PubMed HealthSearch

Biomedical subjects

J Karlsson

Publications and source records attributed to J Karlsson.

At least 19 recordsLinked to original sources

A new diffusion chamber system for the determination of drug permeability coefficients across the human intestinal epithelium that are independent of the unstirred water layer.

A new method for determining permeability coefficients, that are independent of the unstirred water layer (UWL), has been developed. The method was used to determine the cellular permeability coefficient of the rapidly absorbed drug testosterone in monolayers of the human intestinal epithelial cell line, Caco-2. Using a new diffusion cell with an effective stirring system based on a gas lift, the cellular permeability coefficient for testosterone was (1.98 +/- 0.13).10(-4) cm/s which is 3.5-times higher than the permeability coefficient obtained in the unstirred system. The thickness of the UWL obtained with the well stirred diffusion cell was 52 +/- 4 microns. This value is much lower than those previously reported in various well stirred in vitro models. The calculated cellular permeability of testosterone was 13-23-times lower than that for an UWL of the same thickness as the epithelial cell (17-30 microns). We conclude that the permeability of the epithelial monolayer must be included in calculations of the thickness of the UWL.

Cell Line

Bad results after anterior advancement of the tibial tubercle for patello-femoral pain syndrome.

Seventy-one patients with patello-femoral pain syndrome were re-examined an average of 10 (range 8-12) years after anterior advancement of the tibial tuberosity. The clinical results were excellent in 8 (11%), good in 20 (28%), fair in 16 (23%), and poor in 27 (38%). Twenty patients had had a second operation. The results were worse in patients with Outerbridge grade III-IV cartilage damage. Since the clinical results deteriorated with time, this surgical procedure should no longer be used to treat patients with patello-femoral pain syndrome.

Adolescent

Ischaemic heart disease, skeletal muscle fibres and exercise capacity.

Twenty-eight male patients with ischaemic heart disease (IHD) performed OBLA (onset of blood lactate accumulation) exercise stress tests and had muscle biopsies taken from their vastus lateralis muscle the day before coronary bypass grafting. All 28 patients showed the same exercise performance pattern as compared to healthy sedentary, age-matched, controls: a low exercise intensity eliciting a blood lactate concentration of 2.0 mmol x l-1 (WOBLA), WOBLA corresponded to a high fraction (% WOBLA) of WSL (symptom limited or 'maximal' capacity), and a low peak blood lactate concentration. The high % WOBLA and low peak blood lactate indicated a reduced glycogenolytic capacity ('anaerobic' performance). Muscle fibre composition disclosed a high mean value of fast twitch (FT), type II or 'white' muscle fibres, as compared to sedentary healthy controls. This indicated that this patient group constituted an extreme subgroup of the age-matched population. The distorted muscle fibre composition in IHD could reflect both heredity as well as adaptation to physical inactivity, degenerative cytosolic properties, etc. Muscle and blood contents of a mitochondrial electron translocator and nonspecific radical scavenger, ubiquinone or coenzyme Q10(CoQ10), were low, which coincided with an elevated frequency of the fibre subgroup FT(c). The presence of the FT(c) fibre type is assumed to reflect histological trauma.

Adult

Exercise-limiting factors in respiratory distress.

Exercise performance data, circulatory function and respiratory and leg muscle quality, expressed as muscle fiber composition, are reviewed and together with our own data discussed as possible limiting factors for physical performance in chronic obstructive pulmonary disease (COPD). COPD is regarded as synonymous with reduced physical performance, exaggerated breathlessness or dyspnea, muscle hypotrophy and/or wasting and, frequently, malnutrition. Impaired right ventricular circulatory function seems to be essential. The observed preponderance of fast twitch (FT), 'glycogenolytic' and capillary-poor muscle fiber type in the investigated muscles might reflect endowment, a 'hypoxic vasoconstriction'-related downregulation of the other main fiber type: the slow twitch (ST), capillary-rich, fatigue-resistant fiber, and/or selective muscle trauma to ST fibers. Ischemic heart disease (IHD) patients demonstrate a similar fiber type pattern in leg muscles. Both COPD and IHD patients have low leg muscle and plasma deposits of antioxidants such as coenzyme Q10 (CoQ10) and alpha-tocopherol. This could reflect a depressed resistance to radical induced cell trauma and/or malnutrition. The magnitude of the antioxidant reduction is less pronounced in patients rich in FT fibers indicating a ST fiber-related susceptibility to trauma. Treatment of other muscle disorders including heart muscle with, e.g., CoQ10 improves performance due to a causative enhanced antioxidant potential, reduced catabolism and/or an upregulated muscle anabolism, increased mitochondrial volume/function, etc. Such data are lacking in COPD.

Aged

Swedish obese subjects (SOS). Recruitment for an intervention study and a selected description of the obese state.

SOS (Swedish obese subjects) is an on-going intervention trial designed to determine whether the mortality and morbidity rates among obese individuals who lose weight by surgical means (gastric banding, vertical banded gastroplasty and gastric by-pass) differ from the rates associated with conventional treatment. For this purpose, the study is recruiting a sample of obese men and women who constitute a registry of potential subjects from which the participants are drawn. Eligibility criteria for participation in the registry were: age at application 37-57 years and BMI greater than or equal to 34 kg/m2 for men and greater than or equal to 38 kg/m2 for women. Before receiving a health examination, all patients complete extensive questionnaires on current and past health status, utilization of medical care and medications, socio-economic status, psychological profiles, dietary habits, physical activity, weight history, and familial disposition to obesity. Each surgical case is matched to its optimal control in the registry, to ensure that the two groups do not differ systematically with respect to any of 18 matching variables that may affect prognosis. The first 1006 subjects included in the registry have been studied with respect to morbidity and compared with on-going population studies of men and women in Göteborg, Sweden. The relative risks of prevalent disease and symptoms associated with obesity in 50-year-old males and females respectively were 4.3 and 4.7 (dyspnoea), 14.7 and 11.8 (angina), 6.3 (myocardial infarction, males only), 2.1 and 4.5 (hypertension), 5.2 and 6.6 (diabetes), 4.6 and 26.1 (claudication) and 1.7 and 1.8 (gall bladder disease). Correspondingly, obese males and females display elevations of systolic and diastolic blood pressure, fasting glucose, insulin, triglyceride, and uric acid levels. However, total cholesterol was not increased in obese males and was in fact significantly lower in obese compared with reference women. HDL-cholesterol was lower in obese than reference men (data were not available in reference women). The rate of taking sick pensions was over twice as high in SOS obese patients than in population controls. Finally, comparison of measurements with self-reported prevalence estimates revealed a considerable amount of previously undiagnosed hypertension and diabetes in the obese subjects. These data suggest that the excess health risks associated with obesity may not be fully appreciated.

Adipose Tissue

Plasma ubiquinone, alpha-tocopherol and cholesterol in man.

Plasma ubiquinone, coenzyme Q10 or CoQ10 has been analyzed in plasma together with alpha-tocopherol and free cholesterol in healthy sedentary male subjects (SS), endurance trained male athletes (ET) and male patients with severe ischemic heart disease (IHD). Higher means were found in SS compared to both IHD and ET. Moreover, the ratios CoQ10 and alpha-tocopherol over free cholesterol were higher. In all groups significant relationships were found between the two products of the mevalonate pathway: CoQ10 and cholesterol (r ranged 0.66-0.86, p less than 0.01). The two lipophilic antioxidants, CoQ10 and alpha-tocopherol, were interrelated only in IHD (r = 0.86, p less than 0.001), borderline in SS (r = 0.51, p less than 0.05) but not in ET. It is assumed that plasma free cholesterol reflects the capacity to transport lipids and lipophilic compounds in blood. With metabolic stress and an elevated radical formation as in IHD and ET, the lower CoQ10 and alpha-tocopherol to cholesterol ratios mirror a subsequent toll on the scavenging potential. The difference in LDL levels between IHD and ET and the different storage capacity of CoQ10 and alpha-tocopherol might explain the tight coupling in IHD but not in ET. It is possible that the toll reflects both an intra- and extracellular radical quenching activity. The joint effect of the two lipophilic, extracellular antioxidants CoQ10 and alpha-tocopherol role in protecting e.g. LDL particles from peroxidation is suggested.

Cholesterol

Lateral instability of the ankle joint.

Acute lateral ankle ligament ruptures are successfully treated nonoperatively with physiotherapy, peroneal strengthening, and coordination training. About 10-20% of patients may develop functional instability despite adequate nonoperative treatment. Chronic functional instability is not always a severe disability, but reconstruction of the lateral ankle ligaments may be necessary for patients with high demands on ankle stability. More than 50 different surgical procedures for the treatment of chronic lateral ankle joint instability have been described. Most of these are tenodeses where one of the peroneus tendons is used, such as Evans, Watson-Jones, and Chrisman-Snook reconstructions. Good short-term results have been reported, but the long-term results after the Evans and Watson-Jones reconstructions are worse than anticipated. Anatomic ligament reconstruction with shortening, reinsertion, and imbrication of the elongated ligaments, a simple procedure with good long-term results, might be a better alternative than other more complex ligament reconstructions.

Ankle Injuries

[Lateral instability of the ankle joint (1). Non-surgical treatment is the first choice--20 per cent may need ligament surgery].

In cases of lateral ankle injury, although acute ligament ruptures are best treated non-operatively with physiotherapy (range-of-motion and co-ordination training, and peroneal muscle strengthening exercises), about 10-20 per cent of patients nonetheless develop chronic functional instability: While this is not severely disabling, ligament reconstruction may be necessary in specific cases, e g for those with high demands of ankle stability. Of the more than 50 surgical approaches published, several have become classic reconstructive procedures widely used--e g, those of Evans and Watson-Jones (with disappointing long-term results), and that of Chrisman-Snook (with satisfactory long-term outcome). However, anatomical ligament reconstruction (with shortening, re-insertion and imbrication of the healed but elongated ligament) is a simple procedure with good short- and long-term results, which may often be a better alternative than other more complex reconstructive procedures.

Ankle Injuries

[Lateral instability of the ankle joint (2). Active training programs can prevent surgery].

One hundred consecutive patients with chronic lateral functional instability of the ankle were treated non-operatively with physiotherapy (active range-of-motion training, strengthening exercises and co-ordination training with a tilt-board). All patients were evaluated functionally with a special rating scale, and radiologically with standardised stress radiographs measuring anterior talar translation (ATT) and talar tilt (TT). Excellent or good functional results were obtained in 49 of the patients, fair or poor in the remainder. The outcome was better in those with painful functional instability or mild mechanical instability, while those with more pronounced mechanical instability required further treatment (i e, reconstructive surgery). Of 10 patients with generalised joint laxity, only fair or poor results were obtained in seven, all of whom had mechanical instability.

Adult

Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells.

Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10(-8) to 5 x 10(-5) cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10(-6) cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10(-6) cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10(-7) cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption.

Adenocarcinoma

Ultrasonography in the detection of partial patellar ligament ruptures (jumper's knee).

The diagnostic performance of ultrasonography (US) in the detection of partial ruptures in the proximal part of the patellar ligament (jumper's knee) was studied. A total of 81 athletes with chronic localized pain suggestive of jumper's knee underwent US examination, and 25 of these received surgical treatment. Of 25 proven partial tendon ruptures at surgery, US correctly indicated the diagnosis in all cases. A cone-shaped, poorly echogenic area exceeding 0.5 cm in length in the center of the patellar tendon in combination with its localized thickening proved to be a reliable indicator of jumper's knee. One case was a true-negative. No false-negative or false-positive case was observed. Soft-tissue radiography in 14 cases showed a localized swelling but did not detect intratendinous soft-tissue abnormalities. US is the method of choice for the evaluation of jumper's knee, as it is cheap, non-invasive, repeatable, and accurate.

Adult

Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina.

The composition of skeletal muscle fibre expressed as a percentage of slow twitch (ST), type I or "red" and fast twitch (FT), type II or "white" were determined in patients with hypertension (HT) or with severe ischaemic heart disease (IHD) and compared to age matched controls. Similarly, exercise capacity expressed as the cycle intensity eliciting a blood lactate concentration corresponding to 2.0 mmol x 1-1 were compared with healthy controls. Both patient groups had a higher percentage of FT fibres with relatively lower exercise capacities than their controls. The exercise capacities were reduced even when the relationship of decreased capacity with the percentage of increased FT was considered. There was an increase IHD but not in HT in patients with fibre subgroup FTc, which most probably reflected fibre trauma. Both patient groups were low in the skeletal muscle mitochondrial electron carrier and unspecific antioxidant ubiquinone, coenzyme Q10 or CoQ10. Patients with IHD but not HT showed, however, a faster fall in the ratio CoQ10 over ST% the higher the percentage value of ST. The ratio reflects the antioxidant activity related to CoQ10 in the fibre hosting most of the oxidative metabolism. A low ratio indicates a risk of metabolic lesion and cell trauma. This could explain fibre plasticity and offer an alternative cause to heredity in elucidating in deviating muscle fibre composition in patients with HT and IHD.

Adult

Coenzyme Q10, alpha-tocopherol and free cholesterol in HDL and LDL fractions.

Twenty-three randomly selected plasma samples from apparently healthy, middle aged men were analysed for coenzyme Q10 (CoQ10), alpha-tocopherol (AT) and free cholesterol (FC) in: 1) whole plasma, 2) the HDL lipoprotein fraction after LDL precipitation (VLDL + LDL). CoQ10, AT and FC in plasma averaged 0.69 +/- .11, 6.74 +/- 1.78 micrograms x ml-1 and 0.59 +/- .11 mg x ml-1 and in HDL 0.17, 3.24 micrograms x ml-1 and 0.17 mg x ml-1 or 29, 48 and 29% of plasma values. Amounts of CoQ10 and AT were correlated to that of FC in all pools. The amount of HDL-CoQ10 but not of HDL-AT fell, with the HDL-FC expressed as the fraction of plasma FC. In all pools, N-AT versus AT initially increased and then levelled off, indicating saturation like conditions in contrast to CoQ10. Thus, CoQ10 and AT are differently allocated in HDL and LDL. This might have a bearing both on the suggested lipoprotein protection against peroxidation by these two antioxidants, but also on the distribution and allocation in different organs of CoQ10 and AT by HDL and LDL transportation.

Cholesterol

The effect of lidocaine on myocardial ischemia with asanguinous reperfusion. An in vitro study.

The effect of lidocaine on the ischemic nor-mothermic rat heart was studied in a Langendorff preparation. Ventricular fibrillation, total retrograde coronary flow and effluent lactate concentration were monitored in preischemia (control), ischemia (20 min) and reperfusion (20 min). Myocardial metabolites were determined in specimens excised at termination of reperfusion. Six hearts were infused with lidocaine in Ringer solution at onset of ischemia (group A) and six with only Ringer solution (group B). Sinus rhythm proceeded directly to diastolic arrest after 17 sec in group A, while all group B hearts showed ventricular fibrillation before arrest at 174 sec. Effluent lactate concentration was reduced in group A during the first 10 min of ischemia, but not subsequently. After 10 min of reperfusion, coronary flow was reduced by 12% in group A and 20% in group B. ATP was higher and ADP, AMP and IMP were lower in group A than in group B after 20 min of reperfusion. Creatine phosphate showed no intergroup difference, but creatine was higher in group B. Cardiac arrest with lidocaine thus reduced lactate formation during ischemia and lessened high-energy phosphate depletion after reperfusion.

Adenine Nucleotides

Preparation and evaluation of sterically stabilized liposomes: colloidal stability, serum stability, macrophage uptake, and toxicity.

Sterically stabilized liposomes were produced by incorporating a nonionic surfactant, polysorbate 80 (Tween 80), into the lipid bilayer. The sterically stabilized liposomes exhibited a superior entrapment stability compared with surfactant-free liposomes (i.e., liposomes prepared with lipids and cholesterol). The sterically stabilized liposomes were stable at high calcium ion concentrations, and liposome-entrapped carboxyfluorescein was retained within the stabilized liposomes in the presence of serum for at least 5 h. The macrophage uptake of the sterically stabilized liposomes was comparable to that of liposomes containing lipids and cholesterol. The sterically stabilized liposomes were non-toxic, in concentrations up to 3.0 mM, to macrophages. These results indicate that polysorbate 80 can be used to produce stable liposomes without changing the unique macrophage distribution of this drug delivery system.

Cells, Cultured

Separate centre of ossification of the lateral malleolus with instability of the ankle joint.

Four cases of recurrent instability of the ankle joint are reported. The instability was associated with a separate centre of ossification of the lateral malleolus and abnormal movement between the ossicle and the distal fibula. All patients were successfully treated by surgery: two underwent internal fixation and ligamentous reconstruction and two, ligamentous reconstruction after removal of the ossicle.

Adult

A comparison of methodologies in detection of the anaerobic threshold.

Peak cardiopulmonary exercise performance is readily evaluated. The most appropriate methodology for assessment of submaximal exercise performance, however, is a subject of controversy. Therefore, we assessed the difference between conventional methodologies using standard criteria to estimate the onset of anaerobiosis and compared them with known gas exchange and blood lactate [( La]) concentrations. Oxygen uptake (VO2) was determined at both the gas exchange anaerobic threshold (ATge) and the lactate threshold (LaT) using the following three types of commonly used methodologies in a blinded fashion: 1) conventional techniques based on manual inspection of plots of gas exchange indexes and [La] versus time, 2) computerized linear regression analysis of two-segment model plots for VCO2 versus VO2 and log [La] versus log VO2, and 3) fixed values determining the VO2 at a respiratory exchange ratio (VCO2/VO2) of 1.00 and at an [La] of 2 mmol/l. Respiratory exchange data were collected on a breath-by-breath basis in 30 men with documented myocardial infarction. Simultaneously, arterial blood was sampled for [La] every 20 seconds during maximal exercise on an upright bicycle ergometer programmed for a continuous ramp protocol of 15 W/min. The mean (+/- SD) peak VO2 was 1,463 (+/- 312) ml/min. The mean (+/- SD) VO2 values for each method were as follows: (table; see text) These results indicate that a good positive correlation exists between the gas exchange and lactate data by all three approaches. The chosen fixed values yield the highest threshold detection for both ATge and LaT. Detection was lowest using regression analysis for LaT.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged