Upper Range Of Normal Research Articles

U.K. Prospective Diabetes Study XV: Relationship of renin-angiotensin system gene polymorphisms with microalbuminuria in NIDDM

We performed a case-control study to determine whether molecular variants of genes of the renin-angiotensin system were associated with the presence of albuminuria in non-insulin dependent diabetes mellitus (NIDDM). A total of 180 diabetic patients with persistent microalbuminuria [median urinary albumin (interquartile range) of 74 (54 to 126 mg/liter)] were matched with two control groups of diabetic patients without microalbuminuria [median urinary albumin 7 (5 to 10) mg/liter] for variables known to be associated with raised urinary albumin concentration including hemoglobin A1c and triglyceride. One control group was also matched for blood pressure and the other group was not, to allow assessment of interactions with hypertension. Association with the I/D polymorphism of the ACE gene and M235T variant of the angiotensinogen gene (AGT) with microalbuminuria and retinopathy was examined. There were no significant differences in genotype frequency between cases and controls for ACE or AGT irrespective of blood pressure matching. However, among subjects with microalbuminuria, those with the ACE DD genotype had a significantly greater urinary albumin excretion than individuals with a non-DD genotype [median 88 (68 to 170) mg/liter vs. 67 (53 to 113) mg/liter, P < 0.001]. More subjects with the DD than non-DD genotype had persistent albuminuria > 100 mg/liter, twice the upper normal range (60% vs. 38%, P = 0.006). When increased albumin excretion occurs, the presence of the ACE DD genotype appears to be associated with higher urinary albumin levels. No association with retinopathy was observed.

Risk factors for fever in labor

To identify risk factors for fever in labor. A retrospective case-control study was conducted. Maternal sublingual temperature was measured every 2-4 hours during labor in 3109 of 3860 consecutive term parturients presenting from September 1992 through December 1993. Women who had fever (at least one recorded temperature of 38C or more, n = 72) during labor were compared with those who remained afebrile (n = 3037). Furthermore, a matched-pair case-control study was conducted, involving 250 women at term who developed fever in labor and 250 controls matched for parity and duration of labor; all delivered between January 1989 and December 1993. A conditional multiple logistic regression analysis was used to identify independent risk factors for fever during labor. In the case-control study, fever was associated with epidural analgesia, nulliparity, and a long duration of labor. These three variables were also related among themselves. However, multiple regression analysis showed that all three variables were independently associated with maternal temperature. In the matched-pair study, epidural analgesia, rupture of membranes longer than 24 hours, latency phase exceeding 8 hours, and a temperature in the upper normal range (37.5-37.9C) at admission were independent risk factors for developing fever in labor. Epidural analgesia, duration of labor, and a long interval from rupture of membranes to delivery were independent risk factors for maternal fever in labor.

Treatment of patients with Ullrich-Turner syndrome with conventional doses of growth hormone and the combination with testosterone or oxandrolone: Effect on growth, IGF-I and IGFBP-3 concentrations

Thirty-nine girls with Ullrich-Turner syndrome (UTS) (median age 9.5 years) were treated with growth hormone (GH) with either 12 or 18 IU/m2 per week for 12 months followed by combination therapy with either oxandrolone (Ox) (0.0625 mg/kg/day po) or low-dose testosterone (T) (5 mg in every 2 weeks). Growth velocity improved significantly after 12 IU/m2 per week (6.4 +/- 1.7 cm/year vs 4.0 +/- 1.3 cm/year, x +/- SD, P < 0.001) and 18 IU/m2 per week of GH (6.5 +/- 1.3 cm/year vs 4.5 +/- 1.4 cm/year, P < 0.001). Ox, but not T was effective in maintaining growth velocity during the 2nd year of therapy (6.9 +/- 1.3 vs 5.3 +/- 1.5 cm/year). Basal insulin-like growth factor-I (IGF-I) concentrations were in the lower normal range and increased significantly in patients treated with 18 IU/m2 per week (357 +/- 180 ng/ml vs 160 +/- 84 ng/ml) and 12 IU/m2 per week (273 +/- 121 ng/ml vs 140 +/- 77 ng/ml). IGF-I concentrations increased further after addition of Ox (533 +/- 124 ng/ml, P < 0.001) or T (458 +/- 158, P < 0.05). IGFBP-3 concentrations were in the upper normal range before therapy and increased only moderately in both GH dosage groups. However, IGF binding protein-3 (IGFBP-3) concentrations were not affected by additional Ox or T treatment. 1. Conventional GH doses are effective in increasing growth velocity in UTS, especially, when combined with Ox.(ABSTRACT TRUNCATED AT 250 WORDS)

TEN YEARS' EXPERIENCE OF BONE MARROW TRANSPLANTATION FOR GAUCHER DISEASE

Six patients underwent allogeneic bone marrow transplantation (BMT) because of severe Gaucher disease. Their ages was from 2 to 9 years at the time of transplantation. The donors were 4 HLA-identical siblings, a father with one incompatible HLA antigen and an HLA-A, -B, and -DR-identical unrelated donor. Among the donors, three were heterozygous for glucocerebrosidase and three were healthy homozygotes. Four patients underwent total splenectomy and two patients partial splenectomy prior to transplantation. In the former group one patient developed pneumococcal meningitis. In the latter group transfusion requirements were increased. The parental graft was rejected, but 4 of 5 other patients have donor enzyme levels from 2 up to 11 years after BMT. Two patients became mixed chimeras with around 40% of donor erythrocyte markers for one and 80% for the other. One of these had low enzyme activity in his lymphocytes, but the clinical outcome is excellent. This case gives good hope for future trials with gene therapy in Gaucher disease. Glucosylceramide in plasma was within the normal range in all other patients with engraftment, but glucosylceramide in erythrocytes were in the upper normal range in the two chimeric patients with heterozygous donors. Glucosylceramide levels in the liver decreased markedly in the two patients where it was studied. Gaucher cells disappeared in the bone marrow and liver size normalized or decreased within two to three years after BMT. All patients with engraftment had a growth spurt. Skeletal kyphosis was unaffected by BMT in three patients and became apparent in one patient 8 years after BMT. The patients had a favorable psychological development after BMT, with an excellent IQ between 112 and 120 ten years after BMT in the longest survivor. The data suggest that in advanced Gaucher disease BMT still may be a treatment of choice if an HLA-identical related or unrelated donor is available.

Infantile spasms associated with theophylline toxicity

We report on a 6-month-old infant with asthma who developed spasms and hypsarrhythmia on the electroencephalogram (EEG) shortly after starting oral theophylline medication. Theophylline levels at that time were just above the upper normal range. The spasms stopped and the EEG normalized when theophylline was discontinued and nitrazepam therapy started. On follow-up over the next 3 years there was no recurrence of seizures and the child's neurodevelopment has been normal. Nitrazepam was stopped at 10 months and the waking and sleeping EEG were normal at 14 months. We believe that the infantile spasms were caused by theophylline.

The effect of methylene blue phototreatment on plasma proteins and in vitro coagulation capability of single-donor fresh-frozen plasma.

Photodynamic virus inactivation of fresh-frozen plasma (FFP) may result in its impaired coagulation capability. Double-volume plasmapheresis samples from 11 donors were divided in pairs of 250 mL. One group underwent methylene blue (MB) phototreatment (MB-FFP). The other group was treated according to the standards of the American Association of Blood Banks for preparation and storage of FFP. Parameters of hemostasis and clinically important plasma proteins were tested in native plasma, thawed MB-FFP, thawed FFP, and twice-frozen and thawed FFP (FFP-II). Mean activities of factor V (73.4 vs. 94.5%; p < 0.01), factor VIII (58.1 vs. 86.7%; p < 0.001), and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) were reduced in MB-FFP as compared to those in FFP. The comparison of MB-FFP to FFP-II revealed reduced activities of factor VIII (58.1 vs. 85.2%; p < 0.001) and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) but no changes in factor V. Activated partial thromboplastin time in MB-FFP was prolonged beyond the upper normal range (+5.3 sec; p < 0.001) and prothrombin time increased in MB-FFP versus FFP (+0.96 sec; p < 0.001). MB phototreatment reduces the in vitro coagulation capacity of FFP, most likely as a result of the effects of an additional freezing and thawing procedure and photooxidation-induced protein damage.

Plasminogen activator inhibitor 1 activity and lipoprotein(a) in nephropathic patients with non-insulin-dependent diabetes mellitus versus patients with nondiabetic nephropathy.

Increased plasma activity of plasminogen activator inhibitor 1 (PAI-1) is considered as a risk factor for thrombosis associated with atherosclerosis by reduction of fibrinolysis. Since nephropathic patients with non-insulin-dependent diabetes mellitus (NIDDM) are a cardiovascular high-risk group, which has yielded only controversial results as to the regulation of PAI-1, we compared 19 overt nephropathic NIDDM patients (mean age 63 years, serum creatinine 1.9 mg/dl, proteinuria 4.2 g/day) to 17 nondiabetic nephropathic patients with various causes of renal insufficiency (mean age 63 years, serum creatinine 2.8 mg/dl, proteinuria 3.9 g/day). We found normal PAI-1 levels for patients with diabetic nephropathy and significantly elevated PAI-1 levels within the upper normal range for nondiabetic nephropathic patients. Common risk factors in both groups were very high levels of fibrinogen, lipoprotein(a), serum cholesterol, and LDL cholesterol.

Urinary growth hormone excretion in acromegaly: diagnostic value in mild disease activity

The biochemical assessment of disease activity in acromegaly still presents a problem, especially in treated patients with mild clinical symptoms. We therefore examined the diagnostic value of the measurement of urinary growth hormone (GH) excretion in seventy unselected patients with acromegaly of different activity by comparing it to serum GH, serum insulin-like growth factor I (IGF-I) and clinical activity. There were highly significant, positive correlations between urinary GH and serum GH, serum IGF-I as well as clinical activity score (p < 0.00005), although some overlap between the groups was observed. In seven patients with low serum GH values (< 2.0 micrograms/l) discordant results were found. Two of the seven patients were clinically mildly active, but only IGF-I was either elevated or within the upper normal range; in three other patients who appeared clinically cured either IGF-I (N = 1) or urinary GH (n = 2) alone were increased. In the remaining two patients elevated serum IGF-I and urinary GH as well as activity score suggested disease activity. Thus, in the majority of cases, urinary GH was significantly correlated to the other three parameters, but added little information to that obtained by serum IGF-I. In conclusion, urinary GH measurements in difficult cases may provide a more direct information on the GH status than IGF-I.

Calcitonin gene‐related peptide in small cell lung carcinomas

Calcitonin gene-related peptide (CGRP) is a regulatory peptide encoded by the calcitonin gene. CGRP is expressed in increased amounts by the cells of medullary thyroid carcinomas and has been demonstrated by immunohistochemistry to occur in neuroendocrine cells and nerve fibres of lung tissue. Serum CGRP levels were measured in patients with small cell lung carcinomas before treatment (n = 74) and immediately before the second course of chemotherapy (n = 30). In-situ hybridization and immunohistochemistry were performed on tumour tissue and CGRP was extracted from two tumours and characterized by gel chromatography and high pressure liquid chromatography. Serum CGRP levels were elevated in small cell lung carcinomas when compared with healthy controls of similar age and sex (median values 55.0 vs 36.6 pmol/l, P < 0.001), and 27% had levels above the upper normal range. Serum CGRP levels decreased following the initial course of chemotherapy (P < 0.05) but remained elevated when compared to the controls (P < 0.001). In-situ hybridization for CGRP mRNA was positive in three of 17 tumours and immunohistochemistry was positive in seven of 31 tumours investigated. CGRP immunoreactivity extracted from two tumours was characterized by gel chromatography and high pressure liquid chromatography. A major part of the immunoreactivity was demonstrated to represent the intact molecule. We found that patients with small cell lung carcinomas had elevated concentration of serum calcitonin gene-related peptide but only 27% had values above the upper normal range. Serum CGRP is therefore of limited value as a tumour marker. Intact CGRP can be extracted from tumour tissue, but in-situ hybridization and immunohistochemistry showed positive reactions in only a few of the tumours investigated. The elevated serum CGRP levels are therefore likely to be largely of extratumoral origin.

Long-term observation of the changing brainstem auditory evoked potentials in a case of infantile opsoclonus-polymyoclonia syndrome

Brainstem auditory evoked potential (BAEP) studies were repeatedly carried out on a boy with infantile opsoclonus-polymyoclonia syndrome, from 15 months to 39 months of age, the following being revealed: the I–III interpeak latency (I–III IPL) was more or less in the upper normal range until 24 months and then remained at the same level throughout the rest of the observation period, not showing physiological shortening with maturation. It should be noted that the prolongation of I–III IPL continued in spite of the disappearance of the opsoclonus.

Factors influencing the clinical outcome of continuous subcutaneous insulin infusion in routine practice

Possible factors that might influence the outcome of continuous subcutaneous insulin infusion (CSII) treatment were investigated in forty-nine, type 1, diabetic patients with median treatment of 3.25 years in routine diabetes care. In nine patients pump treatment was discontinued largely within the first 6 months. Patients characterized as blue-collar workers discontinued pump treatment at a significantly higher rate. Of the remaining forty patients those with the longest treatment experience were of attracted interest. Among twenty patients who had used CSII three years or more improvement of metabolic control was most evident in patients with high haemoglobin A 1c (HbA 1c) values before CSII ( R-square 0.673, P = 0.0001) and in subjects with low insulin requirements on injection therapy ( R-square 0.334, P = 0.0076). This improvement was not explained by more frequent monitoring of blood glucose only. It was found that those who had the lowest body mass index (BMI) before pump treatment had the more pronounced increase of BMI, while those in the upper normal range had an unchanged or reduced body mass ( R-square 0.271, P = 0.0115). We conclude that high HbA 1c values, low insulin requirements and low body mass in conventional injection therapy are the most important factors when trying to achieve and maintain metabolic improvement in CSII treated type 1 diabetic patients.

Determination of pancreatic lipase by immunoactivation technology

This paper describes the test characteristics and clinical relevance of a newly developed homogeneous enzyme immunoassay IMAC lipase test for the determination of serum pancreatic lipase. The method of determination is based on an immunoactivation technology and utilizes antibody fragments against human pancreatic lipase covalently bound to the marker enzyme horseradish peroxidase. The serum samples of 408 persons were investigated with this new assay. The within-run and day-to-day precision, the linearity, and the recovery of this immunoassay correspond to a very high degree to the requirements made of a modern immunological test. Comparison with an ELISA method resulted in a correlation coefficient of 0.971, whereby the IMAC lipase assay tended to register lower serum values. The serum range for the IMAC lipase test is 0-47 micrograms/L, based on a normal collective of 187 healthy controls. A sensitivity of 95.8% for the diagnosis of acute pancreatitis at a cutoff level of twice the upper normal range and a specificity of 99.3% at an efficiency of 99.8% can be given. The advantage of the IMAC lipase test method is its ability to be adapted to work on automatic laboratory analyzers.

Heparin therapy. Regimens and treatment considerations.

Heparin is a parenteral antithrombotic agent with efficacy in the treatment and prevention of venous thromboembolic disease and in preinfarctional angina. Accumulating evidence also suggests that heparin is useful in the prevention of coronary artery reocclusion after thrombolytic therapy for acute myocardial infarction, and in the prevention of left ventricular mural thrombosis after anterior wall myocardial infarction. Heparin appears to offer only marginal benefit in reducing mortality when given in combination with thrombolytic therapy and aspirin for acute myocardial infarction. When used for prevention of venous thromboembolism in moderate risk patients, heparin should be given subcutaneously in a dose of 5000 U every 12 hours for 5 to 7 days or until the patient is ambulatory. In higher risk patients, such as those undergoing total hip replacement, heparin should be given subcutaneously every 12 hours in a dose to prolong the activated partial thromboplastin time (aPTT) by 4 to 5 seconds into the upper normal range. When used to treat active venous thromboembolism or the peri-infarctional state, heparin should be given by intravenous infusion with loading and maintenance doses to consistently prolong the aPTT to between 1.5- and 2.5-fold the control value (mean of laboratory's normal range). If constant intravenous infusion is not possible, the drug should be given subcutaneously every 12 hours to consistently prolong the aPTT between 1.5 and 2.5 times control. This regimen is also recommended in pregnant women with venous thromboembolic disease or mechanical heart valves.

Diagnosis and therapy surveillance in Addison's disease: rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH, renin activity, and aldosterone.

The rapid ACTH injection test is an indirect screening test for adrenocortical insufficiency. As a supplement to this test, we evaluated the practicability of single measurements of plasma cortisol, ACTH, aldosterone, and PRA as a definitive diagnostic test of primary adrenocortical insufficiency (PAI). We also tested the value of PRA measurements during treatment with hydro- and fludrocortisone (HC and FC) as a guide for correct mineralocorticoid substitution. In 45 patients with PAI, results of the rapid ACTH test and single measurements of the four hormones (all tests between 0800-0900 h) were compared. Single hormone measurements were also made in 55 normal subjects and 46 patients with pituitary disease (cortisol and ACTH only), most of them with mild to severe secondary adrenocortical insufficiency (SAI). The rapid ACTH test was abnormal in 100% of 41 patients with PAI tested. Plasma ACTH, PRA, and the ratios of ACTH/cortisol and PRA/plasma or urinary aldosterone were clearly elevated in 100% of the patients with PAI. The ACTH/cortisol ratio also distinguished 100% of patients with PAI from those with SAI, but not always control subjects from those with SAI. Thus, dynamic tests (CRH or insulin tests) are indicated if SAI is suspected. PAI and involvement of zona fasciculata and glomerulosa function can be diagnosed with high reliability by measuring cortisol, ACTH, aldosterone, and PRA either together with the rapid ACTH test or later, after a short interval of steroid substitution. PRA measurements during treatment with HC and FC correlated better with the mineralocorticoid dose than plasma potassium and sodium levels. PRA measurement is a valuable guide for FC replacement therapy. It should be titrated into the upper normal range to avoid under- and overtreatment.

Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54± 16 I.E.) in the upper normal range (controls, 39 ± 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 ± 13, P < 0.001) with persistent proteinuria and with retinopathy (63 ± 14, P < 0.001). A significant correlation was found between proteinuria and S-ACE ( r = 0.98, P < 0.001) and between retinopathy and S-ACE levels ( r = 0.64, P < 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 ± 9 ng/l) and in control (19 ± 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.

Proteinuria, Renal Impairment, Metabolic Control, and Blood Pressure in Type 2 Diabetes Mellitus

The deleterious effect of hypertension on the course of diabetic retinopathy and the protective influence of antihypertensive therapy are well known. There is, however, little information about the long-term effect of different levels of blood pressure within the normal range on the evolution of renal function in type II diabetes. One hundred ninety-five young normotensive patients with recent-onset type II diabetes, normal renal function, and no proteinuria were followed up for 14 years. Plasma glucose, creatinine, and urinary protein levels and blood pressure were determined periodically. Thirty patients developed hypertension; among them, 18 developed proteinuria (0.3 g/L). Among 144 patients who remained normotensive, 30 developed proteinuria. The mean decline in renal function (decline in reciprocal creatinine [100/creatinine level], expressed as a percentage of the initial value) was 26% for normotensive patients, 43% for normotensive patients with nephropathy, 39% for hypertensive patients, and 52% for hypertensive patients with nephropathy. The degree of metabolic control was not associated with the presence of proteinuria or with the severity of renal impairment. There was a significant association between the mean blood pressure over the whole observation period and the degree of impairment in renal function. This association was significant also in the patients who remained normotensive with and without proteinuria. Minor elevation of blood pressure as well as values in the upper normal range may be associated with acceleration of renal damage in type II diabetes.

Efficacy of low-dose captopril in addition to furosemide and spironolactone in patients with decompensated liver disease during blunted diuresis

The renin-angiotensin-aldosterone system is activated by diuretics and involved in the diuretic resistance of cirrhotic patients with ascites and oedema. In previous studies relatively high doses of captopril (25–400 mg daily) were unsuccessful in promoting diuresis and natriuresis in these patients. We analyzed the efficacy of a low dose of captopril in eight patients with massive ascites resistant to therapy of salt/fluid restriction and increasing doses of spironolactone and furosemide. Mean duration of diuretic use was 73 days (range 7–240 days). After at least 3 days of observation on 80 mg furosemide and 100 mg spironolactone only, captopril was added. Four out of eight patients responded with an increase in natriuresis and diuresis; daily dose of captopril was 20.6 mg in responders and 26.5 mg in non-responders. After the addition of captopril the mean weight change was −7.5 kg in responders and +0.25 kg in non-responders. Mean urinary sodium output in responders increased from 72.8 (S.D. = 35.2) to 128.5 (63.5) mmol within 10 days. Increased diuresis in responders made diuretic reduction necessary: mean furosemide from 80 to 53.3 mg, and mean spironolactone from 100 to 68.1 mg. Creatinine clearances remained stable. High levels of plasma renin activity, plasma aldosterone and angiotensin-II were found in all patients. Non-responders showed more severe hyponatremia and higher vasopressin levels. Natriuretic atrial factor (NAF) was in the upper-normal range or slightly elevated in both groups. In non-responders we noticed low levels of cGMP in 24-h urine, compared with responders. Persisting high angiotensin-II and slightly elevated vasopressin levels may have impaired the function of NAF contributing to the persistently blunted diuresis in non-responders. Low-dose captopril provided a striking improvement of diuretic efficacy in 4 8 diuretic-resistant cirrhotic patients with ascites and oedema, and may, therefore, play an additional therapeutic role in these patients.

Increased plasma amylase in the family of a patient with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency

A patient with 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase, EC 4.1.3.4) deficiency presented consistently above-normal values of plasma amylase (EC 3.2.1.1). Activities measured were in the lower normal range in family members not proven heterozygotes and in the upper normal range in the proven heterozygotes. Heterozygosity was proven by intermediate HMG-CoA lyase activities determined in cultured fibroblasts and in lymphocytes in the parents and the paternal grandmother. Because all of the family members had diseases of the pancreas, colon, and liver, we question whether the heterozygote state contributes to the impaired function of these organs. Our findings of significantly increased amylase activities in the heterozygotes and the patient, in comparison with the other family members, support this hypothesis.

Antral gastrin cell hyperfunction in children: A functional and immunocytochemical report

Antral gastrin cell hyperfunction is a rare condition, often associated with severe duodenal ulcer disease. In children, clinical and functional characteristics of this syndrome are poorly known. Two cases are described here: one child had melena and the other had moderate abdominal pain, both without peptic ulceration. Basal and postprandial increase of gastrin levels showed a response over the upper normal range, indicating gastrin cell hyperfunction. Acid hypersecretion, both basal and after pentagastrin stimulation, was also found in the two children, confirming the biological effect of their sustained hypergastrinemia. Gastrin cell counts were within the normal range, while the number of somatostatin D cells was significantly reduced. This report stresses the importance of diagnosing antral gastrin cell hyperfunction in children because this unrecognized condition may manifest with serious complications (bleeding) or nonspecific abdominal symptoms.

Age-Dependent Vasodilation of the Skin Microcirculation by Atrial Natriuretic Factor

The microcirculatory responses to systemically administered alpha-human atrial natriuretic factor [99-126)hANF) (ANF) were investigated in the skin of eight young (18-25 years) and eight elderly (71-84 years) healthy volunteers in a double-blind, randomized, placebo-controlled study. Laser-Doppler flux (LDF), transcutaneous oxygen pressure (TcPO2), and skin temperatures on the finger (Td) and on the cheek (Tc) were measured during 60 min of i.v. ANF administration at a low rate (0.25 micrograms/min), resulting in plasma ANF concentrations in the upper normal range, and at a high rate (2.0 micrograms/min), inducing a 17- to 23-fold increase in plasma ANF. ANF infusion did not induce consistent changes in TcPO2 or Td at either rate. Placebo-corrected LDF increased significantly following low-rate ANF infusion in the elderly but remained unchanged in the young (mean +/- SD) +22 +/- 21% (p less than 0.05) and +7 +/- 32% (p greater than 0.1), respectively; following high-rate ANF infusion in LDF the changes were greater, with +28 +/- 56% and +19 +/- 42%, respectively. Because of the large SD the increases were no longer significant. During high-rate ANF infusion Tc remained unchanged in the young, but in the elderly Tc decreased--1.1 +/- 1.3% (p less than 0.05), which is probably due to the fall in blood pressure, which was more pronounced in the elderly than in the young: mean arterial blood pressure (MAP) decreased -9 +/- 3% (p less than 0.05) in the elderly and just -6 +/- 3% (p less than 0.05) in the young, both corrected for placebo changes.(ABSTRACT TRUNCATED AT 250 WORDS)