bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular effects of prolonged growth hormone replacement in adults
Authors: BESHYAH S. A. , SHAHI M. , FOALE R. , JOHNSTON D. G.
Published: August 2009

Abstract. Objectives. To study the cardiovascular effects of human growth hormone (GH) replacement therapy in adults.

Intervention. Biosynthetic human GH given in a daily dose of 0.04 ± 0.01 IU kg−1 for 6–18 months in an open trial.

Patients. Thirty‐four GH‐deficient hypopituitary patients on conventional replacement therapy, aged 19–67 years and with a body mass index of 18.0–410.0 kg/m2.

Measurements. Resting blood pressure, exercise tolerance, renal function and routine blood counts were assessed every 6 months. Two‐dimensional echocardiography and Doppler ultrasound scanning were performed at 0, 6 and 12 months of GH therapy.

Results. Exercise time increased significantly on GH from 9.37 ± 2.64min at the start to 10.39 ± 2.86 min (P < 0.001), 10.90 ± 2.48 min (P < 0.001) and 11.11 ± 0.70 min (P < 0.001) at 6, 12 and 18 months respectively. There was no change in the heart rate or in the blood pressure at rest nor at the peak of exercise. No significant changes were observed in measures of cardiac structure (left ventricular mass index, left ventricular posterior wall thickness and interventricular septal thickness), ejection fraction nor in cardiac output. Isovolumic relaxation time, a marker of diastolic function, decreased in 24 patients after 6 months on GH (from 98.6 ± 15.9 to 89.6 ± 15.2 ms; P < 0.03) but it was not different from baseline in the 18 patients who were restudied at 12 months. There was no significant change in the left ventricular filling neither at 6 nor at 12 months. No significant changes were observed in plasma electrolytes, creatinine nor in blood count on GH treatment.

Conclusions. Growth hormone replacement therapy in hypopituitary adults for 6–18 months produced sustained increase in exercise tolerance but was not associated with changes in cardiac structure or systolic function.
Heterozygous familial hypercholesterolaemia: the influence of the mutation type of the low‐density‐lipoprotein receptor gene and PvuII polymorphism of the normal allele on serum lipid levels and response to lovastatin treatment
Authors: VUORIO A. F. , OJALA J.‐P. , SARNA S. , TURTOLA H. , TIKKANEN M. J. , KONTULA K.
Published: August 2009

Abstract. Objectives. To study whether (i) the low‐density‐lipoprotein (LDL)‐receptor gene mutation type itself or (ii) the PvuII restriction‐fragment‐length polymorphism (RFLP) of the intact LDL‐receptor gene affects serum lipid levels and their responses to lovastatin treatment in heterozygous familial hypercholesterolaemia (FH).

Design. Comparison of serum lipid levels in 149 heterozygous FH patients, including 79 patients with the FH Helsinki gene and 70 patients with the FH North Karelia gene, grouped according to the PvuII RFLP status of their nonmutated LDL‐receptor allele; studies of lovastatin responses in 23 FH patients with different mutation types.

Subjects. Molecularly defined heterozygous FH patients.

Interventions. DNA analysis by polymerase chain‐reaction assay (PCR) and Southern blotting, fasting serum lipid measurements in all patients, and administration of lovastatin 40–80 mg daily to 16 FH Helsinki patients and seven FH North Karelia patients.

Main outcome measures. Baseline and post‐treatment serum cholesterol, LDL cholesterol, high‐density‐lipoprotein (HDL) cholesterol and triglyceride levels.

Results. There were no significant differences in serum total or LDL‐cholesterol levels in FH patients with the FH Helsinki gene compared with those carrying the FH North Karelia gene. Regardless of the mutation type, patients without the PvuII site in the normal LDL‐receptor gene (P – subjects) tended to have 6–8% higher serum and LDL‐cholesterol levels than patients possessing this restriction site (P + subjects). Although not statistically significant, this difference is qualitatively and quantitatively similar to that reported in three different non‐FH populations. Treatment with lovastatin brought about similar hypolipidaemic responses in FH patients with either mutation type (FH Helsinki or FH North Karelia) or PvuII RFLP status (P + or P –).

Conclusions. Two LDL‐receptor gene mutations with dissimilar phenotypic characteristics are associated with similar serum lipid levels and response to statin treatment. Our data also support the previous assumption that the PvuII RFLP of the LDL‐receptor gene locus is associated with variation of serum cholesterol levels.
Thrombolysis in ischaemic stroke — how far from a clinical breakthrough ?
Authors: BOYSEN G. , OVERGAARD K.
Published: August 2009

Abstract. Thromboembolic occlusions of the cerebral arteries often recanalize spontaneously, and patients with early recanalization have a better outcome than patients who do not recanalize. Clinical as well as experimental data support the concept of a time window within which brain tissue will profit from restoration of blood flow. In occlusion of middle cerebral artery, internal carotid artery, as well as vertebrobasilar arteries, open studies of intra‐arterial administration of thrombolytic agents have demonstrated recanalization within hours in 40–100% of patients in small series. In intravenous drug administration, recanalization rate was obtained in 34–59% of patients. Favourable outcome was associated with recanalization. Intracerebral bleeding complications with clinical deterioration occurred in about 10% of patients. Three randomized controlled trials comprising 156 patients with acute ischaemic stroke have reported favourable outcome in treated patients, with no difference of intracerebral haemorrhagic complications between treated and controls. Results of ongoing randomized placebo controlled trials are expected in 1995 to disclose whether a clinical breakthrough is achieved or whether haemorrhagic complications will outweigh a beneficial effect of thrombolytic therapy in acute cerebral ischaemia.
Brain repair
Authors: COMPSTON A.
Published: August 2009

Abstract. Significant improvements in the treatment of common neurological diseases can be expected over the next few years from the application of advances now occurring in the basic neurosciences. In many disorders of the central nervous system, disability accumulates as a result of the degenerative process and its failure to repair. In part, this is because with differentiation, cells in the adult nervous system lose the ability to proliferate and migrate. A family of growth factors orchestrates proliferation, migration, differentiation and survival of neurones and glia; because certain of these growth factors also protect from injury cells which they support during development, there should soon be opportunities for limiting damage following a variety of insults and for rescuing degenerating neurones and glia. The discovery that axon regeneration is actively inhibited, perhaps in order to maintain stability in the complex systems and circuits that are established during development, suggests new strategies for enhancing axonal regeneration in spinal and head injury. Recruiting cells that are capable of restoring glial‐neuronal interactions into areas of damage will be an important part of the brain repair strategy but it may prove possible to restore complex cellular arrangements through cell implantation only. Grafted neurones survive, produce appropriate neurotransmitters, form connections and restore some behaviours, but their relative inability to grow limits the degree of structural and functional repair that can be achieved; nevertheless, nerve cell implantation is now being used in the management of certain neurodegenerative diseases of the human central nervous system. There are also prospects for increasing the remyelination which occurs following acute inflammatory disease of the central nervous system, through the combination of immunological treatments that limit the disease process, growth factors that recruit oligodendrocytes and implantation of glial progenitors into demyelinated areas.
Iron deficiency and iron overload in Swedish male adolescents
Authors: OLSSON K. S. , MARSELL R. , RITTER B. , OLANDER B. , ÅKERBLOM Å. , ÖSTERGÅRD H. , LARSSON O.
Published: August 2009

Abstract.Objectives. The present study was undertaken to confirm or reject recent findings indicating a high prevalence of iron deficiency in Swedish male adolescents; a second aim was to study the prevalence of genetic iron overload.

Design. The diagnostic criteria were: anaemia: Hb < 130 g L−1(a); iron deficiency: serum ferritin (SF) < 12 μg L−1+ transferrin saturation (TS) < 16% (b); iron deficiency anaemiaa + b.Iron overload: SF (90th percentile) + TS (90th percentile) in repeat tests.

Setting. Central Sweden.

Subjects. A total 3975 men aged 18 years studied on enrollment into military service.

Results. Serum ferritin averaged 36.8 μg L−1. Anaemia was present in 0.5%, iron deficiency anaemia in 0.17% and iron deficiency in 0.4%. If iron deficiency is defined as SF < 16 μg L−1, as was recently suggested, the prevalence would be 2.8%. Such a cut‐off value would include 73% normal people (false positives). Iron overload had the same prevalence as iron deficiency, 0.4%.

Conclusions. Iron stores, as measured by serum ferritin, are small in young men studied at the end of their growth spurt. However, iron deficiency is rare. Therefore, the present study has not been able to confirm the high prevalence of iron deficiency recently reported. A prevalence of genetic haemochromatosis of 0.4%, confirms earlier findings and would mean that 12.6% of the population are heterozygotic carriers of the iron‐loading genes. These findings give no support for a proposed, more effective iron‐enrichment of food. It is not needed and can be harmful.
Leucocyte doubling time is a useful predictor of progression‐free survival in chronic lymphocytic leukaemia
Authors: AXDORPH U. , NILSSON B. I. , NILSSON B. R. , BJÖRKHOLM M.
Published: August 2009

Abstract. Objective. To assess leucocyte doubling time (LDT) in relation to progression‐free survival in patients with chronic lymphocytic leukaemia (CLL). In addition, to define the impact of a second LDT in both untreated and treated patients.

Design. Retrospective study of LDT in previously untreated patients with CLL.

Subjects and setting. Sixty patients diagnosed over a 13‐year period at a county hospital. In forty‐five of the 60 patients, an LDT could be defined. These patients were included in the final analysis.

Main outcome measures. LDT below and above 12 months, progression‐free and overall survival.

Results. Patients in Binet stages B and C had a median LDT of 4 months as compared to 26 months in stage A patients (P < 0.01). The projected progression‐free survival at 3 years was 24% in patients with an LDT of < 12 months. The corresponding figure for the remaining patients was 68% (P < 0.01). The overall 5‐year survival did not differ significantly between patients with an LDT below and above 12 months, respectively. In seven untreated patients, a second LDT could be calculated which was shorter than the first recorded LDT. A second LDT was also identified in five patients post treatment that was consistently shorter than their first LDT.

Conclusions. Measurement of LDT is a simple complement in predicting progression‐free survival in patients with CLL. Thus, monitoring of LDT may add to the clinical evaluation and therapeutic decision making for the many elderly patients with this often indolent disease.
Iron status markers during pregnancy No relationship between levels at the beginning of the second trimester, prior to delivery and post partum
Authors: Milman N. , Graudal N. , Agger A. O.
Published: August 2009

Abstract. Objective. To evaluate whether levels of iron status markers (haemoglobin, serum transferrin saturation, serum ferritin) in pregnant women, measured in the beginning of the second trimester, could be used to predict levels later in pregnancy, pre partum and post partum.

Design. Randomized, double‐blind, placebo‐controlled parallel study.

Setting. The Birth Clinic at the Department of Obstetrics, Herning Hospital, Herning, Denmark.

Subjects. One hundred and twenty healthy pregnant women between 14 and 18 weeks of gestation.

Interventions. Sixty‐three women were allocated to treatment with tablets containing 66 mg ferrous iron (as fumarate) daily, and 57 women to treatment with placebo.

Main outcome measures. Haemoglobin, serum transferrin saturation, and serum ferritin were measured every 4th week during gestation, prior to delivery, and 1 and 8 weeks post partum.

Results. Correlation matrices during pregnancy and post partum were calculated for each iron status marker separately in iron‐treated and placebo‐treated women. Haemoglobin, transferrin saturation and serum ferritin values at inclusion displayed steadily declining correlation coefficients with values obtained later in pregnancy. There were no clinically relevant correlations to values obtained 8 weeks or less prior to delivery, and no correlations to values post partum. Serum ferritin values at inclusion could not be used to predict values later in pregnancy or post partum.

Conclusion. Haemoglobin, transferrin saturation and serum ferritin values measured in the beginning of the second trimester appear to be unsuitable as guidelines for an individual iron prophylaxis in pregnant women.
Clinical effects of octreotide compared to placebo in patients with gastrointestinal neuroendocrine tumours Report on a double‐blind, randomized trial
Authors: Jacobsen M. B. , Hanssen L. E.
Published: August 2009

Abstract. Objectives. To compare the effect of octreotide with placebo on symptoms, tumour marker and quality of life in patients with gastrointestinal neuroendocrine tumours and liver metastases.

Design. A blinded, placebo‐controlled, cross‐over study was performed. The number of flushing epidodes and diarrhoea episodes were registered for 1 week prior to the study and for the 8‐week duration of the study. Quality of life and 24‐h urinary 5‐hydroxyindoleacetic acid (5‐HIAA) excretion were measured before the start, and at 4 and 8 weeks. Quality of life was registered with the Psychosocial Adjustment to Illness Scale (PAIS) and 5‐HIAA measured by high‐performance chromatography with electrochemical detection. 5‐HIAA values exceeding 45 μmol 24 h−1 were considered to be elevated.

Setting. The study was performed in a tertiary referral centre.

Subjects. Twelve patients were approached; eleven patients were included, with a mean age of 56.5 (range 30–72) years. The primary tumour originated from the small intestine in nine and from the pancreas in two patients. The main symptoms were diarrhoea, flushing and nausea. The 24‐h excretion of 5‐HIAA was increased in all patients.

Interventions. Patients were treated for 4 weeks with octreotide (100 μg) subcutaneously, twice daily, and for 4 weeks on placebo (octreotide vehicle) in random starting order.

Main outcome measures. The main outcome measures were the number of episodes of the main clinical symptom(s) and 24‐h 5‐HIAA excretion.

Results. Octreotide lowered diarrhoea and flushing frequency significantly compared to placebo. 5‐HIAA excretion was reduced during treatment with the active drug. Two domains of the PAIS were significantly improved, indicating that the reduction of tumour marker and symptoms were clinically important.

Conclusions. The clinical effect of octreotide on symptoms in patients with neuroendocrine tumours was demonstrated in a controlled, prospective trial.
Predictors of mortality in hospitalized patients with secondary upper gastrointestinal haemorrhage
Authors: ZIMMERMAN J. , MEROZ Y. , ARNON R. , TSVANG E. , SIGUENCIA J.
Published: August 2009

Abstract. Objectives. To identify clinical, laboratory and endoscopic features of prognostic implication in patients who suffer an upper gastrointestinal haemorrhage whilst hospitalized for other causes.

Design/setting. A prospective longitudinal study of 125 consecutive cases (89 males, 36 females) seen during 1988–1991 in a tertiary care university hospital.

Main outcome measures. The crude and adjusted relative risk of mortality associated with each of the various clinical, laboratory and endoscopic variables.

Results. The rates of endoscopic haemostasis, persistent or recurrent bleeding and surgery to control bleeding were 48, 37 and 12%, respectively; the overall mortality was 28%. A significantly increased risk of mortality was associated with shock prior to onset of bleeding, sepsis, renal failure, cirrhosis, encephalopathy, presence of red blood in the nasogastric aspirate or per rectum, thrombocytopenia, hypoalbuminaemia, elevation of serum bilirubin, aminotransferases or urea levels, endoscopic evidence of active bleeding, the application of endoscopic haemostasis, rebleeding, transfusion of ≥ 6 units of blood, surgical treatment or any subsequent complication. Use of nonsteroidal anti‐inflammatory drugs (27%) was associated with a decreased mortality risk (odds ratio 0.2; P = 0.03). A multivariate analysis showed that the features at presentation which were independently associated with an increased risk of mortality were: a history of cirrhosis, sepsis, shock prior to onset of bleeding, hypoalbuminaemia and elevated serum aminotransferases.

Conclusion. The prognosis of secondary upper gastrointestinal haemorrhage depends on the underlying diseases and on the general condition of the patient, rather than on the actual cause of bleeding.
The prevalence of alcoholism and its relation to cause of hospitalization and long‐term mortality in male somatic inpatients
Authors: WALLERSTEDT S. , DENISON H. , SANDSTRÖM J. , WESTIN J.
Published: August 2009

Abstract. Objective. To investigate the prevalence of alcoholism in patients hospitalized because of somatic disorders, and to analyse morbidity, mortality, and causes of death in those alcoholics.

Design. Inception cohort, 7‐year follow‐up.

Setting. Primary and secondary care clinics at a community hospital in Göteborg, Sweden.

Patients and controls. A convenience sample of all 205 men hospitalized at a medical, surgical, and orthopaedic clinic at a random time‐point. The diagnosis of alcoholism was stated or rejected by means of structured interviews about drinking habits and by scrutiny of records from the hospital, psychiatric clinics, and social authorities. In the study of morbidity pattern and mortality in the alcoholics (n = 52), age‐matched, non‐alcoholic controls were recruited from the same sample.

Main outcome measures. Prevalence of alcoholism; distribution of somatic disorders as cause of hospitalization at inclusion; mortality and risk ratio of death using the death hazard function of the groups compared with that of men of the same age‐distribution in the Swedish population; causes of death during a 7‐year follow‐up.

Main results. Fifty‐two of the 205 hospitalized men (25%) were alcoholics and 16 of these men (31%) were treated for an alcohol‐related disorder. During follow‐up, the mortality rate was about 50% both in the alcoholic and in the control groups. The risk of death ratio was 5.0 [95% confidence interval (CI), 2.9 to 8.3] in the alcoholics and 3.9 (95% CI, 2.2 to 6.4) in the controls. Death from trauma, intoxication, and liver failure occurred exclusively in the alcoholics and accounted for almost one‐third of the deaths after discharge.

Conclusions. Alcoholism was found in every fourth male somatic inpatient, and an alcohol‐related disorder was the cause of hospitalization in one‐third of these men. The long‐term prognosis did not differ from that in non‐alcoholic patients. In the treatment of alcoholics with somatic disorders, it is important to take measures against alcoholism as well.
Heart rate variability in coronary artery disease
Authors: HUIKURI H. V.
Published: August 2009

Abstract. Heart rate variability (HRV) reflects the modulation of cardiac function by autonomic and other physiological systems, and its measurement from ambulatory electrocardiograph (ECG) recordings is a useful method for both clinical and scientific purposes. Heart rate variability can be measured by several linear and non‐linear methods, and various methods can give different information on neural and other physiological influences on the heart. Heart rate variability is abnormal in various settings of ischaemic heart disease, and the most important current application of HRV analysis in clinical cardiology is its measurement in postinfarction patients, in whom abnormal HRV indicates an increased risk of cardiac mortality. Future research may expand the clinical utility of HRV measurement to other clinical situations.
The role of potassium in postural hypotension: electrolytes and neurohumoral factors in elderly hypertensive patients using diuretics
Authors: Luutonen Sinikka , NEUVONEN P. , RUSKOAHO H. , RÄIHÄ I. , RAJALA T. , ANTILA K. , SOURANDER L.
Published: August 2009

Abstract. Objective. To study the association between postural hypotension and (i) electrolyte levels and (ii) neurohumoral factors in elderly hypertensive patients using diuretics.

Design. Cross‐sectional study of patients and controls.

Setting. The subjects were gathered from senior citizen clubs or they were referred to the study by general practitioners. The subjects were examined on a geriatric ward in Turku City Hospital.

Subjects. Seven subjects with postural hypotension and 13 controls.

Measurements. Plasma electrolyte levels and neurohumoral response to head‐up tilt.

Results. There were significantly more hypokalemic subjects in the postural hypotension group (5/7) than in the control group (1/13) (P < 0.01). The plasma potassium level was negatively correlated to plasma aldosterone (r = –0.57; P < 0.01) and renin activity (r = –0.69; P < 0.001). Subjects with postural hypotension had higher levels of noradrenaline, both supine (P < 0.05) and during tilt (P < 0.05). There were no significant differences in supine or tilt levels of plasma adrenaline, vasopressin, atrial natriuretic peptide, aldosterone and renin activity between the groups.

Conclusion. The results suggest that potassium depletion is associated with postural hypotension in elderly hypertensive patients using diuretics. However, it is unclear whether there is a causative link between potassium depletion and postural hypotension or whether they are both caused by some other factor, e.g. volume contraction.
Noradrenaline Involvement in the Negative‐Feedback Effects of Ovarian Steroids on Luteinising Hormone Secretion
Authors: Helena C. V. V. , Szawka R. E. , Anselmo‐Franci J. A.
Published: August 2009

Noradrenaline has been shown to modulate the ovarian‐steroid feedback on luteinising‐hormone (LH) release. However, despite the high amount of evidence accumulated over many years, the role of noradrenaline in LH regulation is still not clearly understood. The present study aimed to further investigate the involvement of noradrenaline in the negative‐feedback effect of oestradiol and progesterone on basal LH secretion. In experiment 1, ovariectomised (OVX) rats received a single injection of oil, oestradiol, or progesterone at 09.00–10.00 h and were decapitated 30 or 60 min later. Levels of noradrenaline and its metabolite, 3‐methoxy‐4‐hydroxyphenylglycol (MHPG), were determined in microdissections of the preoptic area (POA) and medial basal hypothalamus‐median eminence (MBH‐ME) and correlated with LH secretion. Basal LH levels were decreased 30 and 60 min after oestradiol or progesterone injection, and this hormonal response was significantly correlated with a reduction in POA MHPG levels, which reflect noradrenaline release. In addition, noradrenaline levels in the POA were increased, whereas noradrenaline turnover (MHPG/noradrenaline ratio) was decreased 60 min after the injection of both hormones. No effect was found in the MBH‐ME. In experiment 2, i.c.v. administration of noradrenaline (60 nmol), performed 15 min before oestradiol or progesterone injection in jugular vein‐cannulated OVX rats, completely prevented the ovarian steroid‐induced inhibition of LH secretion. The data obtained provide direct evidence that LH secretion in OVX rats is positively regulated by basal noradrenergic activity in the POA, and its reduction appears to play a role in the negative‐feedback effect of ovarian steroids on LH secretion in vivo.
Genetic analysis of xenocoumacin antibiotic production in the mutualistic bacterium Xenorhabdus nematophila
Authors: Park Dongjin , Ciezki Kristin , Van Der Hoeven Ransome , Singh Swati , Reimer Daniela , Bode Helge B. , Forst Steven
Published: August 2009

Xenocoumacin 1 (Xcn1) and xenocoumacin 2 (Xcn2) are the major antimicrobial compounds produced by Xenorhabdus nematophila. To study the role of Xcn1 and Xcn2 in the life cycle of X. nematophila the 14 gene cluster (xcnA–N) required for their synthesis was identified. Overlap RT‐PCR analysis identified six major xcn transcripts. Individual inactivation of the non‐ribosomal peptide synthetase genes, xcnA and xcnK, and polyketide synthetase genes, xcnF, xcnH and xcnL, eliminated Xcn1 production. Xcn1 levels and expression of xcnA–L were increased in an ompR strain while Xcn2 levels and xcnMN expression were reduced. Xcn1 production was also increased in a strain lacking acetyl‐phosphate that can donate phosphate groups to OmpR. Together these findings suggest that OmpR‐phosphate negatively regulates xcnA–L gene expression while positively regulating xcnMN expression. HPLC‐MS analysis revealed that Xcn1 was produced first and was subsequently converted to Xcn2. Inactivation of xcnM and xcnN eliminated conversion of Xcn1 to Xcn2 resulting in elevated Xcn1 production. The viability of the xcnM strain was reduced 20‐fold relative to the wild‐type strain supporting the idea that conversion of Xcn1 to Xcn2 provides a mechanism to avoid self‐toxicity. Interestingly, inactivation of ompR enhanced cell viability during prolonged culturing.
ESX‐1 secreted virulence factors are recognized by multiple cytosolic AAA ATPases in pathogenic mycobacteria
Authors: DiGiuseppe Champion Patricia A. , Champion Matthew M. , Manzanillo Paolo , Cox Jeffery S.
Published: August 2009

The ESX‐1 secretion system of Mycobacterium tuberculosis delivers bacterial virulence factors to host cells during infection. The most abundant factor, the ESAT‐6/CFP‐10 dimer, is targeted for secretion via a C‐terminal signal sequence on CFP‐10 that is recognized by the cytosolic ATPase, Rv3871. However, the selection determinants for other ESX‐1 substrates appear to be more complex. Some substrates, such as ESAT‐6, are secreted despite lacking signal sequences. Furthermore, all substrates require targeting of the other ESX‐1 secreted proteins, a distinguishing feature of this system. How ESX‐1 substrates are selected and the basis for co‐dependent secretion is unknown. Here we show that the EspC substrate interacts with Rv3868, a cytosolic AAA ATPase, through its C‐terminus. Swapping the C‐termini of EspC and CFP‐10 revealed that these signals are functionally distinct, suggesting that the proteins are targeted via interactions with different ATPases. Surprisingly, biochemical purification experiments demonstrate that these substrates and ATPases form multi‐protein complexes inside the cell and identified a new secreted substrate. By interfering with this protein interaction network, we have partially uncoupled co‐dependent substrate secretion. Our results suggest that proper functioning of the ESX‐1 pathway requires the interaction of multiple ESX‐1 substrates and components prior to their secretion. Ultimately, understanding the details of ESX‐1 targeting may allow for engineering of better vaccines to prevent tuberculosis.
SirA enforces diploidy by inhibiting the replication initiator DnaA during spore formation in Bacillus subtilis
Authors: Wagner Jennifer K. , Marquis Kathleen A. , Rudner David Z.
Published: August 2009

How cells maintain their ploidy is relevant to cellular development and disease. Here, we investigate the mechanism by which the bacterium Bacillus subtilis enforces diploidy as it differentiates into a dormant spore. We demonstrate that a sporulation‐induced protein SirA (originally annotated YneE) blocks new rounds of replication by targeting the highly conserved replication initiation factor DnaA. We show that SirA interacts with DnaA and displaces it from the replication origin. As a result, expression of SirA during growth rapidly blocks replication and causes cell death in a DnaA‐dependent manner. Finally, cells lacking SirA over‐replicate during sporulation. These results support a model in which induction of SirA enforces diploidy by inhibiting replication initiation as B. subtilis cells develop into spores.
Schistosomiasis and liver fibrosis
Authors: ANDRADE Z. A.
Published: August 2009

Schistosoma mansoni infection invariably results in liver fibrosis of the host. This fibrosis may be represented by small focal areas of chronic inflammation and excess extracellular matrix deposited in periovular granulomas, distributed in variable numbers at the periphery of the portal vein system. This is the outcome of 90% of the infected population in endemic areas. Conversely, a minority of infected individuals develop extensive disease with numerous granulomas along the entire extension of the portal spaces. This latter situation is mainly dependent on special hemodynamic changes created by a heavy worm load, with the subsequent production of numerous eggs and represents a severe form of a peculiar chronic hepatopathy. Thus, host–parasite interactions in schistosomiasis help us to understand a number of important features of liver fibrosis: its initiation and regulation, the significance of accompanying vascular changes, the dynamics of fibrosis formation and regression with antiparasitic treatment; host genetic and immunological contributions, and the pathophysiology of portal hypertension.
An international quality control programme for PRISM chemiluminescent immunoassays in blood service and blood product laboratories
Authors: Walker S. , Dimech W. , Kiely P. , Smeh K. , Francis B. , Karakaltsas M. , Dax E. M.
Published: August 2009

Background  Laboratories screening for blood‐borne virus infections in blood and blood products are required by international standards and guidelines to ensure that their testing processes remain within control. An effective means of ensuring this aim is through participation in a quality control programme. Analyses of results from a quality control (QC) programme conducted for the Abbott PRISM (PRISM) assays are reported.

Materials and methods  Laboratories participating in the National Serology Reference Laboratory, Australia's PRISM QC programme were provided with aliquots of a multimarker QC sample which were tested regularly in each PRISM subchannel. Test results were submitted to a single database using an Internet‐based QC monitoring system, EDCNet. The QC test results submitted between 15 October 2001 and 5 March 2006 for each PRISM instrument and each lot of PRISM reagent were analysed to determine the imprecision and bias in each test system.

Results  A total of 157 404 test results from approximately 47 000 test runs submitted into the EDCNet database were analysed. Six batches of the multimarker QC samples were tested in 454 PRISM reagent lots. The coefficient of variation of QC sample test results ranged from 9·17 to 15·83%, 8·29 to 9·44%, 10·50 to 15·38% and 7·05 to 10·32% when tested in the PRISM anti‐hepatitis C virus, anti‐human immunodeficiency virus, anti‐human T‐cell lymphotrophic virus and hepatitis B surface antigen assays, respectively. Analysis of QC test results reported from testing in the anti‐HTLV assay detected one lot of reagent (10572HN00) which was identified to be an outlier using Tukey's filter.

Discussion  Analysis of test results of an external QC sample can be used as a statistical process control through ongoing measurement of imprecision. When laboratories test the same QC sample in the same assay and submit test results to a single database, the results can be compared and a measure of bias can be calculated. The resulting QC programme can offer detection of unexpected variation in the testing processes and the source of variation investigated.
Detection of Chalara fraxinea from tissue of Fraxinus excelsior using species‐specific ITS primers
Authors: Johansson S. B. K. , Vasaitis R. , Ihrmark K. , Barklund P. , Stenlid J.
Published: August 2009

Chalara fraxinea (teleomorph: Hymenoscyphus albidus) is known as a serious pathogen of Fraxinus excelsior, causing massive dieback of trees in Europe. The fungus is able to cause latent infections, and has been previously detected as an endophyte in asymptomatic tissues. Chalara fraxinea is a slow grower in culture, and is thus likely to be overgrown by faster growing fungi whenever pure culture isolations are being attempted. This study reports species‐specific ITS primers allowing fast and reliable detection of the pathogen directly from infected tissues of F. excelsior.
Genetic distinctions among the Mediterranean and Chinese populations ofBemisia tabaciQ biotype and their endosymbiontWolbachiapopulations
Authors: Ahmed M. Z. , Shatters R. G. , Ren S.‐X. , Jin G.‐H. , Mandour N. S. , Qiu B.‐L.
Published: August 2009

The sweetpotato whitefly,Bemisia tabaci, is a cryptic species complex composed of more than 24 different biotypes around the world. The Q biotype ofB. tabaci, which is thought to have originated in the Mediterranean Basin, is now a widespread and serious agricultural pest. In this study, the genetic differences among Q biotype populations from Mediterranean countries and China were investigated. Based on their mt COI gene sequences, the Q biotype populations could be divided into two groups, which were labelled as MedBasin 1 and MedBasin 2. MedBasin 1 is indigenous to the western Mediterranean area while MedBasin 2 is indigenous to the eastern Mediterranean area. Genetic variation was greater in the MedBasin 1 populations than in the MedBasin 2 populations. Unlike the introductions into the USA, which involved both Medbasin1 and MedBasin2 populations, allB. tabaciQ biotype populations in China belonged to MedBasin 1.Wolbachiadetection in eight representative Q biotype populations from China, Egypt and Syria indicated that all of the populations were infested withWolbachia, and the infection rate of the Chinese populations (42.5%) were not significantly different from that of Egypt and Syria (51.4%). Phylogenetic analysis indicated that the evolution of theWolbachiapopulations was not closely linked with the evolution of theirB. tabacihosts.
Respiration partitioning in contrasting subtidal sediments: seasonality and response to a spring phytoplankton deposition
Authors: Franco Maria de Assunção , Vanaverbeke Jan , Van Oevelen Dick , Soetaert Karline , Costa Maria José , Vincx Magda , Moens Tom
Published: August 2009

Biomass and respiration rates of bacteria, nematodes and macrobenthos were estimated in relation to the deposition of the spring phytoplankton bloom at two contrasting sites in the Southern North Sea: one with fine‐grained sediment close to the coastline and another with highly permeable sediments. Sediment community oxygen consumption (SCOC) was also measured. Bacterial biomass was relatively similar at both stations, whereas nematode and macrobenthic biomass were higher in fine‐grained sediment. In fine sediments, bacterial biomass increased quickly after deposition of the phytoplankton bloom, whereas the response of nematodes and macrobenthos was delayed. In coarser sediments, nematodes and macrobenthos also showed a fast response in terms of density and biomass. Respiration in permeable sediments was mainly dominated by bacteria at all periods of the year. Hence, nematode and macrobenthic respiration did not contribute strongly to SCOC. This is in contrast to the patterns observed in finer sediments, where both macrofauna and nematodes were important oxygen consumers as well. Macrobenthos contributed more to total SCOC than did nematodes in winter. However, shortly after the arrival of phytodetritus at the sea floor, nematodes and macrobenthos contributed equally to the total SCOC, indicating that all benthic size classes should be taken into account when investigating marine benthic respiration rates.
Cutaneous zygomycosis caused by Saksenaea vasiformis following water‐related wound in a 24‐year‐old immunocompetent woman
Authors: Stewardson Andrew J. , Holmes Natasha E. , Ellis David H. , Howden Benjamin P.
Published: August 2009

We describe a case of cutaneous zygomycosis caused by Saksenaea vasiformis in an immunocompetent 24‐year‐old woman. Diagnosis was based on histological and microbiological examination. The patient made a complete recovery with surgical debridement and antifungal therapy (liposomal amphotericin and posaconazole).
Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis
Authors: Narahara Yoshiyuki , Kanazawa Hidenori , Taki Yasuhiko , Kimura Yuu , Atsukawa Masanori , Katakura Tamaki , Kidokoro Hideko , Harimoto Hirotomo , Fukuda Takeshi , Matsushita Yoko , Nakatsuka Katsuhisa , Sakamoto Choitsu
Published: August 2009

Background and Aim:  Terlipressin has been shown to be effective in the management of hepatorenal syndrome. However, how terlipressin exerts its effect on the renal artery is unknown. The aim of the present study was to assess the effects of terlipressin on systemic, hepatic and renal hemodynamics in cirrhosis.

Methods:  Twenty‐eight patients with cirrhosis and portal hypertension were studied. Systemic and hepatic hemodynamics, hepatic and renal arterial resistive indices and neurohumoral factors were measured prior to and 30 min after intravenous administration of 1 mg terlipressin (n = 19) or placebo (n = 9).

Results:  After terlipressin, there were significant increases in both mean arterial pressure (P < 0.001) and systemic vascular resistance (P < 0.001), whereas heart rate (P < 0.001) and cardiac output (P < 0.001) decreased significantly. There was a significant decrease in the hepatic venous pressure gradient (P < 0.001). Portal venous blood flow also decreased significantly (P < 0.001). The mean hepatic arterial velocity increased significantly (P < 0.001). Although there was a significant decrease in the hepatic arterial resistive index (0.72 ± 0.08 to 0.69 ± 0.08, P < 0.001) and renal arterial resistive index (0.74 ± 0.07 to 0.68 ± 0.07, P < 0.001), portal vascular resistance was unchanged (P = 0.231). Plasma renin activity decreased significantly (P < 0.005), and there was a significant correlation between this decline and the decrease in renal arterial resistive index (r = 0.764, P < 0.005). The effects of terlipressin on systemic, hepatic and renal hemodynamics were observed similarly in patients with and without ascites. Placebo caused no significant effects.

Conclusion:  Terlipressin decreases hepatic and renal arterial resistance in patients with cirrhosis.
Interleukin‐27 polymorphisms are associated with inflammatory bowel diseases in a Korean population
Authors: Li Chun‐Shi , Zhang Qinggao , Lee Kwang‐Jae , Cho Sung‐Won , Lee Kee‐Myung , Hahm Ki‐Baik , Choi Suck‐Chei , Yun Ki‐Jung , Chung Hun‐Taeg , Chae Soo‐Cheon
Published: August 2009

Background and Aims:  The cytokine interleukin (IL)‐27 is composed of two subunits, Epstein–Barr virus‐induced gene 3 (EBI3) and p28, and IL‐27 is a novel IL‐12 family member that mediates between the innate and adaptive immune systems. We previously identified four polymorphisms in the human IL‐27 gene and we suggested that the polymorphism of IL‐27 is associated with the susceptibility to asthma. IL‐27 transcripts are significantly elevated in active Crohn's disease (CD) but not in ulcerative colitis (UC). To determine whether these IL‐27 single nucleotide polymorphisms are associated with the susceptibility to inflammatory bowel disease (IBD), the genotype and allelic frequencies of the IL‐27 polymorphisms were analyzed between the IBD patients and the healthy controls.

Methods:  Genotype analysis of the IL‐27 gene was performed by the single‐base extension (SBE) method. The haplotype frequencies of IL‐27 for multiple loci were estimated using the expectation maximization (EM) algorithm.

Results:  The genotype frequencies of the g.‐964A > G polymorphism in the IBD patients were significantly different from those of the healthy control group (P = 0.001). In both the UC and CD patients, the genotype frequencies of the g.‐964A > G polymorphism were also significantly different from the frequencies of the healthy control group (P = 0.009). The frequencies of the AGT and GGT haplotypes were significantly different between the healthy control group and the IBD patient group (P = 0.00004 and 0.021, respectively).

Conclusion:  Our results suggest that the g.‐964A > G polymorphism of the IL‐27 gene located on the IBD1 locus might be associated with the susceptibility to IBD.
Propranolol reduces variceal pressure and wall tension in schistosomiasis presinusoidal portal hypertension
Authors: Farias Alberto Queiroz , Kassab Fabio , Da Rocha Evandra Cristina Vieira , Dos Santos Bomfim Valdinélia , Vezozzo Denise Cerqueira Paranaguá , Bittencourt Paulo Lisboa , Carrilho Flair José
Published: August 2009

Background and Aim:  Although prophylaxis with β‐blockers has been shown to decrease variceal pressure and wall tension in cirrhotic patients, this has not been demonstrated in non‐cirrhotic portal hypertension caused by Schistosoma mansoni infection.

Methods:  Thirteen patients without history of previous gastrointestinal bleeding were included. All of them had high‐risk esophageal varices at endoscopy. An endoscopic gauge and a high‐frequency endoscopic ultrasonography miniprobe were used to assess transmural variceal pressure and wall tension before and after achieving β‐blockade with propranolol.

Results:  Baseline variceal pressure decreased from 13.3 ± 3.5 to 8.2 ± 2.0 mmHg (P < 0.0001) and wall tension from 500.2 ± 279.8 to 274.0 ± 108.3 mg.mm−1. The overall effect of propranolol on decreasing variceal pressure and wall tension expressed in percentage change in relation to baseline values was 35.7 ± 18.4% and 35.9 ± 26.7%, respectively (P = 0.9993).

Conclusion:  Propranolol significantly reduced variceal pressure and wall tension in schistosomiasis.
Validation of model for end‐stage liver disease score to serum sodium ratio index as a prognostic predictor in patients with cirrhosis
Authors: Lv Xiao‐Hui , Liu Hong‐Bo , Wang Ying , Wang Bing‐Yuan , Song Min , Sun Ming‐Jun
Published: August 2009

Aim:  To evaluate the prognostic ability of model for end‐stage liver disease (MELD) to serum sodium (SNa) ratio (MESO) index and to compare the predictive accuracy of the MESO index with the MELD score and the modified Child–Turcotte–Pugh (CTP) score for short‐term survival in cirrhotic patients.

Methods:  A total of 256 patients with cirrhosis were retrospectively evaluated. The predictive accuracy of the MESO index, MELD score and modified CTP score were compared by the area under the receiver–operator characteristic curve (AUC).

Results:  Using 1‐month and 3‐month mortality as the end‐point, overall, MESO and MELD were significantly better than the CTP score in predicting the risk of mortality at 1 month (AUC, 0.866,0.819 vs 0.722, P < 0.01) and 3 months (AUC, 0.875,0.820 vs 0.721, P < 0.01). In the low MELD group, the AUC of MESO index (0.758, 0.759) and CTP score (0.754, 0.732) were higher than that of the MELD score (0.608, 0.611) at 1 month and 3 months, respectively (P < 0.01). However, in the high MELD group, the AUC of MESO index (0.762, 0.779) and MELD (0.737, 0.773) were higher than that of the CTP score (0.710, 0.752) at 1 month and 3 months, respectively, although there were no significant differences (P > 0.05). With appropriate cut‐offs for the MESO index, the mortality rate of patients in high MESO was higher (57.1% at 1 month and 69.2% at 3 months) than that of the low MESO (5.5% at 1 month and 7.9% at 3 months) (P < 0.01).

Conclusions:  The MESO index, which adds SNa to MELD, is a useful prognostic marker and is found to be superior to the MELD score and modified CTP score for short‐term prognostication of patients with cirrhosis.
Quantitation of tissue polypeptide antigen (TPA) in hepatic and systemic circulation in patients with chronic liver diseases
Authors: Puoti Claudio , Bellis Lia , Guarisco Riccardo , Costanza Olga Mitidieri , Felici Renata , Spilabotti Lucia , Paglia Federica , Galossi Alessandra , Dell' Unto Orlando
Published: August 2009

Background and Aim:  Abnormal serum tissue polypeptide antigen (TPA) values are commonly found in patients with chronic liver damage and liver cirrhosis even in the absence of malignancies. The aim of this study was to compare serum TPA levels in patients with cirrhosis, to examine correlations between TPA levels and the degree of portal hypertension, and to evaluate TPA concentrations in paired hepatic and peripheral blood samples.

Methods:  A total of 128 patients with chronic liver disease of various severity were studied prospectively. TPA concentrations in hepatic vein and peripheral blood were determined, and Hepatic Vein Pressure Gradient (HVPG) was measured.

Results:  TPA levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis, and in systemic circulation than in hepatic vein blood. Peripheral but not hepatic TPA levels did correlate with the HVPG. Subjects with clinically significant portal hypertension (HVPG > 10 mmHg) showed significantly higher peripheral TPA levels than those with HVPG < 10 mmHg.

Conclusions:  Our data suggest that the increased TPA levels observed in cirrhotic patients and the high systemic‐to‐hepatic blood TPA gradient are probably due to the presence of portal‐systemic shunts rather than to hepatic necro‐inflammatory activity. In clinical practice, TPA determination could help us to identify and to follow up cirrhotic patients with more severe portal hypertension.
Preoperative colonoscopy for patients with gastric adenocarcinoma
Authors: Kim Hyung Ook , Hwang Sang Il , Yoo Chang Hak , Kim Hungdai
Published: August 2009

Background and Aim:  In patients with gastric adenocarcinoma (GA), the most common double primary cancer is colorectal cancer. The aim of the present study was to evaluate the necessity of preoperative colonoscopy in patients with GA who have no symptoms of colorectal disease or any past/family history of colorectal cancer.

Materials:  Colonoscopy was carried out in 205 patients before gastric surgery for treatment of GA. The prevalence of colorectal neoplasms (CRN, adenoma and adenocarcinoma) was evaluated according to age, sex, body mass index (BMI) and stage, location and differentiation of GA.

Results:  The median age and BMI were 59 years (range 32–81) and 22.9 (range 17.0–42.3), respectively. There were 135 male patients (65.9%). Synchronous adenoma and adenocarcinoma were detected in 68 (33.2%) and four (2.0%) patients, respectively. Univariate analysis showed that patients 50 years and older, male or with multiple GA had a significantly higher incidence of CRN (P = 0.005, 0.019, and 0.023, respectively). All of the GA patients with synchronous colorectal adenocarcinoma were older than 50 years. The stage, location and differentiation of GA and BMI did not show a significant difference in the incidence of CRN. Multivariate analysis showed that age (50 years and older) was the only risk factor of CRN in GA patients (odds ratio 2.470; 95% confidence interval 1.058–5.767).

Conclusion:  Preoperative colonoscopy for screening of CRN should be considered in GA patients ≥ 50 years because of a relatively high prevalence of CRN and the possibility of synchronous CRC.