[Evaluation of surgical interventions in Denmark].
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Clinical Competence↗
Biomedical subjects
T Krarup
Publications and source records attributed to T Krarup.
New QC process validates new blood gas technology at each measurement.
NPT7, developed by Radiometer Medical, Copenhagen, Denmark, is a blood gas analyzer optimized for the near-patient setting. The analyzer is based on dry, optical technologies and single-use cuvettes. The quality of each individual measurement is validated by a new approach to internal quality control, which has been named QualityGuard. This paper provides an overview of QualityGuard and, using the pCO2 measurement as an example, describes how the different elements of QualityGuard manages the quality control of the NPT7 itself, and of the quality of a measurement.
Blood Gas Analysis↗
No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucose.
AIMS: It has previously been shown that intravenous and subcutaneous administration of glucagon-like peptide (GLP)-1 concomitant with intravenous glucose results in reactive hypoglycaemia in healthy subjects. Since GLP-1 is also effective in Type 2 diabetic patients and is presently being evaluated as a therapeutic agent in this disease, it is important to investigate whether GLP-1 can cause hypoglycaemia in such patients. METHODS: Eight Type 2 diabetic patients (age 54 (49-67) years; body mass index 31 (27-38) kg/m2; HbA1c 9.4 (7.0-12.5)%) and seven matched non-diabetic subjects (HbA1c 5.5 (5.2-5.8)%, fasting plasma glucose 5.4 (5.0-5.7) mmol/l) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body weight (maximally tolerated dose), and 15 min later, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. RESULTS: Hypoglycaemia with a PG at or below 2.5 mmol/l was seen in five of the seven healthy subjects after 60-70 min, but PG spontaneously increased again, reaching 3.7 (3.3-4.0) mmol/l at 90 min. In the patients, PG fell slowly and stabilized at 8.6 (4.2-12.1) mmol/l after 80 min. In both groups, glucagon levels initially decreased, but later increased, exceeding basal levels in healthy subjects, in spite of persistent, high concentrations of GLP-1 (P < 0.02). CONCLUSIONS: Subcutaneous GLP-1 plus intravenous glucose induced reactive hypoglycaemia in healthy subjects, but not in Type 2 diabetic patients. Therefore, a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycaemia in Type 2 diabetes mellitus.
Aged↗
Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.
Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unknown whether hypoglycemic drug therapy can modulate this abnormality. We studied patients with type 2 diabetes and stable ischemic heart disease (n = 28) and lean, healthy control subjects (n = 31). Forearm blood flow was measured by venous occlusion plethysmography during dose-response studies of acetylcholine (ACh) and sodium nitroprusside (SNP) infused into the brachial artery. In the patients and 10 healthy control subjects, ACh was repeated after intrabrachial infusion of insulin. Patients were restudied after 2 months of insulin therapy with four daily subcutaneous injections (treatment group, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high physiological levels (133 +/- 14.6 mU/l in patients) with a minor increase in systemic venous serum insulin. This increased the ACh response by 149 +/- 47, 110 +/- 33, 100 +/- 45, and 106 +/- 44% during the four ACh doses in healthy control subjects (P < 0.0001) but had no effect in patients (P = 0.3). After 2 months, HbA(1c) in the treatment group had decreased from 10.0 +/- 0.4 to 7.5 +/- 0.2%. Although neither the ACh response (P = 0.09) nor the SNP response (P = 0.4) had changed significantly, insulin stimulation had a significant effect, as the ACh response increased by 58 +/- 25, 84 +/- 66, 120 +/- 93, and 69 +/- 36% (P = 0.0002). In the time control group, insulin stimulation remained without effect after 8 weeks (P = 0.7). In conclusion, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.
Acetylcholine↗
Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients.
Incretin hormones importantly enhance postprandial insulin secretion but are rapidly degraded to inactive metabolites by ubiquitous dipeptidyl peptidase IV. The concentrations of the intact biologically active hormones remain largely unknown. Using newly developed assays for intact glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP), we measured plasma concentrations after a mixed breakfast meal (566 kcal) in 12 type 2 diabetic patients (age 57 years [range 49-67], BMI 31 kg/m2 [27-38], and HbA1c 9.2% [7.0-12.5]) and 12 matched healthy subjects. The patients had fasting hyperglycemia (10.7 mmol/l [8.0-14.8]) increasing to 14.6 mmol/l (11.5-21.5) 75 min after meal ingestion. Fasting levels of insulin and C-peptide were similar to those of the healthy subjects, but the postprandial responses were reduced and delayed. Fasting levels and meal responses were similar between patients and healthy subjects for total GIP (intact + metabolite) as well as intact GIP, except for a small decrease in the patients at 120 min; integrated areas for intact hormone (area under the curve [AUC]INT) averaged 52 +/- 4% (for patients) versus 56 +/- 3% (for control subjects) of total hormone AUC (AUC(TOT)). AUC(INT) for GLP-1 averaged 48 +/- 2% (for patients) versus 51 +/- 5% (for control subjects) of AUC(TOT). AUC(TOT) for GLP-1 as well as AUC(INT) tended to be reduced in the patients (P = 0.2 and 0.07, respectively); but the profile of the intact GLP-1 response was characterized by a small early rise (30-45 min) and a significantly reduced late phase (75-150 min) (P < 0.02). The measurement of intact incretin hormones revealed that total as well as intact GIP responses were minimally decreased in patients with type 2 diabetes, whereas the late intact GLP-1 response was strongly reduced, supporting the hypothesis that an impaired function of GLP-1 as a transmitter in the enteroinsular axis contributes to the inappropriate insulin secretion in type 2 diabetes.
Aged↗
Long-term remission of transitional cell carcinoma after Bacillus Calmette-Guerin instillation in the renal pelvis.
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Administration, Intravesical↗
High frequency of sub-optimal semen quality in an unselected population of young men.
Male reproductive function seems to have deteriorated considerably during the past 4-5 decades. However, studies of the reproductive function in unselected populations have not previously been reported. As the large majority of young men in Denmark are subjected to a compulsory medical examination for military service, this provided a unique opportunity to study the reproductive function in an unbiased population. Altogether 891 young men delivered a blood sample in which reproductive hormones were measured. From 708 of these men data were also obtained on semen quality and testis size. The median sperm concentration was 41 x 10(6)/ml (mean 57.4 x 10(6)/ml). Men with ejaculation abstinence above 48 h had slightly higher sperm concentrations (median 45 x10(6)/ml, mean 63.2 x 10(6)/ml), but even in this subgroup, 21 and 43% respectively had sperm counts below 20 x 10(6)/ml and 40 x 10(6)/ml. Among men with no history of reproductive diseases and a period of abstinence above 48 h, as many as 18 and 40% respectively had concentrations below 20 and 40 x 10(6)/ml. Sperm counts were positively correlated with testis size, percentage normal spermatozoa and inhibin B, and negatively correlated with percentage immotile spermatozoa and follicle stimulating hormone. Possible causes for this high frequency of young men with suboptimal semen quality are obscure and need to be explored. Whether these findings apply for young male populations of comparable countries remains to be seen.
Analysis of Variance↗
Evaluation of beta-cell secretory capacity using glucagon-like peptide 1.
OBJECTIVE: Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first compared the effects of intravenous bolus injections of 2.5, 5, 15, and 25 nmol GLP-1 with glucagon (1 mg intravenous) and a standard meal (566 kcal) in 6 type 2 diabetic patients and 6 matched control subjects. Next, we studied another 6 patients and 6 control subjects and, in addition to the above procedure, performed a combined glucose plus GLP-1 stimulation, where plasma glucose was increased to 15 mmol/l before injection of 2.5 nmol GLP-1. Finally, we compared the insulin response to glucose plus GLP-1 stimulation with that observed during a hyperglycemic arginine clamp (30 mmol/l) in 8 patients and 8 control subjects. RESULTS: Peak insulin and C-peptide concentrations were similar after the meal, after 2.5 nmol GLP-1, and after glucagon. Side effects were less with GLP-1 than with glucagon. Peak insulin and C-peptide concentrations were as follows (C-peptide concentrations are given in parentheses): for patients (n = 12): meal, 277 +/- 42 pmol/l (2,181 +/- 261 pmol/l); GLP-1 (2.5 nmol), 390 +/- 74 pmol/l (2,144 +/- 254 pmol/l); glucagon, 329 +/- 50 pmol/l (1,780 +/- 160 pmol/l); glucose plus GLP-1, 465 +/- 87 pmol/l (2,384 +/- 299 pmol/l); for control subjects (n = 12): meal, 543 +/- 89 pmol/l (2,873 +/- 210 pmol/l); GLP-1, 356 +/- 51 pmol/l (2,001 +/- 130 pmol/l); glucagon, 420 +/- 61 pmol/l (1,995 +/- 99 pmol/l); glucose plus GLP-1, 1,412 +/- 187 pmol/l (4,391 +/- 416 pmol/l). Peak insulin and C-peptide concentrations during the hyperglycemic arginine clamp and during glucose plus GLP-1 injection were as follows: for patients: 475 +/- 141 pmol/l (2,295 +/- 379 pmol/l) and 816 +/- 268 pmol/l (3,043 +/- 508 pmol/l), respectively; for control subjects: 1,403 +/- 308 pmol/l (4,053 +/- 533 pmol/l) and 2,384 +/- 452 pmol/l (6,047 +/- 652 pmol/l), respectively. CONCLUSIONS: GLP-1 (2.5 nmol = 9 microg) elicits similar secretory responses to 1 mg glucagon (but has fewer side effects) and a standard meal. Additional elevation of plasma glucose to 15 mmol/l did not enhance the response further. The incremental response was similar to that elicited by arginine, but hyperglycemia had an additional effect on the response to arginine.
Aged↗
[Essential testodynia].
Testodynia can be defined as long-lasting or recurrent testicular pain in younger men with no physical disease in their scrotal contents. The condition is suggested as a psychosomatic disease caused by any unrealized or unsolved existential problem leading to a chronic psychological stress reaction. The stress causes alpha 1-receptor mediated contraction of smooth muscle in the vas deferens and epididymis. The pain arises due to the muscle spasm or sperm obstruction. The therapy is a combination of psychotherapy and alpha 1-receptor blocking agents.
Adult↗
[Evaluation of blood loss and absorption of irrigating fluid in transurethral resection of the prostate].
A questionnaire was sent to all Danish departments performing transurethral resection of the prostate (TUR-P) concerning the use of irrigating fluids and methods to estimate peroperative blood loss and absorption of irrigating fluid. Fifty-six of 60 departments used glycine as an irrigant. Seventeen percent of the departments measured blood loss peroperatively (HemoCue). Only two departments (3%) measured absorption of irrigating fluid quantitatively by the expired breath ethanol method. The other departments estimated blood loss and absorption of irrigant from the colour of the irrigating fluid. From studies of the literature we suggest the use of sorbitol/mannitol as irrigating fluid instead of glycine, as this may have fewer adverse effects, and we recommend quantitative measurements of blood loss and absorption of irrigating fluid to minimise the potentially dangerous consequences of TUR-P.
Blood Loss, Surgical↗
Biologic variability of prostate-specific antigen and its usefulness as a marker for prostate cancer: effects of finasteride. Finasteride PSA Study Group.
OBJECTIVES: The effects of finasteride on prostate-specific antigen (PSA) variability and usefulness in prostate cancer detection were examined. METHODS: Percent change and crossover of PSA levels between the low (1.0 to 3.9 ng/mL) and high (4.0 to 10.0 ng/mL) ranges were evaluated in 72 men with benign prostatic hyperplasia (BPH) and 77 men with both BPH and prostate cancer (PCa) treated with finasteride or placebo for 6 months. Patients with PCa were studied as a model for evaluating the effects on PSA levels in patients with BPH and latent PCa. As recommended on the product label, PSA levels for finasteride-treated patients were doubled for interpretation. RESULTS: In patients with BPH, most placebo- and finasteride-treated patients with low PSA levels at baseline had subsequent PSA levels below 4.0 ng/mL throughout the study. Among patients with high baseline PSA levels, only 1 of 17 finasteride-treated patients, compared with 8 of 13 placebo-treated patients, crossed into the low range. In the BPH/PCa study, most placebo-treated patients maintained PSA levels in the same range (15 of 19 less than 4.0 ng/mL; 14 of 16 greater than 4.0 ng/mL). Almost one third of finasteride-treated patients with low PSA levels at baseline crossed into the high range (8 of 22), whereas most patients with high PSA levels at baseline were not masked with treatment, with PSA levels remaining high (12 of 15). CONCLUSIONS: PSA levels cross between the low and high PSA ranges in both finasteride- and placebo-treated patients with BPH and those with both BPH and PCa. Doubling the PSA levels in finasteride-treated patients allows appropriate interpretation of PSA values and does not mask the detection of PCa.
Adult↗
Na+-K+-2Cl- cotransport in Ehrlich cells: regulation by protein phosphatases and kinases.
To identify protein kinases (PK) and phosphatases (PP) involved in regulation of the Na+-K+-2Cl- cotransporter in Ehrlich cells, the effect of various PK and PP inhibitors was examined. The PP-1, PP-2A, and PP-3 inhibitor calyculin A (Cal-A) was a potent activator of Na+-K+-2Cl- cotransport (EC50 = 35 nM). Activation by Cal-A was rapid (<1 min) but transient. Inactivation is probably due to a 10% cell swelling and/or the concurrent increase in intracellular Cl- concentration. Cell shrinkage also activates the Na+-K+-2Cl- cotransport system. Combining cell shrinkage with Cal-A treatment prolonged the cotransport activation compared with stimulation with Cal-A alone, suggesting PK stimulation by cell shrinkage. Shrinkage-induced cotransport activation was pH and Ca2+/calmodulin dependent. Inhibition of myosin light chain kinase by ML-7 and ML-9 or of PKA by H-89 and KT-5720 inhibited cotransport activity induced by Cal-A and by cell shrinkage, with IC50 values similar to reported inhibition constants of the respective kinases in vitro. Cell shrinkage increased the ML-7-sensitive cotransport activity, whereas the H-89-sensitive activity was unchanged, suggesting that myosin light chain kinase is a modulator of the Na+-K+-2Cl- cotransport activity during regulatory volume increase.
Animals↗
[Pressure pneumothorax after intercostal blockade].
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Humans↗
Biologic variability of prostate-specific antigen and its usefulness as a marker for prostate cancer: effects of finasteride. The Finasteride PSA Study Group.
OBJECTIVES: The effects of finasteride on prostate-specific antigen (PSA) variability and usefulness in prostate cancer detection were examined. METHODS: Percent change and crossover of PSA levels between the low (1.0 to 3.9 ng/mL) and high (4.0 to 10.0 ng/mL) ranges were evaluated in 72 men with benign prostatic hyperplasia (BPH) and 77 men with both BPH and prostate cancer (PCa) treated with finasteride or placebo for 6 months. Patients with PCa were studied as a model for evaluating the effects on PSA levels in patients with BPH and latent PCa. As recommended on the product label, PSA levels for finasteride-treated patients were doubled for interpretation. RESULTS: In patients with BPH, most placebo- and finasteride-treated patients with low PSA levels at baseline had subsequent PSA levels below 4.0 ng/mL throughout the study. Among patients with high baseline PSA levels, only 1 of 17 finasteride-treated patients compared with 8 of 13 placebo-treated patients crossed into the low range. In the BPH/PCa study, most placebo-treated patients maintained PSA levels in the same range (15 of 19 less than 4.0 ng/mL; 14 of 16 greater than 4.0 ng/mL). Almost one third of finasteride-treated patients with low PSA levels at baseline crossed into the high range (8 of 22), whereas most patients with high PSA levels at baseline were not masked with treatment, with PSA levels remaining high (12 of 15). CONCLUSIONS: PSA levels cross between the low and high PSA ranges in both finasteride- and placebo-treated patients with BPH and those with both BPH and PCa. Doubling the PSA levels in finasteride-treated patients allows appropriate interpretation of PSA values and does not mask the detection of PCa.
Adult↗
[On the response "The scientific basis for the assessment of medical technology"].
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Denmark↗
Occlusion of K+ in the Na+/K+/2Cl- cotransporter of Ehrlich ascites tumor cells.
Proteins of n-octyl glucoside solubilized membrane vesicles derived from Ehrlich ascites tumor cells can occlude 86Rb+.K+ displaces 86Rb+ and it is assumed that 86Rb+ can be used as a tracer to measure K+ occlusion. The following observations indicate that the Na+/K+/2Cl- cotransporter is responsible for this occlusion: (1) Na+ does not compete for the K+ binding site, but rather stimulates 86Rb+ occlusion. (2) K+ occlusion saturates with increasing [Na+] and [K+], the respective K0.5 values being 50 +/- 7 microM for Na+ and 371 +/- 63 microM for K+. (3) Preincubation with 1 mM ouabain does not inhibit 86Rb+ occlusion, arguing against the Na+/K+-ATPase as being responsible for the occlusion. This notion is supported by the K0.5 value for K+ being higher than reported for Na+/K+-ATPase and by the stimulatory effect of Na+. (4) The K+ occlusion is sensitive to [Cl-], and the occluded ion is protected by the presence of bumetanide during cation exchange chromatography. Our results suggest that occlusion measurements of substrate ions could be a profitable way to study the ion binding mechanism(s) of the Na+/K+/2Cl- cotransporter.
Animals↗
[Clinical consequences of intranasal insulin therapy in insulin-dependent diabetes mellitus].
Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control, assessed by haemoglobin A1c concentrations, deteriorated after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosal physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time.
Administration, Intranasal↗
Reconstitution of calyculin-inhibited K-Cl cotransport in dog erythrocyte ghosts by exogenous PP-1.
Osmotic swelling of dog and other mammalian erythrocytes activates Cl-dependent K transport, K-Cl cotransport. This activation can be abolished by nanomolar concentrations of calyculin, a potent inhibitor of serine-threonine protein phosphatases. Therefore, K-Cl cotransport is probably activated by dephosphorylation by a type 1 and/or type 2A protein phosphatase (PP-1 and PP-2A, respectively). This was tested directly by incorporating exogenous protein phosphatases into resealed ghosts made from dog erythrocytes previously exposed to calyculin. K-Cl cotransport was nearly completely inhibited in the ghosts. Incorporation of PP-1 reconstituted K-Cl cotransport. Maximal reconstitution was up to 90% of the control flux in the ghosts and 0.1 U PP-1/ml lysate gave half-maximal reconstitution of cotransport. In contrast, PP-2A had no effect. This result with PP-1 provides direct evidence that K-Cl cotransport is activated by PP-1 in dog erythrocytes. Half-maximal activation of K-Cl cotransport required approximately 180 molecules of PP-1 per ghost.
Animals↗