Search PubMed⌕ Search

Biomedical subjects

J Cunningham

Publications and source records attributed to J Cunningham.

At least 55 records · Page 3Linked to original sources
PubMed1999

Teaching and assessing ethics and law in the dental curriculum.

The General Dental Council's recommendations on dental education places a new emphasis on the importance of ethics and law in the dental curriculum, stating that students should have an awareness of moral and ethical responsibilities involved in the provision of care to individual patients and to populations. The duties of care to protect a patient's life and health at all times, to respect their autonomy to make informed choices about what happens to them, and to do this fairly and without prejudice, are widely accepted as the fundamental ethical principles governing all health care. The specifics of these duties of care are detailed in Maintaining Standards: guidance to dentists on professional and personal conduct, published by the GDC.

Adult↗
PubMed1999

Ier5, a novel member of the slow-kinetics immediate-early genes.

We describe here a novel member of the slow-kinetics immediate-early gene family. Ier5 is an intronless gene, encoding a serum- and growth factor-inducible message of 2123 nucleotides that is present in a wide variety of tissues. The predicted open reading frame encodes a 308-amino-acid, highly proline-rich protein with homology to the amino terminus of the immediate-early gene pip92/Ier2/ETR101. Ier5 is predicted to be a nuclear protein and contains a PEST-like sequence, suggesting rapid protein degradation. Multiple phosphorylation sites are present. Ier5 shows growth factor induction kinetics similar to that of pip92/Ier2/ETR101, but unlike pip92/Ier2/ETR101 does not appear to require phosphokinase C activity for transcriptional activation. The sequence of the promoter region of Ier5 was determined and examined for transcription factor binding sites thought to mediate serum and growth factor response. Multiple AP-1 sites and an Ets-1 site were observed, but the CArG and CArG-like boxes of the serum response element were absent. The predicted nuclear localization of Ier5, coupled with the potential for rapid regulation by phosphorylation and/or degradation, suggests that Ier5 may play an important role in mediating the cellular response to mitogenic signals.

3T3 Cells↗
PubMed1999

Isolation and characterization of microsatellite loci in black rhinoceros (Diceros bicornis).

The black rhinoceros (Diceros bicornis) is currently one of the most endangered African mammals as a direct result o habitat destruction and intensive poaching. A microsatellite library was constructed to address a number of population genetic questions. This paper describes the isolation of five black rhinoceros microsatellite loci. Three of these loci were found to be polymorphic. In addition, the paper demonstrates the utility for cross-hybridization of these primers in other species of rhinoceros.

Animals↗
PubMed1999

Comparison of the persistent efficacy of the injectable and pour-on formulations of doramectin against artificially-induced infection with Dictyocaulus viviparus in cattle.

The persistent efficacy of the injectable and topical formulations of doramectin was compared against experimental challenges with infective larvae of Dictyocaulus viviparus in two separate studies. Four groups of 10 randomly-assigned calves, negative for lungworm larvae by the Baermann technique, were used in each study. Calves were treated subcutaneously in the midline of the neck or poured down the midline of the back with saline (1 ml/50 kg. injection: 1 ml/10 kg. pour-on) on Day 0 or doramectin (200 microg/kg = 1 ml/50 kg. injection: 500 microg/kg = 1 ml/10 kg. pour-on) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. Calves were inoculated daily with a gavage of approximately 100 larvae of D. viviparus from days 35 to 49 for the injectable study and days 28 to 42 for the pour-on study. The two larval viability monitor calves received approximately 3000 infective larvae in the same manner on Day 49 or 42 for the injectable and pour-on studies, respectively. Equal numbers of calves from each treatment group as well as the larval viability monitor calves were necropsied on days 14 and 15 after the last lungworm inoculation to enumerate the worm burden. The worms recovered were quantified and identified. For each study, geometric mean worm recoveries for each treatment group were back transformed from the natural log-transformed data (worm count +1) and were used to estimate percentage reduction. Doramectin injectable solution was 100.0% efficacious against lungworms for up to 49 days and the pour-on formulation was 100.0%, 93.1% and 81.5% effective in reducing lungworm infection resulting from challenge infection for up to 28, 35, and 42 days post-treatment, respectively.

Administration, Topical↗
PubMed1999

The failed gastrointestinal anastomosis: an inevitable catastrophe?

BACKGROUND: There is a great deal of conflicting data regarding risk factors for anastomotic leakage, with most studies being small and looking only at anastomoses performed at one level of the gastrointestinal (GI) tract. Surgeons have looked at patient and technical variables with inconsistent findings. The purpose of this study was to evaluate the incidence, possible predictive factors, and results of treatment of anastomotic dehiscence in patients undergoing operations at all levels of the GI tract. STUDY DESIGN: We evaluated the records of 2,842 patients undergoing esophagogastrectomy, total or partial gastrectomy, enterectomy, and partial or subtotal colectomy over a 12-year period. Complete demographic data, comorbidity, and details regarding anastomotic technique were collected on all patients sustaining leaks along with diagnostic methods used, treatment modalities, and outcomes data. Using age and gender-matched case control methodology, we compared patients sustaining an anastomotic leak to those undergoing successful anastomoses. RESULTS: Fifty-one of 2,842 patients (1.8%), ranging from 1.1% of enterectomy patients to 4.8% of total gastrectomy patients, sustained an anastomotic dehiscence. Foregut procedures were accompanied by a significantly increased rate of leakage, and depending on location, diagnosis was made between the 6th and 9th postoperative day. For each procedure, deaths from factors other than leakage far exceeded deaths from leaks. Standard risk stratifiers did not predict occurrence of leakage. Overall, 24% of patients sustaining a leak died, and this complication necessitated multiple reoperations and significantly increased length of hospital stay. CONCLUSIONS: In view of these findings, standard preoperative strategies to prepare these patients for operation may prove unsuccessful, because minimizing the incidence of anastomotic leaks will have little overall impact on survival. In addition, efforts to accomplish early hospital discharge may prove hazardous, because many of these patients manifest their leaks later in the postoperative period than is generally assumed. Improved management of GI tract disruption, including aggressive attempts at diagnosis, ICU care, antibiotics, and nutritional support may further increase survival in these patients.

Anastomosis, Surgical↗
PubMed1999

Speech-sound discrimination in school-age children: psychophysical and neurophysiologic measures.

This study measured behavioral speech-sound discrimination and a neurophysiologic correlate of discrimination in normal school-age children (ages 6 to 15) to determine if developmental effects exist. Just noticeable differences (JNDs) and mismatch responses (MMNs) were assessed for synthetic syllables that differed in third-formant onset frequency (/da-ga/) and formant transition duration (/ba-wa/). These stimuli were selected because children with learning problems often find it difficult to discriminate rapid spectrotemporal changes like /da-ga/, whereas the ability to distinguish /ba-wa/ is relatively unimpaired. Results indicate that JNDs for /da-ga/ show no developmental effects and that JNDs for /ba-wa/ decrease slightly with age (although likely for task-related reasons). MMNs elicited by two /da-ga/ stimulus pairs (onset frequency differences = 20 Hz, 280 Hz) and three /ba-wa/ stimulus pairs (transition duration differences = 3, 5, 15 ms) showed no systematic or significant differences for onset latency, duration, or area as a function of age. Normative JND and MMN data are provided. These norms provide a metric against which children with suspected central auditory processing difficulties or auditory-based language disorders can be compared.

Adolescent↗
PubMed1999

Effects of new analogues of vitamin D on bone cells: implications for treatment of uremic bone disease.

BACKGROUND: The use of calcitriol in the treatment of uremic hyperparathyroidism and renal osteodystrophy is limited in many patients by hypercalcemic side-effects. New less calcemic analogues of calcitriol are being developed, and some are under clinical evaluation. To investigate whether these compounds possess important differences in their action on bone cells, we have studied their effects [with and without parathyroid hormone (PTH)] on the release and synthesis of the resorptive osteotropic cytokine, interleukin-6 (IL-6). METHODS: MG 63 and SaOS-2 human osteoblastic cell lines were cultured for 6 or 24 hours in media containing calcitriol, the sterols of interest, or 1-34 synthetic PTH. IL-6 release was assayed by commercially available enzyme-linked immunosorbent assay. IL-6 mRNA levels were assessed by reverse transcriptase-polymerase chain reaction. RESULTS: We found that calcitriol and paricalcitol behaved in a similar fashion, resulting in increased IL-6 release only at higher concentrations (10(-7) to 10(-9) M). In contrast, 22-oxacalcitriol and 1,25-dihydroxydihydrotachysterol2 stimulated release to a similar extent but at concentrations three to four orders of magnitude lower (10(-11) to 10(-13) M), despite being less potent as suppressers of parathyroid function than calcitriol. Studies of IL-6 mRNA showed a similar pattern of concentration and cell line-dependent transcription. CONCLUSIONS: Compounds stimulating IL-6 release at concentrations achievable during the treatment of uremic hyperparathyroidism might favor continuing linked bone formation and resorption and thereby avoid adynamic bone disease while still allowing profound suppression of PTH.

Bone Diseases↗
PubMed1999

What is the optimal regimen for vitamin D?

The past 30 years have seen substantial advances in our understanding of the pathogenesis of the mineral, hormonal and skeletal disorders that comprise renal osteodystrophy. The introduction of calcitriol and alfacalcidol as treatments for this disorder in the early 1970s represented an enormous step forward in clinical practice, but unfortunately, the subsequent refinement of these therapies still leaves us well short of the ideal: hyperphosphatemia and hypercalcemia induced by the vitamin D metabolites, and failure to control parathyroid hyperplasia, all remain problematic. Novel pulsed regimens using alfacalcidol and calcitriol, while clearly effective, have not fulfilled initial high expectations of superiority in the context of comparative studies. New vitamin D metabolites, some of which have exhibited desirable selectivity in experimental settings with reduced tendency to raise phosphate and/or calcium while maintaining good control of the parathyroid glands, are now being evaluated. Of these, 22-oxacalcitriol, paricalcitol (19 nor-1,25 dihydroxyvitamin D2) and doxercalciferol (1 alpha-hydroxyvitamin D2) have all shown high efficacy when compared with placebo, but so also did alfacalcidol and calcitriol in similar studies in the 1970s and 1980s. The results of randomized studies comparing the new vitamin D metabolites with current standard therapy (alfacalcidol or calcitriol) are either not yet available or show uncertain benefits in relation to hypercalcemia, hyperphosphatemia and hyperparathyroidism. The impact of these new metabolites on the increasing prevalence of low turnover bone disease is unknown, although experimentally there is evidence of potentially important differences at the level of the skeleton.

Animals↗
PubMed1999

Effects of red blood cell transfusion on resting energy expenditure in adolescents with sickle cell anemia.

BACKGROUND: Previous studies indicate that resting energy expenditure is elevated in children with sickle cell anemia, possibly caused in part by hemolysis and increased erythropoietic activity. The purpose of the present investigation was to determine whether erythrocyte transfusion normalizes resting energy expenditure in sickle cell anemia. METHODS: Five adolescents with sickle cell anemia (12-16 years old; 4 boys, 1 girl) were studied before and 1 week after erythrocyte transfusion before elective surgery or at the initial transfusion for growth failure. Resting energy expenditure was measured by indirect calorimetry, and laboratory measures were determined by routine, validated methods. Data comparisons were by nonparametric analysis. RESULTS: After erythrocyte transfusion, total hemoglobin levels increased (difference (D) = 15 g/l; p < 0.05), whereas hemoglobin S (D = -0.36; p < 0.05) and reticulocyte count (D = -0.12; p < 0.05) decreased. Mean pretransfusion resting energy expenditure was elevated to 124% above predicted levels (p < 0.05) and increased further to 134% above prediction (p < 0.05 vs. pretransfusion levels). Plasma triiodothyronine (T3) levels increased (D = 0.17 nmol/l; p < 0.05), reverse T3 (rT3) levels tended to decline (D = -0.04 nmol/l; p = 0.14), and rT3/T3 decreased (D = -0.03; p < 0.05). Plasma insulin-like growth factor-I (IGF-I) levels were low-normal before transfusion and did not change, despite the change in resting energy expenditure. CONCLUSIONS: The results confirm that resting energy expenditure is elevated in patients with sickle cell anemia. However, resting energy expenditure further increased after transfusion, despite decreased erythropoietic activity. A posttransfusion decrease in rT3/T3 may contribute to the increased resting energy expenditure. That there was no change in IGF-I implies that the growth hormone-IGF system is not involved in posttransfusion regulation of resting energy expenditure. Therefore, our data are not consistent with the hypothesis that increased resting energy expenditure in sickle cell anemia is directly related to erythropoietic activity. The mechanisms by which resting energy expenditure increases after transfusion in sickle cell anemia require additional investigation.

Adolescent↗
PubMed1999

Non-invasive RNA-based determination of fetal Rhesus D type: a prospective study based on 96 pregnancies.

OBJECTIVES: To develop a non-invasive method for determining fetal RhD status in order to provide improved care for women most at risk. DESIGN: A prospective study. METHODS: Fetal erythroblasts were enriched from the peripheral circulation of 96 RhD negative women with pregnancies at various stages in gestation using discontinuous density gradients. Amplification of RhD-specific mRNAs was carried out by reverse transcription-polymerase chain reaction assay. RNA, rather than DNA, was selected for amplification because it rarely contaminates samples, thus resulting in fewer false positives; moreover, its presence in multiple copies per cell should enhance the sensitivity of the assay, resulting in fewer false negatives. The study was prospective, relying on postnatal serological confirmation of RhD phenotype. RESULTS: The assay was 75% accurate at predicting fetal RhD status, comparing favourably with standard genomic DNA-based assays. However, we found that accuracy dropped from 85% (29/34) in the third trimester of pregnancy, to 82% (32/39) in the second and 48% (11/23) in the first trimester. Discordant data were due to false negatives in the majority (78%) of cases. CONCLUSIONS: We suggest that reverse transcription may be a useful and perhaps more sensitive alternative to standard genomic polymerase chain reaction in the majority of cases. However, under certain circumstances the absence or reduction of fetal erythroblasts or possibly RhD mRNA in some preparations may compromise the accuracy of the assay.

Biomarkers↗
PubMed1999

Effects of lengthened formant transition duration on discrimination and neural representation of synthetic CV syllables by normal and learning-disabled children.

In order to investigate the precise acoustic features of stop consonants that pose perceptual difficulties for some children with learning problems, discrimination thresholds along two separate synthetic /da-ga/ continua were compared in a group of children with learning problems (LP) and a group of normal children. The continua differed only in the duration of the formant transitions. Results showed that simply lengthening the formant transition duration from 40 to 80 ms did not result in improved discrimination thresholds for the LP group relative to the normal group. Consistent with previous findings, an electrophysiologic response that is known to reflect the brain's representation of a change from one auditory stimulus to another--the mismatch negativity (MMN)--indicated diminished responses in the LP group relative to the normal group to /da/ versus /ga/ when the transition duration was 40 ms. In the lengthened transition duration condition the MMN responses from the LP group were more similar to those from the normal group, and were enhanced relative to the short transition duration condition. These data suggest that extending the duration of the critical portion of the acoustic stimulus can result in enhanced encoding at a preattentive neural level; however, this stimulus manipulation on its own is not a sufficient acoustic enhancement to facilitate increased perceptual discrimination of this place-of-articulation contrast.

Child↗
PubMed1999

Mental health service use: a comparison of treated and untreated individuals with substance use disorders in Ontario.

OBJECTIVE: To determine the prevalence of and factors associated with mental health service use in the past year among respondents with an alcohol or other drug use disorder in a general population survey of Ontario adults. METHOD: Data were obtained from the 1990/1991 Mental Health Supplement to the Ontario Health Survey, which used the University of Michigan Composite International Diagnostic Interview (UM-CIDI). The current study examined 436 respondents aged 15-64 years who met Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria for a substance use disorder in the past year. The 82 respondents who used services for a mental health or substance abuse problem during the past year were compared with the 354 nonusers. Illness severity, disability, health beliefs and attitudes, and predisposing or enabling factors were examined in bivariate and logistic regression analyses. RESULTS: Twenty-two percent of respondents used services in the past year. Having concurrent disorders (comorbidity), troubled relationships with others, and dysfunction in main activity, feeling comfortable talking to a professional about mental health problems, being older and an urban resident, not working or being in school, and having a biological parent with an alcohol or drug problem were all associated with service use. CONCLUSIONS: The results suggest that individual determinants, such as severity of illness, disability, attitudes, and predisposing or enabling variables, all have a role in predicting service use among individuals in the general population who suffer from alcohol and other drug disorders.

Adolescent↗
PubMed1998

Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain.

Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are alpha/beta/gamma heterotrimers assembled from 10 known chains, and they subserve both structural and signaling roles. Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development. Here, we show that the laminin alpha5 chain is required during embryogenesis. The alpha5 chain is present in virtually all BLs of early somite stage embryos and then becomes restricted to specific BLs as development proceeds, including those of the surface ectoderm and placental vasculature. BLs that lose alpha5 retain or acquire other alpha chains. Embryos lacking laminin alpha5 die late in embryogenesis. They exhibit multiple developmental defects, including failure of anterior neural tube closure (exencephaly), failure of digit septation (syndactyly), and dysmorphogenesis of the placental labyrinth. These defects are all attributable to defects in BLs that are alpha5 positive in controls and that appear ultrastructurally abnormal in its absence. Other laminin alpha chains accumulate in these BLs, but this compensation is apparently functionally inadequate. Our results identify new roles for laminins and BLs in diverse developmental processes.

Animals↗
PubMed1998

cDNA cloning, in vitro expression, and biochemical characterization of cholinesterase 1 and cholinesterase 2 from amphioxus--comparison with cholinesterase 1 and cholinesterase 2 produced in vivo.

We have isolated cDNAs coding for the complete amino acid sequences of cholinesterase 1 (ChE1) and cholinesterase 2 (ChE2) from amphioxus. Both ChE transcripts have the characteristics of H-type catalytic subunits, which are inserted in the membrane via an ethanolamine-glycan-phosphatidylinositol anchor. The members of the catalytic triad of ChEs, the three pairs of cysteine residues involved in intrachain disulfide bonding, a cysteine near the carboxy terminal of both sequences, which could mediate interchain disulfide bonding, and 11 of the 14 aromatic amino acids that line the catalytic gorge of AChE are conserved. A remarkable difference between the two enzymes is in the region of the acyl-binding pocket, which plays an important role in determining substrate specificity in cholinesterases. ChE2 contains a sequence that resembles the acyl pocket of invertebrate ChE, while the acyl-binding site of ChE1 is novel. There are also differences between the two enzymes in the peripheral anionic site, which mediates inhibition by certain ligands. In vitro expression in COS-7 cells demonstrates that ChE2 hydrolyzes acetylthiocholine almost exclusively, while ChE1 hydrolyzes both acetylthiocholine and butyrylthiocholine. Both enzymes are inhibited comparably by BW284c51, but ChE1 is considerably more resistant to inhibition by propidium, ethopropazine, and eserine than is ChE2. Velocity sedimentation indicates that ChE1 and ChE2 are present as amphiphilic and nonamphiphilic G2 forms in vivo and in vitro. Another molecular form, which sediments at 17 S, is also present in vivo. Nondenaturing gel electrophoresis in conjunction with digestion by phosphatidylinositol-specific phospholipase C demonstrates that the vast majority of ChE1 and ChE2 is present as ethanolamine-glycan-phosphatidylinositol-anchored G2 forms in vivo. ChE1 also possesses an ethanolamine-glycan-phosphatidylinositol-anchor in vitro; however, ChE2 produced in vitro could not be detected on nondenaturing gels.

Acetylthiocholine↗
PubMed1998

Hospital-acquired blood stream infections in New Zealand.

AIM: To determine the number and rates of hospital-acquired blood stream infections in New Zealand public hospitals. METHOD: From October 1994 to December 1996 each of the 23 Crown Health Enterprises (CHEs) provided the Crown Company Monitoring Advisory Unit with data on the number of episodes of hospital-acquired blood stream infection (HA-BSI) and the number of inpatient admissions. RESULTS: During the 27 month study period, 3049 episodes of HA-BSI occurred in an inpatient population of 1 300 892 giving a national average rate of 0.23%. HA-BSI rates were highest for the six tertiary level, metropolitan CHEs (range 0.19% - 0.56%) in which 79% of all HA-BSIs occurred. CONCLUSION: The HA-BSI rate for New Zealand is within the range that would be expected for a developed country with a comprehensive health service. The variability between CHEs in terms of the clinical services provided and case mix differences invalidates direct comparison of HA-BSI rates. Surveillance for HA-BSI should continue with the collection of data which would allow meaningful comparison of similar tertiary level services.

Bacteremia↗