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Biomedical subjects

E Bodd

Publications and source records attributed to E Bodd.

At least 19 recordsLinked to original sources
PubMed2001

Relations between medical history, clinical findings and plasma N-terminal proatrial natriuretic peptide in patients in primary health care.

BACKGROUND: recent studies indicate that measurement of natriuretic peptides may be a valuable tool to improve the quality of the diagnosis of heart failure in general practice. AIM: the aim of the present study was to examine the relationship between the plasma level of the natriuretic peptide N-terminal proANP and symptoms and signs of heart failure in patients from general practice in the Oslo area. METHODS AND RESULTS: we undertook a survey of 499 patients consecutively enrolled from the practice of 27 practitioners. One hundred and twenty-nine patients were classified as having possible or some degree of heart failure. The plasma concentration of N-terminal proANP increased with severity of heart failure as judged from clinical examination. In multivariate analysis age, history of heart disease, plasma creatinine, use of beta-blockers and digitalis, oedemas and atrial fibrillation were the main determinants of plasma N-terminal proANP. CONCLUSION: while there was an overall increase in N-terminal proANP values with increasing symptoms and degree of heart failure, no single finding was closely related to N-terminal proANP. Treatment effects and diagnostic errors may both influence the relationship between N-terminal proANP and clinical findings. The current study has demonstrated the feasibility of using N-terminal proANP by general practitioners for the potentially improved diagnosis of heart failure. Further research is required to determine the precise role of this assay in clinical practice.

Aged↗
PubMed1995

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

1. The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan were investigated in 10 healthy subjects. 2. The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t1/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3. Two subjects had significantly lower urinary recovery (0.48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmO) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4. Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5. Serum and urine samples taken more than 8 and 24 h after administration of ethyl-morphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6. The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology, and no firm conclusions about the source of morphine are possible based on serum samples obtained more than 24 h after drug administration.

Adult↗
PubMed1994

Fluvastatin efficacy and tolerability in comparison and in combination with cholestyramine.

The aim of this study was to investigate the new synthetic HMG-CoA reductase inhibitor, fluvastatin, for efficacy, safety and tolerability in comparison to cholestyramine. One hundred fifty one primary hypercholesterolaemic patients participated in this double-blind, parallel-group, randomized study. During the first 12 weeks of the study, fluvastatin (20 mg and 40 mg daily) was compared with cholestyramine (16 g per day). In the subsequent, 6-week part of the study, the comparative efficacy, safety and tolerability of 20 mg fluvastatin, combined with cholestyramine (4 g, 8 g, or 16 g) were assessed. Fluvastatin (40 mg) reduced LDL cholesterol by 28.0%, triglycerides by 10.5% and increased HDL cholesterol by 3.7%. Cholestyramine (16 g) reduced LDL cholesterol by 35.0%, but raised triglycerides and HDL cholesterol by 12.3% (p < 0.01) and 3.7% respectively. The combination of fluvastatin 20 mg and cholestyramine (4 g, 8 g and 16 g) induced the following reductions in LDL cholesterol: 30.4%, 35.6% and 46.6% respectively. There was no significant change in triglycerides in either group although HDL cholesterol was raised by 4.9%, 8.3% and 7.2% respectively. One patient treated with fluvastatin and two treated with cholestyramine were withdrawn from the study due to elevation of liver transaminases. The most frequent subjective adverse effects in both treatment groups were mild, transient gastrointestinal complaints. Thus, fluvastatin was effective as a lipid-lowering agent; the effect was further enhanced when fluvastatin was combined with cholestyramine.

Anticholesteremic Agents↗
PubMed1994

A comparison of octreotide, bromocriptine, or a combination of both drugs in acromegaly.

We investigated the pharmacokinetics of bromocriptine and octreotide, both individually and in combination, in 12 patients with active acromegaly. The pharmacodynamics of the drugs were assessed by 12-h profiles of GH secretion and insulin-like growth factor-I (IGF-I) measurements. During the 42-day study period, bromocriptine was administered for 28 days (from day 8; 5 mg, orally, twice daily) and octreotide (200 micrograms, sc, twice daily) from days 15-42. IGF-I levels, 12-h GH, and plasma bromocriptine and octreotide profiles were obtained on days 0, 14, 28, and 42. During bromocriptine treatment, both the area under the GH day curves (AUC) and mean IGF-I decreased to 64% (95% confidence limits, 43-72% and 48-82%, respectively) of initial values. During octreotide treatment, the respective values were 23% (18-30%) and 32% (21-36%), which were greater decreases than those during bromocriptine treatment [36% (95% confidence limits, 32-54%) for AUC for GH and 50% (95% confidence limits, 34-58%) for IGF-I]. With combined treatment, the AUC for GH was reduced to 16% (12-21%) and that of IGF-I to 25% (16-27%) of initial values. This combination was more effective than bromocriptine [25% (95% confidence limits, 22-37%) for AUC for GH and 39% (95% confidence limits, 25-43%) for IGF-I] and octreotide alone [78% (95% confidence limits, 53-89%) for AUC for GH and 78% (95% confidence limits, 57-98%) for IGF-I]. The pharmacokinetic parameters of octreotide were unchanged by the coadministration of bromocriptine. The bioavailability of bromocriptine increased by approximately 40% when bromocriptine was administered together with octreotide compared with administration alone (P < 0.01). Bromocriptine disposition parameters were unaltered. In conclusion, treatment of acromegalics with a combination of octreotide and bromocriptine increases the bioavailability of bromocriptine and reduces both GH and IGF-I levels more effectively than treatment with either drug alone. This presents the possibility of less frequent drug administrations, lower doses of octreotide, and, consequently, lower treatment costs.

Acromegaly↗
PubMed1993

Different biotransformation of morphine in isolated liver cells from guinea pig and rat.

The biotransformation of morphine was characterized in freshly isolated parenchymal and non-parenchymal liver cells from rats and guinea pigs in suspension culture to establish an in vitro model for morphine metabolism. Liver cells were prepared by a collagenase perfusion technique, and separated by differential centrifugation. Morphine metabolism was investigated at different concentrations (1, 5, 100 and 200 microM). Samples were taken repeatedly during 2-4 hr of incubation, and subsequently analysed on a HPLC system employing both UV and electrochemical detection. In suspensions of hepatocytes from both animal species morphine-3-glucuronide (M3G) was the major metabolite of morphine, and was formed at comparable rates at all concentrations examined. Guinea pig hepatocytes in addition produced considerable quantities of morphine-6-glucuronide (M6G), whereas this metabolite was detected only intracellularly in minor quantities in rat hepatocytes. The ratio between the two morphine glucuronides (M3G/M6G) in suspensions of guinea pig hepatocytes was approximately 4:1. N-Demethylation of morphine was more pronounced per mg cell protein in rat hepatocytes compared to guinea pig cells. Metabolic activity towards morphine was not detected in non-parenchymal cells of the two species. The morphine glucuronidation pattern found in guinea pig hepatocytes resembles to a greater extent than that found in rat hepatocytes the pattern found in in vivo studies of humans. It was concluded that isolated guinea pig parenchymal cells appeared to be a promising in vitro system for studies of morphine glucuronidation, and to observe metabolism in general.

Animals↗
PubMed1992

[Is fenoterol therapy related to increased asthma mortality?].

Retrospective case-control studies suggest a connection between chronic treatment with fenoterol and other beta-2-agonists and increased mortality from asthma. These studies are extremely difficult to assess from a methodological point of view. They raise important questions, however, and force us to critically reevaluate our present therapeutic approach. In the acute situation, beta-2-agonists might be life-saving, and we must therefore be cautious in readily accepting a causal relationship between beta-2-agonist treatment and death from asthma. Probably, retrospective case-control studies are inadequate to establish a clear-cut association between beta-2-agonist therapy and death from asthma. This will require prospective randomized studies including large asthma populations providing accurate information on both chronic and acute drug treatment, and the end-point is death from asthma.

Asthma↗
PubMed1992

Oestriol in the prophylactic treatment of recurrent urinary tract infections in postmenopausal women.

A block randomized, double-blind, group-comparative, placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women. 40 women, median age 78 years (66-91), 20 in each group, were treated with oestriol three mg p.o. per day or corresponding placebo for four weeks, followed by one mg per day for eight weeks. The main response parameter was the number of urinary tract infections per week in the two treatment periods. Both oestriol and placebo reduced the number of infections per week significantly in both periods, compared with the pretreatment period. There was no difference between oestriol and placebo treatment in the first period. In the second period, however, oestriol treatment was significantly more effective than placebo (p = 0.05). Correspondingly, there was a significant difference between the two groups in the vaginal pH at the end of the study (p less than 0.05). We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women.

Aged↗
PubMed1991

Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in children.

The pharmacokinetics of cefetamet were determined after intravenous (i.v.) administration of cefetamet and oral administration of cefetamet pivoxil syrup to patients between the ages of 3 and 12 years. The patients were hospitalized for reconstructive urological surgery; to prevent infection, prophylactic i.v. cefetamet was administered on the day of surgery and oral cefetamet pivoxil was administered 2 days later. After i.v. administration, the mean (+/- standard deviation) half-life of cefetamet was 1.97 +/- 0.60 h (n = 18), which was different from the 2.46 +/- 0.33 h reported for nine adults (22 to 68 years old) in a previous study. The average values for the mean residence times were 2.35 +/- 0.94 and 2.83 +/- 0.34 h and the average values for the fraction of the dose eliminated unchanged in the urine were 79.9% +/- 8.99% and 80% +/- 11% in children and adults, respectively. Plots of mean systemic clearance and steady-state volume of distribution versus body weight for the children and comparative adults were linear on log-log coordinates, and the slopes of the plots were 0.661 and 0.880, respectively. These slope values suggested that mean systemic clearance values per unit of body surface area were similar in children and adults and that maintenance doses for children should be the adult maintenance dose multiplied by the child's surface area divided by 1.73 m2. The mean (+/- standard deviation) oral bioavailabilities of cefetamet pivoxil were 49.3% +/- 15.7% in 3- to 7-year-old children who received a 500-mg dose and 37.9% +/- 10.0% in 8- to 12-year-old children who received a 1,000-mg dose. These values were not different from that observed in the adult group after two 500-mg tablets. Likewise, the peak concentration of cefetamet in plasma and its time of occurrence in children were in line with the values which have been observed for adults.

Administration, Oral↗
PubMed1990

Morphine-6-glucuronide might mediate the prolonged opioid effect of morphine in acute renal failure.

1. A 43-year-old male developed acute kidney failure due to ethylene glycol poisoning. He was treated with bicarbonate to combat metabolic acidosis, ethanol as an antimetabolite and haemodialysis to remove the glycol and its toxic metabolites. He was kept on a respirator and sedated with morphine. Peritoneal dialysis was given for 36 d. Following sedation with morphine for 11 d, the patient was given naloxone and then extubated. The antidote had to be continued for 14 d to prevent respiratory depression, until kidney function improved. 2. Only morphine-6-glucuronide (M-6-G) was found in the plasma and CSF at concentrations which might explain the opioid effects observed in the patient during the days after the cessation of morphine treatment. The ratio of the area under the concentration-time curve (AUC) of morphine-3-glucuronide (M-3-G) to M-6-G was 2:1. The elimination half-lives of M-3-G and M-6-G were 55 and 82 h, respectively. The clearance data indicate that most of the glucuronides were eliminated by peritoneal dialysis during renal failure. 3. The data suggest that M-6-G exerts opioid effects and is retained in acute kidney failure. Morphine should therefore not be used preferentially as a sedative/analgesic in pronounced kidney failure.

Acute Kidney Injury↗
PubMed1987

Oral administration of codeine in the presence of ethanol: a pharmacokinetic study in man.

Three healthy male volunteers were given a codeine (1 mg/kg) solution in the absence and presence of ethanol in a cross-over designed study. The blood ethanol concentration was kept at approximately 16 mM for 8 hrs. Blood samples were taken at several occasions during the first day after the codeine administration. Urine was sampled during three days. There were no significant differences in the area under serum concentration versus time curve in the absence and presence of ethanol with respect to free codeine, total codeine and total morphine. The fraction of codeine glucuronized in serum (approximately 94%), the maximum serum concentration of free (0.34 microM) and total codeine (6.3 microM), the time to reach the maximum serum concentration values (approximately 65 min.) were also similar in the absence and presence of ethanol. The accumulated percentage of the codeine dose given which was found as codeine and morphine and their conjugates in the urine ranged from 50 to 91 percent in the different subjects. The accumulated percentage of the administered codeine dose found as free morphine in the urine, was significantly lower in the ethanol exposed individuals (0.18 +/- 0.03%) compared to the controls (0.39 +/- 0.09%). The percentage of the codeine dose found in the urine in the control situation as free codeine (5.2 +/- 2.2%) was not statistically different from the amount found in the urine after ethanol treatment (4.3 +/- 2.0%). The percentage glucuronized morphine (95.3 +/- 0.4%) and codeine (91.9 +/- 2.2%) in the urine in the absence of ethanol was similar to glucuronized morphine (95.3 +/- 2%) and codeine (93.1 +/- 3%) after ethanol exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Transport and distribution of alpha-tocopherol in lymph, serum and liver cells in rats.

Rats were cannulated in the major mesenteric lymph duct and given an intraduodenal bolus of unlabeled and alpha-[3H]tocopherol, and [14C]oleic acid in soybean oil. The appearance of alpha-tocopherol in lymph was negligible during the first 2 h and peaked 4-15 h after feeding, whereas no detectable amount was recovered in the portal vein. Intestinal absorption via the lymphatic pathway was 15.4 +/- 8.9% (n = 10) and 45.9 +/- 10.8% (n = 4) for alpha-tocopherol and [14C]oleic acid, respectively. About 99% of alpha-tocopherol in lymph was associated with the chylomicron fraction (d less than 1.006 g/ml). In non-fasting rats, 51% of serum alpha-tocopherol was associated with chylomicrons/VLDL (very-low-density lipoprotein, d less than 1.006 g/ml) and 47% with HDL (high-density lipoprotein, 1.05 less than d less than 1.21 g/ml). Our study revealed that the liver, skeletal muscle and adipose tissue contain approx. 92% of the total mass of alpha-tocopherol measured in ten different organs. Parenchymal and nonparenchymal liver cells contributed to 75% and 25% of the total mass of alpha-tocopherol in the liver, respectively.

Animals↗
PubMed1986

The effect of ethanol intake on propoxyphene absorption and biotransformation in dogs.

The effect of ethanol (0.5 and 1.0 g/kg) on gastrointestinal absorption and presystemic biotransformation of propoxyphene (4 mg/kg) was studied in dogs in a crossover design. Low ethanol doses (0.5 g/kg) had no effect on the bioavailability of propoxyphene. High ethanol doses (1.0 g/kg) enhanced the bioavailability of orally administered propoxyphene significantly (p less than 0.05). With this dose of ethanol, the area under the blood concentration versus time curve (AUC)0-5 h of propoxyphene was approximately 200% of the control value. The level of norpropoxyphene, a major metabolite of propoxyphene, was significantly decreased (p less than 0.05) after administration of high ethanol doses. In all blood samples, after propoxyphene administration, an unidentified metabolite of propoxyphene was found, which formation was dose dependently inhibited by ethanol.

Administration, Oral↗