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

This retrospective study of 10 patients with hyperthyroidisma and diabetes mellitus concerned 8 women and 2 men, aged from 15 to 77 years. The two disease developed at the same time in 8 cases. Diabetes mellitus occurred first in 2 cases. Common signs were loss of weight. Hyperthyroidism led to tachycardia at more than 100 bpm. Diarrhea was observed simultaneously in 2 cases and muscular weakness in 5. Goiter was found in 10 cases with a diffuse aspect. Graves' disease was diagnosed with exophthalmia in 9 cases and affected both eyes in 8. Elevated levels of thyroid hormones confirmed diagnosis in 8 cases. Diabetes was insulin-dependent in 3 cases and non-insulin dependent in the 7 others. IDDM patients (2 female and 1 male) were aged 15, 17 and 38. Keto acidosis was the first symptom in all cases. NIDDM patients (6 female and 1 male) were aged between 37 and 77.
 ...
PMID:[Hyperthyroidism and diabetes mellitus: analysis of 10 African cases]. 1037 13

Primary human skeletal muscle cell cultures derived from muscles of a myotonic dystrophy (DM) fetus provided a model in which both resistance to insulin action described in DM patient muscles and the potential ability of insulin-like growth factor I (IGF-I) to circumvent this defect could be investigated. Basal glucose uptake was the same in cultured DM cells as in normal myotubes. In DM cells, a dose of 10 nM insulin produced no stimulatory effect on glucose uptake, and at higher concentrations, stimulation of glucose uptake remained significantly lower than that in normal myotubes. In addition, basal and insulin-mediated protein synthesis were both significantly reduced compared with those in normal cells. In DM myotubes, insulin receptor messenger RNA expression and insulin receptor binding were significantly diminished, whereas the expression of GLUT1 and GLUT4 glucose transporters was not affected. These results indicate that impaired insulin action is retained in DM cultured myotubes. The action of recombinant human IGF-I (rhIGF-I) was evaluated in this cellular model. We showed that rhIGF-I is able to stimulate glucose uptake to a similar extent as in control cells and restore normal protein synthesis level in DM myotubes. Thus, rhIGF-I is able to bypass impaired insulin action in DM myotubes. This provides a solid foundation for the eventual use of rhIGF-I as an effective treatment of muscle weakness and wasting in DM.
 ...
PMID:Insulin-like growth factor I circumvents defective insulin action in human myotonic dystrophy skeletal muscle cells. 1046 98

Surgery and accidental trauma are associated with a transient period of insulin resistance, substrate catabolism and muscle weakness. In the present study, we evaluated the changes in the force-generating capacity of chemically skinned single muscle fibres following abdominal surgery. Biopsies of the m. vastus lateralis were obtained in three patients 1 day before and 3 or 6 days after surgery. Part of the biopsy was frozen for histochemical analysis of the fibre cross-sectional area (FCSA) and myofibrillar protein content, and another part was used for single-fibre contractile measurements. All patients developed insulin resistance following surgery. The maximum velocity of unloaded shortening of single muscle fibres did not change following surgery. The FCSA did not decrease after surgery, as determined either from histochemical sections or from single fibres measured at a fixed sarcomere length of 2.76+/-0.09 microm (mean+/-S.D.). Further, the force-generating capacity of the single fibres, measured as maximal Ca(2+)-activated force (P(0)) or as P(0) normalized to FCSA (specific tension), remained unchanged, as did the myofibrillar protein content of the muscle. In conclusion, the muscle weakness associated with post-operative insulin resistance is not related to a decreased specific tension or a loss of myofibrillar proteins. Other potential cellular mechanisms underlying post-operative weakness are discussed.
 ...
PMID:Post-operative effects on insulin resistance and specific tension of single human skeletal muscle fibres. 1049 45

The authors present a case report of a 13.5 yrs old girl. The first manifestation of her diabetes was the sudden decrease of her vision due to bilateral cataract. There was no report of perinatal of actual infection, previous trauma, radiation exposure or drug consumption. She was hypermetropic, for that she regularly underwent ophthalmological examination, including fundoscopy. In the patient's history the usual presenting signs of diabetes i.e. weight loss, polyuria, polydipsia, weakness were absent. Upon admission in the hospital, blood sugar was 32.3 mmol/l, HbAIC 12.3%. After correction of her mild ketoacidosis and controlling her elevated serum glucose level she undervent bilateral cataract phacoemulsification, and artificial lens implant on day 14th and 58th. The patient regained her previous visual acuity, while her diabetes was controlled with 0.83 IU/kg/day of insulin. In the Hungarian literature the authors did not find any similar case. In the literature 22 similar cases were described.
 ...
PMID:[Acute metabolic cataract as a first manifestation of IDDM in an adolescent girl]. 1050 80

A 5-year-old female Collie dog showed excessive salivation, vomiting and neurological signs, including hind-limb weakness, mental dullness and subsequent recumbency with paddling movements of the limbs. Blood glucose and insulin concentrations were 35 mg/dl and 70.0 microU/ml, respectively. At necropsy, two masses, one at the caudal edge of the pancreas and the other in the omentum, were found and diagnosed as insulinoma. Histological examination of the brain showed early signs of acute neuronal necrosis exclusively in the superficial layers of the cerebral cortex, in addition to spongy changes in the dentate gyrus of the hippocampus. The light microscopical findings were identical in character and distribution with those of naturally occurring hypoglycaemia in humans and experimentally induced hypoglycaemia in animals.
 ...
PMID:Hypoglycaemic brain lesions in a dog with insulinoma. 1062 92

A 35-year-old obese man presented with a chief complaint of hand dryness of 5 years' duration. He was a store manager and denied exposure to chemicals, repetitive trauma, chronic irritation, and hard manual labor. However, he did admit to frequent hand washing. He had no itching or swelling in his hands, but on occasion he had tenderness in the dry areas. He had no personal or family history of diabetes, heart disease, or renal disease, and he stated that at his annual physical examination 6 months earlier, routine blood work was normal. He reported polyuria (every 2 hours), nocturia (five times per night), and polydipsia but no weakness, weight loss, visual changes, or neurosensory changes. Examination revealed xerosis of his hands and "pebbles" on the dorsal aspect of his fingers. The papules were most dense over the knuckles and interphalangeal joints (figures 1 through 3). He also had dozens of acrochordons (i.e., cutaneous papillomas, or skin tags) 1 to 4 mm in diameter on his neck, axilla, and groin. No other cutaneous lesions were noted. Specifically, there was no scleredema adultorum, necrobiosis lipoidica diabeticorum, acanthosis nigricans, bullae, or patchy pretibial pigmentation, although he did have several brown macules 1 to 5 mm in diameter on the sides of his lower legs. The macules had been present for years. Levels of hemoglobin A1c and glycated hemoglobin were 7.5% and 9.5%, respectively (normal, 4.4% to 5.9% and 5.0% to 7.3%). The patient was referred to his family physician, and his diabetes has been well controlled with insulin.
 ...
PMID:Finger 'pebbles'. A dermatologic sign of diabetes mellitus. 1072 45

Diabetic polyneuropathy is the most frequent neuropathy in western countries. In Germany, there are 3.5 to 4 million diabetic patients. Diagnosis should rule out other polyneuropathies and assess two out of the five diagnostic criteria: neuropathic symptoms, neuropathic deficits, pathological nerve conduction studies, pathological quantitative sensory testing and pathological quantitative autonomic testing. So far, the pathophysiology of diabetic neuropathy remains to be fully understood. Among the various pathophysiological concepts are the Sorbitol-Myo-Inositol hypothesis attributing Myo-Inositol depletion to the accumulation of Sorbitol and Fructose, the concept of deficiency of essential fatty acids with reduced availability of gamma-linolenic-acid and prostanoids, the pseudohypoxia- and hypoxia-hypothesis attributing endothelial and axonal dysfunction and structural lesions to increased oxidative stress and free radical production. Obviously, the hyperglycemia induced generation of advanced glycation end products (AGEs) also contributes to structural dysfunctions and lesions. Elevated levels of circulating immune complexes and activated T-lymphocytes as well the identification of autoantibodies against vagus nerve or sympathetic ganglia support the concept of an immune mediated neuropathy. The reduction of neurotrophic factors such as nerve growth factor, neurotrophin-3 or insulin-like growth factors also seems to further diabetic neuropathy. The symmetrical, distally pronounced and predominantly sensory neuropathy is far more frequent than the symmetrical neuropathy with predominant motor weakness or the asymmetrical neuropathy. The painless neuropathy manifests with impaired light touch sensation, position sense, vibratory perception and diminished or absent ankle deep tendon reflexes. The painful sensory diabetic neuropathy primarily affects small nerve fibers and accounts for decreased temperature perception and paresthesias. The proximal, diabetic amyotrophy evolves subacutely or acutely, induces motor weakness of the proximal thigh and buttock muscles and is painful. Cranial nerve III-neuropathy is also painful and has an acute onset. Truncal radiculopathy follows the distribution of truncal roots and frequently causes intense pain. Autonomic neuropathy occurs with and without somatic neuropathy. The most important therapy is to attempt optimal blood glucose control, to reduce body weight and hyperlipidemia. Symptomatic therapy includes alpha-lipoic acid treatment, as the antioxidant seems to improve neuropathic symptoms. Aldose reductase inhibitors might reduce sorbitol and fructose production and normalize myo-inositol levels. However, there are no aldose reductase inhibitors available in Europe as yet. Evening primrose oil, containing gamma-linolenic acid, might improve nerve conduction velocities, temperature perception, muscle strength, tendon reflexes and sensory function. Substitution of nerve growth factor showed promising results in pilot studies but failed in a large-scale multicenter study. Symptomatic pain treatment can be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, anticonvulsants such as carbamazepine, gabapentin or lamotrigine, or anti-arrhythmic drugs such as mexiletine. Topical capsaicin application should reduce neuropathic pain but also induces local discomfort in the beginning of therapy. Vasoactive substances, so far have not proven to be of major benefit in diabetic neuropathy. Physical therapy and thorough footcare are of primary importance and allow prevention of secondary complications such as foot amputations.
 ...
PMID:[Diabetic somatic polyneuropathy. Pathogenesis, clinical manifestations and therapeutic concepts]. 1092 53

Carnitine is a conditionally essential metabolite that plays a critical role in cell physiology by participating in transesterification reactions and preventing organic acid accumulation. A number of disease states are characterized by carnitine depletion that may lead to metabolic and clinical disturbances. In maintenance hemodialysis, carnitine is lost through dialytic membranes, leading in selected patients to carnitine depletion with a relative increase of the esterified forms. Carnitine supplementation after or during dialysis counteracts such alterations and may be associated with some clinical benefits. Recent meta-analyses of the literature indicate that carnitine supplementation in hemodialysis patients may improve the hematological status (allowing a reduction of the requirement for erythropoietin), the exercise tolerance, the plasma lipid profile, and the intradialytic symptoms. In addition, carnitine supplementation may improve cardiac functions, protein metabolism, and insulin resistance. Carnitine supplementation has been recently approved by the US Food and Drug Administration not only for the treatment, but also for the prevention of carnitine depletion in dialysis patients. Furthermore, clinical guidelines developed by both American and European nephrological societies suggest that a trial with carnitine supplementation could be recommended in selected dialysis patients who do not adequately respond to standard therapy for certain conditions, such as severe and persistent muscle cramps or hypotension during dialysis, lack of energy affecting quality of life, skeletal muscle weakness or myopathy, cardiomyopathy, and anemia of uremia unresponsive to or requiring large doses of erythropoietin.
 ...
PMID:Carnitine metabolism in uremia. 1157 25

Myotonic dystrophy 1 (DM1) is the most common inherited neuromuscular disease in adults. The disorder, characterized by myotonia, muscle wasting and weakness, cataract, insulin resistance, and mental impairment, is caused by the expansion of an unstable CTG repeat located in the 3' untranslated region of DMPK. The repeat expansion suppresses the expression of the homeobox gene SIX5. We describe here an experimental system to identify downstream transcriptional targets of mouse Six5 in order to elucidate the role of SIX5 in the pathogenesis of DM1 and development. By overexpressing a constitutively active Six5 (VP16-Six5wt) using adenovirus-mediated gene transfer in P19 cells and subsequent expression profiling using cDNA arrays, 21 genes, whose expression level increased by the treatment, were identified as potential target genes. Genes expressed in the somites, skeletal muscles, brain and meninges comprised the majority, suggesting the role of Six5 in the development and function of mesodermal tissues and brain. We provide evidence that Igfbp5 encoding a component of IGF signaling is a direct Six5-target. Moreover, the overall expression level of Igfbp5 was decreased in Six5-deficient mouse fibroblasts, and the response of human IGFBP5 to MyoD-induced muscle conversion was altered in cells of DM1 patients. Our results not only identify Six5 as an activator that directs Igfbp5 expression but also suggest that reduced SIX5 expression in DM1 might contribute to specific aspects of the DM1 phenotype.
 ...
PMID:Identification of transcriptional targets for Six5: implication for the pathogenesis of myotonic dystrophy type 1. 1197 64

Peripheral neuropathy and hypotension were found in a diabetic dog with profound weakness. Insulin therapy controlled the diabetes mellitus. As the blood glucose was normalized, the neurologic signs and hypotension resolved, suggesting a causal relationship.
 ...
PMID:Peripheral neuropathy and hypotension in a diabetic dog. 1200 74


<< Previous 1 2 3 4 5 6 7 8 9 10