PubMed Health⌕ Search

Biomedical subjects

T Knudsen

Publications and source records attributed to T Knudsen.

At least 19 recordsLinked to original sources
PubMed2006

Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone.

BACKGROUND: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. METHODS: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles. RESULTS: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences. CONCLUSION: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.

Administration, Oral↗
PubMed2002

Effect of profound acid suppression in functional dyspepsia: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. METHODS: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d (n = 100) or placebo (n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. RESULTS: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% Cl of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. CONCLUSION: A subset of patients with FD will respond to therapy with omeprazole.

Adult↗
PubMed2001

[Cyclosporine treatment of patients with active ulcerative colitis refractory to high-dose glucocorticoid].

In around 30-40% of patients with acute severe ulcerative colitis the disease is refractory to treatment with high-dose glucocorticoids. Adding intravenous cyclosporine to the therapy in these patients has shown encouraging short-term results. Case notes of twenty-three acutely ill patients, who received intravenous cyclosporine during the period 1992 to 1998 due to failure of high-dose glucocorticoid (n = 20) or due to medical complications (n = 3) which made surgery difficult, were reviewed. Eight patients had their first episode of ulcerative colitis whereas 15 had relapse or chronic active disease. Cyclosporine (4 mg/kg/dag) was added to glucocorticoid treatment after a median of 11 days. Clinical remission was achieved in 13 patients (57%) after a median of nine days, of these five subsequently underwent surgery. Ten did not obtain remission and went to surgery. Approximately a third of acutely ill ulcerative colitis patients refractory to standard treatment with high-dose glucocorticoids will benefit from intravenous cyclosporine in the longer term.

Adolescent↗
PubMed1997

Role of the Na+/K+-ATPase in regulating the membrane potential in rat peritoneal mast cells.

1. The aim of this study was to investigate the effect of the Na+/K+-ATPase on the membrane potential of peritoneal mast cells isolated from male Sprague-Dawley SPF-rats. 2. Experiments were performed at 22-26 degrees C in the tight-seal whole-cell configuration of the patch-clamp technique by use of Sylgard-coated patch pipettes (3-6 M[omega]). High-resolution membrane currents were recorded with an EPC-9 patch-clamp amplifier controlled by the 'E9SCREEN' software. In addition, a charting programme on another computer synchronously recorded at low resolution (2 Hz) membrane potential and holding current (low-pass filtered at 500 Hz). 3. Na+/K+-ATPase activity was measured as the ouabain-sensitive change in the zero-current potential. The zero-current potential in rat peritoneal mast cells measured 2 min after obtaining whole-cell configuration amounted to 1.7 +/- 2.5 mV (n = 21). Ouabain (5 mM), a Na+/K+-ATPase-inhibitor, had only a very minor effect upon the membrane potential under resting conditions (n = 3). 4. When mast cells were superfused with nominal calcium-free external solution, the cells hyperpolarized (delta mV: 20.2 +/- 3.8 mV (n = 5)). In addition, when the mast cells were preincubated in nominal calcium-free external solution for 12 +/- 1.6 min before whole-cell configuration, the membrane potential amounted to -53.7 +/- 9.8 mV (n = 8). A subsequent superfusion with ouabain (5 mM) depolarized the membrane potential (ouabain-sensitive hyperpolarization (delta mV): 23.0 +/- 8.4 mV (n = 8)). 5. A high intracellular concentration of Na+ ([Na+]i) (26.6 mM) also resulted in hyperpolarization (delta mV: 20.2 +/- 9.1 mV (n = 7)), but only when ATP was present. A subsequent superfusion with ouabain (5 mM) repolarized these cells to -1.2 +/- 14 mV (ouabain-sensitive hyperpolarization (delta mV): 19.7 +/- 7.7 mV (n = 7)). 6. The size of the [Na+]i-dependent hyperpolarization was dose-dependent. Low [Na+]i (1 mM) had no effect on membrane potential and these cells were unaffected by superfusion with calcium-free external solution. 7. These data thus directly confirm that the stimulant effect of calcium-free external solutions on the ouabain-sensitive changes in the zero-current potential, and hence the Na+/K+-ATPase, is mediated through [Na+]i and that the activity of the Na+/K+-ATPase can have an important influence on the resting membrane potential in rat peritoneal mast cells.

Animals↗
PubMed1995

[Intestinal ischemia. Clinical picture and examination methods].

A review of chronic intestinal ischaemia with special emphasis on symptoms, clinical findings, diagnostic procedures and treatment is given. Chronic intestinal ischaemia is not a frequent disease and is often caused by arteriosclerosis. The symptoms are postprandial abdominal pain accompanied by weight loss. The weight loss is mainly caused by reduced food consumption. The diagnosis is traditionally based on angiography and it is recognised that two of the three arteries to the intestines must be affected before the symptoms are experienced. Recently, more functional tests have become available. Especially the measurements of splanchnic blood flow before and after a test meal are used. The lack of a postprandial rise in blood flow is taken as evidence for intestinal ischaemia. Noninvasive methods such as duplex scanning with measurement of portal flow and tonometry seem promising. The treatment is surgical reconstruction of the blood flow or, more recently, percutaneous transluminal angioplasty. The results are generally excellent, although percutaneous transluminal angioplasty in some cases needs to be repeated. The diagnosis and treatment are for a specialist with a special interest. The patients should be concentrated in just a few centres.

Chronic Disease↗
PubMed1995

The Na+/K(+)-pump in rat peritoneal mast cells: some aspects of regulation of activity and cellular function.

The mast cell contains potent mediators of inflammation which are released after IgE-directed and non-IgE-directed stimulation of the cell. This highly specialized cell is therefore ascribed a role in the pathogenesis of disease states in which the inflammatory response plays a role for the development of the clinical symptoms. Thus, besides being of interest in basic research, studies of the cellular processes leading to release of inflammatory mediators from the mast cell also have important clinical implications. The aim of the present work has been to document the existence of the Na+/K(+)-pump in rat peritoneal mast cells, to investigate the regulation of the pump activity and to explore whether modulation of the pump activity interferes with the cellular stimulus/secretion coupling mechanism. The Na+/K(+)-pump activity following stimulation of the mast cell was also investigated. The pump activity was assessed as the ouabain-sensitive cellular potassium uptake with 86Rb+ as a tracer for potassium. The histamine release from the mast cell following IgE-directed and non-IgE directed stimulation of the cell was used as a parameter for cellular degranulation. Histamine was measured by spectrofluorometry. The finding of an ouabain-sensitive uptake mechanism in the mast cell documents the presence of a functional Na+/K(+)-pump in this cell. The pump activity is inhibited by lanthanides and by the divalent cations calcium, magnesium, barium and strontium. The pump has a large reserve capacity which probably is caused by a low intracellular concentration of sodium. This enables the pump to respond to changes in the intracellular sodium concentration. The inhibitory effect of di- and trivalent ions on the pump activity is probably a result of the inhibitory effect of these ions on the cellular sodium uptake. The digitalis glycosides, ouabain and digoxin, but not the more lipophilic drug digitoxigenin, increase both IgE-directed and non-IgE-directed histamine release from the mast cell in a calcium-free medium, while there is no effect of digitalis glycosides in a medium containing physiologically relevant concentrations of calcium. The effect of digitalis glycosides on the histamine release is dependent on the drug concentrations used and the time of preincubation. An increase in the intracellular concentration of sodium secondary to inhibition of the Na+/K(+)-pump is the effector mechanism likely to explain the effect of digitalis glycosides on the mast cell histamine release. Increases in intracellular sodium might affect the intracellular concentration of calcium via changes in Na+/Ca(2+)-exchange. IgE-directed and non-IgE-directed stimulation of the mast cell activates the Na+/K(+)-pump. In case of compound 48/80-induced histamine release, the pump is stimulated for at least 2 hr. It is proposed, that the poststimulatory activation of the Na+/K(+)-pump is due to increased cellular sodium uptake associated with the release process. This sodium uptake may occur via Na+/Ca(2+)-exchange, Na+/H(+)-exchange, Na+/K+/2Cl(-)-cotransport or a non-selective ion channel. Besides describing aspects of the function and regulation of the Na+/K(+)-pump in the rat peritoneal mast cells, this thesis points to the potential role of sodium transport mechanisms in mast cell physiology. Pharmacological manipulations of such transport mechanisms might in the future add to the treatment of allergic diseases.

Animals↗
PubMed1993

Effect of ouabain, digoxin and digitoxigenin on potassium uptake and histamine release from rat peritoneal mast cells.

Rat peritoneal mast cells were used to study the effects of digitalis glycosides on potassium uptake and histamine release induced by compound 48/80, substance P and egg-albumin (immunological release). In the absence of calcium all glycosides inhibited potassium uptake. Ouabain and digoxin enhanced the histamine release while digitoxigenin either had no effect or was slightly inhibitory. In the presence of calcium, the glycosides only affected potassium uptake and histamine release slightly. In the presence of lithium or lanthanum the enhancement of the histamine release was counteracted. Hydrophilic digitalis glycosides seem to enhance histamine release secondary to an increase in intracellular sodium. Lipophilic glycosides have no effect on the release.

Animals↗
PubMed1993

Activation of the Na+/K(+)-pump in rat peritoneal mast cells following histamine release: a possible role in cell recovery.

1. The activity of the Na+/K(+)-pump in rat peritoneal mast cells was measured at various time intervals after induction of cellular histamine release by compound 48/80 or by the antigen-antibody reaction. The Na+/K(+)-pump activity was assessed as the ouabain-sensitive potassium uptake of the cells using 86Rb+ as a tracer for potassium (K+(86Rb+)-uptake). 2. Stimulation of the cells with compound 48/80 induced a time and concentration dependent increase of the Na+/K(+)-pump activity. The pump activity was maximal 2 min after stimulation of the cells. Then, the activity gradually decreased and reached a level not significantly different from the controls after 2 h of incubation. 3. When the cells were stimulated by the antigen-antibody reaction, there was also a rapid (within 5 min) stimulation of the Na+/K(+)-pump. In contrast to the stimulation with compound 48/80, the pump activity returned to the control level after 60 min of incubation with antigen. 4. The ouabain-resistant potassium uptake of the cells was increased after stimulation of the cells, regardless of the secretagogue used. This probably reflects the increased surface area of the cells present after the histamine release. 5. On the basis of the present results, we suggest a role for the Na+/K(+)-pump in the recovery process of the mast cell following histamine release.

Animals↗
PubMed1992

[Measurement of intestinal blood supply in patients with suspected intestinal ischemia].

The object of the investigation was to illustrate the diagnostic yields of measurement of the intestinal blood supply before and after a test meal and of abdominal angiography recorded in patients in whom chronic intestinal ischaemia is suspected. A retrospective review including 18 patients (age range 36-79 years) was undertaken. The diagnosis of chronic intestinal ischaemia was established in four patients on the basis of measurement of the blood supply to the intestine and abdominal angiography and vascular reconstructive interventions could be performed. These interventions were technically successful in three cases. Control flow measurement was only performed in one patient after the operation. This showed normalized postprandial blood flow. By large, measurements of the blood supply to the intestine were free from complications. In cases of suspected chronic intestinal ischaemia, the combination of abdominal angiography and measurement of the blood supply to the intestine appear to supply the necessary information for selection of patients for vascular surgical interventions.

Abdominal Pain↗
PubMed1992

Ouabain enhancement of compound 48/80 induced histamine secretion from rat peritoneal mast cells: dependence on extracellular sodium.

Purified populations of rat peritoneal mast cells were used to study the effect of ouabain on compound 48/80-induced histamine secretion and on 86Rb+ uptake. 86Rb+ was used as a tracer for extracellular K+. The calculated value of the ouabain-sensitive uptake of K+ and 86Rb+ was considered a measure of the Na(+)-K+ pump activity of the cells. Ouabain caused an immediate inhibition of the pump activity and a time-dependent increase in histamine secretion in the absence of extracellular calcium. No effect on the secretion was observed in the presence of calcium. The effect of ouabain on the secretion occurs in the presence of sodium but not when sodium was replaced by lithium. Preservation by ouabain of a high intracellular sodium content in sodium-loaded cells was associated with preservation of the secretory response in a calcium-free medium. In the presence of lanthanum in a calcium-free medium, the pump activity was inhibited and the enhancement by ouabain of the secretion of histamine was blocked. A less marked inhibition of the pump was found in a calcium-free medium containing magnesium. The inhibition exerted by magnesium was concentration-dependent (0-5 mM) as was the counteraction of magnesium of the enhancement of ouabain of the secretion of histamine. These observations indicate that the enhancement by ouabain of the secretory response of mast cells preincubated in a calcium-free medium is associated with accumulation of sodium inside the cell. In addition to a decreased rate of sodium-calcium exchange caused by a decreased inward directed sodium gradient, the mechanism by which ouabain enhances the secretory response is likely to involve an increased binding of calcium to membrane binding sites.

Animals↗
PubMed1991

Differential effect of extracellular calcium on the Na(+)-K+ pump activity in intact polymorphonuclear leucocytes and erythrocytes.

The effect of extracellular calcium on the Na(+)-K+ pump activity in human polymorphonuclear leucocytes and erythrocytes was studied and compared with the activity in mixed peritoneal leucocytes from rats. While there was maximal decrease in the pump activity (25-30%) of leucocytes from both rat and human by calcium 0.6 mM, a concentration of 0.1 mM caused a substantial decrease indicating a high sensitivity for extracellular calcium. In contrast, calcium had no effect on the pump activity in erythrocytes. The effect of calcium on the pump activity in leucocytes may be due to regulation of the influx of sodium across the plasma membrane, since in human leucocytes calcium had no effect on the pump activity if the cells were loaded with sodium.

Animals↗
PubMed1990

[The mast cell].

A review is presented of the most important morphological and functional characteristics of the mast cell. The cell is ovoid and contains heparin-containing granules in the cytoplasm. These stain metachromatically. In addition to heparin, the granules contain histamine and other inflammatory mediators. The cell is localized perivascularly in the loose connective tissue. The mast cell secretes histamine by exocytosis when it is stimulated immunologically by binding of a specific antigen to IgE molecules in the cell membrane. Histamine secretion may also be induced by non-immunological stimulators such as polymeric amines, neuropeptides and calcium-ionophores. Calcium plays an important role in the secretory process. Immunological secretion of histamine requires the presence of extracellular calcium whereas secretion induced by polymeric amines and neuropeptides can utilize the intracellular calcium depots. Phosphatide inositides released from phospholipides in connection with cell activation release calcium from the intracellular depots and probably play a part in histamine secretion. In addition, the protein phosphorylization reactions catalized by proteinkinase C, probably contribute in the process of secretion. Finally, secretion of histamine depends upon the ATP content of the cell.

Animals↗
PubMed1990

Regulation of the Na(+)-K+ pump activity and estimation of the reserve capacity in intact rat peritoneal mast cells.

Evidence is provided that regulation of the Na(+)-K+ pump activity in rat peritoneal mast cells occurs mainly through stimulation of the pump from inside the plasma membrane by sodium. It is demonstrated that there is a large reserve capacity for the exchange of intracellular sodium with extracellular potassium in these cells. The maximal pump activity was estimated to be 3230 pmol/10(6) cells per min and Km for extracellular potassium was 1.5 mM.

Animals↗
PubMed1990

Reversal by EGTA of the enhanced secretory responsiveness of mast cells due to treatment with ouabain.

The effect of EGTA on the enhancement by ouabain of compound 48/80-induced secretion from mast cells was compared with the effect on the Na(+)-K+ pump activity. The time-dependent secretory enhancement by ouabain was blocked by addition of EGTA to the cell suspension concomitantly with the addition of ouabain, and EGTA caused a large increase in the pump activity. Addition of 10 microM EGTA to ouabain-treated cells stopped but did not reverse the enhancement. The experiments show that the effect of ouabain was due to changes in a calcium pool utilized in compound 48/80-induced secretion following changes in the Na+,K+ pump activity.

Animals↗
PubMed1990

Inhibition of Na(+) -K+ pump activity by divalent cations in intact peritoneal mast cells of the rat.

1. The inhibition by the divalent cations magnesium, barium and strontium and the trivalent ion lanthanum of the Na(+) -K+ pump in the plasma membrane of rat peritoneal mast cells was studied in pure mast cell populations by measurement of the ouabain-sensitive uptake of the radioactive potassium analogue, 86rubidium (86Rb+). 2. Exposure of the cells to magnesium induced a time- and concentration-dependent decrease in the ouabain-sensitive K+(86Rb+)-uptake of the cells without influencing the ouabain-resistant uptake. The time-dependent decrease was apparent after incubation of the cells for 10 min or more, but no decrease was observed after 2 min incubation when the cells are supposed to be loaded with sodium due to the cell isolation procedure. 3. Barium and strontium caused concentration-dependent decreases in the ouabain-sensitive K(+) -(86Rb+) -uptake of the cells but the ouabain-resistant uptake was not changed. Half maximum decrease in the ouabain-sensitive K+(86Rb+)-uptake was observed with 1.8 mM magnesium, 1.2mM barium and 0.7 mM strontium. 4. The trivalent ion lanthanum blocked almost completely the ouabain-sensitive K+(86Rb+)-uptake at a concentration of 1 microM as does 1 mM calcium. Combining either of these ions with magnesium had no further inhibitory effect on the ouabain-sensitive uptake. 5. In conclusion, in addition to the previously suggested modulation by calcium of the activity of the Na+ (-)K+ pump, evidence is provided in this investigation that the modulation may be a more general effect of divalent and polyvalent cations present in the extracellular space through their influence on the sodium permeability of the plasma membrane.

Animals↗
PubMed1989

[Use of helium spirometric pulmonary function tests by general practitioners at a hospital outpatient department].

The case records of 94 helium spirometric pulmonary function investigations on patients referred by their general practitioners to the clinical-physiological department, Svendborg Hospital during 1985 and 1986 are reviewed. In 35% of the cases, the diagnosis on referral was "dyspnoea of unknown origen". Half of the results of the investigation were abnormal and it is concluded that this investigation is suitable for differentiating the patients who have reduced ventilatory capacity as the reason for the dyspnoea. 11% of the material consists of patients with bronchial asthma. According to the literature, these patients could be monitored advantageously instead with current peak-flow measurements. 18% of the investigations were carried out on patients with chronic bronchitis. The authors consider that a single spirometric measurement should be replaced by current monitoring of the forced expiration in litres and the forced vital capacity. Investigations undertaken as part of assessment for pensioning constotuted 18%. It was apparent from a questionnaire investigation that the general practitioners obtained considerable information from the result of the investigation. This information was independent of the result of the investigation. The profits were greatest when the investigation resulted in alteration of medication than when this was not the case.

Adolescent↗
PubMed1989

Na+ -K+ pump activity in rat peritoneal mast cells: inhibition by extracellular calcium.

1. Pure populations of rat peritoneal mast cells were used to study cellular potassium uptake. The radioactive potassium analogue, 86rubidium, was used as a tracer for potassium for measurements of the activity of the cellular potassium uptake process. 2. The ouabain-sensitive and the ouabain-resistant potassium (86rubidium) uptake of mast cells incubated in the presence of calcium, 1 mmol l-1, were very low, 52 and 147 pmol per 10(6) cells min-1. 3. Calcium-deprivation of the cells uncovered a large capacity ouabain-sensitive potassium (86rubidium) uptake mechanism. The activity of the uptake mechanism was decreased by reintroduction of calcium into the cell suspension, and it was dependent on cellular energy metabolism, temperature and pH. 4. The potassium (86rubidium) uptake of mast cells incubated in a calcium-free medium occurs through an active and ouabain-sensitive mechanism that has the nature of an enzyme, and it is mediated by the Na+ -K+ pump located in the plasma membrane. It is demonstrated that the activity of the Na+ -K+ pump mechanism is inhibited by low concentrations of extracellular calcium (0.1-1.2 mmol l-1). The possibility is discussed that calcium-deprivation may increase the pump activity by increasing the permeability of the plasma membrane for Na+.

Animals↗