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Biomedical subjects

R M Walker

Publications and source records attributed to R M Walker.

At least 19 recordsLinked to original sources
PubMed1995

Living wills and resuscitation preferences in an elderly population.

BACKGROUND: Living wills are considered clear and convincing evidence of a person's preferences for end-of-life treatment. Unfortunately, living wills often use vague language that forces physicians and others to infer specific treatment choices, like the choice to forgo cardiopulmonary resuscitation (CPR). To test the validity of such inferences we examined the relationship between living will completion and CPR preference. We also examined whether CPR choices were fixed or could be influenced by detailed information on CPR. METHODS: We interviewed 102 retired elderly persons, many of whom had living wills. We obtained CPR preferences in five hypothetical scenarios before and after providing CPR information. We then analyzed differences in desire for CPR between the group of subjects with living wills and the group without. RESULTS: In each scenario there were subjects in both groups who desired CPR. The group with living wills desired less CPR in scenarios involving functional impairment and cognitive impairment, but not in scenarios involving current health, severe illness, and terminal illness. After receiving CPR information, both groups changed their preferences such that intergroup differences were no longer seen. CONCLUSIONS: Preferences for CPR among subjects with living wills are not homogeneous, but distributed across the clinical scenarios. Therefore, one cannot infer CPR preference from the mere presence of a living will. Cardiopulmonary resuscitation information can influence preferences even among persons with living wills, implying that preferences are neither fixed nor always based on adequate information. Physicians should view vaguely worded documents as unreliable expressions of treatment preference that should not supplant informed discussion.

Aged↗
PubMed1991

DNR in the OR. Resuscitation as an operative risk.

Should do-not-resuscitate (DNR) orders be routinely rescinded when terminally ill patients undergo palliative surgery? If so, patients will be forced to balance the benefits of palliative surgery against the risks of unwanted resuscitation. If physicians are required to honor intraoperative DNR orders, they may feel unacceptably restrained from correcting adverse effects for which they feel responsible. This dilemma has been overlooked by DNR policies. This article argues for the permissibility of honoring intraoperative DNR orders. The patient's right to refuse treatment outweighs physicians' concerns about professional scrutiny over intraoperative deaths. Physicians' moral concerns about hastening patient death are important but may be assuaged by (1) emphasizing patients' acceptance of operative mortality risk; (2) viewing matters as analogous to surgery on Jehovah's Witnesses who refuse lifesaving transfusion; (3) viewing the patient's intraoperative death as a double effect, that is, an unintended negative effect that is linked to the performance of a good act (palliation); and (4) distinguishing this from assisted suicide.

Christianity↗
PubMed1991

Beneficial effects of hyperbaric oxygen therapy in Nocardia brasiliensis soft-tissue infection.

OBJECTIVE: To report the success of hyperbaric oxygen therapy in the treatment of Nocardia brasiliensis mycetoma. We believe this to be only the second report in the medical literature of hyperbaric oxygen therapy used in the therapy of nocardial disease. CLINICAL FEATURES: A 78-year-old man presented to a general hospital outpatient clinic after eight months with a painless swollen left foot. There was no significant medical history, no trauma had occurred, and no foreign body had been detected. The dorsum of the foot had a discharging sinus, from which N. brasiliensis was isolated. INTERVENTIONS: After unsuccessful treatment with surgical debridement and high-dose antibiotic therapy, hyperbaric oxygen therapy was administered in a multiplace recompression chamber (one hour of treatment at 1.8 atmospheres absolute followed by a 30 minute "ascent" to surface pressure). A total of 19 treatments were administered. OUTCOME: Successful healing of an N. brasiliensis mycetoma of the left foot. CONCLUSION: In this case of N. brasiliensis mycetoma involving the lower extremity, the conventional management of surgery and antibiotic therapy was unsuccessful, and only with the addition of hyperbaric oxygen therapy did clinical recovery occur.

Aged↗
PubMed1991

Preclinical toxicity studies of an adenosine agonist, N-(2,2-diphenylethyl) adenosine.

N-(2,2-Diphenylethyl)adenosine (DPEA) has been identified as a potential antipsychotic agent acting via stimulation of adenosine receptors. The projected human therapeutic dose, based on animal studies, is 2-3 mg/kg. DPEA has been tested for potential toxicity in mice, rats, dogs and monkeys. Following single oral doses, median lethal dose values were approximately 10-fold greater in rats than in mice, although similar clinical signs including reduced activity, prostration, and necrosis of the tail were seen in both species. DPEA was well tolerated at daily doses up to 40 mg/kg in rats for 2 weeks. A no observed effect level (NOEL) was not identified in the dog or monkey studies. Reduced activity, dacryorrhea, ptosis, hypothermia, necrosis of the tail, and death occurred in rats given 120 and 160 mg/kg. Pathologic changes consisted of pancreatitis, gastric erosion/ulceration, lymphocyte depletion of the thymus, and pulmonary congestion and hemorrhage at 80 mg/kg or greater. In dogs, sporadic emesis was noted at 12.5 mg/kg and greater, and significant pathologic changes consisted of coronary arteritis associated with myocardial lesions and lymphocyte depletion at 25 and 50 mg/kg, pancreatic acinar necrosis at 50 mg/kg, and renal tubular degeneration at 12.5 mg/kg and greater. Emesis and depression were noted at 25 and 50 mg/kg in monkeys. Renal tubular dilatation and degeneration at 25 and 50 mg/kg were noted in the monkeys. These studies demonstrated that DPEA produced a range of adverse effects in common laboratory animal species.

Adenosine↗
PubMed1990

Preclinical toxicology of the anticonvulsant calcium valproate.

The oral toxicity of the anticonvulsant calcium valproate with selected comparisons to valproic acid and sodium valproate was evaluated in mice, rats and Beagle dogs. Median lethal doses of the three forms of valproate in rodents ranged from 1100 to 3900 mg/kg. Clinical signs in acute studies and reductions in body weight or body weight gain and food consumption at high doses in rats and dogs during 2-, 13- and 52-week studies were considered to be central nervous system related. In the 13-week study in rats (calcium valproate at 200, 400, 800, 1200 and 1600 mg/kg and sodium valproate at 1200 mg/kg), reduced plasma globulin levels and low white blood cell counts due to suppressed neutrophil maturation were noted at doses of 800 mg/kg and higher. Platelet counts were reduced at 1200 and 1600 mg/kg. Testicular atrophy occurred at 1200 and 1600 mg/kg. In dogs given calcium valproate at 100, 200 and 400 mg/kg for 13 weeks, testicular atrophy was seen at 400 mg/kg and mild hepatocellular changes at all doses. In rats given calcium valproate at 125, 250 and 500 mg/kg for 1 year, reduced plasma protein and globulin levels and a dose-dependent increased incidence and severity of atrophic pancreatitis were noted at 250 and 500 mg/kg. Calcium valproate, given for 1 year to dogs at doses of 50, 100 and 200 mg/kg, was well tolerated. These studies indicated that calcium valproate has a toxicity profile similar to other forms of valproate.

Animals↗
PubMed1989

Renal and hepatic toxicity of a benzopyran-4-one in the Cynomolgus monkey.

The administration of PD 119819, a novel benzopyran-4-one brain dopamine autoreceptor agonist, to Cynomolgus monkeys was followed by deposition of needle-like drug crystals in the bile canaliculi, hepatocytes, proximal renal tubules and renal parenchyma. The crystals were associated with a granulomatous inflammation, and histological and biochemical evidence of hepatic and renal cell damage. Although metabolism differences may be the reason why primates, but not rodents, developed these changes, this form of crystallization appeared to be primarily a result of the insolubility of PD 119189 at alkaline pH.

5'-Nucleotidase↗
PubMed1989

The illusion of futility in clinical practice.

The claim that a treatment is futile is often used to justify a shift in the physician's ethical obligations to patients. In clinical situations in which non-futile treatments are available, the physician has an obligation to discuss therapeutic alternatives with the patient. By contrast, a physician is under no obligation to offer, or even to discuss, futile therapies. This shift is supported by moral reasoning in ancient and modern medical ethics, by public policy, and by case law. Given this shift in ethical obligations, one might expect that physicians would have unambiguous criteria for determining when a therapy is futile. This is not the case. Rather than being a discrete and definable entity, futile therapy is merely the end of the spectrum of therapies with very low efficacy. Ambiguity in determining futility, arising from linguistic errors, from statistical misinterpretations, and from disagreements about the goals of therapy, undermines the force of futility claims. Decisions to withhold therapy that is deemed futile, like all treatment choices, must follow both clinical judgments about the chance of success of a therapy and an explicit consideration of the patient's goals for therapy. Futility claims rarely should be used to justify a radical shift in ethical obligations.

Attitude of Health Personnel↗
PubMed1989

Medical ethics education: coming of age.

Medical ethics education is instruction that endeavors to teach the examination of the role of values in the doctor's relationship with patients, colleagues, and society. It is one front of a broad curricular effort to develop physicians' values, social perspectives, and interpersonal skills for the practice of medicine. The authors define medical ethics education as more clinically centered than human values education and more inclusive of philosophical, social, and legal issues than is interpersonal skills training. The authors review the history of the emergence of medical ethics education over the last 20 years, examine the areas of consensus that have emerged concerning the general objectives and premises for designing medical ethics programs, and describe teaching objectives and methods, course content, and program evaluation used in such programs on both preclinical and clinical levels. The four interrelated requirements for successful institutionalization of medical ethics education programs are defined and discussed, and the paper ends with an overview of the uncertain future of medical ethics education, an accepted but still not fully mature part of physician training in the United States. An extensive reference list accompanies the article.

Bioethical Issues↗
PubMed1989

Development of a teaching program in clinical medical ethics at the University of Chicago.

The University of Chicago Pritzker School of Medicine has developed and evaluated an extensive teaching program in clinical ethics coordinated primarily through the Center for Clinical Medical Ethics. The program provides medical students with a foundation in medical ethics during the four years of medical school and augments the clinical ethics knowledge and teaching skills of the housestaff and clinical faculty at the University of Chicago. Together, medical student teaching and clinical faculty development have made clinical ethics an integral part of medical education at the University of Chicago. Through these efforts, the teaching program aims to incorporate clinical ethics considerations into medical decisions and in this way contribute to improving patient care. (A detailed overview of all clinical ethics instruction at the school is provided.)

Bioethical Issues↗
PubMed1988

Chronic toxicity of the anticonvulsant zonisamide in beagle dogs.

The chronic toxicity of the new anticonvulsant drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide) was evaluated in a detailed 52-week study in which dose levels of 0, 10, 30 and 75 mg/kg/day were administered orally in gelatin capsules to groups of five Beagle dogs per sex. Potential toxicity was based on the effects of zonisamide on body weight and food consumption; clinical and ophthalmic examinations; electrocardiography and heart rates; clinical biochemistry, hematology and urinalysis determinations; organ weights and gross and histopathologic evaluations; electron microscopy of high dose and control male dogs; and plasma zonisamide concentrations. Zonisamide was relatively well tolerated during the study. In animals given 75 mg/kg/day, early body weight losses occurred and therefore, from Weeks 2 and 3 until study termination, for males and females respectively, the high dose was given as two equal portions (i.e., 37.5 mg/kg each) approximately 3-4 hr apart. Clinical laboratory analyses in the dogs given 75 mg/kg revealed a small but statistically significant decrease in plasma albumin concentration and a small increase in alkaline phosphatase activity. In animals given 75 mg/kg, liver weights were increased and a brownish discoloration of the liver was noted grossly at necropsy. No significant light microscopic changes were evident; however, electron microscopic evaluation of the liver tissue from the 5 male dogs given 75 mg/kg revealed the presence of concentric lamellae of paired smooth membranes which were not seen in control animals. At the 10 and 30 mg/kg dose levels, plasma zonisamide concentrations reached steady-state and were proportional to dose, but at 75 mg/kg, plasma levels were disproportionately higher and never achieved steady-state. The results of this study indicated that at the high dose level of 75 mg/kg, chronic administration of zonisamide had a mild effect on the liver, particularly the endoplasmic reticulum.

Administration, Oral↗
PubMed1987

Furosemide toxicity in isolated mouse hepatocyte suspensions.

Incubation of freshly isolated mouse hepatocytes with 0.5 or 1.0 mM furosemide caused a depletion of cellular acid soluble sulfhydryls to approximately 20-30% of control over the course of 4.5 h. The depletion was accompanied by a reduction in cell viability (indicated by the lactate dehydrogenase latency test) which was significant (P less than 0.05) for 0.5 mM but not for 1.0 mM furosemide at 4.5 h. Ultrastructurally, 0.5 or 1.0 mM furosemide caused cytoplasmic changes including loss of glycogen, disaggregation of polyribosomes, vesiculation of endoplasmic reticulum, and occasional appearance of lamellar bodies consisting of concentric arrays of paired smooth membranes. These concentrations of furosemide also caused cell surface changes, including loss of microvilli, development of an irregular shape compared to the spherical appearance of untreated hepatocytes, and the development of occasional blebs. The appearance of pale staining hydropic cells was indicative of the final stages of cell death. N-Acetylcysteine (6.0 mM) was effective at preventing the depletion of soluble sulfhydryls, the loss of viability, and the ultrastructural effects of 0.5 or 1.0 mM furosemide, suggesting a role for soluble sulfhydryls in the pathogenesis of furosemide hepatotoxicity.

Acetylcysteine↗
PubMed1984

Prophylactic antibiotics in appendicectomy: a prospective double blind randomized study.

Our double blind prospective randomized trial comparing intravenous cefoxitin with rectal metronidazole in appendicectomy reveals both groups to be similar regarding basic data, with no significant difference in the results between the two drugs. Nearly all the wound infections occurred after the patient went home. Most were minor infections and the overall infection rate was 6%. The intravenous route was the more certain but the more expensive. Bacteriology suggests that the same flora were present in the appendiceal wall of normal and acute non-perforated appendices. This would suggest bacteriologically that the same risks exist with non-inflamed appendicectomy as occurs with inflamed non-perforated appendices. These findings support the use of short course prophylaxis in appendicectomy.

Adolescent↗
PubMed1983

Ultrastructural effects of acetaminophen in isolated mouse hepatocytes.

The ultrastructure of isolated mouse hepatocytes shows good correlation with that of cells from intact liver. Incubation of isolated mouse hepatocytes with 1.0 mM acetaminophen causes a variety of cytoplasmic and cell surface lesions, as well as cell death. The changes are similar or equivalent to those caused by acetaminophen in vivo. The most prominent feature of damage in isolated hepatocytes is bleb formation, which is also seen occasionally in control incubations. The protective compound alpha-mercaptopropionylglycine and the antidote N-acetylcysteine both prevented the acetaminophen-induced changes. It is suggested that the in vivo counterpart to the blebs are endocytic vacuoles which form at cell margins due to the intravascular pressure of the sinusoids. It is suggested that the cell surface changes both in vivo and in isolated hepatocytes are caused by some dysfunction to the microfilament component of the cytoskeleton.

Acetaminophen↗
PubMed1983

Increased acetaminophen-induced hepatotoxicity after chronic ethanol consumption in mice.

The effect of chronic ethanol consumption on acetaminophen (200, 400, and 600 mg/kg) toxicity was determined by maintaining mice for 10 days on diets consisting of chow and one of the following drinking solutions: 10% ethanol + 10% sucrose, 8% sucrose, or tap water. Toxicity as manifested by mortality, liver enlargement, and liver congestion was greatest in the ethanol-treated group. We suggest that the greater mortality was a result of the increased liver congestion and consequent hypovolemia. Despite the increased levels of cytochrome(s) P-450, covalent binding of [3H]acetaminophen reactive metabolite(s) to liver protein was not higher in ethanol-treated animals. This can be explained by the higher initial glutathione concentration and/or ability to replenish glutathione in the ethanol-treated group. We suggest that the enhancement of acetaminophen toxicity by ethanol is the result of an effect of ethanol on hepatocyte membranes which renders the cells more susceptible to toxic injury.

Acetaminophen↗
PubMed1983

Scanning electron microscopic examination of acetaminophen-induced hepatotoxicity and congestion in mice.

Acetaminophen-induced hepatotoxicity and associated hepatic congestion were investigated by scanning and correlative transmission electron microscopy. Acetaminophen (750 mg/kg orally) causes changes in cell surface morphology and the relationship between hepatocytes and sinusoidal lining cells. There is endocytic vacuolation at lateral and sinusoidal margins of centrilobular hepatocytes, loss of microvilli, Disse space enlargement, dilation of bile canaliculi, and disappearance of the studlike projections from hepatocyte lateral surfaces. Erythrocytes enter the enlarged Disse space and endocytic vacuoles via enlarged pores in sinusoidal lining cells, thereby collapsing the sinusoids. Lining cells are not lost, but apparently held in position by preservation of intercellular junctions, cytoplasmic projections from hepatocytes, and anchorage by fat-storing cells within the Disse space. Congestion can abate by 24 hours, indicating that erythrocytes can return to the general circulation from the Disse space.

Acetaminophen↗