Changes in plasma and muscle creatine concentration after increases in supplementary dietary creatine in dogs.
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Biomedical subjects
Publications and source records attributed to M Murphy.
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OBJECTIVES: Several studies have noted the impact of socioeconomic factors on access to expensive medical care, but none of those studies controlled for self-reported health and functional status or attitudes about treatment alternatives when analyses were completed. Because these factors may be correlated with socioeconomic status, the failure to control for them may have led to bias in other studies. The authors merged data from secondary sources with telephone survey data from a national sample of 456 end-stage renal disease patients to show how estimates of the effects of socioeconomic factors change when self-reported health and functional status and attitudes about treatment are incorporated into statistical models. The authors also showed how kidney transplant rates would change if socioeconomic factors no longer influences organ allocation decisions. METHODS: Weibull proportional hazard analyses were used to show relationships between socioeconomic measures and waiting list entry and kidney transplant rates, before versus after accounting for self-reported health and functional status, attitudes about treatment, and other variables. Simulation analyses were used to estimate the number of waiting list spots and transplant operations that would move from economically advantaged to disadvantaged persons if socioeconomics no longer influenced organ allocation decisions. RESULTS: Incorporating information about health and functional status, attitudes about treatment, and other factors into the hazard models often reduced the estimated impact of socioeconomic measures on the odds of (1) being on a waiting list for a cadaver kidney transplant and (2) receiving a transplant. Simulations showed that 30 to 65 waiting list spots or transplant operations per 1,000 patients would shift from economically advantaged to disadvantaged persons if socioeconomics no longer influenced organ allocation decisions. CONCLUSIONS: Successful efforts to level the playing field would result in substantial redistributions of kidney transplants from economically advantaged to disadvantaged persons.
A discussion of occult breast carcinomas in breast reduction surgery has not occurred in the last 25 years. My recent experience in discovering two occult breast carcinomas in breast reduction specimens led to the creation of a survey of local plastic surgeons and a review of the literature with the goal being precise recommendations for such occurrences. Our survey of breast reductions performed on 2576 patients shows a 0.16 percent incidence of occult breast carcinoma, significantly lower than the 0.38 percent incidence seen in the Snyderman and Lizardo study of 1959. This decrease in the rate of occult breast carcinomas could be explained by many advances in early detection, improvements in patient education, and more thorough pathologic examination of the surgical specimens. The results of this survey and review suggest that we as plastic surgeons performing breast reduction surgery be well versed in all aspects of breast cancer detection, evaluation, and treatment.
Protein kinases C are a family of serine threonine protein kinases that play key roles in extracellular signal transduction. Inappropriate activation of protein kinase C has been implicated in the pathophysiology of many diseases, including diabetes mellitus. Indeed, protein kinase C activation may contribute not only to the pathogenesis of diabetic complications such as nephropathy and retinopathy, but also to insulin resistance. Growing awareness that protein kinase C isoforms subserve specific subcellular functions has led to the development of isoform-specific inhibitors, which may be useful investigational tools and therapeutic agents for attenuating the effects of inappropriate protein kinase C activity. Here we review the role played by protein kinases C in diabetic nephropathy and the recent progress that has been made to modulate its activity using specific inhibitors.
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The Cyberknife is an image-guided "frameless" dedicated radiosurgical device. This instrument has several distinct advantages over frame-based systems, including improved patient comfort, increased treatment degrees of freedom, and the potential to target extracranial lesions. Clinical results thus far with respect to the treatment of malignant intracranial tumors has been promising. Additionally, the Cyberknife will likely revolutionize the application of radiosurgery to extracranial sites. A description of the components, treatment planning, and clinical results of the Cyberknife will be reviewed.
OBJECTIVE: Our aim was to obtain mental health patients' views on psychiatrists' and case managers' attire. METHODS: Eighty-six patients treated at a community mental health service were surveyed. Various types of commonly worn attire were listed. Respondents were asked to choose what they thought was most appropriate for their psychiatrist and case manager to wear. RESULTS: Over 50% of respondents felt that psychiatrist or case manager dress was not an important issue. However, those who felt that it was preferred less formal attire. CONCLUSIONS: Psychiatrists and case managers in a community mental health team could consider adopting less formal attire. This conclusion is limited by the small sample and may be relevant to rural areas only. Further research is needed in urban centres. Implications of these findings are discussed.
PURPOSE: p27 is an inhibitor of the cell cycle with potential tumor suppressor function. Decreased levels of p27 protein expression have been correlated with poor prognosis in patients with breast and colorectal carcinomas. Although as many as a third of patients with clinically localized prostate cancer will have relapse after radical prostatectomy, predicting who will have recurrence remains enigmatic. We examined the ability of p27 protein levels to predict outcome in patients with clinically localized disease who underwent radical prostatectomy. MATERIALS AND METHODS: p27 protein expression was evaluated in 86 patients with clinical stage T1-2 prostate cancer who were treated with radical prostatectomy. Archived paraffin embedded specimens were sectioned and immunostained with p27 antibody, and scored by 2 independent observers in a blinded fashion. The absence or presence of p27 protein was then correlated with biochemical relapse in univariate and multivariate analyses. RESULTS: In a multivariate analysis that included age, preoperative prostate specific antigen, Gleason score and pathological stage p27 was a strong independent predictor of disease-free survival (p = 0.0184, risk ratio 3.04), second only to pathological stage (p = 0.0001, risk ratio 6.73). Even more strikingly, multivariate analysis demonstrated that p27 was the strongest predictor of biochemical recurrence (p = 0.0081, risk ratio 4.99) among factors studied in patients with pathological T2a-T3b disease. CONCLUSIONS: Absent or low levels of p27 protein expression appear to be an adverse prognostic factor in patients with clinically organ confined disease treated by radical prostatectomy. This marker appears to be especially useful in those patients in whom surgery is believed to be potentially curative, that is patients with pathological T2-T3b disease. Patients with low or absent p27 protein expression may be candidates for novel adjuvant therapies.
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OBJECTIVE: To study the effectiveness of a 1990 ban by New York state on entry to more than one waiting list for a cadaver kidney transplant, and the impact of the ban on equity in access to transplantation. DATA SOURCES: (1) Waiting list files from the Organ Procurement and Transplantation Network, (2) the Health Care Financing Administration's Medicare Program Management and Medical Information System, and (3) U.S. Census Public Use Files. STUDY DESIGN: Multivariate hazard models were used to estimate the impact of the ban of the overall odds of multiple listing and on the odds of multiple listing at in-state and out-of-state transplant centers. After estimating the relationship between multiple listing and subsequent transplantation, we used simulation techniques to estimate the effects of a complete multiple listing ban on group waiting time differentials. Independent variables included demographic/socioeconomic characteristics, measures of ESRD severity, general transplantation suitability, measures that affect the likelihood of finding a good donor organ, and measures of the productivity of the transplant/dialysis center. PRINCIPAL FINDINGS: The ban was associated with a 66 percent reduction in the rate of multiple listing for New York patients, and multiple listing at in-state transplant centers declined by 87 percent. Simulation results suggested that even a completely effective ban would produce only small, mixed equity effects. CONCLUSIONS: While the ban was effective in reducing the proportion of patients who registered at multiple transplant centers, taken together the results suggest that banning multiple listing is not likely to result in large improvements in equity in access to transplantation.
BACKGROUND AND AIMS OF THE STUDY: Bovine pericardium has been used as a biomaterial for heart valves since the late 1960s. Cross-linking agents have been applied routinely to reduce host-tissue response, including antigenicity, and to improve tissue leaflet durability. Evaluation of improvements in bovine pericardial valve leaflet calcification and flexibility require that in vitro systems be developed to correlate data with results from in vivo studies. This study describes an in vitro test system used to evaluate the effects of two surface-modifying treatments on pericardial tissue hemocompatibility. METHODS: Non-fixed and glutaraldehyde fixation-processed (GA) bovine pericardial tissues were exposed to anticoagulated whole blood for 60 min. Blood was then removed, and platelet-poor plasma prepared and frozen at -70 degrees C until analyzed for kallikrein activation and release of platelet factor 4 (PF4). Blood-exposed tissue samples were analyzed for fibrin (ogen) binding with an anti-fibrinogen antibody and for tissue cellular responsiveness (blood cell adherence and aggregation) by scanning electron microscopy. RESULTS: Conditions were determined for minimum extent of pumping action by the minicam system required to allow for solution movement while not tearing or wearing the tissue. A blood-tissue exposure time of 60 min provided sufficient first-pass exposure to evaluate the acute blood-tissue response. The relative degree of both kallikrein activation and PF4 release was greater in the non-fixed tissue but a greater number of fibrin(ogen) molecules per cm2 was found on GA-treated tissue. Scanning electron microscopy showed a differential cell response of non-fixed tissue compared with GA-treated tissue. CONCLUSION: This non-static test system demonstrated great promise for use in routine in vitro hemocompatibility testing of blood-contacting biological biomaterials.
We identify child-level and parent-level characteristics associated with children's patterns of leaving home. We use a multilevel discrete-time hazards model to examine the impact of family and demographic factors at both levels, and utilize the Alternating Conditional Expectation algorithm optimally to transform the dependent and independent variables. We find that measured variables at both the child and the parent level have important influences, as do period and cohort factors. However, unmeasured parent-level factors have an influence on the departure of children that is broadly similar in magnitude to measured factors.
Propylene glycol and mineral oil are commonly used in the veterinary profession for treatment of bovine ketosis and equine impactions, respectively. Accidental administration of 6.0 ml propylene glycol/kg of body weight in horses causes severe depression, ataxia and malodorous breath and feces. However, appropriate medical therapy can result in successful treatment of this toxicosis.
Cancer progression occurs because of imbalance in the processes of proliferation, differentiation and programmed cell death. In prostate cells, these processes are regulated at least in part by androgens. Structural alterations occur in a variety of genes regulating such processes. In order to obtain meaningful information on the biologic behavior of prostate cancers, it is important to assess androgen dependence and alterations in key genes regulating cell cycle kinetics as well as the aberrant response in cellular proliferation and death that such genetic events bring about. Most genetic alterations resulting in cancer progression alter normal cell cycle progression. Assessment of cell division cycle alterations by means of quantitative methods may have prognostic value, while interference with cell cycle regulatory proteins may result in powerful therapeutic tools. Here we review the methodologies utilized in the assessment of cell cycle kinetics and the abnormalities in proliferation and apoptosis encountered in prostate cancer. In addition, alterations in novel, important genes likely to have an impact on the behavior of prostate cancer and its precursor lesions are discussed. Molecular assessment of genetic alterations in genes that play a pivotal role in prostate cancer coupled with quantitative cytometry of cell kinetics may be utilized for a more precise evaluation of biologic behavior of prostate neoplasms.
OBJECTIVE: To investigate various aspects of dentists' beliefs and practices with respect to helping their patients stop smoking. DESIGN: Postal questionnaire survey conducted in 1996. SETTING: The general dental practitioners on the health authority lists of Berkshire, Buckinghamshire, Northamptonshire and Oxfordshire. SUBJECTS: The 869 dentists registered on 1 April 1996. RESULTS: A high response rate (78%; 674/869) was obtained. The majority of respondents (82%; 95% CI: 79, 85) thought dentists should encourage their patients to stop smoking although only 37% (95% CI: 34, 41) believed dentists to be effective in smoking cessation and even fewer (18%; 95% CI: 15, 21) routinely recorded their patients' smoking status. Of respondents, 51% (95% CI: 46, 55) said they always discussed smoking with patients who had periodontal problems but only 9% (95% CI: 7, 12) always did so with patients who had no major oral health problem. Newer graduates were more likely to routinely record their patients' smoking status (P = 0.02), and to think that doctors' advice (P = 0.001) and nicotine replacement therapy (P < 0.001) were effective in promoting smoking cessation. Dentists in mainly private practices were more active than those in NHS or mixed practices in recording patients' smoking status (P < 0.001) and in discussing smoking (P = 0.002). CONCLUSIONS: Most respondents thought that dentists should encourage their patients to stop smoking but few are active in this area.
We demonstrate that in Saccharomyces cerevisiae, the tandem array of ribosomal RNA genes (RDN1) is a target for integration of the Ty1 retrotransposon that results in silencing of Ty1 transcription and transposition. Ty1 elements transpose into random rDNA repeat units and are mitotically stable. In addition, we have found that mutation of several putative modifiers of RDN1 chromatin structure abolishes silencing of Ty1 elements in the rDNA array. Disruption of SIR2, which elevates recombination in RDN1, or TOP1, which increases psoralen accessibility in rDNA, or HTA1-HTB1, which reduces histone H2A-H2B levels and causes localized chromatin perturbations, abolishes transcriptional silencing of Ty1 elements in RDN1. Furthermore, deletion of the gene for the ubiquitin conjugating enzyme Ubc2p, which ubiquitinates histones in vitro, derepresses not only Ty1 transcription but also mitotic recombination in RDN1. On the basis of these results, we propose that a specialized chromatin structure exists in RDN1 that silences transcription of the Ty1 retrotransposon.
Although a number of cytokines have been implicated in tissue regeneration, it is unknown which ones actually function in vivo. Here, we use mice with a targeted mutation in the leukemia inhibitory factor (LIF) gene to examine the role of LIF in muscle regeneration. Using a muscle crush model, we show that muscle regeneration in LIF knockout mice is significantly, reduced compared to control littermates. Further, targeted infusion of LIF in both normal and LIF knockout animals stimulated muscle regeneration, but the stimulation observed was much greater in the mutant animals than in controls. In contrast, interleukin-6 and transforming growth factor-alpha, which also stimulate myoblast proliferation in vitro, had no effect on regeneration. These findings demonstrate directly that LIF is involved in regeneration of injured muscle and points to the use of LIF as a therapeutic agent in the treatment of neuromuscular disease.