The contribution of plasma (R)- & (S)-warfarin and vitamin K concentrations to intra-individual variability in anticoagulation.
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Biomedical subjects
Publications and source records attributed to T J Butler.
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BACKGROUND: The prevalence of gingival overgrowth induced by chronic medication with calcium channel blockers is uncertain. Although there have been several studies examining this question, the results are conflicting, with previous estimates ranging from 20% to 83%. There have been only 2 studies examining the prevalence of overgrowth induced by diltiazem and amlodipine, with estimates of 74% and 3.3%, respectively. METHODS: The current study aimed to address the problems associated with these studies by examining a sample of patients taking one of 3 calcium channel blockers, who were drawn from a community-based population in northeastern England. Nine hundred eleven (911) subjects were recruited from general medical practices in the area. Of these, 442 were taking nifedipine, 181 amlodipine, and 186 diltiazem. In addition, 102 control subjects were examined. Drug and demographic data for each subject were recorded. The periodontal condition of all subjects was assessed including plaque index, papillary bleeding index, and a photograph of the anterior gingivae for subsequent analysis of overgrowth severity. RESULTS: More than six percent (6.3%) of subjects taking nifedipine were seen to have significant overgrowth. This overgrowth was statistically greater than the amount of overgrowth seen in either of the other 2 drug groups or the control population. The prevalence of gingival overgrowth induced by amlodipine or diltiazem was not statistically significant when compared to the control group. The severity of overgrowth within the nifedipine group was found to be related to the amount of gingival inflammation and also to the gender of the subject, with males being 3 times as likely to develop overgrowth than females. CONCLUSIONS: The prevalence of clinically significant overgrowth related to chronic medication with calcium channel blockers is low, i.e., 6.3% for nifedipine. Males are 3 times as likely as females to develop clinically significant overgrowth. The presence of gingival inflammation is an important cofactor for the expression of this effect.
OBJECTIVE: The aim of the study was to evaluate the effectiveness of a sugar-free medicines campaign using suitable prescribing and purchasing indicators. BASIC RESEARCH DESIGN: Quantitative analysis of sugar-free medicine use, before (1995) and after (1996) the campaign. CLINICAL SETTING: Two test and two control districts in north east England. PARTICIPANTS: General medical practitioners (GPs) and community pharmacists. INTERVENTION: A 12-month campaign involving development and distribution of information packs designed to increase the proportion of prescriptions dispensed sugar-free for paediatric use. MAIN OUTCOME MEASURES: Changes in the proportion of the following which were sugar-free: (a) for target prescribed medicines (i) number of prescriptions dispensed. (ii) number of prescribed daily amounts (PDA); (b) for target over the counter (OTC) medicines, (i) number of bottles sold, (ii) number of standard daily amounts (SDA) sold. RESULTS: Quantitative analysis of prescriptions and OTC sales showed statistically highly significant changes towards sugar-free prescribing and dispensing of prescribed medicines but only small increases in the proportion of some sugar-free OTC sales. CONCLUSIONS: The impact of the campaign was shown to be greatest in changing prescribing habits of GPs with less effect on OTC medicine use. The outcome measures used were suitable for quantitative evaluation of the campaign. POST-CAMPAIGN DEVELOPMENT: Sustainable changes in GPs' prescribing behaviour can be facilitated by software suppliers' modifications to computing software used for prescription writing.
PURPOSE: To determine the resistance of the human posterior lens capsule and zonules to disruption during cataract surgery. SETTING: Wet lab at Walkergate Hospital, Newcastle upon Tyne, England. METHOD: Human donor eyes were obtained after removal of a corneoscleral disc. Lens extraction was performed by an extracapsular technique leaving an intact capsular bag. The resistance of the zonules and posterior capsule to disruption by aspiration was measured in each eye, and the resistance of the zonules to damage from direct mechanical stretch was determined. RESULTS: Posterior capsules tolerated a median suction pressure of 200 mm Hg (range 150 to 300 mm Hg) before disruption. Values for female eyes were slightly greater than for male; no significant correlation with age was shown. The zonular fibers tolerated a median suction pressure of 200 mm Hg (range 150 to 300 mm Hg). The median mechanical zonular stretch tolerance was 3.00 mm (range 2.75 to 4.00 mm). No significant correlation was found between zonular suction tolerance or stretch tolerance and sex or between suction tolerance and age, but a negative relationship was noted between maximum tolerated stretch and age. CONCLUSION: Setting the maximum aspiration pressure during irrigation/aspiration to 150 mm Hg should help prevent capsular or zonular rupture. If more powerful aspiration is required, it should be used with great care so as not to engage the capsule.
Three hundred and ninety boys aged 2, 4 or 6 years from Riyadh, Saudi Arabia, took part in a survey in 1993/94. The main aims of the study were first, to identify factors related to malnutrition in young children since a study of older children from the same area 1 year before had shown malnutrition to be strongly related to prevalence of developmental defects of enamel (DDE) of permanent teeth and, second, to identify factors related to the prevalence of developmental defects of primary teeth. Enamel defects were recorded by clinical examination of the buccal surfaces of all primary teeth by 1 examiner using the DDE index. A questionnaire to parents provided information on socio-economic status, illness in the mother and child, infant feeding, trauma to teeth and toothbrushing. A 24-hour dietary record, to estimate water and milk intake, and a 24-hour urine collection were obtained for each child twice. Nutritional status was calculated from height for age using WHO methods. Multiple regression analyses revealed four variables related (p<0.05) to malnourished status: low birth-weight, low volume of water drunk, child stopped breast- and bottle-feeding before 1 year of age, and low class urban or rural area of residence. Birth-weight was itself related to area of residence (p = 0.02), parental education (p = 0.02) and maternal illness during pregnancy (p = 0.06). Malnutrition (p<0.001), low birth-weight (p<0.001), childhood illness (p<0.001), brushing of child's teeth (p = 0.003) and swallowing toothpaste (p<0.001) were related to the prevalence of developmental defects of primary teeth. This study indicated several independent variables which may be related to the prevalence of enamel defects in primary and permanent teeth, but longitudinal studies are required to determine which are causes and which are markers of these developmental defects.
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A rare state of acquired hypercoagulability known as heparin-associated or heparin-induced thrombocytopenia and thrombosis (HATT, HITT) exists. It appears to be caused by an antibody reaction with heparin-platelet factor 4 complexes. A mild and severe form exist, but both varieties occur after exposure to heparin. The authors describe a fatal neonatal case of hypercoagulability on extracorporeal membrane oxygenation, and their evaluation that determined the etiology as type II HATT. They discuss the pathophysiology of HATT as well as possible alternative anticoagulation approaches.
BACKGROUND/PURPOSE: Cardiopulmonary resuscitation (CPR) is reported to be used in a significant number of neonates before initiation of extracorporeal membrane oxygenation (ECMO). This report establishes the incidence of infants who require CPR before initiation of ECMO and elucidates survival rates and long-term neurological outcomes. In addition, the authors sought prognostic factors that could reliably predict survival or long-term neurological outcome before initiating ECMO support. METHODS: The Extracorporeal Life Support Organization (ELSO) registry provided data on 839 neonates who received CPR before ECMO from January 1989 to April 1995. Supplemental questionnaires on 414 infants were returned from 64 ECMO centers regarding details of the CPR event and subsequent neurological development. One-year neurological evaluations were provided on 112 infants. Data were analyzed for statistical significance using chi2, multiple logistic regression, and Kruskal Wallis one-way analysis of variance as applicable, with significance set at P < .05. RESULTS: The incidence of infants requiring pre-ECMO CPR was 13.1%. Infants who received pre-ECMO CPR had a survival rate of 60.8% versus 81.6% survival for infants who did not require CPR (P < .00001). Analysis of ELSO registry data showed survival was significantly associated with primary diagnosis, location of CPR, last pH level before ECMO, and the presence of intraventricular hemorrhage. Questionnaire data on 12-month neurological assessment showed 63% had no impairment and 4% were graded as severely impaired. Twelve-month neurological outcome was significantly associated only with primary diagnosis. CONCLUSION: A survival rate of 60.8% with good neurological outcome at 12 months in 63.4% of infants suggests that CPR alone should not be a contraindication to placing a neonate on ECMO.
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To further elucidate the role of atrial natriuretic peptide (ANP) in preeclampsia, its metabolic clearance (MCRANP) was determined concomitantly with its effects on sodium excretion (UNa), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF). Ten untreated preeclamptic primigravidae (PET) were studied at 29-37 wk gestation and again 4 mo postpartum (PP). Basal plasma concentration of ANP was significantly increased in PET compared with PP (14.8 +/- 1.9 vs. 4.1 +/- 0.5 pmol/l, respectively; P < 0.0001). MCRANP in PET and PP was 5.0 +/- 0.8 and 4.9 +/- 0.5 l/min [not significant (NS)], respectively. In PET, infusion of ANP produced (basal vs. ANP) a natriuresis (UNa 0.14 +/- 0.02 vs. 0.28 +/- 0.04 mmol/min, P < 0.001) and an increase in GFR (97 +/- 7 vs. 106 +/- 8 ml/min, P < 0.05), with ERPF unchanged (609 +/- 24 vs. 634 +/- 29 ml/min, NS). In PP, ANP infusion also produced a natriuresis (UNa 0.20 +/- 0.02 vs. 0.25 +/- 0.02 mmol/min, P = 0.01), no significant change in GFR (109 +/- 7 vs. 102 +/- 4 ml/min), and a significant reduction in ERPF (514 +/- 22 vs. 409 +/- 18 ml/min, P < 0.0001). Analysis of variance demonstrated a greater natriuretic effect of ANP in PET compared with PP (P < 0.05), similarly a significant difference in the effect of ANP on ERPF (P < 0.01) and GFR (P < 0.05) was seen but not on filtration fraction (P = 0.35).
Fourteen-year-old boys from three regions of Saudi Arabia were surveyed in 1992/3. These regions were Jeddah (which receives desalinated water containing 0.22 mgF/l), Riyadh (receiving water containing 0.78 mgF/l) and Qassim (2.66 mgF/l). For each of these urban communities an adjacent rural community was selected; these received water with 0.25, 0.80, and 2.71 mg/l, respectively. Subjects from the urban communities were classified into high, medium and low socio-economic status based on area of residence, income and education level of parents. Nutritional status was calculated from height and age using WHO methods and expressed as height for age percentage of the median of the reference population (HAM); children with HAM scores of less than 95% were classed as malnourished. The developmental defects of enamel index was recorded on the buccal surface of all permanent teeth, by one examiner. Colour photographs of anterior teeth were read 'blind' to investigate examiner bias between regions-there was no bias. A total of 1,539 children were examined who had been continuously resident in that community. Overall, 83% of subjects had one or more enamel defects with a mean number of teeth affected per person of 9.6. Diffuse defects were the most common. Multivariate analyses revealed that all three variables-region, nutritional status, socio-economic status-were statistically significantly related to the prevalence of defects and the number of teeth affected: prevalence was highest in the region with the highest water fluoride concentration, in rural areas and in malnourished subjects. Maxillary incisor teeth were the most affected teeth in all regions. The findings have implications for those in public health who determine optimum fluoride levels in drinking water in Saudi Arabia and beyond.
A large number of liquid oral medicines contain sugars and there is concern for the dental health of children requiring this medication long-term for chronic medical problems. Ninety-four chronically sick children aged 2-17 years taking sugar-based or sugar-free liquid oral medication for 1 year or more, and their 92 siblings were dentally examined. The medical problems of the sick children included epilepsy, cystic fibrosis, chronic renal failure, asthma, recurrent urinary tract infections, cardiac disease and chronic constipation. Ordinal logistic regression analysis compared differences between sick children and their healthy siblings and showed the only significant confounding factors related to dental health to be age (for dmfs p = 0.013, DMFS p < 0.001) and exposure to fluoridation (for DMFS p = 0.0097, DFS (approximal) p = 0.013). Children taking long-term liquid oral medicines had significantly more caries of deciduous anterior teeth than their siblings (p = 0.046).
We previously demonstrated the sequestration of nifedipine in gingival crevicular fluid (GCF), especially in patients exhibiting significant gingival overgrowth. The aim of the present study is to determine the role of site specific periodontal factors in this phenomenon. 10 adult patients exhibiting nifedipine induced gingival overgrowth were studied. In each patient GCF was harvested from two sites that demonstrated inflammation and increased probing depth as well as from two clinically healthy sites. The concentration of nifedipine was determined using gas chromatography. Drug concentrations were significantly increased in the presence of inflammation (p = 0.004) and plaque (p = 0.029) whilst increased probing depths and gingival overgrowth were not significantly related to drug sequestration. We can conclude that inflammatory changes in gingival tissues appear to be a significant determinant for the sequestration of nifedipine in the GCF.
Ultrasound assessment of patients with renal impairment commonly includes measurement of bipolar renal length. Reduction in length is considered to indicate chronic renal disease and is a factor in deciding whether to proceed to renal biopsy. To date, no published data are available on interobserver and intraobserver variation in sonographic renal length measurement in adults. Bilateral renal lengths were measured in 20 adult subjects, with no history of renal disease, by three experienced operators, on two separate occasions. Limits of agreement for replicate measurements by each ultrasonographer and for replicate measurements by each pair of ultrasonographers were determined. Values of repeatability (a measure of intraobserver variation) and reproducibility (a measure of interobserver variation) were calculated for all renal length measurements, and for right and left renal lengths separately. Results indicate that replicate renal length measurements differ by less than 1.85 cm in 95% of cases, and the magnitude of variations is similar when measurements are made by either single or different ultrasonographers, and are similar for right and left renal length measurements. This suggests that sonographic bipolar renal length measurements in normal adult kidneys are reasonably reliable. In diseased kidneys, however, in which identification of renal poles is difficult, interobserver and intraobserver variation may be much greater.
The rate of cell division of human embryos in vitro was estimated throughout the preimplantation period. Seventy-five human embryos were assessed by performing nuclei counts on whole mount preparations at 24 h intervals between day 2 and day 6 of development. The results indicate that the cell doubling time increases after the first two division cycles. The mean (+/- SEM) doubling time between day 2 and day 6 was 31 +/- 2.51 h. At the end of the designated culture periods, embryos were exposed to a microtubule disrupting agent, which caused the nuclei to arrest in metaphase. Thus, a profile of the mitotic activity at given stages of development was obtained. The numbers of actively dividing cells were frequently lower than anticipated, indicating that nuclei counts cannot be directly correlated with continuing mitotic activity.
Compromised masticatory efficiency places edentulous persons at risk of consuming a diet low in non-starch polysaccharide (NSP) ('dietary fibre'). No study has quantified NSP intake in edentulous people using a valid and reliable method of dietary assessment. The aim of this study was to provide quantitative data on NSP intake of edentulous persons, together with information on its dietary sources. Using the dietary history method, habitual intake of NSP was compared between edentulous persons (n = 30) and dentate persons (n = 30) between the ages of 40 and 60. Groups were matched for sex and social class. The edentulous group had a median NSP intake of 73 (31-211) g/week. This was significantly lower than that of the dentate group of 106 (25-225) g/week (P = 0.014). Neither group completely met current UK guidelines. NSP intake of 56% (n = 17) of the edentulous group was below 84 g/week, whilst 17% (n = 5) of the dentate group was below this figure--a level of intake below which increased occurrence of gastrointestinal complaints has been observed. The dentate group obtained significantly more NSP from all rich sources, including wholemeal breads, cereals, vegetables and fruit. Depending on their form and preparation, such foods are not necessarily difficult to chew. Specific advice on food selection is required to ensure the edentulous patient has an adequate intake of NSP. Education of the dentist for this purpose is of paramount importance.
Systemic heparinization is required for both neonatal and paediatric extracorporeal membrane oxygenation (ECMO). However, it places the patient at risk of serious haemorrhage. We report an alternative: 'selective' heparinization of the ECMO circuit using a continuous infusion of heparin near the venous catheter as blood enters the circuit, and a simultaneous protamine infusion near the arterial catheter as blood enters the patient. Theoretically, the circuit remains heparinized while the patient maintains near-normal clotting activity. Three healthy piglets were placed on venoarterial ECMO in standard fashion. When the animal and its extracorporeal circuit flow were stable, a protamine infusion was begun: 1 mg of protamine to neutralize each 100 units of infused heparin. No haemodynamic instability was noted during the five hours of each study. Mean activated clotting times (ACT) were significantly lower in all three piglets than in their respective circuits (p < 0.001). We conclude that 'selective' heparinization of the ECMO circuit is possible using continuous infusions of protamine and heparin in a short-term piglet model.
BACKGROUND: This study was done to determine the safety and success of orotracheal intubation with planned neuromuscular blockade in patients who are severely injured. The study was performed at Carle Foundation Hospital, designated Level I trauma center located in east central Illinois. STUDY DESIGN: A retrospective review of the trauma registry and medical records of all patients requiring emergency airway control from September 1, 1987 to September 30, 1991 was performed. Two hundred twenty-nine patients who were critically injured were reviewed, the mean injury severity score was 29 (range of 3 to 75), the mean revised trauma score was 9 (range of 3 to 12), the mean Glasgow Coma Scale was 9 (range of 3 to 15), and the mean age was 31 years (range of one to 94 years). RESULTS: Indications for intubation included hemodynamic instability or altered level of consciousness (66.4 percent), or both, combative or uncooperative behavior (33.2 percent), and need to secure airway for transport (0.4 percent). Two hundred twenty-three (97.4 percent) patients were successfully intubated. Six (2.6 percent) patients required cricothyroidotomy and one (0.4 percent) patient was aspirated during intubation. Eight (3.5 percent) patients had cervical spine injuries but had no complications from orotracheal intubation. In the combative group, 32 (42 percent) patients had significant head injuries and 17 (22 percent) had other potentially life-threatening injuries. CONCLUSIONS: Orotracheal intubation with planned neuromuscular blockade and in-line cervical traction is a safe, effective method for airway control in patients who are severely injured. This technique is also indicated to expedite therapy in combative, uncooperative patients because of the high incidence of significant life-threatening injuries to the brain and other organs.