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J Lantos

Publications and source records attributed to J Lantos.

At least 37 records · Page 2Linked to original sources
PubMed1997

Community equipoise and the architecture of clinical research.

We have argued for a revision of Freedman's concept of clinical equipoise to a broader sense of community that includes physicians and patients. Community equipoise is an essential condition for physicians and patients to answer these questions: Should there be a trial? If so, what kind? We have argued that community equipoise exists because of changes in the knowledge gap between physicians and patients and in the moral justification of medical decision-making. Finally, we have briefly examined the social aspect of medical knowledge to argue that it necessarily includes patients and their values. In effect, community equipoise is not so much an effort to change things, as to explain the way they are. We suggest that patients can participate at a number of points in the process of drug study design and approval: (1) study design with attention to criteria for eligibility, endpoints, and choice of methodology, (2) research review and approval with attention to enhancing community participation in IRB activities, and (3) interim evaluation of ongoing studies with attention to including patient and clinician values in the decisionmaking. Clinical trials are a tool. Like a gun or a bomb or the very drugs they test, they are powerful tools to achieve their ends. The issue is how to properly use such tools as randomization, placebo controls, endpoints, and eligibility. To the extent that community equipoise exists prior to a trial, it means that clinical researchers and patients have collectively addressed the risk and benefit trade-offs that govern the decision to start and to end a clinical trial. In this way, trials can be both valid and valued.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Physicians' experience with allegations of medical malpractice in the neonatal intensive care unit.

OBJECTIVE: To assess the personal experience of all practitioners of neonatal intensive care unit (NICU) medicine in the United States with the medical malpractice system; in particular, to assess the circumstances of malpractice allegations in which they themselves had personal experience, and to extrapolate from their individual experiences to the field of neonatology in general. DESIGN: Written survey of all MDs practicing NICU medicine in the US. PARTICIPANTS: Two thousand four hundred ninety-eight NICU physicians as determined from three sources: a) the American Board of Medical Specialists; b) the American Academy of Pediatrics Section of Neonatal/Perinatal Medicine; and c) a listing of neonatologists provided by Ross Laboratories. MAIN OUTCOME MEASURES: Responses to survey questions. RESULTS: We received 1813 responses, representing approximately 75% of all physicians practicing NICU medicine in the US. Overall, 43% of respondents had experienced at least one claim of malpractice against them. The probability of a malpractice allegation increased with years in practice, from approximately 20% for NICU physicians in practice </=5 years (65/337), to approximately 60% for NICU physicians in practice >15 years (276/469). Men and women were equally likely to have been sued, accounting for years in practice. Physicians practicing in community NICUs were more likely to be sued than those in university settings. On a scale of 1 to 4 (4 being most reasonable) the median assessment of the reasonableness of malpractice allegations was 1, mean 1.2. On a scale of 1 to 4 (4 being the highest) the median assessment of effectiveness of the current system in identifying true malpractice was 1, mean 1.4. The respondents believed that approximately 80% of malpractice allegations were inappropriate; conversely, they believed that approximately 80% of true medical malpractice escaped detection. On a scale of 1 to 4 (4 being the highest), the median assessment of the detrimental effect of the present malpractice system on health care was 4, mean 3.4. CONCLUSIONS: Most NICU physicians will be sued if they practice long enough. In this context, efforts to use malpractice claims to seek out evildoers (such as underlie the National Practitioners Data Bank) appear ill-conceived. Similarly, exhortations for physicians to become either more educated or more sensitive are unlikely to reduce malpractice claims. Our data suggest that malpractice in the NICU appears to function more like a lottery than like a mechanism for either quality assurance or just retribution.

Community Health Services↗
PubMed1997

The values of detection of free radical mediated reactions in patients.

The peroxidative processes and individual antioxidant protection were measured in patients with different cardiovascular diseases. We concluded that monitoring of this system we were able to detect not only the actual changes of lipid peroxidation and antioxidant defence mechanisms, but additionally the therapeutic efficacy of the treatment.

Adrenergic beta-Antagonists↗
PubMed1997

Inflammatory mediators and surgical trauma regarding laparoscopic access: free radical mediated reactions.

In this prospective study the free radical mediated reactions, the changes of endogenous antioxidant defense mechanism and activation of leukocytes were measured from the blood of patients undergoing elective cholecystectomy because of symptomatic cholecystolithiasis. The patients were randomised into two groups. Group one contained 21 patients treated by open cholecystectomy(OC). Group two consisted of 21 patients treated by laparoscopic cholecystectomy (LC). Both groups had similar patient characteristics. Patients with acute cholecystitis, pancreatitis, choledocholithiasis or other disease were excluded. Values from patients in both groups were compared. The measured biochemical parameters are the following: malondialdehyde (MDA) as a marker of the free radical induced lipid peroxidations, reduced and oxidised glutathione (GSH-GSSG), as endogenous scavengers as well as markers of oxidative stress and myeloperoxidase activity (MPO) of leukocytes. The results showed significantly lower values of postoperatively measured MDA, GSH-GSSG, and MPO activity of leukocytes in patients with laparoscopic cholecystectomy, indicating a lesser stress response and tissue trauma in this group of patients. The results correspond to the favourable results of most other trials evaluating clinical aspect of LC.

Antioxidants↗
PubMed1997

Inflammatory mediators and surgical trauma regarding laparoscopic access: acute phase response.

Numerous studies have tried to compare different aspects of patient response to laparoscopic cholecystectomy (LC) versus open cholecystectomy (OC). Our study focused on the acute phase response in order to clarify the better patient recovery following LC. Sixteen patients scheduled for elective cholecystectomy were equally allocated into groups of OC and LC. Blood samples were collected before and for four days after the procedures. Levels of interleukin 6 (IL-6) and C-reactive protein (CRP) were determined by ELISA technique. IL-6 value increased ten fold on the first postoperative day (52.8 pg/ml) in the OC group with a return to baseline value by the fourth postoperative day. In contrast a moderate increase postoperatively (12.1 pg/ml) with a fast normalisation of IL-6 value by the second postoperative day was noted in LC group. A similar pattern was observed in the CRP level. CRP peaked to 84.1 mg/l by the second follow-up day after OC, while only an insignificant rise to 52.7 mg/l was registered in the LC group with again a faster return to baseline value. The marked contrast between the two groups with regard to IL-6 and CRP changes clearly underlines a diminished acute phase response following LC, which verifies LC as probably a less traumatic procedure.

Acute-Phase Reaction↗
PubMed1997

The effects of bisaramil and antiarrhythmics on free radical generation of isolated neutrophil granulocytes.

The aim of this study was to investigate the effect of bisaramil--an antiarrhythmic drug under clinical trials--on free radical generation of isolated polymorph neutrophil granulocytes (PMN) and to compare its activity with well-known antiarrhythmics. PMNs were isolated from healthy beagle dogs, and superoxide radical generation was induced by phorbol-myristate-acetate. Free radical generation capacity of stimulated PMNs were measured. Bisaramil exerted a concentration dependent inhibitory effect on stimulated free radical generation. At the investigated concentration range of the antiarrhythmics only propafenon, mexiletine and diltiazem showed similar activity as bisaramil, but clear concentration dependency could not be seen in any of the cases. According to the results of this study inhibition of stimulated free radical production by isolated PMNs can not be closely related merely to either membrane stabilizing or Ca-antagonistic activity of drugs. In vitro inhibitory action of bisaramil on free radical generation indicates a possible cardioprotective effect existing independently of its antiarrhythmic one. This observation may be important in outlining the range of clinical indications of bisaramil as it may also be useful in the treatment of reperfusion injury.

Animals↗
PubMed1997

Monitoring of plasma total antioxidant status in different diseases.

The pathological increase of oxygen free radical generation has already been recognised in more than one hundred diseases. To gain information about the consequences of oxidative stress the investigation of plasma antioxidants seems to be plausible. In our study we used a new kit (RANDOX, England) for measurement of total antioxidant status (TAS) to determine whether it has diagnostic value in comparison with our earlier results of measuring other parameters of oxidative stress in the following diseases: i./In the group of patients with ischemic heart disease (n = 19) the TAS elevated from 1.08 +/- 0.13 to 1.16 +/- 0.11 mM after 2 weeks of cardioprotective drug administration showing the beneficial effect of drug treatment. ii./In the group of patients with essential hypertension (n = 47) its values were below the normal range (1.11 +/- 0.15 mM) at the time of the first investigation and increased gradually following antihypertensive treatment. iii./The changes of TAS values of patients who underwent open (n = 21) or laparoscopic (n = 21) cholecystectomy indicated the less surgical trauma following laparoscopic procedures. Our results suggest that determination of TAS is a valuable and reproducible method to detect the actual antioxidant status in patients.

Antihypertensive Agents↗
PubMed1997

Cardioprotection during heart ischemia-reperfusion.

Oxygen reactive species play a significant role in reperfusion tissue damages. In this study we aimed to investigate the mechanisms of injury regarding changes of neutrophil function. In our experiments the left descending coronary artery (LAD) was ligated in Beagle dogs for 1 hour followed by one hour reperfusion. Animals were divided into two groups: Group I. dogs (n = 10) served as control: Group II. the animals (n = 10) were treated by cardioprotective drug Bisaramil. Peripheral blood samples were taken for neutrophil isolation before operation and subsequent reperfusion (5 min, 1 hour). The stimulated superoxide radical generating capacity of polymorphonuclear leukocytes (PMN) was measured. The lipid peroxidation (MDA), amount of reduced glutathione (GSH) and activity of superoxide dismutase (SOD) were measured in non-ischemic and ischemic parts of left ventricle. There was no significant changes either in control or in treated animals in respect to changes of neutrophil radical production after one hour LAD ligature, however there was a significant discrepancy (p < 0.001) between control and treated animals following a 1 hour reperfusion. The values of MDA in the ischemic-area increased characteristically in the Group I. parallel with decrease of scavenger GSH and SOD. In contrast in Group II., where depleted PMN radical production was observed endogenous scavengers were preserved on a higher level. In summary we can conclude that diminished superoxide radical production of circulating neutrophils during reperfusion has beneficial effects on tissue injury caused especially by free radicals.

Animals↗
PubMed1997

Inflammatory mediators and surgical trauma regarding laparoscopic access: neutrophil function.

Polymorphonuclear leukocytes (PMN) are well recognised as being the principal cells in the inflammatory response reaction. The current investigation was designed to evaluate the stimulated state of neutrophils in patients undergoing open (OC) and laparoscopic cholecystectomy (LC). The superoxide radical generation of isolated PMN and its lag time, and PMN elastase were measured in peripheral venous blood samples collected from 42 patients. The observation period started on the day of hospital admission and ended on the 5 th day. Our results showed that although there were no characteristic changes in the superoxide radical production of PMN in the LC group, we found a marked depletion already by the first day in OC group which persisted during the whole observation period. There was an elevation of PMN elastase on the first postoperative day in both groups, but in the laparoscopically operated patients it decreased considerably on the 3rd postoperative day while in the OC group it maintained a high level. The same discrepancy was present between the two groups on the 5th day. Decreased free radical production of isolated PMN may reflect depleted neutrophil functional state, while changes of PMN elastase indicates increased harmful potential. These data suggest the differences in neutrophil activation between the two groups can be partially responsible for the better outcome in patients operated by laparoscopic cholecystectomy.

Acute-Phase Reaction↗
PubMed1996

Effects of bisaramil on coronary-occlusion-reperfusion injury and free-radical-induced reactions.

The aim of this study was to determine whether bisaramil-an antiarrhythmic compound under clinical investigation-influences the reperfusion-induced arrhythmias and biochemical parameters characterizing occlusion-reperfusion-induced free-radical reactions. The left descending coronary artery (LAD) was occluded for 60 min in anaesthetized dogs followed by one hour of reperfusion. Blood samples were taken at different times of the occlusion and reperfusion for the determination of plasma concentration of malondialdehyde (MDA), reduced (GSH) and oxidized glutathione (GSSG); furthermore of the activity of catalase and superoxide dismutase (SOD). Free-radical generating capacity of polymorph neutrophil granulocytes (PMN) was also measured. At the end of the experiments heart tissue samples were excised from the injured areas and from the intact part of the left ventricular muscle. In tissues samples the concentrations of MDA and GSH and the activity of SOD were determined. Bisaramil was given as an i.v. bolus injection at a dose of 2 mg kg-1 several minutes prior to the end of LAD-occlusion; then the administration was repeated in the 30th minute of reperfusion. In the control group (10 dogs) ventricular fibrillation (VF) occurred in seven cases which resulted in death in three. In the bisaramil-treated group, however. VF was seen in three cases and no death was recorded. Bisaramil inhibited the elevation of the plasma concentration of MDA and GSSG during the reperfusion and abolished the decrease in the plasma concentration of GSH during the occlusion and reperfusion. The activity of SOD and catalase in plasma was much better preserved in the bisaramil-treated group then in the controls. Bisaramil significantly inhibited the increase of the superoxide-radical generating capacity of PMNs during the reperfusion. The data obtained from myocardial tissue samples supported the cardioprotective effect of bisaramil. The biochemical investigation of ischemic-reperfused myocardium showed that bisaramil promoted preservation of SOD-activity and of tissue glutathione. Results of this study clearly showed that bisaramil has a significant effect on ischemiareperfusion injury. Besides its inhibitory effects on ischaemia-reperfusion induced arrhythmias it has a special benefit in influencing free-radical mediated damage leading to better preservation of membranes and to limitations of irreversible cell injuries.

Animals↗
PubMed1996

The relationship between physician behaviors and blood gas values in the first hours of life--implications for "standards" of medical care for infants with respiratory distress.

It is standard practice for physicians to use blood gas (BG) evaluations when evaluating neonates with respiratory distress. In this study we addressed two questions: (1) What is the distribution of BG values in a population of infants receiving BG evaluation in the first 4 hours of life; and (2) How does the behavior of physicians correlate with BG values in these infants? We discuss the implications of our findings for claims about "standards" of medical care for newborn infants with respiratory distress. We reviewed medical records for 226 infants with birthweight > 2000 grams who were not intubated at the time of first BG determination. For 199 arterial samples, mean values were pH = 7.31 +/- 0.9 (SD); PaCO2 = 38.5 +/- 11.9 torr; PaO2 = 104 +/- 52 torr; and base excess (BE) = -6.5 +/- 3.8 mEq/L. These values did not differ significantly from previously published data for normal term infants without respiratory distress. However, the a/A ratio (0.45 +/- 0.19) for patients in our distressed population was significantly lower than reported for normal infants (0.65 +/- 0.10). For 186 infants admitted directly to our Newborn Intensive Care Unit, the elapsed time from birth to BG 1 was 1.07 +/- 0.64 hours. This value did not vary significantly as a function of severity of illness, assessed by pH, PaCO2, PaO2, a/A ratio, or BE. No blood gas parameter was simultaneously sensitive and specific for predicting subsequent mechanical ventilation. PaCo2 1 > 80 torr was associated with subsequent mechanical ventilation in 4 of 4 infants; however, the positive predictive value of PaCO2 1 was < 50% for levels below 80 torr, and only 4 of 22 infants eventually intubated were identified by a value of PaCO2 1 > 80 torr. The power of "abnormal" values of PaO2, a/A ratio, pH, or BE to predict subsequent intubation was even lower than PaCO2. Jurors in medical malpractice cases are instructed to define negligence as a deviation from the "skill and care ordinarily used in similar cases," and to determine the existence or absence of negligence guided by the testimony of "expert" witnesses. Recognizing that anecdotal recall of experience, even by "experts," may be inaccurate and is often systematically biased (the "Monday morning quarterback" phenomenon), we propose that the testimony of expert witnesses ought to conform, whenever possible, to a data-based description of medical care that actually is "ordinary used in similar circumstances". Our current observations suggest that (1) expert opinions of the "standard" to evaluate neonatal respiratory distress with a BG sample should reflect that the time scale is 1 to 2 hours, not 10 to 20 minutes; and (2) expert opinions that "abnormal" BG values either "require" or "preclude" intubation for most newborn infants with respiratory distress find little support in data. Clinical observation, not BG values, appears to be the most powerful "standard" by which physicians determine whether to initiate mechanical ventilation for newborn infants with respiratory distress.

Blood Gas Analysis↗
PubMed1996

Reassessing medical students' willingness to treat HIV-infected patients.

BACKGROUND: Past research has demonstrated that some physicians do not feel obligated to care for patients infected with the human immunodeficiency virus (HIV). This study sought to characterize the attitudes that affect medical students' willingness to treat HIV-infected patients and to determine which attitudes are most amenable to intervention. METHOD: All 414 matriculating medical students at three Chicago schools were surveyed in 1994. After reliability-testing the attitudinal scales, the authors created a predictive model by using multiple regression analysis. RESULTS: A total of 297 (72%) of the matriculating students responded. Ninety-two percent of the students agreed that patients with HIV would be welcome in their medical practices. As in past studies, a strong sense of professional obligation was associated with willingness to treat, and fear of infection and homophobia were associated with decreased willingness to treat. The authors' measure of concern about social stigma was also associated with decreased willingness. Together, these factors accounted for 53% of the variance in the Willingness to Treat scale. CONCLUSION: In addition to confirming the predictors found in previous studies, this study demonstrated that perceived social stigma is a measurable predictor of decreased willingness to treat (with the understanding that willingness to treat is influenced by both personal and social factors). A comprehensive approach, not only in curriculum design but also in admission and policy, might better prepare students to treat HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Birth weight-specific mortality for extremely low birth weight infants vanishes by four days of life: epidemiology and ethics in the neonatal intensive care unit.

BACKGROUND: The persistent differences between those who question the appropriateness of aggressive resuscitative measures for many extremely low birth weight (ELBW) infants (birth weight < 1001 g) and those who generally initiate such treatment has been a source of ongoing tension for physicians, parents, judges, and policymakers. We believe that much of this tension may be a result of the way the issue is framed. We began this study with the intuition that although many ELBW infants die, most succumb quickly. Were this true, discussions that considered only survival rates might miss the point. A more relevant statistic might be the degree to which interventions prolong dying, extend suffering, or use resources for infants who will eventually die. METHODS: We determined the survival and nonsurvival for 429 ELBW infants admitted to our neonatal intensive care unit (NICU) for 3 years. We noted particularly the relationship between birth weight, illness severity (fraction of inspired oxygen [Fio2] requirement for infants requiring mechanical ventilation), and the time course of mortality for nonsurvivors. We next calculated a resource utilization index (NICU bed days occupied by survivors and nonsurvivors) for each patient and for the population as a whole. Finally, we determined how NICU resources were distributed among infants who eventually died and those who survived. RESULTS: Of the 429 ELBW infants alive on day of life (DOL) 1,202 (47%) survived to be discharged. on DOL 1, both birth weight and illness severity independently predicted likelihood of survival. Approximately 80% of ELBW deaths occurred in the first 3 days of life-- consequently, once an infant had survived to DOL 4, the likelihood of survival was dramatically enhanced (81% for the 249 patients alive on DOL 4). In addition, although survival for DOL 4 infants continued to depend on illness severity, survival no longer depended on birth weight. These observations on DOL 4 were confirmed in the subpopulation of 212 infants whose birth weight was < 750 g. Overall, although 53% of ELBW babies admitted died, only approximately 13% of all NICU bed-days (a proxy for resource allocation) were devoted to infants who did not survive. This figure did not vary as a function of birth weight. CONCLUSION: Generally, when we talk of survival rates to parents, ethics committees, or policy makers, we base our predictions largely on birth weight. The data presented here suggest that predictions should be corrected by including DOL and that, when this is done, the prognostic value of birth weight rapidly diminishes. In addition, birth weight-specific mortality and day of death for nonsurvivors correlated inversely; that is more of the smaller infants died, but the doomed ones died more quickly. Consequently, medical resources allocated to nonsurvivors remained low, and independent of birth weight. This formulation lends weight both to the reasonableness of physicians in offering NICU care to ELBW infants, with unlikely prospects for survival, and of parents and surrogate decision-makers in requesting/ assenting to it.

Bed Occupancy↗
PubMed1994

Ethics, randomization, and technology assessment.

Randomized controlled trials raise a number of ethical issues. Physicians who participate in such trials must be in a state of "equipoise," or genuine uncertainty about the relative merits of the two arms of the trial. Otherwise, they would be ethically compelled to recommend the treatment they preferred. However, an agreement to participate in a masked trial is an agreement to deny oneself access to the knowledge that might allow one to judge which therapy is better. Physicians may dodge this dilemma in a number of ways. First, they may refuse to participate in randomized control trials. However, this does not allow assumptions about treatment to be tested. Second, they may judge participation ethically acceptable if other clinicians believe that an alternative treatment is better. By this formulation, individuals do not need to be in a state of equipoise, as long as the expert medical community is. Finally, they may use alternative methodologies, such as retrospective studies; crossover studies; or nonmasked, nonrandomized selection of alternative treatments with careful risk stratification and data collection. All of these solutions may be valid ways of dealing with the ethical dilemmas associated with randomized controlled trials.

Ethics, Medical↗
PubMed1994

Alterations in malondialdehyde concentration of jugular vein blood following transient brain ischemia. The effect of lactic acidosis.

Ischemia was induced for 10 min with a subsequent 60-min reperfusion and the changes of the malondialdehyde (MDA) concentration in the blood samples from the jugular vein were investigated in normo- and hyperglycemic dogs. Selective brain ischemia was evoked by the increase in cerebrospinal fluid (CSF) pressure. The experiments were carried out in 4 experimental groups. In sham operated animals (Group I) the blood MDA concentration did not change. The venous blood MDA content significantly elevated for 10 min after the start of reperfusion in normoglycemic animals (Group II). To study the effect of acidosis during ischemia and reperfusion on brain lipid peroxidation (LP) processes 1 and 2 g/kg glucose infusion was used in Groups III and IV. As an effect of ischemic lactic acidosis due to hyperglycemia the elevation of MDA concentration in the jugular vein blood was higher and it lasted longer than in the cases of normoglycemia. This finding supports the hypothesis that free radical reactions and LP processes play an important role in the enhanced brain damage caused by tissue acidosis.

Acidosis, Lactic↗
PubMed1994

Ethical issues. How can we distinguish clinical research from innovative therapy?

The difference between research and innovative therapy is based on the goals rather than the risks or newness of the therapy. The threat to patients from research is not that an untested treatment may be hazardous. Instead, the danger is that the loyalty of their physician may be compromised by the goals of research. In the traditional conception of research, it is assumed that we know what constitutes standard therapy and how effective it is. The goal of research is to compare the effectiveness of an innovation with the standard therapy. However, when rapid progress is being made, it becomes difficult to measure improvements due to introduction of new therapies. It is difficult to determine which of many successful therapies is "best." As a result, rapid progress makes all therapies, including both new ones and old ones, nonvalidated therapies. In such situations, scientific norms about the degree of certainty that we must have in order to judge a therapy as being efficacious are based on the values of the individuals involved; rather than on any value-free statistical or scientific calculations. There are identifiable communities (ethnic groups) that are specifically effected by certain genetic diseases, as well as communities consisting of patients who have certain nongenetic diseases. When these groups (patient advocates) and communities are politically organized, they should be consulted and allowed to participate in the process of devising strategies to evaluate new therapies.

Clinical Trials as Topic↗