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Biomedical subjects

C Edmonds

Publications and source records attributed to C Edmonds.

At least 19 recordsLinked to original sources

Microbiological and metal contamination of watercress in the Wellington region, New Zealand--2000 survey.

OBJECTIVES: To investigate potential microbiological and metal contamination of watercress and to assess the public health risks associated with harvesting and consumption of watercress. METHOD: During March and April 2000, samples were taken from 11 known or potential watercress collection sites in the Wellington region. Microbiological testing included bacterial counts for presumptive and faecal coliforms (watercress); total coliforms (growing water); and Escherichia coli (E. coli) and presence/absence tests for Campylobacter species (growing water and watercress). Watercress concentrations of a range of metals were also measured. RESULTS: All of the sites showed significant levels of E. coli in samples of both watercress and water. The E. coli levels in water were well above recommended freshwater recreational contact safety guidelines at most sites. Campylobacter was detected in the growing waters at all sites (80% of the samples) and in 11% of the watercress samples. Mean metal concentrations in watercress did not exceed the NZ Food Regulations (1984) levels at any of the sites. However, lead concentrations at the urban sites and one of the semi-urban sites would have exceeded the new Australia New Zealand Food Standards Code maximum levels (2003). CONCLUSIONS AND IMPLICATIONS: The consumption of raw watercress contaminated with enteric pathogens could potentially cause serious gastrointestinal illness (e.g. campylobacteriosis) and people gathering watercress could also be at risk of infection from contact with contaminated surface waters.

Campylobacter↗

Integrated cardiac care.

In 1984 physicians at the Texas Heart Institute developed Cardiovascular Care Providers Inc, the first packaged-pricing plan for cardiovascular surgery. Under this arrangement, all services, including physician and hospital charges, are covered by a global payment package (bundled service). The resulting flat fee is lower than the sum of the individual charges. Since November 1984 the plan has been offered to the non-Medicare (less than 65 years old) population through contracts with self-insured corporations, prepaid health plans, union trusts, and foreign governments. In 1993 it was extended to Medicare patients who require coronary artery bypass grafting. Our experience has shown the plan lowers cost, increases patient access, allows payers to forecast their expenses, and streamlines the billing process, while maintaining a high quality of care and enabling patients to choose their own providers. Our success with this approach is attributed not only to the plan's simplicity, but also to the fact that it is physician directed and organ specific, involving many related specialties. Equally important keys to success include our hospital's large patient population and extensive database. Similar packaged-pricing plans have been adopted by several other cardiovascular centers. The approach is now being evaluated by Medicare in 6 other hospitals nationwide. With time, this approach is likely to become an increasingly popular reimbursement option.

Capitation Fee↗

CardioVascular Care Providers. A pioneer in bundled services, shared risk, and single payment.

In 1984, physicians at the Texas Heart Institute developed CardioVascular Care Providers, Inc., the 1st packaged pricing plan for cardiovascular surgery. Under this arrangement, all services (including physician and hospital charges) are covered by a global payment package (bundled service). The resulting flat fee is lower than the sum of the individual charges. Since November 1984, the plan has been offered to the non-Medicare (< 65-year-old) population through contracts with self-insured corporations, prepaid health plans, union trusts, and foreign governments. In 1993, it was extended to Medicare patients who require coronary artery bypass grafting. Our experience has shown that the plan lowers costs, increases patient access, allows payers to forecast their expenses, and streamlines the billing process, while maintaining a high quality of care and enabling patients to choose their own providers. Our success with this approach is attributed not only to the plan's simplicity but also to the fact that it is physician-directed and organ-specific, involving many related specialties. Equally important keys to success include our hospital's large patient population and extensive database. Similar packaged pricing plans have been adopted by several other cardiovascular centers. The approach is now being evaluated by Medicare in 6 other hospitals nationwide. With time, this approach is likely to become an increasingly popular reimbursement option.

Cardiovascular Diseases↗

Intraoperative anaphylaxis due to exposure to latex (natural rubber) in children.

Intraoperative anaphylaxis secondary to exposure to latex is a serious and potentially life-threatening phenomenon that has been recognized more frequently in recent years. Between 1989 and 1992, twenty-one patients had a Type-I (anaphylactic) reaction to latex intraoperatively at The Children's Hospital of Philadelphia. Twelve (57 per cent) of these patients had spina bifida. Six patients (29 per cent) had cerebral palsy, and five of them had a ventriculoperitoneal shunt. Of the remaining three patients, one (5 per cent) had exstrophy of the bladder, one had VATER syndrome, and one had Duchenne muscular dystrophy. All of the patients had had at least two previous operative procedures. Overall, sixteen patients (76 per cent) had a ventriculoperitoneal shunt. The manifestations of the allergic reaction included a rash in fifteen patients (71 per cent), hypotension in fifteen, tachycardia in eleven (52 per cent), bronchospasm in ten (48 per cent), bradycardia in two (10 per ent), and cardiac arrest in two. The symptoms occurred within minutes after the induction of the anesthesia in all but one patient, in whom hypotension and cardiovascular arrest developed approximately one hour after the beginning of the operation. Two patients had a full cardiopulmonary arrest while under the anesthesia. All twenty-one patients responded to management; there were no deaths. Of the six patients who had cerebral palsy, five had been managed with a ventriculoperitoneal shunt because of hydrocephalus following a previous intraventricular hemorrhage that was related to prematurity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Differential expression of interphotoreceptor retinoid-binding protein, opsin, cellular retinaldehyde-binding protein, and basic fibroblastic growth factor.

The mRNA for rat interphotoreceptor retinoid-binding protein (IRBP) consists of 5.2 kb and 6.4 kb transcripts which are expressed early during retinal development. Here, we characterized rat IRBP cDNA and genomic clones, determined the mechanism generating the two transcripts and compared their expression to mRNAs for opsin, cellular retinaldehyde-binding protein (CRAlBP) and basic fibroblast growth factor (bFGF). We found that human and rat IRBPs have a high degree of sequence homology (86% amino acid identity over the fourth repeat). RNA-PCR studies and Northern blot analysis, showed that the 6.4 kb mRNA has a longer 3'-untranslated region (UTR) than the 5.2 kb message. Both IRBP transcripts, but not the mRNA for opsin are present in the neonatal and adult pineal. During development, the mRNAs for IRBP and opsin reach one-half of their maximal levels by P5 and P11, respectively. The ratio of the two IRBP mRNAs remains constant throughout life. In contrast, the ratio of the longest to the shortest opsin mRNA decreases between E19 and 1 year of age. Immunohistochemistry demonstrated a marked increase in the amount of IRBP in the interphotoreceptor matrix between P1 and P9 corresponding to the enhanced expression of this mRNA. Up-regulation of opsin mRNA expression during the second postnatal week corresponds to the emergence of the outer segments. The temporal expression of CRAlBP is similar to IRBP while bFGF is not expressed until after photoreceptor differentiation is complete. In summary, two 3'-transcription termination sites explain the difference in IRBP mRNA sizes. The different temporal and tissue specific patterns of IRBP and opsin expression suggest that separate mechanisms control the expression of these two genes. The expression patterns of IRBP and CRAlBP are consistent with the role of vitamin A as a morphogen and bFGF in neuronal maintenance.

Age Factors↗

Graves' ophthalmopathy in relation to cigarette smoking and ethnic origin.

OBJECTIVE: We aimed to study the effect of cigarette smoking on the prevalence and severity of Graves' ophthalmopathy (GO). PATIENTS: One hundred and fifty-five newly diagnosed patients with Graves' disease (GD) were diagnosed clinically and by routine biochemical methods. Twenty-five per cent (39) were of Asian origin. METHODS: Eye signs were classified according to the American Thyroid Association Classification. A detailed smoking questionnaire and data from hospital notes were used to calculate an index of cigarette consumption. RESULTS: Thirty-four per cent of all patients had Graves' ophthalmopathy, and the prevalence in males (26%) and females (36%) did not differ significantly. There was a prevalence of 42% among Europeans compared to 7.7% in Asians (P = 0.0002). The overall risk for Europeans for developing Graves' ophthalmopathy was 6.4 (1.78-22.7 confidence interval) times higher than for Asians. Corrected for the ethnic factor the increased risk from smoking for Europeans was 2.4 (1.12-5.18, 95% confidence interval) times higher. There was a significant dose effect (P = 0.008). CONCLUSIONS: The present findings confirm an effect of cigarette smoking on Graves' ophthalmopathy and in addition show that Europeans have a substantially greater risk of developing Graves' ophthalmopathy than have Asians.

Adolescent↗

Croup. A common cause of airway obstruction in children.

Although viral croup is usually a self-limiting disease, its signs and symptoms are distressing enough to make parents seek immediate medical advice. This is fortunate because a much more serious disorder may be present. Indeed, morbidity requiring hospitalization may occur, as may a true emergency. Drs Thomsen and Edmonds discuss the epidemiology and current management of croup and related conditions.

Airway Obstruction↗

The region of the HPV E7 oncoprotein homologous to adenovirus E1a and Sv40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation.

Some genital human papillomavirus (HPV) types, such as 16 and 18, are highly associated with malignant cervical tumors while others, such as HPV 6, are only rarely found in these malignancies. The E7 oncoproteins of HPV 6, 16 and 18 each have a 17 amino acid region with striking homology to adenovirus E1a and SV40 LT. E1a, LT and the E7 oncoprotein of HPV16 all bind the cellular Rb protein in vitro, and for E1a and LT this region of homology contains sequences essential for interaction with Rb. We have now found that in HPV 16 E7 this region (amino acids 21-37) contains two separate biochemical activities, each of which contributes to E7-mediated transformation. Rb binding was localized to the N terminus of this region, while the C terminus was shown to serve as a substrate for casein kinase (CK) II, which phosphorylated serine-31 and serine-32. Replacement of the two serines by non-phosphorylatable amino acids led to a reduction in transforming activity and abolished phosphorylation but did not affect Rb binding. Rb binding and CK II phosphorylation were also examined for the E7 proteins of HPV 6 and HPV 18. HPV 16 and 18 E7 bound similar amounts of Rb, but HPV 6 E7 consistently bound less. Phosphorylation rates also varied, with HPV 18 E7 being 2-fold faster than HPV 16 E7, which in turn was 2-fold faster than HPV 6 E7. We conclude that Rb binding and phosphorylation of E7 by CKII are independent activities which are required for efficient transformation by E7 and that these activities correlate directly with the relative oncogenic potential of these viruses.

Adenovirus Early Proteins↗

Analysis of human papillomavirus type 16 open reading frame E7 immortalizing function in rat embryo fibroblast cells.

The E7 open reading frame of human papillomavirus type 16 (HPV-16) encodes a protein that can immortalize primary rat cells, cooperate with the ras oncoprotein to transform low passage rat cells and transform established rodent cells to anchorage independence. The immortalizing and cooperation functions have been investigated using a series of point mutations that introduce single amino acid changes into the E7 protein in two distinct regions. Certain mutations altering amino acids conserved between the E7 protein of genital HPV types, the adenovirus E1a protein and simian virus 40 large T antigen abolished the ability of the E7 protein to immortalize or cooperate with ras in a focus forming assay. Mutations in a consensus sequence for a casein kinase II recognition site, which is also shared by E1a and large T, reduced immortalizing activity, but did not affect the ability to cooperate with ras. Single mutations disrupting cysteine motifs, which form putative zinc-binding sites in the second region, reduced the activity of the E7 protein, whereas double mutants, in which neither of the cysteine motifs remained intact, showed no or very low activity. The activity of the mutants in immortalization and cooperation assays was essentially the same as their transforming activities in NIH 3T3 cells. This indicates that these three functions of E7 map to overlapping domains which cannot be separated by these mutations in the region of E1a/large T homology or the cysteine motifs.

Amino Acid Sequence↗

Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH3T3 cells.

Previous studies have demonstrated that the HPV-16 E7 gene product encodes the major transforming activity of the virus in rodent cell systems. In this study we have generated a series of point mutations affecting the region of HPV-16 E7, which shows homology to adenovirus E1a conserved domain (CD)1. In conjunction with previously described mutants in the region of E7 with similarity to E1a CD2 and SV40 LT, we have investigated three known activities of the E7 protein; transformation, association with the cellular RB protein and induction of cellular DNA synthesis. The results show that RB binding correlates with the ability of E7 to induce cellular DNA synthesis and mediate cell transformation. In addition an unidentified function of E7, which is necessary for transformation of NIH3T3 cells, but does not affect RB binding or the ability to induce cellular DNA synthesis, has also been demonstrated. This study therefore identifies two separate regions of the E7 gene necessary for transformation of established cells. One of these, in the region of E7 which shows similarity to E1a CD2 and LT, is required for RB binding and DNA synthesis. The other region important for transformation, in the N-terminus of E7, is separable from the RB binding/DNA synthesis function.

Amino Acid Sequence↗

Demonstration and partial characterization of ADP-ribosylation in Pseudomonas maltophilia.

ADP-ribosylation of proteins occurs in many eukaryotes, and it is also the mechanism of action of a growing number of important bacterial toxins. To date, however, there is only one well-characterized ADP-ribosylation system where the ADP-ribosyltransferase and the substrate protein are both bacterial in origin, namely within the nitrogen-fixing bacterium Rhodospirillum rubrum. The present paper demonstrates the endogenous ADP-ribosylation of two proteins of Mr 32,000 and 20,000 within Pseudomonas maltophilia, a Gram-negative aerobe. The proteins have been partially purified: two apparently separate species of modified protein can be separated by ion-exchange chromatography and gel filtration (V0 and Mr 158,000 - Vi). The substrate protein(s) either has, or is co-eluted with, NAD+ glycohydrolase activity. The modification is mono-ADP-ribosyl in nature. The linkage between the acceptor amino acid and the ADP-ribose moiety is alkali-labile and stable to hydroxylamine, possibly indicating an S-glycosidic bond. The activity appears to be a true ADP-ribosylation reaction and not an NAD+ glycohydrolase activity followed by non-enzymic addition of ADP-ribose to protein. The results presented here indicate that ADP-ribosylation may have a wider significance within prokaryotic systems than previously thought.

ADP Ribose Transferases↗

A point mutational analysis of human papillomavirus type 16 E7 protein.

The E7 open reading frame of human papillomavirus type 16 (HPV16) has been shown to be selectively retained in cervical tumors and to encode both transforming and trans-activating functions in murine cells, supporting the notion that expression of E7 contributes towards the progression of premalignant cervical lesions. A comparison among E7 sequences of different HPV types reveals some homology at the amino acid level. Of particular interest are two regions, one which contains significant homology to a region of adenovirus E1a and simian virus 40 large T (LT), and a second region which contains two conserved Cys-X-X-Cys motifs. To determine the importance of these domains to the function of the E7 protein, a series of mutants carrying substitutions at amino acids in the region of E1a-LT homology and at the Cys-X-X-Cys motifs were constructed. The mutated E7 sequences were placed under the control of a strong heterologous promoter (Moloney long terminal repeat), and the activity of the mutants was assayed in NIH 3T3 cells, a cell line in which both the transforming function and the trans-activating function of E7 could be determined. A single amino acid substitution analogous to a mutation in E1a which destroys the transforming ability of this protein abolished both transformation and trans-activation by E7. Mutations at the Cys-X-X-Cys motifs demonstrated that this region contributes to the transforming potential of E7, although proteins in which both motifs were interrupted retained a low level of transforming activity. Mutations in the region of E1a-LT homology which occur within a recognition sequence for casein kinase II did not markedly affect transforming activity of E7 but severely reduced trans-activating ability. This indicates that efficient trans-activation is not required for transformation by HPV16 E7 in these cells.

Amino Acid Sequence↗

Quantitative cell-adhesion assay for Clostridium difficile cytotoxin.

A quantitative assay for Clostridium difficile cytotoxin has been developed, based on the observation that suspended fibroblasts exposed to cytotoxin fail to adhere to plastic. A dye-binding technique was used to quantitate adherent cells, in order to obviate microscopy. Adherent BHK cells were fixed with glutaraldehyde and cell protein was stained with Coomassie blue R-250. Cell-bound dye was eluted and estimated spectrophotometrically. The amount of eluted dye was proportional to the number of adherent cells and cell staining was time dependent. Cytotoxin was purified by gel-permeation and ion-exchange chromatography and migrated as a single band on SDS-PAGE. After exposure of suspended BHK cells to purified cytotoxin, their adhesion to plastic was inhibited in a manner which depended on concentration of cytotoxin and on time and temperature of exposure. This study provides the basis for a C. difficile cytotoxin assay that is quantitative, rapid and reproducible and may have wider applicability in the study of other toxins or agents that inhibit cell adhesion.

Animals↗

Neurobehavioural effects of professional abalone diving.

In a study of 33 commercial abalone divers from the Port Lincoln area of South Australia nervous system function was examined using a battery of neurobehavioural tests. Their performance was compared with that of non-diver controls matched for age, sex, education level, job type, language abilities, and cigarette and alcohol consumption. Abalone divers showed significantly poorer vision, learning, and short term memory performance and increased tremor relative to their controls. The reaction time of abalone divers, however, was as fast as or significantly faster than that of controls but their error rates were much higher, indicating that abalone divers were sacrificing speed for accuracy. Despite their apparent risk taking approach to these tests, the performance of abalone divers suggests some impairment of nervous system function.

Adult↗

Does non-clinical decompression stress lead to brain damage in abalone divers?

Abalone divers are subject to considerable decompression stresses and could be at risk of progressive cognitive impairment. A sample of abalone divers was compared with a sample of fishermen, by means of a battery of neuropsychological tests. No evidence of cognitive impairment was found in the divers, in spite of evidence of their exposure to decompression stress. The implications for other professional divers and for recreational underwater divers who follow standard decompression protocols are reassuring.

Adult↗

Hearing loss in Australian divers.

Permanent hearing loss of the sensorineural type has been demonstrated to be an occupational hazard of professional SCUBA divers. An audiometric survey was performed on a group of professional abalone divers, all of whom had experienced excessive exposure to dysbaric conditions. The results of this survey revealed that, even allowing for the very liberal requirements of the Australian Standard for divers, over 60% had unacceptable sensorineural, high frequency deafness. In half these cases deafness was unilateral, and in half bilateral. Making allowance for age, two-thirds had hearing loss to a degree which is compensable, according to the method of the National Acoustic Laboratories (1974) for determining proportional loss of hearing.

Adult↗