7 young, healthy, male subjects performed exercise on bicycle ergometers in two 20 min periods with an interval of 1 h. The first 10 min of each 20 min period consisted of arm exercise (38--62% of Vo2 max for arm exercise) or leg exercise (58--78% of Vo2 max for leg exercise). During the last 10 min the subjects performed combined arm and leg exercise (71--83% of Vo2 max for this type of exercise). The following variables were measured during each type of exercise: oxygen uptake, heart rate, mean arterial blood pressure, cardiac output, leg blood flow (only during leg exercise and combined exercise), arterio-venous concentration differences for O2 and lactate at the levels of the axillary and the external iliac vessels. Superimposing a sufficiently strenuous arm exercise (oxygen uptake for arm exercise greater than 40% of oxygen uptake for combined exercise) on leg exercise caused a reduction in blood flow and oxygen uptake in the exercising legs with unchanged mean arterial blood pressure. Superimposing leg exercise on arm exercise caused a decrease in mean arterial blood pressure and an increased axillary arterio-venous oxygen difference. These findings indicate that the oxygen supply to one large group of exercising muscles may be limited by vasoconstriction or by a fall in arterial pressure, when another large group of muscles is exercising simultaneously.

The microvascular permeability to small and large molecules was studied during good and poor metabolic regulation in ten short duration juvenile diabetics. The following variables were measured; daily urinary albumin and beta2-microglobulin-excretion rates, whole body transcapillary escape rate of albumin (TER), glomerular filtration rate (GFR), capillary filtration coefficient (CFC), and capillary diffusion capacity (CDC). The urinary albumin and beta2-microglobulin concentration were measured by sensitive radioimmunoassays; TER was detemined from the initial disappearance of intravenously injected 125I-labelled human serum albumin; GFR was measured on the forearm by straingauge plethysmography and CDS for 51Cr-EDTA clearance; CFC was measured on the forearm by straingauge plethysmography and CDC, for 51Cr-EDTA was determined in the jyperaemic anterio tibial muscle by the local clearance technique. All the above mentioned variables, except CDC, were significantly increased during poor metabolic regulation, indicating a functional microangiopathy. The mechanisms of these alterations appear to be increased filtration pressure in the microcirculation and/or increased porosity of the microvasculature. The findings of increased microvascular albumin passage are compatible with the hypothesis that the organic - histologicallly demonstrated - diabetic microangiopathy is a long-term effect of periods of increased extravasation of plasma proteins, with subsequent protein deposition in the microvascular wall, i.e. the concept to plasmatic vasculosis.

In a placebo-controlled study, the safety and efficacy of the selective alpha 1-adrenoceptor-blocking agent doxazosin 4 mg once daily in the symptomatic treatment of benign prostatic hyperplasia (BPH) were evaluated. One hundred patients were primarily included in a 9-weeks study, and after this 75 patients accepted to continue in the present 20 weeks extension. Of the patients in the doxazosin-group (DG) 61% reported overall improvement against 53% in the placebo-group (PG)--(p = 0.56). In the DG, 49% of obstructive symptoms were improved compared to 27% in the PG (p < 0.01), and a reduction of 60% of irritative symptoms was found in the DG against 36% in the PG (p < 0.01). Daytime frequency was reduced by median 1.5 in the DG and remained unchanged in the PG (p < 0.01). Nocturia was reduced by median 1 and 0.5 respectively (p = 0.06). Maximum urinary flow rate (MFR) was improved by median 1.5 ml/s in the DG, while it deteriorated by median 0.5 ml/s in the PG (p < 0.05), Considering postvoid residual urine volume, cystometry variables (first sensation and bladder capacity), changes in sexual function and adverse events there was no difference between the two groups. In conclusion, doxazosin 4 mg once daily in long-term treatment of patients with BPH reduces both obstructive and irritative symptoms, daytime voiding frequency and although only slightly, significantly augments MFR without interference with sexual function and without other serious adverse effects.

Kidney function was studied in nine, metabolically well controlled, short-term insulin-dependent male diabetics before and during glucagon infusion of 4 to 5 and 8 to 10 ng/kg/min. Glomerular filtration rate, effective renal plasma flow (steady-state infusion technique, with urinary collections, using 125I-iothalamate and 131I-iodohippurate), and urinary albumin and beta 2-microglobulin excretion rates were measured. The mean plasma glucagon concentration increased during infusion from 254 +/- 19 pg/ml to 440 +/- 31 pg/ml (low dose) and 730 +/- 52 pg/ml (high dose). Glomerular filtration rate increased in all subjects from 133 +/- 5 before the glucagon infusion to 141 +/- 4 with the low dose, and 148 +/- 7 ml/min/1.73 m2 with the high dose (p < 0.01). The increase in glomerular filtration rate correlated with the rise in plasma glucagon concentration (r = 0.67; p < 0.01). Renal plasma flow increased from 530 +/- 21 before the glucagon infusion to 555 +/- 20 with the low dose and 572 +/- 29 ml/min/1.73 m2 with the high dose (p < 0.01). Urinary beta 2-microglobulin excretion rate rose from 5.8 +/- 1.0 before infusion to 8.7 +/- 1.7 with the low dose, and 17.9 +/- 5.7 micrograms X 10(-2)/min with the high dose (p < 0.01). Urinary albumin excretion remained unchanged during the glucagon infusion. These results suggest that glucagon may contribute to the reversible elevation of glomerular filtration rate typically found in poorly regulated insulin-dependent diabetics, but not to the moderate elevation found in well controlled diabetics.

The safety and efficacy of the selective alpha 1-blocking agent doxazosin 4 mg once daily in the symptomatic treatment of benign prostatic hyperplasia were evaluated in a randomized, double-blind and placebo-controlled 9-week study of 100 patients. By patients' overall assessment of voiding difficulties, 79% in the doxazosin group (DG) and 44% in the placebo group (PG) reported improvement (p = 0.001). In the DG, improvement was noted in 63% of obstructive symptoms compared to 32% in the PG (p = 0.015), whereas improvement was noted in 76% and 45%, respectively, of irritative symptoms (p = 0.12). Daytime frequency was reduced by 1.5 in the DG and increased by 0.3 in the PG (p = 0.001), and nocturia was reduced by 1.1 and 1.0, respectively (p = 0.12). Maximum urinary flow rate was improved by 1.5 ml/s in the DG, while it deteriorated by 0.3 ml/s in the PG (p = 0.11). Considering postvoid residual urine volume, cystometry variables (first sensation and bladder capacity) and adverse events there was no difference between the two groups. In conclusion, doxazosin 4 mg once daily is safe and effective in relieving symptoms in patients with BPH.

The immediate effects of selective (Pl) andnon-selective (pl + 2) Padrenoreceptor blockade on local blood flow and substrate exchange were studied in young male subjects at rest and during dynamic forearm exercise. After a control period of rest, exercise and recovery, atenolol (PI), propranolol (/31+2) or placebo was infused into the right brachial artery during a second period of rest, exercise and recovery.2. Neither atenolol nor propranolol influenced forearm blood flow during exercise. Atenolol and propranolol reduced the increase in lactate release from the forearm during exercise by 39 and 34% respectively. Neither agent influenced oxygen and glucose uptake. Propranolol increased forearm uptake of free fatty acids during exercise by 135%.A concomitant fall in forearm respiratory quotient indicated an increased utilization of free fatty acids.Atenolol did not affect free fatty acids uptake or respiratory quotient.3. Blockade of vascular P,-receptors does not seem to be important for the blood flow regulation during muscular exercise. Both selective and non-selective Padrenoreceptor blockade reduce the lactate release from exercising skeletal muscle, but appear to have different effects on fat metabolism.

Kidney function was studied in 9 normal males before and during a 2 h growth hormone (GH) infusion of 50 ng/kg/min. The following variables were measured during each 20 min clearance period: glomerular filtration rate, GFR, effective renal plasma flow, RPF (steady state infusion technique with urinary collections using [125I]iothalamate and [131I]iodohippurate), and urinary albumin and \g=b\2-microglobulin excretion rates (radioimmunoassays).The GH infusion resulted in a 10-fold increase in plasma GH concentration.All the above mentioned variables remained practically unchanged during the infusion except for a small (\m=-\5%)but significant decrease in renal plasma flow (P < 0.01). Our negative results contrast to the findings of increased GFR and RPF during prolonged GH administration and suggest that GH requires several hours or days for its renal effects to become manifest.

Objective. To investigate the clinical outcome in patients with clinically suspected pulmonary embolism (PE). Design and setting. In a retrospective design we studied 588 consecutive patients with suspected PE and referred for lung scintigraphy from 1995 to 1998. The mean follow-up time was 653 424 days. Results. The diagnosis of PE was con®rmed in 194 and excluded in 394 patients, respectively. The overall prevalence of PE was 33%. Amongst clinical and paraclinical variables, age, chronic obstructive pulmonary disease (COPD), heart rate, pleuretic pain, presence of deep venous thrombosis (DVT), electrocardiographic signs of right ventricular (RV) strain were identi®ed as independent predictors of the diagnosis of PE. Amongst patients with PE anticoagulation was given in 96% for at least 3 months and 13% received thrombolytic therapy. Recurrent PE was seen in 6% of patients with PE whereas none of the patients with no diagnosis of PE suffered PE during follow-up. The 1 year mortality was 18% amongst patients with PE and 15% in patients with excluded PE (P NS). The cause of death amongst patients with PE was cancer (49%) and PE (28%), whereas patients without PE had an excess mortality because of cancer, COPD, acute myocardial infarction and heart failure. Conclusion. Patients admitted to hospital on suspicion of PE have increased risk of adverse clinical outcome whether the diagnosis of PE is con®rmed or not. This indicates that the patients where the diagnosis is excluded often suffer from other serious illness that warrants further investigations.