The effects of retinoic acid on the insulin-like growth factor axis in primary tissue culture from hyperparathyroidism.

BACKGROUND: The importance of the IGF system in HPT has been previously demonstrated. Additionally, the role of vitamin A in HPT has been reported. Retinoic acid (RA), a derivative of vitamin A, is a ligand for the IGF II receptor (IGF2R). We have evaluated the interactions of RA with the IGF system in a primary parathyroid cell culture model. MATERIALS AND METHODS: Primary cell cultures were prepared from nine patients. Following adhesion, the cells were transferred to serum-free medium and dosed once with growth factors +/- RA for 96 hours. Proliferation was assessed by measuring tritiated thymidine incorporation. RESULTS: Compared with the control group (100%), both IGF I and II increased DNA synthesis significantly. Retinoic acid significantly reduced the basal DNA synthesis to 82.2% +/- 4.2% compared with control (P < 0.05). Retinoic acid x10(-5) M completely abrogated the proliferative actions of IGF II (70.2% +/- 9.7%, P < 0.05) but had no significant effect on the IGF I response (P > 0.05). To evaluate the role of IGF2R or IGFBPs in mediating the actions of RA, the IGF II analogs [Leu27]IGF II (10-20-fold reduced IGF I receptor affinity) and des(1-6) IGF II (lower IGFBP binding affinity) were used. The IGF II inhibitory effect of RA was enhanced in the presence of analogs [Leu27]IGF II (P = 0.052) but not with des(1-6)IGF II (P > 0.05), compared with wild-type IGF II. CONCLUSIONS: These data implicate a novel antiproliferative role for RA in enhancing the pericellular clearance of IGF II via the IGF2R preventing ligand activation of the IGF I receptor. This may have broader implications for RA effects in other tumors.

Emotion-related primary and secondary appraisals, adjustment and coping: associations in women awaiting breast disease diagnosis.

OBJECTIVE: Different emotions are to some extent associated with different ways of coping. Cognitive processes involved in determining emotional reactions may influence coping (perhaps through directing attention or generating salient information). This study explored possible appraisal-coping associations by examining whether a set of appraisal components identified in emotion theory were also associated with coping. DESIGN: The study examined concurrent associations between appraisal components, emotional adjustment, and coping in 148 women with suspected breast disease. METHOD: Questionnaire measures of primary and secondary appraisal components identified in emotion theory, anxiety, depression, and coping were sent to women during the waiting period between GP referral and attendance at a 'one-stop' breast-disease diagnosis clinic. RESULTS: Consistent with expectations, appraisal components were associated with both emotions and coping. Elevated anxiety was associated with appraisals of low emotion-focused coping potential; avoidance coping was associated with motivational incongruence, self-accountability, and pessimistic appraisal of emotion-focused coping potential; acceptance/resignation coping was associated with self-accountability and pessimistic appraisals of both future expectancy and emotion-focused coping potential. CONCLUSION: This study presents a theoretically driven approach to exploring associations between emotions and adjustment efforts. In keeping with expectations, a number of appraisal components identified in emotion theory were found to be associated with both emotion and coping.

An investigation into the relationship between salivary cortisol, stress, anxiety and depression.

This study examined the relationship between indices of self-reported emotional distress and absolute versus change in cortisol levels. Fifty-four women attending a diagnostic breast clinic completed scales measuring stress, anxiety and depression and provided five saliva samples over the course of a single day for the measurement of cortisol. No significant relationships were evident between absolute cortisol levels and the distress measures. Analysis of the change in cortisol levels revealed a non-linear interaction effect between stress and anxiety and time of day. There was a non-linear relation between time of day and cortisol levels, but the extent of the non-linearity was dependent upon levels of stress and anxiety, not depression. A relationship was apparent between indices of distress and change in cortisol levels, but not absolute levels of the hormone.

Selective estrogen receptor modulators inhibit the effects of insulin-like growth factors in hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (HPT) predominantly affects perimenopausal women, leading to speculations that an estrogen imbalance may be liable. We have previously demonstrated the importance of the insulin-like growth factor (IGF) axis in HPT. Because the antiestrogen tamoxifen has been shown to modulate the IGF axis, we examined the interactions of selective estrogen receptor modulators (SERMs) and IGF in HPT. METHODS; Estrogen receptors were evaluated by Western immunoligand blotting. Sixteen parathyroid glands from 19 patients were included. After adhesion, the cells were treated with IGF (I or II) +/- estrogen +/- SERMs (tamoxifen, ICI 182,780) for 96 hours in serum-free media. Proliferation was assessed by measuring tritiated thymidine incorporation. RESULTS: Both primary and secondary HPT express estrogen receptors alpha and beta. Primary and secondary HPT had comparable responses to SERMs, they were analyzed together. Compared with control (100%), IGFs (I and II) induced a significant increase in DNA synthesis. Estradiol at 10(-8) and 10(-7) mol/L (physiologic range) had no significant effects on IGF (I and II, P >.05). Both tamoxifen and ICI 182,780 inhibited basal DNA synthesis (P <.05) and abolished the effects of both IGF I and II (P <.05). CONCLUSIONS: SERMs are capable of reducing basal and IGF-stimulated DNA synthesis. This reduction in proliferation has implications for cancer biology and therapeutic potential for SERMs in HPT.

Use of octreotide and lanreotide in the treatment of symptomatic non-resectable carcinoid tumours.

BACKGROUND: Carcinoid tumours are rare neoplasms that secrete hormones and biogenic amines, most commonly serotonin. Octreotide and long acting lanreotide are found to be useful in the management of carcinoid syndrome by its interaction with somatostatin receptor, found on the carcinoid tumour. The aim of this study is to look at the efficacy of octreotide and long acting lanreotide in the treatment of symptomatic non-resectable carcinoid tumours. METHOD: The effects of octreotide and long-acting lanreotide were studied in 10 patients with symptomatic non-resectable carcinoid tumours. RESULTS: Symptom improvement occurred in nine of 10 patients. Three patients responded only to octreotide, three patients responded to both octreotide and long-acting lanreotide and three patients only responded to long-acting lanreotide. Slight reductions in 24-h urine 5-hydroxyindoleacetic acid levels occurred in three of six patients but no patients were found to have objective tumour regression on computed tomography scan. CONCLUSIONS: Octreotide and long-acting lanreotide are useful palliative treatments for the control of symptoms in patients with non-resectable carcinoid tumours but there is no evidence of tumour stasis.

Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma.

Despite adverse side effects, phenoxybenzamine has been widely used for the preoperative management of patients with pheochromocytoma. Doxazosin, a specific a 1-adrenoceptor antagonist, has a pharmacologic profile more suited to controlling blood pressure in such patients. A sequential study of 35 patients with pheochromocytoma encompassed a definite and prescribed change in preoperative drug management from phenoxybenzamine to doxazosin. Hemodynamic, pharmacologic, and biochemical indicators of a- and b-adrenoceptor blockade were measured before, during, and after anesthesia and surgery in 8 patients pretreated with phenoxybenzamine and 27 patients pretreated with doxazosin. Doxazosin (2-16 mg/day) was as effective as phenoxybenzamine in controlling arterial pressure and heart rate before and during surgery, but doxazosin caused fewer undesirable side effects both before and after surgery. Following phenoxybenzamine therapy substantial a 1-adrenoceptor blockade, detected as a right shift of phenylephrine dose-response curves, persisted for more than 2 days postoperatively, whereas after doxazosin it was undetectable on the first postoperative day. Doxazosin provided safe, efficacious pre- and perioperative control of arterial pressure. In patients with predominantly norepinephrine-secreting tumors, pretreatment 24-hour urinary norepinephrine excretion gave an indication of the daily doxazosin requirement.