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Biomedical subjects

J E Bredesen

Publications and source records attributed to J E Bredesen.

At least 19 recordsLinked to original sources
PubMed1998

[Digitalis poisoning treated with a specific antidote].

Toxicity by digitalis is a common problem in everyday clinical practice. In this paper three cases of severe poisoning with digitoxin with maximal S-digitoxin levels of 115, 150 and 239 nmol/l are described. All patients received specific digoxin Fab-fragment intravenously. Administration of antidotes resulted in a favourable outcome in all three patients. So far, the use of digoxin-specific antibodies has been limited to a few cases of severe intoxication where life-threatening arrhythmias and hyperkalaemia were present. We discuss whether a more liberal indication should be accepted.

Anti-Arrhythmia Agents↗
PubMed1998

Ethanol treatment in ethylene glycol poisoned patients.

Two otherwise healthy 16-y-old female patients were treated with sodium bicarbonate and ethanol after the ingestion of unknown quantities of ethylene glycol. Patient 2 was admitted twice for ethylene glycol poisoning in unrelated events. In patient 1, the maximum levels of ethylene glycol and glycolate in plasma were 14 mmol/L (0.9 g/L) and 8.2 mmol/L (0.5 g/L), respectively. In patient 2, the maximum levels of ethylene glycol in plasma during the 2 admissions were 18 mmol/L (1.1 g/L) and 45 mmol (2.8 g/L), respectively. In patient 1, a blood ethanol concentration between 130-140 mg/dL (28-30 mmol/L) was reached 3 h after the start of ethanol administration and maintained for 22 h. During this period, ethylene glycol metabolism was effectively inhibited as indicated by S-glycolate levels and that 88% of the eliminated ethylene glycol was accounted for in the urine. This suggests that ethanol therapy alone may be sufficient for patients admitted early with low serum ethylene glycol concentrations. During the admissions of patient 2, the blood ethanol concentrations were presumed to effectively inhibit ethylene glycol metabolism as judged from normal acid/base parameters. However, during the second admission the bolus infusion of ethanol was associated with respiratory arrest. During both admissions for patient 2, hemodialysis constituted the major route of ethylene glycol elimination.

Adolescent↗
PubMed1997

Transdermal nitroglycerin: clinical and pharmacokinetic consequences of renewing the patch and the application site.

OBJECTIVE: We examined whether nitroglycerin (glyceryl trinitrate, GTN) patch treatment for 24 h could induce local cutaneous changes that impaired drug delivery and clinical efficacy. METHODS: Twenty angina patients were exercise-tested after 2 and 24 h of treatment and then 2 h after patch renewal. The patch was either renewed on a new skin location or on the previous application site in a randomised, double-blind, cross-over protocol. GTN plasma concentrations and finger plethysmography were obtained before and after each exercise test. RESULTS AND CONCLUSIONS: The clinical efficacy, the effect seen on plethysmography and the GTN plasma concentrations tended to increase after patch renewal, regardless of the application site of the renewed patch. Hence, cutaneous changes of clinical importance could not be demonstrated.

Administration, Cutaneous↗
PubMed1996

[Theophylline poisoning--clinical course and treatment].

After about half a century of treatment of asthma and chronic obstructive pulmonary disease, theophylline still occupies a central position in the treatment of these conditions. Severe poisonings are rare and may occur as a result of chronic over-medication or acute self-poisoning. The clinical course depends not only on the amount taken and the peak serum concentration, but also on whether the intoxication is acute or chronic. The therapeutic range is narrow (55-110 mumol/l). Total body clearance of theophylline varies considerably between individuals, and drug interactions are common. These circumstances lead to relatively high risk of poisoning. Clinical features vary from moderate gastrointestinal discomfort, particularly nausea, tremor and tachycardia, to life-threatening conditions affecting the cardiovascular and central nervous systems. Treatment is discussed in connection with a presentation of three case histories.

Adult↗
PubMed1994

Osmolal and anion gaps in patients admitted to an emergency medical department.

1. Osmolal and anion gaps are helpful in the diagnosis and evaluation of intoxications with methanol and ethylene glycol. Reported reference values for osmolal gap and anion gap are -1 (+/- 6) mosm kg-1 H2O and 16 (+/- 2) mmol l-1, respectively. However, we have repeatedly found unexplained increased gaps in patients admitted to our department, and the relevance of the established reference values has been questioned. 2. Osmolal and anion gaps were determined in an unselected population of patients consecutively admitted to an emergency medical department. In the case of unexplained gaps, the blood samples were analysed with respect to the presence of alcohols and organic acids. 3. We included all accessible patients admitted during 14 days. Appropriate blood samples were obtained in 177 patients (88 male, 89 female), with a mean age of 65 years (range 17-94). 4. The mean and (standard deviation) for osmolal and anion gaps in our material were 5.2 mosm kg-1 H2O (7.0) and 12.9 mmol/l (4.2). Neither methanol nor ethylene-glycol was detected in serum from any patients. Small amounts of ethanol were found in 5 patients, and high lactate levels explained in part the most extensively increased anion gaps. However, the calculated analytical standard deviation accounted entirely for the variation in our material, and we suggest that the present reference values be adjusted.

Acid-Base Equilibrium↗
PubMed1992

Heating and cooling of the nitroglycerin patch application area modify the plasma level of nitroglycerin.

19 healthy volunteers wore a nitroglycerin patch releasing 10 mg per 24 h for 2 h. Subsequently, the skin area surrounding the patch was exposed to 15 min of local heating with an infrared bulb (Group A, n = 10), or local cooling with an ice-pack (Group B, n = 9). The patch was protected by an insulating shield (Styrofoam). After 10 min of heating, the median (Walsh) plasma nitroglycerin level increased from 3.1 to 7.6 nmol.l-1. Body temperature remained constant. After 15 min of cooling the median plasma level had dropped from 2.1 to 1.4 nmol.l-1. The results demonstrate that changes in skin temperature may cause extensive short-term changes in the bioavailability of nitroglycerin. Presumably, a subcutaneous or cutaneous reservoir builds up during transdermal treatment, and changes in regional cutaneous blood flow affect the rate of drainage from the reservoir into the systemic circulation.

Administration, Cutaneous↗
PubMed1991

Transdermal nitrate therapy: bioavailability during exercise increases transiently after the daily change of patch.

Ten volunteers carried a 10 mg 24 h -1 transdermal glyceryl trinitrate (GTN) patch for 24 h before moderate exercise. Plasma GTN-concentration increased significantly (P less than 0.05) by 19% to peak value at 15 min. Two hours after patch renewal repeat exercise increased GTN concentration by 56% (P less than 0.001). The two nitrate-concentration curves differed significantly (P less than 0.0001). Thus, change of patch augmented nitrate availability during exercise.

Administration, Cutaneous↗
PubMed1990

Midazolam and nitrazepam in the maternity ward: milk concentrations and clinical effects.

1. In a randomized study of 22 patients in a maternity ward, the residual concentrations of two hypnotics, midazolam 15 mg p.o. and nitrazepam 5 mg p.o., in early breast milk and plasma were measured 7 h after intake on day 2 to day 6 postpartum. Milk pH, milk fat and binding to plasma proteins were also investigated. Sleep variables were scored on questionnaires. 2. No measurable (less than 10 nmol l-1) concentrations of drug in milk were found in the group receiving 15 mg midazolam at night, either after the first night or after the fifth night. Additional investigations in two mothers demonstrated that midazolam and its hydroxymetabolite disappeared rapidly from milk with undetectable levels after 4 h. The mean (s.d.) milk to plasma ratio for midazolam was 0.15 (0.06) in six paired samples. It may be assumed that practically no midazolam is transferred via early milk to the baby if the baby is nursed more than 4 h after tablet intake. 3. Milk nitrazepam concentrations increased significantly from the first (30 nmol l-1) to the fifth morning (48 nmol l-1) in the group receiving 5 mg nitrazepam at night. The mean (s.d.) milk to plasma ratio of nitrazepam after 7 h was 0.27 (0.06) in 32 paired samples, and did not vary from day 1 to day 5. Plasma protein binding of nitrazepam in puerperal women was found to be lower than that in plasma of healthy controls. The average amount of nitrazepam received by the breast-fed baby in the morning was calculated to increase from 1 to 1.5 micrograms 100 ml-1 breast milk, from days 1 to 5. In the mothers nitrazepam was associated with better hypnotic effect, but a higher incidence of complaints than midazolam. 4. Milk pH, assuming anaerobic conditions, was found in 10 women to average 6.91 +/- 0.09 (s.d.) on days 2-6 postpartum, which is less than previously reported. 5. It is concluded that both hypnotics may be used safely for a few days in the maternity ward. However, possible long-term effects in the suckling infant of small doses of benzodiazepines ingested with breast milk remain to be investigated.

Adult↗
PubMed1990

Pharmacokinetic studies of antibacterial agents using the suction blister method.

The suction blister technique was used for pharmacokinetic studies with sulfonamides and trimethoprim. Blisters produced by suction (-0.3 kg/cm2) for 1.5 h contained approximately 0.15 ml fluid with a protein content of 40-50% of that in plasma, the main protein fractions being present in the same ratio as in plasma. 2 g sulfaisodimidine was given as bolus injection, i.v. infusion or orally to groups of 4 volunteers. The peak blister fluid concentrations after oral administration (120 +/- 18 mmol/l) was only marginally lower than the concentrations after i.v. infusion (122 +/- 28 mmol/l) and i.v. bolus injections (134 +/- 37 mmol/l). The total drug blister fluid concentration started to decrease before the plasma level was reached. However the relative concentration increased from 53% of that in plasma at 8 h to 66% at 12 h after drug administration. Considering the protein binding of the drugs, the interstitial fluid levels of free drug were presumably higher than the plasma level after 8 h. Comparison of drug concentrations in blisters produced before and after the drugs were given showed higher concentrations in the latter for the first 2-6 h. However, after 8-12 h the concentrations of the drugs in the two types of blisters were similar. The suction blister method produces blisters of uniform size. The drug concentrations in different experiments showed the coefficient of variation for blister fluid concentrations to be no greater than for plasma levels. The consistent results of the standardized suction blister method makes this method useful for studying drug penetration to extravascular compartments in humans.

Adult↗
PubMed1989

Effects of flunitrazepam and triazolam in man: are they influenced by the time of ingestion?

Five healthy young volunteers were given flunitrazepam 1 mg, triazolam 0.25 mg or placebo at 2 a.m. or 9 a.m. in a double blind, cross-over study. The aim was to investigate the cyclic variations mainly in residual effects of the drugs, but also in sleep onset latency and pharmacokinetics. The study suggested cyclic variations in mood, psychometric tests and in sleep onset latency.

Adult↗
PubMed1988

Benzodiazepine-receptor antagonist, a clinical double blind study.

In a double blind study including 18 patients in whom a benzodiazepine intoxication was suspected, the first specific benzodiazepine antagonist was compared to placebo. There was a highly significant effect on consciousness, all patients given antagonist awaked, usually within minutes. No adverse effects were observed. In 2 patients the clinical condition deteriorated 1 to 2 hrs after the antagonist was given. This might endanger intoxicated patients withdrawing from medical attention.

Adult↗
PubMed1988

Haemodialysis or haemoperfusion in severe salicylate poisoning?

Two cases of severe salicylate poisoning with maximal plasma levels of 6.9 and 8.9 mmol/l are described. In addition to supportive treatment and forced alkaline diuresis, one case was treated with haemoperfusion and the other with haemodialysis. The use of the same blood pump and blood flow allowed us to compare directly the effect of these methods in removing salicylate. There was a non-significant higher dialysance (mean 86 ml/min, s.d. +/- 8) than haemoperfusion clearance (mean 81 ml/min s.d. +/- 17) at a blood flow of 200 ml/min. As haemodialysis offers the theoretical advantage of correcting acid-base and electrolyte disturbances, does not trap platelets and has a lower heparin requirement, the present comparison indicates that haemodialysis is preferable when extracorporal elimination is indicated in salicylate poisoning.

Acid-Base Equilibrium↗
PubMed1987

Meprobamate kinetics during and after terminated hemoperfusion in acute intoxications.

We report four cases of severe meprobamate intoxication. Maximal plasma levels reached 800 (176), 816 (180), 863 (190) and 923 mumol/l (203 mg/l). All patients survived without sequelae including one patient resuscitated from cardiac arrest. The clinical course was complicated by coma, hypotension, and hypothermia in all patients. Three cases were treated with charcoal hemoperfusion with mean hemoperfusion clearance ranging from 134-164 ml/min compared to 174 ml/min in one case treated with resin filter and the same blood flow of 200 ml/min. In two cases, a mean renal meprobamate clearance of 15 and 23 ml/min was calculated comprising only 9-15% of the hemoperfusion clearance. The amount of meprobamate removed by hemoperfusion ranged from 1.6-6.2 g. In one case, the half-life of plasma meprobamate during hemoperfusion was 2.6 hours compared to 8.3 hours after hemoperfusion. Thus the half-life was reduced more than 3-fold. These data show that hemoperfusion may be indicated in severe meprobamate intoxication.

Adult↗
PubMed1986

Residual effect of single and repeated doses of midazolam and nitrazepam in relation to their plasma concentrations.

Twelve healthy volunteers were given either midazolam 15 mg or nitrazepam 5 mg for 7 consecutive days in a randomized cross-over trial. Self-assessment of sleep, mood or condition on awakening and adverse effects was performed, and the volunteers underwent evaluation of psychomotor performance. Hypnotic effect, judged by the classical sleep variables, showed that the drugs were more or less equal and were superior to placebo. Nitrazepam consistently produced an impaired condition on awakening and also clearly displayed a spectrum of adverse motor effects. Motor tests revealed impairment induced by both drugs, but, in the midazolam group the effect subsided during the trial period. Both drugs had a significant effect on memory, midazolam appearing to perturb certain memory functions to a greater extent than did nitrazepam. The residual plasma concentration of midazolam 11 h after treatment correlated well with the scores obtained in several of the psychomotor tests, whereas plasma nitrazepam levels were not related to performance in any subtest. When discontinued neither drugs, induced any rebound phenomenon. However, the adverse effects of nitrazepam appeared to be carried over into the adjacent placebo period.

Adult↗
PubMed1986

Increased uptake of transdermal glyceryl trinitrate during physical exercise and during high ambient temperature.

In a study of GTN absorption during exercise and high ambient temperature, 12 healthy volunteers carried 10 mg glyceryl trinitrate (GTN, nitroglycerin) transdermal patches for 6 hours during each of 3 days. During a control day the mean plasma GTN concentration ranged from 1.0 nmol/L (SD +/- 0.8 nmol/L) to 1.5 nmol/L (SD +/- 1.0 nmol/L), whereas during a bicycle ergometer day mean GTN concentration was increased to 3.1 nmol/L (SD +/- 1.7 nmol/L, p less than 0.001). During a sauna day volunteers stayed for 20 minutes in a sauna, and mean GTN concentration in plasma rose to 7.3 nmol/L (SD +/- 1.7 nmol/L, p less than 0.001). Systolic blood pressure increased during exercise (p less than 0.01) but decreased significantly in the sauna (p less than 0.01). Headache was noted frequently (9 of 12 subjects) and dizziness by a few (3 of 12). The demonstrated increased transdermal absorption in our study may infer an increased effect during workload. Whereas the increase in transdermally absorbed GTN may be beneficial to the exercising angina patient, increased effects of GTN may be undesirable in hot surroundings. A study on angina patients is justified to assess whether this phenomenon bears clinical relevance.

Administration, Topical↗
PubMed1986

Relationship between alpha 1-acid glycoprotein and distribution of disopyramide and mono-N-dealkyldisopyramide in whole blood.

The binding of disopyramide (DP) and mono-N-dealkyldisopyramide (MND) was measured by equilibrium dialysis in spiked whole blood (10 mumol l-1 DP or MND) from 50 patients having a serum concentration of alpha 1-acid glycoprotein (AAG) ranging from 0.40 to 3.14 g l-1, as well as in whole blood from five healthy subjects, spiked with different concentrations of AAG ranging from 0.61 to 3.33 g l-1. The binding ratio (moles bound divided by moles unbound) in all samples increased from 1.0 to 8.0 for DP and 0.6 to 3.3 for MND with increasing AAG concentrations. The binding varied according to the AAG concentrations both in patients and healthy subjects. Similarly total and free plasma concentrations of DP and MND were also measured. With increasing AAG concentrations the total concentrations measured increased from 9.0 to 15.9 mumol l-1 for DP and from 6.8 to 11.8 mumol l-1 for MND whereas the free concentrations decreased from 3.8 to 0.5 mumol l-1 for DP and from 5.0 to 2.0 mumol l-1 for MND. With increasing AAG concentrations the whole blood/plasma concentration ratio decreased from 1.11 and 1.47 to 0.63 and 0.85 for DP and MND respectively. The ratio between their concentration in cells and the unbound concentration in plasma, however, was constant over the whole AAG concentration range. The mean ratios for all samples were 3.0 and 3.1 for DP and MND respectively, indicating that both compounds are bound or distributed to the blood cells. The distribution of the drugs in whole blood changed according to increasing AAG concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗