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Biomedical subjects

G D Borasio

Publications and source records attributed to G D Borasio.

At least 55 records · Page 3Linked to original sources
PubMed1997

Palliative care in amyotrophic lateral sclerosis.

The poor prognosis of amyotrophic lateral sclerosis (ALS) makes palliative care a challenge for the neurologist. Most disabilities associated with progressive disease can be ameliorated by symptomatic treatment. Prognosis and treatment options should be openly discussed with the patient and his/her relatives. Nutritional deficiency due to pronounced dysphagia can be efficiently relieved by a percutaneous enterogastrostomy. Respiratory insufficiency can be treated by non-invasive ventilation at home, provided the familial environment is supportive. Adequate assistance and palliative treatment in the terminal phase is of paramount importance.

Advance Directives↗
PubMed1997

Palliative therapy in the terminal stage of neurological disease.

As recently pointed out by the American Academy of Neurology, providing adequate palliative care to dying patients is the duty of every neurologist. Because of a lack of relevant articles in the neurological literature, we have compiled current treatment recommendations for the most important symptoms arising in the endstage of neurological diseases. These recommendations include treatment of dyspnea, death rattle, restlessness, pain, thirst, depression, and others. A discussion of difficult decisions is included, e.g., the appropriate extent of fluid substitution or the ethical implications of sedation in the terminal phase. It is hoped that this compilation may provide a basis for future research in palliative therapy in neurology.

Adult↗
PubMed1997

[Recommendations of Bavarian Muscle Centers of the German Neuromuscular Disease Society for home ventilation of neuromuscular diseases of adult patients].

During recent years home ventilation has been shown to be useful for a growing number of patients with neuromuscular diseases and respiratory insufficiency caused by weakness of the respiratory muscles. Despite its technical simplicity, home ventilation leads to a number of social, ethical, medical and infrastructural problems. This consensus paper discusses the special situation of patients with neuromuscular diseases in home ventilation and describes the current thinking in the following topics: (1) definition of home ventilation; (2) aims of home ventilation; (3) indications and preconditions of home ventilation; (4) techniques and forms of home ventilatory support; (5) preparation for and practical questions of home ventilation; (6) stopping home ventilation.

Adult↗
PubMed1997

[Considerations in patient education in amyotrophic lateral sclerosis (ALS)].

Given the relentless progression of amytrophic lateral sclerosis (ALS) and the lack of causative therapy, breaking the news to ALS patients and their families is a daunting task for any physician. Obviously, such a task cannot be standardized. However, it is now recognized to be the first and one of the most sensitive and important steps in palliative care. Information should be offered in a stepwise fashion, in the presence of the patient's family. All questions from the patient should be discussed openly, with emphasis on the positive aspects. Available therapeutic options should be reviewed, pointing out the fact that all symptoms of ALS can be alleviated by palliative therapy. At the onset of dyspneic symptoms, the terminal phase of the disease and the option of mechanical ventilation should be discussed.

Adaptation, Psychological↗
PubMed1997

Amyotrophic lateral sclerosis: lessons in trial design from recent trials.

The recent history of clinical trials in ALS is marked by a great diversity in trial design. This has limited the comparability of the trial results, and has resulted in intense discussions about which parameters should or should not be evaluated when testing a new drug for ALS. This article discusses, without any claim to completeness, some aspects of trial design in relation to past, ongoing and future ALS trials, including: choice of endpoints, measurement of disease progression, assessment of quality of life, placebo-controlled trials, open-label trials, collaboration with the industry, and methods for investigating mechanisms of action of experimental drugs.

Amyotrophic Lateral Sclerosis↗
PubMed1997

A novel SOD1 mutation in an Austrian family with amyotrophic lateral sclerosis.

We report on an Austrian pedigree with autosomal dominant amyotrophic lateral sclerosis (ALS), diagnosed in six patients from two generations. The only surviving clinically affected family member was examined in our ALS clinic. Historical information on other affected individuals was obtained from knowledgeable family members. The mean +/- S.D. age of onset of the disease was 54 +/- 6.9 years, with a range of 43-66 years. The duration of the index patient's disease until death was 8 months. Using single strand conformational polymorphism (SSCP) analysis, we studied the index patient's exons 1, 2 and 4 of the Cu/Zn superoxide dismutase gene (SOD1) on chromosome 21. A variant banding pattern was observed for exon 1. Sequencing studies showed a previously undescribed T to A missense mutation at position 8 in exon 1 of the SOD1 gene. This mutation results in the elimination of an Eco57I restriction site. Whereas the index patient was heterozygous for this restriction site, 50 unrelated healthy controls and an unaffected brother were not. The mutation lies in a region involved in dimer contact in the three-dimensional structure of the SOD1 protein. This region comprises other known sites for ALS-causing mutations.

Adult↗
PubMed1996

p21ras supports the survival of chick embryonic motor neurones.

Various trophic factors present in muscle extract can promote the survival of cultured motor neurones. However, little is known about the signal transduction pathways used in these cells. The proto-oncogene product p21ras has been shown to play an important role in proliferative and differentiative signalling pathways. We report here that cytoplasmic introduction of its oncogenic form, p21ras(G12V), fully supports the in vitro survival of chick embryonic motor neurones. The proto-oncogenic form of p21ras also showed a dose-dependent survival effect, while a C-terminally truncated counterpart of p21ras(G12V) was ineffective. These results suggest an involvement of p21ras in signal transduction pathways leading to motor neurone survival and may be of relevance for the development of therapeutic strategies for motor neurone disease.

Animals↗
PubMed1996

[X chromosomal bulbospinal neuropathy (X-BSN, Kennedy syndrome): an illness with repetitive triplet sequences. Case report, differential diagnosis and molecular genetics aspects].

X-chromosomal recessive bulbospinal neuronopathy (X-BNS, Kennedy's disease) is an important differential diagnosis of amyotrophic lateral sclerosis. We present the data of ten own patients along with a review of the literature on this uncommon disease which is caused by an expanded CAG-repeat in the androgen receptor gene. This mutation probably affects the transcription regulating activity of the androgen receptor in neurons. Signs and symptoms of X-BSN can be derived from partial insensitivity for androgens and a mixed, mainly motor neuronopathy. The clinical diagnosis is based on: 1. lower motor neuron weakness of bulbar and proximal limb muscles with onset in the third to fifth decade, 2. cramps and pronounced fasciculations, particularly of facial muscles, 3. postural tremor, 4. diminished or absent sensory action potentials inspite of only minor sensory impairment, 5. gynecomastia, and 6. infertility, diabetes mellitus and hyperlipoproteinemia in a minority of cases. Unlike amyotrophic lateral sclerosis, disease progression is slow with barely shortened life expectancy, which should be stressed in patient counselling. Causal treatment is as yet unavailable but several aspects of palliative medicine should be considered.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Ras p21 protein promotes survival and differentiation of human embryonic neural crest-derived cells.

We have previously shown that the oncogene product p21 Ras is essential for the survival and neurite outgrowth-promoting activity of nerve growth factor on cultured chick embryonic sensory, but not sympathetic neurons. In order to extend our observations to the human system and to non-neuronal cells, we introduced the oncogenic form of p21 Ras into the cytoplasm of three different types of cultured human embryonic neural crest derivatives (8th-11th gestational week): dorsal root ganglion neurons, sympathetic neurons, and adrenal chromaffin cells. These cells are dependent on nerve growth factor for survival and/or fibre outgrowth in vitro. In dorsal root ganglion neurons, p21 Ras promoted survival and fibre outgrowth which was quantitatively and qualitatively comparable to the nerve growth factor effect (84% vs. 95%, control 18%). Sympathetic neurons showed a similar effect, albeit with a higher background survival (91% vs. 93%, control 58%). On chromaffin cells, which respond to nerve growth factor with pronounced fibre outgrowth in culture, the effect of p21 Ras was again comparable to that of nerve growth factor (35% vs. 30%, control 5%). The survival and fibre outgrowth-promoting effects of p21 Ras on human embryonic dorsal root ganglion neurons, sympathetic neurons and chromaffin cells suggest an involvement of p21 Ras in the intracellular signal transduction of nerve growth factor in human neural crest-derived cell populations.

Cell Differentiation↗
PubMed1995

Postoperative neuropsychological dysfunction and cerebral oxygenation during cardiac surgery.

In 41 patients undergoing cardiac operations with extracorporeal circulation, oxidized cytochrome a,a3(CtO2), deoxygenated hemoglobin (Hb), and oxygenated hemoglobin (HbO2) were measured in brain tissue by near-infrared spectrophotometry (NIRS) intraoperatively. Monitoring also included electroencephalography (EEG) and jugular-bulb venous saturation (SBJO2). All operations were performed using membrane oxygenators, moderate hypothermia (26-28 degrees C) and pH alpha-stat management. During cardiopulmonary bypass (CPB) CtO2 and HbO2) were reduced, reaching minimal values when rewarming was instituted. At the end of the operation CtO2 and HbO2 had regained initial levels. During CPB, arterial PCO2, pH, and temperature were closely related to CtO2 (r = 1000, r = -0.964 and 0.929 respectively; p < 0.001, p < 0.001, and p < 0.003 respectively). Neuropsychological testing by the Mini-Mental-State Test indicated reversible postoperative neuropsychological deficits in four patients. There patients had a lower CtO2 minimum compared to those without these deficits (-4.5 mumol/L v. -0.7 mumol/L; p = 0.036). These findings support the hypothesis that neuropsychological deficits in patients after cardiac surgery can be caused by intraoperative cerebral hypoxia.

Adult↗
PubMed1994

NGF-response of EGF-dependent progenitor cells obtained from human sympathetic ganglia.

Signalling molecules are thought to play a significant role in determining the fate of neural crest progenitor cells. The human sympathetic chain was identified at 6.5, 7.5, 8.2, 10.2 and 11.4 postconception (PC) weeks demonstrating low affinity nerve growth factor (NGF) receptors, and was processed for tissue culture. In the presence of epidermal growth factor (EGF), floating spheres of proliferating progenitor cells were developed in vitro. In the absence of EGF progenitor cells differentiated into tyrosine hydroxylase (TH)-immunoreactive neuronal and TH-negative flat cells. NGF treatment significantly increased neurite outgrowth and survival of TH-immunoreactive cells. The multipotent cells we isolated differ from previously reported sympathoadrenal progenitors in that they give rise to TH immunoreactive neurones precociously sensitive to NGF.

Cell Survival↗
PubMed1994

[Palliative therapy in neurology].

Palliative therapy aims at increasing the quality of life in patients with a terminal illness. This article provides an overview of the available therapeutic options for the most important symptoms occurring in late-stage neurological disease, including restlessness, drowsiness, death-rattle, shortness of breath, pain, seizures, raised intracranial pressure, thirst and hunger.

Cause of Death↗
PubMed1993

Kinetic and structural analysis of the Mg(2+)-binding site of the guanine nucleotide-binding protein p21H-ras.

The coordination and binding of the Mg2+ ion in the nucleotide-binding site of p21 have been investigated using site-directed mutagenesis, kinetic methods, and phosphorous NMR. Mg2+ in the p21.nucleotide.Mg2+ complex appears to be in fast equilibrium with the solvent. The dissociation constant between Mg2+ and the p21.GDP complex was determined to be 2.8 microM. It decreases 30- or 16-fold on substituting Ser-17 or Asp-57 with alanine, respectively, whereas the T35A mutation has no effect. All three mutations influence the dissociation constants and the association and dissociation rate constants of the interaction between guanine nucleotides and p21, but to a different degree. We conclude that Thr-35 is only complexed to Mg2+ in the GTP conformation and both Asp-57 and Ser-17 appear to be critical for both GDP and GTP binding. 31P NMR spectra of the GDP and Gpp(NH)p (guanosine-5'-(beta,gamma-imido)triphosphate) complexes of mutated p21 show a remarkable perturbation of the guanine nucleotide-binding site compared to wild-type protein. The mutant proteins show reduced GTPase rates, which are not stimulated by the GTPase-activating protein GAP. p21(S17A) has been reported to function just as p21(S17N) as a dominant negative inhibitor of normal p21. We find that it inhibits oncogenic p21-induced survival of primary neurons.

Amino Acid Sequence↗
PubMed1993

Involvement of ras p21 in neurotrophin-induced response of sensory, but not sympathetic neurons.

Little is known about the signal transduction mechanisms involved in the response to neurotrophins and other neurotrophic factors in neurons, beyond the activation of the tyrosine kinase activity of the neurotrophin receptors belonging to the trk family. We have previously shown that the introduction of the oncogene product ras p21 into the cytoplasm of chick embryonic neurons can reproduce the survival and neurite-outgrowth promoting effects of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and of ciliary neurotrophic factor (CNTF). To assess the potential signal-transducing role of endogenous ras p21, we introduced function-blocking anti-ras antibodies or their Fab fragments into cultured chick embryonic neurons. The BDNF-induced neurite outgrowth in E12 nodose ganglion neurons was reduced to below control levels, and the NGF-induced survival of E9 dorsal root ganglion (DRG) neurons was inhibited in a specific and dose-dependent fashion. Both effects could be reversed by saturating the epitope-binding sites with biologically inactive ras p21 before microinjection. Surprisingly, ras p21 did not promote the survival of NGF-dependent E12 chick sympathetic neurons, and the NGF-induced survival in these cells was not inhibited by the Fab-fragments. The survival effect of CNTF on ras-responsive ciliary neurons could not be blocked by anti-ras Fab fragments. These results indicate an involvement of ras p21 in the signal transduction of neurotrophic factors in sensory, but not sympathetic or ciliary neurons, pointing to the existence of different signaling pathways not only in CNTF-responsive, but also in neurotrophin-responsive neuronal populations.

Animals↗
PubMed1992

Cerebrovascular complications of bacterial meningitis in adults.

We performed a prospective study of the type, frequency, temporal profile, and prognostic role of cerebrovascular complications in 86 adults with bacterial meningitis. Cerebral angiography was performed in 27 patients (31.4%) who had focal deficits either clinically, on cranial CT, or both, and in patients who had persistent coma without explained cause despite 3 days of antibiotic therapy. Alterations of the vessel systems, including involvement of major arteries at the base of the brain, medium-sized arteries, small vessels, and major sinuses and cortical veins, were present in 13 of the 27 patients who had angiography. Typical cerebrovascular complications were arterial narrowing of the supraclinoid portion of the internal carotid artery; vessel wall irregularities, focal dilatations, and occlusions of distal branches of the middle cerebral artery; focal abnormal parenchymal blush; and thrombosis of the sagittal superior sinus and cortical veins. Prognosis for those patients with cerebrovascular complications was unfavorable. Six patients died, one remained in a vegetative state, four were moderately or slightly disabled, and only two recovered completely. The study showed that angiographically documented cerebrovascular complications are the most frequent intracranial complications in bacterial meningitis of the adult (37.1%) and are major determinants in the prognosis of this disease.

Adult↗