bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient reporting of potential adverse drug reactions: a methodological study
Authors: Jarernsiripornkul N. , Krska J. , Capps P. A. G. , Richards R. M. E. , Lee A. 
Published: March 2003

Aims  To develop a systematic generic method of enabling patients to report symptoms which they believe to be due to a particular prescribed drug.Methods  A piloted body system‐based questionnaire was distributed to patients registered with 79 medical practices in Grampian prescribed one of nine recently marketed ‘black triangle’ drugs. These comprised four antidepressants, three antiepileptics and two analgesics. This requested respondents to identify any symptoms experienced over the previous year which they thought could be due to the ‘black triangle’ drug they had used. A sample of medical records was examined to compare symptoms recorded with those reported by patients. A classification system was developed for the study to enable the assessment of symptoms reported for their potential relationship to patients' drug therapy. All symptoms reported were classified, taking into account information provided by patients on their concomitant drugs and diseases. A specialist pharmacist independently re‐classified a sample of the symptoms to validate the process.Results  A 36.3% response rate was obtained (837/2307) with 742 respondents (88.6%) reporting at least one symptom. The median per patient was 6.0 (range 0–71), with almost half (406, 48.5%) reporting fewer than five symptoms. Most symptoms (71.0%) were classified as being probably or possibly related to the drugs studied. Agreement between researcher and specialist on the classification of 75.3% of 716 symptoms was obtained (Kappa=0.563). Responses from patients prescribed antidepressant drugs were more likely to include symptoms potentially caused by these drugs (74.5% of all symptoms reported) than those from patients prescribed analgesics (67.4%) or antiepileptics (65.1%, χ2 = 23.858, d.f. = 2, P < 0.001). Patients reporting large numbers of symptoms were more likely to report some which were classed as unlikely to be an ADR or unattributable (χ2 = 80.587, d.f. = 3, P < 0.001). Of the 742 reporting symptoms in questionnaires, 402 (54.2%) claimed to have reported some or all of these to their doctor. Only 162 (22.6%) of 716 patient‐reported symptoms were documented in the primary care medical records of 103 patients prescribed tramadol or venlafaxine.Conclusions  Respondents were clearly willing to report symptoms, the majority of which were classed as possibly/probably related to the drugs studied. The results suggest that patients do not report all symptoms they suspect to be ADRs to their GP and that GPs do not record all symptoms which may be reported to them. The method could help to identify problems which patients perceive as being related to their drug therapy and contribute to increased ADR reporting.
Pharmacokinetics of moxifloxacin, a novel 8‐methoxy‐quinolone, in patients with renal dysfunction
Authors: Stass H. , Kubitza D. , Halabi A. , Delesen H. 
Published: March 2003

Aims  To evaluate the influence of impaired renal function on the plasma and urinary pharmacokinetics of moxifloxacin, a novel 8‐methoxy‐quinolone antibacterial drug.Methods  Twenty male and 12 female subjects (8 healthy subjects, 24 patients with impaired renal function), 18–75 years of age were investigated in parallel fashion with four groups stratified according to creatinine clearance (CLCR; n=8 for each group). The pharmacokinetics of moxifloxacin and the metabolites M1 (sulphonate metabolite) and M2 (glucuronide) in plasma and urine were determined repeatedly up to 96 h after single oral doses of 400 mg. Patients were monitored intensively with regard to clinical and laboratory safety and tolerability.Results  Single doses of 400 mg moxifloxacin were safe and well tolerated. The urinary excretion of moxifloxacin (Aeur, P: 0.0002) and renal clearance (CLR, P<0.0001) were reduced with decreasing CLCR, mean Cmax was slightly reduced (Cmax‐ratio 85.0%, 90% CI 67.9, 106.4% severe renal impairment vs healthy subjects) but the AUC was unchanged even in severe renal impairment (AUC‐ratio 101.3%, 90% CI 79.7, 128.6%). The mean AUC of the N‐sulphonate M1 was slightly increased (by about 53% for the most severe disease) by impaired renal function, but there was no significant correlation between individual AUC and CLCR, whilst Aeur and CLR were significantly correlated with CLCR. In contrast, for the acylglucuronide M2, Aeur (P: 0.0026), CLR (P<0.0001) and AUC (P: 0.0011) were directly correlated with CLCR.Conclusions  Renal dysfunction had little effect on the plasma pharmacokinetics of either moxifloxacin or metabolite M1, although their renal clearance and urinary excretion were reduced. In contrast renal dysfunction did result in changes in the plasma pharmacokinetics of metabolite M2, causing greater and longer exposure. However the extent of these changes is unlikely to be of clinical relevance.
Efficacy of calcium channel blockers as maintenance therapy for asthma
Authors: Ann Twiss Mary , Harman Eloise , Chesrown Sarah , Hendeles Leslie 
Published: March 2003

Aims  Previous bronchoprovocation studies indicate that nifedipine attenuates airway responsiveness to several stimuli whereas diltiazem has no effect. The aim of this study was to determine whether such studies predict the efficacy of calcium channel blockers as maintenance therapy for persistent asthma.Methods  Twenty‐one otherwise healthy adults with persistent asthma, mean age 25 years, completed treatment with maximum tolerated doses of placebo (P), nifedipine (N), and diltiazem (D) in a double‐blind, randomized, three‐treatment, three‐period, crossover manner, each for 4 weeks. Frequency and severity of asthmatic symptoms were recorded twice daily, as well as peak expiratory flow and frequency of ‘prn’ use of inhaled terbutaline. Blood pressure, heart rate, P‐R interval of the ECG and spirometry were measured biweekly. At the end of each treatment, airway responsiveness to exercise was measured.Results  The mean (s.e. mean)% of days with wheeze was 69±7% during P, 75±6% during N and 72±6% during D (P=0.7). FEV1 was 79±2% of predicted during P, 81±2% during N and 79±2% during D (P=0.6). The decrease in FEV1 after exercise was 32±4% during P, 32±5% during N and 27±4% during D (P=0.5). Heart rate was elevated during N (P=0.0002) whereas P‐R interval was prolonged during D (P=0.0001).Conclusions  Maintenance therapy with calcium channel blockers, at doses that produce cardiovascular effects, do not suppress the signs and symptoms of persistent asthma. Previous bronchoprovocation studies did not predict these results.
Comparative human pharmacokinetics and metabolism of single‐dose oral and intravenous sildenafil
Authors: Muirhead Gary J. , Rance David J. , Walker Donald K. , Wastall Philip 
Published: March 2003

Aims  To characterize the absorption, metabolism and excretion of an oral and intravenous (IV) dose of radiolabelled [14C]‐sildenafil citrate in healthy male subjects. Specific objectives were to measure the cumulative amount of drug‐related radiolabelled material excreted in the urine and faeces to characterize urinary and faecal radioactivity as unchanged sildenafil or its metabolites, and to quantify blood and plasma total radioactivity and unchanged drug concentrations.Methods  Six healthy male subjects between the ages of 45 and 58 years were enrolled in an open‐label, parallel‐group study; three subjects received the oral dose and three received the IV dose. Oral drug was administered as a single dose of 50‐mg [14C]‐sildenafil, and IV drug was administered as a single dose of 25‐mg [14C]‐sildenafil infused over 25 min. Each dosage form contained 50 µCi of radioactivity. For radioactivity assays, whole blood, plasma, urine and faeces samples were taken predose and at specified intervals up to 5 days postdose. Plasma samples were assayed for sildenafil and the metabolites UK‐103,320 and UK‐150,564. Metabolite profiling was also performed in plasma, faeces and urine.Results  Absorption of sildenafil after oral administration was rapid and approximately 92% whilst the absolute bioavailability was limited to 38%, due to first‐pass metabolism. Mean AUCt values showed that sildenafil accounted for about 60% of the total circulating radioactivity in the plasma after IV administration and for 32% after oral administration. Concentrations of radioactivity in whole blood were lower than in plasma, indicating limited penetration of sildenafil into blood cells. No unchanged sildenafil was detected in either urine or faeces, demonstrating that metabolism was the major mechanism of drug clearance. The principal routes of metabolism were N‐demethylation, oxidation and aliphatic dehydroxylation. Sildenafil was well tolerated, with treatment‐related adverse events reported by three subjects. Two of these were mild, and there was one case of moderate leg pain.Conclusions  The pharmacokinetics of radiolabelled [14C]‐sildenafil were consistent with rapid absorption, first‐pass metabolism and primarily faecal elimination of N‐demethylated metabolites.
Daytime liver glycogen accumulation, measured by 13C magnetic resonance spectroscopy, in young children with Type 1 diabetes mellitus
Authors: Matyka K. , Dixon R. M. , Mohn A. , Rajagopalan B. , Shmueli E. , Styles P. , Dunger D. B. 
Published: March 2003

AbstractAim  To examine daytime liver glycogen accumulation in prepubertal children with Type 1 diabetes mellitus (Type 1 DM) compared with non‐diabetic controls.Methods  Liver glycogen content was ascertained in the fasting (morning) and fed (afternoon) state using 13C magnetic resonance (MR) spectroscopy. Data were analysed from six children with Type 1 DM (median (range) age 8.7 (6.3–12.2) years), who were all on conventional insulin regimens, and six healthy controls (age 8.9 (7–10.2) years).Results  Children with diabetes tended to have lower fasting glycogen values than controls but this did not reach statistical significance (median (range) 154 (70–177) vs. 178 (120–203) mM glycosyl units, Type 1 DM vs. controls respectively; P = 0.06). Glycogen increased in all children with diabetes during the day and concentrations were similar to those in controls by the afternoon (175 (157–299) vs. 172 (136–238) mM glycosyl units; P = 0.7).Conclusions  The ability of young children with Type 1 DM to replace liver glycogen depleted after an overnight fast was at least as good as that in control subjects, suggesting that impaired glycogen storage is not a contributory factor in nocturnal hypoglycaemia.Diabet. Med. 18, 659–662 (2001)
The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population
Authors: Bentzen J. , Poulsen P. , Vaag A. , Beck‐Nielsen H. , Fenger M. 
Published: March 2003

AbstractAims The apolipoprotein B codon 2488 polymorphism has been associated with the metabolism of lipoproteins in subjects with Type 2 diabetes. However, no data are available on the influence of the polymorphism on insulin or glucose metabolism. This study examines the impact of the polymorphism on parameters associated with the insulin resistance syndrome in Danish twins.Methods The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55–74 years.Results The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin, as measured at 120 min in an oral glucose tolerance test. Subjects with the genotype T2488T had 14% higher triglyceride levels (P = 0.02) and 31% higher insulin levels (P = 0.004) than subjects with genotype C2488C. In twins discordant for genotype, the T‐allele was associated with higher levels of triglyceride (P = 0.04) and insulin (P = 0.02) and lower levels of HDL‐cholesterol (P = 0.04).Conclusion The T‐allele of the codon 2488 polymorphism influenced parameters related to the insulin resistance syndrome, i.e. increased levels of insulin, increased levels of triglyceride and decreased levels of HDL. As the polymorphism is silent, these effects must be mediated through linkage to other polymorphisms in apolipoprotein B or other genes on chromosome 2.
Sound lateralization during passive whole‐body rotation
Authors: Lewald Jörg , Karnath Hans‐Otto 
Published: March 2003

AbstractThe effect of passive whole‐body rotation about the earth‐vertical axis on the lateralization of dichotic sound was investigated in human subjects. Pure‐tone pulses (1 kHz; 0.1 s duration) with various interaural time differences were presented via headphones during brief, low‐amplitude rotation (angular acceleration 400°/s2; maximum velocity 90°/s; maximum displacement 194°). Subjects made two‐alternative forced‐choice (left/right) judgements on the acoustic stimuli. The auditory median plane of the head was shifted opposite to the direction of rotation, indicating a shift of the intracranial auditory percept in the direction of rotation. The mean magnitude of the shift was 10.7 µs. This result demonstrates a slight, but significant, influence of rotation on sound lateralization, suggesting that vestibular information is taken into account by the brain for accurate localization of stationary sound sources during natural head and body motion.
The African Enigma: Low Prevalence of Gastric Atrophy, High Prevalence of Chronic Inflammation in West African Adults and Children
Authors: Campbell David I. , Warren Bryan F. , Thomas Julian E. , Figura Natalia , Telford John L. , Sullivan Peter B. 
Published: March 2003

ABSTRACTBackground. Helicobacter pylori infection is very common in Africa, yet peptic ulcer disease and gastric malignancy are rare.Aim.The aim of this study was to quantify mucosal responses to H. pylori in Gambian adults and children and to estimate the prevalence of antibodies to bacterial virulence factors (cagA and vacA) in a symptomatic population.Patients and methods.Adults (mean 36 SD 12 years) with dyspepsia and children (mean 1.4 years SD 0.4 years) with malnutrition underwent gastroscopy with biopsy. Blood was simultaneously drawn for cagA and vacA antibody status. Histopathological scoring used the modified Sydney classification.Results.Both adults (n = 45) and children (n = 37) mainly demonstrated chronic mild antral inflammation. Only 2/83 cases of focal atrophy (GA) and 4/83 cases of intestinal metaplasia (IM) were observed. Adults tended to demonstrate more frequent acute (AI) and chronic inflammation (CI) (38% compared with 18% and 85% compared with 72%, respectively). Sixty‐seven percent of children were cagA IgG+ and 21%vacA IgG+ and 93% of adults were IgG cagA+ and 86%vacA+. There were no differences in mucosal responses between those who were cagA or vacA positive compared with those who were negative.Conclusion.Gambian adults and children mount a CI response to H. pylori but GA, IM and AI are uncommon. cagA and vacA are commonly expressed in Gambian strains of H. pylori. Further studies are needed in order to confirm that GA and IM are not late findings in old age.
Anatomical and physiological characteristics of ostrich (Struthio camelus var. domesticus) meat determine its nutritional importance for man
Authors: COOPER Ross Gordon , HORBAÑCZUK Jaroslaw Olav 
Published: March 2003

ABSTRACTThe ostrich is increasingly gaining interest as a livestock animal because of its potential to produce healthy red meat with a low fat content. This article describes the characteristics of ostrich meat that allow it to be marketed as a healthy alternative to beef. The muscles utilized for human consumption include the dorsal Muscularis obturatorius medialis and the hindquarters. The trade names of ostrich muscles are currently not standardized and classification is based on location and scientific nomenclature. Meat cuts of a high commercial value reach as much as 80–90% in the ostrich compared with approximately 45% in other species. Described here are key product characteristics important in its marketing, including fat content, cholesterol, fatty acids, sodium, iron, color, flavor and odor, tenderness, pH and water‐holding capacity.
Regulation of fermentation in a ruminal bacterium, Streptococcus bovis, with special reference to rumen acidosis
Authors: ASANUMA Narito , HINO Tsuneo 
Published: March 2003

ABSTRACTWhen high‐starch diets are fed to ruminants, Streptococcus bovis often predominates in the rumen and produces lactate as the major fermentation product. Lactate production by S. bovis is regulated by the activity ratio of lactate dehydrogenase (LDH) to pyruvate formate‐lyase (PFL) in response to an energy supply or the intracellular pH. The activities of LDH and PFL are affected not only by the amounts of enzyme proteins, but also by the concentrations of allosteric effectors, such as fructose‐1, 6‐bisphosphate (FBP) and triose phosphates. Synthesis of LDH and PFL is regulated at the transcriptional level in opposing directions. The inverse relationship between LDH and PFL synthesis amplifies a change in the proportion of lactate in the total fermentation products. A high capacity to regulate lactate production in response to low pH allows S. bovis to grow at low pH and as one of the most acid‐tolerant bacteria among the prevailing ruminal bacteria, S. bovis also has a high capacity to extrude intracellular H+ by an F1F0 H+‐ATPase, which is important for acid tolerance. In addition, S. bovis is able to augment H+‐ATPase synthesis at the transcriptional level in response to low pH. The activities of H+‐ATPase and pyruvate kinase are enhanced by FBP and strongly inhibited by inorganic phosphate (Pi). Intracellular FBP and Pi concentrations affect sugar metabolism in S. bovis through regulation of the expression of catabolic genes and controlling the activity of sugar transport systems. Synthesis of the enzymes involved in sugar transport and fermentation appears to be regulated by the catabolite control protein A (CcpA) –phosphotransferase system (PTS) system.
Net grassland carbon flux over a subambient to superambient CO2 gradient
Authors: Mielnick P. C. , Dugas W. A. , Johnson H. B. , Polley H. W. , Sanabria J. 
Published: March 2003

AbstractIncreasing atmospheric CO2 concentrations may have a profound effect on the structure and function of plant communities. A previously grazed, central Texas grassland was exposed to a 200‐µmol mol−1 to 550 µmol mol−1 CO2 gradient from March to mid‐December in 1998 and 1999 using two, 60‐m long, polyethylene‐ covered chambers built directly onto the site. One chamber was operated at subambient CO2 concentrations (200–360 µmol mol−1 daytime) and the other was regulated at superambient concentrations (360–550 µmol mol−1). Continuous CO2 gradients were maintained in each chamber by photosynthesis during the day and respiration at night. Net ecosystem CO2 flux and end‐of‐year biomass were measured in each of 10, 5‐m long sections in each chamber. Net CO2 fluxes were maximal in late May (c. day 150) in 1998 and in late August in 1999 (c. day 240). In both years, fluxes were near zero and similar in both chambers at the beginning and end of the growing season. Average daily CO2 flux in 1998 was 13 g CO2 m−2 day−1 in the subambient chamber and 20 g CO2 m−2 day−1 in the superambient chamber; comparable averages were 15 and 26 g CO2 m−2 day−1 in 1999. Flux was positively and linearly correlated with end‐of‐year above‐ground biomass but flux was not linearly correlated with CO2 concentration; a finding likely to be explained by inherent differences in vegetation. Because C3 plants were the dominant functional group, we adjusted average daily flux in each section by dividing the flux by the average percentage C3 cover. Adjusted fluxes were better correlated with CO2 concentration, although scatter remained. Our results indicate that after accounting for vegetation differences, CO2 flux increased linearly with CO2 concentration. This trend was more evident at subambient than superambient CO2 concentrations.
Acid‐induced duodenal mucosal nitric oxide output parallels bicarbonate secretion in the anaesthetized pig
Authors: HOLM  , JOHANSSON  , PETTERSSON  , FÄNDRIKS  
Published: March 2003

We recently showed the involvement of the L‐arginine/nitric oxide (NO) pathway in acid‐induced duodenal mucosal bicarbonate secretion in rats. The aim of the present study was to confirm this observation in pigs by direct measurements of NO production. Experiments were performed on 16 anaesthetized pigs of both sexes treated with guanethidine (6 mg kg−1, intravenously). A duodenal segment, devoid of pancreaticobiliary influxes, was perfused with saline and the duodenal mucosal bicarbonate secretion was calculated from continuous measurements of pH and Pco2. The perfusate contents of NO and its oxidative product nitrite were determined by chemiluminescence, after reduction of nitrite to NO.Luminal acidification with 30 mM hydrochloric acid increased the output of bicarbonate as well as NO to the perfusate, by 195 ± 45% and 106 ± 10%, respectively. These responses to acid were markedly inhibited by adding the NO synthase inhibitor NG‐monomethyl‐
L‐arginine (L‐NMMA, 0.3 mM) to the perfusate. The inhibitory effect of L‐NMMA could be reversed by administration of L‐arginine (3 mM).The study presents simultaneous measurements of bicarbonate and NO outputs to a duodenal luminal perfusate. The results strongly support the view that the L‐arginine/NO pathway is involved in the acid‐induced duodenal mucosal bicarbonate secretory response.
Effects of moderate and intensive training on the hypothalamo–pituitary–adrenal axis in rats
Authors: CHENNAOUI M. , GOMEZ MERINO D. , LESAGE J. , DROGOU C. , GUEZENNEC C. Y. 
Published: March 2003

ABSTRACTThe influence of the two distinct training programmes, moderate (M) and intensive (I), on hypothalamo–pituitary–adrenal (HPA) axis was investigated, in rats. Changes in plasma concentrations of adrenocorticotropin hormone (ACTH) and corticosterone were followed in response to (i) a 60‐min acute running session performed on 2nd, 4th and 6th of the seven training weeks (ii) an acute restraint stress of 40 min applied after the final training programme. After 2nd, 4th and 6th week of the two training programmes, a 60‐min running resulted in an enhanced secretion of ACTH and corticosterone, compared with both the baseline values (i.e. before running) and to the sedentary (S) group. However, on 4th and 6th weeks compared with 2nd week, ACTH and corticosterone remained elevated in intensive group when they are significantly reduced in moderate group. We could suggest that a moderate training resulted in an adapted hormonal response whereas a deadapted process occurred for the intensive programme. The day after the last training session, basal ACTH, corticosterone and corticosteroid‐binding globulin (CBG) capacity were not affected by training. Hypothalamic corticotropin‐releasing factor tissue‐content (CRF) was increased significantly in the two trained groups. When compared with the sedentary group, the body weight of the rats in the two trained groups was significantly decreased with a total adrenal mass increasing but only in intensive group. The surimposed restraint stress resulted in significant increases in plasma ACTH and corticosterone both in trained and in sedentary animals. This result suggests that the adapted HPA axis response induced by both a moderate and intensive training do not prevent against the effects of a novel stress such as restraint stress.