bluuebunny/crossref_metadata_2025 huggingface dataset:
The outcomes of assisted reproductive technology cycles in patients with one or two ovaries
Authors: Levi Rafael , Özçakir Hasan Tayfun , Alatas Erkan , Göker Ege Nazan Tavmergen , Tavmergen Erol
Published: October 2003

Aim: To provide a comparison between the follicular response to ovulation induction, and the pregnancy rate of women with a single or two ovaries, undergoing assisted reproductive technology.

Methods: To evaluate the outcome of assisted reproductive technology, 46 treatment cycles in women with one ovary were compared to 123 cycles in women with two ovaries.

Results: The mean age of the patients in the two groups were not similar (34.4 ± 3.8 and 33.1 ± 4.0, respectively). The one ovary‐group had significantly higher mean baseline Follicle Stimulating Hormone levels and required more ampoules for induction. Although the induction period was longer in the one‐ovary group, the outcome of the assisted reproductive technology in both groups was similar. The maximum E2 levels on the day of Human Chorionic Gonadotropin administration were significantly lower in the one‐ovary group, although endometrial thickness appeared to be the same in both groups. The patients with two ovaries had a significantly higher mean number of mature or immature oöcytes aspirated, as well as embryos transfered. Although there was no statistical difference between the two groups following assisted reproductive technology, the pregnancy rate in the two‐ovary group was more than double that of the one‐ovary group.

Conclusion: The potential for success after in vitro fertilization is not impaired in women with one ovary.
Fetal hepatic hemangioma representing non‐reassuring pattern in fetal heart rate monitoring
Authors: Morimura Yutaka , Fujimori Keiya , Ishida Tomohiko , Ito Akiko , Nomura Yasuhisa , Sato Akira
Published: October 2003

To the best of our knowledge, this is the first report of a non‐reassuring fetal pattern caused by a hepatic hemangioma that was found during fetal heart rate monitoring. A 37 weeks’ gestation, a 32‐year‐old‐woman was referred to our hospital for evaluation of a rapidly growing fetal abdominal tumor. Fetal heart rate monitoring revealed a non‐reassuring pattern, and a cesarean section was performed as a result. Examination of the 2820 g female infant suggested a hepatic hemangioma accompanying an intratumor hemorrhage and coagulopathy. The infant died 2 days after birth. The autopsy confirmed that the cause of death was a result of a hepatic hemangioma. Frequent monitoring of fetuses and ultrasound examinations are necessary for determining the timing of delivery and for a favorable prognosis.
In utero diagnosis of an aneurysm of the vein of Galen causing hydrocephalus and heart failure
Authors: Hirose Masaya , Yomo Hiroko , Akiyama Minoru , Kimura Toshio , Noda Yoichi
Published: October 2003

A prenatally diagnosed aneurysm of the vein of Galen was presented in the fetus of a patient referred to our hospital at 31 weeks of gestation. Ultrasonography demonstrated polyhydramnios, cardiomegaly, dilatation of the right atrium and superior vena cava, tricuspid valve regurgitation, hydrocephalus, and a large hypoechoic mass with blood flow in the suboccipital region. Skin edema was shown thereafter. A 3262‐g male was delivered by cesarean at 35 weeks of gestation. Computed tomography imaging demonstrated a large mass in the suboccipital region, after which thrombocytopenia appeared and the neonate died at 18 days of age.
Favourable effect of regular intake of fermented milk containing Lactobacillus johnsonii on Helicobacter pylori associated gastritis
Authors: Pantoflickova D. , Corthésy‐Theulaz I. , Dorta G. , Stolte M. , Isler P. , Rochat F. , Enslen M. , Blum A. L.
Published: October 2003

Background : Lactobacillus johnsonii (Lj1) had an in vitro and in vivo inhibitory effect on Helicobacter pylori. Fermented milk containing Lj1 (LC1), coadministered with antibiotics had a favourable effect on H. pylori gastritis.

Aim : Evaluate the effect of LC1 intake without antibiotics on H. pylori gastritis.

Methods : Fifty H. pylori positive healthy volunteers were randomised in a double‐blind study to LC1 or placebo. Gastric biopsies from the antrum and corpus were obtained before, and after 3 and 16 weeks of treatment, for histology and quantitative cultures.

Results : Severity and activity of antral gastritis was reduced after 16‐week LC1 intake (pretreatment and 16‐week inflammatory cell score: 6.0 ± 0.8 vs. 5.3 ± 0.1; P = 0.04). H. pylori density decreased in the antrum after LC1 intake (3‐week: 4.4 ± 0.6; 16‐week: 4.3 ± 0.5 log10 colony forming units (cfu) vs. pretreatment 4.5 ± 0.4 log10 cfu; P = 0.04, respectively). Mucus thickness increased after 16 weeks of LC1 consumption (change of mucus thickness with LC1 and placebo in the antrum: 0.6 ± 1.3 vs. ‐0.2 ± 1.0, P = 0.01; in the corpus: 0.3 ± 1.1 vs. ‐0.6 ± 1.5, P = 0.03).

Conclusion : LC1 intake had a favourable, albeit weak, effect on H. pylori associated gastritis, particularly in the antrum. Regular ingestion of fermented milk containing L. johnsonii may reduce the risk of developing disorders associated with high degrees of gastric inflammation and mucus depletion.
The CD36 protein functions as an immunogenic domain of the RT8 alloantigen
Authors: Mlejnek P. , Křen V. , Liška F. , Zídek V. , Landa V. , Kurtz T. W. , Pravenec M.
Published: October 2003

Completely concordant distributions of Cd36 and Rt8 deletion/null and wild‐type alleles among inbred and congenic strains, together with Western blot analysis of RT8/CD36 proteins, indicated that the CD36 protein functions as an immunogenic domain of the RT8 alloantigen.
Rapid denaturing high‐performance liquid chromatography (DHPLC) for mutation scanning of the transforming growth factor β3 gene using a novel proof‐reading polymerase
Authors: Bayat A. , Walter J. M. , Lamb H. , Ferguson M. W. J. , Ollier W. E. R.
Published: October 2003

We have utilized a novel variation on the conventional denaturing high‐performance liquid chromatography (DHPLC) technology, which we term rapid DHPLC, combining changes in instrumentation, cartridge technology and analysis conditions to enable significant increases in throughput to be achieved. In addition, the use of a novel proof‐reading polymerase for sample amplification with a low misincorporation rate enables simplification of the DHPLC patterns and hence enhanced mutation detection recognition. This scheme for increasing DHPLC throughput has been tested by scanning the transforming growth factor (TGF) β3 gene for the presence of mutations for which there is limited published or on‐line data available regarding the presence of gene polymorphisms. TGFβ isoforms have multiple roles in cell division, growth, proliferation, transformation and differentiation. TGFβ3 is a TGFβ cytokine isoform, and has an important role in embryogenesis, cell differentiation and wound healing. The TGFβ3 gene consists of seven exons and six introns spanning 43 000 bp of the human genome on chromosome 14q23–24. The rapid DHPLC approach enabled scanning of all seven exons and part of the promoter region (1000 bp upstream from exon 1 in the 5′‐flanking regions) of the TGFβ3 gene in 95 Caucasian individuals in only 8 days, in comparison to the 17 days it would have previously taken. Mutations were clearly identified in the promoter region of the TGFβ3 gene but were absent from the exonic regions. Understanding the genetic variations affecting the TGFβ3 gene is important as this molecule has multiple regulatory functions on a variety of cell types.
Analysis of Fc gamma receptor II (CD32) polymorphism in populations of African and South Asian ancestry reveals east–west geographic gradients of allele frequencies
Authors: Carrington C. V. F. , Norman P. J. , Vaughan R. W. , Kondeatis E. , Ramdath D. D. , Hameed K. , Stephens H. A. F.
Published: October 2003

Analysis of FcγRIIA alleles in Pakistanis and in Trinidadians of South Asian, African and mixed ancestry revealed no significant differences between Trinidadian South Asians and Pakistanis. H131 homozygotes were more common among Trinidadian South Asians than among Africans and those of mixed ancestry. Comparison with other populations revealed east–west geographic gradients of allele frequencies.
Geographic patterns of functional categories of HLA‐DRB1 alleles: a new approach to analyse associations between HLA‐DRB1 and disease
Authors: Gibert M. , Sanchez‐Mazas A.
Published: October 2003

Because specific amino acids found within the peptide‐binding cleft of human leukocyte antigen (HLA) molecules have been implicated in HLA/disease associations, an approach which consists in grouping the alleles according to their functional properties at the protein level may enable us to better understand HLA associations than the conventional allelic classification. In this study, we applied this methodology to investigate the associations between HLA‐DRB1 and rheumatoid arthritis. The alleles were first classified into seven functional categories [restrictive supertype patterns (RSPs)], among which three were known to be significantly associated with susceptibility (one category) or resistance (two categories) to rheumatoid arthritis. The frequencies of these categories were then estimated in 104 population samples previously tested for HLA‐DRB1, and their variability was analysed spatially on a worldwide scale by applying an original methodology for detecting discontinuities in geographically patterned data. RSP frequencies were also compared to known values of rheumatoid arthritis prevalence in some populations. The results indicated that the three RSP frequency distributions were geographically structured, and that these patterns could generally be explained by the history of human migrations. However, the peculiar pattern observed for RSP ‘A’ (conferring susceptibility to rheumatoid arthritis) indicated a possible association with some latitude‐dependent disease. Furthermore, the very high correlation coefficient found between RSP ‘A’ frequencies and rheumatoid arthritis prevalence confirmed the significant disease association of this functional category. In contrast, the putative protective effect of the other RSPs (‘De’ and ‘Q’) was not detectable at the worldwide level, but may be significant in specific geographic areas. This study shows that population genetic diversity analyses based on a functional grouping of HLA alleles provide an efficient way to explore the mutual influence of HLA genetic variation and disease.
Non‐equilibrium succession dynamics indicate continued northern migration of lodgepole pine
Authors: Johnstone Jill F. , Chapin F. Stuart
Published: October 2003

Because species affect ecosystem functioning, understanding migration processes is a key component of predicting future ecosystem responses to climate change. This study provides evidence of range expansion under current climatic conditions of an indigenous species with strong ecosystem effects. Surveys of stands along the northern distribution limit of lodgepole pine (Pinus contorta var. latifolia) in central Yukon Territory, Canada showed consistent increases in pine dominance following fire. These patterns differed strongly from those observed at sites where pine has been present for several thousand years. Differences in species thinning rates are unlikely to account for the observed increases in pine dominance. Rates of pine regeneration at its range limits were equivalent to those of spruce, indicating a capacity for rapid local population expansion. The study also found no evidence of strong climatic limitation of pine population growth at the northern distribution limit. We interpret these data as evidence of current pine expansion at its range limits and conclude that the northern distribution of lodgepole pine is not in equilibrium with current climate. This study has implications for our ability to predict vegetation response to climate change when populations may lag in their response to climate.
Effects of free‐air CO2enrichment (FACE) on CH4emission from a rice paddy field
Authors: Inubushi Kazuyuki , Cheng Weiguo , Aonuma Shinichi , Hoque M.M. , Kobayashi Kazuhiko , Miura Shu , Kim Han Yong , Okada Masumi
Published: October 2003

Methane (CH4) is a particularly potent greenhouse gas with a radiative forcing 23 times that of CO2on a per mass basis. Flooded rice paddies are a major source of CH4emissions to the Earth's atmosphere. A free‐air CO2enrichment (FACE) experiment was conducted to evaluate changes in crop productivity and the crop ecosystem under enriched CO2conditions during three rice growth seasons from 1998 to 2000 in a rice paddy at Shizukuishi, Iwate, Japan. To understand the influence of elevated atmospheric CO2concentrations on CH4emission, we measured methane flux from FACE rice fields and rice fields with ambient levels of CO2during the 1999 and 2000 growing seasons. Methane production and oxidation potentials of soil samples collected when the rice was at the tillering and flowering stages in 2000 were measured in the laboratory by the anaerobic incubation and alternative propylene substrates methods, respectively. The average tiller number and root dry biomass were clearly larger in the plots with elevated CO2during all rice growth stages. No difference in methane oxidation potential between FACE and ambient treatments was found, but the methane production potential of soils during the flowering stage was significantly greater under FACE than under ambient conditions. When free‐air CO2was enriched to 550 ppmv, the CH4emissions from the rice paddy field increased significantly, by 38% in 1999 and 51% in 2000. The increased CH4emissions were attributed to accelerated CH4production potential as a result of more root exudates and root autolysis products and to increased plant‐mediated CH4emissions because of the larger rice tiller numbers under FACE conditions.
Solar UV‐B decreases decomposition in herbaceous plant litter in Tierra del Fuego, Argentina: potential role of an altered decomposer community
Authors: Pancotto Verónica A. , Sala Osvaldo E. , Cabello Marta , López Nancy I. , Matthew Robson T. , Ballaré Carlos L. , Caldwell Martyn M. , Scopel Ana L.
Published: October 2003

Tierra del Fuego, Argentina (55°S), receives increased solar ultraviolet‐B radiation (UV‐B) as a result of Antarctic stratospheric ozone depletion. We conducted a field study to examine direct and indirect effects of solar UV‐B radiation on decomposition ofGunnera magellanica, a native perennial herb, and on the native community of decomposer organisms. In general, indirect effects of UV‐B mostly occur due to changes in the chemical composition of litter, whereas direct effects during decomposition result from changes in decomposer organisms and/or differences in the photochemical breakdown of litter. We designed a full‐factorial experiment using senescent leaves that had received either near‐ambient or attenuated UV‐B during growth. The leaves were distributed in litterbags and allowed to decompose under near‐ambient or reduced solar UV‐B during the growing season. We evaluated initial litter quality, mass loss, and nutrient release of decomposing litter, and microbial colonization of both initial litter and decomposed litter. We found that litter that decomposed under near‐ambient UV‐B had significantly less mass loss than litter that decomposed under reduced UV‐B. The UV‐B conditions received by plants during growth, which did not affect mass loss and nutrient composition of litter, affected fungal species composition but in different ways throughout the decomposition period. Before the decomposition trial,Beauveria bassianaandPenicillium frequentanswere higher under reduced UV‐B, whereasCladosporium herbarumand pigmented bacteria were more common under the near‐ambient compared to the reduced UV‐B treatment. After the decomposition period, leaves that had grown under reduced UV‐B showed higher frequency ofPenicillium thomiiand lower frequency ofTrichoderma polysporumthan leaves that had grown under near‐ambient conditions. The UV‐B condition received during decomposition also affected fungal colonization, withPenicillium chrysogenumbeing more frequent in leaves that had decomposed under reduced UV‐B, while the other species were not affected. Our results demonstrate that, in this ecosystem, the effects of UV‐B radiation on decomposition apparently occurred mostly through changes in the fungal community, while changes in photochemical breakdown appeared to be less important.
Topographic and climatic controls on soil respiration in six temperate mixed‐hardwood forest slopes, Korea
Authors: Kang Sinkyu , Doh Sueyoung , Lee Dongsun. , Lee Dowon. , Jin Virginia L. , Kimball John S.
Published: October 2003

To better understand the effects of local topography and climate on soil respiration, we conducted field measurements and soil incubation experiments to investigate various factors influencing spatial and temporal variations in soil respiration for six mixed‐hardwood forest slopes in the midst of the Korean Peninsula. Soil respiration and soil water content (SWC) were significantly greater (P=0.09 and 0.003, respectively) on north‐facing slopes compared to south‐facing slopes, while soil temperature was not significantly different between slopes (P>0.5). At all sites, soil temperature was the primary factor driving temporal variations in soil respiration (r2=0.84–0.96) followed by SWC, which accounted for 30% of soil respiration spatial and temporal variability. Results from both field measurements and incubation experiments indicate that variations in soil respiration due to aspect can be explained by a convex‐shaped function relating SWC to normalized soil respiration rates. Annual soil respiration estimates (1070–1246 g C m−2 yr−1) were not closely related to mean annual air temperatures among sites from different climate regimes. When soils from each site were incubated at similar temperatures in a laboratory, respiration rates for mineral soils from wetter and cooler sites were significantly higher than those for the drier and warmer sites (n=4, P<0.01). Our results indicate that the application of standard temperature‐based Q10 models to estimate soil respiration rates for larger geographic areas covering different aspects or climatic regimes are not adequate unless other factors, such as SWC and total soil nitrogen, are considered in addition to soil temperature.
Historical shrub–grass transitions in the northern Chihuahuan Desert: modeling the effects of shifting rainfall seasonality and event size over a landscape gradient
Authors: Gao Qiong , Reynolds James F.
Published: October 2003

We use a spatially explicit landscape model to investigate the potential role of rainfall on shrub–grass transitions in the Jornada Basin of southern New Mexico during the past century. In long‐term simulations (1915–1998) along a 2700 m transect running from a dry lake bed to the foothills of a small mountain, we test two hypotheses: (i) that wetter winters and drier summers may have facilitated shrub encroachment in grasslands, and (ii) that increases in large precipitation events may have increased soil water recharge at deeper layers, thus favoring shrub establishment and growth. Our model simulations generally support the hypothesis that wetter winters and drier summers may have played a key role, but we are unable to reproduce the major shifts from grass‐ to shrub‐domination that occurred in this landscape during the early part of the 1900s; furthermore, the positive shrub response to wetter winters and drier summers was only realized subsequent to the drought of 1951–1956, which was a relatively short ‘window of opportunity’ for increased shrub establishment and growth. Our simulations also generally support the hypothesis that an increase in the number of large precipitation events may also have favored shrub establishment and growth, although these results are equivocal, depending upon what constitutes a ‘large’ event and the timing of such events. We found complex interactions among (i) the amount/seasonality of rainfall, (ii) its redistribution in the landscape via run‐on and runoff, (iii) the depth of the soil water recharge, and (iv) subsequent water availability for the growth and reproduction of shrubs vs. herbaceous plants at various landscape positions. Our results suggest that only a mechanistic understanding of these interactions, plus the role of domestic cattle grazing, will enable us to elucidate fully the relative importance of biotic vs. abiotic factors in vegetation dynamics in this semiarid landscape.
Effects of climatic change on the phenology of butterflies in the northwest Mediterranean Basin
Authors: Stefanescu Constantí , Peñuelas Josep , Filella Iolanda
Published: October 2003

Phenological changes in response to climatic warming have been detected across a wide range of organisms. Butterflies stand out as one of the most popular groups of indicators of climatic change, given that, firstly, they are poikilothermic and, secondly, have been the subject of thorough monitoring programmes in several countries for a number of decades. Here we provide for the first time strong evidence of phenological change as a consequence of recent climatic warming in butterflies at a Spanish site in the northwest Mediterranean Basin. By means of the widely used Butterfly Monitoring Scheme methodology, three different phenological parameters were analysed for the most common species to test for trends over time and relationships with temperature and precipitation. Between 1988 and 2002, there was a tendency for earlier first appearance dates in all 17 butterfly species tested, and significant advances in mean flight dates in 8 out of 19 species. On the other hand, the shape of the curve of adult emergence did not show any regular pattern. These changes paralleled an increase of 1–1.5°C in mean February, March and June temperatures. Likewise, a correlation analysis indicated the strong negative effect of spring temperature on phenological parameters (i.e. higher temperatures tended to produce phenological advances), and the opposite effect of precipitation in certain months. In addition, there was some evidence to indicate that phenological responses may differ between taxonomic lineages or species with similar diets. We discuss the consequences that these changes may have on species' population abundances, especially given the expected increase in aridity in the Mediterranean Basin caused by current climatic warming. We predict that varying degrees of phenological flexibility may account for differences in species' responses and, for multivoltine species, predict strong selection favouring local seasonal adaptations such as diapause phenomena or migratory behaviour.
A meta‐analysis of the effects of various interventions in preventing endotracheal suction‐induced hypoxemia
Authors: Oh HyunSoo , Seo WhaSook
Published: October 2003

• The purpose of this study was to clarify the effects of interventions that were applied to prevent endotracheal suction‐induced hypoxia by meta‐analysis.

• To obtain a sample for this meta‐analysis, a computerized search was performed through MEDLINE in addition to tracking down additional references cited in bibliographies of past reports. Finally thirty research reports were examined.

• In terms of the application time of oxygenation, insufflation and preoxygenation were the most prevalently used in the studies.

• Regarding the methods of oxygenation, the most prevalent technique for oxygenation was hyperoxygenation in combination with hyperinflation.

• Hyperoxygenation and hyperinflation were most frequently induced by FiO2 of 1 and a 150% tidal volume of three to six breaths, respectively.

• Suctioning was commonly sustained for <15 seconds using pressures of −80 to −120 mmHg and with size 14 French catheters.

• Insufflation was less effective than the other methods examined in the present study.

• From this study, it can be concluded that the interventions that were applied to prevent endotracheal suction‐induced hypoxia, regardless of their application times or methods, reduced suction‐induced hypoxia significantly.
Problems identified in gaining non‐expert consensus for a hypothetical Wound Assessment Form
Authors: Maylor Miles E.
Published: October 2003

• A post‐hoc analysis was carried out of a session on a wound management diploma level module that was intended to promote understanding of the complexity of wound assessment.

• Postregistration student nurses (n = 16) from both hospital and community settings participated in brainstorming of categories (i.e. verbatim expression) they thought should be included in a hypothetical Wound Assessment Form (WAF).

• Ranking of suggested categories indicated in terms of ‘votes’ that the most important was ‘date’, and the least was ‘factors affecting healing’. Some categories were rejected (e.g. exudate).

• Category definitions and rationale were checked after 3 weeks, and compared with those of lecturers in adult nursing (n = 16) to test whether similar themes emerged amongst other non‐experts.

• Postregistration nurses and lecturers gave similar definitions and rationale for categories.

• A limitation of the study was that it was opportunistic and methodology for researching consensus issues had not been investigated. Views represent nurses in a wide spread of disciplines and have to date only been compared with expert consensus derived from published literature.

• Themes to emerge were: the importance of WAFs to record‐keeping, different understanding of terminology and the monitoring of progress and use of intuition.

• It was concluded that the purpose of WAFs needs clarification and research should investigate how change in wounds could take account of differences of personal perception. A new method of charting progress or deterioration is being developed.
Home care with regard to definition, care recipients, content and outcome: systematic literature review
Authors: Thomé Bibbi , Dykes Anna‐Karin , Hallberg Ingalill Rahm
Published: October 2003

• In spite of the fact that home care has grown considerably during the last few years and will continue to grow even more in the future, home care as a phenomenon and a concept is not clearly defined.

• The aim of this study was to review the empirical literature for the description of home care as a phenomenon and as a concept, especially with regard to who the care recipients are, what actions and assessments are performed and what effects are achieved for the care recipient in terms of functional health status and quality of life (QoL).

• Twenty‐six relevant studies meeting the inclusion criteria and requirements for methodological quality were identified.

• The phenomenon of home care is described through content, outcome and objectives. The content of home care involved a range of activities from actions preventing decreased functional abilities in old people to palliative care in advanced diseases.

• The outcome had two different underlying foci: (1) for the benefit of the patient based on the assumption that being cared at home increases their QoL, (2) in the interests of the society, to minimize hospital care by moving activities to the home of the patient.

• The objectives were found to be aiming at improving the QoL and/or maintaining independence, by means of actions and assessments, based on the patient's needs, undertaken to preserve and increase functional ability and make it possible for the person to remain at home.

• In conclusion, home care as a phenomenon was the care provided by professionals to people in their own homes with the ultimate goal of not only contributing to their life quality and functional health status, but also to replace hospital care with care in the home for societal reasons; home care covered a wide range of activities, from preventive visits to end‐of‐life care.
Risk of haemorrhagic stroke in patients with oral anticoagulation compared with the general population
Authors: Själander A. , Engström G. , Berntorp E. , Svensson P.
Published: October 2003

Abstract.  Själander A, Engström G, Berntorp E, Svensson P (Malmö University Hospital, University of Lund, Sweden). Risk of haemorrhagic stroke in patients with oral anticoagulation compared with the general population. J Intern Med 2003; 254: 434–438.

Objectives.  To compare the incidence of haemorrhagic stroke (HS), and the risk of fatal outcome after HS in patients with oral anticoagulation (OA) treatment and in the general population.

Design.  Five‐year cohort study.

Setting.  The Anticoagulation Clinic, Malmö University Hospital, Lund, Sweden.

Subjects.  A total of 4434 patients treated with OA (6693 treatment years) from 1 Oct 1993 to 30 Sept 1998. The population‐based Stroke Register of Malmö, Lund, Sweden (STROMA).

Results.  Forty‐eight patients had HS according to ICD  9 code 430 and 431. HS occurred at a higher age in women compared with men (mean age 79.5 years vs. 74.7 years, P = 0.009). The age‐adjusted relative risk of HS during OA treatment was 10.9 (CI 6.7–17.6) for men and 9.3 (CI 5.7–15.0) for women, as compared with the untreated general population. Number needed to harm (NNH) (person‐years) was 103 for men and 188 for women. Adjusted for age and sex, OA treatment was significantly associated with fatal outcome in patients with HS (OR = 2.6, CI 1.4–4.8).

Conclusions.  Patients with OA treatment had approximately 10 times higher risk of HS as compared with the general population, and the risk increased markedly with age. OA treatment is associated with an increased case fatality in patients with HS.
Endocrine effects of nasal continuous positive airway pressure in male patients with obstructive sleep apnoea
Authors: Meston N. , Davies R. J. O. , Mullins R. , Jenkinson C. , Wass J. A. H. , Stradling J. R.
Published: October 2003

Abstract. Meston N, Davies RJO, Mullins R, Jenkinson C, Wass JAH, Stradling JR (University of Oxford, John Radcliffe Hospital; Oxford Centre for Respiratory Medicine and University of Oxford, Churchill Hospital; Health Services Research Unit; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Infirmary; Oxford, UK). Endocrine effects of nasal continuous positive airway pressure in male patients with obstructive sleep apnoea. J Intern Med 2003; 254: 447–454.

Objective. Obstructive sleep apnoea (OSA) is a relatively common condition producing disabling somnolence and profound physiological responses to hypoxaemic episodes during sleep, including significant oscillations in blood pressure. This study aimed to provide controlled data on the interaction between OSA and endocrine axes to establish whether overrepresentation of pathology such as hypertension and hypogonadism in OSA subjects might have an endocrine basis.

Design, setting and subjects. Parallel randomized sham placebo controlled 1‐month trial of nasal continuous positive airway pressure (nCPAP) in 101 male subjects with OSA presenting to a respiratory sleep clinic.

Methods. Analysis of gonadotrophins, testosterone, sex hormone binding protein (SHBG), prolactin, cortisol, thyroid stimulating hormone (TSH), free thyroxine (free T4), insulin‐like growth factor‐1 (IGF‐1), renin and aldosterone were performed at baseline and after 1 month's active or placebo nCPAP intervention. Quality of life questionnaire scoring was also recorded over the same time period.

Results. Testosterone and SHBG showed significant negative correlations with baseline OSA severity. Active treatment of OSA produced SHBG elevation and TSH reduction (P ≤ 0.03). Both groups showed an increase in aldosterone (P < 0.001) and IGF‐1 (P ≤ 0.03), associated with a large improvement in subjective quality of life scoring.

Conclusions. These findings demonstrate significant changes in endocrine axes not previously reported in a placebo‐controlled trial. OSA is a recognized reversible cause of testosterone reduction; SHBG suppression correlating to baseline OSA severity supports a diagnosis of secondary hypogonadism. Significant rises in aldosterone and IGF‐1 on treatment coincide with increased physical activity and an improved quality of life score.
Effects of short‐term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo‐controlled trial
Authors: Wulffelé M. G. , Kooy A. , Lehert P. , Bets D. , Ogterop J. C. , Borger van der Burg B. , Donker A. J. M. , Stehouwer C. D. A.
Published: October 2003

Abstract.  Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJM, Stehouwer CDA (Bethesda General Hospital, Hoogeveen, The Netherlands; University of Mons, Mons, Belgium; Merck Nederland B.V., Amsterdam; Deaconesses’ Hospital, Meppel; Aleida Kramer Hospital, Coevorden; and Vrije Universiteit Medical Centre, Amsterdam; The Netherlands). Effects of short‐term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo‐controlled trial. J Intern Med 2003; 254: 455–463.

Objective. Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homo‐cysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homo‐cysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin.

Design. Placebo‐controlled, randomized trial. Measurements: at baseline and 16 weeks later.

Setting. This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands.

Subjects. A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty‐seven subjects dropped out (12 placebo and 25 metformin users).

Intervention. Addition of metformin or placebo to insulin therapy.

Primary outcome parameters. Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight.

Results. Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P = 0.039) and with decreases in folate [−7% (−1.4 to −13); P = 0.024] and vitamin B12 [−14% (−4.2 to −24); P < 0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12.

Conclusion. In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.
Effect of short‐term hyperglycaemia on haemodynamics in type 1 diabetic patients
Authors: Jacobsen P. , Rossing K. , Hansen B. V. , Bie P. , Vaag A. , Parving H.‐H.
Published: October 2003

Abstract. Jacobsen P, Rossing K, Hansen BV, Bie P, Vaag A, Parving H‐H (Steno Diabetes Center, Gentofte; University of Aarhus, Aarhus; and University of Southern Denmark, Odense, Denmark). Effect of short‐term hyperglycaemia on haemodynamics in type 1 diabetic patients. J Intern Med 2003; 254: 464–471.

Objectives. Mechanisms underlying glucose‐mediated development and progression of diabetic complications are incompletely understood. We tested the impact of short‐term hyperglycaemia on systemic blood pressure and regulatory hormones in type 1 diabetic patients.

Design and methods. We included 18 patients [13 men, mean (SEM) diabetes duration 10 (1) years] without signs of autonomic neuropathy or renal complications in a randomized single‐blinded cross‐over trial using insulin–glucose clamp technique. Patients were clamped for 90 min to blood glucose of 5 mmol L−1 (euglycaemia) and 15 mmol L−1 (hyperglycaemia) in random order. Blood pressure was measured noninvasively every 5 min (Takeda TM2421 device). Regulatory hormones were determined at the end of each clamp period.

Results. Systolic blood pressure increased [mean (95% CI)] 3 (1, 5) mmHg during hyperglycaemia from 123 (SEM 2) during euglycaemia, P = 0.01. Diastolic blood pressure remained unchanged at 78 (2) mmHg. Hyperglycaemia reduced plasma concentrations of: renin [14 (4, 23)%, P = 0.02], angiotensin II [17 (8, 25)%, P < 0.01] and adrenaline [20 (10, 29)%, P < 0.01]. Plasma concentration of atrial natriuretic peptide increased by 11 (6, 17) pg mL−1 (P < 0.01) from 43 (2) pg mL−1. We calculated a median (range) increase in extracellular volume and plasma volume (PV) of 2.6 (0.7–5.3)% and 5.0 (−4.7 to 8.6)%, respectively.

Conclusions. In type 1 diabetic patients without signs of autonomic neuropathy short‐term hyperglycaemia induced a modest increase in systolic blood pressure and suppression of the renin–angiotensin system, possibly caused by PV expansion because of fluid shift from intra‐ to extracellular compartment.
Expansion of peripheral CD8+ T cells in patients with coronary artery disease: relation to cytomegalovirus infection
Authors: Jonasson L. , Tompa A. , Wikby A.
Published: October 2003

Abstract. Jonasson L, Tompa A, Wikby A (Heart Center, University Hospital, Linköping; Ryhov Hospital, Jönköping; and School of Health Sciences, Jönköping University, Jönköping; Sweden). Expansion of peripheral CD8+ T cells in patients with coronary artery disease: relation to cytomegalovirus infection. J Intern Med 2003; 254: 472–478.

Objectives. The nature of the immune response in coronary artery disease (CAD) is not fully defined. One pathogen that has been linked to atherogenesis, cytomegalovirus (CMV), is known to exert strong and long‐lasting effects on peripheral T cells. In the present study, we investigated the effect of prior CMV infection on the immune system in CAD patients.

Subjects. Patients with stable angina and angiographically verified CAD (n = 43) and clinically healthy controls (n = 69) were included.

Methods. The expression of CD57 and CD28 on peripheral CD4+ and CD8+ T cells was evaluated with three‐colour flow cytometry. The findings were related to serological markers of inflammation, T‐cell activation and CMV seropositivity.

Results. An expansion of CD8+ T cells expressing CD57 but lacking CD28 was seen in the patient group. The numbers of CD8+ CD57+ and CD8+ CD28−T‐cell subsets were independently related to CMV seropositivity (P < 0.001) but also to CAD per se (P < 0.05). Serum concentrations of C‐reactive protein (CRP) and soluble interleukin‐2 receptor (sIL‐2R) were elevated in the patients but not related to CMV or CD8+ T‐cell subsets.

Conclusion. A pronounced shift in peripheral T‐cell homeostasis was observed in CAD patients. Primarily CMV infection but also CAD per se contributed to the expansion of CD8+ T‐cell subsets. The T‐cell changes were not related to a systemic inflammatory response but should rather be considered as markers of a chronic antigen exposure and/or immunosenescence in CAD.
Basal glucometabolic status has an impact on long‐term prognosis following an acute myocardial infarction in non‐diabetic patients
Authors: Tenerz Å. , Nilsson G. , Forberg R. , Öhrvik J. , Malmberg K. , Berne C. , Leppert J.
Published: October 2003

Abstract. Tenerz Å, Nilsson G, Forberg R, Öhrvik J, Malmberg K, Berne C, Leppert J (Central Hospital, Västerås; Karolinska Hospital, Stockholm; and University Hospital, Uppsala; Sweden) Basal glucometabolic status has an impact on long‐term prognosis following an acute myocardial infarction in non‐diabetic patients. J Intern Med 2003; 254: 494–503.

Objectives. Patients with diabetes are known to have a worse prognosis after an acute myocardial infarction (AMI) compared with non‐diabetic patients. The primary aim of this study was to investigate the effect of glucometabolic status on long‐term prognosis in non‐diabetic patients with an AMI. The second aim was to evaluate the extent to which blood glucose levels at admission depended on acute stress, assessed as serum cortisol, previous glucometabolic status, measured as haemoglobin A1c (HbA1c), or both.

Design. In a prospective study of patients with an AMI, blood glucose, HbA1c and cortisol were measured at admission. Fasting blood glucose was determined before discharge and also afterwards, if necessary, for classification. Patients were followed‐up for 5.5 years.

Subjects. Of the 305 consecutive patients 24% were diagnosed as diabetic and 76% as non‐diabetic.

Main outcome measures. Death or non‐fatal myocardial re‐infarction.

Results. In non‐diabetic patients, a Cox regression model was used. With death or re‐infarction as endpoint, the following prognostic factors had an impact on event‐free survival: age (P < 0.001), HbA1c (P = 0.002), cortisol (P < 0.001) and thrombolytic treatment (P = 0.001). There was a correlation between cortisol and blood glucose at admission (r = 0.44, P < 0.001). Fasting blood glucose day 5 showed no association with event‐free survival.

Conclusions. In non‐diabetic patients with AMI, admission HbA1c and cortisol were predictors for 5.5‐year survival without recurrent non‐fatal myocardial infarction. The glucometabolic status of importance for prognosis was detected by HbA1c but not by fasting blood glucose or admission blood glucose, of which the latter was influenced by cortisol.
Obesity – is it a genetic disorder?
Authors: Loos R. J. F. , Bouchard C.
Published: October 2003

Abstract.  Loos RJF, Bouchard C (Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA). Obesity – is it a genetic disorder? (Review). J Intern Med 2003; 254: 401–425.

Obesity is one of the most pressing problems in the industrialized world. Twin, adoption and family studies have shown that genetic factors play a significant role in the pathogenesis of obesity. Rare mutations in humans and model organisms have provided insights into the pathways involved in body weight regulation. Studies of candidate genes indicate that some of the genes involved in pathways regulating energy expenditure and food intake may play a role in the predisposition to obesity. Amongst these genes, sequence variations in the adrenergic receptors, uncoupling proteins, peroxisome proliferator‐activated receptor, and the leptin receptor genes are of particular relevance. Results that have been replicated in at least three genome‐wide scans suggest that key genes are located on chromosomes 2p, 3q, 5p, 6p, 7q, 10p, 11q, 17p and 20q. We conclude that the currently available evidence suggests four levels of genetic determination of obesity: genetic obesity, strong genetic predisposition, slight genetic predisposition, and genetically resistant. This growing body of research may help in the development of anti‐obesity agents and perhaps genetic tests to predict the risk for obesity.
Cell damage and reactive oxygen species production induced by fluorescence microscopy: effect on mitosis and guidelines for non‐invasive fluorescence microscopy
Authors: Dixit Ram , Cyr Richard
Published: October 2003

The green fluorescent protein (GFP) and other intrinsically fluorescent proteins (IFPs) are popular reporters because they allow visualization of cellular constituents in living specimens. IFP technology makes it possible to view dynamic processes in living cells, but extended observation, using fluorescence microscopy (both wide‐field and confocal), can result in significant light energy exposure. Therefore, it is possible that cells experience light‐induced damage that alters cell physiology and confounds observations. To understand the impact that extended viewing has on cells, we obtained quantitative information about the effect of light energy dose and observation conditions on tobacco BY‐2 cell physiology. Our results show a non‐linear relationship between the excitation light intensity and mitotic arrest, and the frequency of mitotic arrest is dependent on the presence of an IFP that absorbs the excitation light. Moreover, fluorescence microscopy induces the production of reactive oxygen species (ROS), as assayed using BY‐2 cells loaded with oxidation‐sensitive dyes, and the level of ROS production increases if the cells express an IFP that absorbs the excitation light energy. The dye oxidation follows sigmoidal kinetics and is reversible if the cells are exposed to low irradiation levels. In addition, the dye oxidation rate shows a non‐linear relationship to the excitation light intensity, and a good correlation exists between photobleaching, mitotic arrest, and dye oxidation. The data highlight the importance of ROS scavenging for normal mitotic progression, and provide a reference for judiciously choosing conditions that avoid photobleaching that can lead to ROS accumulation and physiological damage.
Increased tryptophan decarboxylase and monoamine oxidase activities induce Sekiguchi lesion formation in rice infected with Magnaporthe grisea
Authors: Ueno Makoto , Shibata Hitoshi , Kihara Junichi , Honda Yuichi , Arase Sakae
Published: October 2003

Sekiguchi lesion (sl)‐mutant rice infected with Magnaporthe grisea showed increased light‐dependent tryptophan decarboxylase (TDC) and monoamine oxidase (MAO) activities. TDC and MAO activities were observed before the penetration of M. grisea to rice cells and maintained high levels even after Sekiguchi lesion formation. Light‐dependent expression of TDC gene was observed in leaves inoculated with M. grisea before Sekiguchi lesion formation. Spore germination fluid (SGF) of M. grisea also induced Sekiguchi lesion formation accompanied by increased enzymes activities and tryptamine accumulation. Sekiguchi lesion was also induced by treatments with tryptamine and β‐phenylethylamine, which are substrates for MAO, but was not induced by non‐substrates such as indole‐3‐propionic acid, (±)‐phenylethylamine and tryptophan under light. Light‐dependent induction of Sekiguchi lesion by tryptamine was significantly inhibited in the presence of MAO inhibitors, metalaxyl and semicarbazide, and H2O2‐scavengers, ascorbic acid and catalase. H2O2 in M. grisea‐infected leaves with and without Sekiguchi lesions was demonstrated directly in situ by strong 3,3′‐diaminobenzidine (DAB) staining. On the other hand, H2O2 induced Sekiguchi lesions on leaves of cv. Sekiguchi‐asahi under light, but not in darkness. This difference was associated with the decrease of catalase activity in infected leaves under light and the absence of decrease in darkness. We hypothesize that the H2O2‐induced breakdown of cellular organelles such as chloroplasts and mitochondria in mesophyll cells may cause high TDC and MAO activities and the development of Sekiguchi lesion, and that the sl gene products in wild‐type rice may function as a suppressor of organelle breakdown caused by chemical or environmental stress.
Telomere looping in P. sativum (common garden pea)
Authors: Cesare Anthony J. , Quinney Nancy , Willcox Smaranda , Subramanian Deepa , Griffith Jack D.
Published: October 2003

Telomeres vary greatly in size among plants and, in most higher plants, consist of a long array of 5′‐TTTAGGG‐3′/3′‐AAATCCC‐5′ (TTTAGGG) repeats. Recently, telomeric DNA in human, mouse, oxytricha, and trypanosome chromosomes have been found arranged into loops (t‐loops), proposed to sequester the telomere from unwanted repair events and prevent activation of DNA damage checkpoints. We have asked whether t‐loops exist in the higher order plant Pisum sativum (garden pea). DNA was isolated from the shoots and root tips of germinating seeds. Analysis of the telomeric restriction fragments showed that DNA hybridizing to a (TTTAGGG)n probe migrated as a smear centering around 25 kb, and direct sequencing verified the repeat to be (TTTAGGG)n. Total DNA in isolated nuclei was photo‐cross‐linked, and the telomeric restriction fragments were purified by gel filtration. Electron microscopic (EM) analysis revealed DNA molecules arranged as t‐loops with a size distribution consistent with that seen by gel electrophoresis. Some molecules had loops as large as 75 kb. These results show that the arrangement of telomeric DNA into loops occurs in higher plants.