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Biomedical subjects

K M Olsen

Publications and source records attributed to K M Olsen.

At least 19 recordsLinked to original sources
PubMed1992

Nicotine absorption after pulmonary instillation.

Levels of nicotine in plasma were determined by gas chromatography in eight mongrel dogs after instillation of 0.5 mg of nicotine in 100 microL of normal saline at three levels of the tracheobronchial tree: the trachea, a subsegmental bronchus of the right middle lobe, and a subpleural location of the right middle lobe ("distal"). An equivalent dose was given intravenously (iv). Peak of nicotine concentrations in plasma were significantly lower after instillation at the trachea (11.5 +/- 4.4 ng/mL) and the subsegmental bronchus (18.2 +/- 5.0 ng/mL) than after an iv dose (30.3 +/- 10.7 ng/mL); p < 0.05 for each comparison. In addition, the peak concentration after instillation at the trachea was significantly lower than that after instillation at the distal site (22.1 +/- 6.2 ng/mL, p < 0.05). Time to peak concentration was significantly longer after tracheal instillation (5.3 +/- 3.0 min) than after subsegmental instillation (2.0 +/- 0.0 min) or iv infusion (2.0 +/- 0.0 min); p < 0.05 for each comparison. Total drug absorbed, half-life, and clearance were equivalent from all four sites. This study demonstrated that quantitative absorption of nicotine from the described lung sites is equivalent to that after an iv dose, with slower absorption and lower peak concentrations from the tracheal site.

Absorption↗
PubMed1991

Isopropanol ingestion: a report of six episodes with isopropanol and acetone serum concentration time data.

The disposition of isopropanol and its major metabolite acetone were observed in six isopropanol ingestion episodes among five patients. Serum admission isopropanol and peak acetone concentrations ranged from 16.5 to 220 mg/dL and 141 to 585 mg/dL respectively. Ingestions ranged from 120 to 300 mL of 70% isopropanol with concomitant ethanol ingestion in two episodes. The isopropanol and acetone apparent half-lives ranged from 2.9 to 16.2 hours (h) and 7.6 to 26.2 h respectively. Two episodes of isopropanol ingestion were observed within a 9 month period in patient one. Isopropanol terminal elimination rate constants were 0.043 and 0.085 per hour (per h) with no marked difference in acetone terminal elimination rate constants (0.025 and 0.033 per h). Discrepancy between the two isopropanol elimination rate constants reflected concomitant ethanol abuse with the first ingestion. Reductions in isopropanol and acetone half-lives were also noted among patients requiring ventilatory support.

1-Propanol↗
PubMed1991

The use of selegiline in Alzheimer's patients with behavior problems.

BACKGROUND: Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer's disease that does not cause significant patient sedation. Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens. The purpose of this study was to document the efficacy of selegiline in Alzheimer's patients with behavior problems. METHOD: Eight Alzheimer's patients (6 women and 2 men) ranging in age from 50 to 82 years (mean +/- SD = 74.0 +/- 10.5) were enrolled in this single-blind study. Patients received selegiline 10 mg each day for 8 weeks. Prior to drug administration and at the end of Weeks 1, 2, 4, 6, and 8, patients were evaluated for behavior (BEHAVEAD), cognitive function (Mini-Mental State Examination), and caregiver stress (Caregiver Burden Scale). RESULTS: Of eight enrolled patients, five were available for analysis. No statistically significant differences were found between mean baseline and mean 8-week scores for any of the three tests. However, clinical significance was noted by improvement in cognition (orientation and recall), caregiver stress, and behavior. Behavior was noted to improve in the areas of paranoid and delusional ideation, hallucinations, activity disturbances, anxiety, and phobias. CONCLUSION: These data suggest that some Alzheimer's patients with behavior problems may benefit from selegiline therapy.

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PubMed1990

The importance of mast cells for the neutrophil influx in immune complex-induced peritonitis in mice.

The role of mast cells in polymorphonuclear leukocyte (PMN) influx in Ag-antibody complex-induced peritonitis was evaluated in mast cell-deficient WBB6F1-W/Wv (W/Wv) mice and their normal littermates, WBB6F1-+/+ (+/+). Peritoneal cell influx was evaluated after i.p. injection of preformed immune complexes. The first significant elevation in the PMN count over PBS-treated controls in +/+ mice was observed 2 h after stimulation. During the period of maximum leukocyte concentrations (6 to 10 h), the increase in total cell count was 5-fold and in PMN 25-fold. In W/Wv mice the PMN influx started 2 h later than in the +/+ mice, and the maximum response (8 to 10 h) was only 50% of that in controls. Reconstitution of mast cells in W/Wv mice for 2 wk or more restored the PMN response to immune complexes. Mast cell release due to AG-antibody complexes was evaluated by measuring fluorescence intensity after berberine sulfate staining for heparin in mast cells from unstimulated as well as stimulated +/+ mice. There was a significant decrease in fluorescence intensity as early as 15 min after stimulation. By 30 min the fluorescence intensity had declined by 65%. This indicates extensive mast cell release that started before PMN mobilization. These experiments demonstrate that mast cells make a significant contribution to immune complex-induced inflammation.

Animals↗
PubMed1990

Postoperative analgesic requirements following flumazenil administration.

The effect of flumazenil (RO 15-1788) on postoperative analgesic requirements was evaluated in 30 postoperative patients. This prospective investigation was a double-blind, placebo-controlled trial in patients undergoing general anesthesia supplemented by midazolam and fentanyl or sufentanil. Patients received either flumazenil (n = 20) or placebo (n = 10) by random assignment. Analgesic requirements were measured in morphine equivalents (MEs) and were recorded for a three-hour period following the administration of flumazenil. All patients received the assigned treatment within five minutes of arrival to the postanesthesia room. Total ME requirements were 4.1 +/- 3.8 mg for the flumazenil group and 4.5 +/- 4.6 mg (p = 0.71) for the placebo group. Patient analgesic requirements were also assessed when patients were adequately alert. For the flumazenil group this time period was 6.2 +/- 12.7 minutes versus 52.9 +/- 28.4 minutes for placebo (p less than 0.01). MEs (flumazenil 4.1 +/- 3.8 mg vs. placebo 3.7 +/- 3.2 mg) were not significantly different (p = 0.57) when similar levels of consciousness were compared. The onset of pain was more rapid with flumazenil patients as evidenced by the first analgesic dose at 15.7 +/- 25.1 minutes for the flumazenil group versus 34.7 +/- 43.7 for the placebo group; however, these data were not statistically different (p = 0.144). These results suggest that flumazenil does not increase postoperative analgesic requirements during the immediate postanesthesia period; however, patients receiving flumazenil may experience an earlier onset of postoperative pain.

Adult↗
PubMed1990

Effect of glycated albumin on phenytoin binding in elderly patients with type II diabetes mellitus.

We evaluated the effect of glycated albumin on phenytoin protein binding in 36 elderly (age range 63-94 yrs) patients with type II diabetes mellitus (DM) under diet management. Serum was spiked with 15 mg/L phenytoin and incubated. A serum ultrafiltrate was obtained from each sample for determining total and free phenytoin concentrations. Glycated hemoglobin was determined by boronate-affinity chromatography, and glycated albumin was separated from nonglycated fractions with boronate-agarose gel. Glycated hemoglobin in the study group ranged from 4.3-14.6% (mean 7.8 +/- SD 2.1%) and glycated albumin ranged from 3.7-12.5% (7.4 +/- SD 2.6%). We observed no correlation between glycated albumin and the percentage of free phenytoin (r2 = -0.14; p = 0.419). The concentration of nonglycated albumin ranged from 0.66-4.28 g/dl (mean 3.45 +/- 0.67 g/dl) and was calculated from measured total and glycated albumin concentrations. A correlation between the free fraction of phenytoin and nonglycated albumin was not demonstrated (r2 = 0.22, p = 0.22). In addition, a correlation was not observed between total glycated albumin and the free fraction of phenytoin (r2 = -0.095; p = 0.58). We conclude that elderly patients with type II DM under diet control do not have significant alterations in phenytoin protein binding. The use of total serum phenytoin levels therefore appears appropriate for determining phenytoin dosages in elderly patients with well controlled type II DM.

Aged↗
PubMed1989

Comparison of disposition values obtained by two assay methods for quinidine gluconate in patients with ventricular tachycardia.

Eight patients with previously untreated ventricular tachycardia, age 48.54 +/- 28.02 years (mean +/- SD), were enrolled in a protocol evaluating the disposition of quinidine gluconate as determined by two assay methods. Patients received two infusions of 5 mg/kg over 30 minutes separated by 20-30 (24.9 +/- 4.0) minutes of electrophysiologic testing. Blood samples were obtained at 0.17 hours and just prior to the second infusion, and then at 0.17, 0.25, 0.33, 1.0, 6.0, 12.0, and 24.0 hours after the second infusion. Paired serum samples were assayed for quinidine concentrations by fluorescence polarization immunoassay and high-performance liquid chromatography. The two assays compared well, with a linear regression equation of Y = 0.927X + 0.247 with a correlation coefficient of 0.985. With the exception of the beta elimination rate constant and beta distribution volume, t test comparison of disposition values demonstrated no significant difference. Differences in the estimates of the beta elimination rate constant reflected differences in the two methods and indicated that even though both assays were comparable, subtle differences in specificity could be reflected in significant differences in this variable.

Adult↗
PubMed1989

Disposition of 3-hydroxyquinidine in patients receiving initial intravenous quinidine gluconate for electrophysiology testing of ventricular tachycardia.

The formation rate constant and elimination rate constant for 3-hydroxyquinidine were determined in eight patients with ventricular tachycardia. These two parameters (mean +/- SD) were found to be 0.784 +/- 0.202 and 0.042 +/- 0.058 h-1, respectively. Coefficients of determination for the computer-generated line of best fit for serum concentration-time data were 0.986 +/- 0.008. Patients received two infusions of quinidine gluconate 5 mg/kg over 30 minutes separated by a 20-30 minute electrophysiologic testing period. Unbound and total 3-hydroxyquinidine concentrations were also determined. Among the eight patients, 3-hydroxyquinidine was 61.9 percent bound. Studies in healthy volunteers had shown 50 percent binding. Linear regression of unbound and total 3-hydroxyquinidine was described by the equation Y = 0.3814X-1.448, r = 0.813. Although half-lives of 3.5-12.4 hours had been reported in healthy volunteers, prolonged half-lives were observed in all but two of our arrhythmia patients.

Adult↗
PubMed1988

In vitro toxicity of welding fumes and their constituents.

Welding fumes from a wide variety of processes and applications were assayed for toxicity with BHK21 cell line and SHE primary cells in culture. The most toxic fumes are those from the manual metal arc welding of stainless steel (MMA/SS) (LD50 = 7-14 microgram/ml), although all other welding fumes tested are toxic, with potencies lower by a factor of 10-200. The activity of MMA/SS is presumably due to the presence of high concentrations of Cr(VI) in the soluble fraction: For all other fumes the lowered activity (LD50 = 80-800 microgram/ml) is limited mostly to the insoluble fraction, and in part can be related to the presence of MnO2 and Fe3O4 which are toxic at such levels in these cell culture assays. Slight discrepancies between survival tests for the two cell lines, and between survival and lactate dehydrogenate release for BHK, indicate a differential response to certain constituents of these complex materials. These results suggest the need for a battery of different types of assays for use in an eventual ranking of exposures for the purpose of relative risk assessment.

Air Pollutants, Occupational↗
PubMed1988

Vancomycin serum protein binding determination by ultrafiltration.

Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study. Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay. Ultrafiltrates were obtained by centrifugation at 1000 X g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent. The mean protein binding (mean +/- SD) was 41.95 +/- 14.15 percent. No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted. Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y = 0.597x-0.362 with a correlation coefficient of 0.948.

Adult↗
PubMed1988

Stability of amoxicillin trihydrate-potassium clavulanate in original containers and unit dose oral syringes.

The stability of reconstituted amoxicillin trihydrate-potassium clavulanate oral suspension both in original containers and pre-packaged in commercially available oral syringes stored at various temperatures was determined. Amoxicillin trihydrate 125 mg/5 mL-potassium clavulanate 31.25 mg/5 mL and amoxicillin trihydrate 250 mg/5 mL-potassium clavulanate 62.5 mg/5 mL were reconstituted according to the manufacturer's instructions. The reconstituted suspensions in the original containers and in five brands of oral syringes were stored at 5 degrees C and 25 degrees C and -10 degrees C, 5 degrees C, and 25 degrees C, respectively, for 0, 2, 4, 7, and 14 days. The concentrations of amoxicillin trihydrate and potassium clavulanate remaining after storage were assayed in triplicate by reverse-phase high-performance liquid chromatography, using a stability-indicating method. An F statistic was calculated to determine whether different syringe brands had significantly different effects on drug stability. Amoxicillin trihydrate was stable for at least 10 days in the original containers and all types of oral syringes at 5 degrees C. However, potassium clavulanate was stable for 11.1 days in original containers and less than 5 days in all types of oral syringes at 5 degrees C. The effect of syringe brand on the stability of drugs over time at specific storage conditions and temperature was significant for potassium clavulanate at 5 degrees C and for both amoxicillin trihydrate and potassium clavulanate at 25 degrees C. The manufacturer's guidelines for storage of reconstituted amoxicillin trihydrate-potassium clavulanate oral suspension in the original containers should not be applied to dosages repackaged in unit dose oral syringes.

Amoxicillin↗
PubMed1987

Management of tetanus.

Two cases of tetanus are presented, and the diagnosis, clinical features, and management of tetanus are reviewed. The first patient, an 86-year-old woman, had marked muscle rigidity but was able to breathe spontaneously. A dark eschar with purulent drainage was noted on her left foot, but Clostridium tetani was not isolated. She was placed in a semidark room and was treated with penicillin G; tetanus immune globulin (TIG) 5000 units i.m.; tetanus toxoid 0.5 mL i.m.; diazepam, chlorpromazine, and morphine for sedation, muscle relaxation, and analgesia; ranitidine for stress ulcer prophylaxis; heparin for prevention of deep-vein thrombosis; and peripheral-vein nutrition. Her condition improved gradually, and she was discharged to a rehabilitation institute after 32 days. The second patient, a 46-year-old woman, experienced progressive descending paralysis and required ventilatory support. She had a periodontal abscess, but cultures of the drainage were negative. She was placed in a semidark room and treated with erythromycin, TIG, tetanus toxoid, diazepam, pancuronium bromide, morphine, ranitidine, and heparin. Autonomic instability occurred during the second and third weeks, but cardiac output was maintained without treatment. The patient was extubated after five weeks, and was transferred out of the intensive-care in the following week. The diagnosis of tetanus is based primarily on characteristic findings of muscle rigidity and reflex spasms; cultures for C. tetani are of limited value. A history of trauma or injury is common. Pulmonary infections and cardiovascular instability are the most common complications. Therapy consists of ventilatory support; control of neuromuscular symptoms with benzodiazepines, narcotics, and neuromuscular blockers; antibiotic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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