bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of natural organic matter in nonlinear sorption of 2,4‐dichlorophenol onto soils/sediments
Authors: Yang Kun , Zhu Lizhong , Lou Baofeng , Chen Baoliang
Published: January 2004

Sorption of 2,4‐dichlorophenol (2,4‐DCP) onto 17 lake/river sediments, one red soil, pure minerals, and humic acid was comparatively studied. The isotherms of 2,4‐DCP onto soil/sediment samples and humic acid are notably nonlinear at low concentrations and can be described by a simple dual‐mode model: qe = KpCe + Q0bCe/(1 + bCe). No significant sorption of 2,4‐DCP on pure minerals (montmorillonite and amorphous silicon oxide) was detected. Strong correlations of natural organic matter content to model parameters Kp, Q0, and Q0b were observed, while no significant effects of soil/sediment specific surface area and total clay content on sorption were observed. It is hypothesized that most of the nonlinear sorption behavior can be attributed to the soil/sediment organic matter contents as opposed to mineral contents because of the predominance of strongly hydrated cations (e.g., Na+, Ca2+, Al3+, Mg2+) in natural waters. The treatment of K*oc (K*oc = Kp/foc), Qoc (Qoc = Q0/foc), and Loc (Loc = Q0b/foc) as constants for a given solute represents an important step toward establishing a quantitative relationship between nonlinear sorption and solute molecular structure and offers a way to approximately calculate the nonlinear sorption from soil/sediment foc.
Impairment of Hepatic Microcirculation in Fatty Liver
Authors: IJAZ SAMIA , YANG WENXUAN , WINSLET MARC C. , SEIFALIAN ALEXANDER M.
Published: January 2004

Fatty liver or hepatic steatosis, which is the result of the abnormal accumulation of triacylglycerol within the cytoplasm of hepatocytes, is a common histological finding in human liver biopsy specimens that is attributed to the effects of alcohol excess, obesity, diabetes, or drugs. There is a general consensus that fatty liver compromises hepatic microcirculation, the common exchange network upon which hepatic arterial and portal inflows converge, regardless of underlying etiology. A significant reduction in hepatic microcirculation has been observed in human fatty donor livers and in experimental models of hepatic steatosis. There is an inverse correlation between the degree of fat infiltration and both total hepatic blood flow and flow in microcirculation. Fatty accumulation in the cytoplasm of the hepatocytes is associated with an increase in the cell volume that reduces the size of the hepatic sinusoid space by 50% compared with a normal liver and may result in partial or complete obstruction of the hepatic sinusoid space. As a result of impaired hepatic microcirculation, the hepatocytes of the fatty liver have reduced tolerance against ischemia‐reperfusion injury, which affects about 25% of the donors for liver transplantation because severe steatosis is associated with a high risk of primary nonfunction after liver transplantation.
A Model of Nitric Oxide Capillary Exchange
Authors: TSOUKIAS NIKOLAOS M. , POPEL ALEKSANDER S.
Published: January 2004

Objective: Our aim was to develop a mathematical model that describes the nitric oxide (NO) transport in and around capillaries. The model is used to make quantitative predictions for (1) the contribution of capillary endothelium to the nitric oxide flux into the parenchymal tissue cells; (2) the scavenging of arteriolar endothelium‐derived NO by capillaries in the surrounding tissue; and (3) the role of myoglobin in tissue cells and plasma‐based hemoglobin on NO diffusion in and around capillaries.

Methods: We used a finite element model of a capillary and surrounding tissue with discrete parachute‐shape red blood cells (RBCs) moving inside the capillary to obtain the NO concentration distribution. An intravascular mass transfer coefficient is estimated as a function of RBC membrane permeability and capillary hematocrit. A continuum model of the capillary is also formulated, in which blood is treated as a homogeneous fluid; it uses the mass transfer coefficient and provides a closed‐form analytic solution for the average exchange rate of NO in a capillary‐perfused region.

Results: The NO concentration in the parenchymal cells depends on parameters such as RBC membrane permeability and capillary hematocrit; the concentration is predicted for a wide range of parameters. In the absence of myoglobin or plasma‐based hemoglobin, the average tissue concentration generally ranges between 20 and 300 nM. In the presence of myoglobin or after transfusion of a hemoglobin‐based blood substitute, there is minimal NO penetration into the tissue from the capillary endothelium.

Conclusions: The model suggests that NO originating from the capillary wall can diffuse toward the parenchymal cells and potentially sustain physiologically significant concentrations. The model provides estimates of NO exchange and concentration level in capillary‐perfused tissue, and it can be used in models of NO transport around arterioles or other NO sources.
Microvascular Abnormalities in Chronic Heart Failure: A Cross‐Sectional Analysis
Authors: HOUBEN ALPHONS J.H.M. , BELJAARS JEROEN H. , HOFSTRA LEO , KROON ABRAHAM A. , DE LEEUW PETER W.
Published: January 2004

Objectives: Similar to what has been found in hypertension, elevated peripheral resistance in chronic heart failure (CHF) might be related to microvascular constriction and rarefaction. Our objective was to evaluate both structural and functional microvascular changes in patients with CHF in relation to left ventricular function and neurohumoral activation.

Methods: In 25 patients with mild and severe CHF (New York Heart Association class I‐II [n = 11] and class III‐IV [n = 14]) and 10 age‐matched healthy subjects, we studied microvascular density, diameters, and morphology of the bulbar conjunctiva and skin nailfold using intravital microscopy.

Results: Total conjunctival microvascular density was higher in patients with mild heart failure compared with healthy controls, whereas it was lower in severe heart failure (medians, 6.75, 4.31, and 3.56 mm/mm2, respectively, p < 0.01). In patients with heart failure, venular density was correlated with left ventricular ejection fraction. Nailfold capillary recruitment during postocclusive reactive hyperemia, a measure of functional reserve capacity, was impaired in patients with severe CHF (p < 0.05). Furthermore, in severe CHF, more abnormal capillaries and enlarged diameters were found in the nailfold (p < 0.05).

Conclusions: In heart failure, several microvascular abnormalities occur that differ, depending on the severity of this condition.
Blood—Brain Barrier Permeability Precedes Senile Plaque Formation in an Alzheimer Disease Model
Authors: UJIIE MAKI , DICKSTEIN DARA L. , CARLOW DOUGLAS A. , JEFFERIES WILFRED A.
Published: January 2004

Objective: To establish the generality of cerebrovascular pathology frequently observed with Alzheimer disease, we have assessed blood‐brain barrier (BBB) integrity using the Alzheimer disease model Tg2576 mice in which cognitive deficits and neuritic plaque formation develop around 10–12 months of age.

Methods: We assessed BBB integrity using well‐established methods involving albumin and Evans blue uptake and introduce the use of a novel perfusion protocol using succinimidyl ester of carboxyfluorescein diacetate.

Results: BBB permeability is increased in the cerebral cortex of 10‐month‐old Tg2576 mice preceding Alzheimer disease pathology presentation. Furthermore, when compared with their nontransgenic littermates, 4‐month‐old Tg2576 mice exhibit compromised BBB integrity in some areas of the cerebral cortex. An age‐related increase in albumin uptake by the brains of Tg2576 mice, compared with nontransgenic mice, was also observed. These findings were supported by quantitative Evans blue analysis (p = 0.07, two‐way analysis of variance).

Conclusion: A breakdown of BBB was evident in young 4‐ to 10‐month‐old Tg2576 mice. Compromised barrier function could explain the mechanisms of Aβ entry into the brain observed in experimental Alzheimer disease vaccination models. Such structural changes to the BBB caused by elevated Aβ could play a central role in Alzheimer disease development and might define an early point of intervention for designing effective therapy against the disease.
Identification of a Novel Route of Iron Transcytosis across the Mammalian Blood‐Brain Barrier
Authors: MOROO IKU , UJIIE MAKI , WALKER BRANDIE L. , TIONG JACQUELINE W.C. , VITALIS TIMOTHY Z. , KARKAN DELARA , GABATHULER REINHARD , MOISE ALEXANDER R. , JEFFERIES WILFRED A.
Published: January 2004

Objective: This study was undertaken to assess the role of p97 (also known as melanotransferrin) in the transfer of iron into the brain, because the passage of most large molecules is limited by the presence of the blood‐brain barrier, including that of the serum iron transporter transferrin.

Methods: To study the function of the soluble form of p97, we followed the uptake of radioiodinated and 55Fe loaded p97 and transferrin by the brain during a 24‐hour period.

Results: We show that the soluble form of p97 has the ability to transcytose across the murine blood‐brain barrier, and its transcytosis can be inhibited in a specific manner. We also provide evidence that p97 transports iron into the brain more efficiently than transferrin.

Conclusions: These data support the idea that p97 is an important iron transporter across the blood‐brain barrier in normal physiology and possibly in neurodegenerative diseases, such as Alzheimer disease, in which iron homeostasis in the brain becomes disrupted.
Hodgkin's lymphoma, Epstein–Barr virus reactivation and fatal haemophagocytic syndrome
Authors: Hasselblom S. , Linde A. , Ridell B.
Published: January 2004

Haemophagocytic syndrome is a serious disorder, often related to Epstein–Barr virus (EBV) or other infectious agents. Frequently an underlying immune abnormality or a T‐cell lymphoma is present. The combination of haemophagocytosis and Hodgkin's lymphoma seems to be rare. A 70‐year‐old female with rheumatoid arthritis was admitted with constitutional symptoms, persistent fever, pancytopenia, deranged liver enzymes, lymphadenopathy and splenomegaly. A fatal coagulopathy supervened. The clinical picture and the bone marrow findings indicated a haemophagocytic syndrome and a lymph node biopsy disclosed an EBV‐positive Hodgkin's lymphoma. EBV serology pointed at viral reactivation and a high EBV DNA content was detected in serum by real‐time quantitative PCR analysis (5.5 × 106 copies per mL). The case history is presented and the literature is reviewed.
Acute myocardial infarction: an unusual culmination of rheumatic pancarditis and antiphospholipid antibody syndrome
Authors: Izhevsky D. , Maple J. T. , Ommen S. R.
Published: January 2004

A 29‐year‐old man with history of antiphospholipid antibody syndrome (APS) and two prior episodes of acute rheumatic fever developed a third episode of acute rheumatic fever. This was complicated by acute myocardial infarction due to spontaneous arterial thrombosis of the left anterior descending and right coronary arteries. We postulate that rheumatic pancarditis created an inflammatory, thrombogenic environment that facilitated coronary artery thrombosis secondary to APS, a novel association. Our patient was left with significant left ventricular dysfunction at a young age, and cases such as this emphasize the need for early recognition and proper treatment of APS. Further, the pathogenesis of thrombosis in APS is incompletely understood, and the cellular and molecular basis for this, including the role of ‘second hits’, are areas needing further investigation.
Risk modifiers for peripheral sensory neuropathy in HIV infection/AIDS
Authors: Lopez O. L. , Becker J. T. , Dew M.‐A. , Caldararo R.
Published: January 2004

The objective of this study is to examine the risk factors associated with the development of sensory neuropathy in human immunodeficiency virus (HIV)‐infected patients in 292 HIV+ patients recruited through a community‐based sentinel survey. We determined the clinical and treatment factors associated with the presence of peripheral sensory neuropathy in HIV+ subjects at baseline examination, and at 1‐year follow‐up. Baseline examination was assessed with a logistic regression analysis controlling for age, education level, history of drug/alcohol use, and anti‐retroviral treatment. The risk of developing new peripheral neuropathy at follow‐up was determined using a Cox proportional hazard model analysis. At study entry, neuropathy (n = 64) was associated with acquired immunodeficiency syndrome (AIDS), nucleoside analogue reverse transcriptase inhibitors (NRTI) (i.e. ddC), and history of alcohol abuse. After 1‐year follow‐up, the development of neuropathy was predicted by AIDS, age (older subjects), and NRTI use.

These findings indicated that AIDS, age, alcohol abuse/dependence, and anti‐retroviral medication use are important predictors of motor/sensory peripheral neuropathy in the HIV infection. The peripheral neurotoxic effect of anti‐retroviral medication should be taken into account in the design of long‐term therapies.
Spasms in children with definite and probable mitochondrial disease*
Authors: Sadleir L. G. , Connolly M. B. , Applegarth D. , Hendson G. , Clarke L. , Rakshi C. , Farrell K.
Published: January 2004

The diagnosis of mitochondrial encephalomyopathies is complex and a system for classification of the diagnosis as definite, probable, and possible has been proposed. The objective of this study was to explore the spectrum of epileptic disorders associated with probable and definite mitochondrial disease in children using this classification system. The patient population with mitochondrial disease and epilepsy was selected from a tertiary care children's hospital. Interictal electroencephalograms and video‐EEG recordings were used to characterize seizure types. Ten children fulfilled the criteria for probable or definite mitochondrial disease and had epilepsy. Four had siblings with a similar clinical phenotype. Spasms were the most common seizure type and were the initial seizure type in seven patients and two siblings. Four patients had only partial seizures, with or without generalization, and one patient had seizures that were difficult to classify. Blood lactate concentrations were elevated consistently in patients with partial seizures alone but were occasionally normal in children with spasms. Spasms were the most common presenting seizure type in children with probable and definite mitochondrial disease.
An occipital lobe epileptogenic focus in a patient with West Nile encephalitis
Authors: DellaBadia J. , Jaffe S. L. , Singh J. , Minagar A.
Published: January 2004

Although most human cases of West Nile (WN) fever are benign, approximately 1% produce severe neurological illness. Meningitis and/or encephalitis comprise 75% of hospitalized cases with seizures in 10–15%. Occipital lobe seizures, often mimicking other primary seizure types due to extra‐occipital spread, is uncommon in adults and especially so from an infectious origin. A case of WN encephalitis presenting with a simple partial seizure, focal motor, resulting from an occipital epileptogenic focus is reported. The atypical epileptogenic location of the case and the observed frequency of seizures in WN encephalitis suggest that this virus is particularly irritative to cortical neuronal networks. Thus when seizures especially with atypical EEG patterns present during an acute febrile illness in the warmer months, WN encephalitis should be considered.
Comparison of motor fluctuations and l‐dopa‐induced dyskinesias in patients with familial and sporadic Parkinson's disease
Authors: Papapetropoulos S , Argyriou A. A , Ellul J , Chroni E
Published: January 2004

The aim of the present work was to study the characteristics of motor complications in a group of familial Parkinson's disease (fPD) patients in comparison with matched sporadic PD (sPD) patients. Fifty‐one fPD and 51 sPD patients matched for age and disease duration, used as controls, were included in the study. The Unified Parkinson's Disease Rating Scale was completed during clinical examination and all patients were questioned about the characteristics of motor complications. The mean time from start of l‐dopa therapy to the onset of motor fluctuations (MF) and l‐dopa‐induced dyskinesias (LID) as well as the mean time from symptom onset to the development of MF and LID was significantly shorter in the fPD group of patients. An analysis revealed a higher occurrence of MF and LID in fPD patients in the group with disease duration of 5 years or less. FPD may be associated with a higher prevalence and earlier onset of motor complications during the initial stages of the disease. Genetic factors may contribute to the specific characteristics of motor complications in fPD.
The 40‐mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mg
Authors: Diener Hans‐Christoph , Ryan Robert , Sun Wei , Hettiarachchi Jayasena
Published: January 2004

Meta‐analysis provides valuable information regarding relative efficacies of triptans, but head‐to‐head comparator studies remain the gold standard. Three similar head‐to‐head trials comparing eletriptan 40 mg (E40) with sumatriptan 100 mg (S100) provide a rare opportunity and sufficient power, for robust comparisons of efficacy. Data were combined from three double‐blind, placebo‐controlled, first‐dose, first‐attack acute migraine treatment studies comparing E40 (n = 1132), S100 (n = 1129), and placebo (n = 645). The primary outcome was headache response at 2 h. Secondary outcomes included headache response at 1 h, pain‐free and functional responses, and sustained headache and pain‐free responses. Odds ratios were calculated for summary estimates of probability of response. There were higher headache response rates with eletriptan versus sumatriptan at 2 h (67% vs. 57%; P < 0.0001) and 1 h (34% vs. 26%; P < 0.0001). Eletriptan also had higher 2 h pain‐free (35% vs. 25%; P < 0.0001) and functional responses (67% vs. 58%; P < 0.0001). Sustained headache (42%) and pain‐free (22%) response rates were higher for eletriptan versus sumatriptan (34%, P < 0.0001; 15%, P < 0.0001). The probability of response for eletriptan versus sumatriptan ranged from 36% higher (relief of nausea) to 64% higher (sustained pain‐free rate). Combined analysis demonstrates that E40 has superior efficacy versus S100 across all clinically relevant outcomes.
The systemic amyloidoses: clearer understanding of the molecular mechanisms offers hope for more effective therapies
Authors: Merlini G , Westermark P
Published: January 2004

Knowledge about the systemic amyloidoses has increased considerably during the last few years. This group of diseases is characterized by great biochemical variability, including at least 11 different amyloid fibril proteins and a remarkable range of clinical manifestations. With the understanding that the pathogenesis is different in the various forms of amyloidosis, it is now being increasingly accepted that an early and accurate diagnosis, including that of the underlying biochemical nature, is crucial for a successful treatment. The elucidation of the molecular mechanisms involved in amyloidogenesis is at the basis of the recent blossoming of new, innovative and more effective therapeutic approaches.
Microalbuminuria and stroke in a British population: the European Prospective Investigation into Cancer in Norfolk (EPIC‐Norfolk) population study
Authors: Yuyun M. F. , Khaw K.‐T. , Luben R. , Welch A. , Bingham S. , Day N. E. , Wareham N. J.
Published: January 2004

Objectives. To examine the relationship between microalbuminuria and incident stroke in the general population.

Design. Population‐based prospective cohort study.

Setting. Participants were recruited in a primary care setting from 35 participating general practice units in Norfolk, UK.

Subjects and main outcome measures. The study population consisted of 23 630 individuals aged 40–79 years recruited between 1993 and 1997 for the EPIC‐Norfolk Study and followed up for an average of 7.2 years. Random spot urine specimens were collected at baseline and albumin‐to‐creatinine ratio measured. Participants were categorized into normoalbuminuria, microalbuminuria and macroalbuminuria groups. During follow‐up, the main end point was stroke incidence (fatal and nonfatal), ascertained from the UK Office for National Statistics and from the National Health Service Health District database of all hospital admissions.

Results. A total of 246 stroke events occurred during follow‐up [crude incidence rate of stroke, 1.5 per 1000 person years (pyrs)]. The age‐adjusted incidence of stroke increased significantly across categories of baseline albuminuria (0.9, 1.1 and 1.4/1000 pyrs for tertiles of normoalbuminuria, 2.6/1000 pyrs for microalbuminuria, and 6/1000 pyrs for macroalbuminuria in the total population,P < 0.001 for trend). In all women and men, the multivariate hazard ratio [95% confidence interval (CI)] for stroke associated with microalbuminuria was 1.49 (1.13–2.14) and macroalbuminuria 2.43 (1.11–6.26). After stratifying by stroke subtype, microalbuminuria was only independently predictive of ischaemic stroke, with hazard ratio (95% CI) of 2.01 (1.29–3.31).

Conclusion. Microalbuminuria is independently associated with approximately 50% increased risk of stroke in the general population. Microalbuminuria may be useful in identifying those at increased risk of stroke in the general population.
QRS prolongation on surface ECG and brain natriuretic peptide as indicators of left ventricular systolic dysfunction
Authors: Krüger S. , Filzmaier K. , Graf J. , Kunz D. , Stickel T. , Hoffmann R. , Hanrath P. , Janssens U.
Published: January 2004

Objective.  To determine whether the combination of prolonged QRS duration and brain natriuretic peptide (BNP) levels predicts left ventricular systolic dysfunction (LVSD) with a higher accuracy compared with QRS duration or BNP alone.

Setting.  University hospital.

Methods.  We studied 128 consecutive patients with suspected cardiac disease. At rest the QRS duration on 12‐lead ECG and BNP levels were determined. A left ventricular ejection fraction (LVEF) <50% at echocardiography was defined as LVSD.

Results.  QRS duration in the LVSD group (n = 66, LVEF 30 ± 8%) was longer than in the group without LVSD (n = 62, LVEF 60 ± 5%; QRS 129 ± 34 vs. 96 ± 20 ms, P < 0.001). BNP was higher in the LVSD group compared with controls (467 ± 397 vs. 169 ± 242 pg mL−1, P < 0.001). A QRS duration of >0.1, >0.11 or >0.12 s was highly specific (63, 90 and 98%) but less sensitive (84, 81 and 75%) for the prediction of LVSD. A QRS cut‐off value of 106 ms was moderately sensitive (65%) but very specific (87%) for the prediction of LVSD, whereas a BNP cut‐off value of >84 pg mL−1 was highly sensitive (89%) but only modestly specific (58%). The positive likelihood ratio for LVSD of abnormal BNP (2.0) and QRS prolongation >0.1 s (2.3) was improved by the combination of both criteria (5.1). In multivariate analysis, BNP and QRS duration were independent predictors of LVSD.

Conclusions.  The combination of abnormal BNP and QRS prolongation yields a higher positive likelihood ratio for the detection of LVSD compared with the two criteria alone.
Is the relationship between type of alcohol and mortality influenced by socio‐economic status?
Authors: Nielsen N. R. , Schnohr P. , Jensen G. , Grønbæk M.
Published: January 2004

Objectives.  To assess the impact of socio‐economic status on the relationship between type of alcohol and all‐cause mortality.

Design.  A prospective population study.

Setting.  The Copenhagen City Heart Study, Denmark.

Subjects.  A total of 14 223 men and women participated in the first examination of The Copenhagen City Heart Study in 1976–1978. The participants were followed up until 18th of September 2001 during which 7208 persons died. The effect of beer, wine and spirits on mortality was stratified according to levels of education, income and cohabitation, and the association was examined after controlling for intake of the other types of alcohol, and for sex, smoking, physical activity and body mass index.

Main outcome measures.  Number and time of death from all causes.

Results.  Consumers of wine were better educated and wealthier compared with beer and spirits drinkers. The association between type of beverage and mortality was noticed to differ according to socio‐economic level, especially where the apparent protective effect of wine consumption tended to be strongest in the lower income and educational groups.

Conclusions.  This study finds the specific effects of beer, wine or spirits to moderately diverge in the socio‐economic groups. Future studies addressing the association between the type of beverage and mortality may need to more thoroughly take socio‐economic factors into account.
Metformin and lactic acidosis: cause or coincidence? A review of case reports
Authors: Stades A. M. E. , Heikens J. T. , Erkelens D. W. , Holleman F. , Hoekstra J. B. L.
Published: January 2004

Objective.  Metformin has been associated with the serious side‐effect lactic acidosis. However, it remains unclear whether the use of metformin was a cause or a coincidence in lactic acidosis.

Design.  A literature search of the Index Medicus (1959–66) and of the databases Embase, Medline, Medline Express (1966–99) was performed using the keywords metformin, biguanides and lactic acidosis. All articles of cases with metformin‐induced lactic acidosis (MILA) were cross‐referenced.

Subjects.  Cases were included for analysis if they met the following criteria: serum pH ≤7.35, lactate concentration ≥5 mmol L−1.

Intervention.  A forum of six experts in intensive care medicine independently categorized the cases in MILA unlikely (score 0), possible MILA (score 1) or probable MILA (score 2).

Main outcome measures.  Statistical analysis included the paired interobserver agreement (κ) and multivariate regression analysis.

Results.  Of 80 reported cases, 33 were excluded because of insufficient quality. The forum scores of the remaining 47 cases were distributed normally with a mean score of 7 (range 2–10). The κ‐value was 0.041 (SD = 0.24, range −0.514, 0.427). Neither lactate concentration nor mortality correlated with serum metformin concentrations.

Conclusions.  Given the low interobserver agreement and the lack of any relationship between metformin levels and outcome parameters, the concept that there is a simple, causal relationship between metformin use and lactic acidosis in diabetic patients has to be reconsidered.
Apolipoprotein B and apolipoprotein A‐I: risk indicators of coronary heart disease and targets for lipid‐modifying therapy
Authors: Walldius G. , Jungner I.
Published: January 2004

Although LDL cholesterol (LDL‐C) is associated with an increased risk of coronary heart disease, other lipoproteins and their constituents, apolipoproteins, may play an important role in atherosclerosis. Elevated levels of apolipoprotein (apo) B, a constituent of atherogenic lipoproteins, and reduced levels of apo A‐I, a component of anti‐atherogenic HDL, are associated with increased cardiac events. Apo B, apo A‐I and the apo B/apo A‐I ratio have been reported as better predictors of cardiovascular events than LDL‐C and they even retain their predictive power in patients receiving lipid‐modifying therapy. Measurement of these apolipoproteins could improve cardiovascular risk prediction.
Sudden cardiac death in the young in Sweden: electrocardiogram in relation to forensic diagnosis
Authors: Wisten A. , Andersson S. , Forsberg H. , Krantz P. , Messner T.
Published: January 2004

Objectives.  To study electrocardiogram (ECG) in relation to forensic diagnosis in young persons who suffered a sudden cardiac death (SCD) in Sweden during 1992–99.

Design.  A register study of a national database of forensic medicine in Sweden, selecting all cases of SCD 15–35 years of age. In this group, 12‐lead ECGs and clinical data were searched for in military conscription and medical records. The ECGs were re‐analysed and classified according to the Minnesota code criteria.

Setting.  The whole nation of Sweden.

Subjects.  Sudden cardiac death victims (66 individuals), 15–35 years of age, where it was possible to obtain an ECG recording.

Results.  We observed major or minor ECG abnormalities in 82% of the subjects. The most common changes were T wave abnormalities (35%), ST segment changes (32%) and conduction defects (20%). The ECGs were evaluated as pathological in 50% of the cases, more often in arrhythmogenic right ventricular cardiomyopathy (88%) and hypertrophic cardiomyopathy (82%). Cardiac‐related symptoms were seen in 76% of the total group and there was a family history of a similar cardiac condition in 18%.

Conclusions.  Pathological ECGs were common in young SCD victims, in spite of being taken many years before death. An ECG could help identify prospective victims of SCD, and should always be taken in cases with possible cardiac‐related symptoms or a family history of SCD. The pathological ECGs were often found in connection with routine screening at military enlistment for men, which raises the question of a routine screening in the young, including women.
Early alterations in the postprandial VLDL1 apoB‐100 and apoB‐48 metabolism in men with strong heredity for type 2 diabetes
Authors: Johanson E. H. , Jansson P.‐A. , Gustafson B. , Lönn L. , Smith U. , Taskinen M.‐R. , Axelsen M.
Published: January 2004

Objectives.  To study the postprandial triglyceride‐rich lipoprotein (TRL) metabolism, specifically the concentrations of very low‐density lipoproteins (VLDL); from intestine (apoB‐48) and liver (apoB‐100), in men with normal fasting triglycerides but at increased risk of developing type 2 diabetes.

Design.  Cross‐sectional study.

Subjects and settings.  Sixteen healthy men with at least two first‐degree relatives with type 2 diabetes were individually matched with 16 control subjects without known diabetes heredity for: age, body mass index, and fasting triglyceride level. They underwent an 8‐h meal tolerance test (919 kcal, 51 g fat) during which lipoproteins were separated by density gradient ultracentrifugation. They were characterized by euglycaemic hyperinsulinaemic clamp, peak VO2, 7‐day diet registration and computed tomography.

Results.  The relatives were, as expected, more insulin resistant than the controls and had increased concentration of postprandial VLDL1 particles (49% higher for VLDL1 apoB‐48, P = 0.04 and 21% higher for VLDL1 apoB‐100, P = 0.048). The elevation was related to insulin sensitivity, but not to lifestyle and body composition. Moreover, the concentration of postprandial triglycerides in VLDL1 fraction was inversely related to low‐density lipoprotein (LDL) size in both relatives (rs = −0.60, P = 0.03) and controls (rs = −0.72, P = 0.004). There were no differences in the concentration of triglycerides or apoB‐48 and apoB‐100 particles in the other fractions (plasma, chylomicron or VLDL2).

Conclusion.  Increased postprandial concentration of TRLs in the VLDL1 fraction seems to be present at an early stage in the development of diabetes and probably contributes to the excess risk of future coronary events in insulin‐resistant men.
A new Q/QS pattern on the resting electrocardiogram is associated with impaired insulin secretion and a poor prognosis in elderly men independently of history of myocardial infarction
Authors: Dunder K. , Lind L. , Zethelius B. , Lithell H.
Published: January 2004

Objectives.  To evaluate risk factors and prognosis of subjects who had developed a new Q/QS pattern on the resting electrocardiogram (ECG) in relation to history of myocardial infarction (MI).

Design.  Cross‐sectional and prospective population‐based cohort study.

Setting.  Uppsala, Sweden.

Subjects.  In 1970–73, all 50‐year‐old men in Uppsala, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease. The present study included the 1221 subjects who also were re‐examined at age 70.

Results.  Subjects with a new Q/QS pattern on the resting ECG at age 70 were characterized by impaired insulin secretion compared with those without Q/QS, and a higher prevalence of diabetes compared with the control group. In Cox proportional hazard analysis a new Q/QS pattern at age 70 was a significant predictor of cardiovascular mortality (hazard ratio : 1.67, 95% CI: 1.22–2.26) and total mortality (hazard ratio: 1.31, 95% CI: 1.04–1.62) (after age 70) during 9.4 years follow‐up, also when adjusted for other risk factors and MI diagnosis.

Conclusion.  The finding of a new Q/QS pattern on the resting ECG, regardless of history of MI was associated with impaired insulin secretion and was an independent predictor of total and cardiovascular mortality. Therefore, these subjects must be given a high priority to preventive measures against both coronary heart disease and diabetes.
Family burden of cardiovascular mortality: risk implications for offspring in a national register linkage study based upon the Malmö Preventive Project
Authors: Nilsson P. M. , Nilsson J.‐Å. , Berglund G.
Published: January 2004

Objective.  To investigate the adjusted relative risk of cardiovascular disease (CVD) events in offspring of parents with cardiovascular mortality before 75 years.

Setting.  The city of Malmö, Sweden.

Design.  A follow‐up study based on register linkage analyses.

Subjects and methods.  In the Malmö Preventive Project (MPP), a total of 22 444 men and 10 902 women attended the screening programme between 1974 and 1992. At the screening conventional risk factors for CVD were measured (blood pressure, lipids, glucose, smoking and social class).

Main outcome measures.  Parental CVD mortality was determined via register linkage analysis between the Multiple‐Generation Register and the National Mortality Register (NMR). CVD events (morbidity and mortality) in offspring were collected from national registers. The relative risk for CVD events in offspring, in relation to parental CVD mortality, was adjusted for age and risk factors at screening.

Results.  The age‐adjusted relative risk (RR; 95%CI) for a son to experience a CVD event was increased in relation to a maternal positive family history of CVD mortality before 75 years when compared with no maternal history, RR 1.74 (1.43–2.11). This RR decreased to 1.51 (1.23–1.84; P < 0.001) after full adjustment for risk factors. The corresponding fully adjusted RRs for father–son heritage was RR 1.22 (1.02–1.47; P < 0.05), mother–daughter RR 0.87 (0.54–1.41), and father–daughter RR 1.20 (0.83–1.73).

Conclusion.  The existence of maternal CVD mortality before the age of 75 years implies a substantial risk increase for CVD morbidity and mortality in sons that cannot be explained by social background, lifestyle, or conventional cardiovascular risk factors in the adult offspring.
Birth weight and cardiovascular risk factors in a cohort followed until 80 years of age: the study of men born in 1913
Authors: Eriksson M. , Wallander M.‐A. , Krakau I. , Wedel H. , Svärdsudd K.
Published: January 2004

Objectives. To analyse whether there is a relation‐ship between birth weight and cardiovascular risk factors given the influence of potential modifying factors from birth time, former generations and adult life.

Design. Population‐based cohort followed until 80 years of age.

Setting. Sweden.

Subjects. A total of 478 singleton men born in 1913 and participating in a population study in Gothenburg, Sweden, from age 50.

Main outcome measures. Systolic blood pressure (SBP), antihypertensive treatment, incident diabetes mellitus, and serum total cholesterol, serum triglycerides and waist circumference as both continuous variables and in the highest quintiles of their distributions.

Results. After adjustment for the influence of birth time variables, hereditary factors and anthropometric and socio‐economic adult life variables, SBP decreased by 3.7 mmHg per 1000 g increase of birth weight, the prevalence of antihypertensive treatment decreased by 32%, diabetes decreased by 53%, serum total cholesterol decreased by 0.20 mmol L−1and being in the top quintile of serum cholesterol decreased by 23%. The population risk percentage due to a birth weight ≤3000 g was for all three outcomes 3.8% and for antihypertensive treatment, diabetes and cholesterol 0.2, 18 and 2.5%, respectively.

Conclusions. Low birth weight thus seems to affect the development of increasing SBP, antihypertensive treatment, diabetes and high cholesterol even when potential effect modifiers from birth time, former generations and adult life were taken into account. In the general population, the risk percentage due to a birth weight ≤3000 g was largest for diabetes.
U‐shaped relationship between mortality and admission blood pressure in patients with acute stroke
Authors: Vemmos K. N. , Tsivgoulis G. , Spengos K. , Zakopoulos N. , Synetos A. , Manios E. , Konstantopoulou P. , Mavrikakis M.
Published: January 2004

Objective.  To evaluate the relationship between systolic blood pressure (SBP) or diastolic blood pressure (DBP) on admission and early or late mortality in patients with acute stroke.

Design.  Prospective study of hospitalized first‐ever stroke patients over 8 years.

Setting.  Stroke unit and medical wards in a University hospital.

Subjects.  A total of 1121 patients admitted within 24 h from stroke onset and followed up for 12 months.

Main outcome measures.  Mortality at 1 and 12 months after stroke in relation to admission SBP and DBP.

Results.  Early and late mortality in patients with acute ischaemic or haemorrhagic stroke in relation to admission SBP and DBP followed a ‘U‐curve pattern’. After adjusting for known outcome predictors, the relative risk of 1‐month and 1‐year mortality associated with a 10‐mmHg SBP increase above 130 mmHg (U‐point of the curve) increased by 10.2% (95% CI: 4.2–16.6%) and 7.2% (95% CI: 2.2–12.3%), respectively. For every 10 mmHg SBP decrease, below the U‐point, the relative risk of 1‐month and 1‐year mortality rose by 28.2% (95% CI: 8.6–51.3%) and 17.5% (95% CI: 3.1–34.0%), respectively. Low admission SBP‐values were associated with heart failure (P < 0.001) and coronary artery disease (P = 0.006), whilst high values were associated with history of hypertension (P < 0.001) and lacunar stroke (P < 0.001). Death due to cerebral oedema was significantly (P = 0.005) more frequent in patients with high admission SBP‐values, whereas death due to cardiovascular disease was more frequent (P = 0.004) in patients with low admission SBP‐values.

Conclusion.  Acute ischaemic or haemorrhagic stroke patients with high and low admission BP‐values have a higher early and late mortality. Coincidence of heart disease is associated with low initial BP‐values. Death due to neurological damage from brain oedema is associated with high initial BP‐values.
Changes in blood pressure and body weight following smoking cessation in women
Authors: Janzon E. , Hedblad B. , Berglund G. , Engström G.
Published: January 2004

Objective.  Few have studied the long‐term effects of smoking and smoking cessation on weight gain and blood pressure increase and compared with the age‐related increases experienced by most adults. This study compared the development of weight and blood pressure in female never smokers, continuing smokers and smokers who quit smoking.

Design.  Weight, systolic (SBP) and diastolic (DBP) blood pressure and smoking habits were assessed at baseline and re‐assessed after a mean follow‐up of 9.0 ± 5.8 years.

Setting.  Population‐based cohort.

Subjects.  A total of 2381 female never smokers and 1550 female smokers. At the re‐examination, 388 of the smokers had quit smoking.

Results.  Mean weight gain was 7.6 ± 6.1, 3.2 ± 5.8 and 3.7 ± 5.2 kg, respectively, in quitters, continuing smokers and never smokers (P < 0.001). In women without blood pressure treatment, mean SBP increase was 20.9 ± 16.8, 19.1 ± 15.8 and 16.1 ± 16.3 mmHg, respectively, in these groups (P < 0.001). Mean DBP increase was 6.2 ± 8.7, 5.7 ± 9.3 and 3.1 ± 8.0 mmHg, respectively (P < 0.001). After adjustments for potential confounders, the increased weight gain in quitters remained highly significant. The differences in SBP and DBP increase were attenuated after adjustments, but remained significant. Incidence of hypertension (≥ 160/95 mmHg or treatment) was significantly higher in quitters [adjusted odds ratio (OR): 1.8; CI: 1.4–2.5] when compared with continuing smokers (OR: 1.3; CI: 1.07–1.6) and never smokers (reference).

Conclusion.  Over a long follow‐up, weight gain was approximately 3–4 kg higher in quitters when compared with continuing smokers or never smokers. Although the differences in blood pressure increase were moderate, smoking cessation was associated with an increased incidence of hypertension.
Where are clinical trials going? Society and clinical trials
Authors: Sleight P.
Published: January 2004

Clinical trials now increasingly impinge on society at large. First there is growing emphasis from health organizations on the need for unbiased evidence about the effectiveness of promoted remedies. Second, as most novel treatments accrue increased costs to society, these need to be evaluated in terms of value for money. Third, there has been confusion and concern about the resolution of conflicting evidence, especially the role of advertising and commercial pressures from a powerful pharmaceutical industry motivated by profit. Fourth, there is concern about research fraud and the ethics of clinical trials. Fifth, there is increasing suspicion of political advice, which sometimes has sought to reassure an anxious public on the basis of complex and possibly inadequate scientific information.

Some of these issues are addressed by truly independent and properly constituted data and safety monitoring committees, which are of particular importance when academic investigators or universities have a large financial conflict of interest. This is now more problematic with the current encouragement of investigator‐led spin‐off companies. These issues are best resolved by independent financial support (from government or other institutions) rather than relying on the commercial sponsor.
Historical and contemporary multilocus population structure of Ascochyta rabiei (teleomorph: Didymella rabiei) in the Pacific Northwest of the United States
Authors: Peever T. L. , Salimath S. S. , Su G. , Kaiser W. J. , Muehlbauer F. J.
Published: January 2004

The historical and contemporary population genetic structure of the chickpea Ascochyta blight pathogen, Ascochyta rabiei (teleomorph: Didymella rabiei), was determined in the US Pacific Northwest (PNW) using 17 putative AFLP loci, four genetically characterized, sequence‐tagged microsatellite loci (STMS) and the mating type locus (MAT). A single multilocus genotype of A. rabiei (MAT1‐1) was detected in 1983, which represented the first recorded appearance of Ascochyta blight of chickpea in the PNW. During the following year many additional alleles, including the other mating type allele (MAT1‐2), were detected. By 1987, all alleles currently found in the PNW had been introduced. Highly significant genetic differentiation was detected among contemporary subpopulations from different hosts and geographical locations indicating restricted gene flow and/or genetic drift occurring within and among subpopulations and possible selection by host cultivar. Two distinct populations were inferred with high posterior probability which correlated to host of origin and date of sample using Bayesian model‐based population structure analyses of multilocus genotypes. Allele frequencies, genotype distributions and population assignment probabilities were significantly different between the historical and contemporary samples of isolates and between isolates sampled from a resistance screening nursery and those sampled from commercial chickpea fields. A random mating model could not be rejected in any subpopulation, indicating the importance of the sexual stage of the fungus both as a source of primary inoculum for Ascochyta blight epidemics and potentially adaptive genotypic diversity.
Direct and maternal genetic relationships of lamb live weight and carcass traits in Swedish sheep breeds
Authors: Näsholm A.
Published: January 2004

Possibilities to include carcass traits recorded at commercial slaughterhouses in the genetic evaluation of sheep in Sweden were investigated by estimating direct and maternal genetic parameters for 4‐month weight (4MW), carcass weight (CW), carcass fatness grade (FAT), and carcass fleshiness (FLESH) using multiple‐trait animal models. Data included two sets of breeds, the so‐called white breeds (Swedish landrace breeds, Texel, Dorset, Oxford Down, Suffolk, East Friesian Milk Sheep, and Swedish crossbred) and the Gotland breed. There were 30 625 observations on 4MW and 5062 observations on carcass traits for the white breeds. For the Gotland breed the numbers were 43 642 and 7893, respectively. The results showed that it is feasible to use field‐recorded carcass traits in the genetic evaluation. To consider the effects of selection and to utilize all information in an optimal way multiple trait animal models should be used. Direct and maternal heritabilities for 4MW and CW varied between 0.04 and 0.18 and heritabilities for FAT and FLESH between 0.21 and 0.29. Direct and maternal genetic correlations between 4MW and CW were high (0.61–0.97). Genetic correlations were higher between the weights and FLESH (0.11–0.62) than between the weights and FAT (−0.23 to 0.40). Genetic correlations between FAT and FLESH were moderate (0.38–0.45). Heritabilities for CW were higher if 4MW was included in the analyses and the effect of selection on 4MW was stronger for CW than for FAT or FLESH. The importance of maternal effects on carcass traits was discussed.
EFNS task force – therapy of nystagmus and oscillopsia
Authors: Straube A. , Leigh R. J. , Bronstein A. , Heide W. , Riordan‐Eva P. , Tijssen C. C. , Dehaene I. , Straumann D.
Published: January 2004

An overview of possible treatment options for oculomotor disorders that prevent clear vision is given. Downbeat nystagmus, upbeat nystagmus, seesaw nystagmus, periodic alternating nystagmus, acquired pendular nystagmus, and saccadic oscillations such as opsoclonus/ocular flutter are discussed. In addition, superior oblique myokymia and vestibular paroxysmia are reviewed. All treatment recommendations available in the literature are classified as class C only. In general, only some of the patients benefit from the treatment.