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Biomedical subjects

K Dahl

Publications and source records attributed to K Dahl.

At least 19 recordsLinked to original sources

Sentinel node lymphocytes: tumour reactive lymphocytes identified intraoperatively for the use in immunotherapy of colon cancer.

The sentinel node is the first lymph node to receive lymphatic drainage from a tumour and is usually the first site of metastases. Today, the sentinel node is used for tumour staging. Here, we focus on its immunological role and investigate lymphocytic function in sentinel nodes, identified intraoperatively by peritumoural dye injection, from 15 patients with colon cancer. Tumour infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and peripheral blood leukocytes were studied by flow cytometry, proliferation assays and interferon-gamma secretion after activation with autologous tumour homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the proliferation assays, lymphocytes from sentinel nodes proliferated dose dependently and secreted interferon-gamma upon stimulation with tumour homogenate. The responses were of varying magnitude and tended to be weaker in metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched source of tumour reactive lymphocytes, and may be useful in future trials of adoptive immunotherapy.

Aged↗

Solvent dependence of the spectra and kinetics of excited-state charge transfer in three (alkylamino)benzonitriles.

Steady-state absorption and emission spectra and emission decay kinetics are reported for 4-aminobenzonitrile (ABN), 4-(1-azetidinyl)benzonitrile (P4C), 4-(1-pyrrolidinyl)benzonitrile (P5C), and 4-(1-piperidinyl)benzonitrile (P6C) in 24 room temperature solvents. In solvents of modest to high polarity, P4C, P5C, and P6C exhibit dual fluorescence and emission decays characteristic of the transformation from an initially prepared (LE) state to a more polar charge transfer (CT) state, whereas ABN does not undergo this reaction. The frequencies of the steady-state absorption and emission spectra of all of these solutes can be rationalized using a dielectric continuum description of the solvent and considering only the minima on the reactive surfaces, which are assumed to involve both an intramolecular (twisting) and a solvation coordinate. Characteristics of the gas-phase solutes deduced from this analysis are in good agreement with electronic structure calculations and indicate that differences in their spectra mainly reflect differences in the relative energies of the gas-phase LE and CT states. The relative yields of LE and CT emission are not described as satisfactorily by this model, and reasons for this failure are discussed. The kinetics of the LE --> CT reaction vary considerably with solute and solvent. In many solvents, the emission decays of P4C are reasonably described by a simple two-state kinetic scheme with time-independent rate constants. In P5C and P6C multiexponential decays are observed that reflect time-dependent shifts of the component spectra as well as time-dependent reaction rates. A simplified analysis of these complex dynamics provides estimates for both the free energy change Delta(r)G and (average) LE --> CT rate constant k(f) for a wide range of solute and solvent combinations. The driving force for reaction (-Delta(r)G) follows the order P6C > P5C > P4C and increases with increasing solvent polarity. The reaction rates are correlated to Delta(r)G and follow the opposite trend. The relationships observed between k(f) and Delta(r)G suggest that static solvent effects, i.e., barrier height changes, are the primary determinants of the solvent dependence in P4C. Correlations between barrier-corrected rates and solvation times suggest that dynamical solvent effects contribute substantially to the solvent dependence of the rates in P5C, and especially P6C.

Journal Article↗

Identification of sentinel nodes in patients with colon cancer.

AIMS: Lymphatic mapping and sentinel node biopsy entails better staging in malignant melanoma and breast cancer and we used this technique in patients with colon cancer to possibly improve detection of lymphatic spread. METHODS: Thirty patients with invasive adenocarcinomas were investigated. The tumour status in identified sentinel node(s) was compared with the status in all other harvested regional nodes for each patient. Patients were followed at regular visits for more than 30 months. RESULTS: Sentinel nodes were identified in all cases, either per-operatively (28 cases) or at dissection of the formalin-fixed specimen (2 cases). The sentinel nodes were diagnostic for the entire lymphatic field in 28 patients and the false negative rate was 2/12. In four cases, the sentinel nodes were the only metastatic nodes. After at minimum 30 months, three patients had died of colon cancer metastases. CONCLUSION: This method improved the identification of patients with lymph-node metastases, especially those with only few metastatic nodes. Patients dying from metastatic disease had lymph-node metastases at diagnosis.

Adenocarcinoma↗

The bacterial flora of alpha-Gal knockout mice express the alpha-Gal epitope comparable to wild type mice.

The human genome possesses pseudogenes for the enzyme alpha1,3 galactosyltransferase and hence, human cells and tissues do not express the Galalpha terminated trisaccharide structure Galalpha1-3Galbeta1-4GlcNAc, the so-called alpha-Gal epitope. Circulating antibodies specific for this carbohydrate epitope are, however, present in high amounts in humans. It has previously been hypothesized that the antibody production is induced by the presence of the alpha-Gal epitope in the cell walls of the enteric flora, especially Enterobacteriaceae spp. However, in mice, in which the epitope has been deleted by targeted mutation of the gal-transferase gene, alpha-Gal antibodies do not appear without prior immunization, although the mice through their growth probably have been exposed to a normal bacterial flora of e.g. Enterobacteriaceae spp. It is unknown whether there are different types of immune reactions to antigenic carbohydrate expressing bacteria and whether there are discrepancies in the enteric flora between these knockout mice and their wild type litter mates. In this study the enteric flora of alpha-Gal knockout and wild type mice was compared both in relation to the prevalence of different types of bacteria in the two groups of mice, as well as in relation to the expression of the epitope on the surface of Enterobacteriaceae spp. Our results showed that the enteric flora did not differ significantly between knockout and wild type mice and that it was comparable to the flora known to be present in the intestines of other mice. All Enterobacteriaceae spp. examined expressed the alpha-Gal epitope no matter whether they were isolated from knockout or wild type mice. It is, therefore, discussed whether it is more reasonable to assume that alpha-Gal antibodies in mammals that do not produce alpha1,3 galactosyltransferase such as in the knock mice and in humans are the result of another antigen stimulant than these common representatives of the enteric flora, that we isolated from the two types of mice. Possible candidates for a carrier in humans could be bacteria or viruses not isolated from barrier-bred mice.

Animals↗

Bronchogenic cyst in a German shepherd dog.

Intermittent episodes of fever, severe dyspnoea and cyanosis were observed in a two-and-a-half-year-old male German shepherd dog. The clinical signs were of sudden onset but disappeared within eight hours, in five almost identical episodes over a period of 40 days. Radiological examination of the thorax revealed a large rounded area of radiolucency surrounded by a thin radiopaque structure. The lesion increased in volume between examinations, but otherwise remained similar in appearance. It could not be confirmed from the radiographs whether the structure was situated in lung tissue or mediastinum. Bronchoscopic examination revealed no abnormal findings and there was no bacterial growth from samples taken 30 days after the onset of symptoms. A large, vesicular structure, partly adherent to the mediastinum, was surgically removed from the left cranial lung lobe. The structure was 8 to 10 cm in diameter and partly filled with mucoid pink fluid. Histological examination revealed that the wall contained traces of bronchial epithelial cells. On bacteriological examination of the fluid, Gram-positive, mucus-forming bacteria were present. The definitive gross pathological and histopathological diagnosis was a bronchogenic cyst which had developed secondarily to bronchiectasis. Bronchitis and peribronchitis were also identified. The dog recovered well after surgery and, at the time of writing, was in active duty as a police dog, showing no signs of respiratory illness.

Animals↗

Cardiovascular morbidity and risk factors in renal transplant patients.

BACKGROUND: Cardiovascular disease is now the major cause of death in renal transplant patients. This study aimed to assess the prevalence of cardiovascular disease in stable renal transplant patients as compared with the general background population, and to assess risk factors for cardiovascular disease in this patient group. METHODS: A cross-sectional multicentre study comprising 406 stable renal transplant patients (age 47+/-16 years, 60% males, 71% taking cyclosporin A) were assessed clinically and biochemically 48 months (median) after transplantation and compared with the general population. Multivariate analysis was used to assess the relation between cardiovascular disease and risk factors. RESULTS: Hypertension was present in 55% of males and 34% of females (P<0.001), in 51% with cyclosporin A and in 33% without (P<0.001). Ischaemic heart disease (i.e. angina pectoris and/or previous myocardial infarction) was present in 14% (males: 18%, females: 10%, P<0.05) and in 24% of diabetics vs 12% of non-diabetics (P<0.01). Cerebro- and peripheral vascular disease was found in 3% and 4%, respectively. Odds ratio for angina pectoris (patients vs general population) was: in age group 40-49 years (males/females), 12/16; 50-59 years, 6/4; 60-69 years, 3/4. Ischaemic heart disease was, besides age and gender, independently associated with total cholesterol (P<0.01), and peripheral vascular disease to systolic blood pressure (P<0.01). CONCLUSIONS: Cardiovascular disease is highly prevalent in renal transplant patients, and is independently associated with age, gender, total cholesterol and systolic blood pressure.

Adult↗

Total arterial compliance in ambulatory hypertension during selective beta1-adrenergic receptor blockade and angiotensin-converting enzyme inhibition.

Aortic root flow and pressure estimates were obtained noninvasively with Doppler echocardiography and calibrated subclavian artery pulse tracing in 30 subjects with ambulatory hypertension in a randomized, crossover study with 4 weeks' treatment and washout periods. Total arterial compliance, assessed by use of a three-element Windkessel model of the arterial tree, increased 42% with atenolol (50-100 mg once daily), and 7% (p = NS) with captopril (25-50 mg twice daily). Atenolol reduced mean arterial pressure by 15%, heart rate by 22%, and cardiac output by 14%, and increased acceleration time of aortic root flow by 17% and stroke volume and ejection time each by 11%. Captopril reduced mean arterial pressure and total peripheral resistance each by 7%. Acceleration time of aortic root flow, ejection time, heart rate, stroke volume, and cardiac output were not significantly changed by captopril. We conclude that total arterial compliance, at the operational blood pressure, increases during selective beta1-adrenergic receptor blockade in subjects with ambulatory hypertension. Although the main mechanism may be a reduction in mean arterial pressure, it should be considered whether reduced heart rate may play an additional role. The nonsignificant increase in total arterial compliance during angiotensin-converting enzyme inhibition may primarily be a consequence of a modest reduction of the mean arterial pressure.

Adrenergic Antagonists↗

Different indentation velocities activate different populations of mechanoreceptors in humans.

We have examined whether different skin machanoreceptors are activated by different indentation velocities of a tactile probe. Indentations of 300 microns at velocities of 100 and 400 microns/ms were applied at the dorsolateral side of the foot and at the tip of digit III. Compound sensory action potentials (CSAPs) were recorded from the sural and median nerves, respectively. The amplitudes of the tactile CSAPs were < 1-2 muV, and less than 15% of the CSAPs evoked by electrical stimulation. The areas of the polyphasic tactile CSAPs were 35-38% smaller at 100 microns/ms than at 400 microns/ms. The maximal sensory nerve conduction velocities (SNCVs) were higher in the median than in the sural nerves. In both nerves, the SNCVs were similar at electrical and 400-micron/ms tactile stimulation but 11-17% lower at 100-micron/ms stimulation. Cocaine hydrochloride was applied iontophoretically at the dorsolateral side of the foot, causing a decrease of 50% of the CSAP evoked by 100 microns/ms but only 14% at 400 microns/ms. These studies suggested that identation at 400 microns/ms activated mainly deeply placed (Pacini corpuscles) and to some extent superficial mechanoreceptors, whereas the 100-micron/ms indentation activated primarily superficially situated receptors (Meissner corpuscles, and some slowly adapting units).

Action Potentials↗

Antihypertensive treatment with candesartan cilexetil does not affect glucose homeostasis or serum lipid profile in patients with mild hypertension and type II diabetes.

This multicentre, randomized, controlled clinical trial assessed the effects of candesartan cilexetil (cand.cil.), a novel angiotensin II antagonist selective for the AT1 receptor with long-lasting antihypertensive activity, compared to placebo on glucose homeostasis and serum lipid profile in mild hypertensives with type II diabetes. A total of 161 men and women, 30-75 years old, with mild hypertension (sitting diastolic blood pressure 90-100 mmHg) and type II diabetes (HbA1c 5.5-9.0%), both measured after a 4-week placebo run-in period, were randomized to double-blind treatment with cand.cil. 8 mg o.i.d. (n = 83) or placebo (n = 78). Dose was increased to 16 mg o.i.d. if diastolic blood pressure remained >90 mmHg. At randomization and after 12 weeks of treatment HbA1c (primary effect variable), blood glucose and the serum lipid profile (including total cholesterol, HDL and LDL cholesterol, triglycerides) were assessed. The statistical analysis of the differences between treatments was based on changes from randomization to the end of the study. Cand.cil. had no significant effect on HbA1c, blood glucose and serum lipids compared to placebo. The median HbA1c both at baseline and after 12 weeks was 7.1% in patients on cand.cil., and 7.2% and 7.1% in patients on placebo. The 95% confidence interval for the median difference in change between the groups was narrow (-0.25; 0.16), including zero, which excluded any clinically important difference. The same held true for blood glucose (-1.10; 0.20), total cholesterol (-0.40; 0.20) and the other lipid parameters. More than 60% of the patients reached a diastolic blood pressure <90 mmHg; adverse events and withdrawals were similar in both groups. Thus, in patients with mild hypertension and type II diabetes, cand.cil. 8-16 mg o.i.d. for 12 weeks does not affect glucose homeostasis and serum lipids. Blood pressure was controlled in most patients, and cand.cil. was well tolerated.

Adult↗

Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome.

AIM: To perform a clinical trial of selegiline in 25 patients with chronic fatigue syndrome (CFS) where patients were told they would receive placebo or active agent at different times during the 6-week trial. We chose selegiline, a specific monoamine oxidase (MAO) B receptor inhibitor, because a prior trial of lowdose phenelzine, a nonspecific MAO inhibitor, showed a small but significant therapeutic effect. METHODS: Questionnaires comprised of 19 tests of mood, fatigue, functional status and symptom severity were collected at the start and end of the trial as well as 2 weeks after its start. The trial was done in three 2-week blocks: in the first, 2 placebo pills were given per day; in the next, one 5-mg tablet of agent and one placebo were given per day, and in the last, a 5-mg tablet of agent was given twice a day. The plan was to compare the changes in the 19 tests during the placebo phase to those found in the active treatment phase in 19 patients completing the trial. FINDINGS: Significant improvement in 3 variables-tension/anxiety, vigor and sexual relations-was found. A significant pattern of improvement compared to worsening was found for the 19 self-report vehicles during active treatment as compared with placebo treatment. Evidence for an antidepressant effect of the drug was not found. CONCLUSIONS: Selegiline has a small but significant therapeutic effect in CFS which appears independent of an antidepressant effect.

Activities of Daily Living↗

Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression.

Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms during a constant routine were assessed in 6 female controls and 6 female patients with hypersomnic winter depression (seasonal affective disorder, SAD) before and after morning bright light treatment. After sleep was standardized for 6 days, the subjects were sleep-deprived and at bed rest for 27 hours while rectal temperature, cortisol, and TSH levels were assessed. The minimum of the fitted rectal temperature rhythm was phase-delayed in the SAD group compared to the controls 5:42 AM vs. 3:16 AM (p < .005); with bright light treatment, the minimum advanced from 5:42 AM to 3:36 AM (p = .06). The minimum of the cortisol rhythm was phase-delayed in the SAD group compared to the control group, 12:11 AM vs. 10:03 PM (P < .05); with bright light treatment, the minimum advanced from 12:11 AM to 10:38 PM (P = .06) [corrected]. The acrophase of the TSH rhythm was not significantly phase-delayed in SAD subjects compared to control, though the trend appeared to be toward a phase-delay (p = .07). After bright light therapy, the TSH acrophase was not significantly different in the SAD subjects; the trend was a phase-advance (p = .09). Overall, the data suggest that circadian rhythms are phase-delayed relative to sleep in SAD patients and that morning bright light phase-advances those rhythms.

Adult↗

[Acute respiratory distress due to fat embolism].

BACKGROUND: Acute respiratory distress occurring in a child without any past medical history can have different origins. Pulmonary edema can be lesional or hemodynamic in origin. Bronchoalveolar lavage often allows indication of the type of lesional oedema. CASE REPORT: A 13-year old child was hospitalized for acute respiratory distress 24 hours after knee surgery complicated by a fracture of the tibial metaphysis. There were no clinical manifestations of airway obstruction. Chest X-ray showed pulmonary parenchymous pathology. Pulmonary edema secondary to congestive heart failure was eliminated by doppler echocardiogram. The cause of lesional pulmonary edema was found with bronchoalveolar lavage that showed fat drops in the cytoplasm of many alveolar macrophages. CONCLUSION: Fat embolism syndrome may be confirmed by examination of bronchoalveolar lavage fluid.

Acute Disease↗

Left ventricular systolic and diastolic function assessed with two-dimensional and doppler echocardiography in "white coat" hypertension.

OBJECTIVES: The aim of this study was to investigate left ventricular function in subjects with "white coat" hypertension, defined as office arterial diastolic pressure > or = 90 and ambulatory daytime pressures < 140/90 mm Hg. BACKGROUND: The white coat arterial pressure response may, by influencing left ventricular function, have a confounding effect in studies of heart disease. METHODS: Two-dimensional and Doppler echocardiography combined with the calibrated subclavian arterial pulse tracing, were used to assess variables of left ventricular function in 26 subjects with white coat hypertension (office arterial diastolic pressure > or = 90 and < 115 mm Hg and ambulatory daytime diastolic pressure > or = 90 mm Hg) and 32 normotensive subjects. RESULTS: In subjects with white coat hypertension, systolic arterial pressure during the echocardiographic examination was significantly higher than ambulatory daytime systolic pressure. This pressure response was positively related to the ratio of the systolic to diastolic pulmonary venous flow peak velocities and to the peak velocity of flow reversion during atrial systole; it was inversely related to the ratio of early to late mitral flow peak velocities. Left ventricular stroke volume, ejection fraction and velocity of circumferential fiber shortening did not differ in the study groups, but left ventricular external work and end-systolic wall stress were increased in the white coat group. CONCLUSIONS: The arterial pressure response in subjects with white coat hypertension is associated with increased left ventricular external work, increased end-systolic wall stress and alterations of left ventricular filling but normal ejection fraction and velocity of circumferential fiber shortening.

Blood Pressure↗

Hemodynamics in white coat hypertension compared to ambulatory hypertension and normotension.

Hemodynamic alterations associated with the blood pressure response in subjects with white coat hypertension may provide insight into the pathophysiologic mechanisms of this condition. Systemic arterial hemodynamics were investigated with a recently validated method based on noninvasive estimates of aortic root pressure and flow in 28 subjects with white coat hypertension (diastolic pressure > or = 90 mm Hg measured by the general practitioner [GP arterial pressure] and ambulatory daytime pressures < 140/90 mm Hg), in 23 subjects with previously untreated, ambulatory hypertension (GP diastolic pressure > or = 90 and < 115 mm Hg and ambulatory daytime diastolic pressure > or = 90 mm Hg), and in 32 normotensive subjects. The groups did not differ significantly concerning age, gender, body surface area, heart rate, stroke index and cardiac index, but total peripheral resistance index was increased and total arterial compliance reduced in the white coat group and the hypertensive group compared to the normotensive group. The subjects in the white coat group with a systolic arterial pressure during echocardiography that was > 5 mm Hg higher than the ambulatory daytime systolic pressure (n = 19) had increased cardiac index, increased total peripheral resistance, and decreased total arterial compliance compared to the normotensive group. The subjects in this group with a hemodynamic pattern characterized by a high ratio of cardiac index/peripheral vascular resistance were significantly younger than the subjects with the opposite pattern. Thus, the blood pressure increase in subjects with white coat hypertension is associated with increased cardiac output, increased peripheral vascular resistance, and reduced total arterial compliance, but the hemodynamic pattern may be influenced by age.

Adult↗

Hyperlipidaemia in renal transplant patients.

OBJECTIVES: The aim of study was to assess the prevalence and severity of hyperlipidaemia in renal transplant patients in a Nordic country. DESIGN: Multicentre, cross-sectional study. SETTING: Outpatients and ward inpatients registered from 23 hospitals covering all regions of the country. SUBJECTS: Renal transplant patients with a functioning graft were registered: 406 patients in all; that is, 43% of the national renal transplant population. All patients used prednisolone, 71% used cyclosporine, either with (51%) or without (20%) azathioprine. Total cholesterol values from general population were obtained from a national survey. MAIN OUTCOME MEASURES: Blood lipids and their relation to clinical parameters. RESULTS: Total cholesterol was significantly higher in transplant patients than in the general population for both genders and all age groups (P < 0.01). Female patients had higher total cholesterol (mean +/- SD: 7.49 +/- 1.61 mmol L(-1)) than males (7.01 +/- 1.55 mmol L(-1); P < 0.001), and also higher HDL cholesterol (1.55 +/- 0.43 vs. males: 1.32 +/- 0.46 mmol L(-1); P < 0.001). Triglycerides were equally elevated in both genders, and 33% had values above 2.2 mmol L(-1). Reduced creatinine clearance, a high body-mass index, female gender, hypertension, and coronary artery disease were independently associated with higher total cholesterol. Beta blockers were associated with lower HDL cholesterol and higher triglycerides, and diuretics with higher triglycerides. Blood lipid levels were not associated with cyclosporine immunosuppression. CONCLUSION: Hyperlipidaemia is prevalent after renal transplantation, and is associated with impaired graft function, hypertension, and with the use of beta blockers and diuretics, but not with the use of cyclosporine.

Adrenergic beta-Antagonists↗

[Diagnosis and treatment of high blood pressure. How to invest?].

High blood pressure is a major risk factor for development of cardiovascular diseases. During 1992 and 1993, several national consensus reports about treatment of arterial hypertension have been published. There are discrepancies between the recommendations contained in the reports, which has caused uncertainty among physicians. We discuss the basic problems connected to evaluation and recommendation, and the demand for standardization and organization of the health service programme for patients with high blood pressure. It is possible to learn from, and thereby achieve better quality of medical practice, through a continuous registration of our routines and results. The Trondheim model is designed to depict specific information from the primary health services in a follow-up programme. This information is sampled in a data base from which primary physicians can obtain feedback on statistical evaluations twice a year. This is defined as a quality assurance programme to secure and improve the quality of the medical service to patients with high blood pressure.

Humans↗