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Biomedical subjects

B Lindström

Publications and source records attributed to B Lindström.

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

A model for prediction of endometrial cancer.

An epidemiological statistical model was designed to identify women at low and high risk of developing endometrial cancer (EC). The model was based on a number of easily identified clinical factors such as hirsutism, parity, diabetes mellitus, body mass index (BMI) and smoking. A retrospectively collected series of 77 women aged 31 to 45 years with EC and a prospectively collected series of 122 women aged 43 to 70 years with EC were compared with 1409 controls. The participation frequencies in the two case materials were 83 and 87%, respectively. The series were examined by means of a questionnaire. In a stepwise multiple logistic regression analysis of the entire series the following variables were found to be significant; hirsutism, parity, BMI, diabetes mellitus and smoking.

Adult↗
PubMed1989

Pharmacokinetic interactions of penicillamine in rheumatoid arthritis.

The pharmacokinetic effect of the combined treatment of penicillamine with indomethacin and chloroquine was investigated in patients with rheumatoid arthritis. The mean plasma penicillamine concentration increased by 26% during indomethacin and 34% during chloroquine treatment. This new pharmacokinetic interaction may have important clinical implications.

Adult↗
PubMed1989

Oral terbutaline alone and in combination with theophylline: dose, plasma concentration, and effect in long-term treatment of bronchial asthma.

Oral terbutaline, in gradually increasing doses from 2.5 to 10 mg three times daily (t.i.d.) was administered to 12 patients with chronic bronchial asthma. There was a linear relationship between dose and steady-state plasma concentrations in individual patients, but the plasma levels varied fourfold between patients taking similar doses. The need for other medication tended to decrease, and the symptom score, peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV1) improved significantly during the treatment, with a roughly linear dose-effect relationship for the doses 2.5, 5 and 7.5 mg t.i.d. An increase in the dose from 7.5 to 10 mg did not improve PEFR and FEV1 any further. Side-effects were generally few and mild. Oral theophylline 200 mg t.i.d. added to terbutaline 10 mg t.i.d. brought about a further improvement in pulmonary function without adding any troublesome side-effects. Our data indicate that there is little to gain by prescribing terbutaline doses higher than 7.5 mg t.i.d. Instead, theophylline might be added, since this combination seems to have a favourable therapeutic index.

Administration, Oral↗
PubMed1988

Dry mass and water content in the corneal epithelium and superficial stroma during healing of corneal alkali wounds.

The dry mass contents of the rabbit corneal epithelium and of the superficial stroma were determined during healing of a standardized corneal alkali wound. Quantitative microradiography was applied to freeze-sectioned corneal specimens. This method allows a morphological resolution of the order of 1 micron and quantitative dry mass determinations in volumes down to about 100 microns 3. For comparison, the epithelial morphology was studied using Toluidine Blue stained sections. Flat epithelial cells covered the wound surface during the first day, the dry mass content being equivalent to that of the normal wing cells. The dry mass content in the epithelium and, indirectly, the water content, followed the hydration state of the superficial stroma. A progressive thickening of the epithelium and a varying morphological picture were found during the first 2 months following initial damage. Normal thickness and cytoarchitecture were found after 6 months. Generally, the dry mass content of the epithelium was reduced compared with physiological values for 2 months. Later, the cells close to the stroma regained normal values. Cells in the middle zone and the superficial zone reached normal values after 6 months. The significance of the endothelial damage for the hydration state of the epithelium was discussed.

Animals↗
PubMed1988

Human liver morphine UDP-glucuronyl transferase enantioselectivity and inhibition by opioid congeners and oxazepam.

1. Morphine uridine diphosphate glucuronyl transferase (UDP-GT) was studied in human liver microsomes. The (-)- and (+)-morphine enantiomers were used as substrates and inhibitors, such as oxazepam and various opioid congeners were employed to characterize the different glucuronidation pathways. The kinetics of the oxazepam inhibition were studied in the rat liver. 2. The overall glucuronidation of (+)-morphine was higher than that of (-)-morphine. The morphine congeners tested, potently inhibited the formation of (-)-morphine-3-glucuronide ((-)-M3G), except for normorphine and codeine. The formation of (+)-morphine-6-glucuronide [+)-M6G) was potently inhibited by only dextromethorphan and (+)-naloxone. All drugs except normorphine inhibited the formation of (+)-M3G by 18-50%. 3. The metabolism of (-)-morphine to (-)-M3G was more sensitive to oxazepam inhibition than the formation of (+)-M3G from (+)-morphine in the rat liver. 4. The glucuronidation of natural morphine is subject to in vitro interaction with oxazepam and several opiate drugs. Our study supports the theory of more than one type of UDP-GT being involved in morphine glucuronidation.

Animals↗
PubMed1988

Oral praziquantel kinetics in normal and Schistosoma haematobium-infected subjects.

The kinetics of praziquantel was studied in normal and Schistosoma haematobium-infected Ghanaian subjects. There was a wide interindividual variation in half-life (t1/2), Cmax, Tmax, area under the curve (AUC) (0-8 h), and urinary recovery. No differences were noted between the two groups with regard to Tmax, AUC (0-8 h), and t1/2. Mean Cmax was higher in the patients than in the control subjects. The 8-hr urinary recovery of praziquantel was higher in the subjects with urinary schistosomiasis. The amount of praziquantel excreted unchanged in urine was 0.0052 +/- 0.0027% (SD) of the dose for the control subjects and 0.0054 +/- 0.0027% (SD) for the patients.

Administration, Oral↗
PubMed1987

Fibrinopeptide A and fibrinogen fragment B beta 15-42 and their relation to the operative trauma and post-operative thromboembolism in neurosurgical patients.

In an earlier study on post-operative thromboembolism in neurosurgery the incidence of deep vein thromboses (DVT) diagnosed by the fibrinogen uptake test and phlebography was reduced to the same extent by two different prophylactic methods (low dose heparin or calf muscle stimulation + dextran). However, patients with lower limb paresis due to a brain lesion experienced relatively often a less successful prophylaxis compared to patients with spinal lesions. There are few reports on successful clinical methods for haematological screening of post-operative DVT. The aim of this study was to examine possible haematological indicators for post-operative thromboembolism and secondarily to elucidate whether there exist some special coagulatory or fibrinolytic characteristics in patients who had been operated upon for brain lesions. We have studied two specific coagulatory factors (FPA reflecting thrombin generation and B beta 15-42 reflecting plasmin activity) in connection with neurosurgical operations. Patients in the above-mentioned study on post-operative DVT operated upon for malignant cerebral tumours or intracranial vascular disease exhibited post-operatively higher values for FPA compared to other neurosurgical diagnoses. B beta 15-42 was higher in the malignant tumour group and almost significantly higher in the intracranial vascular group (p less than 0.065). These differences could not be ascribed to the occurrence of DVT. Another 15 patients divided into a minor and a major lesion group were investigated with determination of both parameters pre- and post-operatively. Concerning FPA an increase was noticed post-operatively compared to pre-operatively in the major lesion group.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Diseases↗
PubMed1987

Chloroquine excretion following malaria prophylaxis.

Urinary excretion of chloroquine and its desethyl-metabolite was monitored for up to 395 days after the last dose of oral chloroquine (300 mg base) taken once weekly for 10 weeks as malaria prophylaxis. Concentrations in plasma could be followed for up to 70 days after the last dose. A three exponential decay was applied to the urinary excretion data. The half-life of the terminal phase varied from 45 to 55 days for chloroquine and from 59 to 67 days for the metabolite. Mean residence time was approximately 20 days for the parent compound and 35 days for the metabolite, indicating that the terminal phases are of less importance for the effective half-lives.

Adult↗
PubMed1987

The behaviour of corneal epithelium following a standardized alkali wound.

The short and long-term healing of the rabbit corneal epithelium was studied after a standardized alkali wound. The wound was inflicted by applying a round filter paper, 5.5 mm in diameter, soaked in 1 N NaOH, for 60 seconds on the central cornea. The wound size and intensity was chosen not to cause melting and perforation, and not to cause vascular ingrowth. n-Heptanol corneal wounds of the same size were used as control. The eyes were followed for 8 weeks. Two phases of epithelial healing were discerned. The initial healing phase lasted 48 h during which the would was completely resurfaced. In spite of the more extensive tissue damage caused by alkali, the initial epithelial healing rate was faster than in n-heptanol wounds. The late healing phase consisted of recurrent epithelial break down, sometimes seen preceded by epithelial blister formation. Four weeks after trauma the state of epithelial healing was at its worst.

Alcohols↗
PubMed1987

Some effects of metolazone on electrolyte transport.

Metolazone action was studied 1) in vitro on isolated operculum of Fundulus heteroclitus (active chloride transport) using an Ussing chamber (metolazone conc 500 microM) and in vivo 2) using the modified Sperber technique in the hen (metolazone infusion rate 0.75-1.2 micrograms/kg/min) and 3) in healthy volunteers using clearance techniques (metolazone infusion rate 10 mg/h). Metolazone reduced (p less than 0.05) short circuit current potential differences with 20% from average control values (p less than 0.05), while direct current resistance was unchanged. This is comparable to thiazide but much lower than loop diuretic effects. True tubular excretion fraction of metolazone before and after novobiocin (2.7 mumol/kg/min coinfusion averaged 14.1 and 4.5%, resp. (p less than 0.01; n = 8). Thus metolazone is partly eliminated by renal tubular secretion. However, the diuretic effect (sodium, chloride and potassium excretion)--and clearances of Cr51-EDTA and I125-Na-o-iodohippurate--were symmetrical, i.e. independent of metolazone urinary excretion rate, as previously shown for thiazides. Renal clearance of metolazone in healthy volunteers. (HPLC-method) averaged 173 +/- 20 ml/min (n = 8). Probenecid (1 g iv.) significantly reduced the renal clearance of metolazone to 33 +/- 7 ml/min and potassium excretion with maximum 30%, while diuretic and saluretic effects were significantly increased with maximum 30%. Thus, also in humans the diuretic effect of metolazone is not coupled to the urinary excretion rate of the drug, but suggests that its diuretic effect is elicited primarily from the peritubular side of the nephron. Probenecid apparently dissociates sodium from potassium excretion effects of metolazone. This implies a luminal, sodium-independent kaliuretic effect of the drug.

Adult↗
PubMed1987

Bioavailability of prednisolone in asthmatic patients with a poor response to steroid treatment.

The absolute bioavailability of prednisolone was assessed in ten asthmatic patients who responded poorly to ordinary doses of corticosteroids so-called "steroid-resistant" bronchial asthma. Plasma levels of prednisolone were measured by a high pressure liquid chromatographic method after oral (20 mg) and intravenous (18.6 mg) single-dose administration. Determination of the number of eosinophils in the blood was used as an estimate of the effect of the drug. The total plasma clearance, plasma half-life and volume of distribution determined from intravenous data were similar to those reported earlier for healthy volunteers and asthmatic patients. Orally administered prednisolone was rapidly absorbed and found to have complete bioavailability. There was a similar decrease in the number of eosinophils in the blood both after oral and after intravenous administration. Thus, the present study does not support the hypothesis that resistance of asthmatic symptoms to oral corticosteroids is due in some cases to poor absorption or rapid elimination of these drugs.

Administration, Oral↗
PubMed1987

Post-mortem concentrations of salbutamol, terbutaline and theophylline in asthma patients.

The concentrations of theophylline, terbutaline and salbutamol in post-mortem blood samples from 68 patients (17-85 years old) with asthma or chronic obstructive lung disease, 54 of whom had died of asthma, were analysed. Information on recent prescriptions was obtained for 61 patients. There was agreement between prescription and drug analysis in the blood in 87% of the patients with regard to theophylline and in 92% for salbutamol and terbutaline combined. Theophylline levels were generally low; 30 patients had concentrations below 25 mumol/l and only three above 110 mumol/l (therapeutic interval 55-110 mumol/l). Both salbutamol and terbutaline were detected in most samples. Fourteen patients had blood concentrations above 200 nmol/l. No definite explanation for these high values could be found. The majority of patients who died from asthma had low drug levels and had not been prescribed corticosteroids.

Acute Disease↗
PubMed1986

Pharmacokinetics of terbutaline during pregnancy.

Terbutaline in plasma was determined in three groups of women by gas chromatography-mass spectrometry. Eight women received a single i.v. dose of 0.25 mg terbutaline sulphate during pregnancy and 3-6 months after delivery. Mean plasma clearance was 29% higher during pregnancy than after delivery. There was a subsequent decrease in mean terminal half-life from 5.3 to 3.7 h and in mean residence time from 5.3 to 3.4 h. There was no change in volume of distribution. A second group of pregnant women in premature labour (n = 8) received oral terbutaline 5 mg t.d.s. The dosing was repeated after delivery. The mean steady state plasma concentration of terbutaline was about 30% lower during pregnancy than after delivery. A third group of women in preterm labour (n = 8) was treated with an i.v. infusion of terbutaline. The concentrations of terbutaline found on cessation of uterine contractions ranged between 12.8 and 31.5 ng/ml. At present there is no basis for formulation of a "therapeutic plasma level" of terbutaline for the treatment of preterm labour.

Administration, Oral↗
PubMed1986

Post-operative thromboembolism in neurosurgery. A study on the prophylactic effect of calf muscle stimulation plus dextran compared to low-dose heparin.

This study compares the safety and effectiveness of two methods for the prophylaxis of post-operative thromboembolism in neurosurgical patients: A: low-dose heparin (5,000 IU X 2 s.c.) started preoperatively and continued daily for one week post-operatively, and B: per-operative electrical calf muscle stimulation with groups of impulses plus post-operative dextran infusions every other day for one week. Neurosurgical patients aged 40 years or more with normal laboratory coagulation values and operated under general anaesthesia were included. The 125:I-fibrinogen uptake test (FUT) was used for screening and phlebography for verification of deep venous thrombosis (DVT). 122 patients entered the study and 104 completed the prophylactic protocol, 58 in group A and 46 in group B. The two groups were comparable according to pre-operative data and distribution of diagnoses. 89 patients completed screening for post-operative DVT. We found an overall incidence of 5/49 (10 percent) DVT in group A and 5/40 (13 percent) in group B, compared to a frequency of 32-50 percent for controls without prophylaxis reported in the literature, In spite of prophylaxis our patients with intracranial neoplasms and intracranial vascular disease showed a relatively higher incidence of DVT, 4/23 (17 percent) and 4/14 (29 percent) respectively, compared to patients with spinal diagnoses 2/25 (8 percent). In combination with cranial diagnoses paretic lower limbs meant an apparent risk factor, 4/7 (57 percent). However, paretic limbs appearing in cases with spinal disorders did not predetermine an unsuccessful prophylaxis, 2/14 (14 percent). Blood loss, transfusion requirements and post-operative complications did not differ significantly between the two prophylactic groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Central Nervous System Diseases↗
PubMed1986

Serum azathioprine and 6-mercaptopurine levels and immunosuppressive activity after azathioprine in uremic patients.

The pharmacokinetics of azathioprine (AZA) and 6-mercaptopurine (6-MP) was studied in uremic patients after 100 mg AZA intravenously (fifteen patients) and orally (eight patients). 6-MP was analysed with gas chromatography mass spectrometry following extractive alkylation. AZA was determined indirectly assuming quantitative conversion to 6-MP in whole blood. The plasma concentration of AZA fell rapidly after i.v. administration. The mean half-time of elimination for the first rapid phase (t1/2 alpha) was 6.1 min (S.D. +/- 4.1) and for the terminal phase (t1/2 beta) 50 min (+/- 31). The total plasma clearance (Cl) was 6.9 1./min (+/- 3.0). AZA was rapidly converted to 6-MP in vivo, and maximal plasma concentrations of 6-MP were found as early as 5 min after i.v. injection of AZA. The mean t1/2 alpha was 4.6 min (+/- 2.2), t1/2 beta 74 min (+/- 58) and Cl 8.0 1./min (+/- 5.8). The plasma levels of both AZA and 6-MP were either low or undetectable 4-6 h after dose. In erythrocytes AZA levels were low or undetectable indicating rapid conversion to 6-MP in these cells. 6-MP concentration - time curve in erythrocytes was similar to that in plasma, except for a somewhat slower terminal phase of elimination. Oral administration of AZA generated flat plasma curves for AZA and 6-MP. The area under the concentration - time curve (AUC) was considerably smaller than after i.v. administration, 18 and 41% for AZA and 6-MP, respectively. There seems to be little danger of accumulation of AZA/6-MP in uremia. We also studied inhibition of Leucoagglutin (LA) stimulated lymphocyte proliferation by patient plasma at different times in six of the patients following AZA i.v. Sera drawn at 5, 10 and 30 min significantly inhibited the LA-induced proliferation, with an estimated minimum effective concentration of 6-MP in the cultures of about 0.02-0.04 microM. This suggests the possibility of a therapeutic effect even of the low plasma levels of 6-MP obtained after AZA orally. The combined use of sensitive pharmacokinetic and immunological assays as described should be useful in studying the relationship between plasma levels of AZA/6-MP and their immunosuppressive effect and toxicity.

Administration, Oral↗
PubMed1986

Evaluation of three qualitative tests for detection of chloroquine in urine--agreement with plasma concentrations determined with liquid chromatography.

Three qualitative tests for detection of chloroquine in urine were compared and evaluated against concomitant plasma concentrations determined with liquid chromatography. All urine tests from five volunteers taking a single dose of 5 mg chloroquine base kg-1 were positive for at least ten days with the Haskins test, and for at least three days with the Wilson Edeson test. Even on the first day, the Dill-Glazko test indicated chloroquine in the urine of one volunteer only. After a single dose of 10 mg kg-1 to five other volunteers the Haskins test was uniformly positive for 14 days while the Wilson Edeson test was positive for four days. The Dill-Glazko test was positive for one day only. No false negative results were obtained with the Haskins test when plasma concentrations were above 0.03 mumol 1(-1), as compared to 0.11 mumol 1(-1) with the Wilson Edeson test. The Dill-Glazko test was uniformly positive when plasma concentrations were above 0.38 mumol 1(-1). The Dill-Glazko test was affected by low urinary pH and by addition of erythrocytes to urine. We conclude that the Dill-Glazko test should not be used.

Chloroquine↗