bluuebunny/crossref_metadata_2025 huggingface dataset:
Passage through bird guts causes interspecific differences in seed germination characteristics
Authors: Traveset A. , Riera N. , Mas R. E.
Published: March 2003

Seed germination characteristics are often modified after seeds are ingested by frugivores. Factors that are intrinsic either to the plant or to the frugivore’s digestive tract are responsible for the great variation observed in germination response.

 Our objectives were to determine whether and how the seed germination patterns of five common western Mediterranean plant species are affected by seed passage through the guts of their major dispersers, and to elucidate the mechanism by which such patterns are changed.

 We used captive birds (Turdus merula and Sylvia melanocephala) to obtain ingested seeds and compared their germination rate (speed) and germinability (final percent germination) with those of controls (uningested, pulp‐removed seeds), controlling for seed age, size and source. Germination was monitored for 2 years in an experimental garden. We evaluated the possible changes in seed traits after ingestion by measuring weight and coat thickness, and by observing seed coat sculpture.

 Rate of seed germination, but not germinability, changed in all species after gut treatment. The greatest effect was in Osyris, in which germination was much enhanced. A great acceleration of germination, which is likely to translate into a seedling size advantage, was also found in Asparagus. In the other three species tested, germination was slower for ingested than for control seeds.

 For Rubus and Rubia seeds, we found a different germination response depending upon the frugivore species tested. A different degree of seed coat scarification caused by differences in gut retention time, chemical and/or mechanical abrasion probably account for such responses.

 In three of the species (Osyris, Rubia and Phillyrea), seed weight decreased after gut treatment. Such weight loss was not caused by any change in coat thickness, but may have been because of the scarification and consequent alteration of the seed coat structure.

 The five Mediterranean species studied germinate when rains are most likely to fall (mostly autumn and spring). The different speed of germination promoted by gut treatment within frugivores may increase the probability that seeds can recruit successfully at a given time and in a given place.

 This study suggests that frugivores contribute to the heterogeneity in germination characteristics not only within plant populations but also within plant communities, each frugivore species having a particular effect on the seeds of each plant consumed.
Host recognition in a desert mistletoe: early stages of development are influenced by substrate and host origin
Authors: Rödl T. , Ward D.
Published: March 2003

In many root parasites, chemical substances from the host are necessary for the successful initiation of germination and holdfast formation, and are the basis for host recognition and localization within the rhizosphere. In contrast, bird‐dispersed mistletoe seeds have no need for the chemical localization of a host, and possible mechanisms of host recognition are poorly understood. Many studies claim that mistletoes germinate readily in the absence of a host and independent of the substrate.

  In this study, the possible occurrence of substrate dependence and host recognition in mistletoes during the establishment ofPlicosepalus acaciaeZucc. seeds onAcacia raddianaSavi was tested experimentally.

  In a laboratory experiment, no influence of substrate on germination could be found, but a significantly higher proportion of the germinated seeds developed a holdfast on natural (bark) substrate than on artificial (plastic) substrate. Moreover, the origin of the bark had a significant influence on holdfast formation frequency.

  Host influence was additionally tested in a reciprocal transplant experiment in two field sites with genetically different populations of the same host species. Those mistletoes of local origin germinated significantly more often than their non‐local counterparts.

  These results suggest the existence of interactions between mistletoe seed and host branch on the basis of chemical cues that are active at an early stage of seedling development and are host‐specific at the level of populations.
No significant relationship exists between seedling relative growth rate under nutrient limitation and potential tissue toxicity
Authors: Almeida‐Cortez J. S. , Shipley W.
Published: March 2003

We asked two questions in this study: (i) is there is there a negative correlation between relative growth rate (RGR) among 19 species of herbaceous Asteraceae grown under nutrient limitation and potential tissue toxicity; and (ii) is the degree of toxicity of these species different than those measured in a previous study, in which the same species were grown under non‐limiting conditions?

 In the present study we grew 19 of the same species as previously in hydroponic sand culture for which the growth rate was limited by nutrient supply, and compared RGR and potential tissue toxicity due to secondary compounds. Under such conditions, RGR was reduced by 25%; specific leaf area was reduced by 32%; root : shoot ratios were increased by 320%; leaf nitrogen content was reduced by 69%; and potential toxicity was decreased by 46%.

 Although nutrient limitation clearly decreased both RGR and potential toxicity, we found no interspecific correlation between RGR and toxicity.

 We conclude that there was no detectable trade‐off between RGR and potential toxicity due to secondary compounds.
Men with acromegaly need higher doses of octreotide than women
Authors: Edén Engström Britt , Burman Pia , Karlsson F. Anders
Published: March 2003

objectiveTo investigate the effect of gender on the response of GH to short‐acting octreotide in patients with acromegaly, and on the GH and IGF‐1 levels during long‐term treatment with a slow‐release formulation of octreotide.

study design and patientsTwenty‐one men (mean age 54 years; range 26–78) and 15 women (mean age 54 years; range 22–74) with acromegaly were treated with subcutaneous injections of 100 µg short‐acting octreotide twice daily. Serum samples for GH were taken before start of treatment, in the morning prior to the injection, and 1, 3, 5 and 7 h after the injection. Thirteen men (mean age 56 years; range 34–78) and 12 women (mean age 64 years; range 28–81) with acromegaly were switched from ongoing treatment with short‐acting octreotide to injections of the slow‐release formulation. A 4‐h GH‐profile and morning IGF‐1 were taken at start and after 3, 9, 15 and 21 months of treatment.

resultsSubcutaneous injections of 100 µg octreotide reduced the mean level of GH during a 7‐h period to a similar extent in men and women compared to the GH levels prior to the injections. During long‐term treatment with similar doses of the depot formulation of octreotide, the mean IGF‐1 level remained significantly higher in the men than in the women, whereas there were no differences in the mean GH levels between the two groups.

conclusionsThe responses to short‐ and long‐acting octreotide illustrate an effect of gender, due to different sensitivity to GH in the periphery. Furthermore, the results show that in the treatment of acromegaly, men will need higher doses of octreotide than women to normalize IGF‐1.
The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV‐1‐infected individuals
Authors: Koks C. H. W. , Crommentuyn K. M. L. , Hoetelmans R. M. W. , Burger D. M. , Koopmans P. P. , Mathôt R. A. A. , Mulder J. W. , Meenhorst P. L. , Beijnen J. H.
Published: March 2003

Aims  To study the effect of fluconazole on the steady‐state pharmacokinetics of the protease inhibitors ritonavir and saquinavir in HIV‐1‐infected patients.

Methods  Five subjects treated with saquinavir and three with ritonavir received the protease inhibitor alone (saquinavir 1200 mg three times daily, ritonavir 600 mg twice daily) on day 1, and the same protease inhibitor in combination with fluconazole (400 mg on day 2 and 200 mg on days 3 to 8). Pharmacokinetic parameters were determined on days 1 and 8.

Results  In the saquinavir group, the median increase in the area under the plasma concentration vs time curve was 50% from 1800 µg l−1 h to 2700 µg l−1 h (P = 0.04, median increase: 900 µg l−1 h; 2.5 and 97.5 percentile: 500–1300), and 56% for the peak concentration in plasma (from 550 to 870 µg l−1, P = 0.04; median increase: 320 µg l−1 h, 2.5 and 97.5 percentile: 60–450 µg l−1). In the ritonavir group, there were no detectable changes in the pharmacokinetic parameters on addition of fluconazole.

Conclusions  Because of the favourable safety profile of saquinavir, dose adjustments are probably not necessary with concomitant use of fluconazole, as is the case for ritonavir.
Evidence of impaired cisapride metabolism in neonates
Authors: Tréluyer Jean‐Marc , Rey E , Sonnier M. , Pons G , Cresteil T
Published: March 2003

Aims  Cisapride has been shown to cause QTc prolongation in neonates in the absence of any of the known risk factors ascribed to children or adults (excessive dosage, drug–drug interactions). Our hypothesis was that the early neonatal liver may show defective elimination of cisapride resulting in its accumulation in the immature child. Owing to the difficulties associated with in vivo pharmacokinetic studies in a paediatric population, we explored the in vitro metabolism of cisapride by human cytochrome P450.

Methods 
Experiments were conducted with recombinant CYPs stably expressed in mammalian cells and with liver microsomes obtained from human foetuses, neonates, infants and adults. Cisapride metabolites were measured by high performance liquid chromatography.

Results
 The rate of biotransformation of cisapride was greater by recombinant CYP3A4 than by CYP3A7 (0.77 ± 0.5 and 0.01 ± 0.01 nmol metabolites formed in 24 h, respectively), whereas CYP1A1, 1A2, 2C8, 2C9 and 3A5 showed no activity. Norcisapride formation was significantly correlated with testosterone 6β‐hydroxylation, a CYP3A4 catalysed reaction (r = 0.71, P = 0.03) but not with the 16‐hydroxylation of dehydroepiandrosterone, catalysed by CYP3A7 (r = 0.30, P = 0.29) by microsomes from a panel of livers from foetuses, neonates and infants. No or negligible cisapride metabolic activity was observed in microsomes from either foetuses or neonates aged less than 7 days, which contained mostly CYP3A7 and no CYP3A4. The metabolism of cisapride steadily increased after the first week of life in parallel with CYP3A4 activity to reach levels exceeding adult values.

Conclusions

 The low content of CYP3A4 in the human neonatal liver appears to be responsible for its inability to oxidize cisapride and could explain its accumulation in plasma leading to the cases of QTc prolongation reported in this paediatric population.
Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers
Authors: Kees F. , Färber L. , Bucher M. , Mair G. , Mörike K. , Grobecker H.
Published: March 2003

Aims  To establish the bioavailability of tropisetron (5 mg) administered orally as capsule compared with 2 mg given intravenously.

Methods  Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropisetron (2 mg) separated by a wash‐out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated.

Results  The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml−1, tmax 2.6 h, t1/2 5.7 h and AUC(0,∞) 32.9 ng ml −1 h. After intravenous administration initial plasma concentration was 15.1 ng ml−1, t1/2 5.6 h, AUC(0,∞) 20.7 ng ml −1 h, V 678 l and CL 1800 ml min−1. An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27–0.99) of oral tropisetron.

Conclusions  Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.
Randomized cross‐over clinical trial to study potential pharmacokinetic interactions between cisplatin or carboplatin and etoposide
Authors: Thomas Huw D. , Porter David J. , Bartelink Imke , Nobbs Joy R. , Cole Michael , Elliott Suzie , Newell David R. , Calvert A. Hilary , Highley Martin , Boddy Alan V.
Published: March 2003

Aims  Cisplatin and carboplatin are often used in combination with etoposide. In a randomized cross‐over study, the potential interaction between the two platinum drugs and the metabolism of etoposide was explored. In vitro investigations using human liver microsomes were also performed.

Methods  Etoposide was administered to 15 patients over 3 days, with the platinum drug administered on day 2. The alternate platinum drug was administered on the second course. The pharmacokinetics of etoposide were determined on all 3 days of each cycle. The effect of platinum drugs on etoposide metabolism by human liver enzymes was explored in vitro.

Results  Neither cisplatin nor carboplatin coadministration affected the pharmacokinetics of etoposide during cycle 1. When carboplatin was administered on course 2, etoposide AUC was 8% higher on day 2 compared with day 1 or day 3 (for day 2 vs day 3, 95% CI: −0.72, −0.08 mg ml−1 min). In contrast, cisplatin on course 2 increased the AUC of etoposide (28%) on day 3 (day 3 vs day 1, 95% CI: 0.67, 2.09 mg ml−1 min), with no effect on day 2. In vitro carboplatin and cisplatin (10–100 µm) inhibited the metabolism of etoposide, if rat liver microsomes were preincubated (30 min) with NADPH and the platinum complexes. With human liver microsomes a small effect on etoposide metabolism, but not on catechol formation, was observed.

Conclusions  The interaction between etoposide and platinum drugs is small and, given the pharmacokinetic variability seen with etoposide, the clinical impact is unlikely to be significant.
Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent
Authors: Hutchinson P. J. , . O'Connell M. T , Coles J. P. , Chatfield D. A. , Coleman M. R. , Al‐Rawi P. G. , Kett‐White C. R. , Gupta A. K. , Menon D. K. , Boniface S. J. , Heazell M. , Kirkpatrick P. J. , Pickard J. D.
Published: March 2003

Aims  Promising pre‐clinical results from laboratory studies of neuro‐protective drugs for the treatment of patients with stroke and head injury have not been translated into benefit during clinical trials. The objective of the study was to assess the feasibility of administrating a potential neuro‐protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury in order to determine the effect of the agent on surrogate endpoints and penetration into the brain.

Methods  Multimodality monitoring including cerebral and peripheral microdialysis was applied to five head‐injured patients on the neuro‐intensive care unit. Chlormethiazole (0.8%) was administered as a rapid (10 ml min−1) intravenous loading infusion for 5 min followed by a slow (1 ml min−1) continuous infusion for 60 min. The following parameters were monitored: heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, continuous arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial temperature, cerebral tissue oxygen pressure, cerebral tissue carbon dioxide pressure, cerebral pH, cerebral temperature, electroencephalograph (EEG), bi‐spectral index, plasma glucose, plasma chlormethiazole, and cerebral and peripheral microdialysis assay for chlormethiazole, glucose, lactate, pyruvate and amino acids.

Results  Despite achieving adequate plasma concentrations, chlormethiazole was not detected in the peripheral or cerebral microdialysis samples. The drug was well tolerated and did not induce hypotension, hyperglycaemia or withdrawal seizures. The drug did not change the values of the physiological or chemical parameters including levels of GABA, lactate/pyruvate ratio and glutamate. The drug did, however, induce EEG changes, including burst suppression in two patients.

Conclusions  Chlormethiazole can be safely given to ventilated patients with severe head injury. There was no evidence of hypotension or withdrawal seizures. Combining a pilot clinical study of a neuro‐protective agent with multimodality monitoring is feasible and, despite the lack of effect on physiological and chemical parameters in this study, may be a useful adjunct to the development of neuro‐protective drugs in the future. Further investigation of the capability of microdialysis in this setting is required. By investigating the effect of a drug on surrogate end‐points, it may be possible to identify promising agents from small pilot clinical studies before embarking on large phase III clinical trials.
Dose–response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate
Authors: Fowler Stephen J. , Orr Linda C. , Wilson Andrew M. , Sims Erika J. , Lipworth Brian J.
Published: March 2003

Aims  With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA‐beclomethasone dipropionate (BDP) vs HFA‐fluticasone propionate (FP).

Methods  Sixteen healthy volunteers were randomised in placebo‐controlled single blind cross‐over fashion to receive 3 weeks with HFA‐FP or HFA‐BDP, given as 1 week cumulative doubling doses (nominal ex‐valve) of 500, 1000 and 2000 µg day−1, with a 1 week placebo run‐in and wash‐out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log‐transformed to normalize their distribution.

Results
 Urine and serum cortisol were suppressed by 2000 µg FP and BDP vs placebo and by 1000 µg BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 µg BDP vs 1000 µg FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04–2.56). There were also more individual low values less than 3 nmol mmol−1 with BDP than FP at 1000 µg: n = 8/16 vs n = 2/16 (P < 0.05).

Conclusions
There was dose‐related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA‐BDP than HFA‐FP at 1000 µg. This suggests that the greater glucocorticoid potency of HFA‐FP may be offset by the greater lung bioavailability of HFA‐BDP
Hospital prescribing errors: epidemiological assessment of predictors
Authors: Fijn R. , Van den Bemt P. M. L. A. , Chow M , De Blaey C. J. , De Jong‐Van den Berg L. T. W. , Brouwers J. R. B. J.
Published: March 2003

Aims  To demonstrate an epidemiological method to assess predictors of prescribing errors.

Methods  A retrospective case‐control study, comparing prescriptions with and without errors.

Results  Only prescriber and drug characteristics were associated with errors. Prescriber characteristics were medical specialty (e.g. orthopaedics: OR: 3.4, 95% CI 2.1, 5.4) and prescriber status (e.g. verbal orders transcribed by nursing staff: OR: 2.5, 95% CI 1.8, 3.6). Drug characteristics were dosage form (e.g. inhalation devices: OR: 4.1, 95% CI 2.6, 6.6), therapeutic area (e.g. gastrointestinal tract: OR: 1.7, 95% CI 1.2, 2.4) and continuation of preadmission treatment (Yes: OR: 1.7, 95% CI 1.3, 2.3).

Conclusions Other hospitals could use our epidemiological framework to identify their own error predictors. Our findings suggest a focus on specific prescribers, dosage forms and therapeutic areas. We also found that prescriptions originating from general practitioners involved errors and therefore, these should be checked when patients are hospitalized.
Change of glycaemic status in Chinese subjects with impaired fasting glycaemia
Authors: Ko G. T. C. , Chan J. C. N. , Cockram C. S.
Published: March 2003

Aims  To examine the risk of progression to diabetes in Chinese subjects with impaired fasting glycaemia (IFG) or normal fasting glucose (NFG).

Methods  Between 1988 and 1996, 657 Hong Kong Chinese subjects underwent annual screening, using an oral glucose tolerance test, until they had developed diabetes, or until June 1997, when the data were analysed. All subjects had a risk factor associated with the development of diabetes such as a history of gestational diabetes or a family history of diabetes. The follow‐up interval for the subjects ranged from 0.87 to 8.54 years and of the 657, 319 had fasting plasma glucose levels of < 7.0 mmol/L where a fasting glucose level of ≥ 7.0 mmol/L was used to diagnose diabetes

Results  Of the 319 nondiabetic subjects, 55 had IFG and 264 had NFG. After a median follow‐up of 1.12 years (range: 0.87–8.54 years), 27 progressed to diabetes. The Kaplan‐Meier analysis of progression to diabetes showed significant differences between subjects with IFG and subjects with NFG. Using Cox regression analysis, IFG (β = 3.51, SE = 1.63, P = 0.032) and smoking (β = 3.60, SE = 1.50, P = 0.017) were found to be independently associated with progression to diabetes.

Conclusions  In Hong Kong Chinese with risk factors for glucose intolerance, IFG status is an independent risk factor for progression to diabetes.

Diabet. Med. 18, 745–748 (2001)
Sex hormones regulate the contribution of PKCε and PKA signalling in inflammatory pain in the rat
Authors: Dina Olayinka A. , Aley K. O. , Isenberg William , Messing Robert O. , Levine Jon D.
Published: March 2003

We have evaluated the contribution of differences in second messenger signalling to sex differences in inflammatory pain and its control by sex hormones. In normal male but not female rats, epinephrine‐induced mechanical hyperalgesia was antagonized by inhibitors of protein kinase Cε (PKCε), protein kinase A (PKA) and nitric oxide synthetase (NOS). Similarly, in PKCε knockout mice, a contribution of PKCε to epinephrine‐dependent mechanical hyperalgesia occurred in males only. In contrast, hyperalgesia induced by prostaglandin E2, in both females and males, was dependent on PKA and NO. In both sexes, inhibitors of mitogen‐activated protein kinase/extracellular‐signal related kinase kinase (MEK) inhibited epinephrine hyperalgesia. In gonadectomized females, the second messenger contributions to epinephrine hyperalgesia demonstrated the pattern seen in males. Administration of oestrogen to gonadectomized females fully reconstituted the phenotype of the normal female. These data demonstrate gender differences in PKCε, PKA and NO signalling in epinephrine‐induced hyperalgesia which are oestrogen dependent and appear to be exerted at the level of the β‐adrenergic receptor or the G‐protein to which it is coupled.
Cellular kinetics of an allergic‐type response in a sheep mammary gland model of inflammation
Authors: Bischof R. J , Meeusen E. N. T
Published: March 2003

Background  Tissue recruitment of eosinophils and activated lymphocytes is a characteristic feature of allergic reactions. However, little is known about the involvement of specific adhesion molecules in the traffic of leucocytes during the allergic response.

Objective  To use a sheep mammary infusion model to characterize the kinetics of cell recruitment and expression of cellular adhesion molecules and activation markers on eosinophils and lymphocytes involved in an allergic‐type response.

Methods  Mature non‐lactating ewes were primed and challenged by direct infusion of the mammary glands with nematode larvae. Using a non‐invasive method of saline infusion and ‘milking’ of the glands, large numbers of inflammatory cells were repeatedly sampled over 10 to 96 h following their migration into the mammary gland lumen, and analyzed by 2‐colour flow cytometry.

Results  Leucocyte recruitment into the mammary lumen was characterized by two separate phases involving an acute neutrophilic response at 10 h post‐challenge, followed by a dramatic reduction in neutrophils and appearance of eosinophils and activated lymphocytes. From 48 h post‐challenge, eosinophils were predominant and represented 40 to 65% of leucocytes in the mammary lavage (MAL). Increases in activated CD4+ T cells and γδ+ T cells were also observed at this time‐point. The kinetics of expression of cell surface molecules on eosinophils and lymphocytes in blood and MAL were compared during the course of the allergic‐type reaction. Adhesion molecule expression on lymphocytes was modulated following allergen challenge and an activation of MAL vs. blood lymphocytes was seen during the later stages of the allergic response. Eosinophil expression of VLA‐4 and l‐selectin was down‐regulated compared with blood at all time‐points examined. There were high levels of expression of CD11b and CD44 on eosinophils during the early compared to the late‐phase of the allergic reaction.

Conclusion  These results indicate the existence of two separate mechanisms of eosinophil recruitment during the allergic inflammatory response.
Specific immunoglobulin E and immunoglobulin G antibodies to toluene diisocyanate‐human serum albumin conjugate: useful markers for predicting long‐term prognosis in toluene diisocyanate‐induced asthma
Authors: Park H.‐S. , Lee S.‐K. , Kim H.‐Y. , Nahm D.‐H. , Kim S.‐S.
Published: March 2003

Background Our previous study reported that more than 50% of toluene diisocyanate (TDI)‐induced asthma patients had persistent asthmatic symptoms even after complete avoidance. Although specific IgE (sIgE) has been detected in a portion of patients with TDI‐asthma, a recent investigation suggests that the presence of serum specific IgG (sIgG), not sIgE, is more closely associated with positive bronchoprovocation test (BPT) results.

Objective To evaluate the possible role of sIgE and sIgG in predicting long‐term prognosis of TDI‐asthma.

Materials and methods Forty‐one TDI‐asthma patients whose diagnosis was confirmed by TDI‐BPT, and 20 unexposed healthy controls were enrolled. Both sIgE and sIgG to TDI‐human serum albumin (HSA) conjugate were detected by ELISA. All patients with persistent asthmatic symptoms took anti‐asthmatic medications during the follow‐up period (mean: 67.5 months) and were instructed to avoid exposure to TDI. Airway hyper‐responsiveness to methacholine (AHM) was monitored every year during the study period. The patients were classified into three groups according to changing patterns of AHM and asthmatic symptoms as follows: group I, no improvement with persistent asthmatic symptoms (n = 12); group II, partial improvement with persistent asthmatic symptoms (n = 13); group III, in remission (n = 16).

Results Favourable prognosis was associated with a mild degree of AHM at initial diagnosis (P < 0.05). Although there were no significant differences in the prevalence of sIgE antibody to TDI‐HSA conjugate among the three groups (P > 0.05), prevalence of sIgG in group I tended to be higher than in group II (0.05 < P < 0.1). However, the levels of sIgG were significantly higher in group I than in group II (P = 0.05), whereas levels of sIgE were significantly higher in group II than in group I (P = 0.014). No significant differences were noted in exposure duration, sex, age, atopic status, and total IgE level among the three groups (P > 0.05).

Conclusion This study confirmed that a favourable outcome is related to a mild degree of AHM and to low levels of sIgG to predict persistent asthmatic symptoms, it also suggested that the presence of high serum‐specific IgE at initial diagnosis may represent a better prognosis.
Atopy may be related to exercise‐induced bronchospasm in asthma
Authors: Koh Y. I. , Choi I. S. , Lim H.
Published: March 2003

Background Recent studies suggest that atopy may be associated with exercise‐induced bronchospasm (EIB) in asthma. However, it is not clear whether atopy is related to EIB, regardless of airway hyper‐responsiveness (AHR) to methacholine, because asthmatic subjects often show AHR to exercise and methacholine simultaneously.

Objective To investigate whether atopy is related to EIB in asthmatic subjects, independently of AHR to methacholine.

Methods Fifty‐eight male asthmatic subjects were studied. Initial spirometry was performed. Skin prick test was carried out, using 53 common allergens including mites dust antigen. Atopy score was defined as a sum of mean weal diameters to all allergens tested. Methacholine bronchial provocation testing was performed. Twenty‐four hours later, free running test was performed. Positive EIB was defined as a 15% reduction or more in FEV1 from baseline after exercise.

Results All subjects had AHR to methacholine. The degree of AHR to methacholine in asthmatics with EIB was similar to that in asthmatics without EIB. However, atopy score and skin reaction to Dermatophagoides pteronyssinus significantly increased in asthmatics with EIB compared with those without EIB (P < 0.05, respectively). Furthermore, the degree of EIB significantly correlated with atopy score in all subjects (r = 0.35, P < 0.01). This relationship was maintained even after the exclusion of EIB‐negative asthmatic subjects.

Conclusion Atopy defined as skin test reactivity may contribute to the development of EIB in asthma, independently of AHR to methacholine.
Endometrial ablation using a distensible multielectrode balloon: a long‐term follow‐up report
Authors: Jones Kevin D. , Spangler Laura , Sutton Christopher
Published: March 2003

Objective  To present long term follow up data on patients treated at The Royal Surrey County Hospital, who took part in an evaluation study of the Vesta™ system.

Study design  A prospective follow‐up study at 3.5–5 years following treatment.

Subjects and methods  Twenty‐five patients were asked to complete a questionnaire detailing their medical history since the initial Vesta™ system procedure, together with a validated pictorial blood loss assessment chart. A life table analysis of the patients enrolled into the European study was also carried out at 2 years.

Results  Of the 25 patients, a TCRE had to be carried out as a second operation in two patients because of continuing menorrhagia, and one patient had a pictorial blood loss score of >150 but did not want further treatment at 5 years. Therefore, treatment with the Vesta™ system failed to relieve the original symptoms or avoid second surgery in 3/25 (12%) of the patients in the long term. Life table analysis of the patients enrolled into the European study has demonstrated a failure rate of 11% at 2 years.

Conclusion  Our long term results suggest that the efficacy of the Vesta™ System at 2 years persists at 3.5–5 years following treatment.
HLA‐DRB1, ‐DQA1, ‐DQB1 and DPB1 susceptibility alleles in Cameroonian type 1 diabetes patients and controls
Authors: Mbanya J. C. , Sobngwi E. , Mbanya D. N. S.
Published: March 2003

It is known that certain combinations of alleles within the human leucocyte antigen (HLA) complex are associated with susceptibility or resistance to type 1 diabetes. Variable associations of DR and DQ with type 1 diabetes are documented in Caucasians but rarely in African populations; however, the role of HLA‐DP genes in type 1 diabetes remains uncertain. In order to investigate the HLA class II associations with type 1 diabetes in Cameroonians, we used sequence‐specific oligonucleotide probing (SSOP) to identify DRB1, DQA1, DQB1 and DPB1 alleles in 10 unrelated C‐peptide negative patients with type 1 diabetes and 90 controls from a homogeneous population of rural Cameroon. We found a significantly higher frequency of the alleles DRB1*03 (χ2 = 17.9; P = 0.001), DRB1*1301 (χ2 = 37.4; P < 0.0001), DQA1*0301 (χ2 = 18.5; P = 0.001) and DQB1*0201 (χ2 = 37.4; P < 0.001) in diabetes patients compared to the control group. The most frequent alleles in the control population were DQA1*01, DQB1*0602 and DRB1*15. The DRB1*04 allele was not significantly associated with type I diabetes in our study population. We observed no significant difference between patients and controls in DPB1 allele frequency. In conclusion, the data in Cameroonian diabetes patients suggest the existence of HLA class II predisposing and specific protective markers, but do not support previous reports of a primary association between HLA‐DP polymorphism and development of type I diabetes .
MICA and MICB microsatellite alleles in HLA extended haplotypes
Authors: Bolognesi E. , D'Alfonso S. , Rolando V. , Fasano M. E. , Praticò L. , Momigliano‐Richiardi P.
Published: March 2003

The present study is a contribution to the definition of the linkage disequilibrium relationship of MICA and MICB with adjacent loci and to the characterization of extended HLA haplotypes. These issues are of importance for the identification of disease associations and for a better definition of donor–recipient compatibility in bone‐marrow grafts through the typing of haplospecific markers. The distribution of the five alleles of MICA and the 13 alleles of MICB microsatellites, located, respectively, in MICA transmembrane exon 5 and in MICB intron 1, was examined in 133 healthy Italian individuals previously typed for HLA class I, class II and complement loci and for the TNFa microsatellite. The MICB microsatellite was also analysed in 49 HTCLs for which MICA typing was already available. Very strong linkage disequilibria with HLA‐B and TNFa were detected in the Italian population for both MICA and MICB microsatellite alleles, in spite of the high mutability rate of the larger MICB alleles. Some strong associations were also detected between MICB and DRB1. The strongest associations (P < 0.001,D′ > 0.7) were those of MICA‐A4 with HLA‐B18, B27 and TNFa1, MICA‐A5 with HLA‐B35, B61 and B62, MICA‐A5.1 with HLA‐B7, B8, B13, B63 and MICB‐CA24, MICA‐A6 with HLA‐B51, MICA‐A9 with HLA‐B39, B57 and TNFa2, MICB‐CA14 with HLA‐B14, B27 and TNFa1, MICB‐CA15 with HLA‐B52, TNFa4 and TNFa13, MICB‐CA17 with HLA‐B7 and TNFa11, MICB‐CA18 with HLA‐B13 and TNFa7, MICB‐CA22 with HLA‐B57, and MICB‐CA24 with HLA‐B8 and TNFa2. From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well‐known Caucasoid extended haplotypes.
Promoter region polymorphism of the CD14 gene (C–159T) is not associated with psoriasis vulgaris
Authors: Karhukorpi J. , Ikäheimo I. , Karvonen J. , Karttunen R.
Published: March 2003

Keratinocytes of psoriatic skin show aberrant expression of membrane‐bound CD14 (mCD14). In addition, soluble CD14 (sCD14) is elevated in the sera of psoriatic patients. The mechanisms leading to increased CD14 expression and secretion in psoriasis are poorly understood. A bi‐allelic polymorphism in the promoter region of the CD14 gene controls CD14 expression on monocytes and sCD14 levels in the sera of healthy subjects. In this context, we explored the CD14 promoter region genotypes of 63 Finnish patients with psoriasis and 126 non‐psoriatic controls using a new ARMS‐PCR method. No differences in the CD14 genotype frequencies were found between the groups. Thus, our results suggest that the enhanced CD14 expression in psoriasis is not attributable to functional variants of CD14 (–159C/T).
A literature review and update on the prevention and management of fluid overload in endometrial resection and hysteroscopic surgery
Authors: Varol Nesrin , Maher Peter , Vancaillie Thierry , Cooper Michael , Carter Jonathan , Kwok Adrian , Pesce Andrew , Reid Geoffrey
Published: March 2003

Objective The purpose of this study is to provide safe guidelines to minimize the risk of fluid absorption and its complications at operative hysteroscopy.

Design Retrospective review of the literature.

Results Two of the major complications of fluid intravasation at hysteroscopic surgery are hyponatraemic encephalopathy and death. Fluid intravasation remains a risk despite optimal instrumentation and the use of minimal pressures to distend the uterus. While multiple factors affect the amount of fluid absorption and significant variability can exist between very similar cases, monitoring of fluid balance remains the most important issue. Techniques relying on volume measurements are less accurate than those using weight measurements and can potentially lead to significant underestimation of fluid absorption. A continuous automated weighing system provides an easy, less time‐consuming and valid method of monitoring fluid deficit. We believe the safe limit for accurately measured fluid loss should be 800 mL, as 1000 mL of glycine intravasation results in a very significant decrease in serum sodium which is sufficient to bring a normonatraemic patient into the abnormal range. It is safer to perform hysteroscopic surgery under local anaesthesia as the earliest symptoms of encephalopathy, i.e. nausea, vomiting, weakness, will alert the surgeon and anaesthesist about impending serious complications, and corrective measures can be taken earlier than when the patient is under general anaesthesia.

Conclusion Fluid overload with subsequent hyponatraemic encephalopathy and death is one of the most significant complications in operative hysteroscopy. Following a protocol which entails the use of local anaesthesia and accurate fluid monitoring and sets a limit to fluid deficit will minimize this risk.
A prospective evaluation of pain and acceptability during outpatient flexible hysteroscopy and endometrial biopsy
Authors: Abbott Jason , Hawe Jed , Phillips Graham
Published: March 2003

Objective To compare the pain of outpatient flexible hysteroscopy and endometrial sampling in women who have abnormal uterine bleeding.

Design A prospective cohort study.

Setting A minimal access gynaecological training unit within a district general hospital in north‐east England.

Subjects 100 women referred consecutively for assessment of abnormal uterine bleeding.

Main outcome measures Pain experienced with hysteroscopy and endometrial biopsy, as assessed by visual analogue score, and patient acceptability assessed by questionnaire.

Results Endometrial biopsy was found to be the most painful part of the assessment and was significantly more painful than either hysteroscopy or insertion of the speculum (P  < 0.0001). The overall success of outpatient hysteroscopy in this series was 93%. On an intention‐to‐treat basis, procedure acceptability was 92% and only 9% of women required additional oral analgesia following the procedures. Of the women, 51% found the experience of outpatient hysteroscopy less painful than a cervical smear.

Conclusion Outpatient flexible hysteroscopy is a viable first‐line investigation for abnormal uterine bleeding. Endometrial biopsy should be used selectively.
Accuracy of emergency department bedside ultrasonography
Authors: Rowland Jane L , Kuhn Marie , Bonnin Robert LL , Davey Michael J , Langlois Suzanne LeP
Published: March 2003

Objectives:

To determine which focused ultrasound examinations can be interpreted accurately by emergency physicians who have limited training and experience. To determine whether image quality and/or the operator’s level of confidence in the findings correlates with accurate scan interpretation.

Methods:

A prospective sample of consenting adult emergency department patients with the conditions was selected for study. Scans were performed by emergency physicians who had attended a 3‐day focused ultrasound examinations instruction course. All scans were videotaped and subsequently reviewed by a radiologist. Accuracy was determined by comparing the emergency physicians scan interpretation with preselected gold standards. Chi‐squared tests were employed to determine if the individual performing the scan, the type of scan, patient’s body habitus, image quality and/or operator confidence were reliable predictors of accuracy.

Results:

Between September 1997 and January 1999, 221  scans were studied. Accuracy varied widely depending on the type of scan performed: aortic scans were 100% accurate whereas renal scans had 68% accuracy. On bivariate analyses, there was little variation in the various operators’ levels of proficiency and accuracy of interpretation was not associated with patient body habitus, image quality or operator confidence.

Conclusions:

Neophytes can accurately perform and interpret aortic scans; additional training and/or experience appear to be necessary to achieve proficiency in conducting most of the other scans studied. Inexperienced operators are unable to discern whether their scan interpretations will prove accurate.
Analysis of the study design and manuscript deficiencies in research articles submitted to Emergency Medicine
Authors: Taylor David McD , Brown Anthony FT
Published: March 2003

Objective:

To describe and analyse the study design and manuscript deficiencies in original research articles submitted to Emergency Medicine.

Methods:

This was a retrospective, analytical study. Articles were enrolled if the reports of the Section Editor and two reviewers were available. Data were extracted from these reports only. Outcome measures were the mean number and nature of the deficiencies and the mean reviewers’ assessment score.

Results:

Fifty‐seven articles were evaluated (28 accepted for publication, 19 rejected, 10 pending revision). The mean (± SD) number of deficiencies was 18.1 ± 6.9, 16.4 ± 6.5 and 18.4 ± 6.7 for all articles, articles accepted for publication and articles rejected, respectively (P = 0.31 between accepted and rejected articles). The mean assessment scores (0–10) were 5.5 ± 1.5, 5.9 ± 1.5 and 4.7 ± 1.4 for all articles, articles accepted for publication and articles rejected, respectively. Accepted articles had a significantly higher assessment score than rejected articles (P = 0.006). For each group, there was a negative correlation between the number of deficiencies and the mean assessment score (P > 0.05). Significantly more rejected articles ‘… did not further our knowledge’ (P = 0.0014) and ‘… did not describe background information adequately’ (P = 0.049). Many rejected articles had ‘… findings that were not clinically or socially significant’ (P = 0.07). Common deficiencies among all articles included ambiguity of the methods (77%) and results (68%), conclusions not warranted by the data (72%), poor referencing (56%), inadequate study design description (51%), unclear tables (49%), an overly long discussion (49%), limitations of the study not described (51%), inadequate definition of terms (49%) and subject selection bias (40%).

Conclusions:

Researchers should undertake studies that are likely to further our knowledge and be clinically or socially significant. Deficiencies in manuscript preparation are more frequent than mistakes in study design and execution. Specific training or assistance in manuscript preparation is indicated. See Commentary, page 407.
Angioedema in the emergency department: A presentation of lymphoma
Authors: Wellwood Jeremy , Taylor Kerry , Wright Susan , Bentley Mark , Eliadis Paul
Published: March 2003

A 58‐year‐old woman presented to emergency departments on several occasions with episodic angioedema. Lymphoplasmacytic lymphoma with an IgM paraprotein (Waldenstrom’s macroglobulinemia) was eventually diagnosed 14 months later in association with acquired C1 esterase inhibitor deficiency. Resolution of the angioedema and C1 esterase inhibitor deficiency was achieved with danazol and treatment of the underlying lymphoma.
HEALTH ISSUES AMONG FILIPINO WOMEN IN REMOTE QUEENSLAND
Authors: Kelaher Margaret , Potts Helen , Manderson Lenore
Published: March 2003

This paper discusses health issues among Filipinas (women born in the Philippines) living in remote and rural environments in Queensland. The sample was recruited as part of the University of Queensland component of the Australian Longitudinal Study of Women’s Health (ALSWH). Most of the women lived in an urban or semi‐urban area (391), whereas 90 lived in rural or remote areas. Community perceptions had a much greater impact on health service utilisation in rural and remote areas than in urban areas. The transition between newcomer and old‐timer is more difficult for Filipinas than for other rural women because they are visibly different from other members of the community and suffer from stigmatisation associated with perceptions of Filipinas as mail order brides. For these women, concerns about confidentiality and a reluctance to ask for support are major barriers to health service utilisation. The area of greatest concern is mental health, particularly in relation to parenting issues. Improving access may involve providing a greater awareness of what services are available and allowing women to access services in a way that does not require them to label themselves or be labelled by others.
INSIGHTS OBTAINED FROM AN EVALUATION OF A FALLS PREVENTION PROGRAM SET IN A RURAL HOSPITAL
Authors: Hathaway Joy , Walsh Jane , Lacey Christine , Saenger Helen
Published: March 2003

An evaluation of a Falls Prevention Program that took place in a 29‐bed rural hospital in New South Wales is described. The aim of the project was to ascertain the overall effectiveness of the Program and to explore the usefulness of the assessment criteria in predicting falls. The sample consisted of 111 participants, representing all patients 65 years and over who were admitted to the general ward of the hospital between January and December 1997. The Falls Prevention Program had reduced the incidence of falls and was found to be effective for those patients requiring minimal assistance with walking. However, it was less effective for those using pick‐up frames or forearm support frames. The patients who fell were more likely to be in the high risk category and it was concluded that while the assessment criteria was useful in predicting falls, the Falls Prevention Program could only limit the number of falls but not prevent them altogether. Age, mental status and mobility of patients in combination with time and location of falls suggested a pattern that was possibly peculiar to this rural hospital, which has implications for funding and staffing.