Effect of haemodialysis on plasma levels of brain natriuretic peptide in patients with chronic renal failure.

1. Plasma human brain natriuretic peptide-like immunoreactivity (hBNP-li) was measured in ten patients with chronic renal failure before and after 4 h of haemodialysis. 2. Plasma hBNP-li was elevated in all patients before dialysis (mean +/- SEM 21.0 +/- 3.8 pmol/l) compared with healthy control subjects (1.3 +/- 0.2 pmol/l, n = 11), but showed considerable inter-patient variability. Before dialysis plasma hBNP-li bore no relationship to the serum creatinine level or to the mean blood pressure. 3. Plasma hBNP-li fell significantly (P = 0.04) during 4 h of haemodialysis. The fall in plasma hBNP-li correlated significantly with the degree of postural blood pressure drop (r2 = 0.44, P = 0.05) and with the fall in body weight (r2 = 0.64, P less than 0.01) after haemodialysis. In all patients, plasma hBNP-li at the end of treatment remained above that in healthy subjects. 4. There was no significant correlation between the fall in plasma hBNP-li and the fall in serum creatinine level, and between the fall in plasma hBNP-li and the fall in supine systolic or diastolic blood pressure, during haemodialysis. 5. We have shown that plasma hBNP-li is elevated in patients with chronic renal failure and is decreased during haemodialysis. The fact that the plasma hBNP-li was not reduced to normal by haemodialysis despite restoration to normovolaemia gives tentative support to the view that, in addition to hypervolaemia, another factor may also be responsible for the elevated plasma hBNP-li seen in these patients.     

Neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma.

1. We investigated the usefulness of neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma using a simple and highly sensitive r.i.a. for human neuropeptide Y. 2. Plasma immunoreactive neuropeptide Y concentrations were measured without extraction in plasma samples (100 microliters) from patients with various diseases. 3. The plasma immunoreactive neuropeptide Y concentration in patients with phaeochromocytoma (172.3 +/- 132.4 pmol/l, mean +/- SD, n = 23) was significantly higher than that in healthy adult subjects (40.1 +/- 10.1 pmol/l, n = 40, P < 0.0001). The plasma immunoreactive neuropeptide Y concentrations in patients with ganglioneuroblastoma (590.7 +/- 563.6 pmol/l, n = 6) and patients with neuroblastoma (566.9 +/- 524.4 pmol/l, n = 15) were significantly higher than those in control children (1-9 years old, 82.2 +/- 39.9 pmol/l, n = 72, P < 0.0001). 4. The plasma immunoreactive neuropeptide Y concentration in patients with essential hypertension (34.0 +/- 3.7 pmol/l, n = 18) was within the normal range, but in patients with chronic renal failure undergoing maintenance haemodialysis (192.1 +/- 68.0 pmol/l, n = 25) and in non-dialysed patients with chronic renal failure (85.1 +/- 23.1 pmol/l, n = 7) it was significantly higher than that in healthy adult subjects (P < 0.0001). 5. Eighty-seven per cent of the patients with phaeochromocytoma, 67% of the patients with ganglioneuroblastoma and 80% of the patients with neuroblastoma showed plasma immunoreactive neuropeptide Y concentrations higher than the upper limits in the control subjects [62 pmol/l (adult) and 160 pmol/l (children)].(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma concentrations and comparisons of brain natriuretic peptide and atrial natriuretic peptide in normal subjects, cardiac transplant recipients and patients with dialysis-independent or dialysis-dependent chronic renal failure.

1. We have developed a radioimmunoassay for the measurement of immunoreactive brain natriuretic peptide (1-32) in human plasma. Simultaneous measurements of atrial natriuretic peptide have also been carried out to allow for direct comparison between circulating brain natriuretic peptide and atrial natriuretic peptide. Plasma levels of immunoreactive brain natriuretic peptide (means +/- SEM) were 1.1 +/- 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in cardiac transplant recipients (18.8 +/- 3.9 pmol/l, n = 12) and in patients with dialysis-independent (8.8 +/- 1.5 pmol/l, n = 11) or dialysis-dependent (41.6 +/- 8.8 pmol/l, n = 14) chronic renal failure. Similarly, in these groups of patients plasma levels of atrial natriuretic peptide were also significantly raised when compared with those in the group of normal healthy subjects. 2. The plasma level of atrial natriuretic peptide was significantly higher than that of brain natriuretic peptide in normal subjects and in patients with dialysis-independent chronic renal failure, with ratios (atrial natriuretic peptide/brain natriuretic peptide) of 2.8 +/- 0.2 and 2.2 +/- 0.3, respectively. However, in both cardiac transplant recipients and patients on dialysis plasma levels of atrial natriuretic peptide and brain natriuretic peptide were similar, with ratios of 1.3 +/- 0.2 and 1.0 +/- 0.1, respectively, in these two groups. 3. Plasma levels of brain natriuretic peptide and atrial natriuretic peptide were significantly correlated in the healthy subjects and within each group of patients. When all groups were taken together, there was an overall correlation of 0.90 (P < 0.001, n = 73).(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of brain natriuretic peptide in plasma samples and cardiac tissue extracts by means of an immunoradiometric assay method

We evaluated the analytical characteristics and clinical usefulness of a commercial immunoradiometric assay (IRMA) kit for brain natriuretic peptide (BNP). Mean (+/-SD) plasma BNP concentrations measured in 129 normal subjects were 2.9+/-2.7 pmol/l (median 2.2 pmol/l; range 0.1-12.4 pmol/l). The mean (+/- SD) value observed in healthy men (2.1 +/- 2.0 pmol/l, n = 49) was significantly (p=0.0009) different to that found in women (3.4 +/- 2.9 pmol/l, n=80). A positive relationship (R=0.214, p=0.0174) was found between BNP values and age. In 65 patients with cardiac diseases, BNP levels increased with the progression of clinical severity of disease; patients with more severe disease [NYHA functional class III-IV, mean (+/- SD) BNP +/- 254 +/- 408 pmol/l, n=22] showed significantly (p<0.0001) increased values compared to patients with mild symptoms of disease (NYHA functional class I-II, mean (+/- SD) BNP=19.6 +/- 17.2 pmol/l, n=43). Furthermore, in 32 patients with chronic renal failure, greatly increased (p<0.0001) BNP values were found both before (mean +/- SD=88. 1+/- 111.1 pmol/l) and after haemodialysis (mean +/- SD=65.6 +/- 76.7 pmol/l), with a significant reduction after haemodialysis (p=0.0004) compared to pre-haemodialysis. The mean (+/- SD) BNP value found in atrial extracts collected during aorto-coronary bypass operations in 15 patients was 14.5 +/- 51.9 pmol/g of cardiac tissue. Moreover, the mean (+/- SD) tissue levels of BNP in 7 heart transplant recipients were 128.4 +/- 117.2 pmol/g of cardiac tissue in atrium, 68.4 +/- 76.7 pmol/g in ventricle, and 10.9 +/- 8.5 pmol/g in interventricular septum. Finally, BNP values found in cardiac tissues of two subjects collected at autopsy were considerably lower (on average 1/1000) than those observed in cardiac tissues of patients with cardiac diseases. The IRMA method for BNP determination evaluated in this study showed a good degree of sensitivity, precision and practicability. Therefore, this method should be a reliable tool for the measurement of plasma BNP levels for both experimental studies and routine assay.     

Plasma glycolate concentrations under conditions of dialysis

Plasma glycollate and oxalate concentrations were measured in 20 patients undergoing chronic haemodialysis treatment. The mean plasma glycollate level was 173.7 +/- 52.9 mumol/l, which was not significantly different from the normal value (means = 145.8 +/- 37.8 mumol/l). The mean plasma oxalate concentration (means = 128.7 +/- 25.6 mumol/l) was about 8 times higher than the value found in normal volunteers (means = 16.8 +/- 6.0 mumol/l). During haemodialysis lasting for 6 hours the plasma oxalate concentration decreased by 53.5%. However, no decline in plasma glycollate levels was noted. Since glycollate was not found in ultrafiltrates obtained in vivo, it is concluded that glycollate is not eliminated during haemodialysis treatment.     

Characterization of subtypes of hypertension in CAPD patients by cyclic guanosine monophosphate.

OBJECTIVE: While most hypertensive patients with end-stage renal disease normalize high blood pressure with fluid removal by continuous ambulatory peritoneal dialysis (CAPD), there is a significant proportion of CAPD patients whose blood pressure can be controlled only by antihypertensive drugs. METHOD AND PATIENTS: To study the hypothesis that such patients are still volume overloaded, we used plasma cyclic guanosine monophosphate (cGMP) as a marker for hydration status. Thirty-two CAPD patients were divided into 3 groups: group 1, normotensive patients (n = 12); group 2, hypertensive patients who normalized their blood pressure with fluid removal (n = 12); group 3, hypertensive patients whose blood pressure was refractory to intensified fluid removal (n = 8). RESULTS: Mean cGMP levels were significantly higher in dialysis-sensitive hypertension (27 +/- 5 pmol/mL) than in dialysis-refractory hypertension (15 +/- 2 pmol/mL), or in normotensive patients (13 +/- 4 pmol/mL). Reduction of excess fluid in volume overloaded hypertensive CAPD patients resulted in a normalization of cGMP levels (14 +/- 8 pmol/mL), but did not affect this volume marker in patients with dialysis-resistant hypertension (10 +/- 4 pmol/mL). CONCLUSION: Plasma cGMP levels are elevated in volume overload-induced hypertension complicating CAPD. Hypertensive CAPD patients whose plasma cGMP levels are within normal limits have raised blood pressure refractory to volume removal. Our findings are consistent with the hypothesis that inadequate removal of excess volume plays a major role in a subset of patients with CAPD hypertension.     

Exaggerated responsiveness of immunoreactive atrial natriuretic peptide to saline infusion in chronic renal failure

Plasma levels of immunoreactive alpha human atrial natriuretic peptide (IR-ANP) were measured in nine patients with chronic renal failure before and after removal of 1.3-3.7 litres of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l: saline). Baseline levels of IR-ANP were elevated but fell by 22% during ultrafiltration. Saline infusion induced a rapid and steep rise in IR-ANP levels which were 150% of baseline while body weight was still 2% below baseline. Changes in plasma renin, angiotensin II, aldosterone and vasopressin during the study were slight compared with the change in IR-ANP, but noradrenaline levels rose threefold during ultrafiltration. There was a significant positive relationship between arterial pressure and IR-ANP levels before and after ultrafiltration. These results lend support to the suggestion that atrial peptides are of physiological importance, especially in states of chronic fluid overload such as chronic renal failure.     

Hormonal profile and serum zinc levels in uraemic men with gonadal dysfunction undergoing haemodialysis

Serum gonadal hormones, gonadotrophins and zinc levels were studied in thirteen men aged 29-62 yr with chronic renal failure undergoing haemodialysis. All patients had decreased libido and impotence. Serum testosterone levels in patients (18.5 +/- 1.3 (SEM) nmol/l) were significantly lower (p less than 0.05) than in the control group (24.1 +/- 2.2 (SEM) nmol/l) although salivary testosterone levels were strictly within the normal range. Mean serum 17-beta-oestradiol and luteinizing hormone levels (0.19 +/- 0.03 (SEM) nmol/l, and 57.4 +/- 13.1 (SEM) IU/l, respectively) were significantly higher (p less than 0.05 and p less than 0.005, respectively) than in the control group (0.11 +/- 0.02 (SEM) nmol/l and 14.8 +/- 1.9 (SEM) IU/l, respectively). Mean progesterone and follicle-stimulating hormone levels in patients were not significantly different from those of control subjects. Mean prolactin values in patients (1,019 +/- 285 (SEM) mIU/l) were significantly higher (p less than 0.01) than in the control group (211 +/- 24 (SEM) mIU/l). Serum prolactin levels in five patients were extremely high (above 1,200 mIU/l). There was no statistically significant difference in serum zinc levels between patients and controls. As salivary testosterone is normal, it seems that hyperprolactinaemia and raised serum 17-beta-oestradiol levels may be responsible, at least in part, for sexual dysfunction in male patients with chronic renal failure receiving haemodialysis.     

Immunoreactive N-terminal pro-atrial natriuretic peptide in human plasma: plasma levels and comparisons with alpha-human atrial natriuretic peptide in normal subjects, patients with essential hypertension, cardiac transplant and chronic renal failure

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1-30). 2. Plasma levels of N-terminal ANP (means +/- SEM) were 235.3 +/- 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 +/- 36.3 pg/ml), in cardiac transplant recipients (1240.0 +/- 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 +/- 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10336.1 +/- 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of N-terminal ANP and alpha-human ANP (alpha-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P less than 0.05 in every case).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma concentrations of atrial natriuretic peptide in various diseases

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.     

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in chronic renal failure

Secretion of ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) is pulsatile in healthy humans. However, the patterns of secretion of ANP and BNP have not been studied in chronic renal failure. The aim of the present study was to test the hypotheses that ANP and BNP are secreted in pulses in dialysis patients, and that pulsatile secretion is regulated by prostaglandins. Blood samples were drawn every 2 min through an intravenously inserted plastic needle over a period of 1-2 h in 13 dialysis patients and 13 healthy control subjects (Study 1), and in 15 healthy control subjects, who participated in a randomized placebo-controlled cross-over study after treatment with indomethacin and placebo (Study 2). Plasma concentrations of ANP and BNP were determined by RIAs, and the results were analysed for pulsatile behaviour by Fourier transformation. The results from Study 1 showed that the secretion of ANP and BNP was pulsatile in nine patients with chronic renal failure. The maximum amplitude was significantly higher in chronic renal failure compared with control subjects for both ANP and BNP (ANP, 4.3 compared with 0.7 pmol/l; BNP, 2.0 compared with 0.3 pmol/l; values are medians) and correlated positively with the mean plasma level of ANP (rho=0.900, P=0.001; n=9) and BNP (rho=0.983, P=0.000; n=9). The frequency was the same for patients and controls. The results from Study 2 demonstrated pulsatile secretion in all subjects, but both the amplitude and frequency were unaffected by indomethacin. The maximum amplitude correlated positively with the mean plasma level of ANP and BNP during both placebo and indomethacin treatment. It can be concluded that the secretion of ANP and BNP is pulsatile with abnormally high amplitude in chronic renal failure, that prostaglandins apparently are not involved in the secretion of these peptides in healthy subjects and that the high secretion rate in chronic renal failure results in higher ANP and BNP in plasma.     

Elevated levels of brain natriuretic peptide in acute hypoxaemic chronic obstructive pulmonary disease.

1. Studies in vitro have recently shown that both atrial natriuretic peptide and brain natriuretic peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain natriuretic peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain natriuretic peptide and atrial natriuretic peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O2, 6.2 +/- 0.4 kPa; arterial partial pressure of CO2, 6.9 +/- 0.1 kPa; forced expiratory volume in 1 s, 0.6 +/- 0.07 litre (27 +/- 3% of predicted)]. All but three patients had oedema on admission. 2. Plasma levels of both brain natriuretic peptide and atrial natriuretic peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 +/- 4.1 pmol/l and 45.0 +/- 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 +/- 0.8 pmol/l and 8.0 +/- 3.5 pmol/l, respectively). Thus, plasma levels of brain natriuretic peptide and atrial natriuretic peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects. 3. There was a significant inverse correlation between the plasma level of brain natriuretic peptide and the arterial partial pressure of O2 (r = -0.65, r2 = 0.42, P = 0.03), but not between the plasma atrial natriuretic peptide level and the arterial partial pressure of O2 (r2 = 0.07, not significant). The arterial partial pressure of CO2 did not correlate with the plasma level of either brain natriuretic peptide or atrial natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma levels of endothelin in chronic renal failure and after renal transplantation: impact on hypertension and cyclosporin A-associated nephrotoxicity.

1. Plasma levels of endothelin were measured in 30 patients with chronic renal failure, 32 patients on chronic haemodialysis treatment and 25 renal graft recipients with stable renal graft function. 2. In patients with chronic renal failure as well as in patients on regular haemodialysis treatment, mean plasma levels of endothelin were significantly increased (4.59 +/- 2.09 pg/ml, 10.08 +/- 3.12 pg/ml, respectively) when compared with normal subjects (1.88 +/- 0.6 pg/ml, P less than 0.01, P less than 0.001, respectively). 3. In the group with chronic renal failure a positive correlation between the plasma level of endothelin and the plasma concentration of creatinine was observed (P less than 0.003). 4. Renal graft recipients on cyclosporin A with stable renal graft function had a normal plasma level of endothelin suggesting that cyclosporin A nephrotoxicity is not mediated by endothelin. 5. Hypertensive patients with chronic renal failure or on regular haemodialysis and hypertensive renal graft recipients did not differ from the corresponding normotensive population with regard to the plasma level of endothelin, demonstrating that an increased plasma level of endothelin does not play a major role in the pathogenesis of renal hypertension.     

Calcium and phosphate metabolism in acute falciparum malaria.

1. Mineral homeostasis was investigated in 172 Thai adults with acute falciparum malaria at presentation (87 males, 85 females; mean age 30 years), and prospectively in a subgroup of 10 severely ill patients. 2. Mild, asymptomatic hypocalcaemia (corrected plasma calcium concentration 1.79-2.11 mmol/l) was found in 61 cross-sectional study patients (35.5%), with no difference between those with uncomplicated (2.16 +/- 0.10 mmol/l, mean +/- SD, n = 89) and severe (2.18 +/- 0.15 mmol/l, n = 83, P = 0.36) infections. Six prospectively studied patients were hypocalcaemic during treatment; simultaneous serum intact parathormone concentrations were inappropriately low (less than 5.0 pmol/l), but rose in three patients to high levels (11.8-16.4 pmol/l) on the fifth day. 3. Plasma phosphate concentration was decreased (less than 0.80 mmol/l) on admission in 74 patients (43.0%) and increased (greater than 1.45 mmol/l) in 15 (8.7%). Severe phosphate depletion (plasma phosphate concentration less than 0.30 mmol/l) occurred in 14 patients, of whom 11 had severe infections. Serum phosphate concentrations in the prospective study patients on admission (0.59 +/- 0.23 mmol/l) correlated significantly with the simultaneous renal threshold phosphate concentration (0.68 +/- 0.33 mmol/l; r = 0.607, P less than 0.025) and both parameters rose in parallel during treatment. 4. Plasma magnesium concentrations were normal (0.75-1.05 mmol/l) in 108 patients (62.8%); 45 cases (26.1%) had hypermagnesaemia and 19 (11.0%) had hypomagnesaemia. 5. These data suggest that mild hypocalcaemia is common in malaria regardless of disease severity; a depressed parathormone response may contribute. Despite malaria-associated haemolysis, hypophosphataemia is also common, but can be severe.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic clearance rate of arginine vasopressin in severe chronic renal failure.

1. The metabolic clearance rate of arginine vasopressin was determined using a constant infusion technique in normal subjects and patients with chronic renal failure immediately before commencing dialysis. Endogenous arginine vasopressin was suppressed in all subjects before the infusion with a water load. 2. Plasma arginine vasopressin concentrations were determined using a sensitive and specific radioimmunoassay after Florisil extraction. The detection limit of the assay was 0.3 pmol/l, and intra- and inter-assay coefficients of variation at 2 pmol/l were 9.7% and 15.3%, respectively. 3. In normal subjects, the metabolic clearance rate was determined at two infusion rates producing steady-state concentrations of arginine vasopressin of 1.3 and 4.4 pmol/l. In the patients with renal failure, a single infusion rate was used, producing a steady-state concentration of 1.5 pmol/l. 4. At comparable plasma arginine vasopressin concentrations, metabolic clearance rate was significantly reduced in patients with renal failure (normal 1168 +/- 235 ml/min versus renal failure 584 +/- 169 ml/min; means +/- SD; P < 0.001). 5. Free water clearance was significantly reduced in normal subjects during the arginine vasopressin infusion from 8.19 +/- 2.61 to -1.41 +/- 0.51 ml/min (P < 0.001), but was unchanged in the patients with renal failure after attaining comparable plasma arginine vasopressin concentrations. 6. In normal subjects there was a small but significant fall in metabolic clearance rate at the higher steady-state arginine vasopressin concentration (1168 +/- 235 ml/min at 1.3 pmol/l versus 1059 +/- 269 ml/min at 4.4 pmol/l; P = 0.016).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma levels of substance P, neuropeptide Y and vasoactive intestinal polypeptide in patients with chronic tension-type headache

Animal and human studies have shown that substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) are involved in the pathophysiology of acute and chronic pain conditions. The primary aim of the present study was to compare plasma levels of SP, NPY and VIP in external jugular vein between patients with chronic tension-type headache and healthy controls. The secondary aim was to examine plasma levels of these neuropeptides in relation to headache state. In addition, we wanted to study the relation between cranial circulation (jugular vein) and peripheral circulation (antecubital vein). Blood from the external jugular and antecubital vein was drawn from 20 patients with chronic tension-type headache and 20 healthy controls. Plasma SP in patients, 2.0 (1.4-2.2) pmol/l, did not differ significantly from plasma SP in controls, 1.7 (1.1-2.1) pmol/l, (P=0.44). No significant differences were found between SP levels on days with headache, 1.5 (0.3-1.7) pmol/l, and SP levels on days without headache, 1.7 (1.1-1. 9) pmol/l, (P=0.06). Plasma NPY in patients, 118+/-3 pmol/l, did not differ significantly from plasma NPY in controls, 113+/-5 pmol/l, (P=0.40). There was no difference between NPY levels on days with headache, 120+/-3 pmol/l, and on days without headache, 118+/-3 pmol/l, (P=0.73). VIP levels in patients, 6 (4-7) pmol/l, did not differ significantly from VIP levels in controls, 5 (5-7) pmol/l, (P=0.50). No significant differences were found between VIP levels measured on days with headache, 5 (4-6) pmol/l, and VIP levels measured on days without headache, 6 (4-7) pmol/l, (P=0.81). Plasma levels of SP, NPY and VIP did not significantly differ between the peripheral and the cranial circulation neither in patients nor in controls (0.05). In summary, the present study indicates that plasma levels of SP, NPY and VIP are normal in chronic tension-type headache patients and largely unrelated to headache state.     

Plasma bone Gla protein concentrations in healthy adults. Dependence on sex, age, and glomerular filtration

Plasma bone Gla protein (BGP) was determined by radio-immunoassay in 266 healthy adults, men (n = 132) and women (n = 134), aged 20-79 years. In the women aged 30-69 years, plasma BGP increased significantly with age (r = 0.44, p less than 0.001), and a particularly steep increase was seen from 1.1 +/- 0.5 (mean +/- 1 SD) in the fifth decade to 2.0 +/- 1.4 nmol/l in the seventh decade. In men, aged 30-69 years, no correlation was found between plasma BGP and age (r = -0.07, NS). Plasma bone Gla protein is removed from the circulation mainly by the kidneys and the increased plasma BGP in the women could be caused by decreased renal clearance. The interrelationship was analysed by means of partial correlation. When creatinine clearance was held constant in women, BGP still correlated positively with age (r = 0.40, p less than 0.001), but not with creatinine clearance (r = 0.003, NS) when age was fixed. Plasma BGP was significantly increased above normal in 35 patients with chronic renal failure (10.2 +/- 14.6 nmol/l). Non-linear regression analysis showed that plasma BGP was within the normal range when 24-h creatinine clearance was greater than 30 ml/min, and large increases in plasma BGP did not occur until the 24-h creatinine clearance was below 20 ml/min. We conclude that, in normal subjects and patients with mild to moderate renal failure, plasma elevations of BGP reflect increased bone turnover rather than decreased renal clearance.     

Increased urinary atrial natriuretic peptide-like immunoreactivity excretion but decreased plasma atrial natriuretic peptide concentration in patients with hyperosmolar-hyperglycemic nonketotic syndrome.

OBJECTIVE: This study was undertaken to measure urinary atrial natriuretic peptide-like immunoreactivity (ANP-LI) and plasma ANP concentration in patients with hyperosmolar-hyperglycemic nonketotic syndrome (HHNS) to investigate the change of renal ANP-LI and cardiac ANP synthesis in volume-depleted diabetic patients. RESEARCH DESIGN AND METHODS: The urine ANP-LI:creatinine ratio, plasma ANP level, and plasma renin activity (PRA) were measured in 12 patients with HHNS during the acute stage and after recovery, in 28 oral hypoglycemic agent (OHA)-treated type 2 diabetic patients, and in 23 normal subjects. ANP and PRA were measured by radioimmunoassay. RESULTS: These HHNS patients had severe hyperglycemia and hyperosmolality as well as increased blood urea nitrogen, creatinine, and PRA levels, as compared with normal subjects and OHA-treated type 2 diabetic patients. In these patients, the urinary ANP-LI:creatinine ratio (11.69 +/- 2.11 pmol/mmol) was significantly increased in comparison with the normal group (1.78 +/- 0.11 pmol/mmol) and OHA-treated diabetic patients (2.43 +/- 0.45 pmol/mmol), whereas plasma ANP concentration (5.12 +/- 0.72 pmol/l) was significantly lower than the corresponding values of the normal group (7.39 +/- 0.85 pmol/l) and OHA-treated diabetic patients (8.43 +/- 1.05 pmol/l). All of these abnormalities were significantly ameliorated after insulin, fluid, and electrolyte replacement. CONCLUSIONS: Our data show that urinary ANP-LI was significantly increased, whereas plasma ANP concentration was decreased, in the face of raised PRA in HHNS patients. This study indicates that renal ANP-LI substances and cardiac ANP may exhibit different responsiveness in diabetic patients with HHNS.     

Effect of glucagon-like peptide 1 (7-36 amide) on insulin-mediated glucose uptake in patients with type 1 diabetes

OBJECTIVE: To examine the insulinomimetic insulin-independent effects of glucagon-like peptide (GLP)-1 on glucose uptake in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: We used the hyperinsulinemic-euglycemic clamp (480 pmol. m(-2) x min(-1)) in paired randomized studies of six women and five men with type 1 diabetes. In the course of one of the paired studies, the subjects also received GLP-1 at a dose of 1.5 pmol. kg(-1) x min(-1). The patients were 41 +/- 3 years old with a BMI of 25 +/- 1 kg/m(2). The mean duration of diabetes was 23 +/- 3 years. RESULTS: Plasma glucose was allowed to fall from a fasting level of approximately 11 mmol/l to 5.3 mmol/l in each study and thereafter was held stable at that level. Plasma insulin levels during both studies were approximately 900 pmol/l. Plasma C-peptide levels did not change during the studies. In the GLP-1 study, plasma total GLP-1 levels were elevated from the fasting level of 31 +/- 3 to 150 +/- 17 pmol/l. Plasma glucagon levels fell from the fasting levels of approximately 14 pmol/l to 9 pmol/l during both paired studies. Hepatic glucose production was suppressed during the glucose clamps in all studies. Glucose uptake was not different between the two studies ( approximately 40 micromol. kg(-1) x min(-1)). CONCLUSIONS: GLP-1 does not augment insulin-mediated glucose uptake in lean type 1 diabetic patients.     

Plasma pyridoxal 5'-phosphate concentrations in relation to apo-aminotransferase levels in normal, uraemic, and post-myocardial infarct sera

The concentrations of pyridoxal 5'-phosphate, and the holoenzyme activities and apoenzyme contents of alanine aminotransferase and aspartate aminotransferase in plasma were determined simultaneously in healthy individuals, patients with renal insufficiency with and without chronic haemodialysis and in patients with acute myocardial infarction. Plasma pyridoxal 5'-phosphate is significantly diminished in uraemic patients and in post-myocardial infarct sera, healthy females have lower pyridoxal 5'-phosphate levels (26.2 +/- 9.0 nmol/l) than healthy males (41.0 +/- 15.1 nmol/l). The stimulation in vitro of the activities of aspartate aminotransferase and alanine aminotransferase by addition of pyridoxal 5'-phosphate (0.1 mmol/l) was found to be independent of the endogenous coenzyme level. In sera of uraemic patients without chronic haemodialysis an inverse statistic correlation between pyridoxal 5'-phosphate-induced stimulation of aspartate aminotransferase activity and the concentrations of urea (r = -0.696) and creatinine (r = -0.715) was found. The respective correlations are much weaker for alanine aminotransferase. The apoenzyme fraction was highest in post-myocardial infarct sera. Follow up of these patients did not reveal any relationship between the fluctuations of pyridoxal 5'-phosphate levels and apoenzyme contents of both alanine aminotransferase and aspartate aminotransferase. The results permit the conclusion that the degree of in vitro stimulation of aminotransferases by pyridoxal 5'-phosphate can not be predicted from the endogenous coenzyme level.