Navigating the chasm between religious and secular perspectives in modern bioethics.

In the past 3 years, three landmark laws relating to bioethics have been passed in the Israeli parliament. These are the Terminally Ill Patient Law (in 2005) and the Organ Donation Law and the Brain Death/Respiratory Law (in 2008). To reach consensus on these difficult issues in a multicultural society such as Israel was not an easy undertaking. Using learning from previous failed attempts, compromise, dialogue and work done in the absence of hysteria and publicity were crucial to the process. In all three laws, compromises were obtained between the secular and religious factions, from which an acceptable law was developed. The Israeli experience is a model of a country working to synthesise an ancient tradition with the complexities of modern life and could serve as an example for other countries struggling with similar issues.

Theological reflections on donation after circulatory death: the wisdom of Paul Ramsey and Moshe Feinstein.

Due to the worldwide shortage of organs for transplantation, there has been an increased use of organs obtained after circulatory death alone. A protocol for this procedure has recently been approved by a major transplant consortium. This development raises serious moral and ethical concerns. Two renowned theologians of the previous generation, Paul Ramsey and Moshe Feinstein, wrote extensively on the ethical issues relating to transplantation, and their work has much relevance to current moral dilemmas. Their writings relating to definition of death, organ transplantation and the care of the terminally ill are briefly presented, and their potential application to the moral problem of organ donation after circulatory death is discussed.

The Holocaust and medical ethics: the voices of the victims.

Fifty-nine years ago, Dr Leo Alexander published his now famous report on medicine under the Nazis. In his report he describes the two major crimes of German physicians. The participation of physicians in euthanasia and genocide and the horrible experiments performed on concentration camp prisoners in the name of science. In response to this gross violation of human rights by physicians, the Nuremberg military tribunal, which investigated and prosecuted the perpetrators of the Nazi war crimes, established ten principles of ethical conduct in medical research in 1949. Foremost among them was the need for voluntary consent of the human subject and that the experiment be conducted to avoid all unnecessary physical and mental suffering. Notwithstanding all these important efforts and impressive achievements in understanding the ethical failings of Nazi physicians, the bioethical community has almost completely ignored the moral challenges facing the victims of the atrocities. These dilemmas and their responses have continued relevance for modern medicine.

Notes on the new Israeli organ donation law-2008.

Israel, like most countries, has a dearth of organ donors with many patients on the transplant waiting list. In March 2008, the Organ Transplant law was passed in the Israeli Parliament. The law states that a person may not give or receive financial rewards for a living or cadaveric organ donation. However, a donor may receive compensation for financial losses accrued as a direct result of organ donation. It is illegal to broker an illegal transaction between potential donors and recipients. An Israeli organization can only support transplants outside of Israel if they are performed in accordance with the local law and do not involve the sale of organs. Underlying this law is the principle that the sale of organs is unethical and the belief that organ donation should be based on altruism. Almost immediately, the law was subject to criticism particularly relating to the fact that it would not help to increase the number of kidneys, because of the lack of significant compensation for donors. It remains to be seen what effect the new law will have on living organ donation in Israel.

Transition from CK-MB to troponin did not improve the 1 year mortality of non-ST elevation acute coronary syndromes.

OBJECTIVE: To examine the hypothesis that transition from creatine kinase MB subunits (CK-MB) to troponin as a more sensitive biomarker of myocardial necrosis reduced the 1 year mortality of non-ST elevation acute coronary syndrome (ACS) patients. DESIGN: Retrospective population based cohort study performed in seven tertiary care hospitals in Israel. The patient population comprised all non-ST elevation ACS admissions during a 5 year period (1999-2004). CK-MB was the biomarker for the diagnosis of myocardial infarction (MI) at the time of admission in 14 037 patients (group 1), while 11 643 patients were admitted after the individual hospital laboratory switched to troponin (group 2). Incidence of ACS types, in-hospital management and 1 year survival was assessed. RESULTS: Group 2 patients had a higher frequency of non-ST elevation MI diagnosis (27.9% vs 17.7%, p<0.001) and were more likely to undergo coronary catheterisation during hospitalisation (44.5% vs 37.5%, p<0.001). One year mortality in non-ST elevation MI was lower in group 2 compared to group 1 (24.6% vs 28.1%, p = 0.002). Similarly, the 1 year death rate in the unstable angina group decreased in group 2 compared to group 1 (7.7% vs 8.5%, p = 0.04). However, the overall non-ST elevation ACS 1 year mortality rate did not change (12.4% vs 11.9%, p = 0.27). In multivariate Cox proportional hazard analysis the transition from CK-MB to troponin had no significant effect on overall 1 year mortality (hazard ratio 0.95, 95% confidence interval 0.89 to 1.03). CONCLUSIONS: Transition to troponin as a diagnostic marker of MI led to an increase in the incidence of non-ST elevation MI. This transition was not associated with a decrease in the 1 year non-ST elevation ACS mortality rate.

Evidence-based medicine: assessment of knowledge of basic epidemiological and research methods among medical doctors.

BACKGROUND: An understanding of statistical methods and basic epidemiology are crucial for the practice of modern medicine. AIMS: To assess (1) the knowledge of basic methods of conducting research and data analysis among residents and practicing doctors and (2) the effect of country of medical school graduation, professional status, medical article reading and writing experience on the level of this knowledge. METHODS: Data were collected by means of a supervised self-administered questionnaire, which was distributed among doctors at Soroka Medical Center, Beer-Sheva, Israel. The questionnaire included 10 multiple-choice questions on basic epidemiology and statistics, and respondent demographical data. RESULTS: Of the 260 eligible doctors, 219 (84.2%) returned completed questionnaires. Of the 219 doctors, 50% graduated more than 8.5 years ago, 39.7% were specialists and the remaining were residents. The most frequent specialty was internal medicine (37.4%). Israel was the most frequent country of graduation (45.7%), followed by the former Soviet Union (Eastern medical education; 38.4%). The median total score of knowledge was 4 of 10 questions (interquartile range 2-6). A higher score was associated with a Western medical education, being a specialist, shorter elapsed time since graduation, higher number of publications and self-reported reading of "methods" and "discussion" sections in scientific articles. CONCLUSION: This study found a low level of knowledge of basic principles of research methods and data analysis among doctors, and this knowledge considerably differed by country of medical school graduation.

Can the routine use of fluoroquinolones for community-acquired pneumonia delay the diagnosis of tuberculosis? A salutary case of diagnostic delay in a pilgrim returning from Mecca.

Guidelines advocate using fluoroquinolones as first-line treatment for community-acquired pneumonia (CAP). However, the use of fluoroquinolones in patients with undiagnosed tuberculosis may cause a delay in the diagnosis of tuberculosis and may also promote the development of resistance to these drugs if used as monotherapy in undiagnosed tuberculosis. We illustrate the former with the following case report of a patient who developed tuberculosis after a pilgrimage to Mecca.

Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients.

OBJECTIVE: To determine levels of serum interferon beta (IFNbeta) neutralizing antibody (NAb) and neopterin-an IFN biologic response marker-in patients with MS treated with Betaseron or Avonex. BACKGROUND: Controversy exists over the relative immunogenicity of IFNbeta-1a and IFNbeta-1b and the reasons for any such difference. To determine the role of patient profile and test methodology in IFNbeta, NAb levels need to be measured blindly and simultaneously in a predefined closely matched MS patient cohort. METHODS: Serum NAb and neopterin levels were measured in closely matched patients on Avonex (n = 98) or Betaseron (n = 64). NAb were determined by Athena Diagnostics and serum neopterin levels by Covance Laboratories using a competitive binding radioimmunoassay. RESULTS: More patients taking Betaseron (22%) than Avonex (7%) had elevated titers of NAb (p = 0.008). Mean serum neopterin levels were lower in patients with high as compared to low NAb titers (p = 0.0002). No difference in mean neopterin levels was found comparing the total Betaseron group to the Avonex group; however, in the subset of patients with low NAb titers, mean neopterin levels were higher in the Betaseron than in the Avonex group (p = 0.027). A random cross-sectional sampling of patients on Avonex showed a decrease in neopterin levels over time between weekly doses. CONCLUSION: NAb are more commonly found with Betaseron than Avonex. More studies are needed to determine the correlation among serum neopterin levels, other biologic response markers, NAb, and disease activity in patients with MS being treated with IFNbeta.

Rate and types of fractures in corticosteroid-treated multiple sclerosis patients.

In a retrospective study of 103 corticosteroid-treated MS patients, the average rate of fracture events was 3.2% of the patients per year over 7.1 (+/- 5.7 SD) years at risk. Fractures of the ribs, pelvis, hip, or vertebrae occurred in 11 patients and became most common 5 years after starting steroids. Relatively high or low cumulative doses of steroids did not correlate predictably with the occurrence of fractures.

Measles virus nucleic acid sequences in human brain.

We constructed a measles virus genomic recombinant DNA library, and used clones coding for portions of the viral P, M and H proteins to probe for measles virus nucleic acid sequences in post-mortem multiple sclerosis, SSPE and control brains. By dot blot hybridization, the probes detected measles virus nucleic acid sequences in as little as 3 nanograms of total RNA extracted from measles virus-infected cells and also in highly diluted RNA extracted from SSPE brain, but did not detect measles virus sequences in RNA extracted from 11 multiple sclerosis or 8 control brains, even at a 1 000-fold higher concentration of RNA. By in situ hybridization, these probes detected measles virus nucleic acid sequences in virtually every cell and the surrounding neuropile of SSPE brain, but again did not detect such sequences in multiple sclerosis or control brains. Our findings using these highly specific probes confirm that measles virus is found in SSPE brains and indicate that measles virus genome is unlikely to be present in multiple sclerosis or normal brains.

Spinocerebellar degeneration and cerebral hypomyelination in a family.

The proband is a 24-year-old woman who developed symptoms of a spinocerebellar degeneration in early childhood. Neurological examination revealed normal cognitive function, optic atrophy, dysarthria, titubation, action tremors, increased deep tendon reflexes, Babinski's signs, and a spastic scissoring gait. The magnetic resonance imaging (MRI) showed an abnormal increased signal on long TR images involving white matter throughout the cerebral hemispheres, most striking in the subcortical white matter, and to a lesser degree in the brainstem, compatible with diffuse hypomyelinating or dysmyelinating diseases. Metabolic and chromosomal studies were normal. Her 49-year-old mother developed similar symptoms in her 20s and is now wheelchair-bound. Findings on neurological examination and MRI were similar to her daughter but more severe. The proband's maternal grandfather had a female cousin who had a neurological illness beginning in her 20s with similar symptoms and signs and died at the age of 44 years. Spinocerebellar degenerations are a group of syndromes with similar clinical manifestations but heterogeneous etiology. We report a family with spinocerebellar degeneration with distinct MRI findings compatible with hypomyelination or dysmyelination which has not heretofore been described. This family may represent a new spinocerebellar syndrome due to an abnormality of as yet an undetermined gene.

Non-competitive regulation of phencyclidine/sigma-receptors by the N-methyl-D-aspartate receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid.

D-(-)-2-Amino-5-phosphonovaleric acid (D(-)AP5), a selective, potent competitive antagonist of N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptors was used to investigate the relationship between NMDA receptors and phencyclidine (PCP) binding. Incubation of rat brain membranes with D(-)AP5 decreased the apparent number of PCP/sigma-receptors in dose-dependent fashion without affecting their affinity for [2-thienyl-3H]cyclohexylpiperidine (TCP). These data, taken together with electrophysiological evidence that PCP non-competitively antagonizes NMDA receptor-mediated transmission, are consistent with the hypothesis that the PCP/sigma-receptor may be situated in or near a channel regulated by an NMDA receptor complex.

Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis.

In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: correlation with clinical and MRI status.

We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.

Retention and use of patient-centered interviewing skills after intensive training.

PURPOSE: Studies show that residents trained in patient-centered interviewing (PCI) are more effective in handling patients' emotions and are more skillful in gathering patients' data. This study evaluated the long-term use of PCI skills. METHOD: Fourteen residents received PCI training during internship, and their skills were evaluated before, immediately after, and two years after their training through directly observed patient interviews. A confidential survey evaluated the residents' actual use of PCI two years after the intensive training. Control groups of 14 interns prior to PCI training and 14 residents from another program not trained in PCI were also surveyed. RESULTS: Residents' use of PCI skills (optimization of setting, establishment of narrative thread, open-to-closed-ended questioning cone, avoid asking more than one question at a time, and (facilitation) were significantly improved, even two years after their training in PCI. The residents who received intensive block training reported using PCI techniques more frequently than did those in the control groups. However, the only significant difference in use of PCI skills between the intervention and control groups was found in reflection of patient's emotions. CONCLUSION: Medical residents retained PCI skills for two years. Further studies are needed to determine whether successful postgraduate training of physicians in PCI translates into a change in behaviors during their professional lives.

Temporal trends in the hospitalization and outcomes of patients with decompensated heart failure Multicenter study.

BACKGROUND: The burden of illness of heart failure (HF) may be changing. We performed a study to define temporal trends in hospital admissions and long-term mortality among patients admitted with acute decompensated heart failure. METHODS: We studied consecutive admissions with HF as a primary diagnosis at seven hospitals from 2000 to 2004. Admissions with a concurrent acute myocardial infarction were excluded from the analysis. Temporal trends in the etiology of HF, associated co-morbid conditions, medications and mortality were identified. RESULTS: A total of 21,581 hospitalizations of 12,769 patients with primary diagnosis of HF were studied (average age 75). Monthly admission rate decreased by 10% over the study period, primarily due to a decrease in HF admissions of IHD etiology. Between 2000 and 2004 there was a significant increase in post-discharge purchase of beta-blockers (from 44.0% to 69.0%, p < 0.001) and statins (from 27.1% to 47.5%, p < 0.001). Mortality at 18 months post-discharge decreased from 38.9% to 33.9%. Multivariable analysis demonstrated that an annual mortality hazard decline could be explained by an increase in beta-blocker and statin use. CONCLUSIONS: The admission of acute HF patients of IHD, but not non-IHD etiology declined throughout the study period. Short term mortality remained stable throughout the study period, while there was a significant improvement in 18 month mortality rates. This reduction can be explained by higher utilization of the health services as can be manifested by an increase in statins and beta-blockers use.

The practical, moral, and ethical considerations of the new Israeli law for the allocation of donor organs.

There is a worldwide shortage of organs for transplantation; the number of patients on the waiting list exceeds the supply of available organs. The demand for organ donation is particularly concerning in Israel. A new Israeli law has been instituted to give those who sign donor cards allocation priority if they are ever in need of an organ transplant themselves. A number of variations on this paradigm that considers the willingness of patients to donate their own organs have since been proposed; however, the new Israeli policy for organ donation is the first time such a law has been implemented nationally. Prioritization of organ allocation to donors comes with a significant moral and ethical debate, and since its implementation in January 2010 there has been much controversy surrounding the new policy. This article provides a description of the new Israeli plan, specifically focusing on the practical, moral, and ethical debates surrounding the new system.

Rethinking ferrule--a new approach to an old dilemma.

The 'ferrule effect' is a long standing, accepted concept in dentistry that is a foundation principle for the restoration of teeth that have suffered advanced structure loss. A review of the literature based on a search in PubMed was performed looking at the various components of the ferrule effect, with particular attention to some of the less explored dimensions that influence the effectiveness of the ferrule when restoring severely broken down teeth. These include the width of the ferrule, the effect of a partial ferrule, the influence of both, the type of the restored tooth and the lateral loads present as well as the well established 2 mm ferrule height rule. The literature was collaborated and a classification based on risk assessment was derived from the available evidence. The system categorises teeth according to the effectiveness of ferrule effect that can be achieved based on the remaining amount of sound tooth structure. Furthermore, risk assessment for failure can be performed so that the practitioner and patient can better understand the prognosis of restoring a particular tooth. Clinical recommendations were extrapolated and presented as guidelines so as to improve the predictability and outcome of treatment when restoring structurally compromised teeth. The evidence relating to restoring the endodontic treated tooth with extensive destruction is deficient. This article aims to rethink ferrule by looking at other aspects of this accepted concept, and proposes a paradigm shift in the way it is thought of and utilised.