Fatigue after aneurysmal subarachnoid hemorrhage evaluated by pituitary function and 3D-CBF.

OBJECTIVE: The reason for longstanding fatigue following aneurysmal subarachnoidal hemorrhage (SAH) is still not clarified. The bleed from supratentorial aneurysms is often in the vicinity of the hypothalamus and pituitary gland making an endocrine dysfunction plausible. METHODS: Ten patients with post-SAH fatigue were investigated with 3D-CBF (SPECT) and underwent an evaluation of the pituitary function. RESULTS: Five had normal pituitary function. Disturbances in the gonadotropin function was detected in three patients and suspected in two. The mean insulin-like growth factor I (IGF-I) value of the patients was in the lower part of the reference range. In the patients with endocrine dysfunction, the 3D-CBF was pathologic in the central structures of the basal region. CONCLUSIONS: The present results indicate that an aneurysmal SAH may result in partially impaired pituitary capacity. This deficit may contribute to fatigue after aneurysmal SAH, but cannot solely explain this disorder. SPECT identified regional tissue damage in the patients with pituitary dysfunction after SAH.

Evaluation of surgery for acromegaly: role of intraoperative growth hormone measurement?

OBJECTIVE: Intraoperative growth hormone (GH ) measurement has earlier been tried to improve surgery for acromegaly. We calculated GH half-life after adenomectomy and evaluated the possible role of this variable in predicting the final outcome of pituitary surgery in 28 consecutive patients with acromegaly. The sensitivity, specificity and predictive values were determined in relation to the results from GH suppression during an oral glucose load and IGF-1 3 months postoperatively. The GH half-life data were also compared to the corresponding results obtained from GH measurements between 60 min and 180 min after adenomectomy, and early, within 1 week, postoperatively. RESULTS: GH half-life < or =31 min was recorded in 8/13 cured patients but also in 2/15 unsuccessful cases. A mean GH concentration < or =4.4 mU/L between 60 min and 120 min after adenomectomy was found in 11/13 cured subjects but also in 3/15 not cured patients. A mean GH < or =4.0 mU/L between 90 min and 180 min was found in 11/13 cured and in 4/15 not cured patients. A mean early postoperative GH concentration < or =2.6 mU/L was noted in all 13 cured patients, but also in 2/13 unsuccessful cases. The specificity of early postoperative GH < or = 2.6 mU/L was 100% compared to 62% for a GH half-life < or =31 min (p<0.05) and 85% for the GH mean values between 60 min and 120 min and 90 min and 180 min, respectively. The sensitivity for persistent disease of values above the four cut-off limits used was between 73% and 87%. The positive predictive value for a mean early postoperative GH value >2.6 mU/L was 100%, and 72% for a GH half-life >31 min (n.s.). CONCLUSION: Although intraoperative GH half-life might be useful in some cases, it was not a reliable tool for predicting outcome of pituitary surgery in acromegaly. In cases with a 51% decrease of a basal GH concentration >5.5 mU/L, mean GH values < or =4 to < or =4.4 mU/L late intraoperatively were more informative but not as good as those obtained from the mean of a series of GH values drawn on one occasion within 1 week postoperatively, offering a 100% specificity for cure if < or =2.6 mU/L. Intraoperative GH half-life measurements should therefore be used with caution. The predictive values of the cut-off limits used in this study should be further evaluated before general application.

Decreased levels of ionized calcium one year after hemithyroidectomy: importance of reduced thyroid hormones.

BACKGROUND: Previously we have found reduced levels of total serum calcium and 1,25(OH)2D3 despite an unaltered stimulated parathyroid hormone (PTH) secretion 1 year after hemithyroidectomy. The present study was undertaken to elucidate the possible relationship between calcium homeostasis, thyroid hormones and bone resorption in a group of 45 consecutive patients subjected to hemithyroidectomy because of a solitary nodule. All patients had free T4 and T3 levels within normal range preoperatively. METHODS: Thyroid hormones, bone mineral and biochemical variables known to reflect calcium homeostasis were studied. Patients were divided into three separate groups depending on their pre- and postoperative thyroid hormone status. RESULTS: One year postoperatively, serum levels of free T4 were decreased and that of thyrotropin (TSH) increased in the entire group of patients. The concentration of ionized calcium was reduced from 1.25 +/- 0.05 to 1.22 +/- 0.04 (p < 0.001) despite an unaltered PTH value (2.8 +/- 1.0 vs. 3.1 +/- 1.5, p = 0.50). A significant reduction in C-terminal telopeptide type 1 collagen (1CTP) indicated decreased bone resorption 1 year after surgery (p < 0.05). Subgroup analysis showed that a reduction in ionized calcium was seen only among patients with a postoperative decrease in free T4. Patients with subclinical hyperthyroidism preoperatively presented the lowest postoperative levels of ionized calcium, significantly reduced levels of 1CTP and increased levels of phosphate and creatinine. Multiple linear regression analysis showed that age (p < 0.05) and postoperatively changed serum levels of TSH (p < 0.05), creatinine (p < 0.05), phosphate (p < 0.001) and FT4 (p < 0.01) were independently associated with altered levels of ionized calcium. CONCLUSION: We conclude that the reduction in ionized calcium 1 year after hemithyroidectomy was not due to PTH deficiency. Instead our results suggest that the reduced effects of thyroid hormones on bone and kidney function is essential.

Urate and arteriosclerosis in primary hyperparathyroidism.

OBJECTIVE: An increased mortality due to cardiovascular disease has been reported in patients with primary hyperparathyroidism (pHPT). An association between urate and cardiovascular disease has been suggested. Metabolic abnormalities in pHPT may include urate. We therefore evaluated the metabolic arteriosclerotic risk profile in pHPT with special focus on the role of urate. DESIGN: Retrospective analysis of data before and 1 year after surgery for pHPT. PATIENTS: 130 consecutive patients, over the age of 44 years, who underwent surgery for pHPT. MEASUREMENTS: Biochemical variables known to reflect risk of arteriosclerotic disease (AD) and renal function tests including measurement of glomerular filtration rate (GFR) were investigated before and 1 year after surgery. RESULTS: pHPT patients with AD (n = 40) were older and had higher serum levels of urate and triglyceride, and more impaired renal function in comparison with patients without AD. PTH and calcium values did not differ. Multiple logistic regression analysis indicated that urate was an independent risk factor for AD in pHPT (P < 0.01). Three variables were shown to be positively associated with urate; male gender (P < 0.01), fasting blood glucose (P < 0.05) and serum level of triglyceride (P < 0.05). CONCLUSIONS: Urate was found to be an independent risk factor for arteriosclerotic disease in primary hyperparathyroidism. Serum level of urate could (in addition to gender) be associated with a metabolic disorder comprising increased glucose and triglyceride levels.

Enhanced endothelin-1-induced contractions in mesenteric arteries from rats with congestive heart failure: role of ET(B) receptors.

Studies of congestive heart failure (CHF) in man and in experimental CHF have demonstrated elevated circulating levels of endothelin (ET). In order to examine whether there are concomitant ET receptor alterations, the vasomotor effects of endothelin-1 (ET-1) and sarafotoxin 6c (S6c) were examined in endothelium-intact and -denuded isolated mesenteric arteries from rats with CHF. CHF was induced by ligation of the left anterior descending coronary artery. Vasomotor responses were studied using small mesenteric arteries (approx. 250 microm in diameter, determined after normalisation). The antagonists IRL2500 and FR139317 were used in order to characterise the ET-1-induced response. In mesenteric arteries with intact endothelium, ET-1-induced contractions were more potent in CHF as compared to sham (pEC(50) 9.6+/-0.2 and 9.1+/-0.1, respectively, P<0.01). In endothelium-denuded arteries, there was no difference in potency of ET-1 between CHF and sham arteries, or in maximum contraction. In the presence of IRL2500, a selective ET(B)-receptor antagonist, ET-1 was more potent in endothelium-denuded arteries of CHF rats, while this difference was not seen in sham arteries. S6c had no consistent contractile or dilatory effect in CHF and sham rats. The results indicate that the enhanced contractile effects of ET-1 noted in CHF might be due to an attenuated endothelial function and that inhibition of smooth muscle cell ET(B) receptors increase the effects of contractile ET(A) receptors in CHF rats.

Enhanced Ca2+-induced contractions and attenuated alpha-adrenoceptor responses in resistance arteries from rats with congestive heart failure.

AIM: The aim of the present study was to examine the role of Ca2+-mediated contractile responses in isolated mesenteric resistance arteries from rats with congestive heart failure (CHF). METHODS: Heart failure was induced by ligation of the left coronary artery. Rats exposed to the same surgical procedure except ligation served as controls (Sham). The following experiments were conducted: (1) passive increase in radial stretch (the length-tension relationship) in Ca2+-free and in depolarizing high K+-solution; (2) the contractile responses to external application of Ca2+ and high K+-solutions in the presence of nifedipine and phentolamine; and (3) a histological evaluation of CHF and Sham vessels. RESULTS: The length-tension induced response in Ca2+-free buffer solution was significantly lower in arteries from CHF rats, starting at a very low tension (0.9+/-0.2 mN/mm for heart failure and 1.7+/-0.2 mN/mm for Sham). This difference, but at a higher degree of stretch, was also present in K+-activated vessels. The external application of Ca2+ in K+-depolarized vascular segments in the presence of phentolamine (1 microM) induced an enhanced contractile response in arteries from CHF rats compared with Sham (4.8+/-0.3 mN/mm and 3.6+/-0.6 mN/mm, respectively, P=0.059). In the absence of phentolamine the reverse response was found (4.0+/-0.4 mN/mm and 5.7+/-0.3 mN/mm for CHF vs. Sham respectively, P=0.035). Application of increasing concentrations of K+-solution induced a stronger contractile response in Sham compared with CHF arteries (Sham 4.9+/-0.4 and heart failure 4.0+/-0.3, P=0.04). Microscopic examination of vessels yielded no difference in gross morphology, media thickness or wall to lumen ratio between CHF and Sham arteries. CONCLUSION: The results indicate an attenuation of alpha-adrenoceptors and a difference of Ca2+-mediated vascular contractility in resistance arteries of congestive heart failure rats.

Postoperative elevated serum levels of intact parathyroid hormone after surgery for parathyroid adenoma: sign of bone remineralization and decreased calcium absorption.

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.

Early postoperative growth hormone levels: high predictive value for long-term outcome after surgery for acromegaly.

OBJECTIVES: To explore the prognostic value of early - within 1 week - postoperative growth hormone (GH) measurements with regard to outcome after surgery for acromegaly in a short- and a long-term perspective. DESIGN: Retrospective study of patients operated on between 1987 and 1998, including follow-up for up to 60 months. SETTING: University hospital. SUBJECTS: Sixty-eight patients with acromegaly. INTERVENTION: Pituitary surgery aiming at adenomectomy with preservation of pituitary function. MAIN OUTCOME MEASURES: The effect of the operation was evaluated after 3 months, mostly by means of an oral glucose load or by insulin-like growth factor 1 (IGF-1). The specificity, sensitivity and the predictive values of an early postoperative mean GH concentration 4.8 mU L-1 had a 77.8% predictive value for persistent or recurrent disease, compared with 85.7% for persistently increased SmC/IGF-1 and 68.8% for an abnormal GH release after TRH 3 months after surgery. In the short-term perspective, the specificity and the predictive value of an early GH 4.8 mU L-1 had a 94.4% sensitivity but a predicative value of only 63.0% for an unsatisfactory effect. CONCLUSION: Measurement of GH within 1 week after surgery is highly predictive for outcome of surgery for acromegaly. Specifically, an early mean GH 4.8 mU L-1 have a high sensitivity for persistent or recurrent disease in both the short- and long-term perspectives, but lower predictive value. The usefulness of the TRH test can be questioned.

Risk factors for postoperative hypocalcemia after surgery for primary hyperparathyroidism.

HYPOTHESIS: A variety of clinical and biochemical variables may be associated with hypocalcemia after surgery for parathyroid adenoma. DESIGN: A prospective study of patients who underwent surgery for solitary parathyroid adenoma. SETTING: A university hospital department of surgery. PATIENTS: Eighty-six consecutive patients who underwent surgery for solitary parathyroid adenoma. INTERVENTION: Parathyroidectomy according to the principles of unilateral neck exploration. MAIN OUTCOME MEASURES: Clinical and biochemical risk factors for early (< or =4 days after surgery) and late (1 year after surgery) postoperative symptomatic and biochemical hypocalcemia. RESULTS: Twenty-two patients developed early symptomatic hypocalcemia. The difference in total serum calcium levels between patients, with and without early symptomatic hypocalcemia, was evident on the third and fourth postoperative days. Serum level of osteocalcin greater than 6.0 microg/L, bilateral neck exploration, and history of cardiovascular disease were risk factors for symptomatic hypocalcemia (odds ratios [95% confidence intervals]: 4.4 [1.4-14.1], 3.8 [1.3-11.6], and 0.1 [0.02-0.60], respectively). Patients with up to 1 risk factor had a possibility of only 7% to develop early symptomatic hypocalcemia. One year after surgery, 16 patients had low levels of total serum calcium (late biochemical hypocalcemia) and were asymptomatic. Preoperative intermittent hypercalcemia was associated with an increased risk for late biochemical hypocalcemia (odds ratio, 3.9; 95% confidence interval, 1.0-16.3). CONCLUSIONS: Clinical and biochemical risk factors for early and late postoperative hypocalcemia in patients who underwent surgery for solitary parathyroid adenoma were found. A clinically useful prognostic index for early symptomatic hypocalcemia was constructed using these risk factors.

Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat.

It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status, the basilar, mesenteric and renal arteries and the iliac vein were studied in vitro. Dilatory responses were determined in relation to pre-contraction by the thromboxane mimetic U46619. Sham-operated animals (Sham) served as controls. U46619 induced stronger contraction in CHF basilar and renal arteries compared with the corresponding segments in Sham. ACh induced concentration-dependent dilations in all vessels examined with no difference of maximum relaxation or potency between CHF and Sham. SP induced weak dilations in all arteries examined while the response was markedly attenuated in CHF iliac veins compared with Sham (Emax% 12.2 +/- 3.4 vs. 32.3 +/- 4.8, P = 0.01). The CGRP induced dilation in the CHF basilar artery was weaker (Emax% 18.6 +/- 6.5 vs. 66.9 +/- 5.0, P < 0.001) and less potent (pEC50: 8.2 +/- 0.2 vs. 9.0 +/- 0.2, P = 0.01) compared with Sham. Further, CGRP was less potent in the renal artery of CHF rats compared with Sham (pEC50: 8.1 +/- 0.2 vs. 9.5 +/- 0.3, P < 0.01). In the CHF iliac vein, CGRP was more potent compared with Sham (pEC50: 9.7 +/- 0.4 vs. 8.3 +/- 0.4, P < 0.05). It can be concluded CHF is accompanied by alterations in the vascular response to the dilatory substances studied. The changes differ between vascular beds and between the different substances.

Hyperthyroidism after surgery for primary hyperparathyroidism.

BACKGROUND: The coexistence of hyperthyroidism and primary hyperparathyroidism (pHPT) has been reported. We have questioned whether hypercalcemia or surgical trauma contribute to transient hyperthyroidism following parathyroid surgery. METHODS: Twenty-six pHPT and eleven breast cancer patients were compared regarding pre-, peri- and postoperative thyrotropin (TSH), free thyroxine (T4) and free triiodothyronine (T3) concentrations. Thyroglobulin concentration, occurrence of autonomous thyroid nodules, and variables reflecting surgical trauma were compared in pHPT patients with and without postoperative hyperthyroidism. RESULTS: Postoperatively, eleven pHPT patients demonstrated T4 and T3 concentrations above normal, and nine developed symptoms of mild thyrotoxicosis. A parallel rise in TSH and T4 concentrations was seen during both parathyroid and breast cancer surgery. Compared with patients with no postoperative hyperthyroidism, patients with postoperative hyperthyroidism showed a parallel rise in mean thyroglobulin and T4/T3 concentrations as well as higher thyroglobulin concentrations. However, there was no difference in variables assessing surgical trauma nor in occurrence of autonomous thyroid nodules. The peri-operative rise in TSH was preceded by a decrease in calcium. CONCLUSION: Transient hyperthyroidism after parathyroid surgery is not infrequent. The condition seems to be self-limiting, since symptoms invariably subsided without treatment. Manipulation of the thyroid gland is most likely the major contributing factor to postoperative hyperthyroidism. However, it may not be the sole explanation, since our data suggest a more multifactorial scenario.

Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment.

OBJECTIVES: Untreated primary hyperarathyroidism (pHPT) is accompanied by an excessive morbidity in circulatory disorders, associated with blood pressure and diabetes. The aim of the present study was to further penetrate the impact of pHPT on glucose, urate, lipid and lipoprotein concentrations, known to be interrelated metabolic cardiovascular risk factors. DESIGN: Longitudinal study of patients with pHPT before and 1 year after surgical treatment. SETTING: Departments of Internal Medicine and Surgery, Lund University Hospital. SUBJECTS: One hundred and seventeen consecutive patients with pHPT referred to surgical treatment. At presentation. 11 patients had previously diagnosed diabetes mellitus. INTERVENTION: All patients were successfully operated for pHPT. MAIN OUTCOME MEASURES: Fasting blood glucose and serum concentrations of cholesterol, triglyceride and urate were determined before and 1 year after surgery. The concentration of LDL- and HDL-cholesterol was separately analyzed in 21 cases. These data as well as the systolic and diastolic blood pressure were related to intact PTH and ionized calcium at presentation. Glomerular filtration was separately measured pre-operatively and related to the urate values. RESULTS: While the mean value for glucose remained unchanged among 11 patients with previously diagnosed diabetes at presentation, a significant decrease of glucose from 5.03+/-0.13 to 4.71+/-0.08 mmol/L (P < 0.05) was found among patients without known diabetes. Out of these patients, eight had diabetic glucose values at presentation, decreasing from 8.35+/-0.54 to 5.10+/-0.35 mmol/L (P < 0.05), and 12 had glucose values indicating impaired glucose tolerance, decreasing from 5.94+/-0.06 to 5.10 +/-0.38 mmol/L (P < 0.05) after surgery. Total cholesterol and trigylceride concentrations were not changed. However, male patients had significantly lower triglyceride levels at follow-up, 1.16+/-0.09 mmol/L compared to 1.57+/-0.14 mmol/L before surgery (P < 0.05). Significantly lower triglyceride values were also found among patients with glucose values indicating impaired glucose tolerance at presentation. The LDL/HDL cholesterol ratio remained normal. The serum level of urate decreased in both male and female patients after surgery, and was positively correlated to the PTH and ionized calcium values and inversely correlated to renal function before treatment. There was no significant correlation between calcium or PTH and the other metabolic variables studied.

Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease.

OBJECTIVES: To evaluate the impact on bone turnover of primary hyperparathyroidism (pHPT) with special reference to patients with mild pHPT, using biochemical markers of bone formation and resorption. DESIGN: A longitudinal study of patients with pHPT before and one year after surgical treatment. SETTING: The Departments of Internal Medicine and Surgery, Lund University Hospital. SUBJECTS: Forty consecutive patients with pHPT. Thirty of these patients had mild pHPT and are reported separately. Data on bone mineral was also compared to a reference population. INTERVENTION: All patients were operated upon and restudied one year later. MAIN OUTCOME MEASURES: Bone resorption and formation was studied by means of the serum concentrations of the telopeptide of the carboxyterminal region of type 1 collagen (ICTP) and of alkaline phosphatase (ALP), osteocalcin and the carboxyterminal propeptide of type 1 procollagen (PICP), respectively. Bone density was measured at the distal radius by single photon absorptiometry (SPA). RESULTS: Bone formation markers consistently decreased after parathyroid surgery: ALP from 3.51 +/- 0.23 to 2.94 +/- 0.21 microkat L(-1) (P < 0.05), osteocalcin from 6.15 +/- 0.53 to 2.89 +/- 0.23 microg L(-1) (P < 0.001) and PICP from 126.4 +/- 10.9 to 96.0 +/- 6.5 microg L(-1) (P < 0.001). In parallel, the ICTP concentration, reflecting bone resorption, decreased from 5.10 +/- 0.54 to 3.94 +/- 0.34 microg L(-1) (P < 0.001). There was not any significant change in distal radius bone mineral 1 one year after surgery. In the subgroup of patients classified as mild pHPT, a significant decrease was noted for osteocalcin, PICP and for ICTP but not for ALP, without significant changes in variables reflecting distal radius bone mineral content. Glomerular filtration rate was inversely correlated to serum levels of intact PTH, ionized calcium, alkaline phosphatase, osteocalcin and ICTP and directly correlated to the 1.25-dihydroxy-vitamin D concentrations. CONCLUSIONS: pHPT is associated with substantial changes in circulating levels of biochemical markers of bone formation and resorption. These findings are also present in patients with mild pHPT. Renal function should be considered in the evaluation of the impact of pHPT on bone turnover.

Persistent elevated serum levels of intact parathyroid hormone after operation for sporadic parathyroid adenoma: evidence of detrimental effects of severe parathyroid disease.

BACKGROUND: A significant number of patients with primary hyperparathyroidism (pHPT) who are surgically treated have increased serum levels of intact parathyroid hormone (PTH) during long-term follow-up despite normocalcemia. The cause and significance of this finding remain to be established. METHODS: A total of 82 patients operated on for sporadic parathyroid adenoma were investigated before and at 8 weeks and 1 year after operation with serum levels of intact PTH, bone mineral content, and biochemical variables known to reflect PTH activity. RESULTS: All patients had low or normal serum levels of calcium during follow-up. At 8 weeks after operation 20 (24%) patients had increased serum levels of PTH. These patients had severe parathyroid disease and low levels of 25(OH) vitamin D before operation. In contrast to patients with normal levels of PTH after operation, they did not have an elevated bone mineral content but had elevated levels of serum creatinin. At 1 year after operation 13 patients had elevated serum levels of PTH. Compared with patients with normal serum levels of PTH, they were older and had an increased frequency of cardiovascular disease and biochemical indications of compromised renal function. They did not have an elevated bone mineral content. CONCLUSIONS: Persistently increased serum levels of PTH indicate harmful effects of pHPT even after surgical cure, especially in elderly patients with severe disease before operation. The results in this investigation therefore favor early treatment of pHPT.

Modulation of vascular contractile responses to alpha 1- and alpha 2-adrenergic and neuropeptide Y receptor stimulation in rats with ischaemic heart failure.

In order to evaluate adaptational changes in vascular function in congestive heart failure (CHF), we studied the contractile responses of isolated arterial and venous blood vessels from rats suffering from CHF induced by coronary artery ligature, resulting in a myocardial infarction. The contractile responses of the basilar, femoral and renal arteries and of the iliac vein were examined in relation to adrenergic and neuropeptide Y (NPY) receptor function by the action of the alpha 1 agonist phenylephrine, the alpha 2 agonist clonidine and NPY. The contractile force was measured (in mN) and in % of K(+)-induced contraction as well as pD2 to each agonist. When stimulated by a 60 mM K(+)-buffer solution, the femoral and renal arteries from CHF rats responded with a stronger contraction (Emax; 9.4 +/- 0.6 and 9.8 +/- 0.6 mN) than the corresponding Sham vessels (Emax; 6.2 +/- 0.7 and 5.6 +/- 0.4 mN respectively, P < 0.001). On the contrary, the iliac vein of CHF responded less to K+ than the Sham iliac vein (Emax 2.5 +/- 0.2 and 3.7 +/- 0.5 mN, P < 0.01). The CHF iliac vein responded with a weaker contraction when stimulated with phenylephrine (Emax 1.9 +/- 0.4 mN) and showed a lower sensitivity (pD2 5.6 +/- 0.1) than the corresponding sham vessel (Emax 5.7 +/- 2.3 mN and pD2 6.3 +/- 0.5, P < 0.05). The CHF renal artery was less sensitive to clonidine (pD2 6.4 +/- 0.6) than the Sham renal artery (pD2 7.2 +/- 0.1, P < 0.05). The results indicate differences between CHF and Sham vessel segments according to both contractile capacity induced by K(+)-depolarization and to agonist induced contractile capacity and sensitivity. The differences are not of general nature but vary according to the vascular bed examined.

Clinical use of laboratory thyroid tests and investigations.

Laboratory thyroid testing involves in vitro tests for autoimmune thyroid disease, thyroid dysfunction and neoplasia, in vivo investigations of thyroid function, and investigations of thyroid morphology. The authors describe, in tabular form, the diagnostic information carried by the tests and their clinical utility as well as clinically relevant interferences.

Relationships between plasma levels of catecholamines and neuropeptides and the survival time in patients with congestive heart failure.

OBJECTIVES: To evaluate the importance of various variables reflecting neuroendocrine activation in relation to prognosis in patients with congestive heart failure (CHF). DESIGN: Plasma levels of noradrenaline, adrenaline, neuropeptide Y, substance P, calcitonin gene-related peptide, vasopressin and atrial natriuretic peptide were measured in patients presenting with CHF and related to survival time. Survival time was calculated from the time-point of this investigation until the month when the patient died or until December 1992. The follow-up period ranged up to 60 months. Seven of the 31 patients were still alive at the end of this period. SETTING: Lund University Hospital, Sweden. SUBJECTS: Thirty-one patients with CHF due to ischaemic heart disease. Six patients had a degree of heart failure corresponding to NYHA I-II and 25 corresponding to NYHA III-IV. Ten of these 25 patients were on angiotensin converting enzyme (ACE) inhibition in addition to therapy with digoxin and diuretics. The catecholamine and neuropeptide levels were compared to those of a control group of 31 healthy subjects aged 20-80 years. INTERVENTION: There were not any specific intervention in addition to the treatment for heart failure as outlined above. MAIN OUTCOME MEASURES: Survival time until death from heart disease or until the end of the follow up period in December 1992. RESULTS: There were inverse relationships between survival time on one hand and plasma values of noradrenaline (r = -0.49; P < 0.01) and atrial natriuretic peptide (r = -0.49; P < 0.01) on the other hand. There was a significant correlation between the plasma values of noradrenaline and atrial natriuretic peptide (r = 0.50; P < 0.01). CONCLUSION: Increased plasma levels of noradrenaline and atrial natriuretic peptide are of major importance as prognostic markers in patients with CHF.

Increased ratio between anaerobic and aerobic metabolism in lymphocytes from hyperthyroid patients.

While an increased oxygen consumption is accepted as one consequence of hyperthyroidism, only few data are available on the role of anaerobic processes for the increased metabolic activity in this disease. In this study we evaluated the relative importance of anaerobic and aerobic metabolism for the metabolic activity in lymphocytes from patients before and after treatment for hyperthyroidism. Total lymphocyte heat production rate (P), reflecting total cell metabolic activity, was determined in a plasma lymphocyte suspension using direct microcalorimetry. The contribution from aerobic metabolism (O2-P) was calculated from the product of the lymphocyte oxygen consumption rate and the enthalpy change for glucose combustion, and the anaerobic contribution as the difference between P and O2-P. The total lymphocyte heat production rate P was 3.37 +/- 0.25 (SEM) pW/cell (N = 11) before and 2.50 +/- 0.11 pW/cell (N = 10) after treatment for hyperthyroidism (p < 0.01) as compared to 2.32 +/- 0.10 pW/cell in a control group (N = 18). The aerobic component O2-P amounted to 1.83 +/- 0.11 pW/cell in the patient group before and 1.83 +/- 0.08 pW/cell after treatment and to 1.71 +/- 0.16 pW/cell in 10 controls. Out of P, the O2-P component corresponded to 56.8 +/- 4.4% in the hyperthyroid state and to 73.7 +/- 3.2% after treatment (p < 0.01) as compared to 73.4 +/- 4.4% in the 10 euthyroid controls. It was concluded that the increased metabolic activity demonstrated in lymphocytes from hyperthyroid patients cannot be explained by an increased oxygen-dependent consumption.(ABSTRACT TRUNCATED AT 250 WORDS)