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Quantitative analysis of synaptophysin immunoreactivity in human neocortex after cardiac arrest: confocal laser scanning microscopy study.

Transient global ischaemia caused by cardiac arrest results in lesions that involve all brain structures. The aim of this study was to investigate the condition of synapses in patients surviving, but remaining in a persistent vegetative state, following resuscitation after cardiac arrest. We performed a quantitative analysis of the distribution and density of elements containing a synaptic vesicle protein--synaptophysin (p38)--in human neocortex in cases which survived for 1 week, 2 months, and 1 year after the cardiac arrest. Neurologically healthy cases that died following an accident served as control. Dual-channel confocal laser scanning microscopy (CLSM) was used to image p38-immunoreactivity (IR) and lipofuscin autofluorescence. In control cases no statistically significant differences were found for p38-IR between layers II-III and V-VII. However, the temporal cortex had a higher density of p38-immunoreactive structures than the motor cortex. In postischaemic cases a reduction in the density of p38-IR elements was apparent, mainly in the frontal and motor cortices and less pronounced in the temporal cortex. The least decrease compared with controls was observed in the visual cortex. In the 1 week survival case, a maximal decrease in p38-IR (35% below control) was found. In this case, the number of p38-IR elements per visual field was decreased, and big aggregates of p38-IR structures were observed. In general, the amounts of p38-IR structures were higher in all of the control cases compared with the postischaemic cases.

Autopsy↗

Prognostic value of 1H-MRS in perinatal CNS insults.

The authors studied 37 term neonates (38-42 gestational weeks) at 1-11 days after central nervous system insult to determine whether proton magnetic resonance spectroscopy (1H-MRS) of the occipital gray/parietal white matter was useful in predicting outcomes. Etiologies included asphyxia, 18; sepsis/meningitis, 8; metabolic disorders, 5; stroke, 4; and trauma, 2. 1H-MRS data (1.5T; 8 cm3 vol, stimulated echo acquisition mode sequence, TE = 20 ms, TR = 3000 ms) were expressed as metabolite peak area ratios (NAA/Cr, NAA/Cho, Cho/Cr) and the presence or absence of lactate. Outcomes were assessed at 6 to 12 months post-insult using the Pediatric Cerebral Performance Scale and were dichotomized as follows: good/moderate outcome (good, mild or moderate disability) or poor outcome (severe disability, persistent vegetative state, death). Neonates with poor outcomes had significantly lower NAA/Cho and significantly higher Cho/Cr ratios in the occipital region, as compared with patients with good/moderate outcomes. No neonates with good/moderate outcomes had metabolite ratios that exceeded 2 standard deviations from the mean. In addition, the absence of lactate on 1H-MRS correlated with a good/moderate outcome. The study also showed that 1H-MRS metabolite ratio data, added to either the Sarnat or EEG scores, enhanced the correlation between these prognostic factors and outcomes. 1H-MRS provides additional objective data early after a wide variety of perinatal neurologic insults to enhance outcome prediction.

Apgar Score↗

Clinical correlates and prognosis in early spindle coma.

OBJECTIVE: To determine the prognostic significance of spindle coma (SC) according to etiology and EEG reactivity. METHODS: We reviewed 15 patients with SC due to various causes within 8 days of coma to determine the prognostic significance of this EEG pattern. RESULTS: The outcome among survivors was favorable: among 13 survivors, 9 were independent in all activities of daily living (ADLs) at 6 months; 3 were dependent in all ADLs; and one remained in coma. EEG reactivity to noxious stimuli best predicted outcome: All patients (whatever the coma etiology) with EEG reactivity survived; conversely, not all patients without EEG reactivity died. CONCLUSION: In our patients, EEG reactivity independent of etiology predicted survival, neurological examination did not predict outcome. Most SC survivors had a meaningful recovery achieving all ADLs. From the literature, the cause of SC was predictive of outcome: encephalopathy, seizures and trauma had the best prognosis while hypoxia, CRA and structural lesions carried the worst. Literature review revealed that 23% of patients [56/242] died or remained in a persistent vegetative state (PVS). Best outcomes occurred when SC was due to drugs, encephalopathy or seizures: (0/14 died or were in a PVS). With trauma 15% [25/169] died or were in a PVS). Intermediate outcomes occurred with hypoxia and cardio-respiratory arrest (CRA): 33% [7/21] died or were in a PVS. The gravest outcomes occurred with brain-stem and cerebral infarctions, and tumors: 73% [22/30] died or were in a PVS.

Activities of Daily Living↗

Civilian gunshot wounds to the brain.

BACKGROUND: Civilian gunshot wounds to the brain are relatively rare, and a much-neglected subject in Taiwan. We present our experience with 16 patients who sustained gunshot wounds to the brain, and then identify factors determining the respective outcomes. METHODS: From 1988-2002, data from 16 patients with civilian gunshot wounds to the brain, who were treated at Taichung Veterans General Hospital, were retrospectively reviewed. Historical information, clinical manifestations, and imaging findings were described. Based on Glasgow Outcome Score (GOS), patients were divided into a poor-outcome group (GOS, 1-2) and satisfactory-outcome group (GOS, 3-5) for further analysis. RESULTS: The overall mortality rate was 31.3% (5 of 16 patients). Thirteen patients underwent surgery, and the surgical mortality rate was 15.4% (2 of 13 patients). Of the 7 patients with a Glasgow Coma Scale (GCS) score of more than 8, all survived with satisfactory outcomes; of the 9 patients with a GCS score of less than 8, 8 had poor outcomes (5 died, and 3 were in a persistent vegetative state); p < 0.005 between the 2 GCS groups. In addition, the rate of satisfactory outcome was significantly higher in 7 patients with limited brain injury, as determined by computed tomography (CT) scan, than in 8 patients with extensive brain injury (86% vs 25%; p < 0.05). CONCLUSION: GCS score on admission, and the extent of brain injury as visualized by CT scan, seem to be the 2 most significant predictors of outcome in cranio-cerebral gunshot wounds. Patients with a GCS score of more than 8, or brain lesions limited to a single lobe of the brain, may benefit from aggressive management.

Adolescent↗

The basis and relevance of emotional dignity.

The paper is a preliminary examination of the origin and role of psychological perception or "feeling" of dignity in human beings. Following Ayala's naturalistic account of morality, a sense of emotional dignity is seen as an outcome of processes of natural selection, cultural evolution, and above all a need for social inclusion. It is suggested that the existence of emotional dignity as part of a human species-related continuum provides an explanation of why we treat those in a persistent vegetative state, the severely and hopelessly mentally impaired, the senile demented, cadavers and archaeological remains with dignity and respect. For older Europeans, dissonance between physical and mental abilities, unfamiliarity with social and cultural changes and relative proximity to death may influence their emotional dignity and hence vulnerability.

Aged↗

Dutch nursing home policies and guidelines on physician-assisted death and decisions to forego treatment.

OBJECTIVE: The purpose of this study was to describe: (a) the prevalence and content of policies on euthanasia or assisted suicide (EAS) in three different types of nursing homes; (b) specific content items of written guidelines for EAS; and (c) the prevalence of guidelines on withholding or withdrawing treatment from severely demented patients and patients in a persistent vegetative state in the nursing homes. DESIGN: Descriptive, cross-sectional. METHODS: We have used a postal survey among directors of patient care of all (n = 304) Dutch somatic nursing homes (meant for physically handicapped patients), psychogeriatric nursing homes (meant for patients suffering from dementia) and combined nursing homes. Data were collected from October 1994 through January 1995. RESULTS: Results indicate that psychogeriatric nursing homes less often had a written EAS policy than somatic and combined nursing homes (62, 68 and 80% respectively). The most frequently reported aspects in the EAS guidelines, by the nursing homes with guidelines based on a policy that EAS was accepted under certain conditions; were consultation of another physician (97%), referral to another physician if the attending physician had in-principle objections (82%), and the involvement of the nurse in the decision-making procedure (82%). Of the nursing homes, 9% reported having specific written procedures concerning withholding or withdrawing treatment from severely demented patients. CONCLUSION: Guidelines in the nursing homes on euthanasia and assisted suicide might be improved. Especially with regard to withholding or withdrawing treatment from incompetent patients, more guidelines should be developed.

Cross-Sectional Studies↗

[Attempted CPR in nursing homes - life-saving at the end of life?].

AIM: We studied the course and success rate of cardiopulmonary resuscitation (CPR) attempted on nursing home residents by a physician-staffed pre-hospital advanced cardiac life support (ACLS) team. METHODS: Ambulance records of nursing home residents from Goettingen/Germany who had a cardiac arrest were examined retrospectively. RESULTS: During a seven-year period (1992 - 1998) the ACLS team was called to 71 residents (mean age 81.8 years) who sustained cardiac arrest. In 25 patients no CPR was attempted: 20 were pronounced dead by the arriving emergency physician, though only in 7 patients obvious clinical signs of death were present. Five patients suffered from a continuous deterioration of their health status and the ACLS team arrived after the process of dying had already started. No CPR attempt was initiated. The ACLS team performed CPR on 46 nursing home residents. In 33 patients (72 % of CPR attempts) no return of spontaneous circulation (ROSC) was achieved. In three patients (6%) palpable pulse returned only transiently. Ten patients (22 %) who showed ROSC were transported to the hospital. Six patients died within 24 hours after having been admitted to the hospital, two patients within the next 8 days. Two patients survived to hospital discharge. The first was a 79-year old woman who returned to the nursing home after three weeks and survived severely mentally disabled another five days. The second was an 83-year-old man who was hospitalised for 20 days, returned in a persistent vegetative state to the nursing home and died 10 months later. A comparison of the arrest characteristics demonstrated that in patients with successful CPR there was a higher incidence of a witnessed collapse, bystander CPR, ventricular fibrillation and cardiac aetiology of arrest. CONCLUSION: In a high rate (35 %) the ACLS team with the emergency physician at the scene withheld CPR efforts in nursing home residents. Even if CPR was initiated, the benefits were very limited with only two patients (4,3 %) surviving severely disabled to hospital discharge.

Aged↗

Neurological outcome in comatose children with bilateral loss of cortical somatosensory evoked potentials.

Bilateral loss of median nerve cortical somatosensory evoked potentials (SEP) in comatose patients is reported to be one of the most discriminating predictors of poor outcome. We reviewed 53 children with bilateral absent cortical SEP with respect to their outcome and their follow-up SEP. Brain injury was caused by global cerebral ischaemia in 18 children, severe head trauma (SHT) in 13, nervous system infections in 10, and other aetiologies in 12 children. Thirty of 53 children died within the first 4 weeks and another 8 children within 4 years after the event. Two children (both ischaemia) survived in a persistent vegetative state, 9 children (1 ischaemia, 2 SHT, 3 nervous system infections, 3 other aetiologies) survived with severe deficits and 4 children (all SHT) with mild or moderate deficits. In 30 children SEP were repeated and in 8 children (5 SHT, 2 nervous system infection, 1 other aetiology) unilateral or bilateral cortical responses reappeared. Although bilateral loss of cortical SEP predicted an unfavourable outcome in most patients, a few comatose children with SHT showed an outcome with mild or moderate neurological deficits.

Adolescent↗

Anencephaly: where do we now stand?

In 1995 the American Medical Association's ethics council issued an opinion calling for the direct procurement of organs from anencephalic newborns, making them an exception to the "dead donor" rule. Such a firestorm erupted that the Council for Ethical and Judicial Affairs withdrew its opinion. Although the AMA has called for further research into possible "consciousness" in anencephalic newborns, present studies convincingly demonstrate that the brain stems of these infants are almost completely devoid of any evidence of even primitive functional organization. New studies indicate that cerebral absence causes unusual behaviors such as stiffening and hyperirritability that can be detected prenatally. Although widespread testing and screening in recent years has drastically reduced the number of anencephalic newborns, the discussion of use continues, raising ethical issues that pertain to other marginal patients such as those in persistent vegetative states. There are two schools of thought on the permissibility of using anencephalic newborns as organ sources: physicalism and personalism. Physicalism holds that all humans are so precious that no exceptions can be made regarding organ procurement, even in the case of anencephaly. Personalism sees moral worth related to one's potential or actual mental capacities, and because of anencephalic newborns' uniqueness, believes considerable liberties can be taken here. Most bioethicists are themselves in the personalist camp, but many have questions about changing the law to allow for a proposal such as the AMA Council's, because of the social impact of that change.

Anencephaly↗

Artificial feeding--solid ground, not a slippery slope.

Decisions about artificial feeding arouse more controversy than those involving any other life-sustaining treatment. Because food and water are generally considered basic elements of humane care, representing love and concern for the helpless, it is often thought that they must always be provided. In a landmark decision, the Supreme Judicial Court of Massachusetts ruled that a feeding tube could be removed from a patient in a persistent vegetative state if this was consistent with his previously expressed wishes. The case of Paul E. Brophy, Sr., is part of an emerging medical and legal consensus on the withholding of artificial feeding from adult patients. The view is growing that tube and intravenous feeding should be likened to other medical interventions and not to the routine provision of nursing care or comfort. Competent patients have the right to refuse such feeding. Feeding can also be stopped incompetent patients who have earlier stated such a wish.

Coma↗

Advance directives for medical care--a case for greater use.

UNLABELLED: BACKGROUND. Advance directives for medical care and the designation of proxy decision makers to guide medical care after a patient has become incompetent have been widely advocated but little studied. We investigated the attitudes of patients toward planning, perceived barriers to such planning, treatment preferences in four hypothetical scenarios, and the feasibility of using a particular document (the Medical Directive) in the outpatient setting to specify advance directives. METHODS: We surveyed 405 outpatients of 30 primary care physicians at Massachusetts General Hospital and 102 members of the general public in Boston and asked them as part of the survey to complete the Medical Directive. RESULTS: Advance directives were desired by 93 percent of the outpatients and 89 percent of the members of the general public (P greater than 0.2). Both the young and the healthy subgroups expressed at least as much interest in planning as those older than 65 and those in fair-to-poor health. Of the perceived barriers to issuing advance directives, the lack of physician initiative was among the most frequently mentioned, and the disturbing nature of the topic was among the least. The outpatients refused life-sustaining treatments in 71 percent of their responses to options in the four scenarios (coma with chance of recovery, 57 percent; persistent vegetative state, 85 percent; dementia, 79 percent; and dementia with a terminal illness, 87 percent), with small differences between widely differing types of treatments. Specific treatment preferences could not be usefully predicted according to age, self-rated state of health, or other demographic features. Completing the Medical Directive took a median of 14 minutes. CONCLUSIONS: When people are asked to imagine themselves incompetent with a poor prognosis, they decide against life-sustaining treatments about 70 percent of the time. Health, age, or other demographic features cannot be used, however, to predict specific preferences. Advance directives as part of a comprehensive approach such as that provided by the Medical Directive are desired by most people, require physician initiative, and can be achieved during a regular office visit.

Advance Directives↗

Gamete retrieval in terminal conditions.

There has been a growing interest and requests by patients facing intensive chemotherapy or surgically ablative procedures for gamete retrieval and preservation for future procreative efforts. There are technical difficulties in this area but little ethical discomfort. More troubling are the issues that arise with a terminally ill, incapable patient-one who is in a persistent vegetative state or who is declared brain dead or who is neurologically devastated with no hope for recovery, but not yet in either of the above states-or with a person who has suddenly died. In these cases, the surviving spouse, partner, or family members may request gamete retrieval for future reproductive efforts. Discussion of this topic within the Ethics Consultation Service at the University of Virginia demonstrated a need for development of insight derived from facts and ethical deliberation to help formulate a policy that would apply to such cases. A group was assembled with the expertise to explore the issue and to help formulate a policy that could be suggested for adoption by the hospital administration. The group consisted of a urologist with experience in sperm retrieval from terminally ill patients; the director of the laboratory supporting the assisted reproductive facility in the Department of Obstetrics and Gynecology; the chairperson of the Ethics Consultation Service (who is also a neonatologist); and 2 members of the Ethics Consultation Service, one a genetic counselor and the other an obstetrician-gynecologist with a master's degree in biomedical ethics. Current literature was reviewed, the expertise of the urological member and the reproductive laboratory director was explored, and the insight of the members of the Ethics Consultation Service was added. We explored the technical aspects of both male and female gamete retrieval and preservation and the reproductive potential of these stored gametes. We present a review of the current literature on both the technical and ethical aspects of the topic. Finally, we present a policy that we deem acceptable for adoption and that should be of value to other practitioners and facilities as they contemplate facing requests for gamete retrieval.

Advance Directives↗

Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema.

OBJECTIVE: To investigate the relation between outcomes of children with diabetic ketoacidosis (DKA)-related cerebral edema and baseline clinical features and therapeutic interventions for treatment of cerebral edema. STUDY DESIGN: All children </=18 years old with DKA and cerebral edema (n = 61) were retrospectively identified from 10 pediatric centers between 1982 and 1997. Demographic, biochemical, and therapeutic data were collected. Ordinal logistic regression analysis was used to identify factors associated with the clinical outcome (death or persistent vegetative state; mild to moderate neurological disability; or normal) after adjusting for known risk factors for the development of cerebral edema as well as the degree of neurologic depression at the time of diagnosis of cerebral edema. RESULTS: Seventeen (28%) children died or survived in a vegetative state; 8 (13%) survived with mild to moderate neurologic disabilities; and 36 (59%) survived without sequelae. Factors associated with poor outcomes included greater neurologic depression at the time of diagnosis of cerebral edema, a high initial serum urea nitrogen concentration, and intubation with hyperventilation to a PCO (2) <22 mm Hg. CONCLUSIONS: After adjusting for potential confounding variables and the degree of neurologic compromise at the initiation of therapy, intubation with hyperventilation is associated with adverse outcomes of DKA-related cerebral edema. Greater neurologic depression at the time of diagnosis of cerebral edema and a higher initial serum urea nitrogen concentration are also associated with poor outcome.

Adolescent↗

Palliative care versus euthanasia. The German position: the German General Medical Council's principles for medical care of the terminally ill.

In September 1998 the Bundesärztekammer, i.e., the German Medical Association, published new principles concerning terminal medical care. Even before publication, a draft of these principles was very controversial, and prompted intense public debate in the mass media. Despite some of the critics' suspicions that the principles prepared the way for liberalization of active euthanasia, euthanasia is unequivocally rejected in the principles. Physician-assisted suicide is considered to violate professional medical rules. In leaving aside some of the notions customarily used in the euthanasia debate, e.g., passive euthanasia, the principles emphasize the obligation of physicians to offer and the right of patients to receive palliative care. The principles explicitly list modalities of basic treatment that are indispensable in all cases, such as the obligation to satisfy hunger and thirst. This statement is meant to resolve the dispute on nutrition and hydration at the end of life, as it shifts the focus of care from maintaining physiological parameters to satisfying subjective needs. For patients in a persistent vegetative state, artificial feeding is held to be obligatory. Yet, the principles make reference to recent German jurisdiction which permit the stopping of artificial feeding if it is in accordance with the patient's presumed will. Additionally, the wording concerning this issue is found to remain unclear. Patients' autonomy is strengthened by explicitly welcoming advance directives as a means to ascertain patients' wills. The principles mark some changes compared to earlier documents. They deserve careful analysis and should be considered in the international debate on issues concerning the end of life.

Advance Directives↗

Outcome after shunt implantation in severe head injury with post-traumatic hydrocephalus.

OBJECT: Post-traumatic hydrocephalus (PTH) is considered a frequent complication after severe head injury (HI). There is little known about outcome following shunt implantation. METHODS: A hospital-based retrospective cross-over study investigated the outcome of 48 patients after severe HI, who had undergone ventricular shunt implantation due to PTH (40 males, mean age at injury 36 years, mean duration from HI to shunt implantation 27 weeks). Telephone interviews with the patients or with caring family members by means of a detailed questionnaire were performed after a mean observation period of 3.3 years after shunt implantation. Outcome was categorized using the Glasgow Outcome Scale (GOS): I: 12 patients, II: 7, III: 16, IV: 9, V: 4 at follow-up. CONCLUSIONS: 52.1% had a clear-cut benefit from shunt implantation, whereas 47.9% had not. Post-traumatic seizures were observed in 31 of 48 patients. Other complications after shunt implantation occurred in 20) patients. Revision of shunt implantation was performed in 15 patients (nine due to technical failure, three haemorrhage, one delayed primary wound closure, and two unknown). Two patients clearly deteriorated after operation (one severe frontal bleeding, one sepsis). The best predictive parameter for outcome after shunt implantation was the pre-operative status, patients in a better clinical condition (pre-operative GOS score 3-severe disabled vs 4-persistent vegetative state) had a better outcome. Patient's age at injury did not seem to influence the outcome. Clinical and computertomographic findings were of rather moderate predictive value as regards short- and long-term outcome after shunt implantation. Cisternography does not seem to be of additional help in the establishment of definite diagnosis of PTH.

Adolescent↗

Post-traumatic cerebral infarction. Neuroimaging findings, etiology and outcome.

PURPOSE: To assess the radiological characteristics of post-traumatic cerebral infarctions (PTCIs), the etiology and site of infarction, and to provide neuroimaging indicators of a poor clinical outcome. MATERIAL AND METHODS: A retrospective study of 16 patients with the neuroimaging-based diagnosis of PTCI was carried out. All CT, MR examinations, cerebral angiograms and medical records of the patients were reviewed. RESULTS: Infarcts were diagnosed in the territory of the posterior cerebral artery in 9 patients, in the middle cerebral artery in 5, in the anterior cerebral artery in 3, lenticulostriate-thalamoperforating in 2, vertebrobasilar in 3, and cortical infarcts in 2 patients. Neuroimaging studies suggested focal mass effect and/or acquired intracranial herniations as the cause of infarction in 13/16 patients (81.2%). In 3/16 patients (18.8%), PTCI was due to vascular injury of which 2 were angiographically documented (carotid artery dissection). Eight of the 16 patients in this study died or were left in a persistent vegetative state. Patients with associated subdural hematoma, brain swelling/edema and traumatic subarachnoid hemorrhage (tSAH) exhibited the worst outcome. CONCLUSION: Gross mechanical shift of the brain and herniation across the falx and/or tentorium accounted for infarction in a majority of cases in our study. The overall death rate was 43.8% and this result suggests that PTCI is an indication of a poor clinical outcome, especially among patients with associated subdural hematoma, brain swelling/edema and tSAH.

Adolescent↗

Legal decisions affecting the limitation of nutritional support.

The withholding of nutritional support from patients is one of the most controversial issues in modern medical ethics and law. Withholding support from a consenting, terminally ill patient is the simplest case situation to defend, but patients in a persistent vegetative state or irreversible, chronic illness, require more careful deliberation. Regarding this issue, five primary principles have been utilized in legal decision making. These include: futility, autonomy, integrity of health professionals, states interests, balancing benefits versus harm and quality of life. The two landmark legal cases which have set the tone for most other court decisions are Paul Brophy and Nancy Beth Cruzan. Both cases clarified the right of competent adults to refuse nutritional support, even if life-saving. In the Cruzan case, however, states were given the authority to request clear and convincing evidence for the previous wishes of the incompetent patient. In summary, competent patients entering a hospice program should make informed decisions about their desires for feeding, as they do with other treatment decisions. Optimally, those wishes should be codified into an advance directive and a proxy decision maker named. If a patient is not competent, and without previously expressed wishes, immediate family members are usually consulted for what they believe are the patient's best interests. Last, although limitations of care for terminally ill children fall under the same general guidelines as for adults, the "Baby Doe Rules" are a complicating factor.

Coma↗

A medical ethics assessment of the case of Terri Schiavo.

The social, legal, and political discussion about the decision to stop feeding and hydration for Terri Schiavo lacked a medical ethics assessment. The authors used the principles of medical indications, quality of life, patient preference, and contextual features as a guide to medical decision-making in this case. Their conclusions include the following: (a) the use of a feeding tube inserted directly in to the stomach constituted artificial treatment; (b) the treatment prolonged biological life but did not lead to a cure and did not restore health; (c) quality of life was absent for the patient, with no sensation and no motor or cognitive functioning; and (d) by preponderance of medical opinion, she would have chosen not to live in a persistent vegetative state. The authors find the withdrawal of treatment was permissible and correct. It was not a choice between living and dying, but a decision of when to allow dying consistent with the patient's choice.

Adult↗