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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most laxatives, if used intermittently in the absence of contraindications, are relatively safe. Bulking agents may diminish absorption of some minerals and drugs, but this is not usually clinically significant. Ispaghula can cause serious allergic reactions. The chronic ingestion of stimulant laxatives has been blamed for the development of the 'cathartic colon', but there are no definitive studies which have demonstrated this. Dantron (danthron) preparations should only be used in older patients and the terminally ill because of the risk of hepatotoxicity with this drug. Oral oxyphenisatine should no longer be used. Senna would appear to be the stimulant laxative of choice during pregnancy and lactation. Bisacodyl is the polyphenolic derivative of choice. Lactulose, sorbitol and lactilol rarely cause significant adverse effects. Magnesium salt laxatives and phosphate enemas can cause serious metabolic disturbances in babies and young children. Liquid paraffin is contraindicated if there is any risk of aspiration. Interference with the absorption of fat soluble vitamins would not appear to be clinically significant. Docusate sodium may potentiate the hepatotoxicity of other drugs, but reports of this are rare. The role of cisapride in constipation has not been established. Antidiarrhoeal drugs are second line drugs whose use is aimed at minimising inconvenience and discomfort. No antidiarrhoeals can be recommended for children under 4 years of age. Loperamide is the drug of choice in older children and adults. The atropine component of diphenoxylate/atropine combinations can cause significant adverse effects. Bismuth salicylate is an inconvenient treatment for travellers' diarrhoea as large frequent doses of the liquid formulation are needed. Some bismuth can be absorbed and there is the potential to cause encephalopathy. Octreotide, methysergide and cholestyramine have a role for specific causes of diarrhoea only. Octreotide is effective in high output states from the small or large bowel, with few adverse effects. Clonidine and lidamidine may have a role in the treatment of chronic diabetic diarrhoea. The role of lidamidine in nondiabetic chronic diarrhoea has not been established.
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PMID:Adverse effects of drugs used in the management of constipation and diarrhoea. 813 86

BW12C79 stabilizes the oxyhemoglobin molecule resulting in a reversible left-shift of the oxygen saturation curve. The activity of a number of bioreductive anticancer drugs, such as mitomycin C, may be enhanced under hypoxic conditions. Twenty-four patients with various malignancies received BW12C79 and mitomycin C. BW12C79 was administered i.v. with a loading dose (20-50 mg/kg) over 1 h followed by a maintenance infusion of 4 mg/kg/h for 5 h. Percentage modification of the oxyhemoglobin (degree of left-shift) was dose related with maximum modification of 56% and was maintained for the duration of maintenance infusion of BW12C79. Hemoglobin electrophoresis showed a fast moving band consistent with the BW12C79-oxyhemoglobin complex. Side effects at the top dose level comprised headache, nausea/vomiting, vein irritation, and myocardial ischemia. One other patient suffered from an acute encephalopathy of unknown etiology a few days following BW12C79. 31P magnetic resonance spectroscopy of exercising calf muscles showed increased breakdown of high energy phosphate stores and a greater reduction in pH. Recovery of the high energy phosphate stores after exercise was slow. These results were consistent with reduced oxygen supply due to either a left shift of the oxygen saturation curve and/or reduced muscle blood flow. BW12C79 did not interfere with the pharmacokinetics of mitomycin C. In conclusion, this phase I study demonstrates the feasibility of achieving a significant left shift in the oxygen saturation curve in cancer patients which is maintained for at least 5 h with acceptable toxicity. The maximum tolerated dose of BW12C79 was 50 mg/kg loading infusion followed by a maintenance infusion of 4 mg/kg/h. Magnetic resonance spectroscopy results were consistent with reduced supply of oxygen to exercising skeletal muscle. BW12C79 may be of potential benefit as an adjunct to bioreductive drugs in the treatment of solid tumors.
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PMID:A phase I study of the left-shifting agent BW12C79 plus mitomycin C and the effect on the skeletal muscle metabolism using 31P magnetic resonance spectroscopy. 824 19

Toxic chemicals in the environment can cause a wide range of neurological disease. High-dose exposures to environmental neurotoxicants have produced encephalopathy in children ingesting chips of lead-based paint, blindness in persons who ingested methanol, blindness and ataxia in persons who consumed organic mercury, spinal cord degeneration and peripheral neuropathy in persons exposed to tri-ortho-cresyl phosphate (TOCP), and Parkinsonism in persons exposed to MPTP or to manganese. Environmental neurotoxicants have also been shown to produce a wide range of subclinical neurotoxic effects, including reduction in intelligence, impairment in reasoning ability, shortening of attention span, and alternation of behavior. The first step in the prevention of environmental neurotoxicity is to test chemicals for their toxic potential. More than 70,000 chemicals are currently in commerce. However, except for pharmaceuticals, fewer than 10% of these chemicals have been tested for neurotoxicity. A logical approach to neurotoxicologic assessment of chemical substances will build on and extend currently available test systems. It will have a tiered structure. The first or screening tier will consist of tests to measure obvious structural and functional changes, often a functional observational battery. Subsequent levels of testing will be guided by the results of initial screening. Toxicologic testing must be supplemented by epidemiologic surveillance of populations exposed to known and suspect neurotoxicants. Screening programs in these populations designed to detect excessive absorption of a neurotoxic agent or subclinical neurological dysfunction can be useful in identifying affected individuals before severe disability occurs.
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PMID:Strategies for the prevention of environmental neurotoxic illness. 847 70

In vivo magnetic resonance spectroscopy (MRS) allows repetitive, noninvasive measurement of cerebral metabolites, including ATP, phosphocreatine (PCr), inorganic phosphate (Pi), intracellular pH, lactate, and N-acetyl aspartate. MRS has been used extensively to study cerebral metabolic changes in neonatal neurologic disorders. In babies with severe hypoxic-ischemic encephalopathy, PCr decreases and Pi increases, causing a fall in PCr/Pi and PCr/ATP, and a rise in Pi/ATP. These changes correlate with neurodevelopmental outcome. Decreased ATP is only seen in extremely severe hypoxic-ischemic encephalopathy and is usually associated with death in the neonatal period. Serial MRS studies may be helpful in selecting babies who would benefit from interventional treatment. Ongoing advances in MRS technology will permit localized, multinuclear spectroscopy, improving our ability to identify cerebral metabolic changes.
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PMID:Magnetic resonance spectroscopy in hypoxic-ischemic encephalopathy. 851 11

This paper elucidates the flaws in the official hypothesis that bovine spongioform encephalopathy originated from alterations in the way that scrapie-contaminated cattlefeeds were manufactured in the UK. An alternative hypothesis is proposed that cites exposure of the bovine embryo to various specific high-dose lipophilic formulations of organophosphates, such as the high-dose phthalimide containing organophosphate phosmet, (which were applied compulsorily and exclusively in the UK during the 1980s/early 1990s) as the primary trigger that initiated the deformation of prion protein and the onset of the bovine spongioform encephalopathy epidemic. The multi-site binding metabolites of these organophosphates penetrate the fetus, covalently phosphorylating various active sites on fetal prion protein. The extra charged phosphate groups left on aged prion protein blocks both proteases and chaperones from accessing their catalytic/bonding sites, creating the undergradable, misfolded isoform of prion protein, PrPsc. The resulting abnormally phosphorylated PrPsc aggregates to freshly synthesized PrPc, transforming it into same; due to a system of positive feedback invoked by the organophosphate-induced blockage of a prion protein-specific protein kinase. Both the timing, distribution and dynamics of usage of these specific organophosphates correlates with the epidemiology of bovine spongioform encephalopathy as well as accounting for the 23,000 cattle that have developed the disease, yet were born after the 1988 ban on scrapie-contaminated cattlefeed.
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PMID:The UK epidemic of BSE: slow virus or chronic pesticide-initiated modification of the prion protein? Part 2: An epidemiological perspective. 873 82

Information concerning developmental aluminum (Al) toxicity is available from clinical studies and from animal testing. An Al toxicity syndrome including encephalopathy, osteomalacia, and anemia has been reported in uremic children receiving dialysis. In addition, some components of the syndrome, particularly osteomalacia, have been reported in non-dialyzed uremic children receiving Al-based phosphate binders, nonuremic infants receiving parenteral nutrition with Al-containing fluids, and nonuremic infants given high doses of Al antacids. The number of children in clinical populations that are at risk of Al toxicity is not known and needs to be determined. Work in animal models (rats, mice, and rabbits) demonstrates that Al is distributed transplacentally and is present in milk. Oral Al administration during pregnancy produces a syndrome including growth retardation, delayed ossification, and malformations at doses that also lead to reduced maternal weight gain. The severity of the effects is highly dependent on the form of Al administered. In the postnatal period, reduced pup weight gain and effects on neuromotor development have been described as a result of developmental exposures. The significance of these findings for human health requires better understanding of the amount and bioavailability of Al in food, drinking water, and medications and from sources unique to infants and children such as breast milk, soil ingestion, and medications used specifically by pregnant women and children. We also need a better understanding of the unique biological actions of Al that may occur during developmental periods, and unique aspects of the developing organism that make it more or less susceptible to Al toxicity.
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PMID:What we know and what we need to know about developmental aluminum toxicity. 877

The therapeutic efficacy of a regimen consisting of intravenous injection of Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine diphosphate for mitochondrial encephalomyopathy (MEM) was examined. This combined therapy was applied to nine patients with MEM, including four with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. For the standard regimen, Cardiocrome was first injected daily, usually for 4 weeks, and later by means of intermittent injections for maintenance treatment. Clinical improvement was obtained in eight of the patients. Improvement was observed in the muscle symptoms of easy fatigability, motor disability and severity of stroke-like episodes, as well as in various other symptoms such as phosphate, tinnitus, headache, corneal edema, chilblains, thalamic pain, respiratory failure, and nystagmus. This clinical improvement was maintained for more than 1 year by additional intermittent injections. In conclusion, this therapy was fairly effective for the management of patients with MEM.
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PMID:Treatment of mitochondrial encephalomyopathy with a combination of cytochrome C and vitamins B1 and B2. 918 76

In this case report a near-term infant with Glucose 6-Phosphate Dehydrogenase (G6-PD) deficiency had an unconjugated bilirubin level of 703 on the 11th day of life but maintained his haemoglobin levels above 11 gm/dl. At 4 months of age he demonstrated the clinical picture of Kernicterus: profound sensorineural deafness and evidence of encephalopathy. However, by 15 months of age his abnormal cerebral and motor signs had regressed to a near-normal level in parallel with a gradual improvement in hearing, which also reached normal levels, first in the right ear, then in the left. At this age residual mental retardation has not been excluded but his communication skills, though delayed by 4-6 months, were moving towards the level when they would be appropriate for his age.
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PMID:Glucose 6-phosphate dehydrogenase deficiency with kernicterus: progressive late recovery from profound deafness. 957 22

We have found that cerebral lactate can be detected later than 1 month of age after neonatal encephalopathy (NE) in infants with severe neurodevelopmental impairment at 1 y. Our hypothesis was that persisting lactate after NE is associated with alkalosis and a decreased cell phosphorylation potential. Forty-three infants with NE underwent proton and phosphorus-31 magnetic resonance spectroscopy at 0.2-56 wk postnatal age. Seventy-seven examinations were obtained: 25 aged <2 wk, 16 aged > or = 2 to < or = 4 wk, 25 aged > 4 to < or = 30 wk, and 11 aged > 30 wk. Neurodevelopmental outcome was assessed at 1 y of age: 17 infants had a normal outcome and 26 infants had an abnormal outcome. Using univariate linear regression, we determined that increased lactate/creatine plus phosphocreatine (Cr) was associated with an alkaline intracellular pH (pHi) (p < 0.001) and increased inorganic phosphate/phosphocreatine (Pi/PCr) (p < 0.001). This relationship was significant, irrespective of outcome group or age at time of study. Between outcome groups, there were significant differences for lactate/Cr measured at < 2 wk (p = 0.005) and > 4 to < or = 30 wk (p = 0.01); Pi/PCr measured at < 2 wk (p < 0.001); pHi measured at < 2 wk (p < 0.001), > or = 2 to < or = 4 wk (p = 0.02) and > 4 to < or = 30 wk (p = 0.03); and for N-acetylaspartate/Cr measured at > or = 2 to < or = 4 wk (p = 0.03) and > 4 to < or = 30 wk (p = 0.01). Possible mechanisms leading to this persisting cerebral lactic alkalosis are a prolonged change in redox state within neuronal cells, the presence of phagocytic cells, the proliferation of glial cells, or altered buffering mechanisms. These findings may have implications for therapeutic intervention.
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PMID:Cerebral intracellular lactic alkalosis persisting months after neonatal encephalopathy measured by magnetic resonance spectroscopy. 1047 43

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia. High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone. Under in vitro conditions, containing 3.26 mg P/dL, the iron (III)-sucrose complex showed the highest phosphate adsorption capacity at pH 2 with artificial gastric juice, 58.9 mg P/g binder. For the 7 day in vivo study, 0% (Group 1), 1% (Group 2), 4% (Group 3), and 8% (Group 4) iron (III)-sucrose complex was admixed into the rodent chow by weight and fed to 15 male Wistar rats. The weight and volume of the feces and urine, and the calcium, iron, and phosphorus excretions in the feces and urine samples were monitored for any signs of irregularity. Total urine outflow was collected during a 24-h period to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The fecal iron excretion was significantly effected by the amount of binder ingested throughout the study for Group 2 (p < 0.001), Group 3 (p < 0.01), and Group 4 (p < 0.001). The urinary calcium excretion (mg/rat/24-h) significantly increased by the 7th day for Group 2 (p < 0.05) and Group 4 (p < 0.01) in comparison to the control. Finally, after 7 days, there was a significant drop in the urinary phosphorus levels (mg P/rat/24-h) in a dose dependent manner for Group 2: from 7.82 +/- 1.46 to 1.98 +/- 0.10 mg P/rat/24-h (102 mg P/dL/24-h; p < 0.05); Group 3: from 6.70 +/- 1.14 to 0.16 +/- 0.09 mg P/rat/24-h (6.0 mg P/dL/24-h; p < 0.01); and Group 4: from 8.25 +/- 0.67 to 0.04 +/- 0.01 mg P/rat/24-h (0.9 mg P/dL/24-h; p < 0.01). The results show that this new adsorbent might provide an alternative to conventional aluminum and calcium containing phosphate-binding agents for combating hyperphosphataemia.
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PMID:Oral phosphate binders: phosphate binding capacity of iron (III) hydroxide complexes containing saccharides and their effect on the urinary excretion of calcium and phosphate in rats. 1051 89


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