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Biomedical subjects

S N Rasmussen

Publications and source records attributed to S N Rasmussen.

At least 73 records · Page 4Linked to original sources
PubMed1989

A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease.

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids.

Administration, Oral↗
PubMed1989

[Small bowel transplantation. Animal experimental and clinical status].

Small bowel transplantation is a logical treatment in patients with the short bowel syndrome. The intestinal function can be permanently reestablished in animals with small bowel autografts. However, small bowel allotransplantation involves a considerable risk of immunological problems because of the large quantity of lymphoid tissue present in the graft. In non-immunosupprimized experimental animals, it triggers a vigorous rejection response and/or graft versus host disease (GVHD). The use of azathioprine and prednisone as immunosuppression has improved the graft survival minimally. The advent of cyclosporine has increased the survival of small bowel allografts in animal experiments considerably. Preoperative graft irradiation reduces the risk of GVHD. Monitoring of graft function is difficult. Histological evaluation of intestinal biopsy specimens is very useful and it can be combined with the determination of the absorptive function by 14C labelled carbohydrates (glucose, maltose). Twelve patients have undergone small bowel transplantation during the period 1964-1987. Eleven patients died a few weeks after the small bowel transplantation, the longest survivor died after 76 days (information is not available about the last small bowel transplanted patient). Four patients were treated with cyclosporine. Although the results so far have been depressing, a fundament has been created for further investigation in the field. Today, small bowel transplantation is an experimental treatment. It should only be considered for patients with serious and immediately life-threatening complications of the short bowel syndrome.

Adult↗
PubMed1989

Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration.

A phenytoin prodrug, 3-phosphoryloxymethyl phenytoin (ACC-9653; 1), has been developed with more favorable physicochemical properties than phenytoin for parenteral administration. The purpose of this study was to evaluate the pharmacokinetic profile of 1 following iv and im administration in adult patients receiving chronic oral phenytoin monotherapy. Each patient (9 males, 1 female) received a single iv dose of undiluted 1 equivalent to their twice daily phenytoin dose (100-200 mg). An equivalent dose of im 1 was administered in the gluteus maximus muscle one week later. Serial blood samples were obtained after each dose. Phenytoin and 1 concentrations were measured using HPLC. Compartmental analysis using weighted nonlinear least squares, and noncompartmental pharmacokinetic analysis were performed on each patient's concentration-time data. Data following iv 1 in eight of ten patients were best described using a two-compartment model. Mean pharmacokinetic parameter estimates for iv 1 in these patients were central volume of distribution (Vdc) of 0.040 +/- 0.0084 L/kg and plasma disappearance half-life (t1/2 alpha) of 8.0 +/- 2.9 min ("conversion" t1/2). Overall mean clearance (CL) was 0.24 +/- 0.080 L/kg/h in the 10 patients. Mean pharmacokinetic parameter estimates for im 1 were a rate constant (ka) of 2.47 +/- 1.41 h-1 and an absolute bioavailability (F) of 100.5 +/- 20.3%. Mean observed tmax values for phenytoin were 0.57 +/- 0.26 and 1.46 +/- 0.76 h following iv and im 1, respectively. Model-independent estimates of clearance agreed well with the compartmental analyses. Steady-state predose phenytoin concentrations did not significantly vary from the comparable concentrations following iv 1 administration (p = 0.22).(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1989

Pharmacokinetics of oral idarubicin in breast cancer patients with reference to antitumor activity and side effects.

The pharmacokinetics of orally administered idarubicin (22.5 mg/m2/week) and idarubicinol were studied for 12 weeks in 14 patients with breast cancer. Plasma concentrations were monitored for 72 hours after the first, fourth, and twelfth doses and trough concentrations after 1, 2, 3, 4, 5, 7, 11, and 12 weeks of treatment. The half-lives of idarubicin and idarubicinol were 19 and 60 hours, respectively. No time-dependent changes or cumulation were observed. The metabolic ratio showed little variation. The plasma AUCs of idarubicin and idarubicinol varied between patients but were fairly constant in individual patients. The sum of the plasma AUCs was lower in patients with rapid progression than in patients who responded to treatment. A correlation between this parameter and the relative decrease in the leukocyte counts was demonstrated (p less than 0.05). No correlation was found between the pharmacokinetic parameters and the time to final progression.

Administration, Oral↗
PubMed1989

Disposition kinetics of disopyramide in human healthy volunteers described by an open three compartment model.

Disposition kinetics of disopyramide was examined in an open randomised cross-over study in 8 healthy volunteers. Disopyramide was randomly administered as a single bolus injection (150 mg) over a period of 5 min. and as an infusion (28.2) mg/h to steady state. Disposition kinetics of disopyramide were most precisely described by an open three compartment model according to Akaike's information criteria. Significant positive correlations (0.909 +/- 0.04, P less than 0.05 (injection study); 0.787 +/- 0.11, P less than 0.05 (infusion study] were observed between total serum concentrations of disopyramide and renal clearance while no significant correlation could be demonstrated between free serum concentrations and renal clearance. This implies a constant value of unbound renal clearance. The results are consistent with non linear kinetics (mainly caused by the variable free fraction of the drug), when based on total serum concentrations. The disposition of unbound disopyramide, however seems to be linear (i.e. the kinetic parameters are independent of dose) in the bolus injection study. Total elimination clearance (free and total), volume of distribution and elimination half-life were significantly higher in the steady state experiment than in the bolus injection study.

Adult↗
PubMed1989

Effects of mesalazine substitution on salicylazosulfapyridine-induced seminal abnormalities in men with ulcerative colitis.

Some semen characteristics of eight male patients with clinically inactive ulcerative colitis were investigated. Semen analysis was carried out twice during salicylazosulfapyridine (SASP) treatment and repeated twice after at least 3 months' treatment with mesalazine. The motility variables all showed significant improvement during mesalazine treatment: the graded motility (p less than 0.05), motility in percentage (p less than 0.01), and the penetration in egg white (p less than 0.05). The semen plasma was analyzed for mesalazine and the metabolite Ac-mesalazine during both regimens. There was no difference in the semen plasma concentration of mesalazine during the two regimens, whereas Ac-mesalazine was significantly higher during mesalazine treatment than during SASP treatment, indicating that other SASP metabolites, most likely sulfapyridine, are the agent causing the abnormal sperm characteristics. We suggest that pure mesalazine preparations are a safer alternative in young men with chronic inflammatory bowel disease.

Adult↗
PubMed1989

The final outcome of patients presenting with their first episode of acute diarrhoea and an inflamed rectal mucosa with preserved crypt architecture. A clinicopathologic study.

When a patient presents with acute diarrhoea, the most important question is whether it represents the first episode of chronic inflammatory bowel disease (CIBD) or acute self-limited colitis (ASLC). The early changes in the rectal mucosa of patients with ASLC have been claimed to be highly diagnostic, the presence of an unspecific inflammatory infiltrate in the lamina propria and the absence of disturbances in the crypt architecture being the characteristic features. Thirty-two patients who in the period 1980-1984 presented with their first episode of acute diarrhoea and whose rectal mucosa showed these histologic features were followed up for 1.5-7 years. Forty-one per cent of the patients were finally classified as having ASLC and 28% as having diseases other than CIBD or ASLC. Thirty-one per cent eventually developed CIBD. Thus the features claimed to be diagnostic of ASLC could not predict the final outcome of the disease in patients presenting for the first time with acute diarrhoea. The histologic interpretation can provide significant information in these patients but should never replace a careful clinical judgement and, if doubt remains, further observation of the patients.

Acute Disease↗
PubMed1988

Influence of renal function on the elimination of morphine and morphine glucuronides.

The influence of renal function, measured by 51Cr-EDTA clearance, on morphine and morphine glucuronide kinetics has been studied in 13 patients after a single i.v. injection of morphine. Unconjugated morphine and morphine glucuronides were measured by a sensitive, specific RIA after extraction from plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r = 0.94, p less than 0.001). A relatively long terminal elimination of half-life of morphine was found in all patients (mean +/- SD: 9.2 +/- 2.5 h), irrespective of glomerular function.

Aged↗
PubMed1988

Phenytoin pharmacokinetics in critically ill trauma patients.

Preliminary data have suggested that phenytoin systemic clearance may increase during initial therapy in critically ill patients. The objectives for this study were to model the time-variant phenytoin clearance and evaluate concomitant changes in protein binding and urinary metabolite elimination. Phenytoin was given as an intravenous loading dose of 15 mg/kg followed by an initial maintenance dose of 6 mg/kg/day in 10 adult critically ill trauma patients. Phenytoin bound and unbound plasma concentrations were determined in 10 patients and urinary excretion of the metabolite p-hydroxyphenyl phenylhydantoin (p-HPPH) was measured in seven patients for 7 to 14 days. A Michaelis-Menten one-compartment model incorporating a time-variant maximal velocity (Vmax) was sufficient to describe the data and superior to a conventional time-invariant Michaelis-Menten model. Vmax for the time-variant model was defined as V'max + Vmax delta (1 - e(-kindt)). Vmax infinity is the value for Vmax when t is large. The median values (ranges) for the parameters were Km = 4.8 (2.6 to 20) mg/L, Vmax infinity = 1348 (372 to 4741) mg/day, and kind = 0.0115 (0.0045 to 0.132) hr-1. Phenytoin free fraction increased in a majority of patients during the study period, with a binding ratio inversely related to albumin. Measured urinary p-HPPH data were consistent with the proposed model. A loading and constant maintenance dose of phenytoin frequently yielded a substantial, clinically significant fall in plasma concentrations with a pattern of apparently increasing clearance that may be a consequence of changes in protein binding, induction of metabolism, or the influence of stress on hepatic metabolic capacity.

Adult↗
PubMed1988

Pharmacokinetics of midazolam and alpha-hydroxy-midazolam following rectal and intravenous administration.

1. In an open cross-over trial, plasma concentrations of midazolam were measured in eight healthy male volunteers following administration of 0.3 mg kg-1 body weight given by the rectal and intravenous routes. 2. Maximum plasma concentrations of 92-156 ng ml-1 (mean 118 ng ml-1) were recorded from 20 to 50 min (mean 31 min) after rectal application. The rectal bioavailability was 40-65% (mean 52%) and the terminal half-life was 114-305 min (mean 161 min). 3. A substantial first-pass hepatic effect was observed following rectal administration. 4. No systemic or local intolerance was noted. 5. In conclusion, the rectal route of administration provides a rapid and reliable absorption of midazolam.

Administration, Rectal↗
PubMed1988

Noradrenaline as a possible mediator in the renal response to vascular expansion with blood in the cat.

In chloralose anaesthetized cats with renal arterial pressure kept constant at 100 mmHg, vascular expansion with precirculated blood, 20 ml kg b.w.-1, caused significant increments in arterial inflow rates of blood to the deep (ARBFD) and superficial (ARBFS) renal venous drainage area of 35 +/- (SE)10 and 19 +/- 6%, respectively, and in the excretion rates of water and sodium of 73 +/- 24 and 75 +/- 28%, respectively, while GFR remained essentially unchanged. In acutely denervated kidneys the responses to expansion were not significantly different from those of innervated kidneys, which indicated largely humoral mediation. Arterial plasma concentrations of noradrenaline, adrenalin, and vasopressin fell significantly to values of a half to one-third of pre-expansion values, while plasma dopamine was not significantly changed by expansion. The response to expansion could be (1) reversed by a 'substituting' intraaortic infusion of noradrenaline, and (2) imitated, without volume expansion, by an infusion of an alpha-adrenergic blocking agent (phentolamine). It is concluded that the renal response (excretory and vascular) to volume expansion with blood is largely humorally mediated and that circulating noradrenaline may play a causal role in the response.

Adrenergic alpha-Antagonists↗