Biomedical subjects
Publications and source records attributed to K Simonsen.
A case of sudden death of a 35-year-old woman due to spontaneous bilateral pneumothorax from rupture of congenital lung cysts is reported. The woman had been attended by two doctors before the lethal outcome. The medicolegal aspects pertaining to medical negligence, the diagnostic difficulties and the rare occurrence of the condition are discussed, as is the autopsy procedure.
Positive pressure during expiration by face masks applied by the patient has gained wide acceptance in the treatment of chronic bronchitis, but the efficacy is still unproven. The effect of 6 months of treatment with PEEP-masks (positive end-expiratory pressure) was therefore studied in 47 patients with severe irreversible obstructive pulmonary disease (forced expiratory volume in one second (FEV1) about 1 l), and mucus hypersecretion. Patients were double-blindly randomized to at least 45 min daily treatment with PEEP-masks with either 10 or 0 cm water pressure. After 6 months of treatment, no statistical difference was found between the two groups in change of median values (month 6 - month 0) of FEV1, forced vital capacity (FVC), arterial oxygen tension (PaO2), amount of sputum or dyspnoea. Median values of arterial carbon dioxide tension (PaCO2) decreased significantly (0.03 kPa) in the placebo group. Cough intensity and dyspnoea during walking on staircases improved significantly in the placebo group. No difference among groups was found in number of days bedridden, hospitalized, number of exacerbations or antibiotic consumption. We conclude, that the use of PEEP-masks in these patients is without clinical documentation and cannot be recommended.
Based on pooled data from three randomized placebo-controlled dose-finding studies in a total of 489 patients, the dose-response relationship for efficacy and adverse events was estimated, using the Michaelis-Menten equation: Effect = maximal effect multiplied by dose/constant plus dose. Three conclusions were derived from the pooled data: (1) A marked increase in efficacy is seen when the reduction in diastolic blood pressure after one week of treatment is compared with that seen after five weeks of treatment, with both placebo and active treatment. Thus, dose increases should preferably be made at intervals of at least four weeks to avoid unnecessarily high doses. (2) Isradipine 2.5 mg twice daily offers an efficacy of approximately 80 percent of the maximum with an incidence of adverse events which, statistically, is not significantly different from the incidence seen in the placebo groups. (3) With continued treatment, a marked decrease in the incidence of adverse drug reactions is seen between the first and fifth weeks, especially with doses at 1.25 and 2.5 mg twice daily. However, with doses above 10 mg per day, this effect is no longer evident.
The influence of rifampicin (450 mg/day for 28 days) on the hepatic microsomal enzymes and thyroid function variables were investigated in 13 healthy male volunteers. After 14 and 28 days of treatment a significant increase in median thyroid volume (determined ultrasonically) was demonstrated (20 ml, range 13-28 before; 26 ml, range 18-48 at day 14, and 24 ml, range 17-40 at day 28) (p less than 0.01). A significant decrease in median serum free T4 index levels was seen (94.1 arbitrary units, range 80.1-123.4 before treatment; 86.8, range 71.7-102.0 at day 14, and 85.3, range 65.5-131.3 at day 28) (p less than 0.01). Serum T4, T3, T3 resin uptake, free T3 index and TSH levels were not significantly altered. Hepatic microsomal enzyme activity assessed by antipyrine clearance was significantly increased (approximately by 85%) at day 14 and 28, whereafter it normalized. The study supports the hypothesis that the increase in thyroid volume after treatment with rifampicin and other hepatic enzyme system inducers (e.g. phenytoin and carbamazepine) is a compensatory mechanism caused by an increased hepatic degradation of thyroid hormones.
In nine healthy volunteers, the clearance and metabolism of acetaminophen 1000 mg i.v. was evaluated with and without two concomitant oral doses of codeine in order to investigate a possible interaction. Plasma acetaminophen was followed for 720 min and urine was collected for 24 h after each dose for determination of metabolites. When codeine was coadministered, the average total clearance of acetaminophen and its clearance by glucuronidation, sulphation and mercapturate formation were 0.58 to 1.12-times the control values. It is concluded that therapeutic doses of codeine do not influence the clearance or metabolism of acetaminophen.
1. In short-circuited toad skin preparations exposed bilaterally to NaCl-Ringer's containing 1 mM SO2(-4), influx of sulfate was larger than efflux showing that the skin is capable of transporting sulfate actively in an inward direction. 2. This active transport was not abolished by substituting apical Na+ for K+. 3. Following voltage activation of the passive Cl- permeability of the mitochondria-rich (m.r.) cells sulfate flux-ratio increased to a value predicted from the Ussing flux-ratio equation for a monovalent anion. 4. In such skins, which were shown to exhibit vanishingly small leakage conductances, the variation of the rate coefficient for sulfate influx (y) was positively correlated with the rate coefficient for Cl- influx (x), y = 0.035 x - 0.0077 cm/sec (r = 0.9935, n = 15). 5. Addition of the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine to the serosal bath of short-circuited preparations resulted in a significant stimulation of the passive Cl- and SO2(-4) permeabilities. 6. It is suggested that SO2(-4) and Cl- ions are transported along the same pathway of the m.r. cells. Depending on the transport mode of the apical Cl- transport system, electro-diffusion, active transport (sulfate:bicarbonate exchange) and self-exchange diffusion take place. Irrespective of the mechanism of transport, sulfate is probably transported as a monovalent anion species.
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The influence of prednisolone on the elimination of antipyrine has been investigated. The one-sample antipyrine clearance was estimated in 23 outpatients with obstructive lung disease before and after treatment with prednisolone 30 or 50 mg/day for 7 days. During prednisolone administration antipyrine clearance decreased from 54.9 +/- 14.8 to 51.7 +/- 14.6 ml/min (mean +/- SD; p less than 0.05). The results indicate that prednisolone decreases the rate of antipyrine elimination, but not to an extent suggesting a clinically important change in hepatic drug metabolism.
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The influence of dose and route of administration on the kinetics of metronidazole and its major metabolites has been investigated in 8 healthy volunteers given 0.5 and 2.0 g i.v. and p.o. Metronidazole elimination kinetics from plasma could be described by an open two-compartment model. The systemic oral bioavailability of both doses was approximately 1. The total systemic clearance of the intravenous 2.0 g dose was 9% lower than that of the 0.5 g dose (p less than 0.05). There were no significant dose-related differences in volume or rate of distribution. The elimination half-life was similar after the four treatments with metronidazole. The major elimination pathways, renal excretion and hepatic oxidation and glucuronidation, accounted for more than 2/3 of the total systemic clearance. Clearance both by hepatic oxidative metabolism and renal excretion was significantly lower after 2.0 than after 0.5 g i.v., whereas there was no significant difference after the oral doses. The results indicate that a high therapeutic dose of metronidazole may be eliminated at a reduced rate, but this is probably not of clinical importance. No single saturable elimination pathway was identified.
After 12 weeks of regular exercise training in 34 patients with moderate essential hypertension, supine systolic blood pressure at rest decrease from 152 +/- 2 (means +/- SEM) to 149 +/- 2 mmHg (p less than 0.05), and diastolic blood pressure from 106 +/- 1 to 102 +/- 1 mmHg (p less than 0.001). At corresponding submaximal exercise levels, diastolic blood pressure also decreased significantly from 110 +/- 2 to 98 +/- 3 mmHg (p less than 0.001), but no significant reduction in systolic blood pressure was observed. Heart rate at the same submaximal work load was significantly reduced (p less than 0.01). This data shows that exercise training might have blood pressure lowering effect in patients with moderate essential hypertension, and might in some patients be an alternative to pharmacological treatment.
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The aim of the present study was to examine the effect of regular exercise training in moderate essential hypertension. Twenty subjects (one woman and 19 men) trained for 45 minutes three times a week for 12 weeks, to 60% of their maximal heart rate. Blood pressure was measured at rest and during a maximal exercise test on bicycle ergometer. All subjects achieved training effect measured as a significant reduction in heart rate at comparable submaximal work level and a significant increase in duration of exercise. Diastolic blood pressure at rest decreased from 107 +/- 7 to 101 +/- 5 mmHg (P < 0.01), and at corresponding submaximal exercise level 116 +/- 11 to 106 +/- 11 mmHg (P < 0.01). No significant reduction in systolic blood pressure was found. Exercise training might in some patients with moderate essential hypertension be an alternative to pharmacological treatment.
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The cardiovascular responses to combined static-dynamic work were measured in three groups of subjects: young men, middle-aged athletes, and coronary patients. The highest work capacity was found in the middle-aged athletes and the lowest in the coronary patients. In all instances the highest values of the rate pressure products were found in the coronary patients and the lowest in the middle-aged athletes. This study indicates that systolic blood pressure response to static-dynamic work increases with age and that lifelong endurance training and being a non-smoker does not seem to alter this.
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