The rat intraovarian interleukin (IL)-1 system: cellular localization, cyclic variation and hormonal regulation of IL-1beta and of the type I and type II IL-1 receptors.

An increasing body of evidence supports the possibility that intraovarian interleukin (IL)-1 plays an intermediary role in the periovulatory cascade. To gain further insight into the intraovarian IL-1 hypothesis, we studied the cellular localization cyclic variation and hormonal regulation of IL-1beta, as well as of the type I and type II IL-1 receptors (IL-1R) in immature rats. In situ hybridization localized IL-1beta and type I IL-1R transcripts to the granulosa cell compartment, the innermost layers of the theca interna and to the oocyte of the untreated immature ovary. Molecular probing of whole ovarian material in the course of a simulated estrous cycle revealed a progressive preovulatory increase in IL-1beta and type I IL-1R transcripts to an in vivo peak at the time of ovulation (3.0- and 2.5-fold increases over untreated controls; P < 0.05). Comparable efforts to localize and probe for type II IL-IR transcripts failed to elicit a detectable signal. The basal in vitro expression pattern of IL-1beta and type II IL-1R transcripts by whole ovarian dispersates revealed an early (4 h) spontaneous increase to a peak (2.1- and 5.8-fold increases over time 0: P < 0.05) followed by a gradual decline to a 48 h nadir. Treatment of whole ovarian dispersates with the IL-1 receptor antagonist (IL-1RA) or with IL-1beta failed to alter the initial (4 h) burst of IL-1beta or of type II IL-1R expression thereby suggesting IL-1-independence. Treatment with hCG proved equally ineffective. However, longer-term treatment of whole ovarian dispersates with IL-1beta produced a significant secondary increase (5.9-fold over time 0; P < 0.05) in IL-1beta (but not type II IL-1R) transcripts by 48 h. This IL-1 effect was completely blocked by co-treatment with IL-1RA thereby suggesting mediation via a specific IL-1 receptor. Qualitatively comparable but quantitatively reduced results obtained for isolated granulosa cells. The basal in vitro expression pattern of type I IL-1R transcripts by whole ovarian dispersates revealed a progressive spontaneous increase (3.1-fold increase overall) over the 48 h culture. Treatment with IL-1beta produced a significant (P < 0.05) increase (5-fold) in type I IL-1R transcripts by 48 h, an effect which was completely blocked by co-treatment with IL-1RA. Taken together, these observations: (1) localize IL-1beta and its type I receptor to granulosa cells, the innermost layers of the theca interna and to the oocyte; (2) confirm their periovulatory in vivo expression pattern; (3) document their expression by untreated cultured whole ovarian dispersates; and (4) demonstrate their in vitro responsiveness to receptor-mediated/IL-1-driven autocrine amplification. The type II IL-1R was undetectable in vivo, its in vitro expression pattern proving IL-1- and hCG-independent. The periovulatory expression pattern of IL-1beta and its receptor (type I) is compatible with the notion that the intraovarian IL-1 system may play an intermediary role in the ovulatory process.

Rat ovarian insulin-like growth factor binding protein-4: a hormone-dependent granulosa cell-derived antigonadotropin.

OBJECTIVE: To assess the in vivo regulation of ovarian insulin-like growth factor binding protein-4 (IGFBP-4) mRNA expression by gonadotropins and estrogen. METHODS: Whole ovarian RNA, obtained from two models of follicular development, was extracted and analyzed by Northern blotting. Immature rats were treated with pregnant more serum gonadotropin (PMSG) followed 48 hours later with hCG, or alternatively were hypophysectomized and treated with FSH and/or diethylstilbestrol (DES). Localization of IGFBP-4 expression was assessed in the former study by in situ hybridization. Finally, the ability of human IGFBP-4 to antagonize FSH-stimulated progesterone accumulation was assessed in vitro. RESULTS: The ovarian content of IGFBP-4 transcripts increased threefold (P < .05) at 12 hours after PMSG but was near baseline at 24 and 48 hours. The abundance of IGFBP-4 mRNA increased (P < .05) again at 6 and 24 hours after hCG. The expression of IGFBP-4 was localized to granulosa cells of preantral (untreated) and small antral (12 hours after PMSG) follicles. No IGFBP-4 expression was noted in large (gonadotropin-primed) antral follicles. Hypophysectomy increased (P < .05) the ovarian content of IGFBP-4 mRNA by 1.5-fold, an effect further enhanced (1.8-fold; P < .05) by the provision of FSH and DES. In vitro studies revealed the ability of increasing concentrations (0.01-1 microgram/mL) of recombinant human IGFBP-4 to inhibit the FSH-supported accumulation of progesterone. CONCLUSION: Increased expression after administration of PMSG, hCG, and FSH/DES suggests that IGFBP-4 is a dynamic and hormonally responsive component of the ovarian cycle. The lack of expression in preovulatory follicles and its antigonadotropic actions in vitro imply that the attenuated expression of IGFBP-4 may constitute a requirement for successful follicular maturation.

Detection and in vivo hormonal regulation of rat ovarian type I and type II interleukin-I receptor mRNAs: increased expression during the periovulatory period.

OBJECTIVE: To study the expression, localization, and in vivo hormonal regulation of type I and type II interleukin-1 (IL-1) receptors in the rat ovary. METHODS: Segments of the cDNAs for rat type I and type II IL-1 receptors were cloned and used as probes in RNase protection assays and in situ hybridization. Tissues obtained from immature rats and hormonally treated rat ovaries were examined. RESULTS: Type I IL-1 receptor (IL-1R(1)) was ubiquitously expressed in rat tissues, including granulosa cells prepared from immature ovaries, whereas type II IL-1 receptor (IL-1R(2)) expression was restricted to macrophages, thymus, and lung. Hypophysectomy and subsequent treatment with FSH and/or diethylstilbestrol did not alter significantly the abundance of IL-1R(1) transcripts in the whole ovary. However, the relative amount of ovarian IL-1R(1) transcripts increased 7.3-fold 6 hours after the administration of hCG to pregnant mare serum gonadotropin-primed immature rats. During this time, IL-1R(1) mRNA was localized primarily in the granulosa cells. The increased expression of IL-1R(1) persisted 24 hours after hCG administration but declined to baseline by 48 hours. Ovarian expression of IL-1R(2) mRNA was observed only before ovulation in amounts that were approximately 70-fold lower than IL-1R(1). CONCLUSION: The increased intraovarian expression of IL-1R(1) in granulosa cells during the periovulatory period implies that this cell type has a heightened receptivity to IL-1 and provides further indirect evidence that this cytokine is involved in the ovulatory process.

In vivo hormonal regulation of insulin-like growth factor binding protein-5 mRNA in the immature rat ovary.

OBJECTIVE: Despite the potential importance of insulin-like growth factor binding protein-5 (IGFBP-5) to follicular development, the hormonal regulation of this antigonadotropic IGFBP has not been investigated. Therefore, it was the objective of this study to eludicate the role of gonadotropins and estrogen in the in vivo regulation of IGFBP-5 mRNA expression. METHODS: Two models of follicular development in immature rats were used. Specifically, rats were hypophysectomized and treated with FSH and/or diethylstilbestrol (DES). Alternatively, terminal follicular development was induced in intact immature rats by pregnant mare serum gonadotropin (PMSG) and hCG. The IGFBP-5 mRNA in whole ovarian RNA was assayed by Northern blot hybridization. Localization of expression in PMSG and hCG-stimulated ovaries was further assessed by in situ hybridization. RESULTS: Expression of IGFBP-5 mRNA was increased in ovaries from hypophysectomized rats. Treatment with FSH and/or DES did not alter the abundance of this mRNA. Treatment with PMSG induced a transient increase in IGFBP-5 expression that was localized in a subset of alpha-inhibin-negative follicles. At later times after PMSG, IGFBP-5 expression persisted in the surface epithelium but was not detected in large preovulatory follicles. In vitro studies affirmed the antigonadotropic action of IGFBP-5. CONCLUSION: In vivo expression of IGFBP-5 in the rat ovary is moderated by hormonal treatment both in terms of total expression and follicular localization.

Effect of systemic hyperandrogenism on the adrenal response to adrenocorticotropin hormone.

A virilized patient with an androgen-producing ovarian tumor was used to illustrate the effect of chronic hyperandrogenism on the adrenal response to ACTH. The accumulation rates of substrates for 3 beta-ol dehydrogenase, 21-hydroxylase, and 11 beta-hydroxylase remained unchanged after oophorectomy. This suggests that chronic hyperandrogenism does not affect the activity of enzymes involved in adrenal steroidogenesis.

Antisera to vasoactive intestinal polypeptide inhibit basal prolactin release from dispersed anterior pituitary cells.

Vasoactive intestinal polypeptide (VIP) has been identified in hypothalamic tissue, is secreted into hypophysial portal blood, and stimulates prolactin (PRL) release in vivo and in vitro. It has been proposed, therefore, that VIP is a physiologic PRL-releasing factor. In this study, we confirm that VIP stimulates PRL release from rat pituitary cells in vitro, and demonstrate that an anti-VIP antiserum blocks VIP-induced PRL secretion. Surprisingly, the anti-VIP antiserum inhibited basal PRL secretion from rat pituitary cells in 3 separate experiments. Data from these experiments were pooled, as the responses were similar, revealing basal PRL release of 10.7 +/- 1.3 ng rPRL/10(5) cells (X +/- SE), while anti-VIP antisera significantly inhibited release to 4.4 +/- 0.6 ng rPRL/10(5) cells (p less than 0.001). PRL release in incubates containing control non-immune sera did not differ from basal release, 8.1 ng rPRL/10(5) cells. A further control experiment was conducted wherein cells were incubated with an anti-ACTH antiserum, representing another hyperimmune serum, which had no effect on PRL secretion. These data suggest that VIP, in addition to its possible role as a hypothalamic-derived PRL-releasing factor, may play a role within the pituitary as a regulator of basal PRL secretion.

[The clinical application of the "locus of resistance" method for axillary plexus block (author's transl)]. / Klinische Anwendung der "Loss of Resistance"-Methode zur axillären Blockade des Plexus Brachialis.

We describe a new method of axillary brachial plexus block, the principle of which is to verify the position of the needle in the perivascular tissue not by paraesthesia but by the "loss of resistance" measured when penetrating the perivascular sheath. This method has been developed from the well known "loss of resistance" technique used in epidural anaesthesia and has been tested in practice as well as in theory. This technique not only guarantees greater accuracy in locating the perivascular tissue, but also opens the possibility of decreasing the incidence of lesions of nerves and vessels.

[Steal-induction with ketamine in childhood: comparison of the postanaesthetic period (author's transl)]. / Vergleich der aufwachphase bei 4 verschiedenen Narkosemethoden im Kindesalter.

The behaviour of 48 children ranging from weeks to eight years was observed and compared after four different anaesthesia methods. Either ethrane or halothane was used with or without induction with ketamine i.m. (5 mg/kg bodyweight). Restlessness, the depth of postanaesthetic sleep, shivering, muscle rigidity and vomiting were evaluated every 15 min. up to one hour postoperatively using a graduation from 1--4. Ketamine combined with halothane showed significantly less postoperative restlessness than all other methods. No statistically proven differences were seen in the other criteria, which were noticed more than once. The psychic effects as well as the practical clinical application of this method are discussed.

[Aminopenicillin rashes - a multicentric prospective study (author's transl)]. / Aminopenicillin-Exantheme - eine multizentrische, prospektive Studie.

538 patients, admitted to the hospitals participating in this study for a variety of indications for antibacterial therapy, were treated by the ampicillin-analogue Epicillin. 42 patients (7.8%) who developed exanthem underwent detailed clinical and immunological investigation. Exanthems were scored according to the form of application and doses of Epicillin as well as to the morphology and time of onset of the exanthem. A variety of serological tests were performed: 1. total IgE (RIST), 2. presence of penicilloyl-specific IgE (RAST), 3. penicilloyl-reactive antibodies using an antiglobulin-haemagglutination-tests. In addition, PHA-induced lymphocyte transformation was studied in 10 patients with exanthems. 38/42 patients developed transient monomorphic morbiliform or scarlatiniform exanthems. 4. exanthems were classified as urticarial or polymorphic. In contrast to the 38 patients, the latter also were positive in the serological tests as it is observed in patients with IgE-mediated penicillin allergy.

Rheospirography for determination of respiratory volume.

The method of rheospirography was investigated in 26 voluntary test persons. By means of a spirometric measuring method and after calibration, quantitative statements about size and changes of respiratory minute volume and inspiratory volume could also be evaluated. Computerizing the computation method, rheospirography is suitable for long-term monitoring in intensive care patients.

[A comparison of two preoperative medications: responses in sedative, psychic and somatic effects (author's transl)]. / Vergleich zweier Prämedikationsmethoden: Psychische, sedative und somatische Reaktionen.

The influence of two different premedication methods on the psychic reaction of the patient and their somatic-vegetative effect was tested in a controlled double-blind study. 96 patients between the ages of 20 and 40 took part in the study and were divided into two groups. Group 1 (n = 47) received meperidine (Alodan) and promethazine (Phenergan). Group 2 (n = 49) were given thalamonal. All patients underwent a personality test (Cattell 16 PF) a day prior to scheduled surgery. After administration of the respective pre-anaesthetic drugs, three different test methods were applied to determine their subjective state. Simultaneously, independent from the patients, their psychic reactions were determined by the anaesthetist. Premedication 2 effected less calm, i.e. decrease of fear, exhaustion and depression, than premedication 1. The somatic-vegetative region exhibited no significant difference except for increased cardiocirculatory symptoms in group 1. Based on the less favourable psychodynamics in patients who received thalamonal, it is not advised as pre-anaesthetic medication.

[Test of an improvised anaesthesia system for newborn infants (author's transl)]. / Erprobung eines improvisierten Narkosesystems für Säuglinge.

Anaesthesia for newborn infants is rarely undertaken in hospitals which have no paediatric surgical department. Using the usual anaesthetic equipment for children on newborns involves many hazards, mainly because of the small respiratory volumes of these little patients, the danger of large deadspace and the high resistance of valves in the equipment. A resuscitation bag for newborns proved to be easy and safe as anaesthesia apparatus, if connected to the output of the anaesthetic machine. Blood gases and respiratory volumes were measured in 17 newborn infants (body weight 1,600 g to 5,280 g) during anaesthesia using endotracheal tubes, masks, controlled and spontaneous respiration.

[Assessment of the cardiac output by impedance cardiography (differential rheography) to give optimum continuous positive pressure ventilation (author's transl)]. / Beurteilung des Herzzeitvolumens durch Impedanzmessung (Differentialrheographie) zur Optimierung der kontinuierlichen Uberdruckbeatmung (CPPV).

It is very important to know the cardiac output in artificial positive pressure ventilation for the determination of the exact dosage of dopamine and the endexpiratory pressure. Invasive monitoring of the cardiac output is not suitable for routine bedside use. In our study we looked into the question of whether the dosage of dopamine in continuous positive pressure ventilation could be controlled by impedance determination. Differential rheography, as described by Kaindl, Polzer, and Schuhfried, was used in the study. Relative changes in cardiac output after dopamine administration are shown with sufficient accuracy using the above-mentioned method.

[Loss of resistance in axillary plexus blockade]. / "Loss of resistance" bei der Plexus Axillaris Blockade.

The results of the "loss of resistance" method for identification of the perivascular space are demonstrated. The axillary plexus with its accompanying structures is embeded in the perivascular space. 20 pressure readings were performed with a special transducer. A statistically significant pressure loss was demonstrated after passing the vascular and nerve sheath. The distinct pressure differences during the tissue penetration are recognized with the finger guiding the syringe, similar to the technique used for peridural anaesthesia. We thus believe that we can offer an exact method for blocking the axillary plexus with maximum safety which does not rely on the cooperation of the patient.

[The continuous perivascular axillary plexus block in hand replantation surgery (author's transl)]. / Die kontinuierliche perivasculäre axilläre Plexus-Blockade bei Replantationen an der Hand.

A modified techniques of axillary plexus block is described which enables prolonged analgesia. The main principle of this techniques is to insert an indwelling canula into the perivascular tissue of the plexus brachialis. A cold local anaesthetic (4 degrees) is injected for controlling the canula site. The indications for this technique are all corrective and reconstructive operations of the upper extremity and the postoperative alleviation of pain. Twenty cases with different indications are discussed in this paper. No allergic, toxic or inflammatory reactions were seen in our patients. They were satisfied with this method of analgesia. The easy application, absence of time limiting factors and suitable intraoperative monitoring are the advantages of the method.

[Pain relief in childbirth; an analysis of the analgesic effects of transcutaneous nerve stimulation (TNS), pethidine and placebos (author's transl)]. / Der Wehenschmerz während der Geburt. Zur Analyse der analgetischen Wirkung der transkutanen Nervenstimulation (TNS) im Vergleich mit Pethidin und Plazebos.

The analgesic affects of TNS, pethidine and placebos on labour pain were studied in 30 parturient women during the first stage of labour. 10 had TNS paravertebrally in the region of the afferent nerves at Th 10-Th 12; one group of 5 had unspecific (wrong) TNS; in another group of five no current was applied (placebo); five women were given 50 mg of pethidine intravenously; five patients acted as a control group. To assess the analgesic effects the women were asked to estimate the intensity of pain (grades 1-6) over a period of 70 minutes. There was no significant difference between the placebo, unspecific TNS and control groups as regarded the increase in pain during the test period. Patients who had received pethidine and those who had been given TNS at the site of the afferent nerves transmitting impulses from the uterus experienced considerable relief of pain. The differences were highly significant. The observations prove the genuine analgesic action of TNS. The use of this technique in obstetrics is discussed.

[Sulfametrol-trimethoprim in the treatment of chronic urinary tract infections]. / Sulfametrol-Trimethoprim in der Behandlung der chronischen Harnwegsinfektion

Thirtyeight patients with a chronic urinary infection (definitions see methods) were treated for 3 months with Trimethoprim-Sulfametrol. During therapy in 19 (70%) out of 27 patients without obstruction in the urinary tract infection could be eliminated. In 3 (27%) out of 11 patients with obstruction in the urinary tract infection was also eliminated. In 2 (18%) of these 11 patients the causative organisms changed to resistant strains. In 2 patients (10%) resp. in one patient without obstruction and one with obstruction in the urinary tract the infection recurred within the follow up of 3 months.