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Biomedical subjects

H B Nielsen

Publications and source records attributed to H B Nielsen.

At least 19 recordsLinked to original sources

Mesenteric, coeliac and splanchnic blood flow in humans during exercise.

1. Exercise reduces splanchnic blood flow, but the mesenteric contribution to this response is uncertain. 2. In nineteen humans, superior mesenteric and coeliac artery flows were determined by duplex ultrasonography during fasting and postprandial submaximal cycling and compared with the splanchnic blood flow as assessed by the Indocyanine Green dye-elimination technique. 3. Cycling increased arterial pressure, heart rate and cardiac output, while it reduced total vascular resistance. These responses were not altered in the postprandial state. During fasting, cycling increased mesenteric, coeliac and splanchnic resistances by 76, 165 and 126 %, respectively, and it reduced corresponding blood flows by 32, 50 and 43 % (by 0.18 +/- 0.04, 0.42 +/- 0.03 and 0.60 +/- 0.04 l min-1). Postprandially, mesenteric and splanchnic vascular resistances decreased, thereby elevating regional blood flow, while the coeliac circulation was not influenced. Postprandial cycling did not influence the mesenteric resistance significantly, but its blood flow decreased by 22 % (0.46 +/- 0.28 l min-1). Coeliac and splanchnic resistance increased by 150 and 63 %, respectively, and the corresponding regional blood flow decreased by 51 and 31 % (0.49 +/- 0.07 and 0.96 +/- 0.28 l min-1). Splanchnic blood flow values assessed by duplex ultrasound and by dye-elimination techniques were correlated (r = 0.70; P < 0.01). 4. During submaximal exercise in humans, splanchnic resistance increases and blood flow is reduced following a 50 % reduction in the hepato-splenic and a 25 % reduction in the mesenteric blood flow.

Adult

The influence of PaO2, pH and SaO2 on maximal oxygen uptake.

Influence of arterial oxygen pressure (PaO2) and pH on haemoglobin saturation (SaO2) and in turn on O2 uptake (VO2) was evaluated during ergometer rowing (156, 276 and 376 W; VO2max, 5.0 L min-1; n = 11). During low intensity exercise, neither pH nor SaO2 were affected significantly. In response to the higher work intensities, ventilations (VE) of 129 +/- 10 and 155 +/- 8 L min-1 enhanced the end tidal PO2 (PETO2) to the same extent (117 +/- 2 mmHg), but PaO2 became reduced (from 102 +/- 2 to 78 +/- 2 and 81 +/- 3 mmHg, respectively). As pH decreased during maximal exercise (7.14 +/- 0.02 vs. 7.30 +/- 0.02), SaO2 also became lower (92.9 +/- 0.7 vs. 95.1 +/- 0.1%) and arterial O2 content (CaO2) was 202 +/- 3 mL L-1. An inspired O2 fraction (F1O2) of 0.30 (n = 8) did not affect VE, but increased PETO2 and PaO2 to 175 +/- 4 and 164 +/- 5 mmHg and the PETO2-PaO2 difference was reduced (21 +/- 4 vs. 36 +/- 4 mmHg). pH did not change when compared with normoxia and SaO2 remained within 1% of the level at rest in hyperoxia (99 +/- 0.1%). Thus, CaO2 and VO2max increased to 212 +/- 3 mL L-1 and 5.7 +/- 0.2 L min-1, respectively. The reduced PaO2 became of importance for SaO2 when a low pH inhibited the affinity of O2 to haemoglobin. An increased F1O2 reduced the gradient over the alveolar-arterial membrane, maintained haemoglobin saturation despite the reduction in pH and resulted in increases of the arterial oxygen content and uptake.

Adult

Contribution of pH, diprotonated phosphate and potassium for the reflex increase in blood pressure during handgrip.

The relative importance of pH, diprotonated phosphate (H2PO4-) and potassium (K+) for the reflex increase in mean arterial pressure (MAP) during exercise was evaluated in seven subjects during rhythmic handgrip at 15 and 30% maximal voluntary contraction (MVC), followed by post-exercise muscle ischaemia (PEMI). During 15% MVC, MAP rose from 92 +/- 1 to 103 +/- 2 mmHg, [K+] from 4.1 +/- 0.1 to 5.1 +/- 0.1 mmol L-1, while the intracellular (7.00 +/- 0.01 to 6.80 +/- 0.06) and venous pH fell (7.39 +/- 0.01 to 7.30 +/- 0.01) (P < 0.05). The intracellular [H2PO4-] increased 8.4 +/- 2 mmol kg-1 and the venous [H2PO4-] from 0.14 +/- 0.01 to 0.16 +/- 0.01 mmol L-1 (P < 0.05). During PEMI, MAP remained elevated along with the intracellular [H2PO4-] as well as a low intracellular and venous pH. However, venous [K+] and [H2PO4-] returned to the level at rest. During 30% MVC handgrip, MAP rose to 130 +/- 3 mmHg, [K+] to 5.8 +/- 0.2 mmol L-1, the intracellular and extracellular [H2PO4-] by 20 +/- 5 mmol kg-1 and to 0.20 +/- 0.02 mmol L-1, respectively, while the intracellular (6.33 +/- 0.06) and venous pH fell (7.23 +/- 0.02) (P < 0.05). During post-exercise muscle ischaemia all variables remained close to the exercise levels. Analysis of each variable as a predictor of blood pressure indicated that only the intracellular pH and diprotonated phosphate were linked to the reflex elevation of blood pressure during handgrip.

Adult

Near-infrared spectrophotometry determined brain oxygenation during fainting.

During orthostatic hypotension we evaluated whether presyncopal symptoms relate to a reduced brain oxygenation. Nine subjects performed 50 degrees head-up tilt for 1 h and eight subjects were followed during 2 h of supine rest and during 1 h of 10 degrees head-down tilt. Cerebral perfusion was assessed by transcranial Doppler determined middle cerebral artery blood velocity (MCA vmean), while brain blood oxygenation was assessed by near-infrared spectrophotometry determined concentration changes for oxygenated (delta HbO2) and deoxygenated haemoglobin and brain cell oxygenation by the oxidized cytochrome c concentration (delta CytO2). During head-up tilt, six volunteers developed presyncopal symptoms and mean arterial pressure (88 (78-103) to 68 (57-79) mmHg; median and range), heart rate (96 (72-111) to 65 (50-107) beats min-1), MCA vmean (59 (51-82) to 41 (29-56) cm s-1), delta HbO2 (by -5.3 (-3.0 to -14.8) mumol l-1) and delta CytO2 were reduced (by -0.2 (-0.1 to -0.4) mumol l-1; P < 0.05). During tilt down the cardiovascular variables recovered immediately and delta HbO2 increased to 2.2 (-0.9-12.0) mmol L-1 above the resting value and also delta CytO2 recovered. In the nonsyncopal head-up tilted subjects as in the controls, blood pressure, heart rate, MCA vmean and brain oxygenation indices remained stable. The results suggest that during orthostasis, presyncopal symptoms relate not only to cerebral hypoperfusion but also to reduced brain oxygenation.

Adult

N-acetylcysteine does not affect the lymphocyte proliferation and natural killer cell activity responses to exercise.

This study evaluated whether N-acetylcysteine (NAC) attenuates the reduced lymphocyte proliferation and natural killer (NK) cell activity responses to exercise in humans. Fourteen oarsmen were double-blind randomized to either NAC (6 g daily for 3 days) or placebo groups. During 6-min "all-out" ergometer rowing, the concentration of lymphocytes in the peripheral blood increased, with no significant difference between NAC and placebo as reflected in lymphocyte subsets: CD4(+), CD8(+), CD16(+), and CD19(+) cells. The phytohemagglutinin-stimulated lymphocyte proliferation decreased from 9,112 +/- 2,865 to 5,851 +/- 1,588 cpm (P < 0.05), but it was not affected by NAC. During exercise, the NK cell activity was elevated from 17 +/- 3 to 38 +/- 4% and it decreased to 7 +/- 1% below the resting value 2 h into recovery. Yet, when evaluated as lytic units per CD16(+) cell, the NK cell activity decreased during and after exercise without a significant effect of NAC. We conclude that NAC does not attenuate the reduction in lymphocyte proliferation and NK cell activity associated with intense exercise.

Acetylcysteine

[Paraneoplastic opsoclonus].

Opsoclonus occurs in a number of clinical settings, but its association with carcinomas in adult patients is rare. We present a case of paraneoplastic opsoclonus in a 63 year-old male who had a small-cell lung cancer. Even though paraneoplastic opsoclonus may be associated with an immunological response, there was no elevation of blood parameters associated with inflammation. The patient was treated with prednisolon without any clinical effect, and died only a few months after opsoclonus was diagnosed.

Carcinoma, Small Cell

Lymphocyte proliferation in response to exercise.

Lymphocyte proliferative responses are often used to evaluate the functional capacity of the immune system in response to exercise. Blood mononuclear cells (BMNC) are stimulated in vitro with polyclonal mitogens and the incorporation of 3H-thymidine into the DNA reflects cell proliferation. The BMNC are most often stimulated with either phytohaemagglutinin (PHA), poke weed mitogen (PWM), concanavalin A (Con-A), interleukin-2 (IL-2), or purified derivative of tuberculin (PPD). The literature concerning lymphocyte proliferation and exercise is reviewed with respect to the type and intensity of exercise, and also the effect of training status. The proliferative responses to exercise are highly heterogeneous, the most consistent finding being that PHA-stimulated cell responses decrease during exercise which may reflect a decreased fraction of CD3+ cells. In contrast, reduced, elevated or even unchanged lymphocyte proliferative response to PHA, PWM, Con-A, IL-2 and PPD have been demonstrated in the recovery period following exercise. Also variable responses are present in trained athletes compared to less fit subjects. Even though this may reflect that the time of 3H-thymidine incorporation into lymphocytes varies, we conclude that a functional evaluation of the immune system in response to exercise cannot be based solely upon measurements of lymphocyte proliferation.

Cell Division

Middle cerebral artery blood velocity during rowing.

Dynamic exercise increases the transcranial Doppler determined mean blood velocity in basal cerebral arteries corresponding to the cortical representation of the active limb(s) and independent of the concomitant rise in the mean arterial pressure. In 12 rowers we evaluated the middle cerebral artery blood velocity response to ergometer rowing when regulation of the cerebral perfusion is challenged by stroke synchronous fluctuation in arterial pressure. Rowing increased mean cerebral blood velocity (57 +/- 3 to 67 +/- 5 cm s-1; mean +/- SE) and mean arterial (86 +/- 6 to 97 +/- 6 mmHg) and central venous pressures (0 +/- 2 to 8 +/- 2 mmHg; P < 0.05). The force on the oar triggered an averaging procedure that demonstrated stroke synchronous sinusoidal oscillations in the cerebral velocity with a 12 +/- 2% amplitude upon the average exercise value. During the catch phase of the stroke, the mean velocity increased to a peak of 88 +/- 7 cm s-1 and it was in phase with the highest mean arterial pressure (125 +/- 14 mmHg), while the central venous pressure was highest after the stroke (20 +/- 3 mmHg). The results suggest that during rowing cerebral perfusion is influenced significantly by the rapid fluctuations in the perfusion pressure.

Adult

Exercise-induced immunomodulation--possible roles of neuroendocrine and metabolic factors.

Acute muscular exercise induces an increased neutrophil count concomitant with recruitment of natural killer (NK), B and T cells to the blood as reflected by an elevation in the total lymphocyte count. Meanwhile, following intense exercise of long duration the lymphocyte count declines, non-MHC-restricted cytotoxicity is suppressed, but the neutrophil concentration increases. In relation to eccentric exercise involving muscle damage, the plasma concentrations of interleukin-1, interleukin-6 and the tumor necrosis factor are elevated. In this review we will propose a model based on the possible roles that stress hormones play a mediating the exercise- related immunological changes: adrenaline and to a lesser degree noradrenaline are responsible for the immediate effects of exercise on lymphocyte subpopulations and cytotoxic activities. The increase in catecholamines and growth hormone mediate the acute effects of exercise on neutrophils, whereas cortisol may be responsible for maintaining lymphopenia and neutrocytosis after exercise of long duration. Lastly, the role of beta-endorphin is less clear, but the cytokine response is closely related to muscle damage and stress hormones do not seem to be directly involved in the elevated cytokine level. Other possible mechanisms of exercise-induced immunomodulation may include the so-called glutamine hypothesis, which is based on the fact that skeletal muscle is an important source of glutamine production and that lymphocytes are dependent on glutamine for optimal growth. Furthermore, physiological changes during exercise, e.g. increased body temperature and decreased oxygen saturation may also in theory contribute to the exercise-induced immunological changes.

Catecholamines

Splenectomy impairs lymphocytosis during maximal exercise.

To evaluate the role of the spleen for the exercise-induced lymphocytosis, six splenectomized subjects and six matched control subjects cycled for 12 min at two submaximal work rates corresponding to 50 and 75% of their maximal work capacity, followed by a supramaximal intensity maintained until exhaustion (16 +/- 1 min; mean +/- SE). Venous blood samples were taken before, during, and 2 h after the maximal load. In both groups, the concentration of lymphocytes became elevated during exercise, but the increase from the level at rest was impaired in the splenectomized subjects compared with that of the controls (118 +/- 34 vs. 238 +/- 38%; P < 0.05). This was reflected in several lymphocyte subsets: cluster designation (CD) 3+ cells (pan T lymphocytes), 69 +/- 19 vs. 204 +/- 37%; CD8+ cells (T lymphocyte subset), 164 +/- 41 vs. 467 +/- 68%; CD16+ cells [natural killer (NK) cells], 291 +/- 88 vs. 870 +/- 177%; CD56+ cells (NK cells), 301 +/- 108 vs. 753 +/- 187%. Also, the specific NK cell lysis of target cells (NK cell activity) during exercise was lower for the splenectomized subjects (30 +/- 7%) than that of the control subjects (52 +/- 10%), but evaluation of lytic units indicates that this was due to a reduced number of NK cells in the assay rather than insufficient cell lysis. Plasma catecholamines reached the same level in the splenectomized subjects and control subjects, which was taken to reflect that the activity of the sympathetic nervous system was similar in the two groups of subjects. Thus the major finding of this study is that the spleen is important for lymphocytosis during exercise, accounting for two-thirds of the increase in T lymphocytes and NK cells.

Adult

Lymphocyte, NK and LAK cell responses to maximal exercise.

To evaluate if exhaustion after maximal exercise suppresses the immune system; ten healthy male oarsmen (maximal oxygen uptake, 5.7 +/- 0.2 l.min-1; mean and SE) performed a six minute "all-out" bout on a rowing ergometer (394 +/- 12 watt). Rowing increased the blood leucocyte count as reflected in the concentrations of lymphocytes, monocytes, and neutrophils. Two hours after rowing the leucocyte and neutrophil numbers remained elevated, while the lymphocyte count decreased below the prevalue. The concentrations of cluster designation CD3+ (pan T), CD4+ (T subset), CD8+ (T subset), CD19+ (B cells), and CD16+ natural killer (NK) cells increased during rowing with the elevation in CD16+ cells being sevenfold. Only the concentration of CD3+ and CD8+ cells decreased below prevalues two hours after exercise. The lymphokine activated killer (LAK) cell activity of blood mononuclear cells (BMNC), and the NK cell activity of BMNC (%lysis per fixed number of BMNC), either unstimulated or stimulated with interleukin-2, interferon-alfa or indomethacin, also increased in response to rowing, and returned to the prevalues after two hours. In contrast, the BMNC proliferative responses did not change significantly. The evaluation of NK and LAK cell activities, and the proliferative responses of BMNC suggest that six minute maximal exercise does not suppress the immune response during recovery, even when a large muscle mass is involved.

Adult

Lymphocytes and NK cell activity during repeated bouts of maximal exercise.

Effects on the immune system of 6-min "all-out" ergometer rowing were investigated over 2 days (2 x 3 bouts) in eight male oarsmen with a maximal oxygen uptake of 5.5 +/- 0.1 l/min (mean +/- SE). Blood samples were obtained before, during, and 2 h after each bout and on the day after the last bout. Compared with levels at rest, the first bout of exercise increased the concentration of leukocytes (2-fold); neutrophilic granulocytes (2-fold); lymphocytes (2-fold); monocytes (2-fold); the blood mononuclear cell (BMNC) subsets CD3+ (2-fold), CD4+ (2-fold), CD8+ (3-fold), CD16+ (8-fold), CD19+ (2-fold), and CD14+ (2-fold); the NK cell activity (2-fold); and plasma interleukin-6 (3-fold) (P < 0.05). During the last bout even higher levels were noted for leukocytes (3-fold); neutrophilic granulocytes (3-fold); lymphocytes (4-fold); the BMNC subsets CD4+ (3-fold), CD8+ (5-fold), CD16+ (13-fold), CD19+ (5-fold), and CD14+ (3-fold); and for the NK cell activity (4-fold) (P < 0.05). During the recovery periods all values were at or above the level at rest, and elevated concentrations of leukocytes (38%), neutrophilic granulocytes (48%), and lymphocytes (46%) reflected in the BMNC subsets and increased NK cell activity (119%) were also noted on the day after the last bout (P < 0.05). The results show that maximal exercise with large muscle groups provokes higher immune responses during repetitive bouts.

Adult

[Free oxygen radicals during transplantation surgery].

Free oxygen radicals are a highly reactive species of molecules characterized by an unpaired electron in the outer electron ring. They are formed continuously in the organism as part of enzymatic reactions, or as byproducts of oxidation processes. Antioxidants are able to eliminate free oxygen radicals, but during ischaemic reperfusion, the capacity of these systems is exceeded resulting in tissue injury, cell necrosis, destruction of enzymes and DNA-damage. Free oxygen radicals thereby play a major role in the tissue injury seen in organs after transplantation surgery and aorta operations. When the endogenous antioxidative capacity is exceeded, protection of lipid membranes against attack by free oxygen radicals by antioxidant supplementation is an alternative strategy for reduction of tissue injury. Since antioxidants are atoxic, they could also be of importance even in small operations, where the tissue blood supply is often periodically cut off.

Antioxidants

From image processing to classification: I. Modeling disturbances of isoelectric focusing patterns.

In order to optimize the conditions for evaluation of isoelectric focusing (IEF) patterns by digital image processing, the sources of error in determination of the pI values were analyzed together with the influence of a varying background. The effects of band distortions, in the spectra of the individual lanes, were examined. In order to minimize the effect of these distortions, optimal conditions for handling IEF patterns by digital image processing were elucidated. The systematic part of the global deformation on the gels was investigated and an algorithm was developed by which it was possible to correct for a part of the individual distortions. The effects of various corrections for lane distortions were illustrated by classification, using different types of discriminant analysis. Finally the background disturbances were examined, and described by a mathematical model.

Algorithms

Restricted pulmonary diffusion capacity after exercise is not an ARDS-like injury.

Pulmonary diffusion capacity (DLCO) is reduced 2 h after various types of exercise, such as rowing, treadmill running, arm cranking and marathon running. The decrease in DLCO may involve alterations in the alveolar-capillary membrane as well as depletion of the central blood volume. We hypothesized that the reduction in DLCO might also be influenced by oxygen free radicals, acute phase proteins and endotoxin, which are also involved in the adult respiratory distress syndrome (ARDS). Ten competitive male oarsmen performed a 6 min 'all-out' ergometer row. Single breath DLCO was determined before and 2 h after rowing and venous blood samples were also obtained during the row. Absolute DLCO decreased by 11% (range 0-20%) 2 h after rowing, whereas the concentration of endotoxin did not change significantly and interleukin (IL)-1-alpha, IL-8 and tumour necrosis factor (TNF)-alpha were below the levels of detection before, during and 2 h after rowing. Oxygen free radicals were evaluated by oxidative modification of amino acids and DNA. Corrected for creatinine in urine voided 3 h post-exercise, the DNA repair product 8-oxo-7,8-dehydro-2-deoxyguanosine (8-oxodG) did not change significantly. The ratio of fluorescence due to dityrosine to that due to tryptophan in plasma proteins increased after exercise. This might reflect an effect of oxygen free radicals, but it might also indicate an altered relative composition of plasma proteins. These results suggest that the reduced pulmonary diffusion capacity following exercise is unrelated to factors typically associated with ARDS.

8-Hydroxy-2'-Deoxyguanosine

Exercise-induced gastric mucosal acidosis.

Gastric acidosis as assessed by tonometry was applied to evaluate changes in splanchnic blood flow during exercise. In six healthy male oarsmen, we determined gastric acidosis in response to 30 min of maximal ergometer rowing. The gastric mucosa carbon dioxide tension was determined by equilibration of isotonic saline to the tonometer. Arterial bicarbonate (HCO3-), pH, arterial oxygen tension (PaO2), and saturation (SaO2) were obtained simultaneously, while pH (pHi) of the gastric mucosa was calculated using the Henderson-Hasselbach equation. During rowing PaO2 and SaO2 decreased to values of 73.7 mm Hg and 95.5%, respectively (P < 0.05). However, during the last minute of rowing the values were normalized with a hyperventilation reducing PaCO2 to 27.1 mm Hg (P < 0.05). Rowing decreased HCO3- from 25.8 (21.4-28.5) to 14.1 (11.6-17.4) mmol l-1, while the gastric carbon dioxide tension increased from 36.8 (24.1-63.9) to 61.7 (48.9-82.0) mm Hg (P < 0.05). Accordingly, pHi decreased from 7.25 (7.04-7.48) to 6.79 (6.67-6.85) (P < 0.05). Arterial pH also decreased (from 7.42 (7.41-7.44) to 7.29 (7.26-7.33) (P < 0.05)), with the enlarged difference between pH and pHi suggesting marked splanchnic hypoperfusion during rowing.

Acidosis

The immune system during exposure to extreme physiologic conditions.

It is not clear how the immune system is modulated in response to physical stress (e.g. trauma, surgery, burn and sepsis). In order to better understand the stress-induced immune changes, effects of isolated stressors are evaluated. Human experiments include hypoxia, head-up tilt, hyperthermina and exercise, which influence all lymphocyte subtypes and especially so the natural killer (NK) cells. In essence, the immune response is enhanced even by light physical stress, but suppressed after prolonged, intense stress.

Exercise