Association between pre-PTCA blood haemoglobin concentration and the risk of symptomatic restenosis after successful PTCA of primary coronary stenoses.

BACKGROUND: Thrombus formation at the dilation site has been suggested to initiate the restenosis process after percutaneous transluminal coronary angioplasty (PTCA). High haemoglobin concentrations may predispose to thrombus formation by increasing blood viscosity, slowing coronary blood flow and increasing thrombocyte adhesion. METHODS: Pre-PTCA blood haemoglobin concentrations (Hb) in 44 patients with symptomatic restenosis > or = 50% of the vessel diameter (Group A) were compared with Hb in the remaining 215 patients in a consecutive study population (Group B). RESULTS: Median Hb (range) was 149 (119-164) g/l in Group A and 142 (117-164) g/l in Group B, P = 0.004. Odds ratio (95% CI) for symptomatic restenosis was 3.22 (1.62-6.42) when Hb was dichotomised according to the median in the entire material. Hb, but not sex was a significant risk factor in multivariate analysis. CONCLUSION: Hb is a hitherto not recognized factor associated with the risk of symptomatic restenosis after PTCA and may be a link coupling male sex with increased risk of restenosis.

Release of prolactin as well as adrenocorticotropin after administration of arginine-vasopressin to healthy men.

The study was undertaken to obtain simultaneous measurements of circulating anterior pituitary hormone levels after the i.v. injection of arginine-vasopressin (AVP). Nine healthy men, mean age 31 years (range 24-41), received single blind with at least one week apart, after resting in the supine position for 30 min, AVP 0.26 microgram/kg body weight i.v. (Pitressin, Parke-Davis) or saline in randomized order. Blood samples were taken at 0, 10, 20, 30, 45 and 60 min for analyses of serum or plasma levels of ACTH, prolactin, TSH, GH, FSH, LH and AVP. The hormone responses after AVP or saline were calculated as the area under the curve (AUC) 0-60 min as well as the change in hormone levels from 0 to 10 min to pick up possible short lasting effects when there was no significant difference in AUC between AVP and control. As expected the highest plasma concentration of AVP was measured 10 min after the injection of AVP and well comparable to those in other studies where AVP was observed to release ACTH. The AUC:s for both ACTH and prolactin levels were significantly increased after AVP in comparison with saline (p = 0.008 and p = 0.038, respectively). The AUC:s for the other hormones measured were not significantly changed after AVP, but there were small but significant changes in the 0-10 min values for TSH and LH after AVP compared to saline. It is concluded that AVP has the potency to release not only ACTH but also prolactin in healthy men.

Vasoactive peptides in Bartter's syndrome.

Patients with Bartter's syndrome exhibit an increased vascular resistance to the pressor effects of angiotensin II and noradrenaline. Further, an increased production of vasodilating renal prostaglandins, perhaps mediating the vascular unresponsiveness, has been hypothesized in this syndrome based on high urinary prostaglandins. To determine whether different peptides might contribute to blood pressure control in this syndrome, the basal immunoreactive plasma levels of an array of vasoactive peptides and catecholamines were analysed in six patients with Bartter's syndrome. Among the vasoconstrictors analyzed, the mean plasma levels of noradrenaline (NA), adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY-LI) were significantly increased as compared to healthy subjects (P = 0.030, 0.046 and 0.001, respectively). The plasma level of the vasodilator substance P (SP-LI) was also higher in these patients (P = 0.057). These results indicate that in Bartter's syndrome the vasoconstrictive effect of catecholamines and angiotensin II may be enhanced by concomitant NPY release. Whether a release of the vasodilator substance P is an independent mechanism or represents a reflex response to the increased secretion of angiotensin II, catecholamines and/or NPY remains to be established. However, the significance of these biochemical findings for blood pressure maintenance in Bartter's syndrome remains to be settled.

Increased plasma level of substance P in patients with severe congestive heart failure treated with ACE inhibitors.

The effects of angiotensin-converting-enzyme (ACE) inhibitors on circulatory regulating mechanisms in congestive heart failure (CHF) were studied by comparison of plasma levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), substance P (SP-LI), calcitonin gene-related peptide (CGRP-LI), vasopressin (ADH-LI), atrial natriuretic peptide (ANP-LI) and renin activity (PRA) in patients with severe CHF (NYHA III-IV) with (n = 15) or without (n = 17) ACE inhibitors in addition to digoxin and diuretic therapy. Data were also compared with those for healthy subjects (n = 31) and patients with moderate CHF (NYHA I-II). Catecholamines and NPY-LI were increased to the same extent in both groups with severe CHF. CGRP-LI showed no changes relative to controls in any of the patient groups, and was not affected by ACE inhibitors. The SP-LI level was significantly increased in all patient groups. Patients with severe CHF on ACE inhibition had a SP-LI level of 4.05 +/- 0.79 pmol l-1, compared to a concentration of 2.28 +/- 0.30 pmol l-1 (P less than 0.05) in the patient group with a comparable degree of CHF but without ACE inhibition. In the latter group, an inverse relationship appeared between the SP-LI and the serum sodium levels (r = -0.68, P less than 0.05). The patients with severe CHF who received ACE inhibitors had significantly lower ADH-LI levels than the patients with a comparable degree of CHF who were not treated with ACE inhibitors, while the ANP-LI levels was increased to a similar extent in both groups.

Early postoperative basal serum GH level and the GH response to TRH in relation to the long-term outcome of surgical treatment for acromegaly: a report on 39 patients.

During a 10-year period 39 patients with acromegaly, aged 23-73 years, underwent selective adenomectomy via a trans-sphenoidal or transfrontal (one case) approach. Six to 12 months after the operation, the serum level of growth hormone (GH) was reduced to less than 5 micrograms l-1 in 28 patients (74%) in at least two of three random samples and/or suppressed to less than 3 micrograms l-1 during an oral glucose load, thus fulfilling the commonly used criteria for a successful operation. In 10 patients these criteria for adequate GH reduction were not fulfilled, but their median S-GH level was reduced from 38 to 11 micrograms l-1 (P less than 0.01) after the operation. Surgery was successful in 11 of 13 (85%) patients with a microadenoma (less than 10 mm in diameter), in 10 of 14 (71%) patients with an adenoma of diameter greater than 10 mm but still enclosed in the sella, and in seven of 11 (64%) patients with locally invasive tumours. Impaired pituitary function was observed in 23% of the patients after surgery, independent of tumour size. In one patient the postoperative period was complicated by a lethal intracranial infection. During follow-up for 1-10 years, four patients relapsed, after 1, 1.5, 6 and 9 years, respectively. Patients for whom surgery appeared to have been ineffective at the evaluation 6-12 months postoperatively, or who later relapsed were identified by early (within 7 d) postoperative serum GH with a sensitivity of 90%. The accuracy for identification of a satisfactory outcome of surgery was 85%, and the predictive value was 90%. The corresponding values for the GH response to TRH measured 6-12 months postoperatively were 47, 40 and 54%, respectively. It is concluded that the basal level of serum GH measured 1-7 d postoperatively has higher sensitivity and specificity than the GH response to TRH 6-12 months postoperatively for evaluation of the effect of surgery on GH overproduction, and that it has a higher predictive power with regard to the long-term outcome of surgery for acromegaly.

Hormonal influence on calcitonin gene-related peptide in man: effects of sex difference and contraceptive pills.

Calcitonin gene-related peptide (CGRP) is one of the peptides encoded for by the calcitonin gene. It has been demonstrated in man to be located in the thyroid and in perivascular nerves and to possess potent vasodilatory properties. In the present study we found plasma levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) to be significantly higher in females than in males and that women on contraceptive pills had significantly higher CGRP-LI levels than women not taking contraceptives. These data are in accordance with one earlier report on an increased CGRP level during pregnancy and suggest a positive influence of the female sex hormones on the plasma CGRP level in man, which should be considered in the establishment of a reference range for this analysis.

Changes in the functional state of the erythrocyte membrane: significance for red cell filterability and blood viscosity.

Blood samples from nine healthy men were studied to determine the effect of ouabain and elevated serum calcium concentration on blood viscosity, measured by a rotational viscometer, and on red cell filterability by the St George's Filtrometer, giving values for clogging particles (CP) and red cell transit time (RCTT). Blood viscosity at a standardized haematocrit of 45% and red cell filterability was investigated in blood samples incubated for 1 h with Ringer's solution only (control), with ouabain (0.70 mmol/l) in plasma, or with serum calcium concentration increased by 3.0 mmol/l by addition of CaCl2. Incubation with ouabain significantly reduced erythrocyte K+ concentration and increased that of Na+. Ouabain caused a decrease in blood viscosity (p less than 0.05-0.005) compared to controls, although there was no decrease in red cell filterability parameters. When incubating with calcium, CP and RCTT increased significantly indicating 'stiffer' red cells, but there was no increase in blood viscosity. It is concluded that blood viscosity may be influenced by red cell factors not detected by CP or RCTT, which in turn appear to reflect red cell deformability with greater sensitivity and specificity than blood viscosity. It is concluded also that the functional state of the cell membrane may be of significance for the rheological properties of erythrocytes.

Gamma 2-MSH in congestive heart failure: relation to atrial natriuretic peptide, arginine vasopressin and catecholamines.

A possible role of the proopiomelanocortin derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has been studied in patients with various degrees of congestive heart failure (CHF). The profile of changes in circulating levels of gamma 2-MSH-like immunoreactivity (-LI) has been compared with those of atrial natriuretic peptide (ANP)-LI, arginine vasopressin (AVP)-LI and catecholamines in CHF. Patients with moderate CHF (New York Heart Association stages I-II) showed significantly higher levels of h-alpha ANP-LI and NA (P less than 0.05) compared to controls. Patients with severe CHF (stages III-IV) had significantly higher levels of all hormones measured compared to controls: noradrenaline, P less than 0.001; adrenaline, P less than 0.001; gamma 2-MSH-LI, P less than 0.001; h-alpha ANP-LI, P less than 0.05; AVP-LI, P less than 0.01. For the catecholamines and gamma 2-MSH-LI there was a significant increase from moderate to severe forms of CHF. A significant correlation was observed between gamma 2-MSH-LI and noradrenaline, and between h-alpha ANP-LI and noradrenaline in patients with CHF. The present results show that gamma 2-MSH-LI is increased only in severe forms of cardiac failure, and that this change is more closely related to the increase in circulating levels of noradrenaline than to increased levels of ANP-LI or AVP-LI.

Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres.

In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP-LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system.

Reduced size of a hormonally silent pituitary adenoma during treatment with CV 205-502, a new dopamine agonist mainly stimulating D2 receptors.

A 39-year-old woman with secondary amenorrhea and visual field defects underwent craniotomy for a large pituitary tumor that was hormonally silent according to measurement of plasma hormone levels and immunohistochemical analysis. During the preoperative investigation, bromocriptine was administered for 1 month, but there was no change in the tumor size as seen on computed tomographic scans. One month after surgery, visual field defects recurred, and a tumor mass comparable to the preoperative state was found on computed tomographic scan. The tumor size gradually diminished during treatment with CV 205-502, a tricyclic benzoquinoline which stimulates mainly D2 receptors and is better tolerated than bromocriptine. The visual fields were completely normalized after 3 months of treatment with the drug, and surgical management of the tumor mass was no longer considered to be necessary. Thus, as in many similar cases, the hormonally silent pituitary tumor in this patient proved unresponsive to bromocriptine treatment. In contrast, the tumor was reduced by therapy with CV 205-502, a drug that is better tolerated and might permit a more intense stimulation of D2 receptors.

Mechanism for the inhibitory action of 2-deoxy-glucose on thyroid hormone secretion in the mouse.

The thyroid gland is richly innervated but the effects of activation of these nerves on thyroid hormone secretion are not yet established. In the present study, intravenous injection to mice of 2-deoxy-glucose (2-DG; 60 mumol/animal) was used to activate the autonomic nerves. The nerve activation occurs through the neuroglycopenia. We found that 2-DG inhibited the thyroid-stimulating hormone (TSH; 70 microU/animal)-induced thyroid hormone secretion, measured as release of radioiodine bound to anti-T4 in radioiodine-pretreated mice. This inhibition by 2-DG was completely reversed by the alpha-adrenoceptor antagonist phentolamine but not affected by the beta-adrenoceptor antagonist L-propranolol or the muscarinic receptor antagonist methyl-atropine. It is therefore concluded that neuroglycopenia-induced activation of the autonomic nerves inhibits TSH-induced thyroid hormone secretion by a mechanism that is reversed by phentolamine. It is suggested that it is mainly the adrenergic nerves that are involved in this action, and, consequently, that the function of the adrenergic nerves in thyroid physiology is to restrain the stimulatory action of TSH.

Studies on blood viscosity during the menstrual cycle and in the postmenopausal period in healthy women.

Blood viscosity was measured in 14 healthy, menstruating women, aged 17-51 years and in 10 healthy, postmenopausal women, aged 55-64 years. The fertile women were studied once a week during a normal menstrual cycle and the postmenopausal women twice with an interval of 2 weeks. Blood viscosity was measured at natural hematocrit as well as at hematocrit 45%. In the postmenopausal women no changes in blood viscosity were found. In the fertile women, blood viscosity at hematocrit 45% was lowest at the start of the menstrual bleeding and increased to a peak at day 7 (p less than 0.01), with a similar pattern when measured at natural hematocrit. Plasma viscosity also had its lowest value at the onset of menstrual bleeding, increasing to a maximum at day 21. Changes in plasma triglycerides, but not in fibrinogen or cholesterol, seemed to contribute to this increase. Plasma factors only partly explained the variations in blood viscosity, and changes in red cell properties were also found to be of importance. The clinical significance of these rheological changes remains to be established, but at least theoretically there may be an increased risk for thromboembolism, e.g. at surgery, during days 5-15 of the cycle. In studies on blood flow and rheological conditions in fertile women, it seems advisable to standardize for time in the menstrual cycle.

Occupational lead exposure and pituitary function.

Twenty-five moderately exposed lead workers (mean blood-lead level 1.9 mumol/l) had lower plasma levels of follicle stimulating hormone than 25 individually matched controls without occupational lead exposure (blood-lead level 0.2 mumol/l). In addition, the ten most heavily exposed individuals had higher levels of thyroid stimulating hormone, and the 14 workers under the age of 40 had decreased plasma levels of luteinizing hormone and serum levels of cortisol, as compared to the controls. All values were within "normal" reference limits. There was no significant change of the plasma testosterone level. These data indicate a complex effect on the endocrine system by moderate lead exposure, possibly mediated by changes at the hypothalamic-pituitary level. Besides the effect on hormone levels, there was also a decrease in plasma selenium level for the lead exposed workers.

Corticosteroid action on choroid plexus: reduction in Na+-K+-ATPase activity, choline transport capacity, and rate of CSF formation.

Glucocorticoids have a well-known clinical effect on brain edema and intracranial hypertension, but the mechanism of action is still poorly understood. In the present report the effect of beta-methasone on choroid plexus transport and CSF formation was studied. Following 5 days of daily treatment with betamethasone the CSF production rate in rabbits was reduced by 43% as measured by ventriculo-cisternal perfusion with radioactive inulin. Accordingly, the transport capacity in the choroid plexus, measured in terms of choline uptake and accumulation in vitro, and the activity of Na+--K+-ATPase decreased in both rabbit (in the lateral ventricles by 31 and 31%, respectively) and rat (by 16 and 24%, respectively). Thus, the demonstrated influence of glucocorticoids on these functions of the choroid plexus seem to be important components in their therapeutic effect on intracranial hypertension.

Effects of VIP and helodermin on thyroid hormone secretion in the mouse.

The two peptides VIP (vasoactive intestinal peptide) and helodermin have both been shown to occur within the thyroid gland: VIP in intrathyroidal nerves and helodermin in the C-cells. Both peptides have previously been demonstrated to enhance the release of radioiodine from the prelabelled thyroid in vivo. Since a considerable amount of radioiodine released from the thyroid under these conditions may be non-hormonal, we reexamined the effects of VIP and helodermin on thyroid hormone secretion by the use of the specific technique of studying the release of radioiodine bound to specific T4 antiserum in mice. We thereby found that anti-T4-bound radioiodine in T3-pretreated animals increased after intravenous injection of VIP (1.5 nmol/animal) to 280 +/- 24% (P less than 0.001), and after intravenous injection of helodermin (1.5 nmol/-animal) to 186 +/- 26% (P less than 0.001) compared to 78 +/- 5% in controls. As a comparison, the corresponding figure after injection of TSH (70 microU/animal) was approximately 350% (P less than 0.001). In contrast, in animals not pretreated with T3, neither TSH, nor VIP helodermin significantly altered the plasma level of anti-T4-bound radioiodine. Also, VIP and helodermin did not change the plasma levels of free T4 in non-pretreated animals. In summary, the sensitive and specific technique of measuring the release of anti-T4-bound radioiodine in vivo after pretreatment with NA 125I and T3 detected a stimulation of the thyroid hormone secretion by VIP and helodermin.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of thyroxine release in vivo: a simple, specific and sensitive method in mice.

When thyroid hormone secretion in vivo was studied by the release of 125I from thyroid to blood after TSH in mice preloaded with the isotope, only 54.4 +/- 2.0% (+/- SE) of plasma 125I was butanol extractable, indicating low specificity for thyroid hormones. To improve specificity plasma 125I was bound to anti-T4 rabbit antibodies and precipitated with goat antirabbit serum. The intraassay coefficient of variation was 2.5%, and anti-T4 bound radioactivity correlated well with that extractable with butanol (r = 0.95, P less than 0.001). The effect of 40-1000 microU TSH intravenously in mice pretreated with 1 microgram T3 3 times during 2 days to suppress endogenous TSH was evaluated 2 hrs after the injection of TSH by 1) conventional radioimmunoassays of total and free stable T4 in plasma (no preloading with 125I), 2) total blood 125I in mice preloaded with 125I, and 3) anti-T4 bound 125I in plasma in mice preloaded with 125I. Stable T4 increased with TSH doses of 70 microU or higher, but the slope was low and the relation between error variance and slope did not permit a useful bioassay. Total blood 125I responded significantly to 40 microU TSH and showed a favourable relation between error variance and slope, but the specificity may be questioned. Anti-T4 bound 125I in plasma also responded significantly to 40 microU TSH and showed a very good relation between error variance and slope. The new technique of measuring anti-T4 bound radioactivity seems to combine the specificity of radioimmunoassay with a precision and sensitivity well comparable to that of the conventional radioiodine release technique.

Suppressed plasma prolactin response to thyrotropin-releasing hormone in hyperthyroidism reproduced by thyroxine but not by triiodothyronine administration to normal subjects.

In 10 hyperthyroid women studied in the follicular phase of the menstrual cycle, basal plasma PRL was normal, but PRL release after TRH was significantly suppressed compared with that in 11 control women. The suppressed PRL response to TRH was not explained by changes in serum estradiol or sex hormone-binding globulin. It recovered after treatment of hyperthyroidism. When normal women were treated with T4 (0.5 mg daily for 6 to 10 days), their mean serum free T4 level increased to about 70% of that in the hyperthyroid patients, whereas their serum free T3 levels increased to a lesser degree. During T4 administration, these women had PRL changes similar to those of the hyperthyroid patients. When the normal women took T3 (60-120 micrograms for 6 to 8 days), their serum free T3 increased to almost the level of the hyperthyroid patients, but the TRH stimulated PRL release remained close to the control level. The PRL increase after dopaminergic blockade with metoclopramide was significantly suppressed in hyperthyroid patients, and they had no PRL response to TRH after pretreatment with metoclopramide. In conclusion, the PRL changes in hyperthyroidism were reproduced by administration of T4, but not by administration of T3 to healthy women. The site of action is suggested to be pituitary, but additional hypothalamic effects cannot be excluded.

Nasal administration of desmopressin by spray and drops.

A solution of desmopressin was administered intranasally as a spray using a metered dose pump, or as drops using a single dose pipette or rhinyle catheter. Volunteers, and patients with diabetes insipidus, were given an intranasal dose of 20 micrograms desmopressin by each method. The antidiuretic activity was measured by determination of urine osmolality and diuresis. Each delivery system was equally effective in producing a rapid onset of activity, a highly reproducible magnitude of effect and duration of the antidiuretic effect which lasted for more than 8 h. The pipette and spray pump offer a choice of single dose administration without preservative, or for chronic use, well-controlled, reproducible dosing, respectively.

Erythrocyte metabolism in hyperthyroidism: a microcalorimetric study on changes in the Embden-Meyerhof and the hexose monophosphate pathways.

Erythrocyte metabolism was studied in vitro by microcalorimetry in 10 hyperthyroid subjects before and after treatment. By inhibiting the enzyme enolase in the Embden-Meyerhof pathway with sodium fluoride (NaF) we have recorded the anaerobic and aerobic contributions in erythrocyte thermogenesis. The decrease in heat production rate in samples with NaF corresponds to the anaerobic contribution, whereas the values from samples with NaF reflect aerobic processes. Before treatment, total heat production rate was 120 +/- 2 mW/l erythrocytes which was higher than the post-treatment value of 99 +/- 2 (P less than 0.001) as well as the value for 14 euthyroid subjects, 108 +/- 2 mW/l (P less than 0.001). The NaF inhibitable rate was 73 +/- 2 before and 63 +/- 1 mW/l after therapy (P less than 0.01). These values correspond to 61 +/- 1 and 64 +/- 1% (n.s.) of the total heat production rate, and were similar to that of 61 +/- 2% for the controls. Heat production rates in the presence of NaF were 47 +/- 1 before and 36 +/- 1 mW/l after therapy (P less than 0.001), representing 39 +/- 1 and 36 +/- 1% of total values, respectively. The present results show that overall metabolism is increased in erythrocytes from hyperthyroid subjects before treatment and returns to normal after normalization of the thyroid function. Moreover, by using microcalorimetry we found that the metabolic activity along the Embden-Meyerhof anaerobic pathway as well as along the hexose monophosphate aerobic pathway in erythrocytes is stimulated by thyroid hormones.