Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified a novel mtDNA mutation in a 29-year-old man with myopathy and diabetes mellitus. This T-->C transition at mtDNA position 14709 alters an evolutionarily conserved nucleotide in the region specifying for the anticodon loop of the mitochondrial tRNA(Glu). The nt-14709 mutation was heteroplasmic but present at very high levels in the patient's muscle, white blood cells (WBCs), and hair follicles; lower proportions of mutated mtDNA were observed in WBCs and hair follicles of all examined maternal relatives. In the patient's muscle, abnormal fibers showed mitochondrial proliferation, severe focal defects in cytochrome c oxidase activity, and absence of cross-reacting material for mitochondrially synthesized polypeptides. These fibers had higher levels of mutated mtDNA than did surrounding "normal" fibers. Although the percentage of mutated mtDNA in WBCs from family members were distributed around the percentage observed in the mothers, the pattern was different in hair follicles, where the mutated population tended to increase in subsequent generations. PCR/RFLP analysis of single hairs showed that the intercellular variations in the percentage of mutated mtDNA differed among family members, with younger generations having a more homogeneous distribution of mutated mtDNA in different hair follicles. These results suggest that the intercellular distribution of the mutated and wild-type mtDNA populations may drift toward homogeneity in subsequent generations.
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PMID:Segregation patterns of a novel mutation in the mitochondrial tRNA glutamic acid gene associated with myopathy and diabetes mellitus. 772 54

We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus.
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PMID:Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation. 772 55

Analysis of 109 well documented cases of permanent total atrial paralysis reported in the literature illustrated the features of this arrhythmia which is a well defined entity consisting of suppression of all electrical and mechanical activity of both atria lasting for more than 6 months. Standard electrocardiogram reveals junctional bradycardia of about 40 bpm without any visible P waves and narrow supraventricular QRS complexes in 80% of cases. This diagnosis can only be confirmed by meticulous bipolar endocavitary recordings exploring all atrial walls without recording an auriculogram and by right intra-atrial and coronary sinus stimulation which proves to be ineffective. This disease has a male predominance in two-thirds of cases and a familial nature in 18% of cases. Seventy one per cent of affected subjects are under the age of 50 years. In 33% of cases, it is associated with Emery-Dreifuss muscular dystrophy, in which it constitutes a specific sign allowing this dystrophy to be differentiated from all other forms, especially facio-scapulo-humeral myopathy, and in 30% of cases, it is associated with a degenerative disease such as diabetes, amyloidosis or primary cardiomyopathy. Idiopathic dilatation of the right atrium is revealed in 15% of cases. The arrhythmia is responsible for syncope or faintness in 31% of cases, cerebral vascular accidents in 21% of cases and heart failure in 35% of cases. Cardiac activation is dependent on a junctional escape rhythm. The mechanism of the lesion responsible is atrial fibrosis which may extend to the sinoatrial node. The treatment of choice consists of implantation of a VVI or VVIR mode cardiac pacemaker in combination with anticoagulant therapy.
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PMID:[Total permanent auricular paralysis. Review of the literature apropos of 109 cases]. 779 52

Corticosteroids are extensively prescribed in advanced cancer for various specific indications (e.g. spinal cord compression), for pain relief, as hormone therapy and to stimulate appetite and wellbeing. Choice of corticosteroid is dictated largely by local fashion, and times of administration are more traditional than pharmacological. Corticosteroids have many potential disadvantages, some life-threatening (e.g. masked septicaemia). Others are seriously debilitating (e.g. myopathy, avascular bone necrosis). Oropharyngeal candidiasis is a common complication. Corticosteroids are withdrawn in about 5% of patients because of unacceptable adverse effects, including moon-face and diabetes mellitus. Corticosteroid hypersensitivity occurs, and the succinate salts have been associated with bronchospasm. Steroid pseudorheumatism may occur with high dose therapy or when tailing off after a prolonged course. Important drug interactions with corticosteroids relate to salt and water retention, and decreased glucose tolerance. Some anticonvulsants cause an increased clearance of corticosteroids and, with dexamethasone, up to a 50% reduction in the anticipated effect. The benefit of corticosteroids in terms of increased appetite, mood and activity has been demonstrated in several controlled trials. The effect may well be time-limited in most patients. In several studies, corticosteroids have resulted in an analgesic-sparing effect. Some centres use very high doses of dexamethasone in cases of spinal cord compression, although the justification for these is not obvious. Corticosteroids are used to help relieve nerve compression pain and in symptomatic raised intracranial pressure. Corticosteroids are also injected locally into or around bone metastases, particularly ribs and the sacro-iliac joints. Epidural injections are used for patients with troublesome intractable low back pain. Corticosteroids are now used less often in hypercalcaemia because of poor response rates. More benefit is obtained, however, if high dosages are used, e.g. prednisolone 60 to 80 mg/day. Dexamethasone is widely used as an antiemetic in association with chemotherapy. Some centres use dexamethasone by continuous subcutaneous infusion in selected patients when the oral route is not feasible. The choice of starting dose of a corticosteroid is largely arbitrary. It is important, however, not to miss a possible treatment benefit by prescribing too low a dose. For most patients, an initial dosage of prednisolone of 30 to 60 mg/day (dexamethasone 4 to 8 mg/day) is appropriate. In patients with anorexia, there are several alternative options that should be considered. There is evidence to suggest that patients with advanced cancer receiving a corticosteroid are not as closely monitored as other patients. There is a need to state clearly in writing the reason(s) for prescription and to review after 1 or 2 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The risks and benefits of corticosteroids in advanced cancer. 781 99

The discovery and production of HMGCoA reductase inhibitor and the fundamental research work of the LDL receptor unraveled a receptor-mediated cholesterol homeostasis. HMGCoA reductase inhibitors are the most commonly prescribed class of lipid-lowering drugs in many countries. The decrease of the intracellular cholesterol caused by the inhibitor induces the compensatory increase of LDL receptor protein at liver plasma membrane. The increased receptor promotes LDL catabolism and results in decrease of plasma LDL. Serious side effects involving the liver or muscle are rare. But the risk of myopathy is increased when the drug is used with other hypolipidemic agents. A principle of the treatment of hyperlipidemia, including secondary one associated with diabetes mellitus and renal disease, by HMGCoA reductase is discussed in this review.
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PMID:[HMG-CoA reductase inhibitor for therapy of patients with hyperlipoproteinemia ]. 785 22

Urinary bladder dysfunction was investigated in spontaneously diabetic Chinese hamsters of the Asahikawa colony (CHAD). The wet weight of the urinary bladder was significantly increased in CHAD when compared with non-diabetic controls. In response to continuous infusion of physiological saline into the bladder under anesthesia, regular micturition was observed in controls. However, the threshold volume (i.e. the minimum volume at which rhythmic contraction appeared) was significantly increased and the amplitude of bladder contractions during micturition was decreased in CHAD aged 3-5 months (duration of diabetes, 0.6-2.2 months), leading to incomplete micturition. The frequency of micturition was also increased. Overflow incontinence was observed in all CHAD aged 13-15 months (duration of diabetes, 10-14 months). Acetylcholinesterase staining and activity in the urinary bladder walls were both significantly decreased in CHAD compared with controls. The in vitro increment of urinary bladder pressure caused by stimulation with bethanechol was not different between CHAD and controls. These findings suggest that CHAD have urinary bladder dysfunction which is caused by autonomic neuropathy and not by detrusor myopathy.
Diabetes Res Clin Pract 1994 Jan
PMID:Urinary bladder dysfunction in spontaneously diabetic Chinese hamsters. 791 Oct 80

Neurotoxicity, manifested primarily by a motor and sensory polyneuropathy, is the principal nonhematological side effect of Taxol. Available evidence suggests that Taxol produces a toxic effect involving either axons or ganglion cell bodies, or both, rather than a myelinopathy. As with other toxic polyneuropathies, patients with preexisting peripheral neuropathies, such as those caused by diabetes mellitus or ethanol, appear to be particularly predisposed to developing neurological toxicity. The incidence and severity of the neuropathic manifestations also appear to be related to the Taxol dose level, the cumulative dose of Taxol, and possibly to the use of Taxol in combination with cisplatin. Rarely, manifestations of autonomic and central nervous system dysfunction occur. Taxol also induces myalgias in the peri-treatment period, especially when used in high doses, and a myopathy has been noted in patients treated with high doses of Taxol administered alone and in combination with cisplatin. Although dose-response relationships for Taxol have not been clearly established, these neuromuscular effects are likely to become a significant clinical problem if higher doses of Taxol are used with hematopoietic colony-stimulating factors. The neuromuscular effects of Taxol, including symptoms, physical and electrophysiological manifestations, and predisposing factors, as well as agents that may be used for neuroprotection, are discussed in this report.
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PMID:Neurotoxicity of Taxol. 791 16

In this preliminary report of a 20-week trial, 66 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hyperlipidaemia who remained eligible after an 8-week dietary stabilization phase were randomly allocated to receive 20 mg of fluvastatin or placebo once daily for 6 weeks. Fluvastatin was subsequently increased to 20 mg twice daily and administered according to the same schedule, versus placebo, for a further 6 weeks. Both dosages of fluvastatin substantially improved serum lipid profiles compared with baseline and placebo. Both dosages of fluvastatin significantly reduced low-density- and very-low-density-lipoprotein (LDL, VLDL), cholesterol and triglyceride (TG) compared with placebo, and both dosages significantly elevated high-density-lipoprotein (HDL) cholesterol. The ratio of LDL to HDL was also significantly decreased. Amongst the 58 patients who completed the study, there was no evidence either of myopathy or of hepatotoxicity; mean creatine kinase values remained stable in the fluvastatin arm. Fasting glucose, glycosylated haemoglobin, and fructosamine levels were not markedly affected by active treatment. No serious adverse events attributable to the drug were reported. In conclusion, both dosages of fluvastatin appear to be effective and safe in the management of hyperlipidaemia in this outpatient, maturity-onset, diabetic population.
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PMID:Efficacy and safety of fluvastatin in hyperlipidaemic patients with non-insulin-dependent diabetes mellitus. 798 2

We report a patient with mitochondrial encephalomyopathy presenting parkinsonism, as well as her brother who had ataxia but not parkinsonism. Both patients had myopathy, deafness, and insulin-dependent diabetes mellitus. The proband was a 55-year-old woman, who has developed progressive difficulty in walking and slowness of movement since 53 years of age, becoming bed-ridden at 55. Neurological examination revealed mental impairment, a masked face, Myerson's sign, vertical supranuclear ophthalmoplegia, and severe sensorineural deafness, hypokinesia, rigidospasticity, and weakness of the extremities. But tremor and cerebellar ataxia were absent. Her 48-year-old brother gradually developed weakness of the lower extremities and drunken gait over a few years. On neurologic examination, vertical supranuclear ophthalmoplegia, moderate sensorineural deafness, and cerebellar ataxia were present, but parkinsonism was absent. Three other siblings were reported to have died in early childhood. Cranial MR imaging showed cerebral atrophy and mild atrophy of the cerebellar vermis as well as mild periventricular hyperintensities in T2-weighted images in both patients. However, no infarcts were seen. Laboratory investigations revealed slightly elevated lactate and pyruvate levels in the proband and elevation of pyruvate in her brother. A biopsy specimen obtained from the quadriceps muscle showed ragged-red fibers with modified Gomori trichrome staining, and a decrease of complex I+III and complex II+III activity in the proband. Mitochondrial DNA (mtDNA) analysis using the polymerase chain reaction and restriction enzyme Apa I showed a point mutation in the tRNA(Leu)(UUR)) gene (an A to G transition at nucleotide 3243) in both patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mitochondrial encephalomyopathy associated with parkinsonism and a point mutation in the mitochondrial tRNA(Leu)(UUR)) gene]. 802 31

Primary defects in mitochondrial function are implicated in over 100 diseases, and the list continues to grow. Yet the first mitochondrial defect--a myopathy--was demonstrated only 35 years ago. The field's dramatic expansion reflects growth of knowledge in three areas: (i) characterization of mitochondrial structure and function, (ii) elucidation of the steps involved in mitochondrial biosynthesis, and (iii) discovery of specific mitochondrial DNA. Many mitochondrial diseases are accompanied by mutations in this DNA. Inheritance is by maternal transmission. The metabolic defects encompass the electron transport complexes, intermediates of the tricarboxylic acid cycle, and substrate transport. The clinical manifestations are protean, most often involving skeletal muscle and the central nervous system. In addition to being a primary cause of disease, mitochondrial DNA mutations and impaired oxidation have now been found to occur as secondary phenomena in aging as well as in age-related degenerative diseases such as Parkinson, Alzheimer, and Huntington diseases, amyotrophic lateral sclerosis and cardiomyopathies, atherosclerosis, and diabetes mellitus. Manifestations of both the primary and secondary mitochondrial diseases are thought to result from the production of oxygen free radicals. With increased understanding of the mechanisms underlying the mitochondrial dysfunctions has come the beginnings of therapeutic strategies, based mostly on the administration of antioxidants, replacement of cofactors, and provision of nutrients. At the present accelerating pace of development of what may be called mitochondrial medicine, much more is likely to be achieved within the next few years.
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PMID:The development of mitochondrial medicine. 809 Jul 15


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