bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of unlicensed and off‐label medications in paediatric gastroenterology with a review of the commonly used formularies in the UK
Authors: Dick A. , Keady S. , Mohamed F. , Brayley S. , Thomson M. , Lloyd B. W. , Heuschkel R. , Afzal N. A. 
Published: March 2003

SUMMARYBackground : Use of unlicensed and off‐label medications is common in hospital based paediatric practice. Whilst inpatient prescription can be closely monitored within the hospital setting, it is subspecialties like paediatric gastroenterology, caring for chronically ill children on an outpatient basis that require administration of regular medications in the community. Local practitioners rely on available paediatric formularies or information provided by the tertiary unit for monitoring and dispensing further prescriptions.Aim : To assess the proportion of unlicensed and off‐label medications prescribed in a paediatric gastroenterology unit to children discharged to the community and assess adequacy of information about these medications in commonly used British formularies.Methods : All prescriptions prescribed over a six‐month period (Jan–Jul 2002) either in the paediatric gastroenterology outpatient department or for children discharged home after an inpatient stay, were retrieved from the pharmacy database. The main outcome measures were to assess the proportion of medications prescribed for unlicensed or off‐label use.Results : 308 patients received 777 prescriptions of which 384 (49%) were for unlicensed or off‐label use. Of these 291 (76%) were off‐label; 208 in relation to indication and 83 to child's age. 93 of the prescribed medications were unlicensed; 37 were due to manipulation of formulation. Of the commonly used formularies in the UK, only ‘Medication for Children®’ contained dosage information on more than half (9/13) of the most often prescribed off‐label/unlicensed medications in paediatric gastroenterology.Conclusions : Use of unlicensed and off‐label medications remains a problem in paediatric practice. Until licensing laws change and more drugs are licensed in children, paediatric gastroenterologists remain responsible for provision of information to families, local practitioners, nurses and pharmacists. Of the commonly used formularies, ‘Medicines for Children’ is the most detailed and comprehensive, and should be available to all general practitioners and pharmacists in the UK. Clear communication between specialist units and local practitioners is imperative to ensure safe and effective prescribing to children.
Arterial blood sampling practices in intensive care units in England and Wales
Authors: O'Hare D. , Chilvers R. J. 
Published: March 2003

A postal survey of arterial blood sampling practices in 280 intensive care units throughout England and Wales found that very few measures are taken to reduce diagnostic blood loss in adult intensive care patients from arterial sampling. The average volume of blood withdrawn to clear the arterial line before sampling is 3.2 ml; subsequently returned to the patient in only 18.4% of intensive care units.Specific measures to reduce the blood sample size by the routine use of paediatric sample tubes in adult patients occurs in only 9.3% of intensive care units. In paediatric units, the average volume withdrawn was 1.9 ml and this was routinely returned in 67% of units. Some aspects of arterial blood sampling practices identified in this survey may contribute to iatrogenic anaemia in intensive care patients.
Pharmacological agents as cerebral protectants during deep hypothermic circulatory arrest in adult thoracic aortic surgery
Authors: Dewhurst A. T. , Moore S. J. , Liban J. B. 
Published: March 2003

SummaryA postal survey was sent to members of the Association of Cardiothoracic Anaesthetists to ascertain current practice in the use of pharmacological agents as cerebral protectants during deep hypothermic circulatory arrest. The response rate was 60%. Eighty‐three per cent of respondents used some form of pharmacological agent specifically for cerebral protection. Fifty‐nine per cent of respondents used thiopental, 29% used propofol and 48% used a variety of other agents, the most common of these being a steroid. There were variations in the dose and timing of administration of drugs. Few respondents believed that there was a body of evidence to support this use of pharmacological agents. Only 35% of respondents believed there to be sufficient evidence to support the use of thiopental. Similarly, only 11% of respondents believe that there is evidence supporting the use of propofol, and 16% the use of steroids. The above findings demonstrate that it would not be possible to create a ‘best practice’ set of guidelines at present. A national database of all cases of adult thoracic surgery involving deep hypothermic cardiac arrest, with methodology and outcome, could probably establish such guidelines, evidence based.
The Sister Anaesthetists of Norwich
Authors: Woollam C. H. M. 
Published: March 2003

SummaryThe administration of general anaesthesia in the UK has generally been carried out by medically qualified staff but there have been instances where this has not been the case. This article describes the role of the ‘Sister Anaesthetists’ who made a significant contribution to the delivery of anaesthesia services at the Norfolk and Norwich Hospital from the end of the First World War until the introduction of the National Health Service in 1948.
Use of intrathecal morphine for postoperative pain relief after elective laparoscopic colorectal surgery
Authors: Kong S‐K. , Onsiong S. M. K. , Chiu W. K. Y. , Li M. K. W. 
Published: March 2003

SummaryLaparoscopic surgery has become popular in recent years, but few studies have addressed analgesia for this type of surgery. We conducted a prospective double‐blind randomised trial on 36 cases of laparoscopic colorectal surgery to determine the influence of intrathecal morphine on postoperative pain relief. All patients received a subarachnoid block with local anaesthetic in addition to general anaesthesia. One group also received intrathecal morphine. A patient‐controlled analgesic (PCA) device was prescribed for pain control postoperatively and the visual analogue score (VAS) was used for pain assessment. The group who received intrathecal morphine used significantly less morphine. There were no adverse cardiovascular effects of the combined anaesthetic technique. Nausea and vomiting remained the main side‐effect of intrathecal morphine but this was easily treated with anti‐emetics.
Multimethod (K–Ar, Rb–Sr, Sm–Nd) dating of bentonite minerals from the eastern United States
Authors: Toulkeridis Theofilos , Clauer Norbert , Chaudhuri Sam , Goldstein Steve L. 
Published: March 2003

Isotopic determinations (K–Ar, Rb–Sr and Sm–Nd), and trace and rare‐earth elemental analyses were made on a few biotite and clay fractions of Palaeozoic bentonite units from the eastern United States. The clay fractions were gently leached with dilute hydrochloric acid to study separately the acid‐soluble minerals intimately associated with the extracted clay particles. The data highlight interesting potentials for this integrated approach to decipher complex tectonothermal evolutions of sedimentary basins. Biotite K–Ar ages are consistent with a Middle Ordovician stratigraphic age for the bentonite units with a mean age of 459±10 Ma. The clay residues give a Sm–Nd isochron age of 397±44 Ma, indicative of their crystallization during Acadian tectonothermal activity at about 200 °C. The clay leachates, which are considered to represent mineral phases different from clay material, yield a distinct Sm–Nd isochron age of 285±18 Ma which is indistinguishable from K–Ar ages obtained previously on the clays, suggesting a thermally induced diffusion of radiogenic 40Ar from clay particles during Alleghenian–Ouachita orogenic activity. The Rb–Sr system of the clay material seems to have been variably disturbed, except for the sample taken near the Allegheny Front for which an age of 179±4 Ma suggests a further localized activity of the thrust system at about 130–150 °C.Clearly the limited number of samples does not allow us to perfectly constrain an evolutionary model. However, analysis of the soluble minerals for their contents in metal and rare‐earth elements suggests that metal‐carrying fluids migrated during the Alleghenian–Ouachita orogenic activity in the eastern North American continent. Consequently, they could have contributed to the concentration of ore deposits in the region, but this possibility needs to be tested with a larger data base.
Structural and topographic evolution of the central Transverse Ranges, California, from apatite fission‐track, (U–Th)/He and digital elevation model analyses
Authors: Blythe  , Burbank  , Farley  , Fielding  
Published: March 2003

Apatite fission‐track (FT) and (U–Th)/He analyses are used to constrain the low‐temperature thermal history of the San Gabriel and San Bernardino Mountains (SGM and SBM), which are part of the southern California Transverse Ranges. FT ages from 33 SGM samples range from 3 to 64 Ma. Helium ages, ranging from 3 to 43 Ma, were obtained from 13 of these samples: all of the He ages are the same or younger than their respective FT ages. FT ages from 10 SBM samples were older, ranging from 45 to 90 Ma. The FT and He data document at least three phases of cooling in the SGM, but only two in the SBM. Prior to ~7 Ma, the thermal history of the SGM appears to have been nearly identical to many of the core complexes in the Basin and Range of south‐eastern California: a major phase of cooling is indicated from ~60 to 40 Ma, with a more recent phase beginning at ~23 Ma and continuing until ~10 Ma. The similarity of this timing to that of core complexes suggests that the SGM also originated as a core complex, when the rocks were adjacent to the Chocolate–Orocopia Mountains, and that some of the range‐bounding faults were initially extensional. In the SBM, the two phases of cooling documented by the FT data occurred from ~65 to 55 Ma, and from ~18 Ma to the present. The timing on the second phase is very poorly constrained and, therefore, we do not speculate on the origin of the SBM.The most recent phase of cooling appears to have begun at ~7 Ma in the SGM, as the result of the onset of contractional deformation. A more accelerated phase of cooling may have begun at ~3 Ma. Distinct variations in the total amounts and rates of cooling between different fault‐bounded blocks within the SGM are documented since 7 Ma. We use these variations in cooling rates to calculate denudation rates, which are then compared to topographic characteristics for each structural block. These comparisons suggest that more rapid bedrock uplift in the eastern and southern part of the range has strongly affected the present‐day physiography. Despite a higher mean elevation, the SBM are much less dissected than the SGM, suggesting that the most recent phase of cooling and bedrock uplift began in the last 3 Myr, much later than the initiation of recent bedrock uplift in the SGM.
Morphology and origin of major Cenozoic sequence boundaries in the eastern North Sea Basin: top Eocene, near‐top Oligocene and the mid‐Miocene unconformity
Authors: Huuse M. , Clausen O. R. 
Published: March 2003

Unconformities in sedimentary successions (i.e. sequence boundaries) form in response to the interplay between a variety of factors such as eustasy, climate, tectonics and basin physiography. Unravelling the origin of sequence boundaries is thus one of the most pertinent questions in the analysis of sedimentary basins. We address this question by focusing on three of the most marked physical discontinuities (sequence boundaries) in the Cenozoic North Sea Basin: top Eocene, near‐top Oligocene and the mid‐Miocene unconformity.The Eocene/Oligocene transition is characterized by an abrupt increase in sediment supply from southern Norway and by minor erosion of the basin floor. The near‐top Oligocene and the mid‐Miocene unconformity are characterized by major changes in sediment input directions and by widespread erosion along their clinoform breakpoints. The mid‐Miocene shift in input direction was followed by a marked increase in sediment supply to the southern and central North Sea Basin.Correlation with global δ18O records suggests that top Eocene correlates with a major long‐term δ18O increase (inferred climatic cooling and eustatic fall). Near‐top Oligocene does not correlate with any major δ18O events, while the mid‐Miocene unconformity correlates with a gradual decrease followed by a major long‐term increase in δ18O values The abrupt increases in sediment supply in post‐Eocene and post‐middle Miocene time correlate with similar changes worldwide and with major δ18O increases, suggesting a global control (i.e. climate and eustasy) of the post‐Eocene sedimentation in the North Sea Basin.Erosional features observed at near‐top Oligocene and at the mid‐Miocene unconformity are parallel to the clinoform breakpoints and resemble scarps formed by mass wasting. Incised valleys have not been observed, indicating that sea level never fell significantly below the clinoform breakpoint during the Oligocene to middle Miocene.
A study of the relation of exposure to quinolones and suicidal behaviour
Authors: Jick Susan S. , Vasilakis Catherine , Martinez Carlos , Jick Hershel 
Published: March 2003

Aims
To investigate the concern, raised by spontaneous reports received by the German regulatory authorities, that use of quinolone antibiotics may increase the risk for suicide and other suicidal behaviours.
Methods
We carried out a nested case‐control study using the General Practice Research Database (GPRD). We compared the risk of suicidal behaviours among users of quinolones, other antibiotics and no antibiotics.
Results
From January 1, 1991 through April 30, 1995 we identified 348 cases of suicide, attempted suicide, or suicidal ideation and 808 controls. Compared with controls, cases who had received a prescription for a quinolone in the 30 days prior to the event had an adjusted relative risk (RR) estimate of 1.5 (95% CI 0.4–6.3) for any suicidal behaviour. Cases who had filled a prescription for a quinolone in the 31 to 180 days prior to their event had an adjusted RR estimate of 0.8 (95% CI 0.4–1.7) compared with controls. Cases who used other antibiotics in the 30 days prior to the event conferred an adjusted RR estimate of 1.1 (95% CI 0.6–2.2), and 0.9 (95% CI 0.6–1.3) for exposure in the 31 to 180 days prior to the event. The results were not materially different when suicide, suicide attempt, and suicidal ideation were analyzed separately.
Conclusions
We conclude that there is no material increased risk of suicidal behaviours for use of quinolone antibiotics compared with non‐use or use of other antibiotics.
Fenoterol increases erythropoietin concentrations during tocolysis
Authors: Gleiter C. H. , Schreeb K. H. , Goldbach S. , Herzog S. , Cunze T. , Kuhn W. 
Published: March 2003

Aims
The present study was carried out to assess the effect of the selective β2‐ adrenoceptor agonists on erythropoietin (EPO) production.
Methods
Routine tocolysis with fenoterol (using the regular rate of 2 μg min−1 ) was used as a clinically easily accessible model.
Results
EPO concentrations had doubled 24 h after the start of tocolysis (P<0.001). This increase lasted over the entire observation period of 48 h. Potassium concentrations fell significantly during the first hours of fenoterol infusion. There was no increase of human placenta lactogen during the period of EPO increase.
Conclusions
The data confirm our earlier results that fenoterol increases EPO concentrations following haemorrhage. In this model it was not necessary to stimulate EPO production prior to pharmacological treatment.
Effect of food on the bioavailability of triclabendazole in patients with fascioliasis
Authors: Lecaillon J. B. , Godbillon J. , Campestrini J. , Naquira C. , Miranda L. , Pacheco R. , Mull R. , Poltera A. A. 
Published: March 2003

Aims
Preliminary results indicate higher absorption of triclabendazole (TCBZ) administered postprandially. Therefore, the influence of food on the pharmacokinetics of TCBZ and its active sulphoxide (TCBZ‐SO) and sulphone (TCBZ‐SO2) metabolites was investigated.
Methods
Two single doses (10 mg kg−1 ) of TCBZ were administered to 20 patients with fascioliasis. Ten patients were first given the drug after a high energy breakfast and then, 48 h later, after an overnight fast. The other 10 patients first received the drug in fasting state and then, 48 h later, after breakfast. A low energy breakfast was served 2 h after drug administration for fasting state.
Results
Compared with the fasting state, an increased AUC and Cmax after food intake (significant, P<0.0001) was shown from the values of TCBZ, TCBZ‐SO and TCBZ‐SO2. The mean AUC for TCBZ (fasting: 1.55, fed: 5.72 μmol l−1 h), TCBZ‐SO (fasting: 177, fed: 386 μmol l−1 h) and TCBZ‐SO2 (fasting: 13.9, fed: 30.5 μmol l−1 h) indicated a large availability increase with food and the strong systemic predominance of the active sulphoxide metabolite over the unchanged drug. (All patients were cured at the end of the trial except one who required a second course of two postprandial doses of triclabendazole (10 mg kg−1 each). Tolerability to the treatment among the patients was good.
Conclusions
The administration of triclabendazole with food is recommended for improved systemic availability in patients with fascioliasis or paragonimiasis.
Plasma hydroxy metronidazole/metronidazole ratio in anti‐HCV carriers with and without apparent liver disease
Authors: Da Silva C. M. F. , David F. L. , Muscará M. N. , Sousa S. S. , Ferraz J. G. P. , De Nucci G. , Polimeno N. C. , Pedrazzoli Jr J. 
Published: March 2003

Aims
To evaluate plasma hydroxy‐metronidazole/metronidazole ratio as a dynamic liver function test in HCV‐infected individuals with/without liver disease, in the absence of liver cirrhosis.
Methods
Metronidazole was administered intravenously in healthy volunteers, asymptomatic anti‐HCV‐positive blood donors, and in chronic hepatitis C patients. Serology to HCV was determined by a second generation assay and confirmed by gelatin particle agglutination test using recombinant antigens C22‐3 and C200. Plasma concentration of metronidazole and hydroxy‐metronidazole was measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min following the end of metronidazole infusion.
Results
Chronic hepatitis C patients had abnormal liver enzymes, while healthy volunteers and anti‐HCV‐positive blood donors had normal liver biochemistry tests. Plasma metronidazole concentration was similar in all groups studied. Plasma hydroxy‐metronidazole/metronidazole ratio was significantly reduced in HCV‐infected subjects, an effect observed 10 min after the end of drug infusion.
Conclusions
Metronidazole clearance is impaired in anti‐HCV‐positive blood donors and chronic hepatitis C patients, indicating that HCV is capable of affecting liver function at early stages of the disease. The metronidazole clearance test can detect impaired liver function in HCV‐infected individuals even in the absence of liver cirrhosis.
Therapeutic drug monitoring—antiepileptic drugs
Authors: Eadie M. J. 
Published: March 2003

Aims
To provide a brief critical review of the basis and contemporary practice of monitoring the concentrations of antiepileptic drugs in biological fluids.
Methods
The review is based on literature data and observations from clinical practice.
Results
As experience has accumulated, monitoring of antiepileptic drug concentrations has come to be applied mainly to certain of the drugs when present in whole plasma. For these drugs there is a reasonably established relationship between drug concentrations and biological effects, but attention still needs to be paid to issues such as the timing of the measurements in relation to drug intake, the presence or absence of steady‐state conditions, the presence in plasma of active metabolites and possible nonlinear pharmacokinetics of particular agents e.g. phenytoin.
Conclusions
Plasma antiepileptic drug concentration monitoring is coming to be used in a more thoughtful and critical manner. Lack of adequate knowledge of matters such as the relationship between the plasma concentrations and antiepileptic and toxic effects of the drugs, not only the newer, but also the longer established ones, in particular clinical situations, remains more important than deficiencies in analytical methodology in limiting the clinical usefulness of antiepileptic drug concentration monitoring.
Pharmacokinetic‐pharmacodynamic model relating zabiciprilat plasma concentrations to brachial and femoral haemodynamic effects in normotensive volunteers
Authors: Bellissant Eric , Giudicelli Jean‐François 
Published: March 2003

Aims
To investigate, in healthy volunteers, the relationships between the plasma concentrations (C, ng ml−1 ) of zabiciprilat, the active metabolite of the angiotensin I‐converting enzyme inhibitor (ACEI) zabicipril, and the effects (E) induced on plasma converting enzyme activity (PCEA, nmol ml−1 min−1 ), brachial and femoral artery flows (BAF, FAF, ml min−1 ), and brachial and femoral vascular resistances (BVR, FVR, mmHg.s ml−1 ) after a single oral administration of two doses (0.5 and 2.5 mg) of zabicipril.
Methods
The study was placebo‐controlled, randomized, double‐blind and crossover. E was related to C by the Hill model, E=Emax.Cγ/(CEγ50+Cγ ), fitted to the data of both doses simultaneously.
Results
We obtained (mean±s.d.) Emax=−99±1%, CE50=2.2±1.0 ng ml−1 and γ=1.0±0.4 for PCEA, Emax=55±26 ml min−1, CE50=5.1±4.0 ng ml−1 and γ=2.4±1.6 for BAF, and Emax=−45±10%, CE50=2.0±1.3 ng ml−1 and γ=2.3±1.4 for BVR. The parameters obtained for FAF and FVR were similar to those obtained for BAF and BVR, respectively. The CE95 (C required to induce 95% of Emax ) varies from 7 to 17 ng ml−1 for haemodynamic effects.
Conclusions
As zabiciprilat peak plasma concentrations average 20 ng ml−1 after the 2.5 mg dose of zabicipril, this dose of the drug should be sufficient to induce optimal haemodynamic effects.