bluuebunny/crossref_metadata_2025 huggingface dataset:
Active fault creep variations at Chihshang, Taiwan, revealed by creep meter monitoring, 1998–2001
Authors: Lee Jian‐Cheng , Angelier Jacques , Chu Hao‐Tsu , Hu Jyr‐Ching , Jeng Fu‐Shu , Rau Ruey‐Juin
Published: November 2003

The daily creep meter data recorded at Chihshang in 1998–2001 are presented. The Chihshang creep meter experiment was set up across the Chihshang thrust fault, the most active segment of the Longitudinal Valley Fault, which is the present‐day plate suture between the Eurasian and the Philippine Sea plates in eastern Taiwan. Near‐continuous data recording at two sites revealed different surface fault motions yet similar annual shortening rates: 16.2 mm at the Tapo site (comprising two connected creep meters) and 15.0 mm at the Chinyuan site (three creep meters straddling parallel fault branches). Four of the five creep meters showed a seasonal variation, with the fault moving steadily during the rainy season from April to October, and remaining quiescent during the rest of the year. The only exception was recorded by the creep meter located on a mélange‐composed hillslope, where local gravitational landsliding played an additional role other than tectonic faulting. Through comparison with daily precipitation data, we inferred that moderate rainfall suffices to trigger or facilitate slippage on the surface fault, during the transition period of the dry/wet season. During the observation period from 1998 to 2001, the subsurface seismicity exhibited clusters of microearthquakes on the Chihshang Fault at depths of 10–25 km. Recurrent earthquakes occurred regardless of whether the season was wet or dry, indicating that the stress relaxation associated with seismicity in the seismogenic zone did not transfer immediately up to the surface. The accumulated strain on the Chihshang Fault at shallow surface levels was released through creep during the wet season. In addition to these short‐term seasonal variations, an apparent decrease in the annual slipping rate on the Chihshang Fault during the last few years deserves further investigation in order to mitigate against seismic hazard.
Nanoscale spatial induction of ultraviolet photoproducts in cellular DNA by three‐photon near‐infrared absorption
Authors: Meldrum Rosalind A , Botchway Stanley W , Wharton Christopher W , Hirst Graeme J
Published: November 2003

The high‐resolution spatial induction of ultraviolet (UV) photoproducts in mammalian cellular DNA is a goal of many scientists who study UV damage and repair. Here we describe how UV photoproducts can be induced in cellular DNA within nanometre dimensions by near‐diffraction‐limited 750 nm infrared laser radiation. The use of multiphoton excitation to induce highly localized DNA damage in an individual cell nucleus or mitochondrion will provide much greater resolution for studies of DNA repair dynamics and intracellular localization as well as intracellular signalling processes and cell–cell communication. The technique offers an advantage over the masking method for localized irradiation of cells, as the laser radiation can specifically target a single cell and subnuclear structures such as nucleoli, nuclear membranes or any structure that can be labelled and visualized by a fluorescent tag. It also increases the time resolution with which migration of DNA repair proteins to damage sites can be monitored. We define the characteristics of localized DNA damage induction by near‐infrared radiation and suggest how it may be used for new biological investigations.
Retention and postinsertion maintenance of bar‐clip, ball and magnet attachments in mandibular implant overdenture treatment: an in vivo comparison after 3 months of function
Authors: Van Kampen Frits , Cune Marco , Van Der Bilt Andries , Bosman Frits
Published: November 2003

Abstract: It could be hypothesised that attachments, which provide more retention against vertical and horizontal dislodgement, will be associated with more favourable parameters of oral function. This in vivo study is designed to provide data regarding initial retention force, loss of retention force after 3 months of function and postinsertion maintenance and complications associated with the use of magnet, bar‐clip and ball attachments in mandibular overdenture treatment. Eighteen edentulous subjects received two permucosal implants in the inter‐foramina region of the mandible, a new denture and three successive suprastructure modalities (magnet‐, bar‐clip and ball attachments). The retention force of the attachments at baseline and after 3 months was measured in a standardised way. The amount and type of postinsertion maintenance that was related to the attachment were evaluated. No differences in retention force at baseline and after 3 months of loading were observed for all three attachment types. The mean retention forces of magnet attachments, bar‐clip attachments and ball attachments were 8.1, 31.3 and 29.7 N respectively. Functional maintenance complications related to the attachments were predominantly observed in 11/36 magnet attachments. Functional problems in the ball attachment group were relatively rare, easily manageable and seen in 4/36 attachments. The bar‐clip attachments exhibited no maintenance problems at all.
Long‐term functional loading of dental implants in rhBMP‐2 induced bone
Authors: Jovanovic Sascha A. , Hunt Dennis R. , Bernard George W. , Spiekermann Hubertus , Nishimura Russell , Wozney John M. , Wikesjö Ulf M. E.
Published: November 2003

Abstract: Osseointegration [direct bone–implant contact (BIC)] is a primary goal following installation of endosseous dental implants. Such bone contact provides stability for the dental implant over time. The objective of this study was to evaluate bone formation and BIC at long‐term, functionally loaded, endosseous dental implants placed into bone induced by recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in an absorbable collagen sponge (ACS) carrier. Mandibular, saddle‐type, alveolar ridge defects (∼15 × 10 × 10 mm), two per jaw quadrant, were surgically induced in each of six young adult American fox hounds. The defects were immediately implanted with rhBMP‐2/ACS. Two defects per animal additionally received a nonresorbable expanded polytetrafluoroethylene (ePTFE) membrane or a bioresorbable polyglycolide fiber membrane. Healing was allowed to progress for 3 months, when the ePTFE membrane was removed, and machined, threaded, titanium dental implants were installed into the rhBMP‐2/ACS induced bone and into the adjacent resident bone. At 4 months of osseointegration, the implants were exposed to receive abutments and prosthetic treatment (two‐ or three‐unit bridges). Some implants were removed for histologic analysis. The remainder of implants were exposed to functional loading for 12 months at which time the animals were killed for histometric analysis. One animal died prematurely due to kidney failure unrelated to the experimental protocol and was not included in the analysis. The 12‐month block sections from a second animal were lost in the histological processing. Four sites receiving rhBMP‐2/ACS and ePTFE or resorbable membranes experienced wound failure and membrane exposure, and subsequently exhibited limited bone formation. Defects without wound failure filled to contour with the adjacent alveolar bone. The newly formed bone exhibited features of the resident bone with a re‐established cortex; however, it commonly included radiolucent areas that resolved over time. Dental implants block biopsied at 4 months exhibited limited, if any, crestal resorption, whereas those exposed to functional loading for 12 months exhibited some crestal resorption. Implants biopsied at 4 months exhibited a mean (± SD) BIC of 40.6 ± 8.2% in rhBMP‐2/ACS induced bone vs. 52.7 ± 11.4% in resident bone. Dental implants exposed to 12 months of functional loading exhibited a mean BIC of 51.7 ± 7.1% in rhBMP‐2/ACS induced bone vs. 74.7 ± 7.0% in resident bone. There were no significant differences between dental implants placed into rhBMP‐2/ACS induced bone and resident bone for any parameter at any observation interval. In conclusion, rhBMP‐2/ACS‐induced bone allows installation, osseointegration, and long‐term functional loading of machined, threaded, titanium dental implants in dogs.
Timing of Ovulation and Conception Rate in Primiparous and Multiparous Cows after Synchronization of Ovulation with GnRH and PGF2α
Authors: Tenhagen B‐A , Wittke M , Drillich M , Heuwieser W
Published: November 2003

Contents

Conception rates after Ovsynch have been higher in primiparous than in multiparous cows. The objective of this study was to investigate whether this difference might be due to differences in ovulation rate or follicular size. The experiment was conducted with 136 Holstein Frisian cows from a commercial herd in Brandenburg, Germany. All cows were synchronized using Buserelin (GnRH analogue) at day −10, Tiaprost (PGF2α analogue) at day −3 and again GnRH at day −1. Timed artificial insemination (TAI) was carried out 16–20 h after the second dose of GnRH on day 0. Milk samples for analysis of milk progesterone were obtained on days −17, −10, −3 and at TAI. Progesterone concentrations were used to determine the stage of oestrus cycle at the start of the synchronization protocol and to investigate the presence of functional luteal tissue before treatment with PGF2α and TAI. All animals were examined by ultrasound at the second treatment with GnRH, at AI, 8 and 24 h after AI. Overall synchronization rate (proportion of cows with an ovulation within 40 h after GnRH) was 86.8% in primiparous and 88.2% in multiparous cows, respectively. Ovulation occurred earlier in primparous than in multiparous cows (p < 0.05) and ovulatory follicles were smaller. Conception rates were numerically higher in primiparous cows but the difference was not significant. Cows that displayed signs of oestrus on day −1 and received an additional AI on this day were more likely to conceive than cows that only received TAI 16 to 20 h after GnRH2. It is concluded that ovulation occurs earlier in primiparous than in multiparous cows after Ovsynch. However, a significant relationship between these differences and the probability of conception could not be established.
Estimating Bargaining Effects in Hedonic Models: Evidence from the Housing Market
Authors: Harding John P. , Knight John R. , Sirmans C.F.
Published: November 2003

Bargaining is common in markets for heterogeneous goods and differences in bargaining power between buyer and seller affect the negotiated transaction price. Previous research has found systematic evidence in the housing markets that weak buyers pay higher prices and weak sellers receive lower prices for their homes. Earlier work has modeled the bargaining effect as a parallel shift in the hedonic function, implicitly assuming that attribute shadow prices were unaffected by the bargaining process. In this paper, we use a sample of home sales where the seller's bargaining power is weakened by the fact that the home is vacant at the time of sale to test whether the effect of bargaining is best captured by a shift in the hedonic constant or whether the attribute shadow prices vary as well. The question is significant for property valuation where estimation of the marginal value of an attribute is commonly used to adjust comparable sales data. We find strong confirmation that bargaining power influences the negotiated price. We also find evidence that bargaining power alters attribute prices, although we do not find a consistent pattern across markets.
The Contribution Internal Auditors Make to Strategic Management
Authors: Melville Rob
Published: November 2003

This paper examines the role of internal auditors in strategic management, in particular their use of the Balanced Scorecard (BSC). The research is empirical, based on the results of a survey of an international, specialist group of professionals. This group comprised both internal auditors and non‐internal auditors. Membership is multinational and a full range of industries was represented. The response rate was more than 22%, and all results were tested for significance. Respondents were asked to evaluate their own and their organisation's attitudes towards a range of statements about strategy and the BSC. The results show that there is a significant awareness of the potential benefits of the Balanced Scorecard and its potential role in good corporate governance practice. It was also clear that ‘soft’ controls and qualitative issues are addressed and reported on.
The influence of arbuscular mycorrhizal colonization and environment on root development in soil
Authors: Atkinson D. , Black K. E. , Forbes P. J. , Hooker J. E. , Baddeley J. A. , Watson C. A.
Published: November 2003

The production of fine roots is one of the principal means by which carbon, fixed during photosynthesis, enters the soil, and quantifying the production for particular combinations of environmental and biotic factors is important for predicting the sequestration of carbon in the soils of grassland ecosystems. Arbuscular mycorrhizal fungi (AMF) can have a major effect on the production of roots, and we studied how colonization by AMF affects the lifespan of roots. Twenty per cent of control roots of Trifolium repens survived for longer than 42 days whereas 37% survived that long in AMF‐colonized plants. The overall survival of the roots of Lolium perenne was less than in T. repens: around 10% of roots survived beyond 42 days and this was not affected by AMF colonization. Previous studies have shown that lifespans of roots can be affected by temperature. We tested the hypothesis that these observations are linked to a change in the morphology of the root system caused by temperature and also by AMF. We found that inoculation with AMF in a microcosm study using Plantago lanceolata grown at various temperatures, with and without AMF, showed no clear effect of AMF on branching patterns. Temperature had a significant effect on total lengths, numbers and branching rates of some higher orders of roots. Total lengths of both secondary and tertiary roots grown at 27°C were about double those of plants grown at 15°C. Colonization by AMF tended to reduce this effect. Evidently the effect of colonization by AMF on root lifespan depends on the species. Increased branching, and thus a greater proportion of ephemeral roots, was responsible for shortening the lives of the roots at increased temperature, which suggests a strong link between lifespan and morphology.
Microbial activity as a major factor in the mobilization of iron in the humid tropics
Authors: Stemmler S. J. , Berthelin J.
Published: November 2003

The relation between the biodegradation and mineralization of soil organic matter and the bacterial solubilization and mobilization of iron in soils of the humid tropics is not clear. We therefore studied how microbial activity mobilized iron in a typical swamp soil of the humid tropics using two complementary approaches. By analysing soil water we found that the swamps (20% of the catchment) are the major sites of mineral weathering. Bacteria caused the solubilization of ferrous iron, produced ammonium, released organic soluble compounds, and caused the disappearance of nitrate. The waterlogged soil of the swamp (Gleysol) degraded and mineralized organic matter, producing CO2 and NH4+, and the amount of that activity depended on the amount, availability and quality of the organic matter. The nature and biomass of autochthonous bacteria were also important. The solubilization of iron was detected in the upper horizons (L1, 0–30 cm; L2, 30–70 cm; L3, 70–100 cm), where both iron and organic matter are available. Highly significant correlations were found between mineralization of organic matter and iron reduction. Quantitatively, we found that 100 µg of organic C being mineralized could reduce and dissolve 38, 97 and 115 µg Fe2+ in the L1, L2 and L3 horizons, respectively, during 30 days. After 30 days, there was a marked change in the relation, suggesting that lack of iron limited reduction. The coupling of iron reduction to the carbon cycle (soil organic matter biodegradation) is significant.
Behavioral measures of drinking: patterns from the Alcohol Interlock Record
Authors: Marques Paul R. , Voas Robert B. , Tippetts A. Scott
Published: November 2003

Aims  This report reviews breath test data captured by the alcohol ignition interlock, a device that prevents a car from starting when BAC (breath alcohol concentration) is elevated.

Design  The predictors were elevated BAC test rates from ignition interlock equipped cars of traffic offenders convicted of DUI (driving under the influence of alcohol) and who used interlocks for 6–18 months. Outcome data were future DUI convictions.

Settings  Québec and Alberta, Canada.

Participants  Approximately 10 000 interlock users from these two culturally distinctive English‐ and French‐speaking Provinces.

Measurement  Predictor patterns were analyzed from among 23 million breath tests. Repeat DUI convictions accumulated up to several years after interlock removal were studied as an outcome to be predicted by the rate of BAC tests ≥20 mg/dl (0.02%) while the interlock was installed. Data were analyzed with sensitivity and survival methods.

Findings  A median of eight interlock breath tests per day per driver were logged (a rate of 3000 tests/year). Less than 1% of all tests were over 0.02%, but the rate of elevated BAC tests, particularly those taken at 7–9 a.m., strongly predicts repeat DUI offenses 2 years hence. The interlock record is an unobtrusive measure of drinking behavior and can be used to profile driver risk.

Conclusions  With new legal mandates, North American use of these DUI control devices is increasing rapidly from the current 5% penetration rate. Interlock data may eventually come to serve as a useful adjunct for patient monitoring by alcohol counselors as well as by courts and motor vehicle authorities.
Patient‐perceived severity of irritable bowel syndrome in relation to symptoms, health resource utilization and quality of life
Authors: Hahn B. A. , Kirchdoerfer L. J. , Fullerton S. , Mayer E.
Published: November 2003

Aim:

In this study of patients with irritable bowel syndrome (IBS), we evaluated the relationship between patient‐rated severity of IBS and patients' physical and psychological symptoms, health care resource use and quality of life.

Methods:

One hundred and twenty‐six patients diagnosed with IBS were administered a series of questionnaires, including the Bowel Symptom Checklist, the Symptom Checklist‐90 R (a psychological symptom checklist), the IBSQOL (a disease‐specific quality of life instrument), the SF‐36 (a general health status instrument), and a health resource utilization assessment that measured health care use, time loss from work, impact on productivity, and days worked with symptoms.

Results:

No relationship was found between IBS severity and gastrointestinal symptoms, except for a feeling of unpassed stool. IBS severity was also not related to psychological symptom severity. Direct traditional indicators of resource use (e.g. physician visits, hospital admissions and emergency room visits) were not significantly associated by severity level; however, indirect measures of resource use (e.g. number of days with pain, productivity and number of bed days) were related to severity. Quality of life was clearly associated with perceived IBS severity. Patients who rated themselves as very severe reported the lowest scores and had the poorest health for all quality of life dimensions measured.

Conclusions:

These findings suggest that perceived IBS severity is defined by the limitations the disease imposes, rather than by the symptoms. Patients with reduced productivity and decreased functioning for most of the quality of life indicators were those who rated their IBS as very severe.
Successful low‐dose amoxycillin, metronidazole and omeprazole combination therapy in a population with a high frequency of metronidazole‐resistant Helicobacter pylori
Authors: Breuer T. , Kim J. G. , Gurer I. E. , Graham D. P. , Osato M. , Genta R. M. , Graham D. Y.
Published: November 2003

Aim:

Effective anti‐Helicobacter pylori therapies with few side‐effects are needed. We studied the effectiveness of a low‐dose combination of metronidazole, amoxycillin and omeprazole for treatment of ulcer patients in Seoul, Korea.

Methods:

Patients with gastric or duodenal ulcer received metronidazole (125 mg b.d.), amoxycillin (500 mg b.d.) and omeprazole (20 mg at bedtime) for 2 weeks. Endoscopic examinations were performed before treatment and at least 6 weeks after completion of antimicrobial therapy. H. pylori status was confirmed by histological examination of two gastric biopsies using the Genta stain.

Results:

Seventy‐nine patients (64 men, 15 women, mean age 46 years) with peptic ulcer were enrolled. H. pylori infection was cured in 56 (71%, 95% CI: 60–81%). The cure rate in non‐smokers was significantly higher than in smokers (88% vs. 65%, P=0.035). Twelve pre‐treatment isolates were available and metronidazole resistance was noted in all; H. pylori infection was cured in 10. Thirty‐six patients cured of H. pylori have been followed for 1 year (mean of 361 days) and 2 cases became reinfected (5.5%, 95% CI: 1–18%).

Conclusions:

The low‐dose combination of metronidazole, amoxycillin and omeprazole was effective even in the face of metronidazole resistance. Recurrence of H. pylori infection is infrequent even in countries with a high prevalence of H. pylori infection.
Gastric emptying of semisolid meal unaltered by 3 days' administration of a sustained‐release preparation of the nitric oxide donor, isosorbide dinitrate
Authors: Stacher G. , Bergmann H. , Stacher‐Janotta G. , Schneider C. , Steinringer H.
Published: November 2003

Background:

Evidence has accumulated that nitric oxide is involved in the regulation of gastrointestinal motor activity. We investigated whether nitric oxide derived from a sustained‐release isosorbide dinitrate (Cedocard retard) had an effect on gastric emptying and on subjective feelings.

Methods:

Twelve healthy males aged 23–32 years received at weekly intervals, for 3 days twice daily, either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate, or placebo, under random double‐blind conditions. After a further dose on day 4, subjects ate a 1168 kJ semisolid meal, the emptying of which was recorded scintigraphically for 50 min.

Results:

Neither dosage of isosorbide dinitrate had an effect on emptying which differed from the effect of placebo and the effects of the two dosages were the same. The radioactivity remaining in the stomach 50 min postprandially was 68.5% ± 4.5 S.E.M. after placebo, 65.4 ± 5.6% after 20 mg isosorbide dinitrate and 66.1 ± 4.4% after 40 mg isosorbide dinitrate. With 40 mg isosorbide dinitrate, all 12 subjects complained of persistent headache, whereas only slight headache was reported by 7 subjects on 20 mg isosorbide dinitrate and by 1 subject on placebo.

Conclusion:

Twenty and 40 mg doses of sustained‐release isosorbide dinitrate twice daily had no effect on the gastric emptying of a semisolid meal, but dose‐dependently induced headaches.
Helicobacter pylori eradication using a 7‐day regimen of low‐dose clarithromycin, lansoprazole and amoxycillin
Authors: Lim A. G. , Walker C. , Chambers S. , Gould S. R.
Published: November 2003

Aim:

To evaluate the efficacy of a 7‐day regimen of clarithromycin 250 mg b.d., amoxycillin 1 g b.d., and lansoprazole 30 mg b.d. as a treatment for Helicobacter pylori infection.

Methods:

H. pylori status of dyspeptic patients was assessed by 13C‐urea breath test and at endoscopy by histology, culture and rapid urease testing of gastric biopsies. Fifty‐one H. pylori‐positive patients were treated with the above regimen. H. pylori status was reassessed by 13C ‐urea breath test not less than 28 days after completing treatment. Adverse events and compliance were evaluated.

Results:

On an intention‐to‐treat basis, H. pylori infection was cured in 77% (95% CI: 65–88%) of patients. Minor side‐effects including diarrhoea, nausea and taste disturbance were reported by 64% of patients. Ninety‐five per cent of patients consumed > 95% of tablets. Metronidazole resistance was 29% but all cultures were sensitive to amoxycillin and clarithromycin.

Conclusion:

This 7‐day treatment with low‐dose clarithromycin was moderately effective in curing H. pylori infection. Although compliance was excellent, there was a high frequency of minor adverse events.
Colonic spread of three rectally administered mesalazine (Pentasa) dosage forms in healthy volunteers as assessed by gamma scintigraphy
Authors: BROWN J. , HAINES S. , WILDING I. R.
Published: November 2003

Background: Rectal administration of enemas, foams and suppositories is the most efficient method of delivering locally‐acting drugs to the distal colon, sigmoid colon and rectum. Healthy volunteers provide an effective population to compare different formulations for rectal drug delivery. However, there is still only limited comparative information available on the dispersion of such dosage forms in human subjects. Therefore, the objective of this scintigraphic study was to compare colonic spread of an enema, a rectal foam and a suppository formulation in healthy volunteers.

Methods: This was a randomized, crossover study in eight healthy male volunteers. Each received Pentasa rectal formulations as either a 100 mL suspension enema (1 g mesalazine), one actuation of a non‐CFC propellant rectal foam (1 g mesalazine in 5 mL concentrate, expanding to 40 mL on actuation), or one suppository (1 g mesalazine) on three separate occasions. The spread of the radiolabelled formulations was assessed over a 4‐h period by gamma scintigraphy.

Results: The formulations were retained by all subjects for the whole of the 4‐h imaging period. The enema spread to the splenic flexure in 7 out of 8 subjects, but was retained in the rectum and sigmoid colon in one individual. The foam spread as far as the descending colon in four subjects. In the remaining individuals the foam was retained in the rectum and sigmoid colon. The spread of the suppository was limited and confined to the rectum.

Conclusions: The findings of this study are consistent with previous research and support the intended clinical uses of the enema, foam and suppository formulations to treat distal ulcerative colitis, proctosigmoiditis and proctitis, respectively. The results highlight the potential of gamma scintigraphy in providing in vivo `proof of concept' data to help verify the targeting of pharmaceutical products to their intended site of delivery.
Omeprazole is more effective than cimetidine for the relief of all grades of gastro‐oesophageal reflux disease‐associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis
Authors: BATE C. M. , GREEN J. R. B. , AXON A. T. R. , MURRAY F. E. , TILDESLEY G. , EMMAS C. E. , TAYLOR M. D.
Published: November 2003

Background: Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis, but excluded the substantial group of gastro‐oesophageal reflux disease (GERD) patients with reflux symptoms but without endoscopic abnormality. This prospective, randomized, double‐blind study compared omeprazole and cimetidine in the treatment of GERD‐associated heartburn both in patients with symptomatic non‐ulcerative oesophagitis and in those with heartburn but without oesophagitis.

Methods: A total of 221 patients with heartburn and oesophageal mucosa grade 0 (normal, n = 51), 1 (no macroscopic erosions, n = 52), 2 (isolated erosions, n = 97) or 3 (confluent erosions, n = 21) were randomized to receive double‐blind either omeprazole 20 mg daily or cimetidine 400 mg q.d.s. for a period of 4 weeks. Those still symptomatic after 4 weeks of treatment received omeprazole 20 mg daily for a further 4 weeks.

Results: There was no correlation between severity of heartburn and endoscopic grade at entry (correlation coefficient = 0.196). After 4 weeks of treatment, the proportion of patients in whom heartburn was controlled (no more than mild symptoms on no more than 1 day in the previous 7) on omeprazole (66%; 74/112) was more than double that on cimetidine (31%; 34/109) (P < 0.0001). There was no significant difference between the relief of heartburn in the 47% of patients without unequivocal oesophagitis (endoscopic grade 0 or 1) and in the 53% of patients with erosive oesophagitis (grade 2 or 3) (P = 0.31). Only treatment with omeprazole (P < 0.0001) and lower severity of heartburn at entry (P < 0.01) were significant in predicting heartburn relief. Amongst those patients requiring an additional 4 weeks of treatment with omeprazole, 67% (54/81) reported that their heartburn was controlled after 8 weeks of treatment.

Conclusion: We conclude that omeprazole is superior to cimetidine for the relief of all grades of heartburn in GERD, whether or not the patient has unequivocal endoscopic oesophagitis.
A new 1‐week therapy for Helicobacter pylori eradication: rani‐ tidine bismuth citrate plus two antibiotics
Authors: SAVARINO V. , MANSI C. , MELE M. R. , BISSO G. , MELA G. S. , SAGGIORO A. , CAROLI M. , VIGNERI S. , TERMINI R. , OLIVIERI A. , TOSATTO R , CELLE G.
Published: November 2003

Background: One‐week triple regimens are currently the most recommended therapy for the eradication of Helicobacter pylori. No previous study has evaluated the efficacy of a short‐term regimen combining ranitidine bismuth citrate with two antibiotics.

Methods: Seventy‐two consecutive H. pylori‐positive dyspeptic patients were recruited for this randomized, three‐centre, open, parallel‐group study. They were subdivided into two groups receiving either ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (group A) or ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s (group B) for 1 week. H. pylori infection was assessed by CLO‐test and histology on both antral and corpus biopsies before and at least 4 weeks after the end of therapy. The bacterium was considered eradicated when both tests were negative. Eradication rates and the number of side‐effects were evaluated in each group. The Chi‐squared test was used for statistical analysis.

Results: One patient with only CLO‐test positivity was erroneously randomized to group B and four patients dropped out of the study (two in group A and two in group B), mainly because they refused the second endoscopy. In group A, H. pylori was eradicated in 31 of 36 patients intention‐to‐treat = 86%; 95% CI = 71–95% and (per protocol 31/34 = 91%; 95% CI = 76–98%). Side‐effects occurred in 10 patients (27%) and they were generally mild. In group B, H. pylori was eradicated in 29 of 35 patients (intention‐to‐treat = 83%; 95% CI = 66–93%; and per protocol 29/33 = 88%; 95% CI = 72–97%). Seven patients (20%) complained of modest side‐effects. There was no significant difference between the two treatment arms (P = N.S.); no severe adverse events occurred and none of the patients was withdrawn from the study because of them.

Conclusions: The co‐administration of ranitidine bismuth citrate plus clarithromycin at low dosage and metronidazole in twice daily doses for 1 week is a short, effective and well‐tolerated regimen for the eradication of H. pylori. These findings should provide the impetus for large‐scale investigations.
Three‐day intravenous triple therapy is not effective for the eradication of Helicobacter pyloriinfection in patients with bleeding gastro‐duodenal ulcer
Authors: Romero‐Gómez M. , Martínez‐Delgado C. , Hergueta P. , Navarro J.‐M. , Garrido‐Serrano A. , Santos O. , Montojo C.
Published: November 2003

Aim : To test the efficacy of an ultra‐short intravenous triple therapy against Helicobacter pylori infection in patients with bleeding peptic ulcer against standard oral 1‐week triple therapy in a randomised, double‐blind prospective trial.

Methods: Patients : (n = 75) with haemorrhagic peptic ulcer and H. pylori infection were randomised into: an Intravenous Group to receive omeprazole, clarithromycin and amoxicillin–clavulanic acid intravenously b.d. for 3 days followed by 7 days of oral omeprazole plus placebo of clarithromycin and amoxicillin; an Oral Group to receive intravenous omeprazole plus placebo of clarithromycin and amoxicillin–clavulanic acid followed by 7 days of oral omeprazole, clarithromycin and amoxicillin b.d. Gastric biopsies were obtained for urease test. A 13C‐urea breath test was performed to check for H. pylori eradication.

Results : Intention‐to‐treat eradication was 50% (19/38) in the Intravenous Group and 78% (29/37) in the Oral Group (odds ratio 3.63; 95% confidence interval 1.32–9.94; P < 0.01; number needed to treat (NNT) = 4). Per protocol eradication was 50% (14/28) in the Intravenous Group and 86% (24/28) in the Oral Group (P < 0.005). There were no statistically significant differences in adverse events between the two treatment groups.

Conclusions : An ultra‐short, 3‐day, intravenous, triple therapy containing omeprazole, clarithromycin and amoxicillin–clavulanic acid cannot be recommended as an effective eradication regimen for H. pylori infection related to haemorrhagic gastro‐duodenal ulcer.
Myelodysplastic syndromes in childhood: report of 49 patients from a French multicentre study
Authors: Bader‐Meunier Brigitte , Miélot Françoise , Tchernia Gil , Buisine Jacqueline , Delsol Georges , Duchayne Eliane , Lemerle Sophie , Leverger Guy , De Lumley Lionel , Manel Anne‐Marie , Nathanson Mireille , Plantaz Dominique , Robert Alain , Schaison Gérard , Sommelet DaniÈle , Vilmer Etienne
Published: November 2003

We describe the clinical, cytological and cytogenetic features of 49 cases of myelodysplastic syndromes (MDS) in childhood. Three children had received prior cytotoxic treatment (group 1); all of these had cytogenetic abnormalities and died shortly after diagnosis. 22 children had constitutional anomalies (group 2). The remaining 24 MDS were considered as ‘primary’ (group 3). Hypoplastic marrow was found in nine cases, and only 53% of the MDS fitted the adult FAB classification. Transformation to AML occurred in 11 cases, development of aplastic anaemia in three cases, and spontaneous remission in one case each of RA and RAEB. Differences were observed between groups 2 and 3 in terms of mean age at diagnosis (11.1 months v 5 years), rate of cytogenetic anomalies (15% v 38%) and rate of progression towards acute leukaemia (13% v 29%). In group 2, all the four girls studied exhibited a polyclonal pattern of X‐inactivation, which suggests that MDS may be only the haematological expression of an embryological defect with different target tissues.

This study suggests that some MDS in childhood can exhibit particular features such as congenital anomalies associated with MDS, bone marrow hypoplasia, polyclonality, and spontaneous remission. It emphasizes that the FAB classification is not adequate for children and addresses the question of whether these MDS are always malignant diseases.
Anti‐CD30 (BER‐H2) immunotoxins containing the type‐1 ribosome‐inactivating proteins momordin and PAP‐S (pokeweed antiviral protein from seeds) display powerful antitumour activity against CD30+ tumour cells in vitro and in SCID mice
Authors: Terenzi Adelmo , Bolognesi Andrea , Pasqualucci Laura , Flenghi Leonardo , Pileri Stefano , Stein Harald , Kadin Marshall , Bigerna Barbara , Polito Letizia , Tazzari Pier Luigi , Martelli Massimo F. , Stirpe Fiorenzo , Falini Brunangelo
Published: November 2003

The anti‐CD30 immunotoxin (IT) Ber‐H2/saporin is effective in patients with refractory Hodgkin’s disease. However, responses are short and partial, one of the main reasons being the inability to repeat IT doses because of formation of human antibodies against the murine antibody and/or the toxin. To overcome this problem, we constructed two new anti‐CD30 ITs by covalently linking the mouse monoclonal antibody Ber‐H2 to the type 1 ribosome‐inactivating proteins (RIPs) momordin (MOM) and pokeweed antiviral protein from seeds (PAP‐S), which do not cross‐react with each other or with saporin. Both ITs inhibited protein synthesis by Hodgkin’s disease and anaplastic large‐cell lymphoma (ALCL)‐derived CD30+ target cell lines with a very high efficiency (IC50 ranging from < 5 × 10−13 m to 2.75 × 10−11m, as RIP). In a SCID mouse model of xenografted CD30+ human ALCL, a 3 d treatment with non‐toxic doses of Ber‐H2/MOM (50% LD50), started 24 h after transplantation, prevented tumour development in about 40% of the animals and significantly delayed tumour growth rate in the others. Main toxicity signs in mice and rabbits were a dose‐related increase of serum transaminases (AST and ALT) and creatine phosphokinase (CPK). LD50 (as RIP) in Swiss mice was 7 mg/kg for Ber‐H2/MOM and 0.45 mg/kg for Ber‐H2/PAP‐S. Sequential administration of two anti‐CD30 ITs (Ber‐H2/MOM and Ber‐H2/saporin) was well tolerated and did not result in formation of antibodies cross‐reacting with the two plant toxins. The results presented in this paper suggest that, in the future, sequential administration of anti‐CD30 humanized antibodies linked to antigenically distinct type 1 RIPs (saporin, MOM, PAP‐S) should be feasible.
A whole blood assay for platelet HPA1 (PLA1) phenotyping applicable to large‐scale screening
Authors: Bessos Hagop , Mirza Shabana , McGill Adam , Williamson Lorna M. , Hadfield Ruth , Murphy William G.
Published: November 2003

Any future programme of antenatal screening of pregnancies for risk of neonatal alloimmune thrombocytopenia will have as a major requirement the availability of cost‐effective assays which can be applied to large numbers of samples. To address this, we developed a competitive ELISA to type whole blood samples for the platelet alloantigen HPA1a, based on the use of purified glycoprotein (GP) IIb/IIIa from donors of known HPA1 genotype along with well characterized anti‐HPA1a antiserum. Microtitre plates were coated with purified GPIIb/IIIa from donors of genotype HPA1a1a/3a3a. Anticoagulated whole blood of unknown HPA1 type was added to each well followed by anti‐HPA1a. Residual antiHPA1a antibody not bound to the platelets in the test blood sample, bound to the immobilized HPA1a on the plate and was quantitated by standard ELISA. 475 blood donors were typed by the assay and the results compared in a blinded comparison with typing in the Capture‐Ptm assay. Concordance was 100% (468 HPA1a positive and seven HPA1a negative). The HPA1 type of control samples stored as whole blood could be discriminated by this assay for up to 23 d of storage at 4°C. This assay should be suitable for use in large‐scale population screening programmes.
A case of ovarian carcinoma with production of granulocyte colony‐stimulating factor
Authors: Sudo Satoko , Yamada Hideto , Kikuchi Ken , Sumie Akihiko , Yamashita Yoichiro , Tumura Norihiko , Kawaguchi Isao , Fujimoto Seiichiro , Kato Atushi , Yamaguchi Jun
Published: November 2003

A 60‐year‐old female with ovarian carcinoma showed marked leucocytosis. After exploratory laparotomy she had received carboplatin‐based chemotherapy, but she died of respiratory failure. In this case the immunohistochemical examination of the tumour cells showed partial‐positive staining for anti‐G‐CSF monoclonal antibody in addition to the elevation of the serum G‐CSF concentration. This case is the first report of an ovarian carcinoma producing G‐CSF.
The thromboxane mimetic, U‐46619, induces the aggregation of fish thrombocytes
Authors: Hill Darryl , Rowley Andrew
Published: November 2003

Fish blood contains nucleated cells termed thrombocytes which are thought to be functionally analogous to mammalian platelets. The present study was undertaken to assess the aggregatory response of peripheral blood thrombocytes from the rainbow trout, Oncorhynchus mykiss. Incubation of Percoll density gradient purified thrombocytes with the thromboxane A2 mimetic, U‐46619 (0.03–10 μM), alone or in the presence of human or trout fibrinogen, elicited a dose‐dependent aggregatory response. A greater amount of aggregation was observed in the presence of fish, rather than human, fibrinogen (e.g. c 55% compared with 15% maximal aggregation respectively). This response was inhibited by pre‐incubation of thrombocytes with the specific thromboxane A2 receptor antagonist, GR32191 (0.01–10 μM) with an IC50 value of 5.7 μM. Ultrastructural and aggregometry studies of thrombocyte aggregation at various time periods (1–12 min) after incubation with U‐46619 (0.5 μM) revealed clear differences between the amount and dynamics of thrombocyte clumping in the presence of human, compared with trout, fibrinogen (final concentration 400 μg ml–1). Thrombocytes rapidly underwent shape change and aggregation after only 1 min incubation without the initial involvement of any other cell types. The maximum degree of aggregation was achieved after 4–8 min with larger aggregates formed in the presence of trout compared than human fibrinogen. Ultrastructurally, the thrombocytes in these aggregates displayed a number of changes compared with non‐stimulated cells, including increased pseudopodial activity, a more pronounced canalicular system and condensation of the nuclear heterochromatin. After 12 min incubation the clumps of thrombocytes showed progressive disaggregatory behaviour, with some cells reverting back to their normal in vivo appearance. Neutrophilic granulocytes, present as contaminants in the thrombocyte suspensions, were occasionally found attached to the thrombocyte aggregates, perhaps suggesting a specific interaction similar to that occurring in mammals. Finally, and also of some significance, was the finding that trout thrombocytes exhibit phagocytic activity in vitro towards cell debris and contaminating bacteria, indicating that this cell type may possess both haemostatic and immunological capacities.
The use of IgH fingerprinting and ASO‐dependent PCR for the investigation of residual disease (MRD) in ALL
Authors: Chim James C. S. , Coyle Luke A. , Yaxley John C. , Cole‐Sinclair Merrole F. , Cannell Paul K. , Hoffbrand Victor A. , Foroni Letizia
Published: November 2003

In acute lymphoblastic leukaemia (ALL), investigation of minimal residual disease by conventional morphology and immunology fails to detect levels of residual disease of <1 leukaemic in 10–100 normal cells. The use of polymerase chain reaction (PCR) to exploit the diversity of the complementarity determining region (CDR) and immunoglobulin variable heavy chain (VH) family specific usage has greatly improved the sensitivity up to one leukaemic cell in 105–106 normal bone marrow cells. Here we report on a prospective study of 14 patients with ALL of B‐cell lineage by using a combined PCR approach which estimates levels of disease between 1:103 and 1:105. The sequential use of allele‐specific oligoprimer (ASO) independent tests (using framework 1, FR1 and 3, FR3 primers with a JH consensus primer, sensivity up to 1:5×103) and ASO‐dependent PCR (sensitivity up to 1:105) assays were applied to 64 bone marrow (BM) follow‐up samples in a sequential array of tests.

Results presented in this study indicate high concordance of MRD among different tests for samples with level of residual disease >1:5×103. Consequently, samples positive by the FR1 and FR3 fingerprinting tests were confirmed by the more sensitive ASO‐dependent tests, as expected. However, the ASO‐dependent assays revealed levels of disease undetected by the FR1 and FR3 test. Although a higher level of sensitivity is provided by the ASO‐dependent tests, the FR1 and FR3 fingerprinting tests allow MRD investigation in patients with oligoclonal B cell proliferations, CDR3 region of size <15bp or with ASO primers unsuitable for PCR investigation on technical grounds (i.e. background signal). If a sequential order of investigation from less (e.g. FR1 and FR3 fingerprinting) to more sensitive tests (ASO‐dependent) is applied, an indirect estimate of MRD is obtained for patients with level of disease <1:103
Blood clonal B‐cell excess in patients with monoclonal gammopathy of undetermined significance (MGUS): association with malignant transformation
Authors: Isaksson Erika , Björkholm Magnus , Holm Göran , Johansson Bo , Nilsson Bo , Mellstedt HÅkan , ÖSterborg Anders
Published: November 2003

Fifty‐seven patients with monoclonal gammopathy of undetermined significance (MGUS) were analysed for the presence of blood clonal B‐cell excess (CBE), defined as a lymphocyte surface membrane κ/λ light chain ratio outside the normal range (> 3.5 in κ‐type MGUS and <0.9 in λ‐type MGUS). 15 patients (26%) had a CBE. The patients were followed for a median time of 8.4 years (range 0.5–20.2). Eight of the 15 CBE+ MGUS patients (53%) developed a B‐cell malignancy as compared to 7/42 patients (17%) in the CBE group and the difference in event‐free (malignancy‐free) observation time was statistically significant (P = 0.01). Cox's regression analysis showed that the presence of CBE was the most powerful predictor of progression to a malignant disease. Two patients with a normal κ/λ ratio at first test were analysed repeatedly during follow‐up. Subsequently, a CBE appeared which gradually increased in size preceding the clinical diagnosis of a malignant disease.
Identification of early plasma cells in peripheral blood and their clinical significance
Authors: Harada Yuka , Kawano Michio M. , Huang Naihui , Mahmoud Maged S. , Lisukov Igor A. , Mihara Keiichiro , Tsujimoto Takako , Kuramoto Atsushi
Published: November 2003

In the peripheral blood (PB) we detected so‐called early plasma cells that might already be committed to entering the bone marrow (BM). By two‐colour staining with FITC–anti‐CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal centre (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38+++)), and their phenotype was CD38++ CD19+ CD10− CD20− CD21+ CD24− CD39+ CD5− VLA‐4+ VLA‐5− MPC‐1− without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.