Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A review is given on the clinical features of carcinoid syndrome including symptomatology, diagnostics, biochemistry and treatment. We have reviewed the literature on current therapy of carcinoid patients with special emphasis on the use of the somatostatin analogue SMS 20-1995. In addition, we present data on the effects of SMS 201-995 on indices of a clinical, biochemical and tumor growth. Diarrhea is abolished or significantly reduced in 75% of patients, flushing improves in 100%, wheezing in 100% with a decrease in airways resistance, and in one patient myopathy has improved. Blood serotonin is notoriously resistant to intervention and urinary 5-HIAA will decrease in 75% of causes but subsequently rebounds in 38%. Tumors, in general, continue to grow, but this may be slowed or in rare cases tumor growth is arrested. In individual instances the tumor may even infarct, leading to spontaneous cure. Tumors secreting PP, ACTH and calcitonin may be particularly resistant to treatment, whereas VIP secreting tumors appear to be sensitive.
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PMID:Clinical features of carcinoid syndrome and the use of somatostatin analogue in its management. 266 49

Synthetic analogs of growth hormone-releasing hormone, GHRH(1-29)-NH2 and D-Ala2 GHRH(1-29)-NH2 were administered as a bolus intravenous injection to five normal men in a dose range of 0.015 to 0.5 micrograms/kg body weight. Vehicle only was administered in a control study. Peak responses to GHRH analogs occurred at 15 or 30 min. An increase in the integrated plasma growth hormone (GH) response was observed at each dose. The dose-response curve of GHRH(1-29)-NH2 indicated that it has a similar molar potency to GHRH(1-40) and GHRH(1-44). The potency of D-Ala2 GHRH(1-29)-NH2 was approximately twice that of GHRH(1-29)-NH2. Neither analog affected blood levels of PRL, TSH, LH, FSH, ACTH, insulin, glucagon, glucose, cortisol, free thyroxine, and free triiodothyronine. No side effects were noted other than transient flushing with the highest dose administered. The findings demonstrate GHRH(1-29)-NH2 and its D-Ala2 analog are potent stimulators of GH release and have potential application in clinical medicine.
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PMID:Growth hormone responses to growth hormone-releasing hormone (1-29)-NH2 and a D-Ala2 analog in normal men. 286 96

We have attempted to characterize a group of bronchopulmonary neoplasms that share certain structural features with true carcinoids but appear distinctly more pleomorphic and behave far more aggressively. In reviewing our files from 1973 to 1982, 11 such neoplasms were identified; the original diagnoses were "atypical bronchial carcinoid" (3 cases), "malignant carcinoid" (1 case), "bronchial carcinoid" (3 cases), "peripheral carcinoid" (2 cases), and "peripheral oat cell carcinoma" (2 cases). Of the 11 neoplasms, 5 were central and 6 were peripherally located. At presentation, 7 patients had lymph node metastases and 1 had a distant metastasis. No patient had a conventionally defined hormonal syndrome; however, 2 patients had a history of episodic flushing, one of which was associated with diarrhea. All cases were studied by light microscopy and light microscopic immunohistochemistry for NSE (neuron-specific enolase), serotonin, and broad-spectrum neuropeptides. Five cases were studied by electron microscopy. By light microscopy, the tumors were composed of solid clusters of polygonal to fusiform cells in an evident organoid arrangement. Foci of glandular and/or squamous differentiation were seen in 7 cases. Pleomorphism was moderate and mitoses were readily found. Focal necrosis was seen. By immunohistochemistry, 10 cases expressed NSE immunoreactivity. All cases demonstrated hormonal immunoreactivity; in 9 cases, immunoreactivity for more than one hormone was observed. The hormones most frequently expressed were serotonin, bombesin, gastrin, leu-enkephalin, and ACTH. By electron microscopy, all cases studied contained heterogeneous populations of neurosecretory granules; the latter, however, were not abundant and tended to aggregate either in the basal pole of the cells or, more frequently, interlacing "dendritelike" cytoplasmic processes. Aggregates of intermediate filaments were frequently seen. Basal lamina deposition was seen but gaps and larger areas of discontinuity were frequent. We believe that these neoplasms constitute a distinct pathologic entity for which the term "well-differentiated neuroendocrine carcinoma" has been proposed. Clinically, these tumors merit special attention since they are demonstrably more aggressive than true carcinoids but are distinctly less malignant than the intermediate or small cell variants of neuroendocrine carcinoma.
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PMID:Immunohistochemical and ultrastructural analysis of bronchopulmonary neuroendocrine neoplasms. II. Well-differentiated neuroendocrine carcinomas. 608 31

The intestinal carcinoid tumors of 26 patients were stained for the presence of serotonin, gastrin, somatostatin, motilin, secretin, glucagon, pancreatic polypeptide, ACTH, and neurotensin. Argentaffin and argyrophil stains were also performed in all cases. Thirty-five separate tumors (counting metastases and multiple primaries) from the 26 patients were studied. Serotonin was present in 30 of the 35 tumors. Nineteen tumors contained serotonin only. Fourteen tumors contained multiple neuroendocrine products. One tumor contained gastrin only. One tumor did not stain immunohistochemically, but was argyrophilic. Metastatic deposits were studied in nine patients. Some metastases produced the identical neuroendocrine products as the primary tumor, whereas others produced either additional or fewer hormones than the primary tumor. Moreover, different metastases from the same primary tumor were observed to produce different hormones. Argyrophilic cells were present in all cases and were much more numerous than cells staining by immunohistochemistry. Argyrophilic cells probably contain monoamines and polypeptide hormones in addition to those studied in this series. The argyrophil stain was the best general stain in this study for the demonstration of neuroendocrine cells. Argentaffin staining was negative in ten cases that were serotonin positive and two argentaffin positive cases were serotonin negative. The carcinoid syndrome, as clinically defined by the presence of flushing and diarrhea, was noted in five patients, all of whom had serotonin-containing small bowel carcinoids. Endocrine-related symptoms were not clinically appreciated in the remaining patients.
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PMID:The neuroendocrine products of intestinal carcinoids. An immunoperoxidase study of 35 carcinoid tumors stained for serotonin and eight polypeptide hormones. 618 28

Beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) plasma levels were characterized by a significant decrease in postmenopausal females (22 subjects aged from 56 to 70 yr) when compared to fertile women (22 subjects from 31 to 45 yr). On the contrary, ACTH plasma levels determined in 10 of the premenopausal and 13 of the postmenopausal subjects reported above showed constant levels in both groups. A significant increase in the beta-LPH/beta-EP molar ratio was observed in postmenopausal females. The plasma beta-LPH and beta-EP levels studied before and 6 months after ovariectomy, showed a significant decrease in 8 out of 10 patients, while they remained constant in the other 2. Two subjects, in whom postsurgical samples were taken during a flushing episode, showed beta-LPH and beta EP plasma levels which were both higher than the corresponding preovariectomy values. The results suggest that these changes may be important in explaining modifications in behavior and mood frequently found in postmenopausal females and in patients undergoing surgical castration in the fertile age.
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PMID:Beta-lipotropin and beta-endorphin in physiological and surgical menopause. 627 14

Synthetic ovine corticotropin-releasing factor (CRF) was administered to normal male volunteer subjects as an intravenous bolus or 30-s infusion. Doses of CRF ranging from 0.001 to 30 micrograms/kg body wt were administered, and plasma immunoreactive (IR)-ACTH and IR-cortisol concentrations were measured. The threshold dose appeared to be 0.01-0.03 micrograms/kg, the half-maximal dose 0.3-1 micrograms/kg, and the maximally effective dose 3-10 micrograms/kg. Basal concentrations of IR-ACTH and IR-cortisol were 14 +/- 7.6 pg/ml (mean +/- SD) and 5.6 +/- 2.2 micrograms/dl, respectively. IR-ACTH rose as early as 2 min after CRF injection, reached peak levels in 10-15 min, and declined slowly thereafter. IR-cortisol rose at 10 min or later and reached peak levels in 30-60 min. At a dose of 30 micrograms/kg, neither IR-ACTH nor IR-cortisol fell from peak levels of 82 +/- 21 pg/ml (mean +/- SE) and 23 +/- 1.4 micrograms/dl, respectively, during the 2-h course of the experiment, indicating that CRF has a sustained effect on ACTH release and/or a prolonged circulating plasma half-life. There was little or no increase in the levels of other anterior pituitary hormones. At doses of 1 microgram/kg and higher, facial flushing, tachycardia, and, in some subjects, a 15-29-mmHg decline in systemic arterial blood pressure were observed, even though blood volume was replaced and the subjects remained supine. These data indicate that synthetic ovine CRF is a very potent and specific ACTH secretagogue in man. Administered with caution until its vasomotor effects are more fully defined, CRF promises to be a safe and very useful investigative, diagnostic, and, possibly, therapeutic agent in man.
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PMID:Effect of synthetic ovine corticotropin-releasing factor. Dose response of plasma adrenocorticotropin and cortisol. 629 80

Human GRF-(1-44)-NH2 (GRF-44) was administered iv in graded doses of 0.01-10 micrograms/kg to 35 normal young adult men and 38 women. GRF-44 stimulated the release of GH in a dose-dependent fashion, although the individual responses varied widely. The ED50 values for this effect were 0.4 micrograms/kg in men and 0.2 micrograms/kg in women in the midfollicular phase of the menstrual cycle. Maximal responses in men and women were not significantly different, and a dose of 1 micrograms/kg was sufficient to produce a maximal response. There was, likewise, no difference between responses of women tested in the midfollicular and midluteal phases of the cycle. There were no changes in PRL, LH, FSH, TSH, ACTH, beta-endorphin, or cortisol at doses up to 1 microgram/kg; at 10 micrograms/kg, PRL increased by an average of 7.6 ng/ml in the women. Side effects occurred in approximately 20% of both men and women at 1 microgram/kg and in nearly all subjects given 10 micrograms/kg; these consisted primarily of flushing and a sense of warmth. Thus, a dose of 1 microgram/kg GRF-44 is safe and effective, and would appear to be a reasonable choice for use in studying GH responses in normal subjects of other ages and in patients with disorders of GH secretion.
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PMID:Dose-response relationships for the effects of growth hormone-releasing factor-(1-44)-NH2 in young adult men and women. 633 Jan 51

Rats with a bilateral lesion of the olfactory bulb are permanently anosmic. However, this lesion also produces nonspecific behavioral effects that recover over time. In this study olfactory bulb-lesioned animals are given a spatial orientation task--the Morris maze--which supposedly relies on visual and not olfactory cues. In exp. 1 this assumption was verified by subjecting animals with peripherally induced anosmia to the Morris maze (olfactory neurons in the nasal mucosae were destroyed by flushing the nose with ZnSO4). Anosmia did not affect the acquisition rate of the animals. In exp. 2 anosmia was produced by a central lesion to the bulbus olfactorius. Two weeks after lesioning the Morris maze performance is severely impaired. Interestingly, chronic administration (10 micrograms/48 h/rat, during these 14 days, SC) of the ACTH(4-9) analog ORG 2766 diminished the impairment in performance. In exp. 3 olfactory bulb-lesioned animals were allowed 6 wk to recover before Morris maze testing began, to investigate if spontaneous recovery of performance occurred. No difference was seen in the acquisition performance of lesioned animals when compared to sham animals at this timepoint. The effect of the peptide is discussed in the context of an acceleration of the recovery of nonspecific consequences of brain lesioning.
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PMID:Olfactory bulbectomy temporarily impairs Morris maze performance: an ACTH(4-9) analog accellerates return of function. 766 12

The effectiveness and safety of MCI-028, a synthetic human corticotropin-releasing hormone (hCRH), as a diagnostic drug were examined in 65 healthy male and 24 healthy female adult volunteers. Mean maximum concentrations of plasma ACTH and cortisol after intravenous administration of 100 micrograms of MCI-028 were 3.0 and 2.0 times their basal concentrations, respectively, and there were no significant age or sex differences in the responses. Good reproducibility was observed in the responses in 59 male subjects who received a second administration after 1 to 2 weeks. Although slight adverse reactions such as mild and transient hot flushing were observed, these were not serious.
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PMID:Human corticotropin-releasing hormone (hCRH) test: sex and age differences in plasma ACTH and cortisol responses and their reproducibility in healthy adults. 795 23

The pharmacokinetics, responses of plasma ACTH and cortisol, urinary excretion of steroid hormones, and safety of MCI-028, a synthetic human corticotropin-releasing hormone (hCRH), were examined in eight healthy adult male volunteers after intravenous administration of 33, 100 and 200 micrograms of the drug. The disappearance of MCI-028 from plasma could be fitted to a biexponential decay curve, the plasma half-lives (T1/2) were 0.12 to 0.15 h for alpha phase, and 0.57 to 0.67 h for beta phase. Plasma ACTH and cortisol concentrations and the urinary excretion of steroid hormones (particularly free cortisol) increased significantly in relation to the MCI-028 dose administrated. Although hot flushing and an increase in the heart rate were observed at higher doses, they were mild and transient. It is also considered that the urinary excretion of free cortisol after the administration of MCI-028 can be an index reflecting the functioning of this system.
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PMID:Diagnostic study of a synthetic human corticotropin-releasing hormone (hCRH) in healthy adult males: its plasma pharmacokinetics and the effects on the urinary excretion of steroid hormones. 795 25


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