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Biomedical subjects

C J Ryan

Publications and source records attributed to C J Ryan.

At least 19 recordsLinked to original sources

Multisorbent plasma perfusion in fulminant hepatic failure: effects of duration and frequency of treatment in rats with grade III hepatic coma.

Using the model of galactosamine-induced fulminant hepatic failure in the rat, the effects of multisorbent plasma perfusion over Asahi uncoated spherical charcoal, Plasorba (BR-350) resin, and an endotoxin removing adsorbent (polymyxin B-sepharose) were determined in Grade III hepatic coma animals by studying survival as influenced by timing, duration, and frequency of treatment. The effects of treatment on liver cell proliferation and endotoxin removal also were examined. The results demonstrate that duration and frequency of treatment are major contributing factors in the successful application of nonbiological membrane-based multisorbent liver support systems. Examination of the regenerative activity in the liver indicates an enhanced proliferative response following multisorbent plasma perfusion compared with untreated fulminant hepatic failure (FHF) paired controls. Utilizing an endotoxin removal adsorbent alone, a marked reduction in systemic levels of endotoxin in FHF was demonstrated compared with nonperfused FHF paired controls. Despite current emphasis on bioartificial liver support systems, plasma purification by multisorbent systems offers a simple method for the removal of circulating toxic metabolites in general together with specific toxin removal.

Animals↗

Intensive care unit syndrome: a dangerous misnomer.

The terms intensive care unit (ICU) syndrome and ICU psychosis have been used interchangeably to describe a cluster of psychiatric symptoms that are unique to the ICU environment. It is often postulated that aspects of the ICU, such as sleep deprivation and sensory overload or monotony, are causes of the syndrome. This article reviews the empirical support for these propositions. We conclude that ICU syndrome does not differ from delirium and that ICU syndrome is caused exclusively by organic stressors on the central nervous system. We argue further that the term ICU syndrome is dangerous because it impedes standardized communication and research and may reduce the vigilance necessary to promptly investigate and reverse the medical cause of the delirium. Directions for future research are suggested.

Cognition Disorders↗

Angiogenesis inhibitors. New agents in cancer therapy.

Tumours that do not develop a blood supply cannot grow larger than 1 to 2mm3. The growth of a tumour blood supply, called angiogenesis, is a complex process that greatly increases the likelihood of metastatic spread and aggressive tumour behaviour. Molecular processes involved in angiogenesis include stimulation of endothelial growth by tumour cytokine production (vascular endothelial growth factor), degradation of extracellular matrix proteins by metalloproteinases, and migration of endothelial cells mediated by cell membrane adhesion molecules called integrins. These processes are being targeted by several new types of agents broadly classified as angiogenesis inhibitors. Additionally, endogenous angiogenesis inhibitors have been discovered and one of them, endostatin, is currently undergoing clinical trials. The unique targets of these drugs make them distinct from traditional cytotoxic chemotherapeutic agents. Unlike cytotoxic chemotherapy, in which the biological effect of the drug produces the antitumour effect as well as the toxic effect, angiogenesis inhibitors may produce their biological effect independently of the toxic effect. This fact raises important questions among clinical investigators as to what is the most effective way to administer these drugs and monitor their effects. This paper details some of the scientific evidence making angiogenesis an important therapeutic target as well as issues regarding the structure of clinical trials with these new anticancer agents.

Angiogenesis Inhibitors↗

Examination of particulate macroporous hydrogels in an extracorporeal rat haemoperfusion model.

A series of macroporous hydrogels has been synthesized, selected from a range of such materials in which the presence of functional groups has been shown to produce sorbent properties with respect to molecules having clinical significance in the field of liver support. The use of freeze thaw polymerization, together with inverse suspension polymerization in hexane, or in brine, enables macroporous beads ranging in size from 150 to 2000 microm, to be prepared from functional monomers exhibiting a range of chemical functionalities and aqueous solubilities. In order to investigate the behaviour of these rigid porous hydrophilic substrates in haemoperfusion, a rat model was used to explore various aspects of whole blood response. The materials were incorporated into an extracorporeal circuit linking the right carotid artery and left jugular vein of male Sprague-Dawley rats. Erythrocyte, leucocyte and platelet levels were monitored over a 240 min haemoperfusion period. The most significant observation is that, apart from the strongly acidic polyacrylic acid substrate. matrix chemistry has relatively little effect on leucocyte or platelet response. The most important factors appear to be surface area, pore size and surface rugosity, which do produce measurable, but not dramatic differences. This is encouraging for future work, since these variables may be manipulated by polymerization conditions.

Acrylates↗

Recent improvement in results of coronary bypass surgery in octogenarians.

BACKGROUND: Because of concerns regarding the cost-effectiveness of coronary artery surgery in patients 80 years and older, a review of a large experience is appropriate. METHODS: The records of 404 consecutive patients 80 years of age or older having isolated coronary bypass surgery (CABG) from 1985 through 1996 were reviewed. Patients were divided equally into an early and later group. Hospital mortality, complications including major arrhythmias, wound infections and separations, re-explorations, peri-operative Q-wave myocardial infarctions, major organ dysfunction, stroke, time to extubation, post-operative hospital (LOS) and intensive care unit (ICU) lengths of stay were compared. A logistic regression risk model was used to assess the relative contributions of improved technique versus more favorable patient selection. RESULTS: Comparison of the two groups revealed the following: overall hospital mortality decreased from 12.9% to 5.4% (p = 0.003), more markedly so with elective procedures where hospital mortality decreased from 8.1% to 1.2% (p = 0.04). There were significant decreases in time to extubation (2.8 +/- 9.3 days versus 1.2 +/- 2.8 days; p = 0.02), post-operative intensive care unit stay (4.9 +/- 7.1 days versus 2.9 +/- 3.7 days; p = 0.0004), post-operative complication rate (34.2% versus 22.8%; p = 0.03), and post-operative hospital length of stay (14.2 +/- 14.7 days versus 9.8 +/- 9.8 days; p = 0.0005). Post-operative stroke decreased from 7.4% to 5.9%. Mean estimated risk for the two groups was 8.2 +/- 10.2% versus 8.2 +/- 11.4%. CONCLUSION: Coronary surgery can be performed with acceptable risk in octogenarians. Results have improved over the past few years. This improvement is probably not attributable to patient selection.

Aged↗

Pulling up the runaway: the effect of new evidence on euthanasia's slippery slope.

The slippery slope argument has been the mainstay of many of those opposed to the legalisation of physician-assisted suicide and euthanasia. In this paper I re-examine the slippery slope in the light of two recent studies that examined the prevalence of medical decisions concerning the end of life in the Netherlands and in Australia. I argue that these two studies have robbed the slippery slope of the source of its power--its intuitive obviousness. Finally I propose that, contrary to the warnings of the slippery slope, the available evidence suggests that the legalisation of physician-assisted suicide might actually decrease the prevalence of non-voluntary and involuntary euthanasia.

Australia↗

Sex, lies and training programs: the ethics of consensual sexual relationships between psychiatrists and trainee psychiatrists.

OBJECTIVE: The aim of this paper is to chart the ethical territory surrounding the issue of consensual sexual relationships between psychiatrists and doctors training in psychiatry. METHOD: The arguments for and against the prohibition of such relationships are critically examined both in general and in a number of specific circumstances. RESULTS: There should not be a general prohibition against such relationships, but a prohibition should apply in certain special circumstances. Such circumstances include occasions when the psychiatrist is currently supervising the trainee, when a particular psychiatrist has repeated sexual relationships with trainees and when a group of psychiatrists voluntarily pledge to abstain from such relationships. CONCLUSIONS: Institutions involved in psychiatric training should develop guidelines for dealing with such relationships, adopting a generally permissive attitude toward them with clear exceptions in special cases.

Australia↗

The anti-proliferative effect of plasma from rats with acute fulminant hepatic failure.

BACKGROUND: During fulminant hepatic failure (FHF) metabolites normally cleared by the liver accumulate in the circulation and cause hepatic coma. It is believed that the plasma of FHF patients has an inhibitory effect on liver regeneration. Plasma exchange was used to study the effect of plasma collected from donor FHF rats on liver regeneration in two-thirds partially hepatectomized syngeneic animals. METHODS: FHF and hepatic coma were induced in donors by administration of galactosamine at a dose of 1.85 g/kg. Plasma from donors in either grade-II or -IV coma was transfused by plasma exchange into partially hepatectomized animals 2h after resection. RESULTS: The livers from donor animals showed evidence of oval cell activation 1-2 days after galactosamine, but differentiation of oval cells to hepatocytes did not occur before the development of coma. The plasma collected from animals in grade-IV coma totally abolished regeneration in the partially hepatectomized recipients. CONCLUSION: These results support the hypothesis that metabolites present in the plasma during FHF inhibit liver regeneration.

Acute Disease↗

Betting your life: an argument against certain advance directives.

In the last decade the use of advance directives or living wills has become increasingly common. This paper is concerned with those advance directives in which the user opts for withdrawal of active treatment in a future situation where he or she is incompetent to consent to conservative management but where that incompetence is potentially reversible. This type of directive assumes that the individual is able accurately to determine the type of treatment he or she would have adopted had he or she been competent in this future scenario. The paper argues that this assumption is flawed and provides theoretical and empirical evidence for this. If the assumption is false, and those taking out advance directives do not realise this, then the ethical bases for the use of these advance directives-the maximisation of the individual's autonomy and minimisation of harm-are undermined. The paper concludes that this form of advance directive should be abolished.

Advance Directive Adherence↗

Recovery from ischemic acute renal failure: independence from dialysis membrane type.

Exposure to complement-activating cellulosic dialysis membranes has been claimed to adversely affect the course of acute renal failure. To test this hypothesis, male Sprague-Dawley rats were allocated to two groups: in group I, acute renal failure was induced by bilateral renal artery clamping, while group II animals underwent a sham procedure. In each group, the rats were further allocated to undergo hemodialysis with either a Cuprophan, a Hemophan, or a PAN miniDialyzer membrane 3 and 7 days after surgery or no dialysis. The renal function was measured by inulin clearance on the days following dialysis. Temporary occlusion of the renal arteries led to a rapid increase in serum urea and creatinine levels that peaked between 24 and 48 h after surgery and declined slowly thereafter. Peak urea values were similar in the acute renal failure groups. The hemodialysis sessions were well tolerated. Degree and rate of recovery were similar in all acute renal failure groups irrespective of whether they underwent dialysis or not or the type of the dialysis membrane. Complete recovery was observed in all the acute renal failure groups by the end of the observation period. Our findings refute the hypothesis that in ischemic acute renal failure exposure to complement-activating cellulosic dialysis membranes impairs the recovery of renal function.

Acute Kidney Injury↗