Insights into the role of androgen receptor in human testicular peritubular cells.

Contractile smooth muscle-like peritubular cells build the wall of seminiferous tubules in men. They are crucial for sperm transport and complement the functions of Sertoli cells by secreting factors, including glial cell line-derived neurotrophic factor. Previous studies revealed that they also secrete the chemokine C-X-C motif chemokine ligand 12 (CXCL12), which has known roles in spermatogenesis. Peritubular cells express the androgen receptor (AR), which is retained in isolated human testicular peritubular cells. We aimed to explore AR-regulated functions in human testicular peritubular cells. Bearing in mind that infertile men often have high aromatase activity, which may lower intratesticular androgen concentrations, an animal model for male infertility was studied. These mice display an age-dependent loss in spermatogenesis due to high aromatase activity. Human testicular peritubular cells were exposed to dihydrotestosterone or the antiandrogen flutamide. We studied AR, smooth muscle cell markers, glial cell line-derived neurotrophic factor and 15 secreted factors previously identified, including CXCL12. We used qPCR, Western blotting, ELISA or selected reaction monitoring (SRM). In the animal model for male infertility, we employed qPCR and immunohistochemistry. Dihydrotestosterone increased AR and flutamide prevented these actions. The smooth muscle cell markers calponin and smooth muscle actin were likewise increased, while cell size or cellular proliferation was not changed. Dihydrotestosterone did not increase glial cell line-derived neurotrophic factor or CXCL12 secretion but increased levels of serine proteinase inhibitor (SERPIN) E1. The animal model for male infertility with high aromatase activity showed reduced numbers of AR-immunoreactive testicular peritubular cells, suggesting that altered androgen and/or oestrogen levels could influence AR-mediated responses in peritubular cells. Androgens act on human testicular peritubular cells to enhance AR levels, their contractile phenotype and to modulate the secretion of some secreted factors. This study suggests that some aspects of human peritubular cell functions are regulated by androgens.

[Laparoscopic appendectomy--a lot of effort for a minor operation?]. / Entzündeter Blinddarm? Bahn frei für das Laparoskop!

In the hands of an experienced surgeon, laparoscopic appendectomy is by no means a time-consuming procedure that might put the patient at risk. In particular it enables an all round inspection of the abdominal cavity, thus enabling both the detection of diverticular disease and tumors or processes within the true pelvis. The complication-free operation leaves behind only tiny scars, so that, in the event of abdominal complaints at some later date, a mistaken diagnosis of appendicitis might easily be established elsewhere. To help prevent this, the patient must be given the relevant information about the procedure. In addition, provision of the patient with a medical ID card is proposed.

[Laparoscopic resection of the colon]. / Schnell wieder auf den Beinen--aber um welchen Preis?

In terms of achievable outcome, laparoscopic resection of the colon is equally as good as the conventional open procedure. The sole contraindications are patients with severe cardiopulmonary disease, massive adhesions, and peritonitis following a perforation (relative contraindication). The question as to whether the minimally invasive approach is justifiable from the oncological point of view remains to be clarified in further studies.

[Procedural options for laparoscopic inguinal hernial repair--what should the general physician recommend?]. / Serie Schlüssellochchirurgie, Teil 1: Leistenhernien. Bruch-OP mit oder ohne Netz--was können Sie empfehlen?

For the repair of inguinal hernias the conventional Bassini, Shouldice and Lichtenstein procedures, plug repair and laparoscopic procedures are available. The latter may be a totally endoscopic preperitoneal repair (TEP) or a transabdominal preperitoneal meshplasty (TAPP), usually applying polypropylene meshes. In general, alloplastic material should not be used in patients younger than 45, so as to prevent possible groin or testicular complaints, or avoid difficulties with a scar plate in the event of subsequent surgery. Exceptions are, for example, large recurrences or an expressed preference on the part of the patient.

[Fundoplication reborn--thanks to laparoscopic surgical techniques]. / Serie Schlüssellochchirurgie, Teil 2: Fundoplicatio. Reflux-Stopp ohne Risiken und Nebenwirkungen?

Irrespective of the exact procedure employed, laparoscopic fundoplication--in the hands of the expert--is a rapidly performed operation with a low complication rate. Over the long-term, young patients with severe reflux complaints (GERD) in particular should benefit from this operation.

Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells.

Changes in the wall of seminiferous tubules in men with impaired spermatogenesis imply sterile inflammation of the testis. We tested the hypothesis that the cells forming the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), orchestrate inflammatory events and that Toll like receptors (TLRs) and danger signals from the extracellular matrix (ECM) of this wall are involved. In cultured HTPCs we detected TLRs, including TLR2. A TLR-2 ligand (PAM) augmented interleukin 6 (IL-6), monocyte chemo-attractant protein-1 (MCP-1) and pentraxin 3 (PTX3) in HTPCs. The ECM-derived proteoglycan biglycan (BGN) is secreted by HTPCs and may be a TLR2-ligand at HTPCs. In support, recombinant human BGN increased PTX3, MCP-1 and IL-6 in HTPCs. Variable endogenous BGN levels in HTPCs derived from different men and differences in BGN levels in the tubular wall in infertile men were observed. In testes of a systemic mouse model for male infertility, testicular sterile inflammation and elevated estradiol (E2) levels, BGN was also elevated. Hence we studied the role of E2 in HTPCs and observed that E2 elevated the levels of BGN. The anti-estrogen ICI 182,780 blocked this action. We conclude that TLR2 and BGN contribute to sterile inflammation and infertility in man.

Developmental and hormonal regulated gene expression of fibroblast growth factor 2 (FGF-2) and its receptors in porcine endometrium.

This study examined the mRNA levels of the fibroblast growth factor 2 (FGF-2) and two of its receptors, FGFR1IIIc and FGFR2IIIc, at days 12 and 20 of the ovarian cycle (DC 12 and DC 20), days 1 and 12 of pregnancy (DP 1 and DP 12) as well as the influence of progesterone (P) and estradiolbenzoate (EB) on their expression in the endometrium of ovariectomized (ovx) gilts by real-time PCR. Proteins of FGF-2 and FGFR1 were immunolocalized. FGF-2 and FGFR2IIIc mRNAs were always found with a 5- to 30-fold higher absolute concentration compared to FGFR1IIIc. The latter transcript significantly declined between DP 1 and DP 12, whereas FGF-2 and FGFR2IIIc showed no significant changes at that time. FGF-2 transcription was greater at DC 20 than at DC 12, but significantly most transcripts were found in ovx gilts. EB induced a significant suppression of FGF-2 mRNA, an effect which was antagonized by P and even prevented by P+EB. FGFR1IIIc mRNA was significantly increased at DC 20, that of FGFR2IIIc at DC 12 displaying a 10 times higher absolute mRNA amount. Suppression of FGFR1IIIc mRNA by P was abolished by EB while P+EB attenuated this effect. FGFR2IIIc transcripts were equally restrained by P or EB while a combination of both slightly reduced such declines. Localization of FGF-2 and FGFR1 proteins in stromal, glandular and vascular compartments was effected by sex steroids. Both proteins were strongly expressed at DP 12 but not at DP 1. Summarized, differential temporal and spatial localization of FGF-2 and FGFR1 after response to sex steroids support a complex regulation of this ligand receptor system important for proliferation and differentiation of uterine cells including angiogenic processes. While FGFR1IIIc is presumed to be promoted by estradiol FGFR2IIIc appears to be dominated by progesterone implicating different biological importance for a functional endometrium.

Regulation of the VEGF-system in the endometrium during steroid-replacement and early pregnancy of pigs.

Vascular endothelial growth factor (VEGF) and its specific receptors FLT-1 and FLK-1 represent an important ligand-receptor system involved in angiogenesis and permeability. These factors are supposed to be influenced by ovarian steroids involved in developmental changes in female reproductive tissue as oviduct and uterus. The aims of this study were to assess the expression of VEGF and its receptor mRNAs during the early implantation period in porcine endometrium using real-time RT-PCR. Furthermore, effects of estradiolbenzoate (EB) and progesterone (P) on endometrium of ovariectomized (ovx) pigs were examined by RT-PCR and immunohistochemistry. A complete VEGF system was found in endometrial tissue using RT-PCR detecting the main VEGF isoform 188 aa, FLT-1 and FLK-1. A significant upregulation of the mRNAs of VEGF and its receptors was observed in the endometrium during the peri-implantation when compared with the pre-implantation period. Regarding endometrium of non-pregnant ovx-pigs an application of P led to elevated transcript levels of VEGF whereas mRNA-expression was reduced after EB treatment compared to non-treated ovx-animals. When pigs were administrated EB and P simultanously, a decrease in VEGF mRNA concentration was recorded. For FLT-1, none of the steroids increased mRNA expression compared to the ovx-group. Analysis of FLK-1 receptor mRNA demonstrated that only after EB + P treatment mRNA-expression was stimulated but stayed unchanged after P and EB when compared with the ovx-group. Immunohistochemistry revealed FLK-1 and VEGF proteins in glandular and luminal epithelia of the endometrium with emphasized staining after P and P + EB treatment of ovx-pigs. Summarized, altered VEGF and FLK-1 expression during the implantation period as well as under steroid hormones suggest this growth factor as a potent regulator of hyperpermeability supporting the angiogenic process in porcine endometrium.

Expression of endothelial and inducible nitric oxide synthases is modulated in the endometrium of cyclic and early pregnant mares.

The expression of the endothelial and inducible nitric oxide synthases (eNOS and iNOS, respectively) was examined in the endometrium of cyclic and pregnant mares by real-time polymerase chain reaction and immunohistology. The concentration of eNOS mRNA varied throughout the oestrous cycle, with significantly higher transcripts on Day 5 of the oestrous cycle (P < 0.05), whereas iNOS transcription did not change significantly over time (P > 0.05). In early pregnant mares both eNOS and iNOS mRNA increased between Days 12 and 15 (P < 0.05). In cyclic mares, eNOS protein was detected immunocytochemically in endometrial epithelia, the basement membrane, the endothelial layer and smooth muscle cells of the vasculature. Using immunocytochemical methods, iNOS protein was undetectable in the endometrium of cyclic mares but could be demonstrated in pregnant mares. Endometrial epithelia of pregnant mares were immunopositive for both proteins with a more intense labelling for iNOS. Thus, the present study describes for the first time the modulation and spatial distribution of eNOS and iNOS expression during the oestrous cycle and early pregnancy, suggesting that ovarian steroids are differently involved in the regulation of each NOS. Localisation of eNOS protein in endometrial epithelia and various vascular components indicates that this isoform may be involved in the regulation of endometrial cyclicity. The presence and increase of both forms of NOS during early gestation suggest a role for them in the control of endometrial vascular bed and glandular activity to provide a suitable microenvironment for successful pregnancy.

[Lymphographic investigations of oedema of the extremities following reconstructive vascular surgery in the femoro-popliteal territory (author's transl)]. / Lymphangiographische Untersuchungen zum Extremitätenödem nach rekonstruktiven Gefässeingriffen im Femoropoplitealbereich.

In 37 patients, oedema of the legs was observed following successful femoro-popliteal surgery; lymphangiograms were performed between the third and ninth post-operative days and the intact lymph vessels at the knee and at the groin were counted. In 27 patients there was partial to total disruption of the lymphatic vessels. There was a clear correlation between the degree of swelling of the leg and thigh with the number of not divided lymphatic vessels at the knee and groin. In the presence of more than three intact lymph vessels, swelling amounted to only 1 to 2 cm., whereas if all lymph vessels had been divided, swelling amounted to 7 cm. Extensive soft tissue trauma and repeat surgery resulted in a greater reduction in intact lymph vessels and correspondingly more oedema than was found with more conservative surgery and after initial operations. The pre-operative condition of the arteries, the presence of venous disease and the postoperative blood-flow in the leg had no influence on postoperative oedema. In order to avoid post-operative lymphoedema, it is necessary to preserve the lymphatics during surgery. Marked oedema requires treatment consisting of compression bandages and medicaments.

[The value of sonography in the differential diagnosis of pseudotumours of the kidney (author's transl)]. / Bedeutung der Sonographie für die Differentialdiagnostik von Pseudotumoren der Niere.

Two hundred and three patients with urographic appearances suspicious of a space-occupying lesion were examined by sonography. Seventy-nine showed normal results; there were 65 cysts, 20 malignant lesions, 20 pseudo-tumours and 19 with other abnormalities such as hydronephrosis, urolithiasis and inflammatory lesions. Pseudotumours are due to varients of the structure of the kidney, which resemble space-occupying lesions in the excretory urogram. The sonogram shows them as low echo, centrally protruding structures arising from the edge of the parenchyma. Angiographically they are islands of parenchyma with normal vessels. Sonography has proved to be a necessary complement to excretion urography and provides a more certain indication for renal arteriography. Angiography can be limited to changes in the parenchyma, since sonography is able to define cystic processes.

[Sonographic diagnosis of enlarged parathyroid glands in hyperparathyroidism (author's transl)]. / Sonographische Diagnostik vergrösserter Nebenschilddrüsen beim Hyperparathyreoidismus.

Fifty-nine patients suspected clinically of having primary or tertiary hyperparathyroidism have been examined since 1978 in order to localize enlarged parathyroid glands. With glands larger than 5 mm. this proved successful in about 90% of those situated in the neck. The sonographic features of enlarged parathyroid glands are poor echoes, smooth margins and the typical position on the medial and posterior surface of the thyroid gland. A requirement for diagnostic success is the use of modern compound apparatus with digital convertors and focussed high resolution probes.

[Investigations on pain reduction during peripheral angiography (author's transl)]. / Untersuchungen zur Schmerzverminderung bei der Extremitätenangiographie.

An attempt was made to reduce pain during femoral angiography by adding 1 mg. of Lidocaine/ml. contrast medium in the course of 95 examinations. In a further 87 patients, Diazepam was injected intravenously before the injection of the contrast-Lidocaine mixture. Pain and the feeling of heat was compared with a control group who received contrast medium with 10% physiological saline. There was a highly significant reduction in pain sensation as a result of Lidocaine; pain was further reduced by additional Diazepam, which also reduced heat sensation, but resulted in a fall in blood pressure. High risk patients did not suffer any significant complications. Lidocaine is well suited for out patients, but Diazepam requires a longer period of observation. General anaesthesia has been used only if patients insisted on it or if there was known contrast reaction.

[Laparoscopic management of a Spigelian hernia]. / Die laparoskopische Versorgung einer Spieghel'schen Hernie.

The Spigelian hernia occurs where the vertical linea semilunaris, along the lateral border of the rectus muscle, joins the linea semicircularis. The hernia lies in the soft tissue under the aponeurosis of the oblique abdominis muscle; incision of that layer can be avoided by laparoscopic techniques. In this case the hernial canal was closed, firstly with single titanium staples, and secondly with a continuous laparoscopic suture using resorbable material. In suspicious cases laparoscopy should be performed to confirm the diagnosis of a Spigelian hernia. Laparoscopic hernial repair should be evaluated by further usage of this technique.

[Modification of the infrared light coagulator LC 250. Development of probes for endoscopic use]. / Weiterentwicklung des Infrarotlicht-Coagulators LC 250. Entwicklung von Sonden für den endoskopischen Gebrauch.

With regard to prior positive results using the infrared-light-coagulator LC 250 for hemostasis of bleeding parenchymal organs and inoperable tumors, new tubes with 5 and 10 mm diameter were developed for laparoscopic purposes. The first clinical experiences showed the secure and rapid hemostasis after bleedings of the liver following a cholecystectomy, smaller resections and biopsies also resulted after lesions of the abdominal wall. The newly developed applicator consisting of a metal or teflon grip, improved the performance of these probes.

[Preoperative ultrasonic diagnosis and localization of enlarged parathyroid glands in suspected hyperparathyroidism]. / Präoperative sonographische Lokalisationsdiagnostik vergrösserter Nebenschilddrüsen bei Verdacht auf Hyperparathyreoidismus.

Since August 1978, the neck of 68 patients with the clinical diagnosis of hyperparathyroidism was examined by ultrasound. The accuracy of the method increased from 61% during the first period of investigation to 82% using a newly-developed ultrasound scanner. These results are comparable with those obtained by invasive methods like angiography or selective venous blood sampling for the assay of parathyroid hormone. Positive preoperative localization of enlarged parathyroid glands confirmed the diagnosis of HPT. Cases involving acute HPT preoperative localization of enlarged parathyroid glands requires prompt surgical management. Preoperative localization of an adenoma allows direct removal of the enlarged gland and exploration of the others within the immediate section from microscopic examination under surgery.

[Incidence of stab injuries of the heart in the clinic and forensic autopsy practice. Experiences with 6 surgical procedures]. / Häufigkeit von Herstichen in Klinik und rechtsmedizinischem Sektionsgut.

During a period when 6 patients were operated following a cardiac stab wound 4 patients survived the procedure. In 45 persons forensic autopsies were performed. The analysis of both groups elucidate that successful treatment is possible if pericardial tamponade inhibits free bleeding into the cavity of the thorax. But this situation must be treated very quickly avoiding cardiac arrest due to cardial blockage. In contrast to the autopsies in the clinical group no atrial wounds or incisions of coronary arteries were observed.

[The Hickman catheter in bone marrow transplantation, long-term cytostatic and infusion therapy. Experience of 102 catheters in children]. / Der Hickman-Katheter bei Knochenmarktransplantation, langfristiger Cytostatica- und Infusionstherapie. Erfahrungen mit 102 Kathetern bei Kindern.

Right atrial Hickman catheters are used for long-term venous access in children suffering from leukemia and malignoma. Parenteral alimentation, blood withdrawal and bone marrow transplantation can be performed safely without high incidence of cutaneous infections and sepsis due to a long subcutaneous tunnel. Aseptic dressing changes and catheter care are the most important prerequisites for a low complication rate in the use of these catheters. Septicemia and technical complications observed following the use of 102 Hickman catheters in 81 children are reported and discussed.

[Infrared coagulation of the lung. Initial experimental and clinical results]. / Infrarotcoagulation an der Lunge. Erste tierexperimentelle und klinische Ergebnisse.

With regard to the good results which were found using the infrared coagulator (IRC) in hemostasis of liver and spleen experimental and clinical investigations of the lung were performed. Animal experiments elucidated the necessity of ligation of greater vessels as well as bronchi. Secure plugging of lung tissue was also possible following increased positive pressure respiration. A mean maximal extend of necrosis of 3 mm was measured. Clinical use in 11 patients proved secure plugging of tissue due to IRC application. Drainages could be removed within 4 days without appearance of broncho-pleural fistulas.

[Arterial compression syndrome. First the fingers tingle, then thrombosis of the brachial artery]. / Arterielles Kompressionssyndrom. Erst kribbeln die Finger, dann thrombosiert die Arteria brachialis.

The thoracic outlet syndrome and the entrapment syndrome involving the popliteal artery are two major examples of arterial compression syndrome. Since not only the arteries, but also the entire neurovascular bundle is compressed, the initial symptoms are often neurological: paresthesias, tingling, numbness, etc., in particular when certain movements are carried out. In such a case, bilateral blood pressure measurements, provocative tests and Doppler (duplex) examination are indicated. A point that is, perhaps, less well-known is the fact that compression can lead to serious vascular lesions ranging from post-stenotic aneurysms to complete thrombotic occlusion and peripheral emboli. When the diagnosis has been confirmed, early surgery is indicated.