Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Hyatt Regency skywalk collapse (July 17, 1981) provided the emergency medical services system of Kansas City, Missouri, with its greatest challenge ever. Utilizing an EMS-based, centralized, city-wide disaster plan, the rescue operation encountered 113 dead and 188 multiply traumatized patients. The rescue operation could be divided into three areas: initial response, onset triage, and delayed extrication. Success of the operation was credited to several factors, including the centralized urban location of the collapse, short patient transport times, centralized ambulance dispatch, availability of ALS vehicles and personnel to the scene, and mutual aid response. Short-comings of the rescue that became apparent on critical review of the response included poor communications at the scene, lack of physician bystander control, and the need for identification of key personnel at the site. Success in responding to the health care needs of a disaster included a flexible and well-organized disaster response plan as well as the support of a health care system capable of picking up the pieces of the psychological aftermath.
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PMID:The Hyatt Regency skywalk collapse: an EMS-based disaster response. 662 60

Intravenous norepinephrine infusion test was performed in eight patients with amyotrophic lateral sclerosis (ALS) supported by respirators and nine control subjects, to examine alpha-adrenoceptor function of peripheral resistant blood vessels. Baseline plasma norepinephrine concentrations in ALS patients were significantly higher than those in control subjects, indicating basal sympathetic hyperactivity (normal 218.2 +/- 59.7 pg/ml; ALS 450.0 +/- 288.4 pg/ml). The stimulus-response curves in the patients were similar to those in control subjects, and there were no significant differences between mean gains of the stimulus-response curves in both groups (normal 18.7 +/- 5.5; ALS 15.2 +/- 11.2). However, three ALS patients, two of whom had circulatory fluctuation and sympathetic hyperactivity, revealed lower gain levels than the mean minus 2 SD in control subjects (4.7, 1.1 and 3.7). This indicates hyposensitivity or down-regulation of the alpha-adrenoceptor function of peripheral blood vessels in these ALS patients. For early detection of sympathetic hyperactivity and prediction of circulatory collapse, it would be useful to measure the plasma norepinephrine concentration and the gain of the norepinephrine infusion curve in respirator-dependent ALS patients.
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PMID:Hyposensitivity of peripheral alpha-adrenoceptors in respirator-dependent amyotrophic lateral sclerosis assessed by intravenous norepinephrine infusion. 754 19

Circulatory collapse and sudden death was defined retrospectively as one of the major critical problems among 23 respirator-dependent patients with amyotrophic lateral sclerosis (ALS). Six cases died from sudden cardiac arrest or anoxic encephalopathy following the circulatory collapse. In five among the six cases, sudden death or cardiac arrest occurred during sleep at night. Eight cases had had episodes of marked fluctuation of blood pressure before death, including paroxysmal elevation of blood pressure and heart rate, and successive sudden pressure fall without compensatory tachycardia. The spells of hypotension often occurred during sleep. In addition, the prospective study of diurnal variation of blood pressure, heart rate, plasma norepinephrine and plasma renin activity in nine respirator-dependent ALS patients showed continuous tachycardia and more remarkable nocturnal decrease of blood pressure compared with the control subjects. Plasma norepinephrine levels were constantly higher in the ALS patients particularly in a daytime. These indicate the continuous sympathetic hyperactivity in ALS. We discuss the cause of the circulatory collapse and sudden death in the respirator-dependent ALS patients in terms of the autonomic dysregulatory mechanism or the sympathetic hyperactivity.
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PMID:Circulatory collapse and sudden death in respirator-dependent amyotrophic lateral sclerosis. 793 21

Outcome after prehospital cardiac arrest was examined in the EMS system of Bonn, a midsized urban community, and presented according to the Utstein style. The data were collected from January 1st, 1989 to December 31st, 1992 by the Bonn-north ALS unit, which serves 240,000 residents. Fifty-six patients suffered from cardiac arrest of non-cardiac aetiology and were excluded; 464 patients were resuscitated after cardiac arrest of presumed cardiac aetiology (incidence of CPR attempts: 48.33 per year/100,000 population). The collapse was unwitnessed, bystander witnessed or EMS personnel witnessed in 178, 214 or 72 patients, respectively. In these subgroups discharge rates and 1-year survival accounted for 7.3% (4.5%), 22.9% (15.9%) and 16.7% (11.1%), respectively. Thirty-four patients were discharged without neurological deficits (cerebral performance category 1: CPC 1), 22 and nine patients scored CPC 2 or CPC 3, respectively. Nine patients were comatose (CPC 4) when they were discharged and remained in this state until they died. Of the 50 1-year survivors 35 lived without neurological deficit, eight demonstrated mild (CPC 2) and five severe (CPC 3) cerebral disability at 1-year after resuscitation, and, finally, two patients remained comatose for more than 1 year. The Utstein template recommends the selection of patients who were found in VF after bystander witnessed collapse. In our cohort 118 patients met these criteria. Of them 41 (35%) could be discharged from hospital and 28 (24%) lived more than 1 year. The comparison of our data with those from double-response EMS systems of other communities revealed that, in midsized urban and suburban communities the highest discharging rates could be achieved. Our study demonstrated that survival depends crucially on short response intervals and life support which will be performed by well-trained emergency technicians, paramedics and physicians.
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PMID:One-year survival after out-of-hospital cardiac arrest in Bonn city: outcome report according to the 'Utstein style'. 904 96

To investigate the molecular mechanisms of the 'gain of toxic function' of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (Ala 4 --> Thr, Gly 85 --> Arg, Gly 93 --> Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant (mt) Cu/Zn SODs, but not in cells expressing wt Cu/Zn SOD. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mt Cu/Zn SODs promote the formation of aggregates which are toxic to cells.
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PMID:Formation of granular cytoplasmic aggregates in COS7 cells expressing mutant Cu/Zn superoxide dismutase associated with familial amyotrophic lateral sclerosis. 985 58

To investigate the molecular mechanism of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (A1a4Thr, Gly85Arg, Gly93Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant Cu/Zn SODs, but not in cells expressing mutant Cu/Zn SODs. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mutant Cu/Zn SODs promote the formation of aggregates which are toxic to cells.
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PMID:[Familial amyotrophic lateral sclerosis associated with mutant Cu/Zn superoxide dismutase as a conformational disease]. 1079 Oct 98

A 71-year-old man developed dysarthria and difficulty of swallowing in December 1997. He was diagnosed as having the bulbar type of amyotrophic lateral sclerosis (ALS). In November 1998, he was admitted to our hospital to undergo treatment for bulbar palsy and respiratory discomfort. In January 1999, ventilatory support (synchronous intermittent mandatory ventilation) during sleep at night was initiated. Severe progressive hypotension and loss of consciousness were observed soon after the start of artificial respiration, and both symptoms disappeared after artificial respiration was discontinued. This phenomenon was observed consistently during ventilatory support, while unpleasant stimuli such as bronchoscopy and replacement of the cannula tube induced severe hypertension. To clarify the mechanism of underlying these abnormal changes in blood pressure, autonomic function tests were performed while awake during the daytime. Ventilatory support induced a drop in blood pressure accompanied by a decrease in influx speed to the right ventriculum, the latter of which suggested a reduction in venous return. These values returned to the baseline following detachment of the ventilator. A 60 degrees head-up tilt (HUT) angle and standing from a supine position produced orthostatic hypotension, the latter of which was accompanied by a compensatory increase in pulse rate. The basal supine plasma noradrenaline (NA) level was high and the HUT showed a slight elevation of NA. The basal supine plasma arginine vasopressin (AVP) level was within the normal range, whereas the AVP level did not increase during HUT. Urinary secretion rates of NA and 3-methoxy-4-hydroxy-phenylglycol were elevated. A cold pressor test demonstrated reflex hypertension. The oculovagal reflex, coefficient of variation of R-R intervals. (CVR-R) and increase in pulse rate in response to atropine administration were within the normal range. The combination of midodrine, L-dihydroxyphenylserine (DOPS) and increasing intravascular volume via continuous intravenous drip infusion relieved the circulatory collapse during artificial respiration. In conclusion, the present case of ALS had sympathetic hyperactivity, somatosympathetic reflex and dysregulation of the baroreflex arc. Degeneration of central autonomic network, including the hypothalamus and the central nucleus of the amygdala, which has been shown in some ALS patients, might underlie the autonomic abnormalities in this patient.
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PMID:[A case of amyotrophic lateral sclerosis presenting with circulatory collapse during artificial respiration]. 1125 87

We assessed subclinical sympathetic hyperactivity in amyotrophic lateral sclerosis (ALS) patients, which might be followed by an autonomic spell leading to circulatory collapse, or sudden death as the disease progresses, and investigated the effect of tamsulosin hydrochloride (TSHC) on sympathetic hyperactivity. We measured the plasma norepinephrine (NE) concentrations of 41 ALS patients and 10 normal controls. TSHC, a selective alpha 1 blocker. was then administered to 10 ALS patients who had high plasma NE and to the 10 normal controls. Subsequent plasma NE change was evaluated for the possible alleviating effect of TSHC on subclinical sympathetic hyperactivity in ALS. Plasma NE was high in 20 of the ALS patients (48.8%), but had no relation to respiratory problems, which supports the previous speculation that plasma NE increases in ALS are not secondary to respiratory deficit, but reflect the primary pathomechanism of the disease. ALS patients showed a marked decrease in the NE concentration after TSHC administration, whereas there was no change in the controls. In conclusion, TSHC may be useful for suppressing central sympathetic hyperactivity, presumably the primary pathomechanism in ALS, and for preventing autonomic spells during the advanced stage of the disease.
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PMID:Effect of tamsulosin hydrochloride on sympathetic hyperactivity in amyotrophic lateral sclerosis. 1147 51

Gain-of-function mutations of the Cu/Zn superoxide dismutase (SOD1) gene cause dominantly inherited familial amyotrophic lateral sclerosis. The identification of differentially regulated proteins in spinal cords of paralyzed mice expressing SOD1(G93A) may contribute to understanding mechanisms of toxicity by mutant SOD1. Protein profiling showed dysregulation of Stathmin with a marked decrease of its most acidic and phosphorylated isoform, and up-regulation of heat shock proteins 25 and 27, peroxiredoxin 6, phosphatidylinositol transfer protein-alpha, apolipoprotein E, and ferritin heavy chain. Stathmin accumulated in the cytoplasm of 30% of spinal cord motor neurons with fragmented Golgi apparatus. Overexpression of Stathmin in HeLa cells was associated with collapse of microtubule networks and Golgi fragmentation. These results, together with the decrease of one Stathmin isoform, suggest a role of the protein in Golgi fragmentation. Mutant SOD1 co-precipitated and co-localized with Hsp25 in neurons and astrocytes. Mutant SOD1 may thus deprive cells of the anti-apoptotic and other protective activities of Hsp25. Astrocytes contained peroxiredoxin 6, a unique nonredundant antioxidant. The up-regulation of peroxiredoxin 6 probably constitutes a defense to oxidative stress induced by SOD1(G93A). Direct effects of SOD1(G93A) or sequential reactions triggered by the mutant may cause the protein changes.
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PMID:Dysregulation of stathmin, a microtubule-destabilizing protein, and up-regulation of Hsp25, Hsp27, and the antioxidant peroxiredoxin 6 in a mouse model of familial amyotrophic lateral sclerosis. 1550 39

Autophagy constitutes a fundamental survival strategy of cells; its disturbance contributes to the pathogenesis of cancer, liver and immune disease, pathogen infection, myopathies as well as neurodegenerative disorders such as Amyotrophic lateral sclerosis, Parkinson;s, Huntington;s and Alzheimer;s disease. The pathogenesis of neurodegenerative diseases also involves a gradual and progressive loss of neuronal cells. Cells may use different pathways for active self-destruction as reflected by different morphology: while in apoptosis (or "type I") nuclear fragmentation associated with cytoplasmic condensation but preservation of organelles is predominant, autophagic degradation of the cytoplasmic structures preceding nuclear collapse is a characteristic of a second type of programmed cell death (PCD). Linking autophagy to programmed cell death initiated a controversial discussion on how a suggested role of autophagy in cell suicide might meet with its established survival function. To some extent, the diverse morphologies can be associated with distinct biochemical and molecular events [caspase-dependent and -independent death programs, DAP-kinase activity, Ras-expression, induction of autophagy genes, fate of cytoskeleton, among others]. However, there is a broad overlap between cell death pathways. Conceivably, diverse PCD programs emerged during evolution, the conservation of which allows eukaryotic cells a flexible response to physiological or pathological demands.
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PMID:Autophagy--a basic mechanism and a potential role for neurodegeneration. 1641 94


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