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In 13 patients with severe pre-eclampsia mean serum concentrations of cationic trypsinogen and amylase were statistically significantly higher at 64 ng/ml and 1.6 mumol/l, respectively, than the corresponding mean serum concentrations in 30 normal pregnancies, 22 ng/ml and 1.1 mumol/l respectively. These rises exceeded the expected increased values due to the slight reduction of the renal function in the pre-eclamptic patients, and therefore indicate a concomitant injury of the pancreas.

Fivehundred and eighty consecutive breech births during the period 1972-79 were analvsed for factors associated with neonatal mortality. The overall neonatal mortality in breech deliveries in this series of cases was 4.1%. Multivariate analyses (logistic regression) selected only 4 of 56 variables tested as significant (p less than 0.05) risk factors for neonatal death. The overall most important risk factor was low birth weight (p less than 0.0001). In addition, diabetes in the mother, malformations, and Apgar score 5 min less than 7 increased the risk of neonatal death. Cesarean section was carried out in 8.1% during the period 1972-75, but increased to 32.6% from 1976-79 without any reduction in neonatal mortality. Neonatal mortality figures were not significantly improved for infant delivered by cesarean section compared with those born vaginally.

The thromboplastin activity in blood monocytes was investigated in third-trimester pregnancies comprising 11 patients with severe pre-eclampsia, 10 with essential hypertension and 18 normal pregnancies. Thromboplastin activity in unstimulated monocytes from the severe pre-eclamptic group was on average three times that found in the normal pregnant group, but variation was wide and the differences were not statistically significant. Thromboplastin activity in endotoxin-stimulated monocytes was significantly higher in the severe pre-eclamptic group than in the other two groups (normal and chronic hypertensive). In the severe pre-eclamptic group, there was a significant negative linear correlation between thromboplastin activity of the endotoxin-stimulated monocytes and factor VII. Fibrinogen, factor VII and alpha 2-antiplasmin were significantly lower in the severe pre-eclamptic group than in the normal pregnant group, whereas no differences were observed in factors V, VIII, AT-III and prekallikrein.

The thromboplastin activity in blood monocytes from 18 normal third trimester pregnant women has been compared with a group of 20 healthy non-pregnant women. The thromboplastin activity in unstimulated monocytes from the normal pregnant group was on average 40% of the activity in the non-pregnant group (P less than 0.01). In endotoxin stimulated monocytes, the thromboplastin activity was also significantly lower in the pregnant group as compared to the non-pregnant group (P less than 0.001). Fibrinogen and factors V, VII and VIII were significantly higher in the pregnant than in the non-pregnant group, whereas no difference was observed in AT-III, prekallikrein and alpha 2-antiplasmin levels.

Arterial and venous plasma catecholamines were measured in 13 pre-eclamptic and 13 normotensive pregnant women. In the pre-eclamptic group, arterial concentrations were higher for adrenaline (p less than 0,001), noradrenaline (p less than 0.05) and dopamine (p less than 0.01) than in the normotensive group, whereas in venous plasma only adrenaline (p less than 0.01) and dopamine levels were higher (p less than 0.05). Arterial adrenaline concentrations in the pre-eclamptic group were, on average, three times as high as normotensive arterial adrenaline. The arterial-venous (a-v) differences were higher for adrenaline (p less than 0.001) and dopamine (p less than 0.05) in the pre-eclamptic than in the normotensive group. In the pre-eclamptic group, arterial adrenaline was correlated with mean arterial blood pressure (r = 0.89, p less than 0.001) and with increased heart rate (r = 0.78, p less than 0.01). According to these results, both sympathetic nervous and sympathetic adrenal activities are increased in patients with pre-eclampsia.

Fluid transport between the plasma and interstitial fluid compartment is governed by the Starling forces, i.e. the capillary pressure (Pc), interstitial fluid hydrostatic pressure (Pi) and colloid osmotic pressure in plasma (COPp) and interstitial fluid (COPi). The COPp, COPi and Pi were measured in 10 normal pregnant women in the first and 10 women in the third trimester of pregnancy. Interstitial fluid was collected from subcutaneous tissue by implanted wicks and Pi was measured by the 'wick-in-needle' technique. The COPp was reduced from 23.2 mmHg in the first trimester to 21.1 mmHg in the third trimester. Concomitantly, COPi decreased from 13.1 to 8.4 mmHg on the thorax and from 9.6 to 5.5 mmHg at the ankle. Only small changes in Pi were observed. The more marked fall in COPi than in COPp indicates that a rise in Pc, in addition to hypoproteinaemia, contributes to increased capillary fluid filtration in pregnancy. The reduction in COPi opposes the increased filtration and thereby prevents a rise in interstitial fluid volume and oedema formation. These physiological changes imply a reduced safety margin against oedema formation in late pregnancy.

In order to evaluate renal tubular function, beta 2-microglobulin was measured in serum and urine from 15 patients with severe pre-eclampsia and 13 normal pregnant women. In the pre-eclamptic group, the serum beta 2-microglobulin level was significantly higher (p less than 0.05) and urinary excretion/24h significantly lower (p less than 0.05), than in the normal pregnant group. A positive linear correlation between serum uric acid and beta 2-microglobulin was observed both in the pre-eclamptic group (r = 0.79, p less than 0.001) and in the normal pregnant group (r = 0.58, p less than 0.05). This may indicate that production and renal handling of these two substances are interdependent. Tubular function is reduced in normal pregnancy, whereas increased 'net tubular reabsorption' of uric acid and beta 2-microglobulin occurs in pre-eclampsia. The cause of the observed changes in tubular function is still obscure.

The platelet release product beta-thromboglobulin (BTG) in venous plasma, and arterial and venous catecholamines were measured in 13 severe pre-eclamptic and 13 normotensive pregnant women. In the pre-eclamptic group, BTG was significantly higher and the platelet count significantly lower than in the normotensive pregnant group. In the pre-eclamptic group, arterial concentrations were significantly higher for adrenaline, noradrenaline and dopamine, whereas in venous plasma only adrenaline and dopamine were higher. Significant positive correlations appeared in the pre-eclamptic patients between venous BTG and arterial adrenaline (r = 0.82), arterial noradrenaline (r = 0.76) and venous adrenaline (r = 0.55). In the pre-eclamptic group, BTG also highly correlated with systolic (r = 0.84) and diastolic blood pressure (r = 0.77) and heart rate (r = 0.67). These findings indicate that sympathetic nervous tone, as measured by arterial and venous plasma catecholamines, is a good predictor of in-vivo blood platelet activation. In pre-eclampsia, increased sympathetic tone may play a key role in platelet activation and consumption and thus in the activation of the coagulation system.

Twenty-one preeclamptic women had increased venous plasma-free adrenaline (45 +/- 5 vs 27 +/- 2 pg/ml, mean +/- SE, P less than 0.01) and plasma-free dopamine (137 +/- 25 vs 55 +/- 6 pg/ml, P less than 0.01) compared with fifteen normotensive pregnant women. Plasma renin activity (P less than 0.001) and aldosterone concentration (P less than 0.02) were depressed in the preeclamptic and serum potassium increased (P less than 0.02). Plasma adrenaline correlated with blood pressure (r=0.80, P less than 0.001) supporting increased sympathetic nervous tone in the development of preeclampsia.

Capillary hydrostatic pressure has been calculated in normal pregnancy and preeclampsia. In humans, capillary hydrostatic pressure cannot be measured directly but may be calculated when the colloid osmotic pressure in plasma and interstitial fluid and interstitial fluid hydrostatic pressure are known (Starling equation). New methods have made it possible to measure the interstitial fluid colloid osmotic pressure and interstitial fluid hydrostatic pressure. In the present study interstitial fluid was collected from the subcutaneous tissue by implanted wicks (wick method), and interstitial fluid colloid osmotic pressure was determined. Interstitial fluid hydrostatic pressure was recorded by the wick-in-needle technique. Capillary hydrostatic pressure was calculated in 10 women in the first trimester and 10 in the third trimester of normal pregnancy, in 15 patients with mild preeclampsia, and in 13 women with severe preeclampsia. In normal pregnancy, capillary hydrostatic pressure increased by about 30% between the first and third trimesters. In mild preeclampsia, capillary hydrostatic pressure values did not differ significantly from those in the third trimester of normal pregnancy. However, in severe preeclampsia capillary hydrostatic pressure was significantly lower (40%) than in mild preeclampsia. Whether the low capillary hydrostatic pressure is caused by the severe general vasospasm seen in this condition or is a secondary event is unknown.

Plasma and interstitial fluid colloid osmotic pressure (COP) and interstitial fluid hydrostatic pressure (Pi) were measured in 10 normal pregnant women in first and third trimester. Interstitial fluid COP was measured by a "wick" technique and Pi by a "wick-in-needle" technique. The COP was significantly lower both in plasma and interstitial fluid in the third trimester compared to that in the first trimester. However, the fall in COP was more marked in the interstitial fluid than in plasma. Only small changes in Pi were observed. Our results support the view that reduction of COP in interstitial fluid is a major local edema-preventing mechanism. This compensates for the increased capillary pressure and the hypoproteinemia in late pregnancy. The relatively low interstitial fluid COP in third trimester women without edema implies a reduced safety margin against edema formation and may explain why 40-80% of normal pregnant women experience edema.

Mitochondrial dysfunction is a newly found group of inborn errors of metabolism in which there is a failure in the aerobic energy production. Disorders of mitochondrial metabolism exhibit a wide range of clinical symptoms which are related to the nature, severity and tissue distribution of the metabolic defect. Most reported cases are published in the neurological literature. In this report we describe for the first time a family with mitochondrial dysfunction with a high incidence of pre-eclampsia/eclampsia. The diagnosis of a mitochondrial disorder is verified by electronmicroscopic, electromyographic, histochemical and biochemical examinations. During pregnancy, the energy demand is increased due to both fetal and maternal requirements. A mitochondrial dysfunction, clinically symptomless in the non-pregnant state, may therefore become manifest during pregnancy. Characteristic features of pre-eclampsia such as disturbed ion transport, disturbed prostaglandin synthesis, vasoconstriction, platelet aggregation and hyperuricemia may be explained by mitochondrial dysfunction.

Transcapillary fluid dynamics in the follicular and luteal phase in women without symptoms of premenstrual syndrome were studied. Interstitial colloid osmotic pressure was measured by the "wick" method and interstitial hydrostatic pressure by the "wick-in-needle" method in subcutaneous tissue on the thorax and ankle. From follicular to luteal phase, the following changes were observed: Colloid osmotic pressures were significantly reduced, both in plasma (mean 2.5 mm Hg) and in the interstitium (thorax mean 1.9 mm Hg and ankle mean 2.0 mm Hg). The interstitial hydrostatic pressures did not change. There were no significant changes in serum albumin, hemoglobin, or hematocrit. A slight, but significant, weight gain was observed (mean 0.7 kg). The reduced plasma and interstitial colloid osmotic pressures in the luteal phase may be due to water retention, but the observed reductions in colloid osmotic pressures are probably not fully explained by simple dilution. A reduction in total protein mass in the luteal phase is suggested.

The fluid transport between the plasma and interstitial fluid compartment is governed by the Starling forces, i.e. the capillary pressure (Pc), interstitial fluid hydrostatic pressure (Pi) and colloid osmotic pressure in plasma (COPp) and interstitial fluid (COPi). Interstitial fluid was collected from subcutaneous tissue on the thorax and ankle by implanted wicks and Pi was measured using the 'wick-in-needle' technique. In pre-eclampsia, COPp is reduced due to hypoproteinaemia and this predisposes towards loss of fluid from the vascular compartment. An important oedema-preventing mechanism is reduction of COPi, which serves as a homeostatic buffer against increased capillary filtration. This mechanism works in moderate, but not in severe pre-eclampsia. A higher COPi was found both at the thorax (8.3 vs 7.0 mmHg) and ankle (5.9 vs 3.9 mmHg) in the group with severe pre-eclampsia compared with the group moderate pre-eclampsia, in spite of a significant reduction in COPp (15.5 vs 19.9 mmHg). These findings suggest that an increased microvascular permeability of plasma proteins to subcutaneous tissue contributes to COPp reduction in severe pre-eclampsia.

The present study entails clinical evaluation of 77 infertile men with testicular descent disturbances. The results summarize as follows: The incidence of disturbance in testicular descent among infertile men was 15.5%, 15.5% and 4.9% in azoo-, oligozoo- (less than or equal to 10 mill/ml) and normozoo- (greater than 10 mill/ml) spermia, respectively. Out of the 77 men investigated, 50 had a history of true cryptorchidism and 27 retractile testes. 31 of the patients with cryptorchidism had previously been subjected to orchidopexy. In the group of infertile men with a history of retractile testes, 20 subjects still retained palpable pathological changes of the testes. Testicular biopsies (from men with retractile testes and sperm count below 10 mill/ml) demonstrated hypospermatogenesis (germ cell arrest to aplasia). 6) 53% of the subjects exhibited elevated serum FSH. Two men had developed testis tumours (seminoma/teratoma). It is advocated that early hormonal therapy and/or surgical procedures should be initiated in an attempt to improve the chances of future fertility both in cryptorchidism and retractile testes.

Compared with normotensive pregnant women (n = 13), patients with severe pre-eclampsia (n = 13) had increased arterial plasma adrenaline (P < 0.001), peripheral venous adrenaline (P < 0.01), arterio-venous differences of adrenaline (P < 0.001) and venous concentration of the platelet release product beta-thromboglobulin (P < 0.001). In the pre-eclamptic group, arterial adrenaline correlated with mean blood pressure (r = 0.90, P < 0.001), heart rate (r = 0.78, P < 0.01) and beta-thromboglobulin (r = 0.82, P < 0.001), while in the normotensives adrenaline correlated only with beta-thromboglobulin (r = 0.76, P < 0.01). According to these results, sympathetic adrenal tone is increased in pre-eclampsia and may play a role in the pathogenesis of high blood pressure and platelet activation in this disease.

The hemostatic effects of a new triphasic oral contraceptive combination containing ethinylestradiol and the new progestogen gestodene were compared with those of a triphasic combination of ethinylestradiol and levonorgestrel. A total of 19 women who did not use any kind of hormonal contraception 3 months prior to the study were recorded. The following parameters were measured: whole blood clotting time (WBCT), whole blood clot lysis time, fibrinogen, antithrombin III, factors V, VII and VIII. Blood samples were taken before treatment and in cycles 1, 3 and 6. A significant shortening of WBCT was observed in cycle 3 and 6 in both groups and also in cycle 1 in the gestodene group. This may indicate an increased sensitivity for activation of platelets, since the assay appears to be quite sensitive to this process. In the other parameters tested there were no significant changes except for a slight increase in plasma fibrinogen in cycle 1 in the gestodene group.

Of 301 Norwegian female top athletes, all members of the national team in 27 different sports, who were approached with a questionnaire about menstrual function, 278 (92.4%) responded. Ninety-nine of the respondents who used oral contraceptives were excluded. Of the remaining 179, 18 (10.1%) reported secondary amenorrhea (greater than 4 months since the last period) and were chosen for further studies. Blood samples were drawn for hormonal analyses between 10 and 12 a.m. and at least 12 hours after the last training session. Their mean age was 20.8 years (range 18-27), mean height 169.8 cm (160-180), mean weight 58.5 kg (51-67), and their mean age at menarche 14.6 years (13-16.5), significantly older than that of the other top athletes: 13.5 years (p less than 0.05). Their mean number of training hours per week was 16.1 (12-24). Hormonal changes were consistent with simple normoprolactinemic hypothalamic suppression, characterized by low values of FSH, estradiol-17 beta and prolactin. The androgen hormones demonstrated high levels of dihydrotestosterone. Testosterone levels were within normal limits, but in the upper part of the range, whereas sex hormone-binding globulin was in the lower normal range.