Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A five-year-old intact male rottweiler was presented with a history of episodic weakness and mild-generalised seizures. A tentative diagnosis of an insulin-secreting tumour in the pancreas was made based on fasting hypoglycaemia with concomitant hyperinsulinaemia and a subnormal fructosamine value. The diagnosis was confirmed by exploratory coeliotomy, intravenous infusion of methylene blue, histopathology and immuno-histochemical analysis of suspected neoplastic tissue. Fructosamine assays are traditionally used for monitoring the metabolic status of diabetics where a single elevated measurement reflects persistent hyperglycaemia. This report suggests that a single low measurement of fructosamine may indicate persistent hypoglycaemia and may be helpful, in conjunction with an insulin measurement, in the diagnosis of insulin-secreting tumours.
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PMID:Pancreatic insulin-secreting carcinoma in a dog: fructosamine for determining persistent hypoglycaemia. 765 Sep 28

It is well known that diabetic patients are at an increased risk of the earlier development of significant atherosclerotic disease. We wish to report the case of a young insulin-dependent diabetic with an 18 months history of rapidly progressing 'diabetic' retinopathy who presented with right-sided weakness and was found to have severe carotid artery disease. We suggest that the sudden proliferation in his retinopathy was due to retinal ischaemia secondary to the carotid artery stenosis and we wish to present this as a case of ocular ischaemic syndrome in a young diabetic patient.
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PMID:A case of ocular ischaemic syndrome in a young insulin dependent diabetic male. 768 57

In vitro twitch tests were performed on excised muscle bundles from 30 periodic paralysis (PP) patients in an attempt to verify the somatic origin of PP, and to differentiate between the hypokalemic (HypoPP) and the hyperkalemic forms (HyperPP). Seventeen PP patients with a definite diagnosis of familial HypoPP, familial HyperPP (subsequently confirmed by SCN4A mutations), or thyrotoxic PP entered the study, as well as 13 patients with a history of attacks of weakness but with negative clinical provocation tests and therefore ambiguous diagnosis; 15 normal subjects served as controls. In contrast to control, bundles from patients with clear diagnosis went into sustained paralysis on exposure to Cl-free solution. Exposure to K+ channel activators induced a large increase in force. Specifically for HypoPP muscle, low extracellular [K+] decreased twitch force which was further reduced by addition of insulin or adrenaline, whereas HyperPP bundles responded with an irreversible decrease in twitch force when extracellular [K+] was elevated. Out of the 13 patients with unclear diagnosis, the in vitro studies made it possible to classify 10 as HypoPP and one as HypePP (later confirmed by a M1592V mutation). In the remaining two patients who claimed to suffer from paralytic attacks, all in vitro tests were normal, questioning the occurrence of dyskalemic PP. The results demonstrate that in vitro tests can be used to ensure the proper diagnosis to a high percentage when clinical provocative tests have failed.
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PMID:Differential diagnosis of periodic paralysis aided by in vitro myography. 776 90

Haemochromatosis is one of the most common inborn errors of metabolism. In prospective epidemiological studies the frequency of haemochromatosis is 0.0037 (76/20333 subjects) for homozygotes which corresponds to a gene frequency of 0.061 and a frequency of heterozygotes of 0.115. Abnormality in liver function tests, weakness and lethargy, skin hyperpigmentation, diabetes mellitus, arthralgia, impotence and ECG abnormalities are the most frequent findings and symptoms at diagnosis. In recent years about 50% of patients were detected without having liver cirrhosis and 20% of patients did not have any symptoms and pathology except iron overload. Survival analyses in long-term studies showed that in the absence of cirrhosis and diabetes, iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. Patients with massive and long-lasting iron overload had a worse prognosis than those with less severe iron excess. Iron removal in general ameliorated liver disease, weakness and cardiac abnormalities, and also prevented the progression of endocrine alterations. Therapy, however, did not influence insulin-dependent diabetes. Most deaths in patients with hereditary haemochromatosis were caused by liver cancers which often occurred many years after complete iron removal. In patients with haemochromatosis, liver cirrhosis, cardiomyopathy, and diabetes mellitus are also significantly more frequent causes of deaths when compared with the general population. Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.
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PMID:Clinical spectrum and management of haemochromatosis. 788 Nov 58

Inclusion body myositis (IBM) is defined clinically by a characteristic pattern of progressive proximal and distal limb muscle weakness and resistance to steroid therapy, and histologically by the presence of distinctive rimmed vacuoles and filamentous inclusions as well as a mononuclear infiltrate in which CD8+ T cells are predominant. Muscle damage is believed to be mediated by autoimmune mechanisms, but very little information is available on the immunogenic features of IBM. MHC class I and DR antigens were typed on 13 caucasoid patients with IBM using standard serological techniques or by allele-specific oligonucleotide typing. Complement components C4 and properdin factor B (Bf) were typed by immunofixation after electrophoresis. Restriction fragment length polymorphisms (RFLP) in the class III region were analysed using cDNA probes for C4 and 21-hydroxylase (CYP21) after Taq 1 digestion. IBM was associated with DR3 (92%), DR52 (100%) and HLA B8 (75%). The phenotype data were examined for likely haplotypes by considering together the alleles at the class I, DR and complement loci along with the C4 and CYP21 RFLP. Ten of the DR3+ subjects had a 6.4-kb C4-hybridizing fragment characteristic of a deletion of C4A and CYP21-A. These patients probably carried all, or at least the class II and III regions, of the extended haplotype marked by B8/C4A*Q0/C4B1/BfS/DR3/DR52, which has been associated with several autoimmune diseases and is present in 11% of the healthy caucasoid population. Of the remaining subjects, two had evidence of the extended haplotype marked by B18/C4A3/C4BW*0/BfF1/DR3, which is present in less than 5% of the healthy population and has been associated with insulin-dependent diabetes mellitus. These data provide support for an autoimmune etiology for, and genetic predisposition to, IBM.
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PMID:HLA associations with inclusion body myositis. 792 82

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

A 67-year-old male was admitted with the complaint of weakness at hunger early in the morning, when blood glucose was less than 40 mg/dl. The abdominal ultrasonogram and computerized tomogram demonstrated a huge tumor in the right liver lobe. Hypoglycemia disappeared after transcatheter arterial embolization. Then hepatic lobectomy was performed. The tumor was histologically shown to be a fibrosarcoma. Insulin-like growth factor-II was intensely stained in the Golgi area of the tumor cells, suggesting its role in the mechanism of hypoglycemia.
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PMID:IGF-II producing hepatic fibrosarcoma associated with hypoglycemia. 820 62

Decreased muscular activity results in weakness and muscular atrophy. Coincident with this protein catabolic state is glucose intolerance and hyperinsulinemia. Rats were tail suspended for 7 to 14 days to accomplish unloading of the hindlimbs. Insulin resistance was documented in these animals by a 14 day tail suspension-related 26% increase in serum glucose in spite of a 253% increase in serum insulin concentration. Microsomal membranes were prepared from hindlimb muscles and specific binding of insulin and insulin-like growth factor I (IGF-I) were determined in these membranes. Insulin binding was decreased by 27% at 7 days and by 21% at 14 days. In contrast, IGF-I binding was unchanged at 7 days and was increased by 24% at 14 days. Liver membrane insulin receptors also had declined by 14 days of suspension, suggesting that the change in insulin receptors was a generalized, humorally-mediated phenomenon. These data suggest that tail suspension in rats results in insulin resistance, hyperinsulinemia, a decline in insulin receptors in liver and muscle, and a relative increase in muscle membrane IGF-I receptors. These data are consistent with the hypothesis that resistance to insulin's effects on protein metabolism in skeletal muscle may contribute to the protein catabolism associated with decreased muscular activity.
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PMID:Rat tail suspension causes a decline in insulin receptors. 831 11

Based on the known trophic effects of growth hormone (GH) on nerve and muscle 75 patients with ALS were treated for up to 18 months with synthetic human growth hormone (Protropin) or a placebo. The course of ALS was assessed serially using a quantitative (TQNE) neuromuscular and manual exam (MRC) and laboratory chemistries. Average insulin-related growth factor (IGF-I) values increased from 1.2 to 2.3 U/mL in the treated group. Surprisingly, serum insulin levels did not increase. Hyperglycemia was noted in only 2 patients of the 38 patients receiving hGH, and this resolved with cessation of treatment. Over the 12 months of treatment there were 11 deaths (6 controls, 5 treated). Survival analysis, performed approximately 12 months following cessation of treatment, did not reveal a difference between the treatment and placebo group. The TQNE scores declined inexorably in both the control and treated group. Retrospective analysis of the TQNE data indicated a poor prognosis for patients who lost arm strength early. A correlation between the TQNE and MRC scores was evident at early stages of motor unit loss, less so when muscle weakness was advanced.
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PMID:Recombinant growth hormone treatment of amyotrophic lateral sclerosis. 850 60

Muscle weakness and wasting in myotonic dystrophy (MyD) are believed to be due to a decrease in muscle protein synthesis, secondary to insulin resistance. A 4-month, randomized, double blind, placebo-controlled trial was undertaken to assess whether recombinant human insulin-like growth factor I (rhIGF-I) may overcome the insulin resistance. Patients received either 5 mg rhIGF-I (n = 7) or placebo (n = 9), sc, twice daily. Glucose metabolism was assessed by stable label iv glucose tolerance test, amino acid metabolism by L-[13C] leucine turnover, body composition by dual energy x-ray absorptiometry and N excretion, and muscle response by manual muscle strength and neuromuscular function. In the treated group, the insulin sensitivity index, insulin action, and glucose disposal all increased (P < 0.05). Leucine flux and leucine incorporation into protein increased (P < 0.05), and the rate of leucine oxidation to leucine turnover decreased (P < 0.05), findings indicative of increased protein synthesis. Body weight and lean body mass increased, whereas percent body fat decreased (P < 0.05). An increase in manual muscle strength of 0.42 +/- 0.30 (P < 0.02) and in neuromuscular function of 17.5 +/- 11.7 (P < 0.02) occurred in the four patients who received a rhIGF-I dose greater than 70 micrograms/kg, whereas a more modest response occurred in the three patients who received a dose less than 70 micrograms/kg. Two patients showed dramatic improvement. Long term rhIGF-I therapy appears to cause metabolic and muscle improvement in optimally treated MyD patients.
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PMID:Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy--a clinical research center study. 853 Jun 24


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