Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective evaluation of emergency portacaval shunt has been conducted during a 12 year period in 138 unselected, consecutive patients with alcoholic cirrhosis and bleeding esophageal varies. An extensive diagnostic evaluation was completed within seven hours of hospital admission, and the shunt operation was undertaken within a mean of 8.5 hours. Follow-up study was conducted in a special clinic, and the current status of 97.1 per cent of the patients had jaundice, ascites or encephalopathy alone or in combination on admission. Systemic intravenous administration of posterior pituitary extract temporarily controlled the hemorrhage in 94 per cent of the patients, and the emergency portacaval shunt promptly and permanently controlled the varix bleeding in 96 per cent of the patients. Contrary to recent proposals, patients with the highest portal perfusion pressure and, presumably, the largest hepatopetal portal flow had the highest survival rate and those who were presumed from pressure measurements to sustain the smallest portal flow diversion from the shunt had the lowest survival rate. The operative survival rate was 51 per cent, the predicted seven year survival rate for those operated upon seven or more years ago was 42.5 per cent. Encephalopathy requiring dietary protein restriction developed at some time in 17 per cent of the survivors. Sixty per cent of the survivors abstained from alcohol, and 53 per cent resumed gainful employment or full time housekeeping. Preoperative factors that adversely influenced survial rate were ingestion of alcohol within one month of bleeding, ascites, severe muscle-wasting and a small liver. Postoperatively, the single most important factor that compromised long term survival was resumption of alcoholism. In comparisons with our previous prospective studies, emergency portacaval shunt resulted in a significantly greater long term survival rate than did either emergency medical therapy or emergency varix ligation, followed by elective shunt. It is concluded that emergency portacaval shunt is the most effective treatment of bleeding esophageal varices in patients with alcoholic cirrhosis. Criteria for exclusion of those patients who are unlikely to derive long term benefits from portacaval shunt remain to be defined by further studies.
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PMID:Portacaval shunt as emergency procedure in unselected patients with alcoholic cirrhosis. 115 15

Plasma amino acid levels were measured following oral glycine loading in 43 patients with motor neurone disease (MND), eight normal subjects and 18 neurological disease controls with wasting or spasticity from a variety of other causes. Levels at baseline and 1.5 h after loading did not differ, but at 4 h, plasma glycine levels in MND patients remained significantly higher than in normal and neurological controls (P < 0.013). Cerebrospinal fluid glycine levels, which were maximal at 2.5 h, were also significantly higher in MND patients than neurological controls (P < 0.04). These observations suggest a defect of glycine 'housekeeping' in the central nervous system in MND which may be relevant to the pathogenesis of the disease.
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PMID:Abnormal glycine metabolism in motor neurone disease: studies on plasma and cerebrospinal fluid. 841 Aug 84

There have been a number of reports suggesting inhibition of prostaglandin production may impact tumor-mediated wasting and levels of associated humoral factors such as hypercalcemia. These reductions were achieved using traditional nonsteroidal anti-inflammatory drugs (NSAIDs), which are often contraindicated in cancer patients. This is especially true during chemotherapeutic regimens due to concerns of bleeding from gastrointestinal and hematopoietic toxicities associated with inhibition of the housekeeping cyclooxygenase enzyme COX-1. Here, we report that celecoxib, one of the new class of selective COX-2 inhibitors, has the potential to reverse tumor-mediated wasting and associated humoral factors such as interleukin (IL)-6 and hypercalcemia in preclinical models of cachexia. Tumor bearing mice in late stage cachexia regained weight within days of the start of celecoxib treatment. Two models were tested. The first was the Colon 26 (Col26) syngeneic murine model that induces high levels of circulating IL-6 and hypercalcemia. The second was the human head and neck 1483 HNSCC xenograft model, which is less inflammatory and produces less prostaglandin than Col26. Despite the observation that no significant impact on tumor growth was observed between vehicle and celecoxib-treated animals over the course of the studies, celecoxib rapidly reversed weight loss in both cachectic models. With the added safety of celecoxib over traditional NSAIDs, these results suggest a possible therapeutic use for celecoxib for treating tumor-mediated wasting.
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PMID:Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting. 1471 36

Akt activation assists tumor cell survival and promotes resistance to chemotherapy. Here we show that constitutively active Akt (CA-Akt) cells are highly sensitized to cell death induced by nutrient and growth factor deprivation, whereas dominant-negative Akt (DN-Akt) cells have a high rate of survival. The content of autophagosomes in starved CA-Akt cells was high, while DN-Akt cells expressed autophagic vacuoles constitutively, independently of nutrition conditions. Thus Akt down-regulation and downstream events can induce autophagosomes which were not directly determinants of cell death. Biochemical analysis in Akt-mutated cells show that (i) Akt and mTOR proteins were degraded more rapidly than the housekeeping proteins, (ii) mTOR phosphorylation at position Thr(2446) was relatively high in DN-Akt and low in CA-Akt cells, induced by starvation in mock cells only, which suggests reduced autoregulation of these pathways in Akt-mutated cells, (iii) both protein synthesis and protein degradation were significantly higher in starved CA-Akt cells than in starved DN-Akt cells or mock cells. In conclusion, constitutively active Akt, unable to control synthesis and wasting of proteins, accelerates the death of starved cells.
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PMID:Cell survival under nutrient stress is dependent on metabolic conditions regulated by Akt and not by autophagic vacuoles. 1764 59

Dominantly inherited, missense mutations in the widely expressed housekeeping gene, GARS1, cause Charcot-Marie-Tooth type 2D (CMT2D), a peripheral neuropathy characterised by muscle weakness and wasting in limb extremities. Mice modelling CMT2D display early and selective neuromuscular junction (NMJ) pathology, epitomised by disturbed maturation and neurotransmission, leading to denervation. Indeed, the NMJ disruption has been reported in several different muscles; however, a systematic comparison of neuromuscular synapses from distinct body locations has yet to be performed. We therefore analysed NMJ development and degeneration across five different wholemount muscles to identify key synaptic features contributing to the distinct pattern of neurodegeneration in CMT2D mice. Denervation was found to occur along a distal-to-proximal gradient, providing a cellular explanation for the greater weakness observed in mutant Gars hindlimbs compared with forelimbs. Nonetheless, muscles from similar locations and innervated by axons of equivalent length showed significant differences in neuropathology, suggestive of additional factors impacting on site-specific neuromuscular degeneration. Defective NMJ development preceded and associated with degeneration, but was not linked to a delay of wild-type NMJ maturation processes. Correlation analyses indicate that muscle fibre type nor synaptic architecture explain the differential denervation of CMT2D NMJs, rather it is the extent of post-natal synaptic growth that predisposes to neurodegeneration. Together, this work improves our understanding of the mechanisms driving synaptic vulnerability in CMT2D and hints at pertinent pathogenic pathways.
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PMID:Developmental demands contribute to early neuromuscular degeneration in CMT2D mice. 3270 32