1R)‐A1166C‐polymorphism have been implicated in renal insufficiency and hypertension. We studied the association of these RAAS genotypes and non‐genetic factors with transplant function and hypertension after renal graft transplantation (NTX). A total of 229 renal graft recipients, transplanted at a single center, were monitored up to 54 months and genotyped using polymerase chain reaction. The prevalence of the genotypes was comparable to a control group of healthy volunteers. Genotype and clinical outcome was analyzed using anova, while the k‐nearest neighbor method was used for a pattern recognition analysis of the complete database. Hypertension after NTX was not influenced by the RAAS polymorphisms. The DD‐genotype of the ACE‐I/D‐polymorphism was associated with significantly deteriorated renal transplant function during the months 18 to 30 after transplantation according to anova at p < 0.05, as were non‐genetic factors like long hospitalization, poor primary transplant function, and frequent rejections. Pattern recognition identified, the use of cyclosporine (odds ratio of 4.25) and the use of Ang II‐receptor‐blockers at discharge indicating the need of effective antihypertensive treatment (odds ratio of 3.26) as risk factors for transplant function loss. Altogether, the significant impact of the DD‐genotype on the outcome after renal transplantation emphasizes the early identification of RAAS genotypes.
Microbiology, time course and clinical characteristics of infection in critically ill patients receiving packed red blood cell transfusion
Authors: Rachoin J.‐S. , Daher R. , Schorr C. , Milcarek B. , Parrillo J. E. , Gerber D. R.
Published: August 2009

Background and Objectives  Packed red blood cell transfusion has been associated with increased infection in a variety of critically ill patient populations. We evaluated the microbiology and time course of infection in transfused patients in the intensive care unit (ICU) as no data exist on these parameters.

Materials and Methods  We performed a retrospective review of data for all patients admitted to a 24‐bed medical‐surgical ICU at Cooper University Hospital from July 2003 to September 2006 and entered in the Project Impact database.

Results  A total of 2432 patients were admitted during the study period, of which 609 underwent transfusion. Transfused patients were more likely to develop a nosocomial infection (10·5% vs. 4·9%, P < 0·001). ICU and hospital length of stay were longer in the transfused group (P < 0·001 for both). Mortality was also greater (13·1% vs. 8·7%, P = 0·001). Transfused patients had a shorter time from hospital admission to first infection (P < 0·001) and ICU admission to first infection (P < 0·001). Multivariate analysis confirmed transfusion as an independent risk factor for infection, mortality, hospital and ICU length of stay. Methicillin‐resistant Staphylococcus aureus, vancomycin‐resistant enterococcus and Acinetobacter occurred more often in transfused patients. Acinetobacter accounted for a disproportionate share of infections among transfused patients (P < 0·001).

Conclusions  Transfused ICU patients have a higher incidence of nosocomial infection and worse outcomes. Transfused patients had a shorter onset of infection. Acinetobacter infection appears to be particularly common among these patients. Further investigation is merited to better elucidate the mechanism for these findings and their therapeutic and clinical implications.