Diagnostic Value of Vaginal Discharge, Wet Mount and Vaginal pH - An Update on the Basics of Gynecologic Infectiology.

The majority of uncomplicated vulvovaginal complaints (e.g. bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis) can be detected with uncomplicated basic infectiological tests and can usually be treated effectively without requiring further diagnostic procedures. Tests include measurement of vaginal pH, preparation and assessment of wet mount slides prepared from vaginal or cervical discharge, and the correct clinical and microbiological classification of findings. In Germany, at least in recent years, this has not been sufficiently taught or practiced. As new regulations on specialist gynecologic training in Germany are currently being drawn up, this overview provides basic information on gynecologic infectiology and summarizes clinically relevant aspects of recent microbiological findings on the physiology and pathology of vaginal flora. The clinical signs and symptoms of aerobic vaginitis, the pathogenesis of which is still not completely understood, are also reviewed. Finally, the symptoms, indications and risk factors for pelvic inflammatory disease (PID) are presented. In contrast to the above-listed infections, PID requires immediate culture of the pathogen from samples (e.g. obtained by laparoscopy) with microbiological diagnostic procedures carried out by specialist laboratories. A schematic summary of all pathologies discussed here is presented.

Impact of Patient and Procedure Mix on Finances of Perinatal Centres - Theoretical Models for Economic Strategies in Perinatal Centres.

Introduction: In Germany, cost and revenue structures of hospitals with defined treatment priorities are currently being discussed to identify uneconomic services. This discussion has also affected perinatal centres (PNCs) and represents a new economic challenge for PNCs. In addition to optimising the time spent in hospital, the hospital management needs to define the "best" patient mix based on costs and revenues. Method: Different theoretical models were proposed based on the cost and revenue structures of the University Perinatal Centre for Franconia (UPF). Multi-step marginal costing was then used to show the impact on operating profits of changes in services and bed occupancy rates. The current contribution margin accounting used by the UPF served as the basis for the calculations. The models demonstrated the impact of changes in services on costs and revenues of a level 1 PNC. Results: Contribution margin analysis was used to calculate profitable and unprofitable DRGs based on average inpatient cost per day. Nineteen theoretical models were created. The current direct costing used by the UPF and a theoretical model with a 100 % bed occupancy rate were used as reference models. Significantly higher operating profits could be achieved by doubling the number of profitable DRGs and halving the number of less profitable DRGs. Operating profits could be increased even more by changing the rates of profitable DRGs per bed occupancy. The exclusive specialisation on pathological and high-risk pregnancies resulted in operating losses. All models which increased the numbers of caesarean sections or focused exclusively on c-sections resulted in operating losses. Conclusion: These theoretical models offer a basis for economic planning. They illustrate the enormous impact potential changes can have on the operating profits of PNCs. Level 1 PNCs require high bed occupancy rates and a profitable patient mix to cover the extremely high costs incurred due to the services they are legally required to offer. Based on our theoretical models it must be stated that spontaneous vaginal births (not caesarean sections) were the most profitable procedures in the current DRG system. Overall, it currently makes economic sense for level I PNCs to treat as many low-risk pregnancies and neonates as possible to cover costs.

Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation.

BACKGROUND: During human pregnancy, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11beta-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. OBJECTIVE: To examine developmental changes in placental 11beta-HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. METHODS: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11beta-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. RESULTS: Placental mRNA expression of 11beta-HSD2 and PGDH increased significantly with gestational age (r=0.55, P=0.0002 and r=0.42, P=0.007). In addition, there was a significant correlation between the two enzymes (r=0.58, P<0.0001). CONCLUSIONS: In the course of pregnancy there is an increase in 11beta-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11beta-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11beta-HSD2 up-regulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins.

Decreased gene expression of 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase in human placenta of patients with preeclampsia.

Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective was to investigate a possible relation between 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), converting cortisol to cortisone, and PGDH gene expression in the placenta of patients with preeclampsia. In placental tissue taken from 20 healthy women with normal pregnancy, 20 premature babies born after labor before term, and 18 neonates after preeclamptic pregnancy, 11beta-HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative competitive PCR. When comparing matched pairs, there were 3-fold lower 11beta-HSD2/glyceraldehyde-3-phosphate dehydrogenase (11beta-HSD2/GAPDH) mRNA levels in placentas of patients with preeclampsia than in controls [0.18 +/- 0.04 relative units (RU) and 0.61 +/- 0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH mRNA concentrations (0.28 +/- 0.15 RU and 0.50 +/- 0.18 RU, P = 0.0003). PGDH and 11beta-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11beta-HSD2/GAPDH, but not PGDH, showed a significant correlation to birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01). Results could be confirmed by competitive PCR. We conclude that, in preeclampsia, 11beta-HSD2 mRNA expression is reduced, leading to the known decrease of 11beta-HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished conversion of placental cortisol may lead to reduced PGDH mRNA expression as found in the present study.

7-Deazaadenines bearing polar substituents: structure-activity relationships of new A(1) and A(3) adenosine receptor antagonists.

A series of 28 new pyrrolo[2,3-d]pyrimidine-4-amines, pyrimido[4, 5-b]indole-4-amines, and tetrahydropyrimido[4,5-b]indole-4-amines was synthesized and their adenosine receptor affinity determined in radioligand binding assays at rat A(1) and A(2A) adenosine receptors (ARs). Selected compounds were additionally investigated in binding assays at recombinant A(3) ARs. The 2-phenyl residue in (R)-7-(1-methylbenzyl)-2-phenylpyrrolo[2,3-d]pyrimidine-4-amine (ADPEP, 1) and in the corresponding pyrimido[4,5-b]indole (APEPI, 3) could be bioisosterically replaced by heterocyclic rings, such as 2-thienyl and 4-pyridyl. The resulting compounds retained high affinity and selectivity for A(1) ARs. Judging from the investigation of selected compounds, it appears that they are also potent at human A(1) ARs and selective not only versus A(2A) ARs but also highly selective versus A(2B) and A(3) ARs. The p-pyridyl-substituted derivatives 11 and 27 (APPPI) may be interesting pharmacological tools due to their fluorescent properties. Pyrrolo[2,3-d]pyrimidine-4-amine derivatives which were simultaneously substituted at N7 and N(4), combining the substitution pattern of ADPEP (1) and DPEAP (2), showed very low affinity for A(1) ARs. This finding supports our previously published hypothesis of different binding modes for pyrrolopyrimidines, such as ADPEP (1) and DPEAP (2). DPEAP (2), a pyrrolo[2,3-d]pyrimidine-4-amine substituted at the amino group (N(4)), was found to exhibit high affinity for human A(3) ARs (K(i) = 28 nM), whereas N(4)-unsubstituted analogues were inactive. DPEAP (2) and related compounds provide new leads for the development of antagonists for the human A(3) AR.

Ludwig Fraenkel: 'spiritus rector' of the early progesterone research.

The search for the corpus luteum hormone progesterone took more than three decades and the efforts of many scientists all over Europe and the USA. In 1934, after a dramatic neck-and-neck scientific race, four research groups independently from each other reported on the successful isolation of the pure substance. Two of the groups were from the then-German cities of Breslau and Danzig, the others were from the USA and Switzerland. Possibly, the Breslau group had already had the purified hormone as early as 1933. At that time, gynecologist Ludwig Fraenkel (1870-1951) had been their 'spiritus rector' for more than three decades. It was Fraenkel himself who at the beginning of the century, in examining a hypothesis of the anatomist Gustav Jacob Born (1851-1900), had provided experimental proof for an endocrine function of the corpus luteum. Later on, Fraenkel enlisted the help of chemist Karl Heinrich Slotta (1895-1987) in the purification of the hormone. This took place after important requirements for the isolation and for the semiquantitative determination of the hormone (e.g. Corner-Allen test) had been established elsewhere. Also belonging to the Breslau research group were Erich Fels (1897-1981) and Heinrich Ruschig (born in 1906). Fels was an assistant to Fraenkel, Ruschig a PhD candidate directed by Slotta. Shortly after the group had succeeded in purifying progesterone, the Breslau group was broken apart by the National Socialist's racial policies: Fraenkel, Fels and Slotta were forced into emigration.

[Ludwig Fraenkel, corpus luteum and discovery of progesterone]. / Ludwig Fraenkel, das Corpus luteum und der Weg zum Progesteron.

In 1934, after a dramatic neck-and-neck scientific race, four research groups independently from each other reported on the successful purification of progesterone. Two of the groups were from the then-German cities of Breslau and Danzig, the others were from the USA and Switzerland. Possibly, the Breslau group had already had the purified hormone as early as 1933. At that time, gynecologist Ludwig Fraenkel (1870-1951) had been their "spiritus rector" for more than three decades. It was Fraenkel himself who at the beginning of the century, in examining a hypothesis of the anatomist Gustav Jacob Born (1851-1900), had provided experimental proof for an endocrine function of the corpus luteum. Later on, Fraenkel enlisted the help of chemist Karl Heinrich Slotta (1895-1987) in the purification of the hormone. This took place after important requirements for the isolation and for the semiquantitative determination of the hormone (e.g. the Corner-Allen-Test) had been established elsewhere. Also belonging to the Breslau research group were Erich Fels (1897-1981) and Heinrich Ruschig (born in 1906). Fels was an assistant to Fraenkel, Ruschig a PhD-candidate directed by Slotta. Shortly after the group had succeeded in purifying Progesterone the Breslau group was broken apart by the National Socialists' racial policies: Fraenkel, Fels and Slotta were forced into emigration.

8-(Sulfostyryl)xanthines: water-soluble A2A-selective adenosine receptor antagonists.

8-(Sulfostyryl)xanthine derivatives were synthesized as water-soluble A2A-selective adenosine receptor (AR) antagonists. meta- and para-sulfostyryl-DMPX (3,7-dimethyl-1-propargylxanthine) derivatives 11a and 11b exhibited high affinity to rat A2A-AR in submicromolar concentrations, and were 20- to 30-fold selective versus rat A1-AR. Styryl-DMPX derivatives were inactive at human A2B- and A3-AR. 1,3-Dipropyl-8-p-sulfostyrylxanthine (13) or only a 7-methyl derivative (14) showed similar (13) or higher (14) A2A affinity than 11a and 11b but showed no (13) or only a low degree (14) of selectivity versus A1-, A2B-, and A3-AR. The A2A-selective sulfostyryl-DMPX derivatives exhibit high water-solubility and may be useful research tools for in vivo studies.

Bioactive pyridoacridine alkaloids from the micronesian sponge Oceanapia sp.

The Micronesian sponge Oceanapia sp. afforded three pyridoacridine alkaloids: the known compounds kuanoniamine C (1) and kuanoniamine D (2), as well as the new N-deacyl derivative (3) of the kuanoniamines. Compounds 1 and 2 exhibited insecticidal activity toward neonate larvae of the polyphagous pest insect Spodoptera littoralis (LC50 of 156 and 59 ppm, respectively), when incorporated into artificial diet. Both compounds also showed toxicity in the brine shrimp lethality test with a LC50 of 37 micrograms/mL (compound 1) and 19 micrograms/mL (compound 2), respectively. The N-deacyl derivative did not show any remarkable effect in both bioassays. Cytotoxcity of the alkaloids was studied in vitro, using two human cell lines. The new derivative (3) appeared to be active in the same range of concentrations as kuanoniamine C (1) and D (2). The IC50 of 3 was 1.2 micrograms/mL toward HeLa cells and 2.0 micrograms/mL toward MONO-MAC 6 cells. In receptor binding assays compound 2 showed affinity to A1- and A2A-adenosine receptors with Ki values of 2.94 and 13.7 microM, respectively. Compound 1 was less active than compound 2, whereas compound 3 showed no affinity toward adenosine receptors. In addition, compounds 1-3 exhibited moderate affinity to benzodiazepine binding sites of GABAA receptors.

Aza-analogs of 8-styrylxanthines as A2A-adenosine receptor antagonists.

In the present study we synthesized aza-analogs of 8-styrylxanthines, in which the ethenyl bridge is replaced by an imine, amide, or azo function, in order to investigate structure-activity relationships of the 8-substituent of A2A-selective xanthine derivatives. Thus, various 8-substituents were combined with theophylline or caffeine, respectively, and affinities of the novel compounds for adenosine A1- and A2a-receptors were determined and compared with those of analogous 8-styrylxanthine derivatives. 8-(Benzylideneamino)caffeine derivatives exhibited high affinity and selectivity for A2A-adenosine receptors, but were unstable in aqueous buffer solution at physiological pH values. 8-(Phenylazo)caffeine derivatives were less potent than corresponding 8-styrylcaffeine derivatives at adenosine receptors. The most potent azo compound of the present series was 8-(m-chlorophenylazo)caffeine (14b) exhibiting a Ki value of 400 nM at A2A-adenosine receptors and 20-fold selectivity versus A1-receptors. Due to the facile synthetic access to 8-(phenylazo)xanthine derivatives, which are obtained by coupling of 8-unsubstituted xanthines with phenyldiazonium salts, 14b may be an interesting new lead compound for the development of more potent and selective A2A-antagonists with azo structure.

Synthesis and structure-activity relationships of 3,7-dimethyl-1-propargylxanthine derivatives, A2A-selective adenosine receptor antagonists.

A series of 8-substituted derivatives of 3,7-dimethyl-1-propargylxanthine (DMPX) was synthesized and investigated as A2A adenosine receptor antagonists. Different synthetic strategies for the preparation of DMPX derivatives and analogues were explored. A recently developed synthetic procedure starting from 3-propargyl-5,6-diaminouracil proved to be the method of choice for the preparation of this type of xanthine derivatives. The novel compounds were investigated in radioligand binding studies at the high-affinity adenosine receptor subtypes A1 and A2A and compared with standard A2A adenosine receptor antagonists. Structure-activity relationships were analyzed in detail. 8-Styryl-substituted DMPX derivatives were identified that exhibit high affinity and selectivity for A2A adenosine receptors, including 8-(m-chlorostyryl)-DMPX (CS-DMPX, Ki A2A = 13 nM, 100-fold selective), 8-(m-bromostyryl)-DMPX (BS-DMPX, Ki A2A = 8 nM, 146-fold selective), and 8-(3,4-dimethoxystyryl)-DMPX (Ki A2A = 15 nM, 167-fold selective). These and other novel compounds are superior to the standard A2A adenosine receptor antagonists KF17837 (4) and CSC (5) with respect to A2A affinity and/or selectivity.

[Room with a view for the "daughters of pain": 1828 was the beginning of new obstetrics in Erlangen]. / Zimmer mit Aussicht für die "Schmerzenstöchter": 1828 begann die klinische Geburtshilfe in Erlangen.

The roots of clinical obstetrics at the University of Erlangen go back as far as the end of the 18th century. In 1796, Christian Friedrich Deutsch (1768-1843) was appointed as the first university teacher solely responsible for obstetrics. At the same time, he was also vehemently committed to the creation of a clinical institution for the purpose of training in obstetrics. For several reasons, the opening of a maternity home in a converted private house on the outskirts of town did not take place until 1828 under the leadership of Anton Bayer (1791-1832). In 1854/55, it was possible to move into a new building situated directly next to the university hospital; this new building was planned by Eugen Rosshirt (1798-1872). The increasing number of births and students as well as the introduction of gynecology finally led to the establishment, in 1878, of the first gynecological hospital in the sense understood by us today. The hospital was designed by Karl Schröder (1838-1887) who was the first Erlangen teacher of obstetrics to complete his habilitation in this field and probably has to be considered as the founder of the science of obstetrics at the University of Erlangen.

[Champagne administered by spoon for peritonitis after cesarean section. From the history of obstetrics in Erlangen--data from about 60,000 deliveries in 100 years]. / Bei Peritonitis nach Sektio Champagner löffelweise. Aus der Geschichte der Geburtshilfe in Erlangen--Daten von rund 60,000 Entbindungen in 100 Jahren.

The University of Erlangen has been engaged in clinical obstetrics for approximately 170 years. During this time, Erlangen University's delivery house, opened in 1828 and at first having considerably less than 50 births a year, developed into a perinatal centre with approximately 1,700 births a year. For the period from 1880 to 1981, a group of MD students reviewed the existing records and evaluated 60,000 births with respect to more than 40 parameters. Part of the results obtained are shown with special reference to operative obstetrics. Apart from the general influence of the scientific development on decisions and results within obstetrics, individual factors were also recognizable, factors which are linked with the experiences, insights and specialized working areas of the particular head of the hospital.

[In the light of a petroleum lamp the operation could begin. Richard Frommel (1854-1912): pioneer in treatment of ruptured extrauterine pregnancy]. / Beim Schein einer Petroleumlampe konnte die Operation beginnen. Richard Frommel (1854-1912): Pionier bei der Behandlung der rupturierten Extrauteringravidität.

Richard Frommel (1854-1912) can be called an outstanding German gynaecologist during the late 19th century. This article is intended to give a picture of his life, work, and personality. Frommel was director of the department of obstetrics and gynaecology at the university of Erlangen from 1887 to 1901. Science owes to him, amongst other contributions, an important impulse for changing the therapy of ruptured ectopic pregnancy. Up to the present day Frommel's name together with that of Johann Chiari (1817-1854), serve as eponyms for a special form of the amenorrhoea-galactorrhoea syndrome, namely, the persistent one-post partum. It remains puzzling why Frommel resigned office, when he was just 46 years old, giving up gynaecology completely only a short time later.

[Conception and pregnancy without complications in parenteral home nutrition]. / Konzeption und komplikationsloser Schwangerschaftsverlauf unter parenteraler Heimernährung.

A case is reported of conception and successful completion of a pregnancy in a 31 year old woman maintained on home parenteral nutrition while suffering from a primary distension of the intestinal lymphatic vessels and intestinal loss of protein. A healthy, 3400 g female infant was born near term by cesarean section. This case confirms the few so far published experiences showing that conception and maintenance of the pregnancy under total parenteral nutrition needs no or just a slight adaptation of the regimen.