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Biomedical subjects

S E Husted

Publications and source records attributed to S E Husted.

At least 73 records · Page 4Linked to original sources

Renal blood flow and pelvic pressure after 4 weeks of total upper urinary tract obstruction in the pig. The effect of a TxA2 synthetase inhibitor on active preglomerular vasoconstriction.

In 8 female pigs complete unilateral ureteral obstruction was investigated over a 4 weeks period. The pigs were monitored with intrapelvic pressure measurements and by 131-I-hippuran scintigraphy twice a week; one group without and one with TxA2 blocking, UK-38,485 [3-(1H-imidazol-1-yl-methyl)-2-methyl-1H-indol-1-propanoic acid], which is a well-known selective thromboxane synthetase inhibitor. During the course of obstruction there was an ipsilateral linear reduction of split function to background level and a net reduction in total hippuran clearance in both groups. On the obstructed side there was a linear reduction of hippuran clearance from 116 +/- 26 ml/min to 11 +/- 3 ml/min during the first 2 weeks of obstruction. The TxA2 synthetase inhibitor, 5 mg/kg reduced se-TxB2 to almost zero for at least one hour after i.v. administration. One week after obstruction the pelvic pressure was 45 +/- 5 cm H2O) administration of the TxA2 synthetase inhibitor. The pelvic pressure remained elevated throughout the period of observation. The study confirmed earlier work which showed that total ureteral obstruction caused complete cessation of kidney function within a few weeks, but contradicts previous studies because there was no increase in renal blood flow after thromboxane blockade. These differences may be explained by several mechanisms. The continuing increase in pelvic pressure suggested that it was not only a preglomerular vasoconstriction which was responsible for the renal flow reduction, but that there was also a postglomerular vasoconstriction.

Animals↗

Effect of bepridil on metabolic control and insulin secretion in diabetics.

In a double-blind cross-over study bepridil 900 mg followed by 300 mg daily for 11 days was given to 37 insulin (Type I) or non-insulin (Type II)-dependent diabetic patients. It did not modify the metabolic control of the patients as levels of glucose in blood and urine, doses of insulin and oral hypoglycaemic drugs, energy intake, and the number of hypoglycaemic attacks during therapy were unchanged. The serum concentration of C-peptide was not modified in either type of diabetic patient, and serum insulin in the Type I but not in the Type II patients was slightly higher during active drug treatment. No adverse organotoxic or arrhythmogenic effects or changes in possible atherogenic lipid fractions in serum could be demonstrated during bepridil therapy.

Adult↗

Pelvic pressure measurements in the totally obstructed pyeloureter of the pig in 4 weeks.

The pelvic pressure was measured with a noninvasive technique in 7 pigs with a total unilateral obstruction of the ureter lasting 4 weeks. Pressure measurements were performed once a week. Although there was a wide pressure variation both intra- and interindividually during the 4 weeks, all systems had an elevated pressure (greater than 25 cm H2O) after 4 weeks. This study shows that the pelvic pressure can remain elevated in the chronically totally obstructed pyeloureter.

Animals↗

Dual inhibitory action of ATP on adrenergic neuroeffector transmission in rabbit pulmonary artery.

The aim of this study was to determine whether the inhibitory action of ATP on sympathetic neuroeffector transmission in the isolated pulmonary artery is due to ATP itself or one of its dephosphorylated breakdown products, ADP, AMP or adenosine. Furthermore, the mechanism of the inhibitory action was investigated. ATP (10(-6)-3 X 10(-4) M), the degradation-resistant ATP-analogue, beta, gamma-methylene-5'-triphosphate (10(-5)-3 X 10(-4) M), ADP (10(-6)-3 X 10(-4) M), AMP (10(-5)-3 X 10(-4) M), adenosine (10(-5)-3 X 10(-4) M) and 2-chloroadenosine (10(-7)-3 X 10(-4) M) reduced the contractions evoked by field-stimulation. This was also the case for prostaglandin E2 (3 X 10(-9)-3 X 10(-7) M), while prostaglandin F2 alpha (1.4 X 10(-8) M) slightly augmented the neurogenic response. The time course of the inhibitory effect of purinergic compounds on the stimulation evoked contractions was studied. In the case of ATP and ADP the inhibition was biphasic: an initial marked block (1 min. after drug addition) which in the continued presence of either compound recovered partially 10 min. later and then remained almost constant for another 90 min. The other purinergic agents caused a monophasic reduction. In the presence of indomethacin (5 X 10(-5) M), ATP and ADP also reduced the neurogenic contractions in a monophasic manner. Indomethacin did not alter the beta, gamma-methylene-5'-triphosphate-induced inhibition. Dilazep (3 X 10(-6) M) plus deoxycoformycin (3.6 X 10(-6) M), augmented the inhibitory effect of ATP. In contrast, theophylline (5 X 10(-5) M) did not alter the effect of ATP. The inhibitory effect of ATP (10(-4) M) on stimulation-evoked contractions was inversely proportional to the extracellular Ca2+ concentration (0.3-5.2 mM) and to frequency of stimulation (3-15 Hz). These results suggest that ATP initially causes a presynaptic inhibition of noradrenaline release evoked by field-stimulation. This phase I block is probably mainly due to an ADP-mediated short-lasting release of prostaglandins of the E type. The continuous inhibition (phase II) is probably due to ATP and its metabolites, possibly mainly adenosine. The phase II inhibition may possibly involve a decreased entry of Ca2+ into adrenergic nerve terminals during depolarization.

Adenosine↗

Renal effects of acute exposure to toluene. A controlled clinical trial.

Urinary excretion rates of beta 2-microglobulin and albumin were measured in 43 male printing trade workers and 43 age-matched male controls before and during exposure to toluene, 382 mg/m3, for 6 1/2 hours in a climate chamber. There were no significant changes in renal excretion rates of albumin and beta 2-microglobulin during toluene exposure indicating that no causal relationship exists between moderate exposure to organic solvents and renal injury.

Adult↗

Renal effects of chronic exposure to organic solvents. A clinical controlled trial.

Chronic effects of organic solvents on renal function were measured by creatinine clearances and urinary excretion rates of beta 2-microglobulin and albumin. Forty-three male printing trade workers occupationally exposed to different organic solvents for 9-25 years were compared with 43 age-matched male controls. No differences were found either in creatinine clearances or average basal levels of beta 2-microglobulin and albumin excretion rates, whereas a positive relation could be demonstrated between alcohol consumption on the day before the trial and urinary excretion rate of albumin. This investigation did not reveal any adverse renal effects of moderate chronic exposure to organic solvents in a group of active trade workers.

Albuminuria↗

Acute effects of acetylsalicylic acid on renal and hepatic function in normal humans.

The effect of a single oral dose (1 g) of acetylsalicylic acid (ASA) on renal function and hepatic enzymes as well as prothrombin time was studied in two series of experiments on normal human volunteers. Radioimmunoassay of albumin and beta 2-microglobulin excretion rates in urine revealed a statistically significant increase in both beta 2-microglobulin and albumin excretion rates within 2 h after dosage. Hepatic enzymes were not influenced by a single dose of ASA, while a statistically significant reduction in prothrombin time was registered. High-pressure liquid chromatography was used for measuring serum levels of ASA and salicylic acid (SA). Peak levels of 500 mumol/l and 150 mumol/l for SA and ASA, respectively, were found.

Adolescent↗

Prevention of postoperative deep venous thrombosis. Low-dose heparin versus graded pressure stockings.

In a prospective, controlled clinical study prevention of postoperative deep venous thrombosis by low-dose heparin (Heparin Leo 5 000 I.U. subcutaneously twice daily) was compared with graded compression stockings (TED stockings, Kendall Co.). One hundred and twelve patients, admitted during a period of one year for elective major surgery, were allocated to one of the two treatment groups. In order to detect deep venous thrombosis the 99mTc-plasmin test was performed before the operative procedure and again 5 days later. Ninety-seven patients completed the study (45 patients in the heparin group and 52 patients in the stocking group). Venous thromboembolism was detected in 4 patients (8.9%) in the heparin group and in 3 patients (5.8%) in the stocking group (p greater than 0.05). In 6 patients the plasmin test was positive and one patient in the heparin group died following pulmonary embolism. It is concluded that graded compression stockings can be used as an alternative to low-dose heparin for prophylaxis against deep venous thrombosis in elective general surgery.

Adult↗

Deep vein thrombosis detection by 99mTc-plasmin test and phlebography.

During a 2-year period the diagnostic value of 99mTc-labelled-plasmin test was evaluated in 63 patients admitted with clinical signs of deep vein thrombosis (DVT). In comparison with a conventional phlebography the diagnostic sensitivity and specificity of the plasmin test was 0.97 and 0.55, respectively. The predictive value in positive cases was 0.79 and in negative 0.92. The sensitivity was highest for thrombosis in the calf and popliteal regions, while the specificity was higher for thrombosis in the femoral veins. It is concluded that the 99mTc-labelled-plasmin test is suitable for DVT-screening in groups of high-risk patients and is simple and rapid. In positive cases the DVT diagnosis must be verified by phlebography.

Adolescent↗

The influence of age on renal and extrarenal effects of frusemide.

The effect of frusemide 80 mg i.v. was compared during 24 h in 10 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the 0 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the 0 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the elderly. The endogenous 24 h creatinine clearance was reduced by 12% (P less than 0.01) in both age groups. The frusemide induced changes in the 8 h serum concentration curves for albumin differed significantly between the two groups (analysis of variance, P less than 0.01). The drug induced increase in albumin concentration became significant in the young 5 min after the injection. In the elderly it took more than 15 min before the increase in serum albumin reached significance. The average maximal increase in albumin concentration was 14.3% in the young and 9.7% in the elderly (P less than 0.05). No difference was seen between the two age groups in the significant frusemide induced increases in the 24 h albumin excretion but in the elderly a significantly larger decrease in the 24 h excretion of beta 2-microglobulin was observed (P less than 0.05). No significant age difference was observed in the initial significant increases in diastolic blood pressure observed in both age groups or between the later changes in systolic blood pressure which was significantly reduced in the young only. The slower haemoconcentration response in the elderly seemed associated with the slower secretion rate of frusemide to the tubular lumen. We found no evidence of an age related difference in tubular cell response to frusemide. It is emphasized that a maximal initial frusemide response in the elderly, in contrast to what was found in the young, probably was not achieved by the 80 mg i.v.

Adult↗