Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392326 (discomfort)
 22,423 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In search of new practical diagnostic methods for the early diagnosis of hereditary medullary carcinoma of the thyroid (MCT) calcitonin release has been studied following induction by pentagastrin, cholecystokinin-pancreozymin (the C-terminal octapeptide, C8-CCK, and the native swine extract), and ethanol in eighteen cases of MCT (all but one clinically occult), three 'borderline cases', seven first degree relatives of patients with hereditary MCT and thirty-five healthy controls. Pentagastrin, subcutaneous (s.c.) or intravenous (i.v.), induced a pronounced and rapid increase of serum calcitonin within 2-5 min. The elevation was roughly proportional to the tumour mass as estimated at operation. Seventeen out of eighteen MCT patients responded to s.c. pentagastrin with a significant increase in serum calcitonin and the response correlated well with that induced by calcium infusion test. Only two blood samples, at times 0 and 5 min, were necessary for diagnosis. In the MCT patients, i.v. pentagastrin produced more pronounced elevations of serum calcitonin than did s.c. pentagastrin, whereas no increase was seen in the control group. The subjective discomfort caused by i.v. pentagastrin was somewhat more intense but lasted shorter than that induced by s.c. administration. No serious complications were seen. All of nine MCT patients responded to C8-CCK with increments in serum calcitonin exceeding those of the control group and both of two responded similarly to the native cholecystokinin-pancreozymin extract. Generally the serum calcitonin response was lower and more variable after C8-CCK than after s.c. or i.v. pentagastrin, and the subjective discomfort was also more pronounced with abdominal cramps during the injection. Ethanol in the dose used was the least effective stimulator for serum calcitonin release. Clinically suspected MCT carriers with palpable tumours can be diagnosed by determination of the basal, i.e. non-stimulated serum calcitonin levels. Other possible Sipple genome carriers, who are at the time clinically healthy with normal basal serum calcitonin, should be subjected to a s.c. or i.v. pentagastrin stimulation test at each examination. These tests are much simpler to perform than a calcium infusion, test, but seem to have about the same sensitivity.
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PMID:Screening for medullary carcinoma of the thyroid in families with Sipple's syndrome: evaluation of new stimulation tests. 40 80

A 23-year-old woman with Albright's syndrome (polyostotic fibrous dysplasia of bone, precocious puberty and irregular cutaneous pigmentations) had sustained multiple fractures and was grossly disabled. Evaluation disclosed markedly raised serum alkaline phosphatases and a high urinary excretion of hydroxyproline, suggesting an accelerated bone turnover, while calcium metabolism was virtually undisturbed. During 12 months therapy with calcitonin, however, no apparent benefit was recorded and there was no evidence of any significant metabolic effects of the treatment. Initial discomfort with nausea and vomiting disappeared after dose reduction whereas diffuse bone and muscle pain, which gradually increased after a few months treatment, did not subside until after cessation of the therapy.
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PMID:A case of Albright's syndrome treated with calcitonin. 47 95

For patients who require treatment over a period of some years, intranasal administration of synthetic salmon calcitonin (SSCT) obviates the discomfort associated with administration by injection. Moreover, this mode of administration is not associated with the side effects normally encountered when calcitonin is injected intramuscularly or subcutaneously. The aim of this study was to assess, in normal subjects, the biological activity of nasal SSCT by comparing the fluctuations of parameters reflecting calcium-phosphorus metabolism after nasal instillation, injection of SSCT and injection of placebo, respectively. In nine healthy subjects, this instillation of 200 IU of SSCT into the nasal cavity caused a fall in serum calcium, a fall in serum phosphorus and a transient rise in parathyroid hormone levels similar to that observed after the intramuscular (i.m.) injection of 80 IU of SSCT. SSCT whether administered by the nasal route or by injection, does not inhibit endogenous calcitonin secretion. There were no changes in serum beta-endorphin, magnesium or erythrocyte magnesium levels after administration of calcitonin by the intranasal route or by injection.
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PMID:Assessment of the biological effectiveness of nasal synthetic salmon calcitonin (SSCT) by comparison with intramuscular (i.m.) or placebo injection in normal subjects. 350 25

Annual bone loss rate was estimated in a group of randomly selected 150 nonsurgical and nonosteoporotic early postmenopausal women, 42-56 years, with the use of the mathematical equation proposed by Christiansen et al. (OSTEOTREND-R) [1]. Fifty-six women were characterized as high turnover patients (estimated annual bone loss more than 2.7%). These high turnover patients were included in a double-blind, placebo-controlled clinical study. Patients were divided into two groups of 28 women each. The first group of patients received 100 IU of salmon calcitonin intranasally daily for 1 year and the second group intranasal spray of placebo daily. Blood and urine biochemical parameters as well as bone mineral content of the spine and proximal forearm were determined initially and at the end of 6 and 12 months. No other side effects were noted apart from discomfort of nasal mucosa in two patients (one in each group). The group of calcitonin-treated patients showed a dramatic decrease in bone loss rate as estimated with the use of biochemical bone markers at the end of 6 and 12 months (3.7% versus 0.8% and 0.0% at the end of 6 and 12 months, respectively, P < 0.001) whereas in the placebo group, bone loss rate remained unchanged (4.2% versus 4.1% and 4.3% at the end of 6 and 12 months, respectively). The calcitonin-treated patients showed a significant increase in bone mineral content of spine and proximal forearm (P < 0.001 at the end of 6 and 12 months, respectively). On the other hand, a significant decrease in all measurement sites appeared in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of bone loss in early nonsurgical and nonosteoporotic high turnover patients with salmon calcitonin: the role of biochemical bone markers in monitoring high turnover patients under calcitonin treatment. 779 44

Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures. Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. < or = 2 years), the incidence of osteoporotic fractures. A large multicentre 5-year study with adequate statistical power to confirm the effect of intranasal salcatonin on reducing osteoporotic fracture rates in postmenopausal women is currently under way. The intranasal formulation of salcatonin offers a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intramuscular injections. Adverse events associated with the intranasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis. Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal salcatonin is an attractive alternative for the management of osteoporosis.
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PMID:Intranasal salcatonin (salmon calcitonin). A review of its pharmacological properties and role in the management of postmenopausal osteoporosis. 893 99

An intricate surveillance network consisting of enteroendocrine cells, immune cells and sensory nerve fibres monitors the luminal and interstitial environment in the alimentary canal. Functional bowel disorders are characterized by persistent alterations in digestive regulation and gastrointestinal discomfort and pain. Visceral hyperalgesia may arise from an exaggerated sensitivity of peripheral afferent nerve fibres and/or a distorted processing and representation of gut signals in the brain. Novel strategies to treat these sensory bowel disorders are therefore targeted at primary afferent nerve fibres. These neurons express a number of molecular traits including transmitters, receptors and ion channels that are specific to them and whose number and/or behaviour may be altered in chronic visceral pain. The targets under consideration comprise vanilloid receptor ion channels, acid-sensing ion channels, sensory neuron-specific Na(+) channels, P2X(3) purinoceptors, 5-hydroxytryptamine (5-HT), 5-HT(3) and 5-HT(4) receptors, cholecystokinin CCK(1) receptors, bradykinin and prostaglandin receptors, glutamate receptors, tachykinin and calcitonin gene-related peptide receptors as well as peripheral opioid and cannabinoid receptors. The utility of sensory neuron-targeting drugs in functional bowel disorders will critically depend on the compounds' selectivity of action for afferent versus enteric or central neurons.
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PMID:Gastrointestinal afferents as targets of novel drugs for the treatment of functional bowel disorders and visceral pain. 1169 40

Hypercalcemia is one of the metabolic complications associated with cancer. To assess the frequency of hypercalcemia in patients with squamous cell carcinoma (SCC), 242 patients who were evaluated as having SCC in the oral cavity between July 1995 and June 2001 were investigated. All patients were periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dl. By this definition, hypercalcemia was detected in 12 of the 242 patients (5.0%). All 12 patients were at an advanced stage of oral SCC. In these 12 patients, the serum level of parathyroid hormone-related protein (PTH-rP) was also significantly elevated. Therefore, we diagnosed these diseases as humoral hypercalcemia of malignancy (HHM). Moreover, we studied the efficacy of anti-hypercalcemic therapy on the quality of life (QOL). The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 was used for estimation of QOL. The patients with HHM who were administrated drugs such as bisphosphonate and calcitonin showed a reduction in their Ca and PTH-rP levels, and the six of ten EORTC QLQ-C30 subscales (emotional functioning, cognitive functioning, fatigue, dyspnoea, nausea/vomiting and appetite loss) were also improved after the anti-hypercalcemic therapy. However, these suppressive effects were temporary. The median survival time after the diagnosis of HHM was only 54.9+/-18.3 days (range 27-86 days). Therefore, HHM in SCC appears to be an ominous prognostic sign. Although anti-hypercalcemic therapy has a palliative role, the patients may be in less discomfort during the terminal stage of their illness.
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PMID:Hypercalcemic complication in patients with oral squamous cell carcinoma. 1272 78

The bowel exhibits reflexes in the absence of CNS input. To do so, epithelial sensory transducers, such as enterochromaffin (EC) cells, activate the mucosal processes of intrinsic (IPANs) and extrinsic primary afferent (sensory) neurons. EC cells secrete serotonin (5-HT) in response to mucosal stimuli. Submucosal IPANs, which secrete acetylcholine and calcitonin gene-related peptide, initiate peristaltic and secretory reflexes and are activated via "5-HT1P" receptors. Release of neurotransmitters is enhanced by 5-HT4 receptors, which are presynaptic and strengthen neurotransmission in prokinetic pathways. 5-HT3 receptors mediate signaling to the CNS and thus ameliorate cancer chemotherapy-associated nausea and the visceral hypersensitivity of diarrhea-predominant irritable bowel syndrome (IBS-D); however, because 5-HT3 receptors also mediate fast ENS neurotransmission and activate myenteric IPANs, they may be constipating. 5-HT4 agonists are prokinetic and relieve discomfort and constipation in IBS-C and chronic constipation. 5-HT4 agonists do not initiate peristaltic and secretory reflexes but strengthen pathways that are naturally activated. Serotonergic signaling in the mucosa and the ENS is terminated by a transmembrane 5-HT transporter, SERT. Mucosal SERT and tryptophan hydroxylase-1 expression are decreased in experimental inflammation, IBS-C, IBS-D, and ulcerative colitis. Potentiation of 5-HT due to the SERT decrease could account for the discomfort and diarrhea of IBS-D, while receptor desensitization may cause constipation. Similar symptoms are seen in transgenic mice that lack SERT. The loss of mucosal SERT may thus contribute to IBS pathogenesis.
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PMID:Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome. 1579 84

In patients with pseudohypoparathyroidism, hormonal resistance first affects parathyroid hormone (PTH), which leads to calcipenia, a decrease in renal vitamin D activation, and a tendency to bone receptor remodeling. However, because G proteins are ubiquitously distributed, multiple hormonal resistance occurs in pseudohypoparathyroidism type Ia and type Ic, impairing responses to other calciotropic hormones (PTHrP, calcitonin), TSH, and also pituitary and hypothalamic hormones, and to neurosensory stimuli. The diversity of multihormonal resistance contributes to the various phenotypes of the disease. Some clinical discomfort and medical consequences of the disease can be treated or prevented with hormone supplementation or modulation.
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PMID:Multihormonal resistance to parathyroid hormone, thyroid stimulating hormone, and other hormonal and neurosensory stimuli in patients with pseudohypoparathyroidism. 1678 31

Malignant mesenchymoma of the thyroid is extremely rare. We report such a tumor involving the bilateral lobes of the thyroid which showed simultaneous chondrosarcomatous, osteosarcomatous, fibrosarcomatous and rhabdomyosarcomatous differentiation. The patient was a 52-year-old woman admitted with a history of facial swelling, neck thickness and swallowing discomfort of one month's duration. Sonographic examination indicated a thyroid mass involving the bilateral lobes. Macroscopically, the tumors of both lobes were well demarcated, solid, greyish-white, and multinodular on the cut surface. Some nodules were translucent in appearance and hard in texture. Microscopically, the tumor was composed of small primitive mesenchymal cells with osteoid formation resembling the small cell variant of osteosarcoma interspersed with multiple cartilaginous nodules that indicated chondrosarcomatous differentiation. Some tumor cells showed prominent rhabdomyoblastic differentiation with eosinophilic cytoplasm and eccentric nuclei. Fibrosarcomatous areas were also observed. Immunohistochemically, the small primitive mesenchymal cells were positive for vimentin and CD99 and negative for CD56, Syn, CgA, CK, TG, TTF-1, calcitonin, and S-100. The tumor cells in the rhabdomyosarcomatous area were MyoD1 and muscle-specific actin positive. Molecular analysis for BRAFand RAS gene alterations showed no point mutation. The tumor recurred four months after surgery and tumor thrombi were suspected in the bilateral internal carotid arteries on ultrasonography. Primary malignant mesenchymoma of the thyroid is a high-grade malignant tumor with a poor prognosis. Its differerential diagnosis includes anaplastic carcinoma and other rare sarcomas with chondroid, osteoid, and other mesenchymal metaplasia.
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PMID:Malignant mesenchymoma of the thyroid: case report and literature review. 2057 98


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