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G D Borasio

Publications and source records attributed to G D Borasio.

At least 19 recordsLinked to original sources
PubMed2006

Protective effect of metabotropic glutamate receptor inhibition on amyotrophic lateral sclerosis-cerebrospinal fluid toxicity in vitro.

Conflicting results have been reported concerning the toxicity of cerebrospinal fluid from patients with amyotrophic lateral sclerosis (ALS-CSF) when added to neuronal cultures. The possible toxic factor(s) and the exact mode of action (e.g. requirement of glial cells) have not been identified so far. Glutamate is a potential candidate for this toxic effect, since antagonists of ionotropic glutamate receptors have been shown to attenuate ALS-CSF toxicity. We studied the effects of ALS-CSF on mixed and motoneuron-enriched chick embryonic spinal cord cultures. We found a toxic action of ALS-CSF in both culture types which could not be attenuated by 5 kDa-filtration or 15 min 90 degrees C heating. Nevertheless, the metabotropic glutamate receptor (mGluR) group I antagonist 1-aminoindan-1,5-dicarboxylic acid, but also the group I agonist (s)-3,5-dihydroxyphenylglycine (DHPG) exerted protective effects against ALS-CSF toxicity. In this experimental setting, DHPG may functionally act via a receptor blockade due to sustained activation. No protective effect was seen with the mGluR group III inhibitor (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). Addition of DHPG did not increase the protective action of the AMPA inhibitor 6-chloro-4-hydroxyquinoline-2-carboxylic acid (6-CKU). Addition of l-glutamate did not mimic these toxic ALS-CSF effects in motoneuron-enriched cultures. Our experiments demonstrate that ALS-CSF toxicity is mediated by a small heat-resistant molecule which may act directly on neurons. Since blockade of group I mGluRs exerts a protective effect, the possibility of targeting these mGluRs pharmacologically in motoneuron disease should be kept in mind.

Aged↗
PubMed2006

A clinical interview assessing cancer patients' spiritual needs and preferences.

We conducted a phase-I study to test the practicability and usefulness of a short (15-30 min) clinical interview for the assessment of cancer patients' spiritual needs and preferences. Physicians assessed the spirituality of their patients using the semi-structured interview SPIR. The interview focuses on the meaning and effect of spirituality in the patient's life and coping system. Visual Analogue Scales (VAS) and Questionnaires were completed following the interview for rating whether SPIR had been helpful or distressing, and to what extent spirituality seemed important in the patient's life and in coping with cancer disease. Thirty oncological outpatients who all agreed to participate were included. The majority wanted their doctor to be interested in their spiritual orientation. Patients and interviewing physicians evaluated the SPIR interview as helpful (patients mean 6.76 +/- 2.5, physicians 7.31 +/- 1.9, scale from 0 to 10) and non-distressing (patients 1.29 +/- 2.5, physicians 1.15 +/- 1.3, scale from 0 to 10). Following the interview, doctors were able to correctly gauge the importance of spirituality for their patients. Patients who considered the interview as very helpful (VAS > 7) were more often female (P = 0.002). There were no differences between patients who evaluated the SPIR as very helpful and those who did not, as far as diagnosis, educational level or belonging to a religious community were concerned. The present study shows that a short clinical assessment of cancer patients' spirituality is well received by both patients and physicians. The SPIR interview may be a helpful tool for addressing the spiritual domain, planning referrals and ultimately strengthening the patient-physician relationship.

Adaptation, Psychological↗
PubMed2005

EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives.

Despite being one of the most devastating diseases known, there is little evidence for diagnosing and managing patients with amyotrophic lateral sclerosis (ALS). Although specific therapy is lacking, correct early diagnosis and introduction of symptomatic and specific therapy can have a profound influence on the care and quality of life of the patient and may increase survival time. This document addresses the optimal clinical approach to ALS. The final literature search was performed in the spring of 2005. Consensus recommendations are given graded according to the EFNS guidance regulations. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. People affected with possible ALS should be examined as soon as possible by an experienced neurologist. Early diagnosis should be pursued and a number of investigations should be performed with high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with vital capacity < 50%. Non-invasive positive pressure ventilation improves survival and quality of life but is underused. Maintaining the patients ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be fully discussed early with the patient and relatives respecting the patients social and cultural background.

Amyotrophic Lateral Sclerosis↗
PubMed2004

Individual quality of life of patients undergoing autologous peripheral blood stem cell transplantation.

BACKGROUND: Most quality-of-life (QoL) studies in autologous Peripheral Blood Stem Cell Transplantation (PBSCT) are descriptive and concentrate on symptom severity and functional deficits. The aim of this study is to compare individual QoL (iQoL) with health-related QoL (hrQoL) and functional status of patients before high-dosed therapy/PBSCT. PATIENTS AND METHODS: Multiple Myeloma, non-Hodgkin's Lymphoma and other tumor patients were asked to complete the following measures before high-dosed therapy/PBSCT: the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire Core 30 (QLQ-C30), and the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW), a patient-generated instrument which allows the patients to nominate the five most important domains (cues) for their present QoL. The SEIQoL-DW assessment generates: (1) a global QoL score (SEIQoL-INDEX), calculated as Sigma(levelsxweights); (2) the current overall QoL, rated on a visual analogue scale (VAS). Additional measures included demographic data, clinical disease status of remission and Karnofsky's index. RESULTS: Seventy-nine patients completed both types of questionnaires. The QoL domains nominated by the patients were assigned to groups (aggregated cues), the most frequent of which were family (89%), hobbies/pastimes (74%), health (physical, including mobility) (70%), profession/occupation (51%), social life/friends (47%) and marriage/partnership (33%). There was no correlation between the SEIQoL-DW total scores and the EORTC QLQ-C30 scale or the Karnofsky index. CONCLUSION: Individual QoL as assessed by the SEIQoL-DW is unrelated to standard health-status measures such as the EORTC QLQ-C30 or the Karnofsky index. Patient-perceived iQoL in PBSCT seems to depend largely on areas others than health and physical functioning, with the family playing a prominent role.

Activities of Daily Living↗
PubMed2004

[Attitudes towards patient care at the end of life. A survey of directors of neurological departments].

In view of the increasing importance of palliative medicine and end-of-life care of neurological patients, a survey from the American Academy of Neurology was translated in a validated fashion and sent to all medical directors of neurological departments in Germany. The topics of the survey comprised-based on clinical scenarios-the withdrawal or withholding of life-sustaining measures, physician-assisted suicide (PAS) and euthanasia, advance directives and health care proxies, principles of palliative care, and ethical and legal questions in end-of-life care. Of 411 directors of departments, 152 participated in the survey. Almost all respondents support a patient's right to refuse life-sustaining treatment. Thirty-two percent think it is illegal to administer analgesics in doses that risk respiratory depression. Forty-five percent believe that treating terminal dyspnea with morphine is the same as euthanasia. Despite the fact that 88% of the respondents regard advance directives as helpful, only an average of 4% of their patients have completed one. About one third of the respondents have been confronted with a request by patients for PAS or euthanasia. Thirty-five percent believe that PAS should be made explicitly legal for terminally ill patients. Forty-six percent of the respondents believe that their training in end-of-life care was insufficient, and 91% express interest in education programs on palliative care.

Attitude of Health Personnel↗
PubMed2002

Recombinant human insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Trophic factors, including recombinant human insulin-like growth factor I have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis. Randomised clinical trials of recombinant human insulin-like growth factor I in amyotrophic lateral sclerosis to date have yielded conflicting results. OBJECTIVES: The main objective of this review was to examine the efficacy of recombinant human insulin-like growth factor I in amyotrophic lateral sclerosis. Occurrence of adverse events has also been reviewed. SEARCH STRATEGY: A search was carried out using the Cochrane Neuromuscular Disease Group register for randomised clinical trials of recombinant human insulin-like growth factor I in amyotrophic lateral sclerosis. Enquiries were also made of authors of randomised clinical trials as well as the manufacturers of recombinant human insulin-like growth factor I regarding any other randomised clinical trials which had not yet been published. SELECTION CRITERIA: Types of studies: all randomised controlled clinical trials involving recombinant human insulin-like growth factor I treatment of amyotrophic lateral sclerosis. TYPES OF PARTICIPANTS: Adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. Types of interventions: Treatment with recombinant human insulin-like growth factor I or placebo. Types of outcome measures: Primary: Change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score with 0.1mg/kg/day of recombinant human insulin-like growth factor I after nine months treatment. Secondary: Change in AALSRS with recombinant human insulin like growth factor I 0.1mg/kg/day and 0.05mg/kg/day at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: We identified two randomised clinical trials. Each reviewer graded them for methodological quality. Data were extracted and entered by the lead reviewer and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. MAIN RESULTS: The primary outcome measure was change in disease progression as determined by the Appel ALS Rating Scale total score with 0.1 mg/kg/day of recombinant human insulin-like growth factor I subcutaneously after nine months treatment. The level of significance was lower in the European trial which compared 59 patients on placebo with 124 on insulin-like growth factor I 0.1 mg/kg/day (weighted mean difference -3.30, 95%CI -8.68 to 2.08) than in the North American trial which compared 90 patients on placebo with 89 on recombinant human insulin-like growth factor I 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day (weighted mean difference -6.00, 95%CI -10.99 to -1.01). The combined analysis from both randomised clinical trials showed a weighted mean difference of -4.75 (95% CI -8.41 to -1.09) favouring the treated group. The secondary outcome measures showed similar trends favouring recombinant human insulin-like growth factor I but these did not reach significance at the five per cent level. Similarly the data with the 0.05mg/kg/day dose showed trends favouring recombinant human insulin-like growth factor I at all time points but did not reach significance at the five per cent level at any point. Evaluation of adverse events showed an increased risk of injection site reactions/inflammation with recombinant human insulin-like growth factor I (relative risk 2.53, 95% CI 1.40 to 4.59). The drug was otherwise safe and well tolerated. REVIEWER'S CONCLUSIONS: Recombinant human insulin-like growth factor I may be modestly effective but the evidence currently available is insufficient for a definitive assessment. Further randomised clinical trials need to be done.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Patients' assessment of quality of life instruments: a randomised study of SIP, SF-36 and SEIQoL-DW in patients with amyotrophic lateral sclerosis.

The evaluation of quality of life (QoL) plays an increasingly important role in clinical research and drug trials in ALS. However, most of the scales employed so far are based on a fixed external value system, and may therefore not reflect the patients' subjective perception of QoL accurately. In addition, many ALS patients complain about the psychological distress inflicted by QoL questionnaires which focus on functional status, as they constantly remind patients of their deterioration. We therefore asked 42 ALS patients to assess, using visual analogue scales, their subjective perception of the validity of three QoL instruments as well as the emotional distress caused by them. The scales were: the Sickness Impact Profile (SIP), the Short Form 36 (SF-36), and the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW). Patients were examined at least three times at two-month intervals. The SIP was filled out by all patients, the SF-36 and the SEIQoL-DW were assigned at random. The validity of the SEIQoL-DW was rated higher than that of the SIP (p<0.001) and of the SF-36 (p<0.001). The SIP imparted a higher emotional distress to patients than the SEIQoL-DW (p<0.005), with a trend in the same direction for the SF-36 (p=0.082). The most frequently mentioned QoL-relevant domains in the SEIQoL-DW were family (100%), health (53%), and profession (50%). These results should prompt further discussion and investigation on the most appropriate way to assess QoL in patients with ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2001

The use of alternative medicine by patients with amyotrophic lateral sclerosis.

The use of complementary and alternative medicine (CAM) is increasing in all industrialised countries, especially in patients with chronic and incurable diseases. However, no data are available on the use of CAM by patients with amyotrophic lateral sclerosis (ALS). The German Association for Neuromuscular Diseases (DGM) mailed out a questionnaire on CAM to 350 ALS patients, 171 of whom completed and returned the survey (response rate 49%). The use of CAM was reported by 92 patients (54%). There were no significant demographic differences between users and nonusers. The patients used 73 different methods or substances; some tried up to 11 different treatments. The most widely used methods were: acupuncture (47%), homeopathy (40%), naturopathy (24%) and esoteric treatments (20%). The lower the patients' expectations from CAM, the better was the subjectively perceived effect. In most cases (60%), alternative treatments were performed by a physician. Patients spent on average 4000 (approximately US$4500) on CAM, generally without reimbursement. CAM is most often used in addition to conventional treatments and may be part of the patients' coping strategy. Open communication between patients and physicians is essential to warn the patients of medically or financially hazardous treatments. Future research should look at the possible palliative effects of CAM on symptom control and quality of life of patients and families.

Adult↗
PubMed2001

Immunosuppressant FK506 does not exert beneficial effects in symptomatic G93A superoxide dismutase-1 transgenic mice.

The immunosuppressant drug FK506 has been shown to exert neuroprotective effects in various model systems via inhibition of the protein phosphatase calcineurin (CN). The enzyme Cu/Zn-superoxide dismutase (SOD1), which is mutated in a familial form of amyotrophic lateral sclerosis (ALS), is an endogenous regulator of CN. Altered function of CN may therefore be involved in the pathogenesis of ALS. We tested FK506 in a transgenic mouse model expressing mutated SOD1 for potential beneficial effects. This treatment, initiated after onset of symptoms, did not cause a reduction in the decline of motor function nor did it prolong survival. These results argue against a crucial role of CN in the process leading to motoneuronal degeneration in SOD1-mutated mice.

Amino Acid Substitution↗
PubMed2001

Glial cells of the spinal cord and subcortical white matter up-regulate neuronal nitric oxide synthase in sporadic amyotrophic lateral sclerosis.

Several studies have suggested that excessive generation of nitric oxide (NO) may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). Recently, a selective induction of the neuronal isoform of nitric oxide synthase (nNOS) in glial cells has been reported in an animal model of familial ALS. We therefore examined in postmortem tissue the expression of nNOS in patients with sporadic ALS and patients without any history of neurological disease. Using immunohistochemistry, we found an up-regulation of nNOS in glial cells of the spinal cord and subcortical white matter in ALS patients compared to controls. The enhanced glial nNOS expression seen in ALS patients could conceivably contribute to motoneuronal degeneration through NO-mediated cytotoxic effects.

Aged↗
PubMed2001

The course of the terminal phase in patients with amyotrophic lateral sclerosis.

The fear of "choking to death" is on the mind of most patients suffering from amyotrophic lateral sclerosis (ALS). So far, however, there have been no systematic surveys concerning the dying phase in a general ALS population. We therefore performed a structured telephone interview with the relatives of 121 patients who died from ALS and were followed by the Motor Neuron Outpatient Clinic of the Department of Neurology, University of Munich, Germany. These data are compared with those obtained by a retrospective analysis of medical records of 50 ALS patients who were followed by the Wisdom Hospice, Rochester, UK. The data show that most ALS patients (Germany 88%, UK 98%) died peacefully, and no patient "choked to death". The symptoms most frequently reported for the last 24 hours were dyspnoea, coughing, anxiety and restlessness. Around half (G 55%, UK 52%) of the patients died at home. The main palliative measures in place during the terminal phase were: home mechanical ventilation (G 21%, UK 0%), percutaneous endoscopic gastrostomy (G 27%, UK 14%), morphine (G 27%, UK 82%) and benzodiazepines (G 32%, UK 64%). The use of these palliative measures was judged to be beneficial by almost all relatives. These data support the hypothesis of a peaceful death process in ALS and should be communicated to patients and their relatives, at the latest after the onset of dyspnoea, to relieve unwarranted fears.

Adult↗
PubMed2001

[Neuropsychiatric symptoms in palliative care].

Up to 80% of patients in palliative care suffer from neurological and/or psychiatric symptoms. For many of those symptoms, there are effective treatment options which should be known to the treating physician. The following article reviews clinical, etiological and diagnostic aspects as well as treatment options. For this, a systematic literature search is combined with clinical experience. Pure motor restlessness often is caused by aggravated physical symptoms. Delirium paradoxically often is reversible, even in the palliative setting, but may also be irreversible and a sign of impending death. Fear and depression must not be overlooked as they may effectively be treated. Suicidal ideation may be dealt with without transfer to a psychiatric ward. Physician assisted suicide is critically discussed.

Humans↗
PubMed2001

Palliative care in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disease in adults. The clinical picture consists of generalized fasciculations, progressive atrophy and weakness of the skeletal muscles, spasticity and pyramidal tract signs, dysarthria, dysphagia, and dyspnea. Pseudobulbar affect is common. Disease-specific treatment options are still unsatisfactory. Therapeutic nihilism is not justified as a large array of palliative measures available to enhance the quality of life of patients and their families. Because of its clinical characteristics, ALS represents a paradigm for palliative care in neurological diseases. Numerous projects are being undertaken worldwide in an effort to enlarge the evidence base for palliative interventions in ALS. Palliative care in ALS is a multidisciplinary effort requiring careful coordination. An open and empathic disclosure of the diagnosis is essential. Nutritional deficiency caused by dysphagia can be relieved by a percutaneous endoscopic gastrostomy. Respiratory insufficiency can be effectively treated by non-invasive home mechanical ventilation. The terminal phase of the disease should be discussed at the latest when symptoms of dyspnea appear, in order to prevent unwarranted fears of "choking to death." Psychological and spiritual care of patients and families are important. Collaboration with hospice institutions and completion of advance directives can be of invaluable help in the terminal phase.

Amyotrophic Lateral Sclerosis↗
PubMed2001

A case of amyotrophic lateral sclerosis with a very slow progression over 44 years.

We report on a patient whose neurological and neurophysiological findings fulfil the El Escorial criteria for definite amyotrophic lateral sclerosis (ALS), and who is still alive 44 years after the initial diagnosis. Pertinent differential diagnoses were excluded on clinical and/or genetic grounds. Our patient has no afflicted relatives and her SOD1 testing was negative, thus allowing us to classify her form of ALS as sporadic. Informing ALS patients of the existence of documented cases with long-term survival can be a means of fostering hope when delivering the diagnosis.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Clinical characteristics and management of ALS.

Amyotrophic lateral sclerosis (ALS) is the most common form of degenerative motor neuron disease in adulthood. The clinical picture was accurately described by Charcot over 125 years ago and consists of generalized fasciculations, progressive atrophy and weakness of the skeletal muscles, spasticity and pyramidal tract signs, dysarthria, dysphagia, and dyspnea. Pseudobulbar affect is common. Disease-specific treatment options are still unsatisfactory. However, therapeutic nihilism is not justified as a large array of palliative measures is available to enhance the quality of life of patients and their families. Palliative care in ALS is a multidisciplinary effort requiring careful coordination. An open and frank disclosure of the diagnosis is of paramount importance. Nutritional deficiency due to pronounced dysphagia can be relieved by a percutaneous endoscopic gastrostomy. Respiratory insufficiency can be effectively treated by noninvasive home mechanical ventilation. The terminal phase of the disease should be discussed, at the latest, when symptoms of dyspnea appear in order to prevent unwarranted fears of "choking to death." Collaboration with hospice and completion of advance directives can be of invaluable help in the terminal phase.

Adult↗
PubMed2001

ALS center reports.

Explore the source record for details and available documents.

Academic Medical Centers↗
PubMed2001

Standards of palliative care for patients with amyotrophic lateral sclerosis: results of a European survey.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) may be viewed as a paradigmatic disease for palliative care in neurodegenerative disorders. However, standards of care for ALS are known anecdotally to differ between and even within countries. METHOD: A survey was conducted among the members of the European ALS Study Group on standards of palliative care in the clinical management of patients with ALS and their families, by means of a questionnaire of 111 questions in the following areas: giving the diagnosis, treatment of symptoms, nutrition, community services, respiratory support, and terminal care. Of 110 questionnaires sent out, 73 (66%) were completed and returned from 18 countries, including all major ALS centres in Europe. RESULTS: The main areas of consensus included: presenting the diagnosis in the presence of a relative (85%) and offering a short-term follow-up (90%), regular weight checks (82%), availability of percutaneous endoscopic gastrostomy (PEG) (94%), and discussion of respiratory issues (90%). The main differences between centres concerned symptomatic drug treatment, availability of services, ventilation and terminal care. An additional survey shows considerable interest by the centres in palliative care trials. CONCLUSION: Great efforts are made by the centres to offer the best possible palliative care to ALS patients. The discrepancies in the type of care offered might be resolved by adopting common standards, on the basis of available evidence and mutual consensus. Several areas of ALS patient care would benefit from controlled studies to establish an evidence base for treatment decisions.

Amyotrophic Lateral Sclerosis↗