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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 253 records · Page 14Linked to original sources

The capacity of children's services in New South Wales to meet their responsibilities under the Public Health (Amendment) Act 1992.

From 1 January 1994 the New South Wales government has required directors of licensed children's services to ask parents for proof of their children's immunisation status, to record and update this information and notify public health units of outbreaks of vaccine-preventable disease. Before introduction of the legislation, we studied the health and safety policies and practices of a random sample of 77 long-day-care centres caring for children under two years of age. All but one recorded immunisation in some way; however, of the 73 centres for which adequate information was available, only 22 per cent (95 per cent confidence interval (CI) 14 to 33) recorded immunisation according to the National Health and Medical Research Council schedule. A review of the records of one in four children enrolled in the centres showed that triple antigen (TA) was recorded in some way on 94 per cent (CI 92 to 95) of records, and measles-mumps-rubella (MMR) on 80 per cent (CI 78 to 83) of records. These entries were independently verified for only 31 per cent of TA and 26 per cent of MMR records, and 38 per cent of TA and 41 per cent of MMR records had not been updated when necessary. Only 53 per cent of directors thought that the school-entry legislation would affect children's services. Directors were generally unaware of the role of the public health units and would have had difficulty in managing an outbreak of a vaccine-preventable disease. Without technical and administrative support, the directors will not be able to meet their responsibilities under the legislation.

Child Day Care Centers↗

Post-irradiation somatic mutation and clonal stabilisation time in the human colon.

BACKGROUND: Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics. AIM: To study the clonal stabilisation time in the human colorectum. METHODS: Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy. RESULTS: Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation. CONCLUSIONS: Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems.

Adult↗

Effects of hypoxia and hypercapnia on patterns of sleep-associated apnea in elephant seal pups.

This project examined the effects of alterations in respiratory drive on the occurrence of sleep apnea in Northern elephant seal pups (Mirounga angustirostris). Sleep pattern was unaffected by levels of hypoxia (approximately 13%) or hypercapnia (approximately 6%) that doubled respiratory frequency during slow-wave sleep (SWS). During sleep in air, short periods of continuous breathing (mean length = approximately 2.6 min) alternated with periods of apnea (mean length = approximately 6.1 min). Under hypoxic or hypercapnic conditions, the frequency of occurrence of apneas was reduced primarily due to the occurrence of some sleep episodes without periods of apnea. In episodes in which apneas did occur, they began later in the sleep episodes, but their length and the length of the periods of eupnea were not significantly altered. During each period of eupnea, however, the instantaneous respiratory rate and the total number of breaths increased. Breathing during sleep was restricted to SWS, never occurring during rapid eye movement (REM) sleep, regardless of the respired gas mixture. If the levels of hypoxia and hypercapnia were raised further, all episodes of apnea during sleep could be eliminated together with all episodes of REM sleep. One interpretation of the data is that the threshold for altering breathing during eupnea (instantaneous breathing frequency and number of breaths per episode of eupnea) is lower than that for altering the lengths of the periods of apnea and eupnea and that the muscle atonia associated with REM sleep extends to all respiratory muscles.

Animals↗

Survival benefit from high-dose therapy with autologous blood progenitor-cell transplantation in poor-prognosis non-Hodgkin's lymphoma.

PURPOSE: To compare standard and intensive treatment strategies for patients with high-grade non-Hodgkin's lymphoma (NHL) of poor prognosis, defined by the international prognostic index. PATIENTS AND METHODS: Thirty-four patients received standard chemotherapy with 11 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone, and methotrexate (VAPEC-B), and 33 received intensive treatment with 7 weeks of VAPEC-B, three cycles of ifosfamide/cytarabine, then high-dose busulfan/cyclophosphamide followed by autologous blood progenitor-cell (BPC) transplantation. RESULTS: Twelve of 33 patients in the intensive group and 26 of 34 patients in the standard group have died. The median follow-up time for the surviving patients is 31 months and 68 months, respectively. At 2 years, the actuarial estimates of event-free survival (EFS) were 61% versus 35% (P = .01) and of overall survival, 64% versus 35% (P = .01). A significant reduction in the event rate (progression or death) was maintained after adjustment for age and the number of risk factors. The estimated risk of experiencing an event was 0.37 (95% confidence interval [CI], 0.16 to 0.84) in the intensive group compared with the standard group. CONCLUSION: Patients with poor prognostic features who received high-dose therapy and BPC rescue had a superior EFS. The survival differences observed in this study justify a formal comparison in a randomized study.

Adolescent↗

Research changes a health care delivery system: a biopsychosocial approach to predicting resource utilization in hospital care of the frail elderly.

The social work department of a large New York City teaching hospital has conducted practice research studies over the past five years to better improve the early identification of high risk elderly patients. A recent prospective study is presented of the relationship between functional capacity and discharge status/length of stay, the results of which directly led to a change in the inpatient delivery system. A sample of 250 randomly selected patients, 65 years or older, selected upon admission, were tested using the Katz ADL, the IADL and the Short Portable Mental Status Questionnaire (PMSQ) to distinguish those patients likely to remain hospitalized beyond medical necessity. Results of a logistic regression indicate that low functional capacity patients (IADL: Wald = 5.6; P < .02) were likely to remain beyond medical necessity. The model predicted group membership correctly 90.6% of the time. These findings have led the medical center to develop an acute care geriatric unit in cooperation with an affiliated nursing home.

Activities of Daily Living↗

Increased frequency of HLA-DPB1*0301 in Hodgkin's disease suggests that susceptibility is HVR-sequence and subtype-associated.

Hodgkin's disease (HD) is a complex lymphoma-like disease which occurs as four main subtypes, nodular sclerosing (NS), mixed cellularity (MC), lymphocyte predominant (LP) and lymphocyte depleted (LD). Suggestions from epidemiological studies that HD may represent an unusual response to infection imply that the lack of previous response could be due to genetic factors. Following recent reports suggesting that there is an increased frequency of HLA-DPB1*0301 in Hodgkins disease, we have studied DPB1 in two series of patients using molecular typing methods. One series is a retrospective group of 118 patients over the age of 15 years from a single centre, and the other is a multi-centre prospective group of 45 patients between the age of 16 and 24 years. In both series, the percentage of HD patients with DPB1*0301 is greater than in the controls, confirming that this seems to be an HD-susceptibility allele. However, extension of the analysis in relation to HD subtype shows that the increase in *0301 is present in nodular sclerosing (NS), mixed cellularity (MC) and lymphocyte predominant patients (LP) HD patients, but preliminary evidence suggests an increase in *0401, and possibly *0501 in MC- and LP-HD. The DPB1 hypervariable region (HVR) amino-acid motif Asp55, Glu56 (*0301-like, HVR-C) is increased in NS compared with non-NS (ie MC+LP), whereas the frequency of Ala55, Ala56 (*0401-like) is increased in non-NS compared with NS. Conversely, Asp84, Glu85Ala86(*0301-like, HVR-F) motif is more frequent in NS than non-NS patients, but there is no increase in Gly84, Gly855, Pro86 (*0401-like). These findings suggest that genetic susceptibility in HD may reside at the level of HVR-encoded DPB1 peptide-binding residues, rather than with a specific allele, and that this may in some way influence the HD subtype.

Adolescent↗

Malignant peripheral nerve sheath tumour with vascular differentiation: a report of four cases.

Four cases of malignant peripheral nerve sheath tumour showing vascular differentiation are described. One case was associated with neurofibromatosis 1 and contained angiosarcomatous, cartilaginous and rhabdomyoblastic elements. The other cases occurred in patients without neurofibromatosis and showed a spectrum of vascular lesions ranging from lobulated, haemangioma-like structures to angiosarcoma. These are the first recorded examples of this phenomenon not associated with neurofibromatosis. Immunohistochemical examination demonstrated the endothelial nature of the lesions in all cases and revealed cells positive for alpha-smooth muscle actin, probably pericytes, closely apposed to the endothelium.

Adult↗

Summary of track B: clinical science.

AIM: To review Track B on clinical science. Major topics covered were quantitative HIV-1 plasma RNA measurement, combination antiretroviral therapy, protease inhibitors, treatment of primary HIV-1 infection, HIV-1 drug resistance, future use of antiretroviral drugs, paediatric HIV-1 infection, opportunistic infections and HIV/AIDS in developing countries. QUANTITATIVE HIV-1 PLASMA RNA MEASUREMENT: Quantification of HIV-1 RNA is a predictor of progression of immune deficiency and death in HIV-infected adults and children, and is useful in monitoring response to antiretroviral therapy. THERAPY: Combination antiretroviral therapy is now the standard of care, although questions about optimal starting time and the best initial regimen remain unresolved. Protease inhibitors are a powerful new class of antiretroviral agents which in combination with other drugs can produce profound reductions in plasma HIV-1 RNA levels. Trials are in progress of combination antiretroviral therapy, including protease inhibitors, in persons recently infected with HIV-1 to assess the feasibility of permanent suppression or eradication of HIV-1. Adherence to therapy and drug resistance will become increasingly important subjects. CONCLUSIONS: The genuine improvements in patient management are out of reach to the majority of the world's HIV-infected persons, a conclusion with implications which dampened the optimism generated by the conference.

Adult↗

Preparation, perceptions, and problems: a long-term follow-up study of orthognathic surgery.

Follow-up of patients who have undergone orthognathic surgery is well documented in the literature, usually in the form of questionnaire-based studies or clinical interviews. However, there have been few long-term follow-up investigations. This study aimed to look at the long-term outcomes of such operative procedures. Questionnaires were sent to 68 patients who had undergone joint orthodontic and orthognathic surgery procedures 5 to 16 years previously, after the patients were contacted by telephone to learn the nature of the study. The 49 responses were compared with a previously analyzed preoperative group and a short-term postoperative group (1 to 3 years following surgery) from the same institution. Respondents showed high levels of satisfaction overall, with the majority believing they had made the correct decision to undergo surgery. The main problem areas identified were those concerning presurgical explanations and lack of advice regarding side-effects. This area requires improvement as postsurgical dissatisfaction can be minimized by accurate descriptions of the treatment. A number of respondents reported persistent lip paresthesia and continued limitation of mouth opening. However, the majority of patients commented that these persistent symptoms had no effect on their daily life.

Adult↗

Community health workers' response to violence against women.

This paper reports on a qualitative study of community health workers from a predominantly rural based region in Queensland. The purpose of this study was to determine the community health worker barriers to identification, assessment and intervention on the issue of violence against women. The qualitative research method comprised five structured focus group interviews with 28 community health workers using open-ended questions to explore their perceptions. Analysis of the focus group data revealed that community health workers expressed reluctance to become involved in cases of violence against women. The reasons they provided are grouped under three main themes: barriers to identification; barriers to assessment; and barriers to intervention. Training programs offered to rural community health workers need to be aware of the barriers to identifying, assessing and intervening in cases of violence against women that are highlighted by this study. Further studies are needed to assess the wider relevance of these findings to other groups of community health workers in rural and non-rural settings.

Attitude of Health Personnel↗

News from the divisions: diabetes shared care.

It is not surprising that diabetes care has been a very active area for divisional projects and activities. Diabetes is prevalent in the community (up to one million Australians) and in general practice (1% of GP encounters). Optimal cost-effective diabetes management involves collaboration between general practice and public and private health services--one of the purposes for which divisions were created. Because diabetes is a multisystem chronic disease requiring multi-disciplinary interventions, it has also been a model for applying the health outcomes approach in general practice, especially in New South Wales.

Australia↗

TAP associates with a unique class I conformation, whereas calnexin associates with multiple class I forms in mouse and man.

To define the rules governing de novo assembly of the trimeric class I complex, we have identified the class I folding/assembly intermediates associated with calnexin or TAP, using both human and mouse cell lines. To better characterize the class I H chain structure associated with TAP, mouse mAb that distinguish open (64-3-7+) vs folded (30-5-7+) Ld heavy (H) chains were used. We report here that open forms of Ld are uniquely and specifically associated with TAP and that the conformational change in the class I H chain coincident with peptide binding induces TAP release. Chimeric Ld/Q10 displayed TAP association, demonstrating that soluble class I molecules can bind TAP. As previously reported, beta 2m was found to be required for H chain association with TAP. Interestingly, beta 2m was associated with TAP in the human class I-negative cell line LCL 721.221, suggesting that beta 2m can bind to TAP before class I H chain. In contrast to TAP, which binds a specific class I conformation, calnexin was detected in association with multiple forms of both mouse and human class I. Most significantly, we show for the first time that beta 2m-assembled forms of human as well as mouse class I molecules interact with calnexin. Based on these findings, we propose a model for the sequential assembly of class I heterotrimers and their respective interactions with TAP and calnexin.

ATP-Binding Cassette Transporters↗

Amyloid beta-peptide spin trapping. I: Peptide enzyme toxicity is related to free radical spin trap reactivity.

Synthetic beta-amyloid peptides (A betas) demonstrate lot-to-lot variation in toxicity that has not been adequately explained. Studies from our laboratory have shown that A beta toxicity may result from the ability of the peptide to promote oxidation reactions. Both A beta(1-40) and A beta(25-35) inactivate the oxidation-sensitive enzyme glutamine synthetase (GS) and generate electron paramagnetic resonance (EPR)-detectable products upon reaction with the spin trap phenyl-tert-butylnitrone (PBN). We now report that samples of synthetic A beta(1-40) and A beta(25-35) with attenuated toxicity with respect to peptide-induced GS inactivation, produce qualitatively different EPR spectra when the peptides are incubated with PBN. The results suggest an interpretation of conflicting observations regarding the toxicity of synthetic A betas, and that investigators must be careful to assess the reactivity state of A beta being studied.

Amino Acids↗

Amyloid beta-peptide spin trapping. II: Evidence for decomposition of the PBN spin adduct.

Synthetic beta-amyloid peptides (A betas) react with the spin trap phenyl-tert-butyl nitrone (PBN) to form products detectable by electron paramagnetic resonance (EPR) spectroscopy. At least two EPR-detectable products can be distinguished from the A beta/PBN reaction, and peptide toxicity towards glutamine synthetase enzyme correlates with the type of PBN reaction product observed. We have reacted synthetic A beta(25-35) peptide with [12C]- or [13C]PBN to demonstrate that the two products represent alternate pathways of spin adduct decomposition. Results indicate that the C=N bond of PBN is cleaved by A beta in what we hypothesize is a radical addition-fragmentation reaction.

Amyloid beta-Peptides↗