Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcaemia would seem to be rare during immobilisation, whilst osteoporosis and hypercalciuria are constant. In fact, it often goes unnoticed. The case presented here confirms its predominance in the adolescent male. The reason for immobilisation seems to be irrelevant. The clinical symptoms are very variable: polydipsia, nausea, headache, apathy, anorexia. Blood calcium levels are raised, up to 14 mg%. This hypercalcaemia is due to very marked bone loss in adolescents, secondary to hyper-resorption and a temporary stoppage in osseous formation. The differential diagnosis from primary hyperparathyroidism is sometimes difficult but is aided by laboratory and histological findings. The essential is to consider the possibility of immobilisation hypercalcaemia in the presence of any suggestive symptoms in an immobilised adolescent. Treatment includes a return to weight bearing, adequate water intake and the administration of phosphorus, calcitonin, furosemide, and corticosteroids.
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PMID:[Immobilisation hypercalcaemia (author's transl)]. 59 68

Approximately 85 % of the patients with osteoporosis are suffered from bone pain. And almost 100 % of the patients eagerly ask the physician to relieve their pain. But many physicians concerning treatment of osteoporosis had been interested in increase of bone mineral density, decrease of fracture rate and improvement of bone quality, instead of relief of the pain. A reason of indifference of medical doctor for pain relief would be based on uncertain pathogenesis of bone pain, such as many spinal fractures occurred without pain in the huge study of clinical efficacy of a bisphosphonate. Recently, a detailed study focused on spinal pain revealed that 90% of spinal fracture were accompanied the pain. On the other hand, many bisphosphonates in addition to calcitonin were clarified to show analgesic effect. So many medical doctors have been interested in relief of osteoporotic pain. The purpose of treatment of osteoporosis in 21st century would again become relief of the pain, based on the reduction of fracture rate.
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PMID:[Bone diseases with Pain. Osteoporosis]. 1740 92

The sodium channel NaV1.7 contributes to action potential (AP) generation and propagation. Loss-of-function mutations in patients lead to congenital indifference to pain, though it remains unclear where on the way from sensory terminals to central nervous system the signalling is disrupted. We confirm that conditional deletion of NaV1.7 in advillin-expressing sensory neurons leads to impaired heat and mechanical nociception in behavioural tests. With single-fiber recordings from isolated skin, we found (1) a significantly lower prevalence of heat responsiveness to normally mechanosensitive C-fibers, although (2) the rare heat responses seemed quite vigorous, and (3) heat-induced calcitonin gene-related peptide release was normal. In biophysical respects, although electrical excitability, rheobase, and chronaxy were normal, (4) axonal conduction velocity was 20% slower than in congenic wild-type mice (5) and when challenged with double pulses (<100 milliseconds interval), the second AP showed more pronounced latency increase (6). On prolonged electrical stimulation at 2 Hz, (7) activity-dependent slowing of nerve fiber conduction was markedly less, and (8) was less likely to result in conduction failure of the mutant single fibers. Finally, recording of compound APs from the whole saphenous nerve confirmed slower conduction and less activity-dependent slowing as well as the functional absence of a large subpopulation of C-fibers (9) in conditional NaV1.7 knockouts. In conclusion, the clear deficits in somatic primary afferent functions shown in our study may be complemented by previously reported synaptic dysfunction and opioidergic inhibition, together accounting for the complete insensitivity to pain in the human mutants lacking NaV1.7.
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PMID:NaV1.7 and pain: contribution of peripheral nerves. 3142 77

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease characterised by recurrent ischemic stroke, cognitive decline progressing to dementia, psychiatric disturbances and apathy. More than half of mutation carriers suffer from migraine, most often migraine with aura. Recently, a CADASIL patient was treated with a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor. Monoclonal antibodies targeting the CGRP system have been demonstrated to be safe, well tolerated, and effective in reducing migraine attacks. There is, however, abundant evidence that CGRP is important in maintaining cardiovascular homeostasis under (patho)physiological conditions. CGRP may act as a vasodilatory safeguard during cerebral and cardiac ischemia and blockage of the system could, therefore, potentially worsen ischemic events. Therefore, we caution against treating patients with small vessel diseases, such as the monogenic disorder CADASIL, with these drugs until relevant safety data and long term follow up results are available. Alternative preventive migraine treatments in CADASIL may be acetazolamide, sodium valproate, lamotrigine, topiramate, verapamil, or flunarizine.
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PMID:The potential danger of blocking CGRP for treating migraine in CADASIL patients. 3266 Feb 69