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Biomedical subjects

K Woods

Publications and source records attributed to K Woods.

At least 37 records · Page 2Linked to original sources

Generating ROC curves for artificial neural networks.

Receiver operating characteristic (ROC) analysis is an established method of measuring diagnostic performance in medical imaging studies. Traditionally, artificial neural networks (ANN's) have been applied as a classifier to find one "best" detection rate. Recently researchers have begun to report ROC curve results for ANN classifiers. The current standard method of generating ROC curves for an ANN is to vary the output node threshold for classification. In this work, we propose a different technique for generating ROC curves for a two-class ANN classifier. We show that this new technique generates better ROC curves in the sense of having greater area under the ROC curve (AUC), and in the sense of being composed of a better distribution of operating points.

Diagnostic Imaging↗

Social deprivation and tooth decay in Scottish schoolchildren.

OBJECTIVES: To quantify the association between dental decay in Scottish Schoolchildren & social deprivation as measured by the Carstairs Index from the 1991 census. DESIGN: An ecological study using data from the Scottish Health Boards Dental Epidemiology Programme and The Public Health Common Data set. SETTING: Scottish Health Boards from 1992-3 to 1994-5. SUBJECTS: Random samples of 5,920 five-year-olds, 5,344 12-year-olds and 6,007 14-year-olds across the 15 Health Boards in Scotland. RESULTS: Positive correlations were demonstrated in all age groups; 12-year-olds (r = 0.72) in 1992-3, 5-year-olds (r = 0.8) in 1993-4 and 14-year-olds (r = 0.55) in 1994-5. Dental decay in all age groups was positively and significantly associated with deprivation as measured by the Carstairs index. CONCLUSION: Tooth decay was confirmed as a disease associated with social deprivation in Scotland. The increasing polarisation of decay to socio-economically deprived groups of the population, suggests a 'whole population' approach such as water fluoridation would prevent tooth decay in these deprived groups most effectively. Nevertheless all evidence-based interventions should be used to try to narrow the "Dental Health Divide' by improving the dental health of deprived individuals.

Adolescent↗

Emergency department use of flumazenil prior to poison center consultation.

We studied the frequency of use of flumazenil by emergency departments in our region and compared it to recommendations made by specialists in poison information at our poison control center. For a 5-mo period, we prospectively collected cases involving benzodiazepines or zolpidem. Data was documented only from calls from emergency departments. Emergency department personnel were asked the following: If given, the dose and frequency, contraindications, and adverse reactions. Each case was followed to completion. Flumazenil was not given in 55 cases. Of the remaining 14 cases in which it was given, 10 of the cases received flumazenil prior to poison control center consultation. We noted 1 case of dizziness. Ten cases given flumazenil had contraindications (eg ethanol abuse or possible seizurogenic coingestants). Despite possible contraindications, flumazenil was given 10/14 times (71%) prior to calling the poison control center. These results point to potential overuse of this antidote where contraindications or cautions are suspected in the overdosed patients. Our study suggests that when flumazenil use is contemplated by an emergency department physician, a poison control center consult may have a contrary recommendation.

Antidotes↗

Jarman underprivileged area scores, tooth decay and the effect of water fluoridation.

OBJECTIVE: To examine the association between dental caries and Jarman underprivileged area scores at regional, district and electoral ward level and explore any possible relationship with water fluoridation. DESIGN: An ecological study using the English results from the NHS dental surveys on 5-year-old children in 1991/2 and 1993/4, and the survey of 12-year-old children in 1992/3. Jarman underprivileged area scores were used from the 1991 census. SETTING: The study used former English health authority regions and districts. The electoral wards were in non-fluoridated Salford and Trafford and Liverpool, and fluoridated Newcastle and North Tyneside. SUBJECTS: The random sample of 5-year-old children examined in 1991/2 and 1993/4, and 12-year-old children in 1992/3, in studies coordinated by the British Association for the Study of Community Dentistry. OUTCOME MEASURES: Correlations between regional, district and electoral ward mean dmft/DMFT and Jarman underprivileged area scores. RESULTS: Significant correlations were demonstrated at a regional level in 5-year-old children in 1991/2, district level in 5-year-old children in 1991/2 and 1993/4 and at electoral ward level in both age groups in 1992/3 and 1993/4. Correlation coefficients varied between r = 0.88 to r = 0.46. Multiple linear regression at electoral ward level showed significant interactions between Jarman scores and water fluoridation. There was an average 44 per cent and 43 per cent reduction in caries in fluoridated electoral wards in 5- and 12-year-old children respectively. In deprived electoral wards, with a Jarman score of 40, the reduction in caries increased to 54 per cent and 56 per cent for 5- and 12-year-old children respectively. CONCLUSIONS: Dental caries was associated with Jarman underprivileged area scores. The differential efficacy of fluoridation to deprived areas was demonstrated at electoral ward level. Water fluoridation was confirmed as an evidence based intervention which has halved the amount of tooth decay in 5- and 12-year-old children.

Child↗

A nucleolar RNA helicase recognized by autoimmune antibodies from a patient with watermelon stomach disease.

Watermelon stomach is characterized by prominent stripes of ectatic vascular tissue in the stomach similar to stripes on a watermelon; in patients with this disorder chronic gastrointestinal bleeding occurs and approximately half of these patients have associated autoimmune disorders. In the serum of one patient, an antinucleolar antibody titer of 1:25 600 was found; the antibodies specifically recognized an approximately 100 kDa nucleolar protein, which we referred to as the 'Gu' protein. Its cDNA was cloned and sequenced. The Gu protein is a member of a new subgroup of RNA helicases, the DEXD box family. Gu protein fused with glutathione S-transferase contains ATP-dependent RNA helicase activity which preferably translocates in the 5'-->3' direction. Its RNA folding activity, RNA-dependent ATPase and dATPase activities, and its translocation direction are similar to those of RNA helicase II [Flores-Rozas, H. and Hurwitz, J. (1993) J. Biol. Chem. 268, 21372-21383]. Sequencing of 209 amino acids of RNA helicase II peptides showed 96.7% identity with the cDNA-derived amino acid sequence of the Gu protein. The precise biological roles of this RNA helicase in the biogenesis of ribosomal RNA and the pathogenesis of watermelon disease and autoimmune disorder require further study.

Adenosine Triphosphatases↗

Index of Orthodontic Treatment Need, its use in a dental epidemiology survey calibration exercise.

The Index of Orthodontic Treatment Need (IOTN) was included in a pre-survey calibration exercise of 18 dental epidemiologists. Nine months later 16 of the epidemiologists were re-calibrated in the IOTN. The Index was readily accepted by the experienced dental epidemiological examiners and each examination was estimated to be extended by, on average, less than two minutes. The inter-examiner agreement of the dental health component using the weighted kappa statistic improved from a mean of 0.53 (moderate agreement) for the first calibration to 0.66 (good agreement) at the second calibration. The mean inter-examiner agreement on the aesthetic component using the weighted kappa statistic reduced from 0.52 for the first calibration to 0.49 at the second. Using sensitivity and specificity to measure agreement on the dichotomous decision of those defined as having a definite treatment need, mean sensitivity rose from 0.72 to 0.79 and specificity from 0.90 to 0.97. It is concluded that dental examiners for epidemiological surveys can be trained to use the IOTN by using a pre-calibration exercise and that agreement on the dental health component improves after the index has been used for some months.

Adolescent↗

Stability of foscarnet sodium in 0.9% sodium chloride injection.

The stability of foscarnet sodium in 0.9% sodium chloride injection was studied. Foscarnet sodium 24 mg/mL was added to polyvinyl chloride i.v. bags containing 0.9% sodium chloride injection to give a theoretical foscarnet sodium concentration of 12 mg/mL. Ten bags of solution were stored at 25 degrees C in normal laboratory light, 10 bags were stored at 25 degrees C in the dark, and 10 bags were stored at 5 degrees C in the dark. Samples were analyzed for foscarnet concentration by high-performance liquid chromatography on days 0, 3, 8, 10, 15, and 30. The solutions were visually inspected for particulates, and pH was measured. Foscarnet sodium was stable in all the solutions for up to 30 days under all the storage conditions; mean foscarnet concentrations did not decline below 99% of initial values. No particulates appeared, and there were no important changes in pH. Foscarnet sodium 12 mg/mL in 0.9% sodium chloride injection was stable for up to 30 days when stored at 25 degrees C and exposed to light, 25 degrees C and protected from light, or 5 degrees C and protected from light.

Chromatography, High Pressure Liquid↗

The insulin-like growth factor I generation test in the investigation of short stature.

Genotypic and phenotypic heterogeneity in patients with growth hormone (GH) insensitivity syndrome suggests that partial defects exist in the GH receptor. The insulin-like growth factor I (IGF-I) generation test was assessed as a means of identifying partial GH receptor defects in a heterogeneous group of 22 prepubertal children with short stature. In a subgroup of nine patients with peak GH levels of 63.7 +/- 3.7 mU/l during a glucagon tolerance test, the response to the IGF-I generation test was no different from that for the group as a whole (peak GH, 43.3 +/- 4.5 mU/l), despite the fact that this subgroup exhibited a negative relationship between height SDS and peak GH and a positive relationship between height SDS and IGF binding protein-3. This preliminary study therefore suggests that the IGF-I generation test in its present form will not be useful as a primary screening test for partial GH insensitivity. Despite this, the IGF-I generation test has been extremely useful in the confirmation of the diagnosis of GHIS and may therefore also prove useful in the confirmation of partial defects in the GH receptor. A subgroup of short children with peak GH levels above 40 mU/l had some characteristics of partial GH receptor deficiency. These children, to whom GH therapy would not normally be given, may respond better to recombinant human IGF-I.

Body Height↗

Genetic linkage of Werner's syndrome to five markers on chromosome 8.

Werner's syndrome (WS) is a rare autosomal recessive disease in which the affected individuals display symptoms of premature ageing. The substantial phenotypic overlap between WS and normal ageing indicates that these two conditions may have pathogenetic mechanisms in common. The WS mutation has pleiotropic effects, and patients and their cells show many differences compared with normals. Despite extensive study of the clinical and biochemical features of this disorder, the primary genetic defect remains unknown. We have undertaken a genetic linkage study in an effort to identify the locus of the primary defect. Here we report close genetic linkage of the WS mutation to a group of markers on chromosome 8.

Chromosome Mapping↗

Gelatinolytic metalloproteinase secretion patterns in ocular melanoma.

Fifteen posterior uveal melanoma cell lines were analyzed qualitatively for gelatinolytic and caseinolytic proteinase activity after one to five in vitro passages. All 15 cell lines secreted a gelatinolytic metalloproteinase, with an apparent molecular weight of 72 kD, into protein-free culture media; nine of these secreted an additional gelatinolytic metalloproteinase with an apparent molecular weight of 92 kD. Neither species had the ability to degrade casein. This approach may provide insight into the mechanisms of tumor metastasis in uveal melanoma.

Aged↗

An investigation of parotid gland function and histopathology in autoimmune disease-prone mice of different age groups.

This work aimed to characterize parotid gland function in autoimmune disease-prone murine strains (MRL/n, MRL/l and NZB/W) in relation to increasing age and to relate the extent of functional impairment to the intensity of histopathologic changes observed at the different ages. Pilocarpine-stimulated parotid saliva was collected to assess salivary flow rate and composition. Parotid tissue was then removed for histopathologic assessment. Parotid flow rates were not significantly reduced in autoimmune strains compared to controls but were reduced with age in NZB/W mice and in males of the C57 (control) strain. Age-related salivary compositional changes were present in MRL/l mice and in male NZB/W mice. Focal lymphocytic adenitis increased with age in prevalence and intensity in both sexes. The functional and histopathologic changes were not closely correlated. These results suggest that the parotid gland of autoimmune disease-prone mice provides only a poor replication of the salivary changes in human Sjögren's syndrome. Nevertheless, both the functional and histopathological changes developing in these strains, even though of limited extent, are significantly influenced by age.

Aging↗

The effects of a liquid diet on initial and sustained, stimulated parotid salivary secretion and on parotid structure in the rat.

Adult male rats were maintained on a nutritionally adequate liquid diet, or laboratory chow and water (controls), for 7 days. They were then anaesthetized and parotid flow was recorded after isoprenaline or pilocarpine stimulation, each collected over two, timed sampling periods--an initial 5 min and a subsequent 15 min. The isoprenaline-induced flow rates in liquid diet rats were reduced to 45 and 30% of those in control rats for the first and subsequent samples respectively (p less than 0.02). After pilocarpine stimulation there were no significant differences in the first samples, but in the subsequent samples the flow rate in liquid diet rats was reduced to 54% of that in controls (p less than 0.001). The parotid gland weights were reduced by 35% in liquid diet rats compared to controls (p less than 0.05). On computerized planimetric analysis, parotids (from rats that had not been given secretagogues) had significantly smaller mean acinar areas, mean acinar profile perimeters and mean acinar transection diameters after liquid feeding (p less than 0.001). The findings support the notion that there is a functional reserve capacity available in atrophied glands to support the relatively fast flow that occurs on initial stimulation but which becomes exhausted during sustained stimulation. This exhaustion occurs more severely and more rapidly in the low-volume, protein-rich saliva elicited by sympathomimetic stimulation than in the high-volume, low-protein saliva formed in response to parasympathomimetic stimulation.

Animals↗

Biochemical pharmacology of acyclic nucleotide analogues.

Our studies have shown that the acyclic nucleotide analogues PMEA and HPMPC are able to penetrate into cells and are then activated to mono- and diphosphate derivatives. The latter correspond to triphosphate analogues and presumably serve an important role in the biological activity exerted by these antiviral agents. In support of this idea, the inhibitory effect of PMEApp on HIV reverse transcriptase has been demonstrated with both RNA and DNA template-primer systems. Further studies will be undertaken to determine the effect of HPMPCpp on viral DNA polymerases. Whereas the metabolism of PMEA in CEM cells gives rise to only PMEAp and PMEApp, additional metabolites were obtained in MRC-5 cells; the identity of these metabolites remains to be determined. In the case of HPMPC, a third metabolite was obtained in addition to HPMPCp and HPMPCpp, which has been tentatively assigned as a phosphate-choline adduct by analogy with activation of cytosine-based nucleoside derivatives. The metabolism of HPMPC was unchanged between uninfected and infected cells, indicating that viral enzymes are not necessary for the activation of HPMPC. The long intracellular half-lives of the HPMPC metabolites may have implications for the antiviral efficacy of this compound. The persistence of activated metabolites suggests that infrequent dosing may be possible due to a prolonged antiviral effect. Our results on the effectiveness of infrequent dosing schedules with HPMPC in the treatment of HSV 2 infections in mice support this hypothesis. It is also possible that HPMPCp-choline may serve as a reservoir for HPMPC and therefore for the presumed active metabolite HPMPCpp.

Adenine↗