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Medicine is a human endeavor aided by a sophisticated set of diagnostic tools. Healthcare systems are challenged with incorporating new and unfamiliar technology into existing systems of practice. As diagnostic tools such as artificial intelligence have entered the realm of clinical practice, new opportunities have arisen to optimize healthcare delivery. Overreliance on AI may lead to the dehumanization of medicine. However, with appropriate implementation, AI can free up time and resources to allow healthcare providers to focus on aspects of care that are unique humanistic. Effective medical practice requires availability of data, application of information, and appropriate clinical judgement. A large portion of modern patient care takes place without the presence of the patient. AI has shown the potential to synthesize and summarize vast amounts of data from medical records, clinical trials, and best-practice guidelines. By tailoring all available data to each case, AI can serve as an asset in enhancing diagnostic accuracy and increasing the efficiency of healthcare delivery. However, clinical decisions made between patients and their physicians cannot be reduced to a set of parameters, code, or logic trees. Clinical judgment and the implementation of available information remains necessarily human tasks. Only through a strong therapeutic relationship built on trust and empathy can shared decision making and compliance be attained. We propose a framework through which AI and humanistic medicine can build on one another to create a symbiosis of the highest possible caliber of patient care and healthcare quality.

Balancing efficiency with healthcare quality is an emerging concern around the world. Deep-seated feedback loops are being realized in healthcare systems around the world, driving physician burnout, unnecessary healthcare costs, and suboptimal clinical outcomes. These are not localized or insignificant issues – they are present across cultures, continents, and all medical disciplines. Physician burnout is nearly doubling the rate of medical errors, and physicians involved in major errors are experiencing a threefold increase in suicidal ideation. As the complexity of health systems increases around the world, these trends continue to evolve and perpetuate one another. We have recommended that through non-punitive and interdisciplinary approaches, medical error can be properly disclosed, addressed, and mitigated in future practice. Systemic strategies to optimize healthcare delivery include shifting focus to the quality of care rather than productivity while fostering innovation in clinical practice and policy.

The introduction of an unfamiliar disease has added uncertainty to many aspects of the practice of medicine. Evidence-based-guidelines on the recognition, investigation, and treatment of COVID-19 and its sequelae are in early stages. Clinicians are often left making critical diagnostic and treatment decisions in the absence of clear evidence. Operating in the face of uncertainty has brought to light fallibilities in clinical decision-making processes in healthcare systems around the world. A growing body of literature on COVID-19 and its associated Multisystem Inflammatory Syndrome has revealed self-perpetuating cycles of cognitive biases with far-reaching implications on patients, populations, and healthcare systems. We describe the implications of cognitive biases on decision making processes in the context of the COVID-19 pandemic. In an era when even the most experienced of clinicians find themselves navigating unchartered territory, we must rely on tried-and-true diagnostic decision-making processes to mitigate cognitive biases. To address a challenge of such complexity, we incorporate a problem spaces perspective to clinical decision making, encompasses the broader context in which decisions are made, including workplace environment, team dynamics, patient wishes, practitioner perspectives, framing of the problem, and sociocultural factors. By applying evidence from relevant disciplines, we highlight strategies to mitigate cognitive biases during emerging infectious disease pandemics, including optimizing multidisciplinary decision-making, building redundancies, and strengthening decision making processes. Continuous feedback, recalibration, and reflection will provide a better understanding of the art of diagnostic decision making and improve healthcare quality.

The capabilities of artificial intelligence (AI) in medicine are expanding at an unprecedented pace. AI has the potential to serve as an invaluable asset in harnessing large amounts of data to generate new diagnostic models, inform clinical decision making, and to expand the capabilities of modern medicine. AI has proven beneficial in various fields of diagnostic medicine including radiology, pathology, and laboratory medicine. AI programs have been shown to increase workflow without compromising accurate identification of abnormalities. Aspects of human error in medicine can be mitigated through the use of machine learning programs to serve as quality assurance and failsafe strategy. The advent of AI in healthcare carries many ethical, legal, and accountability challenges. These challenges include issues of transparency, data security, informed consent, and liability. Lack of familiarity with AI systems and fear of unforeseen consequences warrants caution in the implementation of these new tools. However, undue delays in the implementation of AI may unnecessarily hinder the progress of medicine and limit the level of care that can be provided to patients. Healthcare providers should ensure they are well-positioned to adapt to this new technological era of medicine by remaining up to date on the implications of technological advances. Medical education will require continuous revaluation and adaptation to ensure learners gain the appropriate digital literacy to function effectively in AI-assisted medical practice. The implementation of these technologies into healthcare systems represents the greatest healthcare transition of our time. Optimizing this transition in a growing number of medical disciplines will require tactful implementation and diligent risk management.

The quality of healthcare is an emerging concern worldwide. In any health care process, adverse events resulting from errors are inevitable. The role of the medical autopsy is evolving yet it remains a cornerstone in the progress of healthcare quality and diagnostic medicine. Although the autopsy has been instrumental in understanding disease processes for the past 3000 years, there has been a concerning decrease in autopsy rates. This trend is influenced by barriers pertaining to resources, consent, and medicolegal hesitations. Reversing the trend in falling autopsy rates will require recognition of the role of the medical autopsy as an essential feedback mechanism in healthcare quality improvement. The autopsy has shaped the current state of medicine and with appropriate implementation, support, and collaboration will continue to guide the path forward.

Medical error has become a major issue around the globe. When errors occur, healthcare practitioners are faced with the ethical dilemma of if, and to whom to disclose the errors. This dilemma of disclosure is faced by healthcare providers across all disciplines, countries, and generations and has far-reaching implications on the progress of healthcare quality. Medical error disclosure is a necessary step to foster a culture of transparency, strengthen partnerships, and improve the quality of healthcare. Although the principle of medical error disclosure is widely acknowledged and endorsed by providers and patients, disclosure is far from common practice. We reviewed Canadian and global disclosure policies and discuss what steps should be taken to remedy the status quo. We suggest the implementation of a uniform policy centered on addressing errors in an ethical and non-punitive manner while respecting the patient’s right to an honest disclosure be a standard of care.

Protein electrophoresis is commonly used as an aid in the diagnosis of monoclonal gammopathies and is performed in many laboratories in Canada and throughout the world. However, unlike many other diagnostic tests, there is limited guidance for standardization and neither guidance nor specific recommendations for clinical reporting of serum (SPE) or urine (UPE) protein electrophoresis and immunotyping available in the literature. Therefore, a Canadian effort was undertaken to recommend standards that cover all aspects of clinical reporting with an ultimate goal towards reporting standardization. The Canadian Society of Clinical Chemists (CSCC) Monoclonal Gammopathy Interest Group (MGIG), which is composed of CSCC members with an interest in protein electrophoresis, has formed a Monoclonal Gammopathy Working Group (MGWG) to take initial steps towards standardization of SPE, UPE and immunotyping. Candidate standardization recommendations were developed, discussed and voted upon by the MGWG. Candidate recommendations that achieved 90% agreement are presented as consensus recommendations. Recommendations that did not achieve 90% consensus remain candidate recommendations and are presented with accompanying MGWG discussion. Eleven consensus recommendations along with candidate recommendations for nomenclature, protein fraction reporting, test utilization, interference handling and interpretive reporting options are presented.

Disclosure of an adverse event is an important element in managing the consequences of a medical error. The objectives of this study was to review and compare the disclosure policies implemented by individual health care authorities and hospitals in western Canada. The evaluation of the policies of individual health authorities was carried out based on the inclusion of various guidelines including avoidance of blame; support to the staff; an apology or expression of regret; avoidance of speculation; some form of patient support; and education/training to health care workers. The complexities of medical error disclosure to patients present ideal opportunities for medical educators to probe how learners are balancing the ethical complexities involved in error disclosure with other related fields. We suggest that the disclosure policies can provide framework and guidelines for appropriate disclosure that can lead to practices that are more transparent.

Autopsy diagnoses have traditionally been used as the “Gold Standard” for determining the cause of death. The purpose of this study was to use autopsy to determine the rate of concordance and discordance between clinical diagnoses and post-mortem findings in patients admitted to the hospitals of the Saskatoon Health Region. A retrospective record review of the medical and autopsy charts was carried out by three independent observers for all the deceased adult in-patients admitted during 2006 to 2008. In accordance with selection criteria, 102 (59 males; 43 females) cases were assessed. The concordance rate between clinical and autopsy diagnosis was found to be 86.3%. The discordance rate was 12.7% and in 1.0% was inconclusive. We encourage residents and physicians to continue using autopsy as an important tool to extend our understanding of disease processes.

In the present study, we investigated if there are any diurnal variations in serum thyroid stimulating hormone (TSH) levels in normal subjects and any alterations in serum TSH, free thyroxine (fT4), and free triiodothyronine (fT3) levels with aging. Our results showed the presence of a circadian rhythm in serum TSH levels in normal subjects (n = 11; 5 males, 6 females; age range 19–46) with no significant changes in fT3 and fT4, indicating that the regulation of TSH is central rather than peripheral. In addition, we examined samples from 1,571 euthyroid outpatients (513 males, 1,058 females; age range 10–90) over a 6-month period. Serum TSH levels in age groups 50–59, 60–69, 70–79, and 80–89 were found to be progressively higher than those in the age group 10–19 with no significant differences between male and female populations. These findings suggest the presence of an alteration in TSH secretion with aging.

Various strategies have been adopted to reduce medical diagnostic laboratory errors. Proficiency testing (PT) is one of the most efficient external quality assessment (EQA) approaches which include an external assessment of a laboratory’s analytical performance in comparison to its peers or to an accuracy-based reference system. To assess quality, the clinical biochemistry laboratory routinely participated in two external PT programs: Provincial Health Metrx and College of American Pathologists (CAP) survey. In Health Metrx, 598 tests for 43 analyte resulted in 3 discrepancies, yielding a total discrepancy rate of 0.50%. In CAP survey, of 431 tests for 58 analyte, 3 discrepancies resulted, yielding a total discrepancy rate of 0.70%. These results are in sync with the performance criteria and requirements set up by provincial regulatory agencies and both PT surveys. We suggest that proficiency testing programs should be an integral part of quality care to promote continuous quality improvement in healthcare.

Polymorphonuclear (PMN) leukocytes are one of the most important defenses against bacterial infections. The reports of age related functional changes in PMN leukocyte have been conflicting in the literature. We measured the luminol-dependent chemiluminescence (LDCL) activity for reactive oxygen species (ROSs) and superoxide anion (O2-) production in vitro, to study the age related functional changes in PMN leukocyte. Luminol-dependent chemiluminescence activity for ROSs and superoxide anion generation by PMN leukocyte from different age groups did not change significantly. There were no significant differences in total white blood cells and PMN counts in subjects of various ages. These results suggest that there were no significant functional alterations in PMN leukocyte with aging with respect to ROSs and superoxide anion production.

In any health care process, adverse events resulting from errors are inevitable. Failure to inform the patient of adverse events caused by a medical error compromises the autonomy of the patient. Disclosure of an adverse event is an important element in managing the consequences of a medical error. Physicians should seek to disclose medical errors to patients and their families on both ethical and pragmatic grounds. Effective communication between health care providers, patients and their families throughout the disclosure process is integral in sustaining and developing the physician patient relationship.

Oxygen-free radicals have been implicated in hypercholesteolemic atherosclerosis. It is possible that hypercholesterolemia produces oxidative stress in myocardium. We therefore investigated the effects of a high cholesterol diet in the absence or presence of vitamin E on serum cholesterol and lipid peroxidation product malondialdehyde (MDA), chemiluminescence (M-CL), a measure of antioxidant reserve, and activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)] in cardiac muscles of rabbits. Rabbits were divided into four groups: Group I, regular rabbit chow diet; Group II, same as Group I + vitamin E; Group III, high cholesterol diet; Group IV, high cholesterol + vitamin E. The heart was removed under anesthesia at the end of 4 months on their respective diets for various biochemical measurements. Serum cholesterol in Groups III and IV increased to a similar extent. There was an increase in the levels of MDA, M-CL, GSH-Px activity and a decrease in SOD activity in hypercholesterolemic rabbits in the absence of vitamin E. Vitamin E prevented the hypercholesterolemia-induced changes in cardiac MDA, M-CL, and GSH-Px. These results suggest that hypercholesterolemia produces oxidative stress in the myocardium which may be due to a decrease in the antioxidant reserve, and that vitamin E is effective in preventing hypercholesterolemia-induced oxidative stress on the myocardium.

Effects of purpurogallin (PPG), an antioxidant on high cholesterol diet-induced atherosclerosis, and changes in blood lipid profile and lipid peroxidation product malondialdehyde (MDA), aortic tissue MDA, chemiluminescence (M-CL), a marker for antioxidant reserve and antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)] were investigated in rabbits. The rabbits were divided into three groups: Group I, regular rabbit chow; Group II, same as Group I+cholesterol (1%); and Group III, same as Group II+PPG (14 mg/kg, orally, daily). Serum concentrations of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and blood MDA were measured before and after 4 and 10 weeks on the respective diets. The aorta was removed at the end of 10 weeks for assessment of atherosclerotic changes, MDA concentration, M-CL, and antioxidant enzymes. Coronary arteries were also examined for atherosclerotic changes. Serum TC, LDL-C, and LDL-C/HDL-C ratio increased whereas HDL-C decreased in Group II and their values were similar in Groups II and III. Aortic tissue MDA, M-CL, CAT, and GSH-Px activity increased in Group II but these values in Group III were lower than in Group II except for MDA which was greater in Group III than in Group II. Atherosclerotic changes were greater in Group II than in Group III. Histological changes were similar in Groups II and III. Atherosclerotic changes were also observed in the coronary arteries of Groups II and III, however, they were less in Group III than in Group II. Increased levels of aortic MDA and decreased levels of antioxidant reserve, which were associated with the development of atherosclerosis, suggest a role for oxygen radicals in the pathogenesis of hypercholesterolemic atherosclerosis. The protection afforded by PPG, which was associated with reversal of the antioxidant reserve to control level, in spite of hypercholesterolemia, supports the hypothesis that oxygen radicals are involved in the development of hypercholesterolemic atherosclerosis. These results suggest that PPG retard the development of hypercholesterolemic atherosclerosis because of its antioxidant activity without lowering blood cholesterol level.

Oxygen free radicals (OFRs) derived from activated polymorphonuclear (PMN) leukocytes have been implicated in the ischemia-reperfusion cardiac injury. Hypochlorous acid (HOCl) is produced by activated PMN leukocytes and can damage tissue directly or through formation of hydroxyl radicals. We therefore investigated the effects of methionine (a quencher of HOCl) on cardiac function and cardiac contractility; oxygen-free, radical-producing activity of PMN leukocytes (PMN-CL); serum malondialdehyde (MDA); activity of creatine kinase (CK) and MB fraction of CK (CK-MB); blood lactate, and pH and infarct size after 3 hours of reperfusion following 1.5 hours of occlusion of the left circumflex coronary artery (LCX) in anesthetized dogs. The dogs were divided into three groups: Group I, complete ligation of LCX for 4.5 hours; Group II, ligation of LCX for 1.5 hours followed by 3 hours of reperfusion; Group III, similar to Group II but received methionine 60 mg/kg, i.v. 10 minutes before ligation, 10 minutes before reperfusion, and 60 minutes after reperfusion. Measurements of hemodynamic parameters and collection of blood samples for biochemical parameters were made at various intervals. In general, myocardial contractility was unaltered whereas cardiac function decreased to a similar extent in the three groups. The area at risk was similar and infarct size was greater in Groups II and III, but both were greater than in Group I. The size in Group III was smaller than in Group II. CK and CK-MB activity increased in all groups but more in Groups II and III than in Group I. The increases were smaller in Group III than in Group II. PMN-CL activity increased significantly in Group II but remained unchanged in Groups I and III. Serum MDA remained unchanged. Changes in blood lactate and pH were similar in the three groups. These results suggest that (1) the area at risk in unperfused ischemic myocardium is smaller than in perfused ischemic myocardium; (2) reperfusion produced greater myocardial necrosis as compared with unperfused ischemic myocardium; (3) methionine is very effective in preventing ischemia-reperfusion-induced myocardial necrosis.

Platelet-activating factor (PAF) is released in numerous clinical situations. PAF primes or directly activates polymorphonuclear (PMN) leukocytes, which results in release of oxyradicals (O 2 − , H2O2, .OH) and hypochlorous acid (HOCl). The authors investigated the effects of PAF (1 µg/kg IV) in the absence and in the presence of antioxidants (superoxide dismutase [SOD], catalase [CAT], dimethylthiourea [DMTU]) and methionine, a quencher of HOCl, on cardiac function and contractility; blood lactate, gases, and pH levels; serum creatine kinase activity (CK); chemiluminescent activity of PMN leukocytes; and cardiac tissue malondialdehyde (MDA) in anesthetized dogs. Hemodynamic measurements and collection of blood samples for various biochemical measurements were made before and at various intervals up to two hours after PAF administration in the presence and absence of various antioxidants. PAF produced a decrease in indices of cardiac function and contractility and an increase in systemic and pulmonary vascular resistance. There were decreases in the blood pH and PMN leukocyte chemiluminescence and increases in blood lactate, serum CK activity, and tissue MDA content. SOD plus catalase or DMTU plus methionine reduced the effects of PAF on cardiac function and contractility, blood lactate and pH, serum CK, and cardiac tissue MDA. The antioxidants only partially antagonized the deleterious effects of PAF. The combination of SOD + CAT was superior to that of DMTU + methionine in reducing the deleterious effects of PAF. These results suggest that PAF-induced depression of cardiac function and contractility, and the increase in systemic and pulmonary vascular resistance, may be partly mediated by the release of oxyradicals and HOCl from PMN leukocytes. Antioxidants may be beneficial in reducing the deleterious effects of PAF on the cardiovascular system.

We investigated the effects of high cholesterol diet in the presence and absence of probucol on the genesis of atherosclerosis, the blood lipid profile, aortic tissue lipid peroxidation product malondialdehyde (MDA), and aortic tissue chemiluminescence (CL) a marker for antioxidant reserve in rabbits. Five groups each of 10 rabbits were studied: group I, regular rabbit chow; group II, as I + cholesterol (0.5%); group III, as I + cholesterol (0.5%) and probucol (0.5 gm/kg/day); group IV, as I + cholesterol (1%), and group V, as I + cholesterol (1%) and probucol (0.5 gm/kg/day). Blood concentrations of triglyceride (TG), total cholesterol (TC), high density lipoproteincholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) were measured at monthly intervals for 4 months. The aorta was removed at the end of the protocol for assessment of atherosclerotic changes (gross and microscopic), MDA concentration and CL. TC, LDL-C, LDL-C/HDL-C ratio increased in all the groups except group I, while VLDL-C increased in group II only. HDL-C decreased in groups III, IV and V but remained unchanged in groups I and II. There was a decrease in HDL-C and VLDL-C components and an increase in LDL-C components of total cholesterol in all the groups II, III, IV and V, the changes being greater in group IV than in group II. Probucol did not appreciably affect the changes in lipid profile except that it decreased HDL-C significantly. Aortic tissue MDA increased in groups II, IV and V to a similar extent. Aortic CL which was measured only in groups I, IV and V increased to similar extent in the latter two groups. Atherosclerotic changes were greater in group II than in group III but similar to that in groups IV and V. Histological changes were practically similar in groups II, III, IV and V. The increased levels of aortic MDA and CL, which were associated with development of atherosclerosis, suggest a role for oxygen free radicals in the pathogenesis of hypercholesterolemia-induced atherosclerosis. Protection afforded by probucol was associated with a decrease in aortic MDA in spite of hypercholesterolemia. Ineffectiveness of probucol in 1% cholesterolfed rabbits was associated with its inability to reduce MDA and increase antioxidant reserve. These findings further support for the hypothesis that oxygen free radicals are involved in the genesis and maintenance of hypercholesterolemic atherosclerosis.

The present study was conducted to investigate the differences in the vitreous humor biochemical concentrations for vitreous electrolytes and calcium in the same pair of eyes at identical postmortem interval (PMI). The vitreous humor samples were collected independently in both eyes from 48 autopsies (PMI range, 4.5-84.3 hours) with documented time of death. The samples were analyzed for potassium, sodium, chloride, and calcium using a Beckman Coulter LX20 Automated Analyzer based on ion-selective electrode methodology. There were no statistically significant between-eye differences at identical postmortem interval. A significantly high correlation was observed between paired potassium concentrations of both the eyes. A highly significant linear correlation was observed between the individual eye and mean potassium concentrations of both the eyes with postmortem interval. The observed differences were not significantly correlated with postmortem interval. The results demonstrated that the between-eye differences for vitreous electrolytes and calcium are insignificant. Therefore, the utility of vitreous biochemistry, particularly potassium in postmortem interval estimation and other forensic applications, cannot be questioned solely on the basis of these differences.

The prevalence of medical errors in health care systems has generated immense interest in recent years. The research on adverse events in hospitalized populations has consistently revealed high rates of adverse events. Some of these adverse events result from medical errors and a majority of these errors may be preventable. These errors can occur anywhere and at anytime in health care processes. The consequences of these errors may vary from little or no harm to being ultimately fatal to the patients. It is important to recognize that a degree of error is inevitable in any human task and human fallibility in health care should be accepted. The underlying precursors for many of these human errors may primarily be attributed to latent systemic factors inherent in today's increasingly complex health care system. The focus of adverse event analyses on individual shortcomings without appropriate attention to system issues leads to ineffective solutions. The cognitive influence on medical decision-making and error generation is also significant and should not be discounted.

The Institute of Medicine (IOM) report (1999) stated that the prevalence of medical errors is high in today's health care system. Some specialties in health care are more risky than others. A varying blunder/error rate of 0.1-9.3% in clinical diagnostic laboratories has been reported in the literature. Many of these errors occur in the preanalytical and postanalytical phases of testing. It has been suggested that the errors occurring in clinical diagnostic laboratories are smaller in number than those occurring elsewhere in a hospital setting. However, given the quantum of laboratory tests used in health care, even this small rate may reflect a large number of errors. The surgical specialties, emergency rooms, and intensive care units have been previously identified as areas of risk for patient safety. Though the nature of work in these specialties and their interdependence on clinical diagnostic laboratories presents abundant opportunities for error-generating behavior, many of these errors may be preventable. Appropriate attention to system factors involved in these errors and designing intelligent system approaches may help control and eliminate many of these errors in health care.

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. There are many reports indicating the changes in parameters of oxidative stress in diabetes mellitus. In this study we aimed to identify whether oxidative stress occurs in the liver and pancreas in the initial stages of development of diabetes. 2. We therefore investigated the lipid peroxide level (thiobarbituric acid-reactive substances, TBARS) and activities of antioxidant enzymes [superoxide dismutase (SOD), catalase and glutathione peroxidase] in liver and pancreas of control and streptozotocin-induced diabetic rats at various stages of development of diabetes. 3. Male Sprague—Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups consisting of six rats each. Rats in these subgroups were studied at weekly intervals (0 to 6 weeks). Plasma glucose levels, TBARS levels and activities of antioxidant enzymes were measured in liver and pancreas at various time intervals. 4. There was a significant (P < 0.05) and progressive increase in TBARS levels of liver and pancreas in the diabetic group. Total SOD and Cu—Zn-SOD activity increased (P < 0.05) with progression of diabetes while Mn-SOD activity showed no significant change in either tissue. Catalase and glutathione peroxidase activities increased significantly (P < 0.05) in liver and pancreas. 5. Immunohistochemical study of pancreatic islet revealed a decrease in the expression of insulin with progression of diabetes. However, glucagon and somatostatin showed an increase in immunoreactivity and a difference in their distribution pattern. 6. The findings of the present study suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively. In conclusion, the structural damage to these tissues or complications of diabetes mellitus may be due to oxidative stress.

BACKGROUND: Investigations of the effects of high cholesterol diet in the presence and absence of garlic on the genesis of atherosclerosis, the blood lipid profile, aortic tissue lipid peroxidation product malondialdehyde, chemiluminescence, a marker for antioxidant reserve and activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase were made in rabbits. METHODS AND RESULTS: Four groups of 10 rabbits each were studied: group 1 was given regular rabbit chow, group 2 was given rabbit chow diet supplemented with garlic powder (300 mg twice daily orally), group 3 was given 1% cholesterol diet, group 4 was given 1% cholesterol diet supplemented with garlic powder (300 mg twice daily orally). Blood concentration of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured before and after 4 and 10 weeks of experimental diets. The aorta was removed at the end of protocol (10 weeks) for assessment of atherosclerotic changes (gross and microscopic), malondialdehyde concentration, chemiluminescence, and activity of antioxidant enzymes. Total cholesterol, low density-lipoprotein cholesterol and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol increaserd in group 3 and 4; the increase was smaller in group 4 than in in group 3 although not significant. Serum high-density lipoprotein cholesterol decreased to a similar extent in groups 3 and 4. Serum triglyceride and very low-density lipoprotein cholesterol remained unchanged in group 3 but increased in group 4. These values were significantly higher than those in group 1. Garlic in rabbits with control diet decreased the levels of triglyceride and very low density lipoprotein but did not affect the levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol and the ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol. There was an increase in aortic tissue malondialdehyde, chemiluminescence, and activities of catalase and glutathione peroxidase in group 3 compared with those in group 1. Levels of aortic malondialdehyde, chemiluminescence, catalase, and glutathione peroxidase were lower in group 4 compared with group 3; however, values for malondialdehyde and chemiluminescence were lower and that of catalase and glutathione peroxidase were higher in group 4 compared with group 1. Superoxide dismutase activity was similar in all the four groups. Malondialdehyde, chemiluminescence, and activity of catalase of aortic tissue decreased while activity of glutathione peroxidase increased in group 2. Atherosclerotic changes were lower in group 4 compared with group 3. Histologic changes were practically similar in groups 3 and 4. CONCLUSIONS: Increased levels of malondialdehyde, chemiluminescence, and antioxidant enzymes associated with development of atherosclerosis suggests a role for oxygen free radicals in the pathogenesis of hypercholesterolemic atherosclerosis. The protection afforded by garlic was associated with decrease in aortic malondialdehyde and chemiluminescence inspite of no change in serum cholesterol. These findings suggest that oxygen free radicals are involved in the genesis and maintenance of hypercholesterolemic atherosclerosis and that use of garlic can be useful in preventing the development of hypercholesterolemic atherosclerosis.

Oxygen free radicals (OFRs) have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level measured as thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes viz., [superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px)]in the kidney of streptozotocin induced diabetic rats at various stages of development of diabetes. Sprague Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups each consisting of six rats. Rats in subgroups were studied at weekly intervals (0 to 6 weeks). Blood glucose levels were estimated at the time of sacrifice. TBARS levels and activity of antioxidant enzymes were measured in kidney. The levels of TBARS in the diabetic group increased initially, dropped to baseline level after 2 weeks and then progressively increased at 5th and 6th week (p < 0.05). There was an increase in catalase activity at first week after that it decreased as compared to control group. However, GSH-Px activity in the diabetic group increased after 1 week and then remained at the same level except a small drop in the 2nd week. Total SOD and CuZn-SOD activity increased significantly in diabetic kidney as compared to controls at all time intervals, while Mn-SOD activity showed no change. The present findings suggest that oxidative stress accompanies at early onset of diabetes mellitus and the susceptibility of the kidney to oxidative stress during the early stages may be an important factor in the development of diabetic nephropathy.

We investigated the effects of chronic volume overload in the absence or presence of vitamin E supplements on the cardiac function and contractility, cardiac malondialdehyde (MDA) —a lipid peroxidation product —cardiac antioxidant enzyme activity and antioxidant reserve in canine model. The dogs were divided into three groups of seven dogs each: group I, control; group II, mitral regurgitation (MR) of 4 months duration; and group III, MR of 4 months duration receiving vitamin E (40 U /kg /daily) orally. MR was created by detaching two or more chordae tendinae to raise left atrial pressure to 2.5 to three times normal. MR produced a decrease in the index of myocardial contractility with little change in myocardial function. Decrease in myocardial (left and right ventricles) contractility was associated with an increase in cardiac MDA, and a decrease in cardiac antioxidant reserve and antioxidant enzyme activity. Prevention of volume overload-induced decrease in myocardial contractility by vitamin E was associated with a decrease in cardiac MDA and an increase in cardiac antioxidant reserve and glutathione peroxidase activity towards control levels. Superoxide dismutase and catalase activity remained depressed in vitamin E-treated group. The results indicate that chronic volume overload decreases the contractility of both right and left ventricles and is associated with oxidative stress in both ventricles. These results support the hypothesis that oxygen free radicals are involved in the chronic volume overload-induced cardiac depression.

Effects of high cholesterol diet (0.5% and 1%) on the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-P X )] in the aortic tissue of rabbits were investigated in the absence or presence of probucol (0.5 gm/kg daily, orally). Five groups of ten rabbits each were studied. Group I, regular rabbit chow diet; Group II, chow + 0.5% cholesterol; Group III, chow + 0.5% cholesterol + probucol; Group IV, chow + 1% cholesterol and Group V, chow + 1% cholesterol + probucol. The aorta was removed at the end of 4 months for measurement of the antioxidant enzymes. An increase in activity of aortic antioxidant enzymes was noted in cholesterol-fed rabbits (Groups II and IV), being similar for SOD and catalase but higher for GSH-P X in Group IV as compared to Group II. Probucol was ineffective in altering this cholesterol-induced increase in enzyme activity except in Group III where it increased the activity of GSH-P X . These results suggest that aortic antioxidant enzymes are affected in hypercholesterolemia and that probucol is ineffective in altering the aortic antioxidant enzyme activity except gsh-p x activity which increased in 0.5% cholesterol-fed rabbits. The protective effects of probucol against hypercholesterolemic atherosclerosis may be partly due to an increase in the GSH-P X activity at low levels of hypercholesterolemia. At higher levels of hypercholesterolemia, the protective effects of probucol could be due to its antioxidant activity.

Medical errors are a prominent issue in health care. Numerous studies point at the high prevalence of adverse events, many of which are preventable. Although there is a range of severity in errors, they all cause harm, to the patient, to the system, or both. While errors have many causes, including human interactions and system inadequacies, the focus on individuals rather than the system has led to an unsuitable culture for improving patient safety. Important areas of focus are diagnostic procedures and clinical laboratories because their results play a major role in guiding clinical decisions in patient management. Proper disclosure of medical errors and adverse events is also a key area for improvement. Globally, system improvements are beginning to take place, however, in Canada, policies on disclosure, error reporting and protection for physicians remain non-uniform. Achieving a national standard with mandatory reporting, in addition to a non-punitive system is recommended to move forward.

Lipid peroxidation of membranes by oxygen free radicals has been implicated in various disease states. Different antioxidants and iron chelators have been used to reduce lipid peroxidation. Lazaroids have been used for the acute treatment of central nervous system disorders such as trauma and ischemia wherein lipid peroxidative processes take place. In this study we evaluated the effect of lazaroids (U-785 18F and U-74389F) on the release of acid phosphatase activity and formation of malondialdehyde (MDA) in rat liver lyosomes subjected to exogenously generated oxygen free radicals. There was a significant increase in the acid phosphatase release and MDA formation in the presence of oxygen free radicals. This was prevented by both the lazaroids. In a separate study the effect of lazaroid U-74389F was seen on the zymosan-stimulated polymorphonuclear (PMN) leukocyte-derived chemiluminescence. The PMN leukocyte chemiluminescent activity was attenuated by the lazaroid in a dose-dependent manner. These studies suggest that lazaroids may inhibit lipid peroxidation and stabilize the membrane.

The effects of platelet-activating factor (PAF) on cardiac function and con tractility and its mechanism of action are not fully understood. The authors investigated the effects of PAF in the absence or presence of a potent PAF antag onist CV-6209 on the cardiac function and contractility; lipid peroxidation prod uct malondialdehyde (MDA), an indirect measure of oxygen free radicals; serum creatine kinase (CK); blood lactate; and pH in anesthetized dogs. CV- 6209 (1 mg/kg, IV) did not produce significant changes in the various parame ters studied. PAF (1 μg/kg, IV) produced decreases in the cardiac function (cardiac index, left ventricular work index) and indices of cardiac contractility [(+) and (-) dp/dt, dp/dt at CPIP, (dp/dt)/IP, dp/dt at CPIP/IP, Vmax] and in creases in the systemic and pulmonary vascular resistance. It also produced increases in cardiac MDA, serum CK, blood lactate, and H+ and decreases in blood pH and HCO3- . CV-6209 completely prevented the PAF-induced changes in the hemodynamic and biochemical parameters. These results suggest that PAF-induced cardiac depression may be due to PAF-induced release of oxyradicals from neutrophils and that PAF antagonist may be useful in counteracting the deleterious effects of PAF on the cardiovas cular system.

Hypochlorous acid (HOCI), produced by activated polymorphonuclear (PMN) leukocytes, has been reported to depress cardiac function and contractility. Var ious mechanisms exist for activation of PMN leukocytes during hemorrhagic shock and reperfusion. In order to determine the role of HOCI in hemorrhagic shock and reinfusion, the authors studied the effects of shock and reinfusion on the cardiac function, contractility, blood lactate, blood gases, and creatine kinase (CK) and MB fraction of CK (MBCK) with and without methionine (quencher of HOCI) in anesthetized dogs. Dogs were divided into two groups: Group I, hemorrhagic shock (two hours) and reinfusion (two hours): Group II, hemorrhagic shock and reinfusion with methionine treatment. Cardiac index, mean arterial pressure, and index of cardiac contractility were similar in the two groups during shock. Postinfusion recovery of cardiac function and con tractility was better in group II. Increases in blood lactate were similar in the two groups during shock. The rate of return of blood lactate to preshock values after reinfusion was greater in group II. The increases in serum CK and MBCK of the two groups during shock were similar but not significant. Following rein fusion the levels of these enzymes increased significantly, but the increases in group II were less.These results suggest that HOCI produced by activated PMN leukocytes may play a role in cardiac damage during hemorrhagic shock and reinfusion. Methio nine may have beneficial effects in the hemodynamic and metabolic recovery and may reduce cellular damage during hemorrhage shock and reinfusion.

The dramatic decline in the risk of stroke is most likely secondary to a better control of risk factors, especially hypertension. An increase in low-density lipoprotein (LDL) cholesterol or a decrease in high-density lipoprotein (HDL) cholesterol may be additional risk factors for cerebrovascular diseases. In this study, we prospectively evaluated patients with ischemic stroke (except for cardioembolic) and age-matched controls for serum cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, very low-density lipoprotein cholesterol, and apoprotein A and B. Blood levels were determined at least 8 weeks after the acute stroke or transient ischemic attack. Between September 1989 and September 1990,59 patients and 60 controls were investigated. There were no differences among total cholesterol, triglycerides, LDL cholesterol, and apoproteins in the two groups. HDL cholesterol, however, was significantly higher in patients with stroke. In stroke patients, total cholesterol (p < 0.05), LDL cholesterol (p < 0.05), and apolipoprotein B (p < 0.05) were significantly higher in female patients compared to male patients. This study confirms that low HDL cholesterol may be a risk factor for stroke. Additionally, ally, we show that lipid abnormalities may appear to be more significant in women.

Cardiac dysfunction after cardiopulmonary bypass (CPB) has been reported by various investigators. Oxygen free radicals have been shown to depress cardiac function and contractility. To evaluate the possible role of oxygen free radicals (OFR) in post-pump cardiac dysfunction, measurements of cardiac function, OFR producing activity of polymorphonuclear (PMN) leukocytes (PMN chemiluminescence) and malondialdehyde (MDA), a lipid peroxidation product, in blood were made at induction of anesthesia (T1), before cross clamping of the aorta (T2), after closure of the chest (T3), and 24 hours postoperatively (T4) in 21 patients undergoing aortocoronary bypass surgery. The total OFR-derived chemiluminescence at T1, T2, T3, and T4 was 1590 +/- 156, 3169 +/- 338, 1972 +/- 214, and 2614 +/- 366 mv.min.10(6) PMN-1, respectively. Superoxide dismutase (SOD)-inhibitable chemiluminescence at T1, T2, T3, and T4 was 1214 +/- 129, 2674 +/- 328, 1752 +/- 215, and 2139 +/- 292 mv.min.10(6) PMN-1, respectively. Superoxide anion at T1, T2, T3, and T4 was 0.99 +/- 0.14, 1.30 +/- 0.17, 1.07 +/- 0.14, and 1.19 +/- 0.12 nmol.10(6) PMN-1.30 min-1, respectively. Blood MDA at T1, T2, T3, and T4 was 0.17 +/- 0.02, 0.25 +/- 0.03, 0.20 +/- 0.03, and 0.23 +/- 0.02 nmol/ml, respectively. OFR-derived and SOD inhibitable chemiluminescence, superoxide anion, and blood MDA increased significantly during CPB and postoperatively. There were decreases in the blood pressure and stroke volume, and increases in the central venous pressure, capillary wedge pressure, and heart rate during CPB and postoperatively. Cardiac output remained unchanged during this procedure. There was leukopenia during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac troponin (cTn) is a key biomarker for the assessment of myocardial injury, but overutilization of this test has increased workload and costs. We developed and implemented an algorithm to eliminate excessive utilization. Significant reduction was observed after the implementation of the algorithm in total cTnI requests (29.9%; P = .007), requests from outpatient clinics (70.7%; P = .003), and other wards (42.8%; P = .003). Stat requests, the number of third requests, and more than 3 requests per patient were reduced significantly by 42.8% (P = .004), 35.8% (P = .003), and 49.4% (P = .008), respectively. The test and labor costs each were reduced by 29.9% (P = .007 for each). There was no significant change in cTnI orders from emergency and critical care departments. The cTnI testing algorithm reduced unnecessary orders for cTnI tests with no reduction in meeting patients'critical needs. Reduction in unnecessary and inappropriate requests reduces labor and test costs.

In any healthcare process, some error is inevitable.1 As indicated in the US Institute of Medicine's report To Err is Human,2 the challenge is to cut the rate of error to a minimum. In Canada, various strategies are being applied to this end and the Federal Government has established a Patient Safety Institute. The UK likewise has a National Patient Safety Agency. However, in the many countries3 where efforts are being made to reduce adverse events and errors, a neglected issue is honest disclosure to the patient or family. In this paper we examine the central issues, discuss the dilemmas concerning 'apology' and suggest how we might work towards a systematic and effective process.

The issue of medical errors has received substantial attention in recent years. The Institute of Medicine (IOM) report released in 1999 has several implications for health care systems in all disciplines of medicine. Notwithstanding the plethora of available information on the subject, little, by way of substantive action, is done toward medical error reduction. A principal reason for this may be the stigma associated with medical errors. An educational program with a practical, informed, and longitudinal approach offers realistic solutions toward this end. Effective reporting systems need to be developed as a medium of learning from the errors and modifying behaviors appropriately. The presence of a strong leadership supported by organizational commitment is essential in driving these changes. A national, provincial or territorial quality care council dedicated solely for the purpose of enhancing patient safety and medical error reduction may be formed to oversee these efforts. The bioethical and emotional components associated with medical errors also deserve attention and focus.

Oxygen free radicals (OFRs) are known to produce a decrease in cardiac function and contractility. The decrease in cardiac contractility and function in chronic volume overload heart failure might be due to an increased level of OFRs and/or decrease in the antioxidant status. We, therefore, studied the effects of chronic volume overload in the absence and presence of vitamin E (antioxidant) on cardiac function and contractility, cardiac malondialdehyde (MDA), a lipid peroxidation product and a fingerprint for levels of OFRs, cardiac antioxidant enzyme activity and antioxidant reserve in canine model. Volume overload heart failure was produced by creating mitral regurgitation (MR). Volume overload produced a decrease in the index of myocardial contractility manifested by an increase in left ventricular end diastolic pressure LVEDP without a significant change in cardiac index (CI). There was an increase in pulmonary vascular resistance (PVR) and total systemic vascular resistance (TSVR).The decrease in cardiac contractility was associated with an increase in cardiac MDA and a decrease in cardiac antioxidant reserve and antioxidant enzyme activity. Prevention of volume overload induced decrease in cardiac contractility by vitamin E was associated with a decrease in cardiac MDA and an increase in cardiac antioxidant reserve and glutathione peroxidase activity towards control levels. Superoxide dismutase and catalase activity remained depressed in vitamin E-treated animals. These results suggest that the oxygen free radicals are involved in the chronic volume overload heart failure.

We investigated the effects of hemorrhagic shock and reinfusion on the cardiac function and contractility, plasma CK and CK-MB activity and lactate concentration, oxyradical-producing activity of polymorphonuclear leukocytes (PMNL-CL), cardiac chemiluminescence (LV-CL), antioxidant enzyme activity [Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX)] and malondialdehyde (MDA) concentration in anesthetized dogs to determine the role of oxyradicals in cardiac depression and cellular injury in hemorrhagic shock and reinfusion. The dogs were assigned into three groups: I (sham), 4 h duration; II (S + R), 2 h of shock followed by reinfusion for 2 h; III (SOD + S + R), as II but pretreated with PEG-SOD. Hemorrhagic shock was produced by withdrawal of blood to maintain the mean arterial pressure at 50 ± 5 mm Hg. Cardiac function and contractility were depressed during hemorrhagic shock. Plasma CK, CK-MB and lactate increased during shock. Following reinfusion after 2 h of shock hemodynamic parameters and plasma lactate tended to return towards control values. Plasma CK and CK-MB, PMNL-CL and cardiac MDA, total-, Mn- and CuZn-SOD activity increased while LV-CL decreased. In spite of the increase in the antioxidant reserve, there was oxidative damage. Pretreatment with SOD attenuated the deleterious effects of shock and reinfusion on the cardiovascular function, plasma CK, and CK-MB, PMNL-CL, cardiac MDA, SOD, and LV-CL. Protection was incomplete for cardiovascular function and plasma CK and CK-MB. These results suggest that oxyradicals may partly be involved in the deterioration of cardiovascular function and cellular injury during hemorrhagic shock and reinfusion. (Mol Cell Biochem 176: 291-301, 1997)

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level [thiobarbituric acid-reactive substances (TBARS)] and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in aorta, heart and blood of control and streptozotocin-induced diabetic rats at various stages of development of diabetes (0 to 6 weeks). 2. There was no change in the TBARS levels of aorta, heart and blood in the control group. A significant (P < 0.05) increase in TBARS levels of aorta, heart and blood was observed in the diabetic group. 3. There were no significant changes in the activities of superoxide dismutase, catalase and glutathione peroxidase in the aorta, heart and blood of control rats at all time intervals. In the diabetic group, there was a significant (P < 0.05) increase in the activity of superoxide dismutase and glutathione peroxidase in aorta from the fourth week onwards while the activity of catalase increased at all time intervals. In the heart of diabetic rats, the activity of total superoxide dismutase and Cu—Zn-superoxide dismutase increased significantly (P < 0.05) from the second week onwards while activity of Mn-superoxide dismutase decreased at the fourth week and increased at the sixth week. The activity of catalase and glutathione peroxidase increased significantly (P < 0.05) at all time intervals. In the blood, the activity of superoxide dismutase and glutathione peroxidase increased from the third week while catalase activity increased from the fourth week. 4. The present findings suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively.

Glutamate is one of the principal neurotoxins in the pathogenesis of ischemic neuronal injury. Elevated glutamate levels in ischemia have been well documented in many animal stroke models. Recent work in humans also shows a similar trend. We have used our acute focal ischemic model of the human brain to study the response of glutamate levels by in vivo microdialysis during ischemia using two different perfusates. The addition of 30 mM of glucose to the perfusate attenuated the percentages of dialysate glutamate levels from 4.27 +/- 1.7 to 1.34 +/- 0.47 (P0.001) during partial ischemia and from 21.42 +/- 6.05 to 7.25 +/- 1.43 (P0.05) with total ischemia. The pre-ischemic values of glutamate were similar with the two perfusates. These results indicate that the ischemia-induced rise in glutamate is attenuated by exogenous glucose delivery in the human stroke model.

The release of neurotransmitters principally glutamate during cerebral ischemia has been extensively studied. It is well recognized that ischemia induced release of glutamate plays a key role in “excitotoxic” neuronal death. The role of monoaminergic neurotransmitters is however unclear. The purpose of this study was to evaluate the extracellular norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA) and serotonin (5-HT) under varied degrees of ischemia in the acute focal ischemic model of the human brain by in-vivo microdialysis. The ischemic response of these amines was correlated with the glutamate levels. Our study concludes that these amines and metabolites can be detected in the human “stroke” model. No marked fluctuations were noted in the levels of norepinephrine and DOPAC. However, significant changes to partial and total ischemia were noted in the extracellular levels of 5-HIAA and 5-HT. These compounds showed a dramatic increase with the onset of ischemia with higher detectable levels in the partial ischemic state in comparison to the total ischemic dialysate levels. The exact role played by the differential increase in the levels of 5-HT to the other catecholamines in the pathogenesis of ischemic neuronal damage remains unclear and warrants further study.

We hypothesized that oxygen free radicals (OFRs) may be involved in pathogenesis of diabetic complications. We therefore investigated the levels of lipid peroxidation by measuring thiobarbituric acid reactive substances (TBARS) and activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] in tissues and blood of streptozotocin (STZ)-induced diabetic rats. The animals were divided into two groups: control and diabetic. After 10 weeks (wks) of diabetes the animals were sacrificed and liver, heart, pancreas, kidney and blood were collected for measurement of various biochemical parameters. Diabetes was associated with a significant increase in TBARS in pancreas, heart and blood. The activity of CAT increased in liver, heart and blood but decreased in kidney. GSH-Px activity increased in pancreas and kidney while SOD activity increased in liver, heart and pancreas. Our findings suggest that oxidative stress occurs in diabetic state and that oxidative damage to tissues may be a contributory factor in complications associated with diabetes.