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Zusammenfassung: Etwa ein Drittel der Weltbevölkerung ist mit Mycobacterium tuberculosis infiziert und von allen Infektionskrankheiten hat die Tuberkulose die zweithöchste Mortalität. Die pulmonale Tuberkulose ist die häufigste Form; bei extrapulmonalen Manifestationen sind die Lymphknotentuberkulose und der tuberkulöse Pleuraerguss führend. Der tuberkulöse Pleuraerguss ist in der Regel eine akut auftretende Erkrankung, die in den meisten Fällen selbstlimitierend ist. Die Mehrzahl der Patienten entwickelt jedoch nach einer Latenzzeit eine Form der aktiven Tuberkulose, weshalb die korrekte Diagnose und eine adäquate Therapie von entscheidender Bedeutung sind. Der einfachste Weg zur Diagnose einer tuberkulösen Pleuritis ist der Nachweis einer erhöhten ADA (Adenosindesaminase) in einem lymphozytenreichen Erguss. Sollte die Ergussanalyse nicht zur Diagnose führen, kann eine tuberkulöse Pleuritis in mehr als 80% der Fälle mit einer perkutanen Pleurabiopsie gesichert werden. Bei allen Patienten mit unklassifiziertem Pleuraerguss ist nach einer nichtdiagnostischen perkutanen Pleurabiopsie eine Thorakoskopie mit gezielten Pleurabiopsien indiziert, wodurch eine tuberkulöse Pleuritis in nahezu 100% der Fälle diagnostiziert werden kann.

Epileptic discharges from the temporal lobe may influence the release of hormones from the hypothalamic–pituitary axis. If epilepsy surgery influences the underlying epileptic disorder one might expect serum hormone concentrations to return to normal following surgery. PatientsTwenty-two men with epilepsy aged 25 to 48 years (mean, 34.9 years) were investigated before surgery and at 3, 6, and 12 months after surgery. Medication (all patients received carbamazepine) was maintained following surgery.

Adrenomyeloneuropathy (AMN) represents a milder form of X-linked adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder. The disease is characterised by an abnormal accumulation of saturated, very long chain, fatty acids, because of altered peroxisomal ß-oxidation that concomitantly leads to demyelination in the central and peripheral nervous systems. ALD shows a highly variable phenotypic expression and extensive mutation analysis in ALD patients has failed to establish a genotype-phenotype correlation, even in the presence of the same ALD-gene defect. Therefore, we have looked for a relationship between the molecular lesion and the age of onset in 19 patients with a well-classified clinical course of AMN. The nearly complete novel spectrum of ALD gene mutations identified has revealed no obvious correlation between the type of mutation and age of AMN onset in this small series. However, intrafamiliar concordance could be observed with respect to the occurrence of adrenocortical insufficiency. This supports the idea of one (or more) additional gene(s) contributing to the phenotypic expression of ALD.

To determine maximal plasma levels of androstenedione (A) and testosterone (T) which still can be considered non virilizing in 21-hydroxylase deficiency, we investigated plasma levels of these steroids in unaffected children and in adults. For T we found an upper limit of the prepubertal normal range of 16 ng/dl in girls and of 20 ng/dl in boys, with the exception of boys in the first half-year of life in which T is elevated up to the low adult range with peak values in the 2nd and 3rd month. During puberty T values show a significant difference between pubic hair stage 1 and stage 2. T levels below 20 ng/dl can be considered to be non virilizing. For A we found a plasma concentration of 86 ng/dl to be the upper normal level in both sexes before the onset of puberty. A values below this limit are expected to be non virilizing. To evaluate the usefulness of 17-hydroxyprogesterone (OHP) for the prediction of A and T and T and to define “acceptable” OHP levels in CAH we performed simultaneous determinations of OHP, T, and A in prepubertal patients treated for CAH. From these values we calculated the 95% confidence interval for prediction of T and A on known OHP levels. On an OHP value of 1.000 ng/dl, T can be excpected to be between 6 and 60 ng/dl and A between 25 and 320 ng/dl. Because of these wide ranges, OHP has to be considered an unreliable parameter for predicting androgen levels in CAH.

Summary To investigate the effects of fluid expansion on endogenous atrial natriuretic peptide (ANP) and cyclic 3',5'-guanosine monophosphate (cGMP), four male volunteers were studied before, during and after intravasal volume loading. Volume expansion was performed by intravenous infusion of 2,000 ml isotonic saline solution within 30 min. Mean plasma ANP levels increased 2.5-fold from 31.2 pg/ml to 81.7 pg/ml 40 min after the start of infusion. Plasma cGMP levels paralleled the rise in ANP, shwoing a mean cGMP increment from 2.7 pmol/ml to a maximum of 8.2 pmol/ml. Both ANP and cGMP levels were back to basal levels 120 min after termination of the infusion. Stimulation of endogenous ANP release by volume loading suggests that ANP is involved in the regulation of fluid homeostasis in man. The parallel rise in plasma cGMP levels supports the idea that cGMP is a mediator for the effects of ANP.

Summary A boy with male pseuodhermaphroditism described here with normal male caryotype was at first raised as a girl. The error was detected within the first year of life.

The mean growth hormone concentration during a 24-hour period in 7 boys of short familial stature and a growth rate of 3.2–5.4 cm/year was between 1.0 and 4.6 ng/ml serum. In 7 boys with pubertal growth spurt and familial tallness (growth rate 7.2–11.0 cm/year) it varied from 0.97 to 4.4 ng/ml and in 6 boys with constitutional delay of puberty (a growth rate of 4.2–5.2 cm/year prior to puberty) from 1.3 to 4.3 ng/ml.

Summary: Luteinizing hormone (LH), follicle-stimulating hormone (FSH) estrone, and estradiol were measured radioimmunologically in more than 60 plasma specimens of 34 girls suffering from idiopathic precocious puberty. Although the median values of both gonadotropins in the plasma of the patients (LH = 1.0 ng/ml; FSH = 1.6 ng/ml) were higher than those from healthy prepubertal girls (LH = 0.6 ng/ml; FSH = 0.5 ng/ml), only 23 out of 64 LH levels and 30 out of 64 FSH levels exceeded the upper normal limit for age. While the median value of plasma estrone (13 pg/ml) was found to lie within the normal range for prepubertal girls (7–29 pg/ml) and only 13 out of 75 estrone values were pathologically elevated, the median value of plasma estradiol (22 pg/ml) was nearly 3 times higher than the normal median for prepuberty (8 pg/ml). Of 75 estradiol levels, 35 were above normal for age. Grouping the values according to the stage of sexual development revealed considerably lower gonadotropin and estrogen levels in the patients than in normally maturing girls of the same developmental stage. However, patients who were examined repeatedly at short intervals over a 1-month period showed an almost cyclic sequence of their estradiol levels similar to the pattern observed in healthy pubertal girls.Speculation: The findings that plasma estrogens are relatively low in idiopathic precocious puberty in spite of well advanced sexual development suggest that the symptoms of this disturbance do not depend on estrogen concentrations alone. Other factors, such as enhanced receptor sensitivity or changes in the concentration of sexual hormone-binding globulin, must also be taken into consideration.

The affinity and the capacity of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) were determined in 9 patients with Conn's syndrom (PA) and in 3 patients with pseudohypoaldosteronism (PHA). The number of binding sites per cell was 136±39 (mean±SD) in PA. One case with PHA had no MR, and of the other 2 patients, one had 50 and the other 55 receptors per cell. The capacity of normal controls ranged from 200 to 400 receptors per cell (n=20). We conclude that (1) the etiogy of PHA is due to a lack of MR in the target tissues and that (2) a down regulation of MR may exist in PA.

Nested competitive reverse transcription polymerase chain reaction is an effective tool for the quantification of low level expressed mRNAs. Competitive RNA standards with small deletions allow the use cRT-PCR. The sensitivity is further increased by the utilization of nested PCR protocols. To optimize quantification of low abundance mRNAs we modified established protocols for use of automated labstations and semiautomated sequencers. In placental tissue, known for a very high CYP19 (P450AROM, aromatase) expression, cRT-PCR and nested cRT-PCR yielded virtually identical results which could be confirmed by Northern blotting. CYP19 mRNA in breast tumour tissue ranged below detection levels for Northern blotting; however, using our modified assay CYP19 showed 1.5 to 15 fold higher expression levels than in normal glandular breast tissue. Our approach proved to be useful for the quantification of a gene with low level expression. The employment of labstations and semiautomated sequencers allows rapid analysis of large sample numbers.

The patient, diagnosed as a case of testicular feminisation in infancy, was examined at the age of 15 years because of severe symptoms of virilising puberty with poor breast development. Plasma steroid analyses revealed a 10-fold elevated androstenedione concentration (A: 1562 ng/100 ml). Testosterone (T: 266 ng/100 ml) was in the male pubertal range. Thus the A/T-ratio was far above normal. The oestrone/oestradiol ratio was also elevated (Oe1/Oe2: 10.2/2.2 ng/100 ml). A, T, Oe1and Oe2could not be suppressed by dexamethasone, but reacted promptly to fluoxymesterone (A: 781 ng/100 ml). hCG caused a further increase of the A/T-ratio (2220/246 ng/100 ml); ACTH did not alter the A-concentration. These findings together with simular investigations after gonadectomy suggest that the failure to convert A to T and Oe1to Oe2is essentially located in the testes. In vitro incubations of testicular tissue showed reduced 17-ketosteroid reductase activity in tissue slices and in the subcellular fractions microsomes and cytosole. This form of male pseudohermaphroditism can easily be detected already in infancy, if steroid analyses and stimulation tests are performed. In case of female sex assignment patients should be submitted to early orchidectomy in order to avoid virilisation in puberty.

ABSTRACT. An age-related dependence of plasma ANP levels was studied in 163 healthy children (94 boys, 69 girls) between the ages of day 1 and 16 yr. In neonates during the first 2–4 days of life, significantly higher plasma ANP plasma levels (range 129–356 pg/ml, mean 227) were found compared with older infants and children (p<0.001). Beyond the neonatal period through adolescence no significant difference in ANP concentrations could be found between the various age groups. Plasma ANP levels ranged between 2 and 109 pg/ml (mean 47) for all age groups after the newborn period. ANP levels were also determined in 15 adult volunteers and in arterial and venous cord blood of 16 healthy newborns, and concentrations were similar to those found in children. In addition, plasma ANP levels were measured in 40 children with various cardiac diseases; 22 of 40 patients exhibited ANP levels above the upper normal range seen in control children. Of these 22 patients all except two children revealed clinical signs of heart failure. In contrast 15 of 17 children without heart failure showed plasma ANP levels within the range of control children. ANP plasma levels ranged between 93 and 967 pg/ml (mean 284) in patients with heart failure and between 15 and 118 pg/ml (mean 57) in patients without heart failure, respectively. Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload.

Ohne Zusammenfassung:

We applied the ACTH-stimulation test developed in our laboratory for the detection of heterozygous carriers of the 21-hydroxylase deficiency gene to patients suffering from hirsutism (n=89), premature pubarche (n=75), early puberty (n=37), and precocious puberty (n=22). While, in the general population, this test is positive in less than 2%, we found in 33% of hirsute patients, in 41% of patients with premature pubarche, and in 33% of patients with early puberty a hormonal response similar to the one seen in heterozygous carriers for the 21-hydroxylase defect. In contrast, only 18% of patients with precocious puberty responded abnormally. Thus we speculate that, at least in some patients with hirsutism, premature pubarche, and early puberty, heterozygosity for the 21-hydroxylase defect plays a major role in the pathogenesis of these disorders.

Plasma testosterone was investigated by gas-liquid chromatography with an electron capture detector in a cross-sectional study in childhood and during puberty in 214 boys. The testosterone values were correlated with sexual characteristics such as axillary hair, pubic hair, testicular size and bone age.In 22 individuals during puberty a longitudinal study was started, indicating a very steep increase of plasma testosterone between 40 and 240 ng/100 ml. This stage is mostly passed through very rapidly within 10 months.Plasma testosterone, growth velocity and weight gain were correlated in two boys during puberty. The peak of growth spurt occurs between 50 and 170 ng of plasma testosterone.

GnRH antagonists, unlike the GnRH agonists, immediately suppress gonadotropins and testosterone secretion without initial stimulatory effect. We report here on a single-dose study with the new GnRH antagonist Cetrorelix (Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal3, D-Cit6, D-Alal0) in 25 normal men. The study involved five different dose groups (0.25, 0.5, 1.0, 1.5 or 3.0 mg) and subjects were observed over a 40 h period. Five men served as controls. Serum levels of LH, FSH and testosterone decreased rapidly with a dose-related decline for testosterone of 25%, 24%, 41% 53% and 72%, respectively, for testosterone within the first 8 h of antagonist administration. All effects were reversible and no serious side effects were observed. Thus, this GnRH antagonist is active in men even in small doses and could become a new therapeutic tool for sex hormone-dependent diseases. Cetrorelix seems to have the highest suppressive rate per mg peptide of all other antagonists from the literature, such as Nal-Glu (Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal3, Arg5, D-Glu6(AA), D-Alal0), Detirelix (Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Alal0) or 4F (Ac-Δ 3Prol, 4F-D-Phe2, D-Trp3,6). During the time of suppression after a dose of 3 mg there was an LH and testosterone peak in the early morning coinciding with the testosterone peak in untreated men. The GnRH antagonist seems to unmask the circadian rhythm of LH secretion.

In vitro studies have shown that the Sertoli cell is the primary source of inhibin in the male. We measured immunoreactive inhibin with a new two-site immunoenzymatic assay in the plasma of 92 men: 40 normal men, 7 patients with germinal cell cancer after unilateral orchidectomy and 45 patients with the same disease following unilateral orchidectomy and subsequent chemotherapy based on cisplatin. Normal men had inhibin levels of 1.77±0.09 U/l × 10−3(mean±sem). Seven patients after unilateral orchidectomy had inhibin concentrations within the lower normal range (1.23±0.22 U/l × 10−3). Forty-five patients were investigated in a cross-sectional study up to 102 months after completion of chemotherapy. Inhibin levels were within the normal range in 25 patients (1.76±0.114 U/l × 10−3); 18 patients had significantly lower inhibin levels (0.48±0.05 U/l × 10−3, p<0.005) when compared to patients after unilateral orchidectomy. Two patients had elevated inhibin levels (4.4 and 5.6 U/l × 10−3). The proportion of patients with normal and subnormal inhibin was not dependent on the time that elapsed after completion of chemotherapy or on the chemotherapy combination. There was no correlation between immunoreactive plasma inhibin and LH, FSH, testosterone or sperm count. The decrease in inhibin concentrations after chemotherapy may indicate long-term damage to Sertoli cells in some of the patients.

Corticosteroids (CS) are known to be essential for fetal organ maturation and seem to play an important role in both the initiation of parturition and the postnatal adaptation of the human neonate. Pharmacologically, CS are widely used for enhancing fetal lung maturation prior to premature delivery. However, knowledge of endogenous CS and precursor levels throughout fetal and perinatal life and their response to exogenous CS is limited. Therefore, using automated liquid column chromatography plus specific radioimmunoassays, unconjugated aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F) and cortisone (E) were simultaneously followed in 70 amniotic fluid (AF) control samples throughout pregnancy, and in cord and neonatal plasma longitudinally during the first week of life. From 14 to 38 weeks, AF levels of all measured steroids except E rose by 2 to 12-fold on the average (allP<0.001) but declined at term. E increased until 31–35 weeks (P<0.01), then remained almost constant until term. Cord levels of all steroids were substantially higher than those found in AF at term. While levels of the placentally derived steroids P, 17-OHP, DOC and E dropped sharply after birth by several orders of magnitude (P«0.01) showing typical disappearance curves, the biologically most potent CS Aldo and F rose even further immediately after birth. Whereas Aldo levels declined from maxima about 100 times above normal adult levels at 6 h by almost 3-fold until day 7 (P<0.01), F (and also B) fluctuated considerably resembling a damped oscillation and, by day 7, reached mean levels less than half of those seen in later childhood. After betamethasone treatment of the mother, neonatal levels of Aldo and F were suppressed to 24–69% of normal until day 9, whereas those of the other steroids (except E) returned to normal during the first hours of life. Phenobarbital (PB) therapy of the mother led to decreased steroid levels in maternal and umbilical venous plasma at term, while umbilical arterial CS levels, notably those of Aldo and F (P<0.02), were increased when compared with untreated controls, indicating a stimulation of the most potent CS in the fetus after PB. The significance of the findings in view of fetoplacental function and fetal organ maturation is briefly discussed.

The increase of plasma cortisol (F), androstenedione (A), 17α-hydroxyprogesterone (17-OH-P) and testosterone (T) was measured after iv administration of ACTH in heterozygotes for CAH and in controls under two different conditions:Test 1: ACTH stimulation was performed without any particular preparation.Test 2: 1.5 mg of dexamethasone (dex.) was given the evening before the ACTH stimulation.Plasma F, A, 17-OH-P and T were measured by specific radioimmunoassays (RIA). Following ACTH stimulation, the increase of 17-OH-P was significantly higher in CAH-heterozygotes than in controls in both tests (P< 0.0005). Heterozygotes were characterized by a 17-OH-P increase after ACTH stimulation exceeding the +2 sdlimit of the 17-OH-P increase found in controls. The detection of female heterozygotes was considerably improved by the administration of dex. before testing (test 2). In males, however, a better identification of heterozygotes was obtained without previous administration of dex. (test 1). By these tests, 100% of female (test 2) and 79% of male (test 1) CAH heterozygotes could be correctly identified.There were no significant differences in the levels of F, A and T between heterozygotes and controls except for decreased T levels in test 1 (2P< 0.01) in most male heterozygotes after ACTH stimulation.

OBJECTIVES: A new method for the quantitative determination of 17alpha-ethinylestradiol-17beta (EE2) in serum is presented here based on the principle of isotope dilution mass spectrometry (IDMS) with [13C]EE2 as internal standard. The technique was used to determine the concentration profiles of EE2 in the serum of female subjects who had taken oral contraceptives with different progestin components. The method has proved to be very reliable with respect to trueness, specificity, precision and detection sensitivity and offers considerable advantages compared with the immunological methods of measurement used to date. STUDY DESIGN: Forty-seven female volunteers took two different oral contraceptives containing EE2 combined with different progestins in accordance with a cross-over design. After the administration of 30 microg EE2 combined with 75 microg gestodene (EE2/GSD) or 150 microg desogestrel (EE2/DES), blood samples were taken from the subjects on certain days and in certain previously specified cycles in the course of 12 h after medication. RESULTS AND CONCLUSIONS: The biometric analysis of the results showed that the concentration profiles of EE2 were in their statistics, significantly equivalent after the administration of either of the two oral contraceptives. The sometimes contradictory results found in former studies after the administration of the different contraceptives were presumably due to the methodological shortcomings of the radioimmunological measurement technique. With the use of the highly accurate and specific technique of IDMS it can now be unequivocally established that the different progestins in the tested oral contraceptives have no influence on the bioavailability of EE2 (area under EE2 serum concentration curves, as usually defined in pharmacokinetics).

An age-related dependence of plasma ANP levels was studied in 163 healthy children (94 boys, 69 girls) between the ages of day 1 and 16 yr. In neonates during the first 2–4 days of life, significantly higher plasma ANP plasma levels (range 129–356 pg/ml, mean 227) were found compared with older infants and children (p<0.001). Beyond the neonatal period through adolescence no significant difference in ANP concentrations could be found between the various age groups. Plasma ANP levels ranged between 2 and 109 pg/ml (mean 47) for all age groups after the newborn period. ANP levels were also determined in 15 adult volunteers and in arterial and venous cord blood of 16 healthy newborns, and concentrations were similar to those found in children. In addition, plasma ANP levels were measured in 40 children with various cardiac diseases; 22 of 40 patients exhibited ANP levels above the upper normal range seen in control children. Of these 22 patients all except two children revealed clinical signs of heart failure. In contrast 15 of 17 children without heart failure showed plasma ANP levels within the range of control children. ANP plasma levels ranged between 93 and 967 pg/ml (mean 284) in patients with heart failure and between 15 and 118 pg/ml (mean 57) in patients without heart failure, respectively. Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload. (Pediatr Res20 1328–1331,1986)

Summary In 22 patients with osteogenic sarcoma, treated with 103 high-dose methotrexate infusions (6–8.5 g/m2 in 4–6 h) plasma methotrexate levels were measured with a specific and rapid radioimmunoassay. Nontoxic infusions were associated with methotrexate concentrations below 8.0 × 10-6 mol/l at 24 h, 8.0 × 10-7 mol/l at 48 h and 4.25 × 10-7 mol/l at 72 h. All patients with 48 h methotrexate levels above 1 × 10-6 mol/l manifested severe toxicity with myelosuppression and stomatitis due to delayed methotrexate excretion. Rise of serum creatinine was not reliable to predict oxicity. Determination of 48-and 72-h methotrexate concentrations proved to be a valuable method for identifying patients at high risk for toxic side effects. Additional citrovorum factor may thus be given in time.

OBJECTIVEThe present study was designed to assess the diagnostic value of different single measurements in comparison to the classic time-consuming method, the oral glucose tolerance test (OGTT), in acromegaly.
DESIGN, PATIENTS AND MEASUREMENTS IGF-I, free IGF-I, 24-hour-urinary GH (uGH), serum IGFBP-3 and 24-hour-urinary IGFBP-3 (uIGFBP-3) were measured in 12 patients with untreated active acromegaly, in 29 patients who had been treated but were not cured, in 13 patients with cured acromegaly and in 14 healthy control subjects, and compared with the results of the OGTT.
RESULTSIn all patients with active acromegaly, whether they had been treated or not, nadir GH in OGTT was >3 mU/I, whereas nadir GH was &lt;1.88 mU/I in the cured patients and the control subjects. In patients with untreated active acromegaly IGF-I, free IGF-I, uGH and IGFBP-3, but not uIGFBP-3, were significantly higher than in healthy individuals (P&lt;0.0001). Only IGF-I values did not overlap with the control group. In those patients with acromegaly who had been treated but not cured these parameters overlapped with the control group. In patients with acromegaly there was a significant correlation between nadir GH levels in OGTT and IGF-I (r=0.71), free IGF-I (r=0.76, IGFBP-3 (t=0.73) and uGH (r=0.81) (P&lt;0.0001), but no correlation with uIGFBP-3.
CONCLUSIONSOnly be means of the OGTT could patients with active acromegaly be completely distinguished from the control subjects and from cured patients. IGF-I, free IGF-I, IGFBP-3 and uGH were useful in the diagnosis of acromegaly, but of limited value in the follow-up of acromegalic patients after treatment. The determination of free IGF-I, which has yet not been investigated in acromegaly, offered no advantage over that of total IGF-I and IGFBP-3; uIGFBP-3 was not useful in the diagnosis of acromegaly.

Changes in cytosolic free Ca2+influence important granulocyte functions like chemotactic behavior, adherence to endothelia, and phagocytosis. In the following study we used a simple reproducible procedure involving flow cytometry in combination with the fluorescent dye Fluo-3 to measure Ca2+changes in human granulocytes. The aim of our study was to investigate the involvement of protein kinase C in regulating cytosolic free Ca2+concentrations after stimulation of cells with IL-8 and fMLP. Both reagents induced a 5-6 fold increase in cytosolic Ca2+. Experiments conducted in Ca2+-free media showed a minor 18-29% decrease in cytosolic Ca2+response, suggesting that intracellular Ca2+-stores are the main source for Ca2+release after fMLP or IL-8 stimulation. Activators of protein kinase C, phorbol myristate acetate (PMA) and 1-oleyl-2-acetyl-sn-glycerol (OAG), inhibited cytosolic Ca2+-increase completely when induced by IL-8 and by 68-82% in the case of fMLP. Staurosporine, an inhibitor of protein kinase C, was able to attenuate or even abolish the PMA/OAG-effect. Our results show that changes in cytosolic Ca2+due to IL-8 and fMLP signalling can be regulated by protein kinase C in human granulocytes. This regulatory role of protein kinase C involves some form of receptor modulation (i.e. phosphorylation, internalization, shedding).

The pharmacodynamics of plasma testosterone (T) and androstenedione (A) levels were studied in ten hypogonadal boys after oral administration of testosterone undecanoate (TU).Plasma T and A levels were measured by specific radio-immunoassays.Six hours after a single dose of 120 mg TU, there was a significant increase (P< 0.005) in plasma T and A with a median T peak level of 940 ng/100 ml.Furthermore, twelve agonadal boys treated with a mean dose of 60 mg TU/day were examined over a period of 18–24 months. During this therapy, plasma T and A levels were significantly higher than before (P< 0.005), whereas plasma levels of LH and FSH did not decrease significantly. With the exception of one anorchic boy, all patients showed signs of sexual maturation, such as growth of pubic and axillary hair, and steady development of bone age during oral TU treatment.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH) estrone, and estradiol were measured radioimmunologically in more than 60 plasma specimens of 34 girls suffering from idiopathic precocious puberty. Although the median values of both gonadotropins in the plasma of the patients (LH = 1.0 ng/ml; FSH = 1.6 ng/ml) were higher than those from healthy prepubertal girls (LH = 0.6 ng/ml; FSH = 0.5 ng/ml), only 23 out of 64 LH levels and 30 out of 64 FSH levels exceeded the upper normal limit for age. While the median value of plasma estrone (13 pg/ml) was found to lie within the normal range for prepubertal girls (7–29 pg/ml) and only 13 out of 75 estrone values were pathologically elevated, the median value of plasma estradiol (22 pg/ml) was nearly 3 times higher than the normal median for prepuberty (8 pg/ml). Of 75 estradiol levels, 35 were above normal for age. Grouping the values according to the stage of sexual development revealed considerably lower gonadotropin and estrogen levels in the patients than in normally maturing girls of the same developmental stage. However, patients who were examined repeatedly at short intervals over a 1-month period showed an almost cyclic sequence of their estradiol levels similar to the pattern observed in healthy pubertal girls.

The endocrine characteristics of polycystic ovarian disease (PCO) remain ill defined as opposed to its histoiogic features. In this study the hypothalamic-pituitary-ovarian interactions were investigated in 26 patients with PCO and compared to those of nine hirsute, anovulatory and 13 healthy, ovulatory control subjects. The following hormones were determined during the early follicular phase: serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) before and after double stimulation with LH-releasing hormone (LHRH) (two doses of 25 μg intravenously at a 120 minute interval, maximal increments after the first injection, i.e., Δ1, and second injection, i.e., Δ2), basal testosterone (T), dihydrotestosterone (DHT), astrone (E1), and estradiol (E2). LH Δ2was significantly increased in allPCO patients, while LH Δ1was elevated in 18 and basal LH in 12 cases. Basal FSH and FSH Δ1were normal in all subjects, whereas FSH Δ2was higher in two thirds of the women with PCO. A use of peripheral steroids was recorded in the majority Of PCO patients: T in 19, DHT in 16, E1in 19, and E2in 14 of 23 subjects. Patients with PCO were divided into three subgroups according to their basal LH levels and LH response to stimulation with LHRH. The extent of LH deviation from normal was correlated to the degree of steroidal elevation. The nine hirsute women showed normal gonadotropin patterns despite augmented peripheral androgens. It is concluded that an increase of LH Δ2(>12 ng/ml) after LHRH double stimulation combined with positive findings on laparoscopy may be characteristic of PCO in the differential diagnosis of hirsutism, anovulation, and oligomenorrhea.

Summary We studied the effect of coronary-artery bypass surgery on blood cells and platelets. Hematological parameters of eighty-three patients were measured by an automated cell counting and sizing analyzer. Sampling time was from 24 h prior to 10 days after surgery. During this time leukocytes and platelets showed characteristic changes in numbers and size, whereas red blood cells revealed no typical modifications. Even though it seems clear that changes of hematological parameters occur after bypass surgery, it is important to be aware of the actual extent of such changes. Therefore the data of 50 patients who had had no post-operative clinical complications were combined to generate diagrams of those parameters that had changed in a characteristic fashion. The diagrams showing average changes, and 99% confidence intervals in mean platelet volume and platelet count were able to identify seven (out of 7) cases with complications up to 48 h before clinical signs were apparent. Complications ranged from mild (3 cases with infections) to severe (4 cases with thrombosis, embolic thrombosis and/or reinfarction). Diagrams showing changes in leukocyte parameters were able to identify only two cases with infections. Even though the number of cases is yet small, the results suggest that surveillance of platelet parameters may be useful in postoperative care. Furthermore, this study was able to confirm the recent findings of Trowbridge and Martin [18] that an abnormal increase in platelet volume distribution width and low platelet counts found in patients with coronary heart disease may serve as good indicators for the prethrombotic state and the risk of myocardial infarction.

Background. Measuring serum cytokines, pituitary hormones, or acute phase proteins during or after surgery is not an optimal method for quantifying the impact of surgical procedures. In an effort to assess surgical stress by means of the immune response, we focused on changes in cell-mediated and antibody-mediated immunity as illustrated by the type 1/type 2 T-helper (Th1/Th2) cell balance. The sensitivity of this approach was evaluated by comparing laparoscopic and conventional cholecystectomy (LCE, CCE). Methods. In a pragmatic prospective study 43 patients with symptomatic cholelithiasis were operated on either by LCE (n=25) or CCE (n=18). Blood sampling was done 24 hours before surgery, immediately before incision, and 2, 24, and 48 hours after surgery. Cell surface markers and cytokine production were used to characterize the Th1/Th2 balance and were measured by means of flow cytometry and enzyme-linked immunosorbent assay techniques. Results. Activation of Th2 cells evokes the production and secretion of interleukin-4 (IL-4), which up-regulates the expression of immunoglobulin E receptors (FoeRII, CD23) on B cells. Phytohemagglutinin-induced IL-4 production in freshly isolated peripheral blood mononuclear cells from patients increased more after CCE than LCE (IL-4, +41% versus +17%; p<0.05). Also the expression of CD23 on B cells was higher after CCE than LCE (+146% versus +63%; p<0.01). CD30, a membrane molecule that belongs to the tumor necrosis factor receptor superfamily and probably is an important indicator of Th2 activity, was more elevated on T cells from patients who underwent CCE. The Th1 response, characterized by phytohemagglutinin-induced IFN-@c secretion in peripheral blood mononuclear cells and up-regulation of human leukocyte antigen-DR expression on monocytes, was lower after CCE than after LCE. Conclusions. This study shows that surgical stress induces a shift in the Th1/Th2 balance toward Th2, suggesting that cell-mediated immunity is down-regulated and antibody-mediated immunity is up-regulated after surgery. The evaluation of this shift may be clinically meaningful and help quantify even less invasive surgical procedures. When comparing CCE and LCE in this not strictly randomized study, we found LCE to be the less stressful procedure.

Plasma testosterone was determined by radioimmunoassay in 36 prepubertal boys with hypospadia prior to and 3 days after stimulation with 5000 IU of human chorionic gonadotrophin (hCG). As a control group, 30 boys of comparable age, predominantly with unilateral cryptorchidism, were studied. The increase in plasma testosterone levels after hCG was (median and range) 204 (83–393) ng/100 ml in the control group, whereas in the hypospadiac group a median increase of only 90 (33–272) ng/100 ml was found. The difference between the median testosterone levels after hCG stimulation in the two groups investigated is statistically highly significant (P< 0.0001). After hCG stimulation, 13 out of the 36 boys with hypospadia did not reach the lowest stimulated testosterone level (87 ng/100 ml) found in the control group. It is concluded that a substantial portion of the aetiologically obscure cases of hypospadia are caused by an endocrine testicular insufficiency.

Extract: Plasma concentrations of estrone and estradiol were determined by radioimmuno-assay of cord blood from 17 neonates and of venous blood of 15 neonates, 61 boys and 69 girls of all developmental stages, 27 healthy women, 20 healthy men, and 89 male and female adolescents with different disorders of sexual development.In cord blood both estrone and estradiol averaged 15,000 pg/ml. Blood drawn from neonates shortly after birth showed levels between 300 and 500 pg/ml. These levels fell to 5–15 pg/ml within a few days after birth, which is the normal range for both sexes up to 7 years. Before puberty, estrone rises earlier in girls than in boys. The increase of estradiol follows the onset of puberty. Boys reach adult levels in stage IV, whereas girls in stage V still have lower estrogen levels than mature women.We did not find higher levels in 29 adolescents with gynecomastia than in normal adolescents at the same stage of puberty. We observed abnormally high estrogens in children with congenital adrenal hyperplasia, but, in spite of some very high levels, we did not observe premature thelarche or gynecomastia in children with this disease. Six females and 10 males with panhypopituitarism, aged from 10 to 19 years, revealed low values within the infantile range. Six boys between 5 and 14 years who suffered from anorchia had very low levels of estrogen, especially estradiol (which was nearly undetectable). In contrast to patients with functioning testicle tissue, the patients with anorchia did not show any increase of estrogens after stimulation with human chorionic gonadotropin. Abnormally low levels were found in females with Turner's syndrome, but only in those with 45, XO karyotype. Patients with 45, XO/46, XX, or 46, XXp–karyotype had high levels of estrogen which corresponded to clinical signs of advanced puberty.Speculation: As demonstrated by our results, the radioimmunologic method enables us to measure the low estrogen levels which are found in children. This will permit a more intensive examination of the pituitary-gonadal and pituitary-adrenal interrelation in the future.

Summary Atrial natriuretic peptide (ANP) counteracts the destabilization and aggregation of platelets which is induced by vasopressin, angiotensin, and adrenaline.

The mineralocorticoid receptor (MR), a member of the steroid receptor family, acts as a transcription factor and mediates both aldosterone and cortisol effects. Aldosterone specificity in some tissues results from the inactivation of competing cortisol into cortisone by 11beta-hydroxysteroid dehydrogenase. In other tissues MR and the glucocorticoid receptor show overlapping physiological effects or may act together by forming a heterodimer. An additional MR splice variant (MR+4) has been found in different mRNA samples from rat tissues and human white blood cells, thereby implying additional modes of MR-regulated effects. We therefore looked for the presence of these two MR-mRNA isoforms in human classical aldosterone target tissues and various other tissues. MR-mRNA was found in all samples investigated, thereby showing the expression of MR to be more abundant than has been observed thus far. In addition, the MR+4-mRNA variant was also found in all the tissues examined.

Summary To investigate the adrenocortical suppression caused by the anesthetic etomidate, plasma levels of progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycorticosterone (DOC), corticosterone (B), aldosterone (Aldo), 11-deoxycortisol (S), cortisol (F), and cortisone (E) were measured simultaneously before and after a short-term ACTH stimulation test in a 6.5-year-old boy whose convulsions could be kept under control only with constant etomidate infusions. During etomidate therapy, plasma levels of DOC and S were extremely elevated, the progestins P and 17-OHP were slightly elevated, whereas B and Aldo were in the lower normal range, and F and E were markedly decreased. A short-term ACTH stimulation test during etomidate infusion gave a blunted response of B, Aldo, F and E, whereas the level of DOC remained high and S even further increased. P and 17-OHP showed a positive response to ACTH. The ratios of B/DOC and F/S, which reflect adrenocortical 11ß-hydroxylase activity, were extremely decreased during etomidate and did not change after ACTH stimulation. In contrast, the ratios of DOC/P and S/17-OHP, which relect 21-hydroxylase activity, were elevated and remained elevated after ACTH stimulation. After discontinuation of etomidate therapy, all the baseline steroid levels were somewhat elevated, but responded normally to ACTH. These results demonstrate that etomidate causes a specific and reversible blockade of the 11ß-hydroxylation of adrenal steroid synthesis.