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Biomedical subjects

S Husted

Publications and source records attributed to S Husted.

At least 37 records · Page 2Linked to original sources
PubMed1982

Atropine resistance of transmurally stimulated isolated human bladder muscle.

Human detrusor strips were obtained from patients undergoing reimplantation of ureters because of reflux, transvesical prostatectomy, or cysto-urethrectomy en bloc because of bladder malignancy. The strips were electrically stimulated. A frequency-dependent contractant response was obtained that was potentiated by physostigmine and abolished by tetrodotoxin. The maximum response approximately equaled that of acetylcholine in a maximum concentration. In most bladder preparations from patients without known functional bladder disturbances, atropine (0.01 to 0.1 microM) had a marked inhibitory effect, and at concentrations exceeding 1 microM the blockade was complete. In strips obtained from patients undergoing transvesical prostatectomy, and who also had a cystometrically verified unstable bladder, there was a varying degree of atropine resistance, with some preparations showing a 50 per cent resistance to atropine. Prazosin, phentolamine, yohimbine, guanethidine, clonidine, and noradrenaline had no consistent effects on the electrically induced bladder contraction. Nifedipine and nimodipine caused a maximum of 65 per cent inhibition of the response. Addition of nimodipine to atropine-resistant strips when maximum atropine inhibition had been reached abolished the contractions. Omitting calcium from the bath solution rapidly abolished the electrically induced contraction. It is suggested that in the normal human bladder the contraction induced by electrical stimulation is mainly atropine sensitive. However, in the functionally disturbed bladder, part of the bladder contraction is atropine resistant, a finding that may have clinical implications.

Adolescent↗
PubMed1982

Contractile effects of some polypeptides on the isolated urinary bladder of guinea-pig, rabbit, and rat.

In isolated detrusor from guinea-pigs and rats substance P (SP) induced concentration-dependent phasic contractions. Rabbit detrusor strips responded to SP with an initial phasic and an ensuing tonic contraction. The concentration-response curve to SP in this preparation had a biphasic appearance. Eledoisin (E) caused contractile responses similar to those of SP when tested on the guinea-pig detrusor. Somatostatin was tested on the rabbit urinary bladder; it caused a concentration-dependent rise in basal tone, but no phasic contraction. The responses to SP and E were not affected by tetrodotoxin or physostigmine. They were only partly inhibited by high concentrations of atropine and the anticholinergic drug PR 197. Noradrenaline and isoprenaline caused a concentration-dependent inhibition of the peptide induced responses in guinea-pig bladder; at high concentrations in the amines this inhibition was almost complete. Indomethacin did not affect the SP induced contractions in the guinea-pig bladder, reduced the responses in the rabbit detrusor, but increased them in the rat bladder. Contractions elicited by SP and E were rapidly diminished or abolished after 30 min. treatment in a calcium-free medium. The responses were also inhibited by the calcium antagonist nifedipine. In guinea-pig preparations depolarized by potassium (127 mM) both SP and E caused a contractile response approximately 20% of that obtained in normal Tyrode solution. It is concluded that SP and E cause contraction of detrusor by a direct effect on the smooth muscle cells, and that this response is dependent on the extracellular calcium concentration. Prostaglandins may be involved in the SP-induced response of the rabbit detrusor.

Animals↗
PubMed1982

The histopathology of camptomelia (bent limbs). A dyschondrogenesis.

Camptomelia is well established syndrome in which the most prominent osseous feature is bowing of the long bones. Although several patients have died, usually due to respiratory insufficiency caused by defects of the cartilage of the tracheal rings and lower respiratory tract, histologic studies of the bone in camptomelia have led to conflicting conclusions about pathogenesis. A complete autopsy of a neonatal case, including serial sections of the long bones, revealed normal enchondral growth sequences of the epiphyseal plate. In the diaphysis, centering around the angle of the bend, the cylinderization process was markedly abnormal. Extensive new secondary trabeculae formed on the concave (posterior) surface of the bone during resorption on the convex (anterior) surface. A cone of dense new bone formed at the apex at the convex anterior angle of the bend. These findings supported previous suggestions that bone formation and remodeling processes were normal. With the variation of bone involvement in different patients, these features indicate that camptomelia is the result of an abnormality of cartilage anlage formation, probably owing to a transient exogenous teratogen. Camptomelia is the preferred term. Basically, the syndrome is a dyschondrogenesis.

Bone and Bones↗
PubMed1981

Inhibition of adrenergic neuroeffector transmission in rabbit pulmonary artery and aorta by adenosine and adenine nucleotides.

The effect of adenosine and adenine nucleotides on sympathetic neuroeffector transmission in the rabbit isolated pulmonary artery and aorta was studied. Adenosine (10(-5)-3 x 10(-4)M) decreased the contractile response of pulmonary artery and aorta evoked by electrical-field stimulation. The decrease was reversible. No tachyphylaxis developed. Inhibition of either adenosine deaminase by deoxycoformycin (3.6 x 10(-6)M) or of adenosine transport by dilazep (3 x 10(-6)M) did not alter the inhibitory effect of adenosine on the neurogenic contractions in the pulmonary artery. However, deoxycoformycin plus dilazep markedly enhanced the inhibitory effect of adenosine. The calcium antagonists nifedipine (1.5 x 10(-8)M) and nimodipine (1.3 x 10(-8)M) had no effect on the adenosine-induced inhibition. This was also the case with theophylline (5 x 10(-5)M), atropine (10(-7)M), and the prostaglandin synthetase inhibitors indomethacin (5 x 10(-5)M and suprofen (3 x 10(-5)M). The contractile response of the pulmonary artery elicited by exogenous (-)-noradrenaline (NA; 10(-9)-3 x 10(-4)M) was essentially not altered by adenosine (10(-5)-3 x 10(-4)M). Adenosine (10(-4)M) did not alter the spontaneous 3H-outflow from rabbit aorta preloaded with 3H-(-)-noradrenaline (3H-NA). Adenosine (10(-5)-3 x 10(-4)M), ADP (10(-4)M), ATP (10(-5)M), and inosine (10(-4)M) diminished the overflow of tritium from pulmonary artery and aorta preloaded with 3H-NA. The spontaneous outflow of tritium from aorta preloaded with 3H-NA consisted of 3H-NA (17%), 3H-dihydroxyphenylglycol (3H-DOPEG; 30%), 3H-dihydroxymandelic acid (3H-DOMA, 4%), 3H-O-methylated and deaminated metabolites (3H-OMDA; 42%), and 3H-normethanephrine (3H-NMN; 2%). Adenosine (10(-5) and 10(-4)M) enhanced 3H-DOPEG and 2H-NMN, decreased 3H-NA, and did not alter 3H-DOMA and 3H-OMDA. The stimulation-evoked overflow of tritium for aorta preloaded with 3H-NA consisted of 3H-NA (31%), 3H-DOPEG (18%), 3H-DOMA (2%), 3H-ONDA (46%), and 3H-NMN (3%). Adenosine (10(-5) and 10(-4)M) enhanced 3H-NA and 3H-DOPEG, decreased 3H-OMDA and did not alter 3H-DOMA and 3H-NMN. Adeosine (10(-6)-10(-4)M) did not alter the accumulation of 3H-NA (10(-8)M) by aorta. It is concluded that adenosine inhibits vascular sympathetic neuroeffector transmission by diminishing the release of transmitter from the nerve terminals.

Adenine Nucleotides↗
PubMed1981

Substance P and somatostatin and excitatory neurotransmission in rabbit urinary bladder.

The influence of substance P (SP) and somatostatin (SS) on contractions induced by electrical field stimulation, ATP and carbachol were investigated in isolated rabbit urinary bladder. Some experiments were also carried out in rat and guinea-pig detrusor. When added cumulatively to rabbit and rat preparations, SP and SS caused a gradual increase in tone of the preparations. There were no effects on the electrically induced contractions. In rabbit and rat detrusor pretreated with guanethidine, atropine and indomethacin, the contractile response to nerve stimulation was markedly reduced. In this situation SP and SS caused 2-4 fold increase in the electrically induced contractions. Indomethacin abolished the tonic response to ATP in the rabbit detrusor, and reduced the initial phasic contraction by about 30%. Both SP and SS were able to restore the phasic contraction to the level obtained before indomethacin addition. The contractions induced by carbachol in rabbit and rat detrusor were not affected by SP and SS, not even in indomethacin pretreated preparations. The SP-antagonist (D-Pro2, D-Phe, D-Trp9)-SP was tested in isolated rabbit, rat, and guinea-pig detrusor. Concentrations of the antagonist which effectively inhibited contractions induced by a submaximum concentration of SP had no effect on the contractile response to electrical field stimulation in rabbit and guinea-pig preparations, and rather tended to increase the contractions in the rat detrusor. The results suggest that neither SS nor SP is the mediator of excitatory non-cholinergic, non-adrenergic activation of rabbit urinary bladder. A role as local modulators of neuromuscular transmission cannot be excluded.

Adenosine Triphosphate↗
PubMed1980

Contribution of prostaglandins to the adenosine triphosphate-induced contraction of rabbit urinary bladder.

1 Adenosine 5'-triphosphate (ATP) produced an initial rapid, phasic contraction and a later, slowly developing tonic contraction in the isolated detrusor of the rabbit but mainly a rapid, phasic response in the guinea-pig bladder. 2 Electrical field stimulation elicited only a rapid, phasic contraction in both rabbit and guinea-pig bladders. 3 Prostaglandin synthesis inhibition by means of indomethacin and suprofen abolished the tonic response to ATP in the rabbit detrusor, leaving the phasic part of the contraction almost unaffected. The ATP-induced contraction in guinea-pig bladder was not influenced by indomethacin. 4 The contractile response of rabbit urinary bladder to prostaglandins F2 alpha and E2 and to carbachol were not significantly influenced by indomethacin. The contractions induced by the prostaglandins were similar to the tonic response to ATP. 5 Tetrodotoxin, atropine, phentolamine, and theophylline did not alter the ATP-induced contraction. However, the calcium antagonists, nifedipine and nimodipine, abolished the phasic ATP response and greatly reduced the tonic part of the contraction. 6 Tachyphylaxis occurred on repeated addition of ATP; the response to field stimulation was progressively reduced only after indomethacin pretreatment. 7 ATP and prostaglandins may contribute to the non-adrenergic, non-cholinergic component of the excitation of rabbit and guinea-pig bladder.

Adenosine Triphosphate↗
PubMed1980

The binding of furosemide to serum proteins in elderly patients: displacing effect of phenprocoumon.

The percentual binding of furosemide (5 micrograms/ml) was slightly but significantly lower in serum from elderly patients than in serum from normal blood donors (96.5 +/- 0.7 versus 97.9 +/- 0.3). A significant positive correlation was demonstrated between protein binding and albumin concentration in serum. The reduced binding in the elderly could be explained by an observed decrease in the concentration of albumin in the elderly. The percentual binding did not change in samples obtained during the first hour after the intravenous administration of 40 mg furosemide. Of 4-chloro-5-sulfamoyl antranilic acid (CSA) and antranilic acid (A) about 60% were bound to serum proteins in vitro and none of these two compounds affected the protein binding of furosemide. The addition of phenprocoumon (PPC) caused significant decreases in the percentual binding of furosemide in serum (5 microgram/ml) at PPC values of 10 microgram/ml and more. The effect of PPC on the binding of furosemide was studied in vivo in 7 patients receiving 40 mg furosemide intravenously without and with the simultaneous intravenous administration of PPC (3 mg per 10 kg body weight). In good accordance with the in vitro experiments the modest average decrease in furosemide binding, caused by concentrations of PPC not exceeding 6.2 micrograms/ml, was not significant.

4-Hydroxycoumarins↗
PubMed1980

Mechanisms of the responses to non-cholinergic, non-adrenergic nerve stimulation and to ATP in isolated rabbit urinary bladder: evidence for ADP evoked prostaglandin release.

The contractile effects of ATP and related purine compounds on the isolated rabbit detrusor were investigated. It was found that ATP produced an initial rapid, phasic contraction followed by a slowly developing and maintained increase in tension. ADP caused a contraction closely mimicking the tonic response to ATP. The ADP induced contraction and the tonic response to ATP could both be abolished by indomethacin. beta, gamma-methylene ATP (APPCP), which is not degraded to ADP, elicited a rapid, phasic response, which could be abolished by nifedipine. AMP, dibutyryl-cAMP, and adenosine in low concentrations had no contractile effects; high concentrations of adenosine and 2-chloroadenosine, which is resistant to adenosine deaminase, decreased tone and spontaneous activity. The amplitude of the ATP induced contraction was positively correlated to the Ca2+-concentration in the extracellular medium; removal of Ca2+ abolished the ATP contraction before the responses to high K+ and carbachol disappeared. Responses to electrical field stimulation, mediated by non-cholinergic, non-adrenergic mechanisms were abolished by nifedipine and significantly reduced by indomethacin. It is concluded that in isolated rabbit detrusor, a direct contractile response can be elicited only by tripolyphosphates (ATP and APPCP), and that the diphosphate moiety ADP stimulates synthesis of prostaglandins The similarity between the effects of stimulation of non-cholinergic, non-adrenergic neurones and the phasic response to ATP supports the view that in rabbit detrusor ATP may be involved in excitation.

Adenine Nucleotides↗
PubMed1980

The binding of aprindine to serum proteins with statistical considerations concerning the analysis of binding data.

The binding of the potent, basic antiarrhythmic agent aprindine to serum proteins was studied in solutions of human serum albumin (HSA, lyophilized, 98% pure, KABI) and in human sera. The percentual binding in serum (90.9-96.7%) was considerably higher than in HSA solutions. The binding in serum decreased from 95-97% to 91-93% as the aprindine concentration was raised from 4 to 15 micrograms/ml. The serum binding differed significantly in sera from three normal individuals. By plotting (Formula: see text), as a function of bound drug and performing statistical analysis of the curves a striking difference between the number of primary binding sites in serum and in HSA solution was found (N1 for the HSA solution was 0.0016 and for one serum it was 0.020 "per albumin molecule".) The association constants for the primary binding sites (K1) were 4.3 X 10(6)M-1 for serum and 2.1 X 10(6)M-1 for the HSA solution. Furthermore, the analysis indicated that considerably less than one secondary binding site was present for each albumin molecule in the HSA solution. Therefore, no binding of aprindine to albumin molecules has been demonstrated and it is concluded that the entire binding of aprindine in serum as well as in 98% HSA solutions may be due to the presence of acid protein molecules. In particular, low percentual binding in HSA solutions in spite of the high association constant can be explained by a very low concentration of the binding proteins. The addition of propranolol or phenprocoumon did not cause any displacement of aprindine. In the appendix statistical problems in the analysis of the binding curves are elucidated. The experimental variance and the statistical acceptability of the binding model are discussed.

Analysis of Variance↗
PubMed1980

Anticholinergic and calcium antagonistic effects of terodiline in rabbit urinary bladder.

The effects of terodiline on contractions induced in isolated rabbit detrusor by carbachol and potassium, and by electrical field stimulation were investigated. Terodiline relaxed preparations contracted by carbachol and potassium and, when added 15 min before stimulation, decreased the contractile responses to these agents in a concentration-dependent way. Terodiline more effectively inhibited carbachol than potassium induced contractions. The "pure" calcium antagonist nifedipine had the opposite effect. Both atropine and terodiline caused a parallel shift to the right of the concentration-response curve to carbachol. The maximum contractile tension and slope were not affected, suggesting a competitive antimuscarinic effect within the concentration range used. Atropine was approximately 750 times more potent than terodiline. The maximum inhibitory effect of atropine and the calcium antagonist nimodipine on the electrically induced response were 40% and 69%, respectively. Terodiline caused complete inhibition of the response, as also did a combination of nimodipine and atropine. --The results suggest that terodiline in low concentrations has mainly an antimuscarinic action. To this, a calcium antagonistic effect is added at higher concentrations. The two-fold action of the drug makes it an effective inhibitor of bladder contraction, and an interesting tool for investigations of bladder contractility.

Animals↗
PubMed1979

The determination of naproxen by spectrofluorometry and its binding to serum proteins.

A fluorometric method for the determination of naproxen in serum, albumin solutions and protein free buffer solutions is described. The detection limit is about 10 ng/ml. Furosemide, thiopental and salicylic acid did not show any disturbing fluorescence while phenprocoumon did. The in vitro binding of naproxen in albumin solutions and serum was studied by equilibrium dialysis. A small but significant increase was found in the percentual binding in albumin solutions as compared to serum. The percentual binding was not affected by changes in the pH from 5--8. By fitting the binding data to a model assuming two classes of binding sites, association constants and binding capacities were determined. A very high affinity and a high capacity were found. The association constant for the first class of binding sites was higher for human serum albumin than for serum (8.5 versus 5.3 . 10(6) M-1). The difference in the protein binding to the first class of binding sites in human serum albumin and serum can be explained by the existence of a competitive inhibitor in serum.

Albumins↗
PubMed1979

The binding of phenprocoumon to human plasma proteins.

By in vitro experiments with equilibrium dialysis and 5 micrograms PPC per ml an average of 99.7 +/- 0.2% was bound to serum proteins. The binding in a solution with the albumin concentration which was present in the serum samples did not differ from this binding or from the binding in plasma where coagulation was prevented with either heparin or citrate. The binding constant in albumin solutions at 37 degrees was 4.5 +/- 0.31/mol x 10(-5) and an average of 1.16 +/- 0.04 primary binding sites was found. The association constant for the PPC albumin interaction was temperature dependent and the results of thermodynamic calculations suggested a combined ionic and non-polar type of binding as the change in enthalpy contributed with 40% of change in free energy. A large positive entropy change was found (15.79 Kcal/mol/degree K). The addition of phytomenadione to albumin solutions and of menadione to plasma caused a considerable decrease in the protein bound fraction of PPC, indicating the relevance of a study concerning the possible clinical consequences of these interactions.

4-Hydroxycoumarins↗
PubMed1979

The effect of daily administration of naproxen on the prothrombin complex activity in patients under long-term therapy with phenprocoumon.

Out of a total of 150 patients attending an out-patient clinic for anticoagulant therapy, 12 had disorders which normally would indicate a prolonged use of an antirheumatic drug. To 6 of these patients, naproxen (1/4 g twice daily) was given while anticoagulant treatment with phenprocoumon was continued in an unchanged dosage schedule (average dose 2.1 mg/day). On the average, the prothrombin complex activity (PP%) was reduced to a stable level 10--20% below that obtained during a 2-month period before the naproxen treatment was started. No bleeding episodes or other effects were observed. Thus the simultaneous administration of naproxen caused no problems for the maintenance of a stable anticoagulant therapy.

4-Hydroxycoumarins↗
PubMed1978

Pharmacokinetics of sulfadiazine and trimethoprim in man.

Sulfadiazine (SDZ) 800 mg and trimethoprim (TMP) 160 mg were given orally to 10 normal subjects and the concentration of SDZ and TMP in serum and urine was followed for 24 h. Both drugs showed a significant negative correlation between individual "peak" concentrations in serum and the body weight of the subject. Twelve hours after dosing the serum concentration was 12 to 25 microgram/ml for SDZ and 0.3 to 1.1 microgram/ml for TMP. Individual concentration ratios between SDZ and TMP in serum were 4.8 (1 h)--145 (24 h), and in the urine the ratio was close to 6 throughout the 24 h collection period. The range of urinary concentrations was from 65 to 400 microgram/ml for SDZ and from 13.8 to 93.4 microgram/ml for TMP. The fraction (formula: see text) was 21% during the 0--8 h period, 33% during the 8--15 h period and 41% during the 15--24 period. The average "t1/2" was 15.2 +/- 7.4 h for SDZ and 7.4 +/- 1.9 h for TMP. Individual subjects showed a significant correlation between the serum clearance of TMP and SDZ (p less than 0.01) and also between the renal clearance of the two drugs (p less than 0.05). The serum clearance was significantly correlated with the renal clearance for TMP but not for SDZ. For SDZ Vd was significantly negatively correlated with the elimination constant; for TMP no such correlation was found. The serum clearance of SDZ was significantly correlated with the percentage of SDZ which was excreted as the (presumably) acetylated compound. The renal clearance of SDZ was independent of the serum concentration of SDZ. There was a highly significant negative correlation between the renal clearance and serum concentration of TMP, as well as for "acetylated SDZ". The renal clearance of "acetylated SDZ" averaged more than six times that of unconjugated SDZ. With increased urine flow the renal clearances of TMP and SDZ were significantly increased.

Absorption↗
PubMed1977

The influence of age on the response to anticoagulants.

1 A group of 114 patients on long-term anticoagulant therapy was studied. The daily maintenance dose of both phenprocoumon, bishydroxycoumarin and warfarin was found to be significantly lower in patients aged between 61 and 70 years than in the those between 50 and 60 years of age. The mean daily dose of bishydroxycoumarin, hower, when expressed on a weight basis, was not significantly lower in the elderly. 2 For bishydroxycoumarin but not for phenprocoumon and warfarin there was found a statistically significant correlation between the daily maintenance dose and the weight of the patient. 3 The mean daily dose of both bishydroxycoumarin and warfarin was 30-40% lower than that recommended in the literature. 4 'Correction' was made for potential drug interference by excluding patients in continuous medication with order drugs known to influence the treatment with orally administered anticoagulants. The interindividual variation in dosage requirements of coumarin drug was thereby reduced in the age groups above 60 years. 5 The level of vitamin-k dependent coagulation factors, measured by Owren's 'P and P' method (PP%) was significantly lower (P less than 0.001) in patients of advanced age (between 61 and 70 years) than in younger patients (between 50 and 60 years). 6 The plasma concentration of albumin was significantly lower in patients over 60 years than in those under that age. 7 Correlation (P less than 0.01) was found between the daily maintenance dose of phenprocoumon and the plasma concentraction of albumin.

Aged↗