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Biomedical subjects

H Nilsson

Publications and source records attributed to H Nilsson.

At least 109 records · Page 6Linked to original sources

The effect of felodipine on cold-induced digital vasospasm.

Felodipine, a calcium antagonist with pronounced vascular selectivity, was given to 10 patients with cold-induced, digital vasospasm. Placebo and increasing doses of felodipine (2.5, 5, and 10 mg b.i.d.) were given for 2 weeks each. There was a significant decrease in systemic, but not in digital, blood pressure and a significant increase in heart rate during felodipine treatment. The subjective rating of symptoms improved significantly on all doses. No significant effect on cold-induced digital vasospasm during local cooling to 15 and 10 degrees C was registered. Typical side effects of calcium-entry blockers were reported. Moreover, two postmenopausal women reported recurrence of menstrual bleeding and one woman reported vaginal hemorrhagic discharge during treatment. In conclusion, felodipine, although causing a significant, symptomatic relief, had no significant effect on cold-induced digital vasospasm when objective measures were used.

Blood Pressure↗

Transmitter characteristics of small mesenteric arteries from the rat.

We have studied the neurogenic response of small mesenteric arteries from the rat to evaluate the involvement of possible co-transmitters under various modes of stimulation. Segments of small branches of the mesenteric artery were mounted in a myograph and the intramural nerves were activated with transmural electrical stimulation. A single stimulation of the nerves caused a contraction that was reduced by only 20% in the presence of adrenergic blocking agents (prazosin or phenoxybenzamine), whereas the steady-state response to continuous nerve stimulation of high frequency was reduced by 90-95%. In contrast, all responses to applied noradrenaline in doses up to at least 1 mM were eliminated by phenoxybenzamine treatment. The stable ATP analogue, alpha,beta-methylene ATP, reduced the response to a single nerve stimulation by 70%, but reduced the contraction caused by continuous high-frequency nerve stimulation by only 10%. None of these agents affected the response to applied neuropeptide Y (NPY). The response of relaxed vessels to nerve stimulation was totally blocked by the combination of an adrenoceptor-blocking agent and alpha,beta-methylene ATP, although even in this situation a further neurogenic response could be revealed in vessels precontracted with vasopressin. Responses to either single stimuli or brief burst stimulations were potentiated after high-frequency stimulation. Both the adrenergic and non-adrenergic components were enhanced to roughly the same extent. Also the potentiated response was eliminated by the combined application of prazosin and alpha,beta-methylene ATP. The non-adrenergic transmitter in the sympathetic nerves of small arteries thus appears to be the dominant transmitter during low-frequency nerve stimulation, causing rapid but phasic activation. Noradrenaline is the most important transmitter for higher frequencies, exerting slower but sustained contractions. The post-stimulatory potentiation affects both the adrenergic and the non-adrenergic part of the neurogenic response.

Adenosine Triphosphate↗

Endothelium-independent potentiation by neuropeptide Y of vasoconstrictor responses in isolated arteries from rat and rabbit.

An endothelium-dependent action of neuropeptide Y (NPY) has been implicated in studies on various vascular beds. In the present study, the requirement of an intact endothelium for NPY-evoked potentiation of the response to sympathetic nerve stimulation was determined in the small mesenteric arteries of the rat and in the central ear artery of the rabbit. Further, NPY-mediated inhibition of relaxing influences was determined in small mesenteric arteries of the rat. Vascular segments were mounted in a double myograph, where one of the two suspended vessels was denuded of endothelium by gently rubbing the intimal surface. Removal of endothelium was verified by en-face silver staining. In both species, the response to bursts of transmural field stimulation eliciting 10% of maximal contraction was potentiated 2-4 times in the presence of 10 nM NPY, whether the endothelium was present or not. In small mesenteric arteries precontracted with noradrenaline, addition of acetylcholine (I microM) caused relaxation only in vessels with an intact endothelium. Subsequent addition of 10 nM NPY enhanced vasoconstriction in both intact and endothelium-denuded vessels. The endothelium-independent beta-adrenergic agonist isoprenaline (I microM) relaxed both intact and denuded small mesenteric arteries, and in both further addition of 10 nM NPY increased the contraction to about the same extent. The results demonstrate that NPY potentiates the responses to sympathetic field stimulation in small mesenteric arteries from the rat and in central ear artery from rabbit whether the endothelium is present or not. NPY inhibits both endothelium-dependent and -independent relaxations in small mesenteric arteries from rat.

Animals↗

Sympathetic transmission in small mesenteric arteries from the rat: influence of impulse pattern.

We have previously studied the transmitters involved in, and the calcium dependency of, the neurogenic response to continuous, regular nerve stimulation in small mesenteric arteries from the rat. We have now studied responses to irregular nerve stimulation in these respects. Small mesenteric arteries from rat were mounted into a myograph and the intramural sympathetic nerves were activated by field stimulation. Irregular nerve stimulation was patterned after recorded activity in human cutaneous nerves. The response to irregular stimulation was reduced by only approximately 50% in the presence of the alpha 1-adrenoceptor antagonist prazosin. In particular, responses to low-frequency stimulation were resistant to prazosin. When the extracellular calcium concentration was reduced from 2.5 to 1.0 mM, approximately 50% of the response to irregular nerve stimulation remained. Responses to low-frequency stimulation were particularly reduced. Thus in these arteries the neurogenic response is caused by noradrenaline and a, perhaps purinergic, co-transmitter. The co-transmitter is important for the response to low-frequency stimulation and for the initial part of the contraction caused by high-frequency stimulation. Reducing the calcium concentration affects more strongly the response to low-frequency nerve stimulation.

Animals↗

Vascular adrenergic responses in morphine-dependent rats.

The circulatory effects of morphine abstinence have recently been found to involve decreased renal sympathetic nerve activity and increased mean arterial pressure, induced by vasoconstriction. A direct influence of morphine withdrawal on the peripheral vasculature could possibly contribute to the increased resistance. Therefore, contractile responses to transmural nerve stimulation and to applied noradrenaline of peripheral arteries from morphine-dependent and untreated rats were examined in vitro under paired conditions. No increase in contractile response was observed after chronic morphine treatment, either on nerve stimulation or on applied noradrenaline. Instead the smooth muscle sensitivity to adrenergic stimulation was reduced. Consequently, the present study does not support a peripheral adrenergic origin of the vasoconstriction during naloxone-precipitated morphine abstinence.

Animals↗

Induction of mRNA for HLA-DR beta in human keratinocytes cocultured with interferon-gamma.

Explanted human keratinocytes exposed in vitro to recombinant interferon-gamma (IFN-gamma) were investigated for the appearance of mRNA for HLA-DR. Using in situ hybridization with a (35S)UTP-labelled HLA-DR beta cRNA probe, mRNA-positive cells were detected already within 6 h with maximal numbers of positive cells as well as the amount of mRNA per cell after 48 h. The corresponding protein HLA-DR, as analysed by immunoperoxidase staining, was detected on 20%-40% of the cells after 24 h and on almost all cells within 48 h. The expression of HLA-DQ and -DP antigens were always exceeded by that of HLA-DR. Whereas an increase in the concentration of IFN-gamma above 50 U/ml did not affect the maximal level of HLA-DR reactive cells, there was a fourfold increase in the frequency of cells reactive with HLA-DQ and a twofold increase for HLA-DP when the IFN-gamma concentration was raised from 50 to 500 U/ml. When IFN-gamma was withdrawn from the cultures, HLA-DR mRNA and protein synthesis ceased--indicating the continuous need for IFN-gamma to maintain the HLA-DR synthesis in keratinocytes.

DNA↗

The effect of isradipine, a new calcium-channel antagonist, in patients with primary Raynaud's phenomenon: a single-blind dose-response study.

Isradipine is a new potent calcium-channel blocking agent with highly selective action on peripheral vessels. In this single-blind study, its dose-related effect on cold-induced changes in finger systolic pressure (FSP) was investigated in ten female patients with primary Raynaud's phenomenon, and the side effects of isradipine treatment were evaluated. The patients were studied during 9 weeks of treatment. After 3 weeks of placebo, isradipine was given in doses of 1.25 mg b.i.d. and 2.5 mg b.i.d. for 3 weeks each. FSP was measured on local finger cooling to 10 degrees C. FSP at 10 degrees C expressed in percent of the value of 30 degrees C increased from 21 +/- 16% (M +/- SD) after placebo to 42 +/- 28% (p less than 0.05) and 62 +/- 25% (p less than 0.001) after treatment with isradipine 1.25 mg and 2.5 mg b.i.d., respectively. The subjective efficacy of the treatment was assessed with a visual analogue scale (VAS). The VAS rating increased from 17 (range 0-66) after placebo to 39 (range 12-88) (NS) and 68 (range 25-99) (p less than 0.001) after isradipine treatment with 1.25 mg and 2.5 mg b.i.d., respectively. Adverse effects of isradipine therapy were few and did not differ from those reported after the placebo period. This single-blind, dose-response study showed that isradipine in doses of 1.25 mg and 2.5 mg b.i.d. had favorable objective and subjective effects in patients with primary Raynaud's phenomenon and had no serious side effects.

Adult↗

Thermal function of a clothing ensemble during work: dependency on inner clothing layer fit.

A tight-fitting crewneck undergarment (U) and a loose-fitting shirt (S) were studied as part of a commonly used clothing ensemble (Itot = 0.22 m2 K W-1). Ten clothed male subjects performed standardized packing work (VO2 = 0.761 min-1) at three climatic conditions, 20 degrees C and Va = 0.45 m s-1 (0-30 min), at 5 degrees C and Va = 0.39 m s-1 (30-60 min) and at 5 degrees C and Va = 1.23 m s-1 (76-90 min). From 60-75 min the subjects rested at 20 degrees C. The physiological and subjective responses varied with the environment from slightly warm to cool. U resulted in warmer responses than S: torso and upper arm skin temperatures were higher at both 5 degrees C and 20 degrees C, evaporation rate was higher at 20 degrees C, mean skin temperature was higher during work at 20 degrees C, sweating tended to begin earlier and skin wettedness to be higher with U than with S. No differences were observed in core temperature, heart rates, and subjective thermal evaluations. It was concluded that a tight-fitting inner layer (U) compared to a loose-fitting one (S) allows for less cooling of the skin in both a cool and a slightly warm environment.

Adult↗

Sympathetic transmission in small mesenteric arteries from the rat: highly calcium-dependent at low stimulation rates.

In the present study we examine the calcium requirements of the neurogenic response in vitro of small arteries (150-200 microns diameter) from the mesentery of Wistar rats. Intramural nerves were activated with electrical field stimulation. Responses to single impulses and to low-frequency repeated stimulation were reduced or abolished by reducing the Ca2+ concentration in the bathing solution from 2.5 to 1.0 mM. Responses to higher frequencies (16 Hz) were only slightly affected. Since calcium reduction had markedly less effect on responses to direct activation of the smooth muscle and on responses to any dose of exogenous noradrenaline, the calcium reduction had mainly pre-junctional effects. The data show that part of the neurogenic response is highly calcium-sensitive, perhaps more so than would be expected of a purely noradrenergic transmission.

Animals↗

Effects of pre-junctional alpha-receptor blockade on vascular neuro-effector characteristics in rats on high sodium intake.

Various in-vitro studies have indicated a direct attenuating effect of sodium on the affinity of adrenergic alpha 2-receptors. It has been suggested that ingested sodium in this way might increase blood pressure by reducing the activity of central alpha 2-receptors and thereby increasing sympathetic discharge. However, such an effect of sodium would also impair the function of peripheral alpha 2-receptors. In the present study we have therefore investigated the effect of high sodium intake on the alpha 2-receptor-mediated inhibition of the vascular neurogenic response. Male Wistar rats were given 2% NaCl in their drinking water from 4 to 9 weeks of age. Another group receiving plain tap water served as controls. Segments of small branches from the mesenteric artery were mounted in a myograph. Responses to transmural nerve stimulation were determined before and after alpha 2-receptor blockade with either yohimbine or idazoxan. The response to a continuous nerve stimulation that elicited 30% of maximal contraction was increased 2-3 times after addition of either idazoxan (0.1 microM) or yohimbine (0.3 microM), with no significant difference between sodium-treated and control rats; if anything the enhancement was slightly greater in the sodium-treated group. Also, responses to intermittent burst stimulation were increased from 30 to about 80% of maximal response in both rat groups. The results thus indicate that high sodium intake does not affect the inhibitory influence of pre-junctional alpha 2-receptors on the vascular neurogenic response.

Adrenergic alpha-Antagonists↗

Calcium dependency of the post-stimulatory potentiation of the neurogenic response in small mesenteric arteries from the rat.

We have previously shown that the contraction of small mesenteric arteries in response to nerve stimulation is enhanced by preceding high-frequency stimulation. We have now investigated the calcium dependency of this post-stimulatory potentiation. Small arteries (inner diameter 150-250 microns) from normotensive rats were dissected free from surrounding tissue, and segments were mounted in a myograph where the wall tension was measured at well-defined circumferences. Nerve stimulation was performed by field stimulation. A single stimulation of the nerve caused a contraction of 2.6 +/- 0.25% of maximal adrenergic response. After a high-frequency nerve stimulation with 16 Hz and 480 pulses the response to a single nerve stimulation was enhanced 6.6 +/- 1.3 times. The potentiation decayed with a time constant of 93.7 +/- 20.0 s. The amplitude of the post-stimulatory potentiation was dependent on the extracellular calcium concentration during the conditioning stimulation. In a solution containing 2.5 mM calcium the single twitch was enhanced 6.6 times while after exposure to reduced calcium (0.5 mM) it was only enhanced twice. The contraction caused by a short burst of high-frequency nerve stimulation (20 Hz and 10 pulses) was potentiated four times by a conditioning stimulation (16 Hz and 480 pulses), and this potentiation seemed to be independent of the extracellular calcium concentration during the conditioning stimulation. Thus the magnitude of the post-stimulatory potentiation of single nerve stimulations is linearly related to the extracellular calcium concentration during the conditioning nerve stimulation. For the potentiation of the response to burst stimulation no relation was found between the potentiation and extracellular calcium.

Animals↗

On the unpredictable development of congenital cytomegalovirus infection. A study in twins.

Two cases of congenital cytomegalovirus (CMV) infection in twins are reported. In addition, congenital CMV infection in twin pairs described in the literature is reviewed. The relationship of monochorionic vs. dichorionic placentas and monozygosity vs. dizygosity in the development of congenital infection in either one or both members in a pair of twins is discussed.

Cytomegalovirus Infections↗

Propafenone versus disopyramide for treatment of chronic symptomatic ventricular arrhythmias. A multicenter study.

The efficacy and safety of propafenone, 150 mg four times daily, were compared with those of disopyramide, 100 mg four times daily, in a randomized single-blind, cross-over study in 38 patients with symptomatic premature ventricular complexes (PVCs). The 24-hour ambulatory ECG, employed for assessing antiarrhythmic efficacy, was analyzed blindly. The median reduction in the number of PVCs was higher with propafenone than with disopyramide (91.4% vs. 63.5%, respectively, p less than 0.01). A reduction of at least 80% was achieved by propafenone in 22 (59%) and by disopyramide in 16 patients (43%) (NS). Ventricular tachycardias (VTs) were abolished by propafenone in eight out of 11, and by disopyramide in five out of nine patients with VTs (NS) a possible proarrhythmic effect was seen in three patients during disopyramide and in one patient during propafenone treatment. Micturition disturbances (p less than 0.001) and a dry mouth (p less than 0.01) were more commonly associated with disopyramide than with propafenone. In conclusion, in the given dosages, propafenone was superior to disopyramide in suppressing PVCs and had fewer side-effects.

Adult↗

T-cell response to purified protein derivative after removal of Langerhans' cells from epidermal cell suspensions containing keratinocytes expressing class II transplantation antigens.

In a previous study we observed that human epidermal cell (EC) suspensions containing HLA-DR-expressing keratinocytes showed an amplified T-cell response to purified protein derivative (PPD). To evaluate further the possible immunological importance of class II transplantation antigens on keratinocytes we have compared the T-cell response to PPD in the presence of the following stimulator cells: EC suspensions from normal skin, or EC from tuberculin-reactive skin with or without removal of Langerhans' cells. The proliferation of purified T lymphocytes from peripheral blood in response to PPD in the presence of various concentrations of autologous EC was measured by [3H]thymidine incorporation on day 6. In 3 experiments out of 4 the EC from tuberculin-reactive skin, containing 28-76% HLA-DR-expressing cells as judged by immunocytochemistry (which also revealed fairly numerous HLA-DQ/-DP-expressing keratinocytes and a slight increase in CD36- and CD4- but not CD1-expressing cells), induced a more pronounced T-cell response to PPD than did normal EC. This was not the case in the fourth experiment, in which a small number of HLA-DR-(15%) and few if any HLA-DQ-/-DP-expressing keratinocytes were found. Immunomagnetic removal of CD1-reactive Langerhans' cells from the tuberculin-reactive EC suspensions resulted in a reduction of the T-cell response to PPD, in most cases down to background level (T cells alone + PPD). This study does not support the hypothesis that HLA-DR-expressing keratinocytes can in themselves act as antigen-presenting cells.

Adult↗

Removal of Langerhans cells from human epidermal cell suspensions by immunomagnetic particles.

The possibility of eliminating the class II antigen-expressing and antigen-presenting Langerhans cells from normal human epidermal cell suspensions was investigated. Cell suspensions containing 1.7-2.8% Langerhans cells were prepared by enzyme treatment of human skin obtained at plastic surgery. The cells were incubated with mouse monoclonal antibodies directed against the CD1 antigen present on Langerhans cells and were further incubated with magnetic particles, 4.5 micron in diameter, coated with sheep anti-mouse IgG. The optimal ratio between particles and target cells was found to be 40:1. The rosetted Langerhans cells were removed by a cobalt-samarium magnet. In six experiments immunoperoxidase staining revealed 0-0.1% (mean 0.03%) CD1-reactive Langerhans cells in the depleted cell fraction. The alloantigen presenting capacity of the depleted cell fraction, measured by [3H]thymidine incorporation, was abolished.

Antigen-Presenting Cells↗

Appropriate suction device in rescue medicine.

In rescue medicine, a suction apparatus must function in a variety of environmental conditions. To find an appropriate device for the Swedish Air Force air rescue service the Laerdal suction device 790,000 was selected for further testing according to international standards for aviation safety. Tests showed that vibrations had deleterious effects on the internal construction of the suction device. In addition, an electromagnetic field was generated affecting the navigation, autopilot, and communication systems. We conclude that the suction apparatus and probably other devices as well must be tested for their functioning in adverse environments and their ability to meet international aviation safety regulations.

Aviation↗

The effect of the calcium-entry blocker nifedipine on cold-induced digital vasospasm. A double-blind crossover study versus placebo.

The effects of the calcium-entry blocker nifedipine 20 mg, two 10 mg capsules, t.i.d. in patients with cold-induced digital vasospastic disease of idiopathic or traumatic origin was tested in 28 patients, using double-blind crossover technique on both symptoms and test results. The effect of treatment on digital blood pressure during local cooling was assessed using the Nielsen-Lassen method. Symptomatic improvement was reported by 5 patients during placebo treatment and 17 during nifedipine treatment (p less than 0.01). The symptomatic improvement was significant in the total group of patients and in the group of patients with idiopathic vasospastic disease. The digital blood pressure during local cooling improved significantly with nifedipine at 5, 10, 15 (p less than 0.001) and 20 degrees C (p less than 0.05) for the total study population and for the two subgroups except for the change at 20 degrees C in the IDIOP group. At a digital temperature of 10 degrees C, 2 patients reached normal digital blood pressure during placebo treatment compared to 16 during nifedipine treatment (p less than 0.001). The number of side-effects increased significantly (p less than 0.05) during nifedipine treatment. We consider the use of nifedipine in patients with cold-induced digital vasospastic disease to be of great value, especially in patients with digital vasospastic disease of idiopathic origin.

Adult↗

Post-tetanic potentiation of the vascular neurogenic response in rats.

We have previously shown that, at least at frequencies of 4 Hz and above, a previous stimulation of the intramural vasoconstrictor nerves facilitates the subsequent response so that even maximal contractions can develop during periods of stimulation as short as a few seconds. In the present study the facilitating effect of a continuous nerve stimulation was quantitatively tested on 'single-twitch' responses to individual nerve impulses. Small arteries and veins (150-500 micron diameter) from rats were mounted in a myograph at known wall tension, and the intramural nerves were activated at frequencies between 0.1 and 32 Hz. After a period of continuous stimulation the single-twitch responses could be amplified 10-20 times, depending on frequency and duration of the continuous stimulation. No such amplification was observed after application of exogenous noradrenaline. The results therefore reflect a prejunctional frequency-dependent potentiating mechanism which can strongly reinforce sympathetic neuroeffector control. Furthermore, combined with previous data concerning adrenergic transmitter release, the present results seem to be more compatible with the view that the quantum of transmitter released from each varicosity upon activation is less than an entire granule.

Animals↗