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Biomedical subjects

K Skajaa

Publications and source records attributed to K Skajaa.

At least 19 recordsLinked to original sources

Determination of isradipine and its pyridine metabolite in serum by capillary column gas chromatography with nitrogen-selective detection.

A relatively simple, sensitive and precise gas chromatographic method for the determination of isradipine, a calcium antagonist of the dihydropyridine type, and its main metabolite in serum is described. Using a one-step extraction procedure, a wide-bore column and a nitrogen-phosphorus detector, a limit of quantitation of 0.5 and 2.0 nM for isradipine and the metabolite was found. No interferences from several drugs were observed. The method was successfully used in a pharmacokinetic study in hypertensive women during pregnancy.

Calcium Channel Blockers

Serum relaxin as a potential marker for preterm labour.

OBJECTIVE: To determine whether high serum relaxin concentrations in the 30th week of pregnancy were associated with preterm labour. DESIGN: Case-control study. SETTING: Two antenatal clinics of the Department of Obstetrics and Gynecology University Hospital of Aarhus. SUBJECTS: A cohort of 991 women (82% of 1203 eligible) in the 30th week of pregnancy attending one of the two antenatal clinics. The cases comprised 23 (2.4%) women without pre-eclampsia or small for gestational age babies, who were delivered spontaneously before 37 completed weeks gestation. The control group of 46 women was randomly selected from the rest of the cohort, all of them were delivered at term. INTERVENTIONS: Blood samples were collected at 30 weeks gestation and stored for analysis. MAIN OUTCOME MEASURES: Serum relaxin concentrations estimated by ELISA technique, length of gestation at delivery. RESULTS: The mean serum relaxin concentrations in the 30th week of pregnancy was 455 (SD 169) pg/ml and 327 (SD 139) pg/ml in the cases and controls, respectively (P = 0.003, t test). In women with preterm delivery a negative correlation was found between relaxin concentration in the 30th week of pregnancy and the gestational age at parturition (r = -0.53, P = 0.02). CONCLUSION: High relaxin concentrations may be associated with preterm delivery but the present results need confirmation in large scale studies.

Biomarkers

Effects of the thromboxane-receptor antagonists AH 23848 and BM 13.177 on human uteroplacental arteries.

OBJECTIVE: We studied the effects of the thromboxane (Tx)A2-receptor antagonists AH 23848 and BM 13.177 in small isolated human uteroplacental arteries. METHODS: Fetal stem villous arteries and maternal intramyometrial arteries were dissected from placental specimens and from myometrial biopsies obtained at cesarean or from nonpregnant women after hysterectomy. Vascular ring preparations were prepared and mounted in organ baths, and isometric tension was recorded. RESULTS: AH 23848 produced competitive, concentration-dependent inhibition of responses to the TxA2-mimic U46619 in all vessel types tested. Mean (+/- standard error of the mean) pA2 values (the negative logarithm of the concentration of antagonist needed to double the half maximum response [EC50] value for U46619) were 8.69 +/- 0.16 in the stem villous arteries, 9.58 +/- 0.33 in intramyometrial arteries from term pregnant women, and 9.25 +/- 0.47 in intramyometrial arteries from nonpregnant women. In stem villous arteries, the pA2 value for BM 13.177 was 6.15 +/- 0.13, whereas these values in intramyometrial arteries could not be assessed. However, the concentrations needed to produce inhibition of U46619-induced contractions were considerably higher for BM 13.177 than for AH 23848. Both drugs inhibited responses to prostaglandin (PG)F2 alpha and PGE2 in stem villous arteries, while leaving responses to vasopressin in intramyometrial arteries unaffected. No differences in the effects of the two antagonists were found between intramyometrial arteries from nonpregnant and term pregnant women. CONCLUSIONS: Our results suggest that TxA2-receptor antagonists effectively inhibit responses to TxA2 in human uteroplacental arteries, and such drugs may represent an interesting therapeutic approach in preeclampsia.

Adult

Changes in serum electrolytes after transcervical resection of endometrium and submucous fibroids with use of glycine 1.5% for uterine irrigation.

OBJECTIVE: We evaluated the postoperative changes in serum electrolytes in relation to the amount of irrigating fluid absorption and the occurrence of nausea and vomiting after transcervical resection of endometrium and submucous fibroids. METHODS: From May 1989 to October 1991, 101 consecutive patients were operated on for menometrorrhagia with transcervical resection of endometrium and submucous fibroids using glycine 1.5% for uterine irrigation. The deficit of glycine was assessed during and at the end of the operation. During the postoperative course, attention was paid to the occurrence of cerebral confusion, nausea (defined by at least one incident of vomiting), and dyspnea. The serum levels of sodium, potassium, and chloride were assessed before the operation, at the end of the procedure, and after 4, 8, and 12 hours. RESULTS: No marked water intoxication or signs of volume overload were seen, but 33% of the patients had nausea and vomiting in the postoperative period. These patients showed a more pronounced postoperative decrease in serum sodium (P = .0001) and a larger glycine deficit (P = .004) than did patients without nausea. The postoperative decrease in serum sodium correlated significantly to the glycine deficit (R2 = 0.83, P less than .001). CONCLUSION: Postoperative hyponatremia after transcervical resection of the endometrium correlated with the deficit of irrigant fluid but not with the operation time or the total amount of irrigant fluid used. We recommend that serum sodium be controlled and corrected if necessary postoperatively in patients with nausea and vomiting.

Absorption

Influence of vehicle form on efficiency of prostaglandin E2 gel for cervical ripening.

A double-blind randomized controlled trial compared the efficiency of prostaglandin E2 (PGE2) gel in two different vehicle forms, one solid and the other more liquid, with respect to inducing labour in women with highly unfavourable cervical states. 43 received 0.5 mg PGE2 in a solid gel (Cerviprost) and 37 received 0.5 mg PGE2 in a more liquid cellulose-gel. After one application 18 (42%) and 9 (24%), respectively, went into labour (OR 2.8; 95% confidence interval: 0.8-6.0). After two applications of the gel 91 and 76%, respectively, were in active labour or had amniotomy performed as the cervical state had improved (OR 2.9; 95% confidence interval: 0.8-10.3). It is concluded that the solid gel was more efficient and safe than the more liquid gel.

Adult

Effects of magnesium and terbutaline on contractility and K+ uptake in isolated human uterine muscle.

Mg++ (3 and 6 mmol/L), the beta 2-adrenergic agonist terbutaline (1 and 10 mumol/L), and dibutyryl cyclic adenosine 5'-monophosphate (0.1 and 1 mmol/L) suppressed spontaneous activity and the increase in contractile activity induced by ouabain or K(+)-free buffer in isolated human pregnant myometrium. The ouabain-suppressible rubidium 86 or potassium 42 uptake was unaffected by the presence of Mg++ (3 and 6 mmol/L), the beta 2-adrenergic agonist terbutaline (1 and 10 mumol/L), or dibutyryl cyclic adenosine 5'-monophosphate (1 mmol/L). However, loading of the strips with Na+ and incubation in high K+ induced a fivefold increase in rubidium 86 uptake. On the basis of these flux rates, our previous data on the total concentration of sodium-potassium pumps in the human myometrium, and an estimated maximum transport rate of the sodium-potassium pump of 8900 K+ ions per minute at 30 degrees C, it could be calculated that the sodium-potassium pump in the Na(+)-loaded strips reached around 80% of its maximal rate. Taken together, these results showed that the relaxant effects of Mg++, terbutaline, and dibutyryl cyclic adenosine 5'-monophosphate on human myometrium are not due to a stimulation of active sodium-potassium transport.

Biological Transport

Placental abruption. A case-control investigation.

The course of pregnancy and labour, neonatal outcome and social circumstances, were compared between 87 women with placental abruption and a control group of 5697 women. First and second trimester haemorrhage, amniocentesis, congenital malformations, maternal smoking and a job involving much standing or walking were associated with placental abruption.

Abruptio Placentae

Magnesium intake and status and pregnancy outcome in a Danish population.

OBJECTIVE: To investigate the relation between pregnancy outcome and magnesium intake and status. DESIGN: A prospective observational study in which the estimate of nutrient intake and serum samples were obtained before the final outcome of pregnancy was known. A second part of the investigation was a cross-sectional comparison of magnesium status of normal pregnant women and women with certain pathological pregnancies. SETTING: Antenatal clinic associated to the University Clinic of Obstetrics and Gynaecology, University of Aarhus, Denmark. SUBJECTS: 1203 consecutive women in the 30th week gestation were invited to participate in the study, 991 (82.4%) accepted and records for 965 (80.2%) were available for analysis. DATA: Food intake data were collected by a combination of a self administered questionnaire and a structured interview of a dietary history type. Serum samples were obtained from blood withdrawn in the 30th and 37th week gestation. Obstetric data were collected from the midwifery and hospital records. For a second part of the investigation, biopsies from the uterus and the abdominal rectus muscle were obtained from women delivered by caesarean section. RESULTS: In the women with normal pregnancies and in the three groups of pathological pregnancies (pre-eclampsia, SGA-infants and preterm labour) the average magnesium intake was within the range of 200 to 208 mg per 1000 kcal per day (SD 32) and there were no differences between the groups. Neither were differences in serum magnesium observed. Birthweight for gestational age was not influenced by magnesium intake. No differences in magnesium status as assessed by determination of magnesium content in muscle biopsies were found between the normal pregnancies and women with pre-eclampsia, SGA-infants or preterm labour. CONCLUSION: The intake of magnesium seemed adequate, and pre-eclampsia, SGA-infants, or preterm labour did not seem associated with a low dietary intake of magnesium or magnesium deficiency. Routine magnesium supplementation during pregnancy is not recommended for populations of relative good socio-economic status.

Adult

Effects of vasodilators on isolated human uteroplacental arteries.

The effects of the vasodilator drugs hydralazine, labetalol, prazosin, and nitrendipine were studied on responses to K+ (124 mmol/L), noradrenaline, vasopressin, and angiotensin II in small human maternal intramyometrial arteries and on responses to K+, prostaglandin (PG) F2 alpha, and angiotensin II in fetal stem villous arteries. The vessels were dissected from biopsy specimens obtained during term cesareans and mounted in organ baths. Hydralazine failed to inhibit responses to any of the agonists tested in the fetal and maternal arteries. Labetalol and prazosin decreased responses to noradrenaline but did not affect contractions induced by the other agonists in maternal arteries. In fetal arteries, which did not respond to noradrenaline, no effects of labetalol and prazosin were found. Nitrendipine inhibited responses to all the agonists tested in maternal arteries. In fetal preparations, the drug decreased responses to K+ and PGF2 alpha but did not affect contractions induced by angiotensin II. Vasodilator drugs applied for treatment of pregnancy-induced hypertension show differential effects on human maternal and fetal uteroplacental arteries, depending on their mode of action and the agonists responsible for the contractile activation in these vessels.

Angiotensin II

[Complications caused by intrauterine contraceptive devices].

During the period 1981-1982, IUDs were introduced in 1,697 women in the Advisory Clinic for Contraception in the County of Arhus. The course in a period of six years after this was investigated retrospectively in view of the frequencies of complications. A total of 459 IUDs were either lost or had to be removed on account of haemorrhage/pain, infection or pregnancy. Where all types of complications were concerned, higher frequencies of complications were encountered in the younger age groups and in nulliparous women. The dependence of the frequency of complications on the age of the patients was most marked among women who had borne children previously. In the total population, 29% of the women had the IUD removed within a period of three years. In women under the age of 20 years, 45% were removed and, in women over the age of 35 years, only 18% were removed during the same period. The total pregnancy risk was 2.7/100 women after use for two years and 3.2/100 women after three years. In contrast to this, the risk in women under 20 years was 6.6/100 women and 10.8/100 women after use for two and three years, respectively. On account of a high frequency of infection, increased tendency to extrusion and poor effectivity, the use of IUDs in young nulliparous women is not recommended.

Adult

Effects of magnesium and isradipine on contractile activation induced by the thromboxane A2 analog U46619 in human uteroplacental arteries in term pregnancy.

The effects of Mg++ and the dihydropyridine calcium channel blocker isradipine on contractions induced by the thromboxane A2 mimetic U46619 were studied in isolated human uteroplacental arteries. In all preparations investigated U46619 10(-10) to 10(-6) mol/L induced concentration-related contractile responses. In maternal vessels U46619 produced a biphasic concentration-response curve, whereas the compound in fetal vessels produced a sigmoid concentration-response curve parallel to that of prostaglandin F2 alpha. Mg++ (1.0 to 6.0 mmol/L) and isradipine (10(-10) to 10(-5) mol/L) both relaxed U46619-induced contractions by up to about 40%. In preparations precontracted by U46619 and exposed to isradipine 10(-6) mol/L, addition of Mg++ 6.0 mmol/L consistently produced a further small relaxation. Removal of the endothelium or pretreatment with indomethacin 10(-6) mol/L or digoxin 10(-6) mol/L did not influence the inhibition produced by Mg++ or isradipine. In vessels pretreated in Ca(++)-free medium Mg++ 6.0 mmol/L depressed and isradipine abolished responses to Ca++ (0.01 to 4.0 mmol/L) after depolarization with K+ 124 mmol/L. In maternal and fetal arteries stimulated with U46619, however, Mg++ 6.0 mmol/L and isradipine 10(-6) mol/L produced a similar, partial inhibition of responses to Ca++ (0.01 to 4.0 mmol/L). Mg++ seems to inhibit transmembrane Ca++ influx, although less efficiently than the dihydropyridine calcium antagonist isradipine. In addition, Mg++ may interfere with Ca++ at intracellular binding sites. Provided that preeclampsia comprises enhanced vascular actions of thromboxane A2, the present results support the established use of Mg++ in the treatment of this condition and suggest that calcium antagonists are of potential benefit.

Antihypertensive Agents

No effect of intralesional injection of interferon on moderate cervical intraepithelial neoplasia.

Women with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN 2) were treated in a double blind investigation of treatment with intralesioneal interferon alpha-2b (Intron a). Before treatment commenced, the existence and the types of human papilloma-virus (HPV) were assessed in [35S] methionine-labelled cervical biopsies by the determination of specific protein markers. Pronounced side effects occurred in all the women treated with interferon and the trial was stopped when it became apparent that there were no obvious beneficial effects. No positive benefits of interferon treatment were detected on either the CIN 2 or on the persistence of HPV types. It is concluded that intralesioneal injection of interferon has no place in the treatment of CIN.

Adult

The concentration of ouabain binding sites in biopsies of uterine muscle.

The concentration of Na, K-ATPase in biopsies of uterine muscle was determined by measurement of [3H]ouabain binding in the presence of vanadate. For this purpose a method previously described for skeletal muscle (Nørgaard et al. 1983) was modified. Biopsies were obtained from uterine muscle from pregnant women (during caesarian section), non-pregnant women (during hysterectomy) and from adult, non-pregnant guinea-pigs and rats. The ouabain binding site concentration in uterine muscle of the pregnant women averaged 72 +/- 2 pmol g-1 wet wt (n = 8), with an apparent dissociation constant (KD) for ouabain of 3 x 10(-9) mol l-1. The ouabain-binding capacity in uterine muscle of the non-pregnant women amounted to 83 +/- 9 pmol g-1 wet wt (n = 8). In uterine muscle of the guinea-pig, two populations of ouabain binding sites were observed: one with a maximum binding capacity of 230 pmol g-1 wet wt and an apparent KD of 1.6 x 10(-6) mol l-1, and one with a maximum capacity of 62 pmol g-1 wet wt and an apparent KD of 5 x 10(-8) mol l-1. Immediate freezing of the biopsies in liquid N2 and storage at -60 degrees C for up to 6 weeks caused no change in ouabain-binding capacity. The dry weight/wet weight ratio of the samples from different subjects showed values of around 20%. It is concluded that the concentration of Na-K pumps in human uterine muscle can be quantified by [3H]ouabain binding using samples weighing 5-10 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of magnesium on isolated human fetal and maternal uteroplacental vessels.

The effects of Mg2+ were studied in human umbilical arteries, stem villous arteries and maternal intramyometrial arteries. The vessels were dissected and mounted in organ baths, and isometric tension was recorded. In all fetal preparations investigated, Mg2+ (0.5-6.0 mM) in a concentration-related way decreased pD2 values for prostaglandin F2 alpha responses. The maximum response to prostaglandin F2 alpha was depressed in umbilical arteries, but remained unaffected in stem villous artery preparations. In stem villous arteries pretreated in Ca2(+)-free medium, increasing concentrations of Mg2+ markedly depressed the response to Ca2+ after stimulation with K+ or prostaglandin F2 alpha, suggesting that Mg2+ inhibited transmembrane calcium influx and interfered with intracellular calcium effects. In both stem villous and intramyometrial arteries, increasing concentrations of Mg2+ increased EC50 values for responses to K+, whereas Emax values were unaffected. Mg2+ produced relaxation of agonist-induced contractions by up to 60% in stem villous arteries and up to 40% in intramyometrial artery preparations. The relaxant effect of Mg2+ did not seem to be mediated through the endothelium or through changes in the synthesis of prostanoids, since endothelial disruption and treatment with indomethacin left the responses to Mg2+ unaffected. Relaxation of vessels important for resistance regulation in the human uteroplacental vascular bed may be of benefit when uteroplacental blood flow is impaired, and the present results support the established use of magnesium sulphate in the treatment of pre-eclampsia.

Arteries

Incidence of lesions of the saphenous nerve after partial or complete stripping of the long saphenous vein.

To find out whether the usual total stripping of the long saphenous vein in operations for varicose veins could be replaced by a less traumatic removal of only the femoral part of the vein, a randomised prospective study was carried out in 163 consecutive patients, of whom 157 were evaluable. Group A (n = 80) had total stripping and group B (n = 77) had partial stripping (extraction of the long saphenous vein from the groin to immediately below the knee). The two groups, which were comparable, were assessed three months after operation when 75 in group A (94%) and 75 in group B (97%) had excellent or good relief of symptoms and comparable absence of residual varicosities. Lesions of the saphenous nerve were found in 31 in group A (39%) and 5 in group B (7%) (p less than 0.001). There were few other complications. We conclude that preservation of the distal long saphenous vein not only reduces nerve damage, but also retains enough vein for use should coronary artery bypass or peripheral vascular grafting be necessary in future.

Adult

[Magnesium and long-term diuretic therapy].

Thiazides and loop diuretics, facilitate the loss of Mg and K resulting in increased excretion in the urine. Although serum-K and serum-Mg values in patients receiving long-term treatment for hypertension or incompensated heart disease usually are normal, muscle-Mg and muscle-K contents are reduced in around 50% of these patients. Mg deficiency increases K loss and K/Mg deficiencies are frequently observed simultaneously. K repletion is often difficult if the accompanying Mg deficiency is not corrected simultaneously. The K/Mg loss from the muscles is accompanied by reduced concentration of Na,K-pumps. These disturbances may produce muscle symptoms, increased sensitivity to digitalis, inhibition of growth and possibly arrhythmias. Evaluation of the K and Mg status during diuretic treatment should be preferentially based on tissue determinations. The muscle biopsy method is rapid, reliable and may reveal conditions of deficiency. In several cases, oral supplements of Mg have proved to be adequate to restore the normal K/Mg status.

Benzothiadiazines

Reduced concentrations of potassium, magnesium, and sodium-potassium pumps in human skeletal muscle during treatment with diuretics.

Animal studies have shown that potassium depletion induced by diuretics or potassium deficient fodder leads to a selective decrease in the concentrations of potassium and in the concentration of sodium-potassium pumps in skeletal muscle. In 25 patients who had received diuretics for 2-14 years the mean concentrations of potassium, magnesium, and sodium-potassium pumps were measured in skeletal muscle biopsy specimens and were significantly lower than in those from a group of age matched controls. The reductions in all three variables were significant in those patients receiving diuretics for arterial hypertension as well as in those being treated for congestive heart failure. In 14 patients the mean muscle potassium concentration was below the control range, but only one of those was hypokalaemic (3.4 mmol/l), and 13 were receiving potassium supplements. In 15 patients the mean muscle magnesium concentration was below normal, and the mean muscle potassium and magnesium concentrations showed a linear correlation. In 12 patients in whom the mean muscle potassium concentration was below 80 mumol/g wet weight there was a linear correlation between the cellular potassium:sodium ratio and the concentration of 3H-ouabain binding sites indicating that potassium deficiency also leads to a down regulation of sodium-potassium pumps in human skeletal muscle. In spite of potassium supplements long term treatment with diuretics may lead to potassium and magnesium deficiencies, which are not detectable using the standard methods of serum analysis. The changes in concentrations of electrolytes and sodium-potassium pumps associated with treatment with diuretics may impair muscle function and potassium homoeostasis and interfere with the distribution of digitalis glycosides.

Adult

Hemoglobin and hematocrit as risk factors in below-the-knee amputation for incipient gangrene.

The relationship between complication rate and preoperative levels of hemoglobin and hematocrit was investigated in 186 consecutive below-the-knee amputations for incipient gangrene. Arteriosclerotic amputations had successively higher rates of wound complications and reamputation with increasing hemoglobin and hematocrit. No such association was found among diabetics. Thus, hemoglobin greater than or equal to 7.0 mmol/l and hematocrit greater than or equal to 40 were significant preoperative risk factors in below-the-knee amputation for arteriosclerotic incipient gangrene.

Aged