Biomedical subjects

R La Harpe

Publications and source records attributed to R La Harpe.

At least 19 recordsLinked to original sources

PubMed2006

Euthanasia and assisted suicide: comparison of legal aspects in Switzerland and other countries.

The purpose of this paper is to present the legal aspects associated with assisted suicide in Switzerland and compare them with those in other countries. Like euthanasia, assisted suicide is a subject that induces much discussion in many countries. While the law is very liberal in some countries, such as Belgium and the Netherlands (where both euthanasia and assisted suicide take place), these practices are very controversial in other countries, such as France, where they remain taboo subjects. In the United States of America, the laws concerning assisted suicide can differ greatly from one state to another. For example, in Oregon, assisted suicide is allowed if applied by a medical doctor; in others, this act is illegal. In Canada, it is punishable according to the Criminal Code. In Switzerland euthanasia is punishable by law. However, the penal code does not condemn assisted suicide, whether carried out by a medical doctor or another person, provided it is not carried out through selfish motives. The application of these practices has become simplified in recent years and societies for the right to die with dignity based on this principle have come into being (Exit and Dignitas). In the French- and German-speaking parts of Switzerland the association Exit assists individuals living in Switzerland with serious progressive and incurable disease in their engagement to end their life. The association Dignitas, in the German-speaking part of Switzerland, also undertakes--in the same circumstances--to assist individuals coming from foreign countries. Dignitas welcomes several such individuals every year, especially from Germany, where a similar approach does not currently exist.

Cross-Cultural Comparison↗

PubMed2005

Sudden, unexpected death due to undiagnosed frontal glioblastoma in a schizophrenic patient.

The incidence of sudden death due to undiagnosed primary intracranial tumor is low in forensic autopsy. We report a case of a 48-year-old white male, known to be a schizophrenic patient for several years, and in whom a medico-legal autopsy disclosed a large, previously undiagnosed, bilateral frontal glioblastoma infiltrating the genu of corpus callosum. We emphasize the importance of performing complete autopsy, including a thorough neuropathological examination, in all cases of sudden unexpected death, especially in those cases in which no extracerebral cause of death had been established and whose clinical history was primarily of a psychiatric nature.

Brain Neoplasms↗

PubMed2004

Long-term regulation of signalling components of adenylyl cyclase and mitogen-activated protein kinase in the pre-frontal cortex of human opiate addicts.

Opiate addiction involves the development of chronic adaptive changes in micro -opioid receptors and associated pathways (e.g. cAMP signalling) which lead to neuronal plasticity in the brain. This study assessed the status of cAMP and mitogen-activated protein kinase (MAPK) pathways in brains (pre-frontal cortex) of chronic opiate addicts. In these subjects (n = 24), the immunodensities of adenylyl cyclase-I, PKA Calpha, total and phosphorylated CREB were not different from those in sex-, age- and PMD-matched controls. Moreover, the ratio pCREB/tCREB was similar in opiate addicts (0.74) and controls (0.76), further indicating that opiate addiction in humans is not associated with an upregulation of several key components of cAMP signalling in the pre-frontal cortex. In contrast, the components of MAPK cascade (Ras/c-Raf-1/MEK/ERK) were decreased in the same brains. Notably, pronounced downregulations of phosphorylated MEK (85%) and ERK1/2 (pERK1: 81%; pERK2: 80%) were quantitated in brains of opiate addicts. Chronic morphine treatment in rats (10-100 mg/kg for 5 days) was also associated with decreases of pERK1/2 (59-68%) in the cortex. In SH-SY5Y cells, morphine also stimulated the activity of pERK1/2 (2.5-fold) and the MEK inhibitor PD98059 blocked this effect (90%). The abnormalities of MAPK signalling might have important consequences in the long term development of various forms of neural plasticity associated with opiate addiction in humans.

Adenylyl Cyclases↗

PubMed2001

Cyclic AMP-mediated signaling components are upregulated in the prefrontal cortex of depressed suicide victims.

The components of cyclic AMP signaling cascade (catalytic (Calpha) subunit of cyclic AMP-dependent protein kinase (PKA) and cyclic AMP response element binding protein (CREB)) were quantitated by Western blotting in the prefrontal cortex of depressed suicide victims (n=23) and their matched controls (n=14). There was a significant increase in the levels of CREB, both in total (tCREB; 121+/-8% (mean+/-S.E.M.), P<0.02) and phosphorylated (pCREB; 128+/-9%, P<0.01) forms, but not in PKA Calpha levels (109+/-9%, ns), in brains of depressed suicides compared to those in control subjects. The increases in CREB were specifically observed in antidepressant drug-free subjects (tCREB: 137+/-11%, P<0.01; pCREB: 136+/-12%, P<0.02; n=9), but not in the antidepressant-treated subjects (tCREB: 108+/-18%, ns; pCREB: 111+/-17%, ns; n=8). There were significant correlations between the levels of PKA and those of tCREB and pCREB in the prefrontal cortex of depressed suicides. These results indicate that the components of cyclic AMP signaling are upregulated in a coordinated manner in brains of depressed suicides and that this alteration is not related to antidepressant treatment.

Adult↗

PubMed2000

Regulation of nonphosphorylated and phosphorylated forms of neurofilament proteins in the prefrontal cortex of human opioid addicts.

The neurofilament (NF) proteins (NF-H, NF-M, and NF-L for high, medium, and low molecular weights) play a crucial role in the organization of neuronal shape and function. In a preliminary study, the abundance of total NF-L was shown to be decreased in brains of opioid addicts. Because of the potential relevance of NF abnormalities in opioid addiction, we quantitated nonphosphorylated and phosphorylated NF in postmortem brains from 12 well-defined opioid abusers who had died of an opiate overdose (heroin or methadone). Levels of NF were assessed by immunoblotting techniques using phospho-independent and phospho-dependent antibodies, and the relative (% changes in immunoreactivity) and absolute (changes in ng NF/microg total protein) amounts of NF were calculated. Decreased levels of nonphosphorylated NF-H (42-32%), NF-M (14-9%) and NF-L (30-29%) were found in the prefrontal cortex of opioid addicts compared with sex, age, and postmortem delay-matched controls. In contrast, increased levels of phosphorylated NF-H (58-41%) and NF-M (56-28%) were found in the same brains of opioid addicts. The ratio of phosphorylated to nonphosphorylated NF-H in opioid addicts (3.4) was greater than that in control subjects (1.6). In the same brains of opioid addicts, the levels of protein phosphatase of the type 2A were found unchanged, which indicated that the hyperphosphorylation of NF-H is not the result of a reduced dephosphorylation process. The immunodensities of GFAP (the specific glial cytoskeletol protein), alpha-internexin (a neuronal filament related to NF-L) and synaptophysin (a synapse-specific protein) were found unchanged, suggesting a lack of gross changes in glial reaction, other intermediate filaments of the neuronal cytoskeletol, and synaptic density in the prefrontal cortex of opioid addicts. These marked reductions in total NF proteins and the aberrant hyperphosphorylation of NF-H in brains of opioid addicts may play a significant role in the cellular mechanisms of opioid addiction.

Adult↗

PubMed2000

Lethal methadone intoxications in Geneva, Switzerland, from 1994 to 1998.

AIMS: To estimate the number of methadone lethal intoxications in Geneva from 1994 to 1998, where the number of patients in methadone treatment has more than doubled since 1990. DESIGN: Retrospective study of all toxicological, autopsy and clinical data. SETTING: The Geneva Department of Forensic Medicine. PARTICIPANTS: All suspected overdose deaths in Geneva from 1994 to 1998. Cases were selected on the basis that the only cause of death was a potentially lethal drug concentration in the postmortem blood sample. MEASUREMENT: Toxicology and autopsy findings, clinical and drug history. FINDINGS: There were 106 lethal drug intoxications over the period. The overall number of drug intoxication deaths went from 33 in 1994 to nine in 1998. Thirty-six cases had methadone identified in their blood. All the 36 cases but one had medications or other drugs used illicitly present in the blood or urine. Of these 36 cases, 21 were attributed to methadone lethal intoxication. Only seven of these 21 decedents were enrolled in a methadone programmes. The number of deaths attributed to methadone intoxication ranged from three to five per year. CONCLUSION: Most lethal methadone intoxication is due to diverted or illegal methadone in association with medications or other drugs used illicitly. Furthermore, the increase in methadone prescription under strict medical control with health measures aimed at drug abuse prevention did not lead, in our study, to an increase of methadone lethal intoxication and may have been partly responsible for the large decrease of overall drug intoxication deaths during the time of our study.

Adolescent↗

PubMed1999

Up-regulation of immunolabeled alpha2A-adrenoceptors, Gi coupling proteins, and regulatory receptor kinases in the prefrontal cortex of depressed suicides.

Suicide and depression are associated with an increased density of alpha2-adrenoceptors (radioligand receptor binding) in specific regions of the human brain. The function of these inhibitory receptors involves various regulatory proteins (Gi coupling proteins and G protein-coupled receptor kinases, GRKs), which work in concert with the receptors. In this study we quantitated in parallel the levels of immunolabeled alpha2A-adrenoceptors and associated regulatory proteins in brains of suicide and depressed suicide victims. Specimens of the prefrontal cortex (Brodmann area 9) were collected from 51 suicide victims and 31 control subjects. Levels of alpha2A-adrenoceptors, Galphai1/2 proteins, and GRK 2/3 were assessed by immunoblotting techniques by using specific polyclonal antisera and the immunoreactive proteins were quantitated by densitometry. Increased levels of alpha2A-adrenoceptors (31-40%), Galphai1/2 proteins (42-63%), and membrane-associated GRK 2/3 (24-32%) were found in the prefrontal cortex of suicide victims and antidepressant-free depressed suicide victims. There were significant correlations between the levels of GRK 2/3 (dependent variable) and those of alpha2A-adrenoceptors and Galphai1/2 proteins (independent variables) in the same brain samples of suicide victims (r = 0.56, p = 0.008) and depressed suicide victims (r = 0.54, p = 0.041). Antemortem antidepressant treatment was associated with a significant reduction in the levels of Galphai1/2 proteins (32%), but with modest decreases in the levels of alpha2A-adrenoceptors (6%) and GRK 2/3 (18%) in brains of depressed suicide victims. The increased levels in concert of alpha2A-adrenoceptors, Galphai1/2 proteins, and GRK 2/3 in brains of depressed suicide victims support the existence of supersensitive alpha2A-adrenoceptors in subjects with major depression.

Adult↗

PubMed1998

[Victims of violence: importance of medical testimony for the practitioner].

Physicians may be asked to provide care to victims of violence. Adequate diagnostic and therapeutic management must be provided. Establishing a detailed medical testimony can substantially influence the judiciary or administrative procedure's outcome. This paper provides guidelines for writing a medical testimony and describes the criteria that physicians need to consider in order to serve at best the interests of their patient within a mutually trustful relationship.

Adult↗

PubMed1997

Marked decrease of immunolabelled 68 kDa neurofilament (NF-L) proteins in brains of opiate addicts.

NEUROFILAMENT (NF) proteins, the major components of the neuronal cytoskeleton, have been shown to represent previously unknown targets for the chronic effects of morphine in rats. This study was designed to evaluate the abundance of immunoreactive NF-L (68 kDa) proteins in post-mortem brains of chronic opiate addicts who had died of a heroin or methadone overdose. Levels of NF-L proteins were assessed by immunoblotting techniques. Levels of immunoreactive NF-L proteins were markedly decreased (47%, n = 17) in the frontal cortex. The reduced abundance of brain NF-L proteins was not related to the post-mortem delay or to the plasma concentrations of opiates, suggesting that the observed changes represent a specific long-term effect of opiate drugs. Because of the functions associated with NF proteins (e.g. axonal transport), this finding suggests that opiate drugs may induce neuronal damage after chronic abuse in humans.

Adult↗

PubMed1997

Regulation of immunolabelled mu-opioid receptors and protein kinase C-alpha and zeta isoforms in the frontal cortex of human opiate addicts.

To assess the status of opioid receptors in the human brain during the process of opiate addiction, the abundance of immunoreactive mu-opioid receptors was quantitated in postmortem brains of chronic opiate addicts who had died of a heroin or methadone overdose. The immunoreactive levels of the associated enzyme protein kinase C (PKC-alpha and zeta isoforms) and G proteins (G alpha(i1/2) subunits) were also assessed in the same brains. In the frontal cortex of opiate addicts, the abundance of mu-opioid receptors was not different from that obtained in matched controls. The level of Ca2+-dependent PKC-alpha was decreased (25%), whereas that of the atypical PKC-zeta remained unchanged. The density of G alpha(i1/2) proteins also was found to be increased (40%). The results indicate that opiate addiction in humans does not appear to be associated with a reduced density of brain mu-opioid receptors. The sustained down-regulation of PKC-alpha in the brain of opiate addicts would allow the up-regulation of G alpha(i1/2) proteins aimed at compensating the postulated desensitization of the mu-opioid receptor system.

Adolescent↗

PubMed1996

[Drunkenness in traffic in Geneva: distribution and detection].

All cases of inebriety (up to the Swiss Legal BAC: 0.8 gr/kg) in traffic (pedestrians and drivers) recorded by the police during one year are the object of the study. Their frequency and blood alcohol levels are related to individual variables (sex, age, nationality) and also to environmental variables (vehicle, month, day, time). Clinical appreciation of intoxication levels by physicians taking blood samples is also verified. Inherent difficulties of methodological bias coupled to the use of official data, are examined by systematically taking into account the way in which intoxication was detected (with or without accident). In all, 951 cases of alcohol intoxication were studied.

Adolescent↗

PubMed1996

[Drunkenness in traffic in Geneva: occasional abuse or alcoholism?].

The main aim of the study is to measure the importance of alcoholism amongst alcohol intoxication (up to the Swiss legal BAC: 0.8 gr/kg) in traffic. The method used describes the characteristics of all cases of inebriety (amongst pedestrians and drivers) recorded by the police during one year and relates this with complementary data such as the determination of a biological marker of alcohol consumption (Gamma Glutamyl Transferase), or DWI recidivism. Results of general interest are: 22% of recorded cases of alcohol intoxication are recidivists; about one third of the cases of alcohol intoxication registered are due to alcoholism rather than to social drinking. A preventive policy in road traffic safety must integrate the problems, caused by alcoholism, on Public Health.

Accidents, Traffic↗

PubMed1993

Methadone therapy.

Explore the source record for details and available documents.

Cause of Death↗

PubMed1992

[Sudden death during performance of sport: forensic medicine elucidation].

Our study deals with cases of sudden death (non-traumatic death) while playing sport which were examined at the Institute of Forensic Medicine at the University of Geneva, and covers the last ten years: 1980-1989. We discovered 19 cases, all men between the ages of 17 to 67. In the case of the younger sportsmen (under the age of 45-50) or when the causes of mortality were unclear, the police requested an autopsy, which totalled 8 cases. In the other 11 cases, we were asked to make an external examination of the bodies, in order to exclude any signs of violence. Seven sportsmen, aged 36-49, who used to play high-risk sports such as football, tennis, basketball and running were autopsied and presented a myocardial infarct. Its interesting that 2 of these cases had also an old scar of a myocardial infarct. The eighth case was a 17 year old boy who had an already known obstructive cardiomyopathy.

Adolescent↗

PubMed1989

[Scientific training of competition swimmers: contribution of lactic acid level].

This study tries to find a way of improving the effectiveness of the training schedule for swimmers. We regularly measured the level of blood lactate during training in order to estimate as precisely as possible the anaerobic threshold in swimming. As is already known sportsmen improve more rapidly their physical capacity (especially endurance) when they swim at a threshold speed corresponding to 4 Mmol of lactate. We used the following parameters: blood lactate concentration in relation to swimming time, and blood lactate accumulation in relation to covered distance for successive days of training at the same swimming speed. These two complementary procedures allowed us to follow the state of training of each athlete using simple graphs and to better advise him so that he may attain his threshold swimming speed. We have often noticed an improvement of the physical condition: either as an increase in swimming speed for the same accumulation of lactate, or as a decrease in the level of blood lactate for a same swimming speed. Measurements of blood lactate accumulation in relation to covered distance, on the condition that the speeds are more or less the same, allow a more precise estimate of the athletes' performances.

Adolescent↗

PubMedDate not supplied

[Are there environmental factors influencing the choice of death by drowning as a means of suicide in the Geneva canton?].

123 out of 850 suicides that occurred in the Canton of Geneva between 1980 and 1989 were suicides by submersion. 75 women and 48 men committed this kind of suicide. 89 victims (57 women and 32 men) were older than 40 years. In all cases the spatial distance between the residence of the suicides and the nearest river or lake was determined; a correlation with the tendency to commit suicide by drowning was not evident. More than geographical factors, the psychological influences have to be considered.

Adolescent↗

PubMedDate not supplied

[Forensic medicine experiences with methadone substitution in the Geneva canton].

Methadone treatment for heroin addiction has followed three distinct periods in Geneva, Switzerland. The first period (1970-1979) corresponds to the beginning of the heroin addiction epidemic. Treatment was restricted to detoxification and did not succeed in reducing fatal overdoses. During the second period (1980-1989), methadone maintenance program was favoured but access to this program was limited. This period has brought a decrease of illegal heroin consumption and criminality but not of fatal overdoses. Finally, during the third period (since 1990), legislation was changed to allow easier access to methadone maintenance program. As a consequence there was a significant drop in lethal heroin overdoses and in deaths attributed to HIV.

Cause of Death↗

PubMedDate not supplied

[Perpetrator related analysis of intentional homicides in the Genf canton (1971-1990)].

A retrospective offender-related analysis was conducted on all deliberate homicides committed in the canton of Geneva between 1971 and 1990. The cases analyzed included 97 convicted single perpetrators or accomplices and 93 victims. 21 further homicides remained unsolved. 86.6% of the offenders were male; foreigners were over-represented in comparison with Swiss citizens. The average age was 35 years. In a majority of the cases the offender and the victim were partners, came from the same family or were acquainted with each other. Guns or knives were the most frequently used weapons. The criminal offences tried in Geneva were evaluated also with regard to their legal qualification.

Adult↗