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Biomedical subjects

L Johansen

Publications and source records attributed to L Johansen.

At least 19 recordsLinked to original sources

Reproducibility and validity of physiological parameters measured in cyclists riding on racing bikes placed on a stationary magnetic brake.

UNLABELLED: The purpose of this study was: 1) To evaluate the reproducibility of physiological parameters measured during cycle exercise, and 2) To validate the predictive capacity of physiological parameters related to endurance performance. Therefore, physiological variables were measured twice during cycling exercise in a group of seven cyclists. Each cycle exercise session was separated by one week and included progressive submaximal cycling followed by a 5-km time trial. Two and three weeks later, endurance performance was evaluated by calculating average work output during a 50-km time trial (W50km). To simulate cycle performance, the cyclists' private racing bikes were placed on a stationary magnetic brake. No differences were observed between paired physiological observations in the test-retest (P>0.05). The coefficient of variation (CV) was calculated from the differences between test-retest parameters. CV for the maximal oxygen uptake (VO2max), average work output during the 5-km trial (W5km), the calculated work intensity which increased the blood lactate concentration to 2 and 4 mmol/l (W2mM and W4mM) and W50km were 1.9, 2.7, 6.1, 5.9 and 6.3%, respectively, while the 95% confidence interval (CI) showing the expected range for variation in a retest was calculated to be 80 ml.min(-1), 9, 16, 18 and 18 W, respectively. Simple linear regression showed significant correlations between VO2max, W5km, W2mM, W4mM and W50km (r-values: range 0.83-0.98, P<0.01). IN CONCLUSION: 1) Physiological parameters can be reproduced during an exercise test procedure in cyclists riding on racing bikes placed on a stationary magnetic brake, and 2) The validity of VO2max, W5km, W2mM, and W4mM as predictive parameters of endurance was demonstrated.

Adult

Cost of long-term complications of deep venous thrombosis of the lower extremities: an analysis of a defined patient population in Sweden.

BACKGROUND: Little information is available on the epidemiology and economic effect of long-term complications developing after deep venous thrombosis. OBJECTIVE: To determine the extent of, timing of, and treatment costs associated with long-term complications developing after deep venous thrombosis of the lower extremities. DESIGN: 15-year retrospective cohort study. SETTING: County hospital in Sweden. PATIENTS: 257 patients with deep venous thrombosis and 241 age- and sex-matched controls without deep venous thrombosis. MEASUREMENTS: Data on use of health care resources and costs of inpatient and outpatient care, pharmaceutical agents, and treatment of complications. RESULTS: After 15 years of follow-up, 35% of the patients with thrombosis and 57% of the controls were alive. Two hundred forty-two complications were reported among the patients with thrombosis, and 25 similar events were reported among the controls. The average expected present value of the health care cost of treating complications of thrombosis was estimated to be about $4659 in the patients with thrombosis and $375 in the controls. In controls, primary deep venous thrombosis cost about $6000; thus, the additional long-term health care cost of post-thrombotic complications is about 75% of the cost of primary deep venous thrombosis. CONCLUSIONS: The economic effect of post-thrombotic complications is considerable. The use of measures to prevent thromboembolism and its long-term complications are justified on both clinical and economic grounds.

Follow-Up Studies

Secondary aortoenteric fistulae--changes from 1973 to 1993.

AIM: To investigate a series of patients with secondary aortoenteric fistulas and compare it with a previous series (1985-93 vs. 1973-84). DESIGN: Retrospective study of medical records. SETTING: Sixteen vascular surgical centers in Sweden. PATIENTS: Twenty-seven patients were identified making an overall incidence of 0.5% of all aortoiliac operations. Among aneurysm patients the incidence was significantly lower than in the previous series. One patient record could not be identified. Fourteen primary operations were for aortic aneurysm, 12 for occlusive disease and one was an aortorenal vein bypass. RESULTS: Symptoms of the fistula occurred after a median interval of 90 months which is significantly later than the previous series (32 months; p<0.05). The commonest presentation was bleeding followed by septis. The median diagnostic delay was 10.5 days, which was significantly shorter than in the previous series. Most fistulas involved the duodenum (88%). One patient died before surgery. The postoperative mortality was 28%, significantly lower than in the previous series (58%) (p<0.05). At the end of follow up (median 43 months) significantly more patients were alive than in the previous series (42% vs 18%) (p<0.05). CONCLUSION: Over a 21 year period there seems to have been a decrease in the frequency of secondary aortoenteric fistulas after aneurysm surgery, a longer interval before they occur, a shorter diagnostic delay, and a better survival.

Aorta, Abdominal

Muscle lactate metabolism in recovery from intense exhaustive exercise: impact of light exercise.

This study examined the effect of low-intensity exercise on lactate metabolism during the first 10 min of recovery from high-intensity exercise. Subjects exercised (61.0 +/- 5.4 W) one leg to exhaustion (approximately 3.5 min), and after 1 h of rest they performed the same exhaustive exercise with the other leg. For one leg the intense exercise was followed by rest [passive (P) leg], and for the other leg the exercise was followed by a 10-min period with low-intensity exercise at a work rate of 10 W [active (A) leg]. The muscle lactate concentration after the intense exercise was the same in the P and A legs, but after 10 min of recovery, the lactate concentration and the arterial blood lactate level were higher for the P leg than for the A leg (both P < 0.05). During the recovery, the mean blood flow was lower for the P leg than for the A leg (P < 0.05), whereas the mean lactate efflux was not significantly different. During the 10 min of recovery, lactate release accounted for approximately 60% of the change in muscle lactate for either leg. The leg excess postexercise O2 consumption during 10 min of recovery was 440 and 750 ml for the P and A legs, respectively. The present data suggest that a lowered blood lactate level during active recovery is due to an elevated muscle lactate metabolism and is not caused by a transient higher release of lactate from the exercising muscles coupled with greater uptake in other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product.

A chromosomal translocation, t(4;11)-(q21;q23), is associated with an aggressive mixed-lineage leukemia. A yeast artificial chromosome was used to clone the chromosomal breakpoint of this translocation in the RS4;11 cell line. The breakpoint sequences revealed an inverted repeat bordered by a consensus site for topoisomerase II binding and cleavage as well as chi-like elements. The der(11) chromosome encodes a fusion RNA and predicted chimeric protein between the 11q23 gene MLL and a 4q21 gene designated AF4. The sequence of the complete open reading frame for this fusion transcript reveals the MLL protein to have homology with DNA methyltransferase, the Drosophila trithorax gene product, and the "AT-hook" motif of high-mobility-group proteins. An alternative splice that deletes the AT-hook region of MLL was identified. AF4 is a serine- and proline-rich putative transcription factor with a glutamine-rich carboxyl terminus. The composition of the complete MLL-AF4 fusion product argues that it may act through either a gain-of-function or a dominant negative mechanism in leukemogenesis.

Amino Acid Sequence

Absence of phosphocreatine resynthesis in human calf muscle during ischaemic recovery.

Changes in the metabolites phosphocreatine (PCr), Pi and ATP were quantified by 31P n.m.r. spectroscopy in the human calf muscle during isometric contraction and recovery under ischaemic conditions. Time resolution of the measurements was 10 s. During a 30-60 s ischaemic isometric contraction, PCr decreased linearly at a rate of 1.17%/s (relative to the resting value) at a contraction strength equivalent to 70% of the maximal voluntary contraction (MVC) and at a rate of 2.43%/s at 90% MVC. There was a corresponding increase in Pi but the concentration of ATP did not change. pH decreased linearly during contraction by 4.22 and 8.23 milli-pH units/s at 70 and 90% MVC respectively. During a subsequent 5 min interval of ischaemic recovery, PCr, Pi, ATP, phosphomonoesters and calculated free ADP, free AMP and pH retained the value they had attained by the end of contraction with no significant recovery. Thus it is concluded that anaerobic glycolysis and glycogenolysis is halted momentarily on termination of contraction and that PCr is not resynthesized during ischaemic recovery. This paradoxical arrest of glycolytic flow in spite of the very significantly elevated concentration of potent activators such as Pi and free AMP clearly indicates that parameters other than PCr, ATP, Pi, calculated pH, free ADP and free AMP regulate glycolysis and glycogenolysis of human skeletal muscle very efficiently under ischaemic conditions.

Adenosine Diphosphate

Lactate and H+ effluxes from human skeletal muscles during intense, dynamic exercise.

1. Lactate and H+ efflux from skeletal muscles were studied with the one-legged knee extension model under conditions in which blood flow, arterial lactate and the muscle-blood lactate concentration gradient were altered. Subjects exercised one leg twice to exhaustion (EX1, EX2), separated by a 10 min recovery and a period of intense intermittent exercise. After 1 h of recovery the exercise protocol was repeated with the other leg. Low-intensity exercise was performed with one leg during the recovery periods, while the other leg was passive during its recovery periods. 2. Prior to, and immediately after, EX1 and EX2 and then 3 and 10 min after EX1, a biopsy was taken from the vastus lateralis of the exercised leg for lactate, pH, muscle water and fibre-type determinations. Measurements of leg blood flow and venous-arterial differences for lactate (whole blood and plasma), pH, partial pressure of CO2 (PCO2), haemoglobin, saturation and base excess (BE) were performed at the end of exercise and regularly during the recovery period after EX1. 3. The lactate release was linearly related (r = 0.96; P < 0.05) to the muscle lactate gradient over a range of muscle lactate from 0 to 45 mmol (kg wet wt)-1. The muscle lactate transport was evaluated from the net femoral venous-arterial differences (V-Adiff) for lactate. This rose with increases in the muscle lactate gradients, but as the gradient reached higher levels the V-Adiff lactate responded less than at smaller gradients. Thus, the lactate transport over the muscle membrane appears to be partly saturated at high muscle lactate concentrations. 4. The percentage of slow twitch (%ST) fibres was inversely related to the muscle lactate gradient, but it was not correlated to the lactate release at the end of the exercises. In spite of a significantly higher blood flow during active recovery, the lactate release was the same whether the leg was resting or performed low-intensity exercise in the recovery periods. In several other conditions the muscle lactate and H+ gradients would have predicted that the V-Adiff lactate would have been greater than it actually was. Thus, a variety of factors affect muscle lactate transport, including arterial lactate concentration, muscle perfusion, muscle contraction pattern and muscle morphology. 5. The muscle and femoral venous pH declined during EX1 to 6.73 and 7.14-7.15, respectively, and they increased to resting levels during 10 min of either passive or active recovery.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

NMR and analytic biochemical evaluation of CrP and nucleotides in the human calf during muscle contraction.

This study compared biochemical and 31P-nuclear magnetic resonance (NMR) determinations of energy metabolites during isometric contractions of the human calf muscle at various exercise intensities. Seven male subjects performed one-legged isometric contractions at a work load of 28, 64, and 90% of maximal voluntary contraction force (28-, 64-, and 90%-CON, respectively) for 3 min, 40 s, and 40 s, respectively, in a magnet and in an exact model of the magnet with an arrangement for rapid muscle biopsy sampling from the gastrocnemius. The decrease in phosphocreatine (CrP) determined by NMR was 20, 33, and 71% for 28%-, 64%-, and 90%-CON, respectively. These decreases were the same as those determined biochemically (25, 34, and 61%, respectively). Muscle CrP 1 min after 90%-CON was also found to be similar between NMR and biochemical determinations (88 and 74% of resting value, respectively). Although no significant change in muscle ATP was found by NMR, a decrease of 29% was observed biochemically at 90%-CON. The ratio between muscle CrP and ATP was the same between NMR and biochemical determinations except for 90%-CON (1.98 and 0.78, respectively). The increase in muscle ADP determined by NMR was two-, five-, and eightfold higher than that found biochemically for 28%-, 64%-, and 90%-CON, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Elevated muscle acidity and energy production during exhaustive exercise in humans.

This study examined the effect of previous intense exercise on energy production during exhaustive exercise. Subjects (n = 6) performed dynamic knee extensor exercise to exhaustion twice (Ex1 and Ex2) separated by 16 min of recovery consisting of 10 min of rest, 3.5 min of very high-intensity intermittent exercise, and a further 2.5 min of rest. This resulted in an elevated muscle lactate concentration of 13.1 mmol/kg wet wt before Ex2. Muscle lactate concentration was the same at end of Ex1 and Ex2, but the accumulation of lactate and net lactate release during Ex2 was reduced (P < 0.05) by 67 and 38%, respectively. The time to exhaustion was 3.73 and 2.98 min, respectively, and the mean rate of net lactate production for Ex2 was lower (P < 0.05) than for Ex1 (4.6 +/- 1.2 and 9.6 +/- 1.7 mmol.min-1.kg wet wt-1, respectively). Leg O2 uptake was the same for Ex1 and Ex2. Muscle pH (6.85) was lowered (P < 0.05) before Ex2, but at the end of Ex2 (6.77) it tended (P < 0.1) to be higher compared with that at the end of Ex1 (6.73). In summary, the net lactate production rate is reduced but the aerobic energy production is not significantly altered when intense exercise is repeated. Fatigue and the lowered glycolysis do not appear to be caused by the elevated acidity per se before exercise.

Acid-Base Equilibrium

Diagnostic ability of different human milk fat globule antigens in breast cancer.

Human mammary epithelial antigens (HME-Ags) are released into the circulation by breast tumors and not by normal breast tissue (Proc. Natl. Acad. Sci. USA 74: 582-586, 1977). This characteristic made them valuable, together with other breast cancer related antigens later identified, to develop immunoassays useful in the follow-up of breast cancer. Assays for these antigens in serum have less than complete sensitivity and partial specificity, and as a result of this have not been totally successful in studying the relapsing breast cancer patient. In the present work, correlations are made among 3 assays available for breast cancer disease follow-up. They detect HME-Ags, CEA, and the heavy molecular weight mucin of the human milk fat globule (HMFG). Values for sensitivity and specificity for the 3 assays were obtained from approximately 300 samples of patients whose clinical diagnosis at the time of blood drawing was rigorously established. A small but definite advantage in sensitivity is demonstrated for the HME-Ags assay over the other two. A similar advantage is also demonstrated in the sequential follow-up of breast cancer patients, where HME-Ags respond more rapidly in most instances to changes in tumor burden. Further, the ability of increases in levels of these assays to predict relapse was studied in 15 patients who relapsed. HME-Ags demonstrated a predictive value of 73%, while CEA and the heavy molecular weight mucin remained at 47%. The present study exemplifies the search for novel antigens (Ags) with maximal ability to detect breast cancer relapse and with improved sensitivity to monitor tumor burden changes. Here, assays for different antigens to be compared are tested in the same serum samples obtained from carefully staged patients. The results suggest a role as breast cancer markers for antigens of lower molecular weight than the epithelial mucin-like components studied previously.

Antigens, Neoplasm

The presence of human papillomavirus (HPV) in solitary adult laryngeal papillomas demonstrated by in-situ DNA hybridization with sulphonated probes.

Human papilloma virus (HPV) types 6 and 11 have been repeatedly demonstrated in multiple laryngeal papillomas, and there is little doubt that these lesions are caused by HPV. It has been clearly demonstrated in recent reports that the clinical course of solitary adult onset laryngeal papillomas is entirely different from that of multiple papillomas of juvenile as well as of adult onset. We here report the presence of HPV types 6 and 11 in 19 out of 20 solitary papillomas from 16 patients, while HPV types 16 and 18 were totally absent. We conclude that the milder clinical course in such patients is most likely to be due to host factors, rather than to viral factors.

DNA Probes, HPV

Exocrine and endocrine release of kallikrein after reflex-induced salivary secretion.

Exocrine and endocrine release of rat submandibular gland kallikrein has been shown to be low after parasympathetic and beta-adrenergic stimulation but greatly increased after alpha-adrenergic stimulation. In the present study, release of glandular kallikrein was investigated under conditions known to give a reflex-induced salivary gland response. Heat stress induced a rich flow of saliva originating in the submandibular glands. Salivary kallikrein secretory rate was higher than after parasympathetic stimulation but lower than after sympathetic stimulation (P less than 0.005). Only heat stress increased circulating glandular kallikrein (12.7 +/- 0.8 ng ml-1 before heat exposure and 53.3 +/- 14.1 ng ml-1 40 min afterwards, P less than 0.005). There were no indications that the endocrine release of kallikrein was due to non-specific leakage. Atropine abolished heat-induced salivation and endocrine kallikrein secretion, possibly through interference with central pathways (P less than 0.05). However, phentolamine did not, which may indicate as an yet unidentified mediator of endogenous kallikrein release. The salivary gland response to acid and ether was comparable to that observed after parasympathetic nerve stimulation and was abolished by atropine (P less than 0.005). Stimuli known to influence other salivary gland ductal cells, such as aggression and starvation followed by drinking, also did not increase the plasma concentration of glandular kallikrein. The fact that various conditions which induce salivation did not increase circulating glandular kallikrein, coupled with the fact that kallikrein concentration was the highest in animals that died from heat stress, may suggest that the increase in circulating glandular kallikrein seen after heat stress may be pathological and could contribute to the development of heat shock.

Animals

Adjuvant bestatin (Ubenimex) treatment following full-dose local irradiation for bladder carcinoma.

The clinical value of adjuvant bestatin (Ubenimex) immunotherapy has been examined in a group of patients with urinary bladder cancer. Patients with non-metastatic transitional cell carcinoma of the bladder, scheduled for full-dose local irradiation therapy (64 Gy), were randomly allocated to adjuvant oral bestatin treatment (30 mg daily for at least 1 year), starting at completion of irradiation, or no bestatin. The trial included 194 evaluable patients with a follow-up period of 1.5-9.5 years. The overall survival of the two groups of patients did not differ statistically significantly (97 patients in each). Subgrouping of the patient material gave no evidence that the clinical efficacy of bestatin is related to sex, tumor category or malignancy grade.

Adjuvants, Immunologic

Excess antibody immunoassay for the measurement of tonin in rat tissues and plasma.

Tonin, a proteolytic enzyme isolated from the rat submandibular gland, can generate angiotensin II directly from angiotensinogen. To date a method for the measurement of tonin in plasma has not been available and the present paper describes a sensitive and specific excess antibody immunoassay for determination of tonin in tissue homogenates and plasma. Interference from immunologically cross-reacting proteins was evaluated and the assay was found to be specific for tonin. Tonin measured in various tissue homogenates was directly proportional to the amount of sample added, giving a linear dose-response curve. The slope of this curve was determined by the recovery of tonin, which was better than 55% for urine and all tissues tested. The highest concentration of tonin was seen in the submandibular and sublingual gland (69 and 0.7 microgram/mg protein, respectively). The parotid gland, the exorbital lacrimal gland, liver, kidney, pancreas, and lung contained only negligible amounts (less than 4 ng/mg protein). Tonin in plasma was bound to one major inhibitor with a molecular weight of about 650,000-750,000. A partial splitting of the tonin-inhibitor complex was obtained by preincubating plasma with guanidine, allowing tonin to be measured with a recovery of 38 +/- 13% (n = 16) and with a linear dose-response curve. The concentration of immunoreactive tonin in normal arterial plasma from adult male rats was 0.90 +/- 0.53 ng/ml (n = 16). The concentration decreased after removal of the submandibular glands and increased after sympathetic stimulation.

Animals