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Biomedical subjects

S Lundin

Publications and source records attributed to S Lundin.

At least 91 records · Page 5Linked to original sources
PubMed1994

Topical 0.3% and 0.5% podophyllotoxin cream for self-treatment of condylomata acuminata in women. A placebo-controlled, double-blind study.

BACKGROUND: Genital warts are a well-recognized clinical entity and a disease of great antiquity that differ from skin warts both histologically and antigenically. It is a common sexually transmitted disease of high prevalence all over the world. Women are more likely to be unaware of such warts because it is harder for them to examine their genitalia. OBJECTIVE: The purpose of this multicenter, double-blind, placebo-controlled study was to compare the clinical efficacy and tolerance of 0.3% and 0.5% podophyllotoxin in a cream emulsion (castor oil, BP as vehicle) to cure genital condylomata in women. METHODS: Preselected (n = 80) Asian females (mean age 23.6 years), harboring 544 warts (mean 6.8 in number), ranging from 1 to 9 mm in size (mean 2.1 mm) with biopsy-proven diagnosis of condylomata acuminata were randomly allocated to three groups (30 + 30 + 20). At home the patients applied the given trial medication themselves (using the finger) twice a day, for 3 consecutive days per week, and if not cured the same course was extended to 3 more weeks, in total 24 topical applications for 4 weeks. The patients were examined on a weekly basis, and a total regression of warts (biopsy-proven) was evaluated as complete cure. RESULTS: By the end of the study, the placebo group (20 patients, bearing 124 warts) did not show any regression or clinical efficacy, while 41/60 patients (68.3%) and 349/420 warts (83%) were cured in the 0.3% and 0.5% treatment groups (placebo vs. active groups p < 0.001). Patients using the 0.5% active medication had substantially more eliminated warts (205/349, 95.8%) than the 0.3% group (70%). Localized adverse symptoms were mild to moderate and were well tolerated by the patients with no dropout. Forty-three patients (53.8%) did not show any adverse reaction. The most frequent adverse symptoms were tenderness (23/80, 28.8%) and burning sensation (14/80, 17.5%). Among 41/80 (51.25%) cured patients 4 had a relapse after 16 weeks. CONCLUSION: Along with mild, tolerable side effects the study demonstrates that 0.5% podophyllotoxin cream is more efficacious than 0.3% (p < 0.01) and can be considered as a reliable home-based treatment.

Administration, Topical↗
PubMed1994

Bidirectional small-intestinal permeability in the rat to some common marker molecules in vitro.

BACKGROUND: The barrier properties of the small intestine were investigated by studying the bidirectional permeability to five commonly used marker molecules. METHODS: Proximal and distal small-intestinal segments from rats were mounted in diffusion chambers, and the permeation of the markers 3H-mannitol (Mw 182), 51Cr-ethylenediamineteraacetic acid (Mw 341), [mercaptopropionic acid], D-arginine8]-vasopressin (Mw 1069), fluorescein isothiocyanate (FITC)-dextran (mean Mw 3000), and inulin (Mw 5200) was measured across the mucosa in both directions. RESULTS: A generally increased inward (mucosa to serosa) and a decreased outward (serosa to mucosa) permeation of the markers was found in the proximal to distal direction. The inward permeability showed increasing regional differences with decreasing size of the markers. In the absence of the villous epithelium, removed by scraping the intestinal wall, 86% to 62% of the proximal and distal barrier was lost in the inward direction but only 14% to 26% in the outward direction. CONCLUSIONS: The intestinal epithelial barrier is more permeable in the outward than in the inward direction, and regional permeability differences exist in a size-dependent fashion. The results suggest two passage routes, one for the smallest molecule, mannitol, and a second for the larger markers in the present size range, both apparently different from the route for macromolecules such as intact proteins.

Animals↗
PubMed1994

Thoracic epidural anesthesia during coronary artery bypass surgery: effects on cardiac sympathetic activity, myocardial blood flow and metabolism, and central hemodynamics.

The effects of high thoracic epidural anesthesia (TEA) on cardiac sympathetic nerve activity, myocardial blood flow and metabolism, and central hemodynamics were studied in 20 patients undergoing coronary artery bypass grafting (CABG). In 10 of the patients, TEA (T1-5 block) was used as an adjunct to a standardized fentanyl-nitrous oxide anesthesia. Hemodynamic measurements and blood sampling were performed after induction of anesthesia but prior to skin incision and after sternotomy. Assessment of total and cardiac sympathetic activity was performed by means of the norepinephrine kinetic approach. Prior to surgery, mean arterial pressure (MAP), great cardiac vein flow (GCVF), and regional myocardial oxygen consumption (Reg-MVO2) were lower in the TEA group compared to the control group. During sternotomy there was a pronounced increase in cardiac norepinephrine spillover, MAP, systemic vascular resistance index (SVRI), pulmonary capillary wedge pressure (PCWP), GCVF, and Reg-MVO2 in the control group. These changes were clearly attenuated in the TEA group. None of the patients in the TEA group had metabolic (lactate) or electrocardiographic signs of myocardial ischemia. Three patients in the control group had indices of myocardial ischemia prior to and/or during surgery. We conclude that TEA attenuates the surgically mediated sympathetic stress response to sternotomy, thereby preventing the increase in myocardial oxygen demand in the pre-bypass period without jeopardizing myocardial perfusion.

Anesthesia, Epidural↗
PubMed1993

Effect and content of arginine vasopressin in normal and obstructed rat urinary bladder: an in vivo and in vitro investigation.

The present investigation was performed to evaluate the possible role of arginine vasopressin (AVP) in detrusor instability in the obstructed rat urinary bladder. The effect of AVP on normal and obstructed rat detrusor smooth muscle was tested in vivo and in vitro. Arginine vasopressin given as a closed intraarterial injection to the bladder transiently decreased micturition volume and increased micturition frequency during cystometry in control rats. In rats with infravesical outlet obstruction the effect of AVP on cystometrical parameters was negligible. In accordance with this finding, the efficacy of AVP in contracting detrusor muscle in vitro was much lower for obstructed bladders than for controls. The EC50 values were, however, similar. Arginine vasopressin added to the bath had no effect on nerve-mediated contractile responses. Obstruction led to a transient decrease in immunoreactive AVP concentration, but the total amount of AVP per bladder increased significantly after 6 weeks of obstruction as a consequence of the 14-fold increase in bladder weight. The decreased excitatory effect of AVP in obstructed bladder makes a role for this peptide in the development of detrusor instability less likely.

Animals↗
PubMed1993

Epidural clonidine depresses sympathetic nerve activity in humans by a supraspinal mechanism.

BACKGROUND: Epidural administration of the alpha 2-adrenergic agonist clonidine induces hypotension. Animal experiments have indicated a possible spinal mechanism through activation of alpha 2-adrenergic receptors on sympathetic preganglionic neurons, resulting in a decrease of efferent sympathetic activity. However, the pharmacokinetic behavior of epidural clonidine, the high lipid solubility of the drug, and the apparent sedative side effects also indicate a possible supraspinal mechanism. To test this hypothesis, the effect of epidural and intramuscular clonidine on efferent sympathetic nerve activity to the leg was studied with microneurography. METHODS: In 15 healthy volunteers, a lumbar epidural catheter was inserted and multiunit postganglionic sympathetic activity was recorded in a skin or muscle fascicle of the peroneal nerve before and after epidural injection of clonidine. Skin blood flow in the hand and in the foot was measured with laser Doppler flowmetry. In six additional experiments, performed at another time, clonidine was given intramuscularly. RESULTS: After epidural injection of clonidine (3 micrograms/kg) the resting level of skin sympathetic activity decreased to 18 +/- 5% (n = 6; P < 0.001), muscle sympathetic activity expressed as bursts/min to 41 +/- 12% (n = 7; P < 0.01), and integrated muscle sympathetic activity to 41 +/- 13% (n = 7; P < 0.01) of control values after 30 min. However, the capacity for activation of skin sympathetic activity by arousal stimuli and of muscle sympathetic activity by apnea remained. Intramuscular clonidine inhibited both skin sympathetic activity (n = 3) and muscle sympathetic activity (n = 3) to the same extent. Skin blood flow increased whereas blood pressure and heart rate decreased after epidural and intramuscular clonidine. CONCLUSIONS: The comparable inhibition of resting sympathetic nerve activity, paralleled by a decrease in heart rate and blood pressure after both epidural and intramuscular clonidine, indicates that epidural clonidine induces a supraspinally evoked general decrease in sympathetic outflow.

Adrenergic alpha-Agonists↗
PubMed1993

Pharmacokinetics of 1-deamino-8-D-arginine vasopressin after various routes of administration in healthy volunteers.

OBJECTIVE: We investigated the pharmacokinetics and biological effects of 1-deamino-8-D-arginine vasopressin (dDAVP) in healthy adults after intravenous, subcutaneous, intranasal, peroral, sublingual and intrarectal administration. DESIGN: Eight normal volunteers were studied over an 8-hour period after each drug administration, separated by at least one week. For intravenous and subcutaneous administration, the subjects received 2 micrograms of dDAVP. The intranasal and sublingual doses were 20 micrograms and the rectal dose was 50 micrograms. Oral administration of dDAVP was effected with a 200-micrograms tablet. MEASUREMENTS: Plasma and urinary levels of dDAVP were measured using a specific and sensitive radioimmunoassay. RESULTS: A significant increase of urine osmolality was observed after all routes of administration, except the sublingual and intrarectal for up to 8 hours after administration. After intravenous administration, the half-life of elimination (t1/2) of dDAVP was 78 +/- 10 minutes. An extensive adsorption of dDAVP to the plastic syringe was found with intravenous but not with subcutaneous administration. Using the area under the curve of dDAVP from the subcutaneous administration as a reference, bioavailability was found to be 3.4% after intranasal administration and 0.1% after oral administration. After sublingual and intrarectal routes of administration no detectable dDAVP was found in the blood; however, low amounts were found in the total 24-hour urine. CONCLUSION: The bioavailability of dDAVP seems lower than previously reported after intranasal and oral administration.

Administration, Intranasal↗
PubMed1993

Pharmacokinetic properties of the tocolytic agent [Mpa1, D-Tyr(Et)2, Thr4, Orn8]-oxytocin (antocin) in healthy volunteers.

OBJECTIVE: The aim of this study was to study the pharmacokinetics of antocin, the tocolytic oxytocin antagonist [Mpa1, D-Tyr2(Et), Thr4, Orn8]-oxytocin. DESIGN: Antocin was injected intravenously as a bolus dose (5 mumol). Blood samples were taken at intervals for 240 minutes. In addition, the binding of 125I-Tyr10-antocin to blood constituents was determined and compared with 125I-AVP and 125I-[Mpa1, D-Arg8]-vasopressin (desmopressin). SUBJECTS: Eight healthy, non-smoking adults, three male and five female. MEASUREMENTS: Antocin was measured using a specific radioimmunoassay after prior extraction of the plasma. Plasma binding was estimated using polyethyleneglycol precipitation. RESULTS: The rate of plasma disappearance of antocin was best fitted by a biexponential curve. The clearance of antocin was 23.5 +/- 7.6 l/h, the volume of distribution was 13.1 +/- 3.8 l and the biological half-life was 39.0 +/- 4.1 minutes. A greater proportion of 125I-Tyr10-antocin bound to plasma proteins (33.5%) and red blood cells (13%) than did 125I-AVP, 125I-desmopressin and unlabelled desmopressin. CONCLUSIONS: The half-life was longer and the clearance of antocin was less than that found in a previous study when a non-specific antiserum was used. This is most likely because of the extended blood sampling time period which revealed the biphasic decay pattern. The higher plasma clearance of antocin compared to oxytocin and desmopressin may be explained by its increased binding to blood constituents rather than by differences in enzymatic degradation of the molecules.

Adult↗
PubMed1993

Effects of intrathecal morphine and spinal anaesthesia on sympathetic nerve activity in humans.

Microneurography with direct registration of efferent sympathetic nerve activity to muscle or skin was used to study the effect of morphine and procaine given intrathecally to patients scheduled for transurethral resection of the prostate. A lumbar spinal catheter was inserted and multiunit postganglionic sympathetic activity was recorded in a muscle or skin fascicle of the peroneal nerve. After injection of 0.4 mg morphine, sympathetic nerve activity to muscle (n = 6) or skin (n = 2) was recorded for 30 min. Compared with a 10-min control period prior to the injection no change in activity could be observed. In contrast, spinal anaesthesia (procaine 75-100 mg) with an upper level of sensory blockade at T3-T11 completely eliminated intraneurally recorded sympathetic activity within 5 min (n = 8). Skin vasodilation and loss of sudomotor responses in the foot accompanied the neural blockade.

Aged↗
PubMed1993

Evaluation of a new system for ventilatory administration of nitric oxide.

A new system for delivery of nitric oxide (NO) to inspiratory gas consisting of two mass flow regulators and a soda-lime absorber for scavenging of nitrogen dioxide (NO2) is described. The system was evaluated using three different techniques for NO analysis (infrared, chemiluminescence and electro-chemical fuel cell technique). The electro-chemical fuel cell was less sensitive to humidity in the sample and is suitable for clinical routine use. The infrared analyser was very sensitive to humidity and the gas sample must be dried by silica gel, which absorbs NO2 and will cause falsely low NO2 values. NO2 was analysed with ultra-violet methodology. NO2 is highly toxic and the highest recommended occupational health and safety level for inhalation is 5 ppm. The highest values of NO2 in our system were detected before the absorber in the inspiratory limb of the breathing system, being 5 ppm at 100% oxygen and 100 ppm NO using "infant" respiratory settings (3 l/min in ventilation, frequency of 30/min). The corresponding value for "adult" respiratory settings (10 l/min in ventilation, frequency of 15/min) was 3.2 ppm. The absorber reduced these levels to well below 1 ppm. When clinically relevant levels of NO were used (20 ppm), no NO2 could be detected after the absorber, irrespective of oxygen concentration in the breathing gas. It was observed that gas cylinders with NO mixed in nitrogen may initially have a high NO2 concentration (around 12 ppm) and should be flushed thoroughly before use.

Evaluation Studies as Topic↗
PubMed1993

Topical treatment of penile condylomata acuminata with podophyllotoxin 0.3% solution, 0.3% cream and 0.15% cream. A comparative open study.

The purpose of this comparative open study was to determine the clinical efficacy of 0.3% podophyllotoxin both in 70% ethanolic solution and cream preparations on genital warts. Three parallel trial preparations, 0.3% solution, 0.3% and 0.15% cream, were randomly allocated to 60 circumcised Asian males (mean age 19.5 years), with the diagnosis of genital condyloma. Patients applied the trial preparation twice a day for 3 consecutive days. If total elimination was not achieved with one trial, it was extended to 3 similar cycles, in total of 4 weeks duration. Response was calculated with a response rate formula. After 3 weeks of treatment all the patients in the 0.3% solution group were evaluated as cured, with mild localized erythema and burning sensation. In the 0.3% cream preparation group, 75% of the patients were cured, and the remaining 25% were found to be cured after 4 treatments. In the 0.15% cream preparation group, 70% of the patients were evaluated as completely cured after 4 weeks. Non-objective, moderate to mild localized adverse symptoms were reported by both the active cream groups. Three of 54 patients (90%) with complete cure showed relapses after 16 weeks. It was concluded that 0.3% podophyllotoxin is more efficacious in ethanolic solution than in cream preparations.

Adolescent↗
PubMed1993

Metabolism and excretion of nitric oxide in humans. An experimental and clinical study.

Despite the increasing insight in the clinical importance of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF), there is limited information about the metabolism and elimination of this mediator in humans. We studied the degradation of NO in healthy subjects inhaling 25 ppm for 60 minutes and in patients with severe heart failure inhaling 20, 40, and 80 ppm in consecutive 10-minute periods. In other healthy subjects, the renal clearance of NO metabolite was measured. The metabolism ex vivo was evaluated by direct incubation of nitrite, the NO oxidation product, in blood from healthy humans. During inhalation of NO, the plasma levels of nitrate increased progressively, both in the healthy subjects (from 26 to 38 mumol/L, P < .001) and in the patients (from 72 to 90 mumol/L, P < .001). Methemoglobin (MetHb) also increased in the healthy subjects (from 7 to 13 mumol/L, P < .001) as well as in the patients (from 19 to 42 mumol/L, P < .01). No change in nitrosohemoglobin (HbNO) was detected, either in the healthy subjects or in the patients. In arterialized blood (O2 saturation, 94% to 99%), incubated nitrite was semiquantitatively converted to nitrate and MetHb. In venous blood (O2 saturation, 36% to 85%) moderate amounts of HbNO were also formed. Plasma and urinary clearance of nitrate in healthy subjects averaged 20 mL/min. We conclude that uptake into the red blood cells with subsequent conversion to nitrate and MetHb is a major metabolic pathway for endogenously formed NO. Nitrate may then enter the plasma to be eliminated via the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of adrenal function tests on the levels of endogenous digitalis-like substances and some pituitary hormones.

In order to study the influence of the hypothalamic-pituitary-adrenal axis on the levels of endogenous digitalis-like substances (EDLS) in plasma and urine, eight healthy subjects (25-40 years old) were given dexamethasone 1 mg orally and tetracosactide (an ACTH analog) 0.25 mg i.v., on separate occasions. The circulating levels of EDLS, TSH, PRL and AVP following administration of either test drug, and under control conditions, were measured by a RIA for digoxin and specific RIAs for each hormone. Plasma cortisol was measured by liquid chromatography. The area under the curve (AUC) of hormone levels between 08.00 and 09.30 was used for data comparisons. Urine was collected before and after each test dose, and analysed for cortisol levels by gas chromatography/mass spectrometry, and for digitalis-like activity both by RIA and by a bioassay measuring 86Rb-uptake into red blood cells. Dexamethasone suppressed the AUC of plasma and urine levels of cortisol (p = 0.0001 and p < 0.01, respectively) and immunoreactive EDLS (p = 0.0007 and p < 0.01), as well as serum levels of TSH (p = 0.0002) and PRL (p = 0.001), but did not alter AVP levels. The biological digitalis-like activity in the urine measured by the 86Rb-uptake assay was decreased, but not to a statistically significant degree. ACTH increased the levels of cortisol in plasma (p = 0.0001) and urine (p < 0.01) and the immuno-reactive EDLS in plasma (p = 0.03), but not in urine. There were no effects of ACTH on TSH, PRL or AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Regional small-intestinal permeability in vitro to different-sized dextrans and proteins in the rat.

Molecular weight-dependent passage over different regions of the rat small intestine, using different-sized proteins/peptides and fluorescein isothiocyanate-dextrans in the 1- to 70-kDa range, was studied in vitro in modified Ussing chambers. The mucosal to serosal passage was inversely related to the molecular weight. After 120 min the passage in the proximal region usually dominated, but the nonapeptide (mercaptopropionic acid1, D-arginine8)-vasopressin differed by showing a consistently higher passage in the distal region. The similar apparent permeation coefficients obtained for the two macromolecular categories of corresponding molecular weight implied that the non-degradable dextrans could be used as permeability markers reflecting the passage per se of intact proteins. Furthermore, the results indicated two different transmucosal pathways, one of low permeability for molecules > 30 kDa, in which the molecular weight was of minor importance for the passage, and another more permeable one in the 1- to 30-kDa range, in which the passage was highly influenced by the molecular weight.

Animals↗
PubMed1993

Pharmacokinetic and pharmacologic properties of antiuterotonic oxytocin analogs in the rat.

The pharmacologic and pharmacokinetic properties were evaluated in a series of antiuterotonic oxytocin analogs, modified at positions 1, 2, 4, 8 and, in one case, position 9 of the oxytocin (OT) molecule. [Mpa1,D-Tyr2(Et),Val4,Orn8,desGly9]-OT, [Mpa1,Tyr2(Et),Val4,Orn8]-OT and [Mpa1,D-Tyr2,Val4,Orn8]-OT displayed similar plasma clearance rates (Clps) using the constant infusion method in rats. Two analogs, [Mpa1,D-Tyr2(Et),Val4,Orn8]-OT and, particularly, [Mpa1,D-Tyr2(Et),Thr4,Orn8]-OT, were cleared at significantly higher rates compared with the others. [Mpa1, D-Tyr2(Et), Val4, Orn8]-OT and [Mpa1, D-Tyr2(Et), Thr4, Orn8, desGly9]-OT were most potent in eliciting a short-term in vivo antiuterotonic effect, whereas the duration of effect was longest for [Mpa1, D-Tyr2, Val4, Orn8]-OT and [Mpa1, D-Tyr2(Et), Thr4, Orn8, desGly9]-OT. The Clp of [Mpa1, D-Tyr2, Val4, Orn8]-OT was similar regardless of the infusion rate. No relationship between antiuterotonic effect and Clp of the five peptides could be demonstrated, and no significant linear correlation between Clp and effect duration was found. The apparent volumes of distribution for the present analogs were 10-fold larger than the blood volume, a finding to be considered when measuring in vivo antagonistic activity. The 24-h urinary excretion ranged from 14.3 to 25.6% of the i.v. dose and was negatively correlated with peptide lipophilicity. It is concluded that, in addition to diverging pharmacologic properties, peptide analogs may differ markedly in kinetic parameters like Clp, volumes of distribution and urinary excretion despite minor molecular modifications.

Animals↗
PubMed1992

Degradation and inactivation of rat atrial natriuretic peptide 1-28 by neutral endopeptidase-24.11 in rat pulmonary membranes.

Atrial natriuretic peptide (ANP), a 28-residue peptide with cardiovascular and renal effects, is rapidly cleared from the circulation. Beside renal clearance, an extra-renal metabolism by the enzyme neutral endopeptidase-24.11 (NEP-24.11) has been proposed, since specific NEP-24.11-inhibitors increase endogenous plasma-ANP. NEP-24.11 is present in rat lung but its significance for ANP hydrolysis within the lung is unclear. The aim of this study was to investigate a possible degradation of rat ANP in a membrane preparation from rat lung. Hydrolysis products of ANP were separated by HPLC and further characterized by a pulmonary artery bioassay, by radioimmunoassay with different antisera, by peptide sequencing and by masspectrometry. Rat pulmonary membranes degraded ANP to one main metabolite lacking biological activity and with poor cross-reactivity to an antiserum recognising the central ring-structure of the peptide. Formation of the hydrolysis product was prevented by the NEP-24.11-inhibitor phosphoramidon (1 microM). Peptide sequencing of the metabolite revealed a cleavage between Cys7 and Phe8, which was confirmed by mass-spectrometry. The metabolite had an HPLC elution time identical to that of the product formed by purified porcine NEP-24.11. These findings suggest that ANP is metabolized and inactivated by endopeptidase-24.11 in rat lungs, the first organ exposed to ANP released from the heart.

Amino Acid Sequence↗
PubMed1992

Contractile effect and tissue content of arginine vasopressin in the urinary bladder of Brattleboro rats with hereditary diabetes insipidus.

1. Urinary bladders from male rats of the Brattleboro strain with hereditary diabetes insipidus (DI) were analyzed for presence of immunoreactive arginine vasopressin (ir-AVP). Healthy rats were used as controls. 2. Bladders from the DI rats were heavier than controls. Concentration of ir-AVP was lower in DI bladders, but total amount of ir-AVP was similar to that in controls. 3. EC50 values for the AVP concentration-response relations were similar for control and DI bladder strips. Maximum response to AVP relative to response to K+ high solution was lower in the DI group. 4. An AVP receptor antagonist that significantly blocked response to exogenous AVP had no effect on response to field stimulation. 5. We suggest that AVP is synthetized locally and that AVP is not the non-adrenergic non-cholinergic transmitter responsible for the atropine resistant contraction in rat bladder.

Animals↗