bluuebunny/crossref_metadata_2025 huggingface dataset:
LASIK complication: loss of electricity to the microkeratome during the forward pass
Authors: Tuominen Ilpo S. J. , Tervo Timo M. T.
Published: September 2003

Context:  A 32‐year‐old woman was scheduled for myopic laser in situ keratomileusis (LASIK) because of myopia and anisometropia caused by retinal detachment surgery.

Case Report:  During surgery, a sudden malfunction of the microkeratome during the forward pass was experienced. It was not possible to reverse the blade manually along the suction ring. Moreover, disconnecting the suction from the control unit did not help at first, because the suction ring was firmly attached to the ocular surface. However, detaching the suction line from the control unit aborted the vacuum and allowed the surgeon to turn the whole microkeratome backwards, mimicking the normal blade movement. Finally, an almost normal flap was observed, and the operation was successfully completed. Afterwards, the wire to the electromotor of the microkeratome was found to be broken and subsequently replaced.

Conclusion:  This type of unforeseen microkeratome malfunction may result in serious flap or other complications.
Age‐related macular degeneration: filter lenses help in certain situations
Authors: Langagergaard Ulrich , Ganer Hans Jørgen , Baggesen Kirsten
Published: September 2003

Purpose:  To investigate the ability of different filter lenses to enhance the contrast sensitivity of patients with age‐related macular degeneration (AMD).

Methods:  A total of 32 patients with non‐exudative AMD and no other significant eye diseases underwent the study tests using their optimal correction. We used Hyvärinen's contrast sensitivity tests with 100%, 10%, 5%, 2.5% and 1.25% charts. All the tests were made without filter lenses and with the Corning 527 and LVI 527 lenses.

Results:  With the 100% charts, there was a slight tendency towards contrast sensitivity improvement with LVI filter lenses, but the degree of improvement was not statistically significant. With the 10% charts, contrast sensitivity improved significantly with LVI 527 filter lenses, but not with Corning 527 lenses. It was not possible to perform statistical analyses of the results with the 5%, 2.5% and 1.25% charts.

Conclusion:  Use of LVI filter lenses may improve contrast sensitivity in certain situations in patients with AMD.
Ophthalmological evaluation in thyroid‐associated ophthalmopathy
Authors: Åsman Peter
Published: September 2003

Purpose:  Thyroid‐associated ophthalmopathy (TAO) is an autoimmune disorder associated with Graves' disease and can seriously decrease quality of life. Current therapeutic regimens have considerable side‐effects and are not always able to restore normal function and appearance. Timing and a proper choice of therapy are critical but require careful patient evaluation. The present paper aims to describe clinical symptoms and signs of TAO and their relevance for management.

Results and Conclusions:  Thyroid‐associated ophthalmopathy has an initial active inflammatory phase which usually lasts for 6–24 months but which may not infrequently continue for several years. The severity of the subsequent clinical manifestations is determined by the degree of optic nerve involvement, corneal involvement, eye muscle dysfunction and exophthalmus, and also by the degree of subjective illness and disfigurement. Disease severity is the key determinant of indication for therapy, while inflammatory activity is the key determinant of therapeutic choice. Immunosuppressive therapy may be used in the inflammatory stage, while reconstructive surgery should be postponed to the inactive phase. Emergency surgery may be needed for vision‐threatening situations during the active stage.
Sexual harassment and eating disorders in female elite athletes – a controlled study
Authors: Sundgot‐Borgen J. , Fasting K. , Brackenridge C. , Torstveit M. K. , Berglund B.
Published: September 2003

The aims were to examine the percentage of female elite athletes and controls reporting sexual harassment and abuse (SHAB), and whether a higher percentage of female athletes with eating disorders (ED) had experienced SHAB. A questionnaire was administered to the total population of female elite athletes (n = 660) and controls (n = 780) aged 15–39 years. Sexual harassment and abuse were measured through 11 questions, ranging from light to severe SHAB. In addition, questions about dietary‐, menstrual‐ and training‐history and the Eating Disorder Inventory were included. The response rate was 88% for athletes and 71% for controls. Athletes (n = 121) and controls (n = 81) classified as “at risk” for ED and non‐ED controls participated in a clinical interview. A higher percentage of controls compared with athletes reported experiences of SHAB in general (59% vs. 51%, P < 0.001). A lower percentage of athletes had experienced SHAB inside sports than outside sport (28% vs. 39%, P < 0.001). A higher percentage of ED athletes than non‐ED athletes had experienced SHAB (66% vs. 48%, P < 0.01), both inside sport and outside sport. In spite of the fact that a higher percentage of controls compared with athletes had experienced SHAB, it is necessary to formulate clear guidelines, set up educational workshops and implement intervention programs for both ED and SHAB in sport.
Respiratory snorkel and valve system for breath‐by‐breath gas analysis in swimming
Authors: Keskinen Kari L. , Rodríguez Ferran A. , Keskinen Ossi P.
Published: September 2003

The present study aimed to compare a standard facemask (CM) and a newly modified swimming snorkel and valve system (SV) for breath‐by‐breath (B×B) gas analysis (K4 b2, Cosmed, Rome, Italy), and to validate the system under controlled laboratory conditions before being used in swimming. Nine healthy males performed two bouts of a stepwise exercise on an electrically braked stationary bicycle on separate days. Ventilatory and gas exchange parameters were analyzed using the same B×B portable system, with subjects breathing alternatively through the two different valves. Agreement between both methods was evaluated by Passing–Bablok regression analysis. The gas exchange values measured using the SV were highly correlated with those obtained using the CM (R2 values >0.9). However, differences existed between the two series of measurements so that most ventilatory and gas exchange parameters were lower (3–7%) with the SV. The error when using the SV device was mainly systematic along the whole range of measurement. Accordingly, linear regression equations were developed to further improve the accuracy of the measures when using the SV. Therefore, the modified respiratory SV system can be considered as a valid device for collecting expired gas for B×B analysis, comparable to the standard facemask, with the advantage of being suitable for measurements during swimming.
Walking trials in postmenopausal women: effect of low doses of exercise and exercise fractionization on coronary risk factors
Authors: Asikainen T‐M. , Miilunpalo S. , Kukkonen‐Harjula K. , Nenonen A. , Pasanen M. , Rinne M. , Uusi‐Rasi K. , Oja P. , Vuori I.
Published: September 2003

We studied the fractionization of walking training and searched for the minimum dose to affect coronary risk factors in two randomized controlled trials. Altogether 134 (Study I) and 121 (Study II) healthy, sedentary postmenopausal women started the trials, and 130 (Study I) and 116 (Study II) completed them. In Study I the exercise intensity was 65% of the maximal aerobic power (VO2max) and a total of 300 kcal was expended in one (Group W1) or two (Group W2) daily walking bouts. In Study II the exercise was continuous, and the exercise intensity (% of VO2max) and energy expenditure (kcal session−1) were 55% and 300 kcal (Group W3), 45% and 300 kcal (Group W4), 55% and 200 kcal (Group W5) and 45% and 200 kcal (Group W6). All the subjects walked 5 days a week. The outcome measures were blood pressure, serum lipoproteins and blood glucose and plasma insulin in fasting state and also during 2‐h oral glucose tolerance test in Study I. There was no change in diastolic pressure in the original study groups, but in the combined exercise group (W1+W2) in Study I, the mean diastolic pressure declined by −3.0 mmHg (95% con‐fidence interval (CI) −5.5 to −0.4) (P=0.025) in comparison with that of the controls. The mean blood glucose declined by −0.21 mmol L−1 (CI −0.33 to −0.09) in Group W1 and −0.13 mmol L−1 (CI −0.25 to −0.01) in Group W2 compared to controls (P=0.03). Also the 2‐h glucose concentration decreased in Groups W1 and W2 compared to controls. Systolic blood pressure, serum lipoproteins and insulin levels did not change in Study I or Study II. We conclude that our training program with the greatest exercise dose, exercise intensity 65% of VO2max and weekly expenditure of 1500 kcal had a minimal, positive effect on diastolic pressure and blood glucose, and the effect was similar in one or two daily exercise session groups. This exercise dose is probably close to the minimum to affect coronary risk factors in healthy postmenopausal women. To get a more pronounced and clinically relevant effect, a greater exercise dose is needed.
Viscoelastic behavior and structural properties of the coracoclavicular ligaments
Authors: Costic Ryan S. , Vangura Albert , Fenwick Jim A. , Rodosky Mark W. , Debski Richard E.
Published: September 2003

During contact sports such as football, hockey or rugby, the coracoclavicular ligaments are commonly ruptured. Currently, the limited biomechanical data on the properties and function of these ligaments have led to debate on the “gold standard” treatment for these injuries. Therefore, the objective of this study was to characterize the geometry, viscoelastic behavior and structural properties of the coracoclavicular ligaments (n=11). The trapezoid and conoid were found to have similar length (9.6±4.4 vs. 11.2±4.1 mm) and cross‐sectional area (103±43 vs. 69±51 mm2), respectively (P>0.05). Static and cyclic stress relaxation tests were then performed, followed by uniaxial tensile testing with the insertions of each ligament aligned to ensure a uniform distribution of load across the fibers. No significant differences were observed for the trapezoid and conoid during the static (36±8% vs. 31±7%) and cyclic (23±12% vs. 16±6%) stress relaxation tests, respectively (P>0.05). Similarly, no statistically significant differences were found between the trapezoid and conoid for linear stiffness (83±40 vs. 70±23 N mm−1), ultimate load (312±133 vs. 266± 108 N), energy absorbed at failure (820±576 vs. 752± 410 N mm), percent elongation (74±47% vs. 62±22%) and elongation at failure (5.8±2.2 vs. 6.1±1.6 mm), respectively (P>0.05). A comparison of our data to previous studies suggests that the complex fiber orientation of these ligaments has a significant role in determining the maximum load that can be transferred between the clavicle and scapula by each bone–ligament–bone complex. Our findings also further confirm the functional role of the coracoclavicular ligaments in supporting the upper extremity, and provide data for reconstruction and rehabilitation protocols as well as computational models.
The Tour de France: a physiological review
Authors: Lucia Alejandro , Earnest Conrad , Arribas Carlos
Published: September 2003

On 5 July 2003, the Tour de France (TDF) has celebrated 100th running. Instead of a chimney sweep competing during his free time (as in 1903), the recent winner is a highly trained, professional cyclist whose entire life‐style has been dedicated to reach his pinnacle during this event. The TDF has been held successfully for 100 years, but the application of the physiologic sciences to the sport is a relatively recent phenomenon. Although some historical reports help to understand the unique physiological characteristics of this race, scientific studies were not available in Sports Science/Applied Physiology journals until the 1990s. The aim of this article is to review the history of the TDF. Special emphasis is placed on the last decade where classic physiology has been integrated into applied scientific cycling data.
Fractured teeth bonded with dentin adhesives with and without unfilled resin
Authors: Farik Ban , Munksgaard Erik Christian , Andreasen Jens Ove , Kreiborg Sven
Published: September 2003

Fractured incisors were restored by reattaching the fragment to the remaining tooth structure. For this purpose, seven dentin adhesive systems were used with and without an unfilled resin (Heliobond®) and the strength of the restored teeth was tested at a cross‐head speed of either 1 or 500 mm/min. The hypothesis was that the strength of the reattachment would be higher when an unfilled resin was used. The dentin adhesive systems were Prime & Bond NT® (PB), Exite® (EX), One‐Step® (OS), PQ1® (PQ), SingleBond® (SB), Optibond Solo Plus® (OS), and an experimental adhesive (GL). Statistical analysis revealed that with all adhesives except EX, a significantly greater mean fracture strength was achieved when the adhesives were used with the resin (Heliobond). Furthermore, with all adhesives except PB, there was a significantly lower mean fracture strength when tested at 500 mm/min than at 1 mm/min. All the tested adhesives except EX should be used with an unfilled resin when restoring fractured teeth by reattachment.
Factors affecting resorption in traumatically intruded permanent incisors in children
Authors: Al‐Badri Sondos , Kinirons Martin , Cole Ben , Welbury Richard
Published: September 2003

Abstract  – There is a lack of consensus concerning the management of intruded permanent teeth. The objectives of the present study were to determine the prevalence of resorption for intruded permanent teeth and to establish the effect of factors on the timing, prevalence and rate of resorption and to examine the relationship between the timing of onset and the subsequent rate of resorption. Sixty‐one intruded permanent incisors treated at the Paediatric Dentistry units in Belfast and Newcastle upon Tyne, during the period 1990–99 with a minimum follow‐up period of 1.5 years, were studied. The timing and presence of resorption and its rate of occurrence over time were set as the principal outcomes. There was a significantly earlier onset and higher prevalence of resorption in more severely intruded teeth (P < 0.05). There was also a significant relationship between the degree of apical development and resorption with an increased prevalence in the more fully developed roots (P < 0.001). Resorption was detected significantly earlier in teeth with higher rates of resorption (P < 0.05). However, the treatment method did not significantly affect the prevalence or rate of resorption. In conclusion, the occurrence of root resorption after intrusive trauma appears to be related to the severity of the original injury and the stage of root development rather than the repositioning procedure.
Effect of source–sink ratio on seed set and filling in sunflower (Helianthus annuus L.)
Authors: ALKIO M. , SCHUBERT A. , DIEPENBROCK W. , GRIMM E.
Published: September 2003

Poor seed development in sunflower may result from insufficient assimilate supply (source limitation). To test this hypothesis, the effects of changed source–sink ratio on seed set (measured as percentage of empty achenes) and seed filling (measured as dry mass per filled achene) in individual plants were investigated. Source–sink ratio, defined as leaf area per floret (LAF), was experimentally altered using invasive (floret removal, defoliation) and non‐invasive (pulse of chilling, short days or shading during leaf or floret initiation) treatments. Shading at floret initiation proved the most effective non‐invasive method. Generally, an increase, or decrease, in LAF improved, or impaired, both seed set and filling. Increasing LAF by 2.0 cm2[95% confidence interval (1.5, 2.5)] decreased the percentage of empty achenes by 36.9%‐points (−41.9, −30.9) and increased dry mass per filled achene by 20.1 mg (13.6, 26.7) in the capitulum centre. The effect of source–sink ratio on seed set was always strongest in the centre, whereas peripheral whorls were not affected. Achene mass was affected in all parts of the capitulum. It is concluded that source limitation is a major cause for empty achenes in sunflower plants grown under non‐stress conditions.
Sex‐specific survival and parasitism in three‐spined sticklebacks: seasonal patterns revealed by molecular analysis
Authors: Arnold K. E. , Adam A. , Orr K. J. , Griffiths R. , Barber I.
Published: September 2003

A molecular method of identifying sex in three‐spined sticklebacks Gasterosteus aculeatus showed that adult males had a higher prevalence of dermal Glugea anomala cysts than adult females, and young‐of‐the‐year had more than adults. At the end of the breeding season, as predicted, the adult sex ratio became female biased and there was a disproportionate increase in G. anomala parasitism in adult males.
Sea trout migration in the Rhine delta
Authors: Bij de Vaate A. , Breukelaar A. W. , Vriese T. , De Laak G. , Dijkers C.
Published: September 2003

Sea trout Salmo trutta migration in the Rhine delta, The Netherlands, was studied using the NEDAP TRAIL System®, consisting of a chain of fixed detection stations and transponders, each transmitting a unique code. From 16 December 1996 to 31 December 2000, 195 (34%) out of 580 tagged sea trout were detected. Inland migration of sea trout was observed through the sluices in the dam between the Wadden Sea and Lake IJsselmeer (Afsluitdijk), the Nieuwe Waterweg and the sluices in the Haringvliet Dam. Seventy‐five per cent were detected for the first time at one of the detection stations within 30 days after tagging. Inland migration through the sluices in the Afsluitdijk, the Nieuwe Waterweg and the sluices in the Haringvliet Dam was observed for 34, 103 and 70 sea trout, respectively. Based on the number of tagged fish released in the adjacent coastal areas, however, migration through the Afsluitdijk was most important. During migration in fresh water, sea trout was predominantly active during daylight. Fish entering the Rhine delta through the Nieuwe Waterweg or the sluices in the Haringvliet Dam chose eight and six different routes, respectively, for upstream migration. Differences in current velocity in the Rhine distributaries seemed to be an important factor in the choice of migration routes.
Prediction of offspring fitness based on parental genetic diversity in endangered salmonid populations
Authors: Primmer C. R. , Landry P.‐A. , Ranta E. , Merilä J. , Piironen J. , Tiira K. , Peuhkuri N. , Pakkasmaa S. , Eskelinen P.
Published: September 2003

By simulating all possible offspring genotypic combinations based on pair‐wise matings in three vulnerable or endangered populations of salmonids (two Atlantic salmonSalmo salarand one Arctic charrSalvelinus alpinus), family level estimates of potential offspring genetic diversity were calculated using several commonly used genetic diversity estimators (,andHEST). By using this approach, the genetic variability of offspring could be predicted accurately based solely on parental genotype data. In addition, significant associations between offspring genetic variability and fitness‐related traits were observed in the two Atlantic salmon populations and these associations were consistent between fitness measures and either estimated or observed genetic diversity. This indicates that associations with offspring fitness measures can be predicted without genetic analysis of the offspring themselves.
Development and validation of a bioenergetics model for juvenile and adult burbot
Authors: Pääkkönen J.‐P. J. , Tikkanen O. , Karjalainen J.
Published: September 2003

Oxygen consumption of juvenile and adult burbot Lota lota was measured in an intermittent‐flow respirometer to determine the effect of temperature and fish body mass on metabolic rate. These results were combined with data from earlier experiments and the ‘Wisconsin bioenergetics’ model was constructed. The model was validated under laboratory conditions by comparing observed and predicted food consumption and growth of burbot fed on dead vendace Coregonus albula. There was a good correspondence between observed and estimated growth and food consumption under experimental conditions: the mean absolute per cent errors of growth and food consumption were 4·8 and 24·0%. Estimated values with the new model were an improvement over the Atlantic cod Gadus morhua model previously used for burbot. In the field, the reliability of food consumption estimates was verified by using polychlorinated biphenyls (PCB) accumulation as an indirect indicator of the food consumption rate. The total PCB concentration of nine out of 13 burbot was estimated accurately. Thus, the burbot model produced good estimates of food consumption, even under field conditions.
Are female guppies more likely to flee when approached by two males?
Authors: Brewster J. , Houde A.
Published: September 2003

Female guppies Poecilia reticulata often flee when approached by a single courting male but observations show fleeing is more likely when two males approach simultaneously. This may represent a response to a greater cost of being courted by two males.
Automated sperm morphology analysis in fishes: the effect of mercury on goldfish sperm
Authors: Van Look K. J. W. , Kime D. E.
Published: September 2003

This study is the first to examine the morphology of fish sperm using automated sperm morphology analysis (ASMA). The technique was applied to investigate the effect of an environmental pollutant, mercury, on the sperm morphology of goldfish Carassius auratus, and the effects on sperm morphology were compared with those on sperm motility. Goldfish sperm flagellar length was significantly shortened after instant exposure to 100 mg l−1 (368 µM) mercuric chloride, while curvilinear velocity (VCL) and the percentage of motile sperm were significantly decreased at mercuric chloride concentrations of 1 and 10 mg l−1 (3·68 and 36·8 µM), respectively. After 24 h exposure to 0·001 mg l−1 (0·0037 µM) mercuric chloride, flagellar length was significantly reduced in 38% of the spermatozoa. Following exposure to 0·1 mg l−1 (0·37 µM) mercuric chloride for 24 h, however, the majority of spermatozoa (98%), had significantly shortened flagella and increased sperm head length, width and area. Sperm motility was also significantly decreased at 0·1 mg l−1 (0·37 µM) mercuric chloride, probably due to the significantly reduced flagellar length at this concentration. This study shows that the morphological examination of fish sperm by ASMA provides, not only, an excellent tool for monitoring reproductive disruption caused by environmental pollution, but also has applications to other areas of fish reproductive biology, such as cryopreservation and aquaculture.
Holcocera sakura (Lepidoptera: Gelechioidea; Coleophoridae, Blastobasinae), a new species from Japan, associated with Prunus
Authors: OHSHIMA Issei
Published: September 2003

A new species, Holcocera sakura (Lepidoptera: Coleophoridae: Blastobasinae) that is associated with Prunus is described from Japan. This is the first record of the tribe Holcocerini from Japan. A photograph of the imago, and illustrations of wing venation and male and female genitalia are provided. The taxonomic position of this species is discussed.
Analysis of the meal‐dependent intragastric performance of a gastric‐retentive tablet assessed by magnetic resonance imaging
Authors: Steingoetter A. , Kunz P. , Weishaupt D. , Mäder K. , Lengsfeld H. , Thumshirn M. , Boesiger P. , Fried M. , Schwizer W.
Published: September 2003

Background : Modern medical imaging modalities can trace labelled oral drug dosage forms in the gastrointestinal tract, and thus represent important tools for the evaluation of their in vivo performance. The application of gastric‐retentive drug delivery systems to improve bioavailability and to avoid unwanted plasma peak concentrations of orally administered drugs is of special interest in clinical and pharmaceutical research.

Aim : To determine the influence of meal composition and timing of tablet administration on the intragastric performance of a gastric‐retentive floating tablet using magnetic resonance imaging in the sitting position.

Methods : A tablet formulation was labelled with iron oxide particles as negative magnetic resonance contrast marker to allow the monitoring of the tablet position in the food‐filled human stomach. Labelled tablet was administered, together with three different solid meals, to volunteers seated in a 0.5‐T open‐configuration magnetic resonance system. Volunteers were followed over a 4‐h period.

Results : Labelled tablet was detectable in all subjects throughout the entire study. The tablet showed persistent good intragastric floating performance independent of meal composition. Unfavourable timing of tablet administration had a minor effect on the intragastric tablet residence time and floating performance.

Conclusion : Magnetic resonance imaging can reliably monitor and analyse the in vivo performance of labelled gastric‐retentive tablets in the human stomach.
Small bowel stenosis in Crohn's disease: clinical, biochemical and ultrasonographic evaluation of histological features
Authors: Maconi G. , Carsana L. , Fociani P. , Sampietro G. M. , Ardizzone S. , Cristaldi M. , Parente F. , Vago G. L. , Taschieri A. M. , Bianchi Porro G.
Published: September 2003

Aim : To establish whether intestinal ultrasound, clinical or biochemical indices of activity can assess histological features of ileal stenosis in Crohn's disease.

Methods : In 43 patients undergoing surgery for a single ileal stenosis, clinical and biochemical parameters, as well as intestinal ultrasound, were assessed prior to surgery. The echo pattern of thickened bowel segments at the site of stenosis was classified as hypoechoic, stratified or mixed (segments with/without stratification). During surgery, stenoses were identified, resected and then histologically examined using standardized criteria.

Results : Clinical and biochemical indices of activity showed an overall weak positive correlation with histological inflammatory parameters and a negative correlation with fibrosis. The intestinal ultrasound echo pattern at the stenosis site was stratified in 25 patients, hypoechoic in 14 and mixed in four. Stenoses characterized by a stratified echo pattern showed a significantly higher degree of fibrosis, those characterized by hypoechoic echo pattern showed a higher degree of inflammation, while stenoses with a mixed echo pattern showed high degrees of both fibrosis and inflammation.

Conclusion : Ultrasound and, to a lesser degree, clinical and laboratory indices discriminate between inflammatory and fibrotic ileal stenoses complicating Crohn's disease, thus allowing appropriate medical and/or surgical treatment to be defined.
Detection of oxidative DNA damage in oesophageal biopsies of patients with reflux symptoms and normal pH monitoring
Authors: Liu L. , Ergun G. , Ertan A. , Woods K. , Sachs I. , Younes M.
Published: September 2003

Background : Gastro‐oesophageal reflux has been shown to induce oxidative DNA damage.

Aim : To determine whether oxidative DNA damage, detected in oesophageal biopsies by simple immunohistochemical staining, correlates with gastro‐oesophageal reflux disease as determined by pH monitoring.

Methods : The study included 47 patients with reflux symptoms who had oesophageal biopsy and 24‐h pH monitoring studies performed within 3 months of each other with no variation in treatment in the time between the two procedures. Sections of formalin‐fixed and paraffin‐embedded oesophageal biopsies were stained for 8‐hydroxy‐2′‐deoxyguanosine using the standard immunoperoxidase method. Positive nuclear immunoreactivity was considered to indicate oxidative DNA damage.

Results : Seven (33%) of the 21 cases with normal 24‐h pH monitoring results were negative for oxidative DNA damage, compared with only two (8%) of the 26 cases with abnormal 24‐h pH results (P = 0.058, two‐sided Fisher's exact test). Five of the patients with normal 24‐h pH results had oesophageal biopsies performed within 24 h of the monitoring procedure and, of these, four (80%) were positive for oxidative DNA damage, including a case in which both biopsy and 24‐h pH monitoring were performed on the same day whilst the patient was on proton pump inhibitor therapy. All cases with normal 24‐h pH results and positive oxidative DNA damage showed features of reflux on routine morphological evaluation.

Conclusions : Oxidative DNA damage can occur in the absence of acid reflux and despite adequate antisecretory therapy. This may indicate that other agents, such as bile, can induce oxidative DNA damage in an acid‐suppressed environment. The significant discordance between oxidative DNA damage and 24‐h pH results makes the determination of oxidative DNA damage a poor surrogate marker for 24‐h pH monitoring.
Infliximab in the treatment of medically refractory indeterminate colitis
Authors: Papadakis K. A. , Treyzon L. , Abreu M. T. , Fleshner P. R. , Targan S. R. , Vasiliauskas E. A.
Published: September 2003

Aim : To examine the outcome of infliximab intervention in refractory indeterminate colitis.

Methods : Twenty patients with severe, medically refractory indeterminate colitis were treated with infliximab. All patients initially received infliximab, 5 mg/kg, intravenously and, in some patients, the dose was subsequently increased to 10 mg/kg. The number of infusions ranged from one to 16 per patient. Indeterminate colitis was defined as colitis that could not be classified with certainty as Crohn's disease or ulcerative colitis based on traditional clinical, endoscopic and histopathological criteria. The clinical response to infliximab was classified as complete response, partial response or non‐response.

Results : Fourteen of the 20 patients (70%) showed a complete response to infliximab treatment, two showed a partial response and four showed no response. The four non‐responders underwent colectomy with ileal pouch‐anal anastomosis. The resected colon specimen was consistent with ulcerative colitis in all four cases, although two were subsequently re‐classified as Crohn's disease. Eight additional patients were subsequently re‐classified as having Crohn's disease on longer follow‐up evaluation, whilst eight continued to have features of indeterminate colitis. The response rate to infliximab treatment was similar in both groups.

Conclusions : Infliximab is effective in approximately two‐thirds of patients with indeterminate colitis, and thus may be considered for patients with refractory disease prior to colectomy. The follow‐up time afforded by infliximab treatment may allow for more accurate classification of the disease in a significant proportion of patients whose colitis has indeterminate features at initial presentation.
Effect of non‐selective γ‐aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro‐oesophageal reflux in healthy human subjects
Authors: Cantù P. , Carmagnola S. , Savojardo D. , Allocca M. , Penagini R.
Published: September 2003

Background : Transient lower oesophageal sphincter relaxation and low lower oesophageal sphincter pressure are the main mechanisms of reflux. It has recently been shown that the stimulation of γ‐aminobutyric acid type B (GABAB) receptors by baclofen decreases the rate of transient lower oesophageal sphincter relaxation and increases the lower oesophageal sphincter pressure in healthy humans. Valproic acid increases synaptosomal GABA concentrations, thus affecting all types of GABA receptors.

Aim : To evaluate the effect of valproic acid on transient lower oesophageal sphincter relaxation, lower oesophageal sphincter pressure and gastro‐oesophageal reflux.

Methods : Thirteen healthy subjects underwent 2‐h post‐prandial oesophageal motility and pH monitoring on two separate occasions after the oral administration of 1 g valproic acid or placebo.

Results : Valproic acid increased the lower oesophageal sphincter pressure by 41% (14.0 ± 2.1 mmHg vs. 9.9 ± 2.0 mmHg after placebo, P < 0.02), but did not affect the rate of transient lower oesophageal sphincter relaxation (7.9 ± 1.0/h vs. 8.2 ± 0.9/h after placebo), the number of reflux episodes or gastro‐oesophageal reflux.

Conclusions : Non‐selective GABA receptor stimulation may be beneficial to reflux patients with low lower oesophageal sphincter pressure, but exerts a different modulation of transient lower oesophageal sphincter relaxation than the selective stimulation of GABAB receptors.
Bcr‐Abl upregulates cytosolic p21WAF‐1/CIP‐1 by a phosphoinositide‐3‐kinase (PI3K)‐independent pathway
Authors: Keeshan Karen , Cotter Thomas G. , McKenna Sharon L.
Published: September 2003

Summary. Chronic myeloid leukaemia invariably progresses from a drug‐sensitive to a drug‐resistant, aggressive acute leukaemia. The mechanisms responsible for this are unknown, although loss of p53 has been reported in ≈ 25% of cases. Elevated expression of Bcr‐Abl is also associated with disease progression. We have shown that cells expressing high levels of Bcr‐Abl also express elevated levels of p53 and the cell cycle inhibitor, p21WAF‐1. Despite this, cells continue to cycle and are drug resistant. As p21WAF‐1 inhibitory activity is associated with nuclear localization, we investigated its localization in Bcr‐Abl‐expressing cells, and found that it is predominantly cytoplasmic. We have also shown that it associates physically with the serine/threonine kinase AKT, but this association and the cytosolic location of p21WAF‐1 are phosphinositide‐3‐kinase (PI3K) independent. Cytosolic p21WAF‐1 has been reported to have a prosurvival role in other transformed cells. In Bcr‐Abl‐expressing cells, p21WAF‐1 rapidly diminishes as the cells are sensitized to apoptosis, using the inhibitor STI571. It is possible therefore that p21WAF‐1 could also have a positive, prosurvival role in these cells. This study suggests that, by retaining p21WAF‐1 in a cytosolic location, Bcr‐Abl can evade the cell cycle arrest normally induced by nuclear p21WAF‐1 and therefore also enable the cells to negate an important feature of a tumour suppressor response.
Role of DNA mismatch repair genetic polymorphisms in the risk of childhood acute lymphoblastic leukaemia
Authors: Mathonnet Géraldine , Krajinovic Maja , Labuda Damian , Sinnett Daniel
Published: September 2003

Summary. Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer. Genetic variants in the coding regions of the mismatch repair genes MLH1 (Ile‐219Val) and MSH3 (Arg‐940Glu and Thr‐1036Ala) could contribute to an individual's susceptibility as modifiers in leukaemogenesis. To investigate this possibility, we conducted a case–control study on 287 children with ALL and 320 healthy controls both of French–Canadian origin. MLH1 and MSH3 variants, when taken independently, seemed to play little or no role in the aetiology of childhood ALL. However, when the MLH1 genotypes were combined with genotypes previously shown to influence ALL susceptibility, we found that the MLH1 variant Val‐219 further increases the risk of GSTM1 null and CYP1A1*2A genotypes [combined odds ratio (OR) = 6·0, P = 0·002] as well as that of CYP2E1*5 (OR = 15·8, P = 0·001). No association was found with MSH3 variants. This study suggests an association of leukaemogenesis in children with both xenobiotic metabolism and DNA repair, and thus points to the effect of environmental exposure.
Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north‐west England
Authors: McNally Richard J. Q. , Alston Robert D. , Cairns Donal P. , Eden Osborn B. , Birch Jillian M.
Published: September 2003

Summary.Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976–2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0–14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small‐area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0·05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0·001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.
The P2X7 receptor gene polymorphism 1513 A→C has no effect on clinical prognostic markers, in vitro sensitivity to fludarabine, Bcl‐2 family protein expression or survival in B‐cell chronic lymphocytic leukaemia
Authors: Starczynski Jane , Pepper Chris , Pratt Guy , Hooper Laura , Thomas Alun , Hoy Terry , Milligan Donald , Bentley Paul , Fegan Christopher
Published: September 2003

Summary. A cohort of 121 patients with B‐cell chronic lymphocytic leukaemia (B‐CLL) was investigated for a single nucleotide polymorphism in the P2X7 receptor gene (1513 A→C), and the findings were correlated with clinical prognostic markers, in vitro sensitivity to fludarabine, expression of Bcl‐2 family proteins and overall survival. The frequency of the polymorphism in B‐CLL samples was not significantly different from that found in normal healthy controls (P = 0·27; Fisher's exact test). Furthermore, when the B‐CLL patients were analysed according to P2X7 genotype (1513 A/A versus 1513 A/C), there was no significant difference in age at diagnosis, stage at diagnosis, lymphocyte doubling time, time to first treatment, progression‐free survival and overall survival, and neither was there any evidence of bias in terms of VH gene mutational status, CD38 expression, in vitro sensitivity to fludarabine or expression of Bcl‐2, Bax or Mcl‐1 between the two groups. These results indicate that the 1513 A→C polymorphism of the P2X7 gene is unlikely to play a significant role in the pathogenesis or disease progression of B‐CLL.
Intravenous anti‐D as a treatment for immune thrombocytopenic purpura (ITP) during pregnancy
Authors: Michel Marc , Novoa Maria V. , Bussel James B.
Published: September 2003

Summary. This pilot study assessed the safety and efficacy of intravenous anti‐D in eight Rh(D)‐positive women with immune thrombocytopenic purpura (ITP) during the second and third trimesters of pregnancy. The median pretreatment platelet count was 28 × 109/l. The patients received one to seven anti‐D infusions at a mean dose of 62·7 µg/kg, and the response rate to anti‐D was 75%. A haemoglobin decrease of > 2·0 g/dl occurred only once. Fetal hydrops was not identified by ultrasonography. The direct antiglobulin test was positive in three out of seven Rh+ newborns, none of whom was anaemic or jaundiced. Anti‐D is effective and appears to be safe for both mother and fetus.
Elevated levels of cyclin A1 and A (A2) mRNA in acute myeloid leukaemia are associated with increased survival
Authors: Nakamaki Tsuyoshi , Hamano Yasuharu , Hisatake Jun‐ichi , Yokoyama Akihiro , Kawakami Kei‐ichiro , Tomoyasu Shigeru , Honma Yoshio , Koeffler Phillip
Published: September 2003

Summary. Cyclin A (A2) and cyclin A1 are members of the G2 cyclins, which are involved in the control of G2/M and G1/S transitions as well as mitosis. Human cyclin A1 was cloned as an A‐type cyclin that is highly expressed in acute myeloid leukaemia (AML). The clinical significance of these cyclins in myeloid leukaemia remains to be clarified. We investigated the relative levels of these transcripts in 80 patients with de novo AML. Correlations with clinical parameters showed that the initial white blood cell count and serum lactate dehydrogenase levels were inversely associated with cyclin A (A2) mRNA levels (r = −0·276, P = 0·019) and cyclin A1 mRNA levels (r = −0·241, P = 0·042) respectively. They were independently associated with increased overall survival [P = 0·035 for cyclin A (A2) and P = 0·016 for cyclin A1]. Multivariate analysis using Cox's proportional hazard model showed that elevated cyclin A1 mRNA levels contributed significantly to the better prognosis of patients with AML. Furthermore, the analysis of survival probability showed that the group with high levels of both cyclin A (A2) and A1 survived significantly longer than the group with low expression of both these cyclins (P = 0·002). These data indicate that high expression levels of both cyclin A (A2) and A1 are associated with good prognosis in AML patients.
Beta‐adrenergic receptor polymorphisms in patients with elevated factor VIII levels with venous thrombosis
Authors: O'Donnell James , Manning Richard A. , Laffan Michael A.
Published: September 2003

Summary. Beta‐blockers significantly reduce elevated factor VIII (FVIII) levels in patients with venous thromboembolism (VTE). To determine whether β‐adrenergic receptors are important in the aetiology of high FVIII levels, we investigated four coding polymorphisms of the β1‐ and β2‐receptor genes in 64 patients with high FVIII and VTE and 100 healthy controls. Genotypic and allelic frequencies were not significantly different between the patient and control groups. However, a significant dosage effect of the β2 E27 allele on plasma FVIII coagulant activity levels was observed in normal group O individuals.
The use of stimulated granulocyte transfusions to prevent recurrence of past severe infections after allogeneic stem cell transplantation
Authors: Kerr J. Paul , Liakopolou Effie , Brown Jessica , Cornish Jacqueline M. , Fleming David , Massey Edwin , Oakhill Anthony , Pamphilon Derwood H. , Robinson Stephen P. , Totem April , Valencia Alexandra M. P. I. , Marks David I.
Published: September 2003

Summary. The predictable neutropenia that follows allogeneic stem cell transplantation (ASCT) may be associated with recurrence of previous life‐threatening infection. We describe nine patients with either previous invasive aspergillosis (IA) or considered to be at high risk of developing IA who underwent ASCT with prophylactic granulocyte transfusions. The study group, when compared with a control group, had a significant reduction in the incidence and duration of fevers (P < 0·05) and maximum C‐reactive protein (P < 0·05). There were significantly fewer days of neutropenia (P < 0·05). There was also radiological improvement of pulmonary infiltrates in four out of seven assessable patients. No serious toxicity was encountered in donors or recipients. We conclude that prophylactic granulocyte donations can be given safely, and that they significantly reduce the number of days of neutropenia. Further investigation is warranted to determine whether granulocyte donations can prevent the recurrence of IA in patients at risk of fungal infection.
Prevalence and pattern of antinuclear autoantibodies in 347 patients with non‐Hodgkin's lymphoma
Authors: Guyomard Stephanie , Salles Gilles , Coudurier Marie , Rousset Hugues , Coiffier Bertrand , Bienvenu Jacques , Fabien Nicole
Published: September 2003

Summary. The presence of antinuclear autoantibodies (ANA) was investigated in a large cohort of patients with non‐Hodgkin's lymphoma (NHL) in order to assess their frequency, specificity and prognostic relevance. ANA were analysed in 347 patients with different histological subgroups of NHL and in 213 controls using an indirect immunofluorescence technique on HEp2 cells. As the appearance of autoantibodies may be found after treatment of NHL, samples were collected at the time of diagnosis of NHL before any therapy. Sixty‐six (19%) NHL patients and 12 (5·6%) patients from the control group displayed ANA. The prevalence between the two groups was found to be significantly higher in NHL patients (P < 0·0001) with a marked increased prevalence in follicular and mantle cell lymphoma subgroups. Autoantibodies directed against mitotic proteins or mitotic‐associated proteins were found in 6·9% of NHL patients versus 0·5% in the control group (P < 0·001), with a significantly increased incidence in follicular and mantle cell lymphoma subgroups (P < 0·0001). Some 28% of the patients with positive ANA displayed clinical symptoms that could correspond to classical autoimmune manifestations, this frequency appearing to be higher in the marginal zone/mucosa‐associated lymphoid tissue lymphoma subgroup. These data demonstrate a significant incidence of ANA before any treatment in NHL occurrence, which seems to be higher in some histological subgroups with particular ANA, such as ANA directed against mitotic proteins or mitotic‐associated proteins.
Intracranial haemorrhage among a population of haemophilic patients in Brazil
Authors: Antunes S. V. , Vicari P. , Cavalheiro S. , Bordin J. O.
Published: September 2003

Intracranial haemorrhage (ICH) is a common cause of morbidity and mortality in haemophilic patients. The overall incidence of ICH has been reported to range from 2.2% to 7.5% in patients with haemophilia. From 1987 to 2001, 401 haemophilic patients from the Serviço de Hemofilia, Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo were evaluated. The episodes of ICH were documented by CT scan and the anatomic location, clinical presentation, relationship to trauma and clinical factors, including the presence of HIV infection and the presence of inhibitor, were reviewed. Among 401 haemophilic patients, 45 ICH episodes in 35 (8.7%) patients with age ranging from 4 days to 49 years (mean 10.6 years) were observed. A history of recent trauma was documented in 24 (53.3%) cases. Seventeen (37.8%) episodes occurred in more than one site of bleeding, 12 (26.7%) were subdural, seven (15.5%) subarachnoid, four (8.9%) epidural, two (4.4%) intracerebral and one (2.2%) intraventricular. The most frequent symptoms were headache and drowsiness. All patients were submitted to replacement therapy and neurosurgical intervention was performed in eight (17.8%) patients. Despite the treatment, three (8.6%) haemophilia A patients died due to the ICH event and three presented late sequelae. The most important aspect of ICH management is the early replacement therapy in haemophilic patients. This prompt treatment will increase the chances of a better prognosis. Another impact measure consists in the administration of the deficient coagulation factor after every head trauma, even when considered minor.
Practice patterns in haemophilia A therapy – a survey of treatment centres in the United States
Authors: Butler Regina B. , McClure Wilma , Wulff Karen
Published: September 2003

A survey was conducted to ascertain practice patterns for haemophilia A therapy in the United States. Questionnaire data were supplied by 52 haemophilia centres with a total of 4129 patients under treatment. Most participating centres were affiliated with academic/teaching hospitals or institutions. Patients below 5 years comprised 17% of the study population, 6–18 years 41% and >18 years 42%, and the apportionment across severity categories was 53% severe, 17% moderate and 30% mild. Among patients with severe haemophilia, 49% were receiving on‐demand treatment, while 44% were receiving some form of prophylaxis (13% primary, 20% secondary and 11% tertiary). Primary prophylaxis was the most common type in children below 5 years of age, accounting for 25% of this age group. In children 6–18 years old, 58% were on some type of prophylactic regimen, while on‐demand treatment was most frequent among adults. Difficulties of venous access were the most frequently cited barrier to instituting prophylaxis. Catheters were in use among 37% of the patients under primary prophylaxis and 14% of those on secondary prophylaxis. No major differences were observed in forms of therapy used between larger and smaller centres. These observations provide an extensive characterization of haemophilia A practice patterns in the United States.