Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the aldose-reductase inhibitor, tolrestat, on chronic symptomatic diabetic sensorimotor neuropathy were studied during a placebo-controlled, randomised, 52-week multicentre trial. Of the four tolrestat doses investigated, only the highest dose group, 200 mg once daily, showed subjective and objective benefit over baseline and placebo, and further analyses are confined to this group (n = 112) and placebo (n = 107). Painful and paraesthetic symptoms were analysed separately: improvement in paraesthetic symptoms were seen at one year (p = 0.04), though painful symptoms improved on both placebo and active therapies. Significant improvement in both tibial and peroneal motor nerve conduction velocities were seen at 52 weeks. Tolrestat 200 mg once daily was significantly better than placebo in producing concordant improvements in both motor nerve conduction velocities and paraesthetic symptom scores at 24 weeks (p = 0.01), 42 weeks (p = 0.01) and 52 weeks (p = 0.02). Long-term benefit [concordant improvement at 24 weeks maintained until 52 weeks] was seen in 28% of treated patients compared to 5% on placebo (p = 0.001). It is concluded that some sustained improvement in symptomatic diabetic neuropathy may be obtained following aldose-reductase inhibition with tolrestat 200 mg once daily.
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PMID:A multicentre trial of the aldose-reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy. 211 23

A 32-year-old woman is described with polyarteritic changes concentrated to the calves. The disease has manifested itself in several acute episodes with swelling and pain in the calves, following symptomless phases. The response of to corticosteroid therapy has been good. Biopsy of the gastrocnemius muscle revealed peculiar multiple layers of intense NADH-tetrazolium reductase activity resembling annual rings in muscle fibers, a finding which has not been described earlier.
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PMID:Polyarteritis confined to lower extremities. 612 33

The effects of fluvastatin and bezafibrate on lipids, lipoproteins, and apoproteins (apo) were investigated in a multicenter randomized, double-blind, parallel-group study. After 8 weeks of strictly controlled (computer-based assessment) dietary stabilization, patients with primary hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 160 mg/dL; triglycerides < or = 300 mg/dL) were enrolled into a 6-week placebo phase. Altogether, 131 patients were randomized to receive either fluvastatin at 40 mg once daily (n = 64; mean age 53 years) or bezafibrate at 400 mg once daily (n = 67; mean age 52 years) for 12 weeks. Compliance with the diet was monitored (3-day food records) after 6 and 12 weeks. Fluvastatin led to significant reductions in LDL-C (-23%), total cholesterol (-17%), LDL-C/high-density lipoprotein cholesterol (HDL-C) (-24%) and apo B (-19%). Fluvastatin significantly increased LpA-I (+8%) and apo E (+20%). Bezafibrate produced significant reductions in LDL-C (-17%), total cholesterol (-13%), LDL-C/HDL-C (-24%), triglycerides (-28%), apo B (-15%), and LpA-I (-10%) and significantly increased HDL-C (+12%), apo A-I (+9%), apo A-II (+30%), apo E (+14%), and Lp(a) (+3%). No clinically notable increases in levels of liver enzymes or creatine phosphokinase were observed with either treatment. Both treatments were well tolerated. There was a low incidence of adverse events that tended to be mild and included headache, muscular pain, angina, and dyspepsia. The frequency of adverse events was similar in both treatment groups, and no significant differences in dietary behavior were observed. In conclusion, fluvastatin is a well tolerated 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia. Effects of fluvastatin on LpA-I occur irrespective of changes in HDL-C.
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PMID:Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate. 801 68

Pravastatin is a new lipid-lowering drug belonging to the class of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors. Since 1986, more than 15,000 patients have received pravastatin in sponsored clinical research trials with more than 21,000 cumulative patient-years of exposure to the drug. Analysis of long-term follow-up data from 1142 patients participating between 1986 and 1990 in six core randomized clinical trials in the United States confirms the favorable safety profile of pravastatin. Rash, gastrointestinal complaints, musculoskeletal pain, and elevations in liver transaminase levels, whether or not attributed to treatment, were the most common reasons for patients withdrawing from these trials. Ophthalmologic monitoring revealed no adverse effects on the crystalline lens. Safety assessments continue for two core trials in more than 400 patients with up to 7 years of continuous follow-up. The effects of pravastatin on serum cholesterol levels are not influenced by the age, sex, weight, or initial cholesterol level of the patient. Vitamin E, A, and D metabolism remain normal during treatment. Combination therapy with pravastatin and bile-acid-binding resins or niacin is well tolerated, with additive effects on low-density lipoprotein cholesterol. There is limited experience with the combination of pravastatin and gemfibrozil or cyclosporine. An ongoing arteriosclerosis research program with more than 21,000 patients enrolled will further define the long-term safety of pravastatin and its effects on atherosclerosis progression, as well as its role in the primary and secondary prevention of coronary heart disease.
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PMID:Long-term experience with pravastatin in clinical research trials. 845 55

The aim of this study was to test the efficacy of the aldose-reductase inhibitor Tolrestat in the treatment of carpal tunnel syndrome in Type 2 diabetic patients. Seventeen patients were treated with Tolrestat (200 mg daily for 12 months) clinical and neurophysiological evaluations were performed at baseline, 6 and 12 months; symptoms and blood glucose control were assessed at baseline, 2, 6, and 12 months. Thirteen Type 2 diabetic patients suffering from symptomatic carpal tunnel syndrome served as controls. Neurophysiological studies showed improvement in the sensory conduction velocity of the median nerve between forefinger and wrist (baseline 37.5 +/- 4.3 vs 6 months 41.3 +/- 5.7 ms-1, p < 0.0005 and baseline vs 12 months 41.4 +/- 8.2 ms-1, p < 0.005) but not between wrist and elbow. The terminal latency index of the median nerve was unchanged. Paraesthesiae and pain improved in terms of intensity and frequency. Blood glucose control was not significantly changed. We conclude that treatment of this case series with Tolrestat appears to produce beneficial effect on the outcome of carpal tunnel syndrome in diabetic patients.
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PMID:Effect of treatment with an aldose-reductase inhibitor on symptomatic carpal tunnel syndrome in type 2 diabetes. 875 Feb 20

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized 'viral infection' before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.
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PMID:Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. 877 36

One-third of diabetic patients are affected by peripheral neuropathy (PDN) in which the main aetiopathogenetic mechanism seems to be the high blood and nerve glucose content. The results of some long term trials, such as the Diabetes Control and Complications Trial (DCCT) and Stockholm studies, showed clearly that the maintenance of near-normal blood glucose levels and haemoglobin (Hb)A1c below 7.5% with intensive insulin treatment represents the best approach to primary and secondary prevention of the late diabetic complications, including PDN. After 5 years of such treatment DCCT reported that the development of clinical PDN was reduced by 64%. On the other hand, various and important problems still exist in identifying an efficacious aetiological therapy for PDN. In fact, while on the basis of current knowledge we have 2 possibilities for treatment of the pain, optimisation of glycaemic and HbA1c values and correct use of tricyclic antidepressants, none of the various substances tested has proven to be efficacious for PDN. Gangliosides, aldose-reductase inhibitors, including tolrestat, gamma-linolenic acid, levacecarnine (acetyl-L-carnitine) and antioxidants, were all shown to be of poor efficacy and often with significant adverse effects. The maintenance of near-normal glycaemic equilibrium seems currently to be the best way not only to prevent PDN but also to treat it. In the near future more long term trials, with very clear inclusion and exclusion criteria for recruitment, are needed to assist in identifying an efficacious treatment for PDN.
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PMID:Peripheral diabetic neuropathy. Current recommendations and future prospects for its prevention and management. 927 3

The use of topical lignocaine/prilocaine (EMLA, Astra Pharmaceuticals, North Ryde, NSW, Australia) for pain relief for neonatal circumcision is becoming more prevalent. Because of immaturity of the methaemoglobin reductase pathway, the neonate is vulnerable to methaemoglobinaemia which is a recognized complication of prilocaine therapy. This is the second report of methaemoglobinaemia due to the use of EMLA in association with circumcision during the newborn period.
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PMID:Methaemoglobinaemia secondary to topical lignocaine/ prilocaine in a circumcised neonate. 1094 Jan 84

Catastrophic antiphospholipid syndrome (CAPS) is a severe and rare variant of antiphospholipid syndrome (APS) characterized by acute multiorgan failure due to small vessel thrombi in patients with positive antiphospholipid antibodies. We report a fatal case of catastrophic antiphospholipid syndrome in a young woman with a history of polymyositis and Hodgkin lymphoma. The patient was admitted to hospital because of severe foot pain following several weeks of skin ulcerations. Doppler ultrasonography showed evidence of arterial ischemia of the both lower extremities. Despite anticoagulation, immunosuppression, plasmapheresis and antibiotic therapy, she developed cutaneous gangrene, retroperitoneal hematoma, ileus, and acute respiratory and renal failure that resulted in death. Autopsy showed multifocal vascular injury and microthrombi with associated hemorrhages and infarcts in multiple organs. The patient had normal levels of functional protein C and protein S and a normal level of plasma homocysteine. Tests for common thromophilic gene mutations including prothrombin 20210, factor V Leiden 1691, and methylene tetrahydrofolate reductase 677 were negative. To our knowledge, this is the first CAPS patient with molecular studies for genetic prothrombotic mutations. Our report showed that there was no association between the development of CAPS and inherited thromophilia.
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PMID:Catastrophic antiphospholipid syndrome: a rare cause of disseminated microvascular thrombotic injury - a case report with pathological and molecular correlative studies. 1574 23

Myopathy is usually a non-fatal muscle disease involving skeletal muscle weakness, tenderness and pain with the possibility of the plasma creatinine kinase elevation. There are many different types of myopathies, some of which are genetic, inflammatory, or related to endocrine dysfunction. Also, numerous drugs have been reported to possess myotoxic effect. Myopathy is included among the potential side-effects and toxicities associated with the lipid lowering agents, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. However, the precise mechanism of statin-induced muscle toxicity remains unclear. The muscle-related side-effects reported with lipid-lowering drugs are significant but quite rare (0.1%), when used in monotherapy; while the incidence of steroid-induced myopathy has varied from 7 to 60%% and chronic alcoholic myopathy seems to be common complication of alcoholism affecting approximately 50% of patients, respectively. This review focuses on the differential pathophysiological grounds of these muscular injuries induced by statins, fibrates, as well as some other agents: corticosteroids or alcohol. A wide spectrum of possible mechanisms and hypotheses including muscle enzyme defects, changes in mitochondrial function and intracellular metabolism, the influence on the cell membrane stability and drug interactions involving P-glycoprotein or cytochrome P 450 system have been presented.
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PMID:Drug-induced myopathies. An overview of the possible mechanisms. 1584 74


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