Spontaneous rupture of the spleen: ultrasound patterns, diagnosis and follow-up.

Spontaneous rupture of the spleen is an extremely rare complication usually of infectious diseases or disorders of the haematopoietic system and has been described mostly in case reports. The incidence, symptoms, causes, therapy, and prognosis are poorly defined. From July 1985 to January 2000 41 patients with spontaneous splenic rupture were diagnosed by abdominal ultrasound and confirmed by splenectomy (n=12), CT (n=15), and ultrasound follow up (n=26). An ultrasound grading system was retrospectively established based on the degree of splenic injury (grade 0-2=low grade injury, grade 3=high grade injury) and correlated with surgical procedures. 30 day mortality rate was studied in relation to underlying disorders, ultrasound grades and treatment decisions. 21 patients had underlying malignant disorders (group I) and 20 patients had benign diseases (group II). Between group I and II we observed a highly significant difference in 30 day mortality rates (n=7; 38.1% vs n=1; 5%, p<0.01), but no significant difference in high grade injury rate (n=3; 14.3% vs n=2; 10.0%; p=ns) and surgical treatment rate (n=5; 23.8% vs n=7; 35.0%; p=ns). Depending on ultrasound grades the surgical procedures were 0% for grade 0, 16.7% for grade 1, 30.4% for grade 2, and 60% for grade 3. There were no significant differences between patients, who died within the first 30 days (n=9) and those who survived more than 30 days (n=32) regarding high grade splenic injury rate (n=0; 0% vs n=5; 15.6%; p=ns), and surgical treatment rate (n=2; 22.2% vs n=10; 31.2%; p=ns). Spontaneous rupture of the spleen is an extremely rare event. It is associated with a high mortality rate within 30 days in patients with malignant disease. Sonomorphologic grading is helpful for treatment decisions. 30 day mortality rate is correlated with neither ultrasound grades, nor surgical treatment rates.

2-arylalkyl-substituted anthracenones as inhibitors of 12-lipoxygenase enzymes. 1. Structure-activity relationships of the terminal aryl ring.

A series of 2-arylmethyl-substituted anthracenones were synthesized and tested as inhibitors of three types of 12-lipoxygenase isoforms in epidermal homogenate of mice, bovine platelets and porcine leucocytes. Their inhibitory activities were compared with those to inhibit the 5-lipoxygenase enzyme in bovine leucocytes. Structure-activity relationships are described with particular emphasis on modifications of the terminal aryl nucleus. The ability of the compounds to selectively inhibit the 12-lipoxygenase enzymes was dependent on a high overall lipophilicity of the inhibitor, whereas compounds with decreased lipophilicity were also inhibitors of the 5-LO enzyme. Among the more lipophilic inhibitors, the unsubstituted 2-phenylmethyl analogue 6a as well as the carboxylic acid ester 6q appeared to be selective inhibitors of platelet-type 12-LO isoform.

Influence of ABO blood groups on primary hemostasis.

BACKGROUND: Recently, the in vitro bleeding time test (IVBT) was proved to be a very sensitive screening method for the detection of vWD, showing rather good correlation between the closure time and the level of vWF. The vWF levels have been found to be significantly lower in healthy humans who are group O than in those who belong to the other ABO blood groups (non-group O). The aim of this study was to detect whether these differences in vWF levels in normal persons correspond to differences in nonvascular primary hemostasis when investigated by the IVBT. MATERIAL AND METHODS: Healthy blood donors (n = 162) without evidence of hemostatic disorders, without ingestion of drugs for at least 2 weeks, and with normal in vivo bleeding time endpoints, normal factor VIII clotting activity levels, normal structure of vWF multimers, and normal ristocetin-induced platelet aggregation were examined by IVBT. IVBT was performed with two automated systems (Thrombostat 4000, VDG [TST]; and a platelet function analyzer (PFA-100, Dade Behring [PFA]). CaCl2 and ADP were used as aggregants for the two TST tests (TST-CaCl2 and TST-ADP), and ADP- or epinephrine (Epi)-coated membranes were used with the two PFA tests (PFA-ADP and PFA-Epi). RESULTS: Closure time in the IVBT significantly correlated with the blood groups, but in reverse order (as did blood volume; data not shown): TST-ADP (mean +/- SD): group O, 89 +/- 14.6 seconds versus non-group O, 82 +/- 13 seconds (p<0.01); TST-CaCl(2): group O, 154 +/- 28.9 seconds versus non-group O, 140 +/- 31.3 seconds (p<0.01); PFA-ADP: group O, 91 +/- 13.4 seconds versus non-group O, 86 +/- 11.9 seconds (p<0.05); PFA-Epi: group O, 112 +/- 15.4 seconds versus non-group O, 104 +/- 16.7 seconds (p<0.05). Donors with vWF < or =77.5 % had longer closure time than those with vWF >77.5 % (p<0.05). CONCLUSION: Significant ABO-group-specific differences in nonvascular primary hemostasis could be found by IVBT. The differences are small, however, and lie within the normal range. Whether these differences have any biologic relevance can only be speculated.

One hundred percent online identity check of pharmaceutical products by near-infrared spectroscopy on the packaging line.

To increase product safety of pharmaceuticals, a new near-infrared (NIR) method for the online identity check of pharmaceutical finished products was validated. The method comprises a new near-infrared device VisioNIR (Uhlmann VisioTec GmbH, Laupheim, Germany) and the appropriate evaluation statistics. The VisioNIR is applied to the packaging line and provides the possibility to perform a 100% product identity check at full line speed. The products were analyzed applying near-infrared spectroscopy (900-1700 nm) in reflectance mode. The scanned products were two widely used pharmaceuticals named Capsule A (containing 300 mg of paracetamol and 250 mg of chlorzoxazone) and Capsule B (containing 500 mg of paracetamol and 30 mg of codeine phosphate). In order to demonstrate the fitness of the VisioNIR the obtained data were compared with the data acquired by Foss NIRSystems 6500 spectrometer (NIRSystems, Silver Springs, MD). The results obtained by the VisioNIR evaluation statistics were compared with the results obtained by the commonly used principal component analysis. The advantages and the suitability of the method are discussed. In this new configuration NIR spectroscopy offers an excellent possibility for non-destructive 100% online quality control of pharmaceutical products.

Novel genes coding for lithotrophic sulfur oxidation of Paracoccus pantotrophus GB17.

The gene region coding for lithotrophic sulfur oxidation of Paracoccus pantotrophus GB17 is located on a 13-kb insert of plasmid pEG12. Upstream of the previously described six open reading frames (ORFs) soxABCDEF with a partial sequence of soxA and soxF (C. Wodara, F. Bardischewsky, and C. G. Friedrich, J. Bacteriol. 179:5014-5023, 1997), 4,350 bp were sequenced. The sequence completed soxA, and uncovered six new ORFs upstream of soxA, designated ORF1, ORF2, and ORF3, and soxXYZ. ORF1 could encode a 275-amino-acid polypeptide of 29,332 Da with a 61 to 63% similarity to LysR transcriptional regulators. ORF2 could encode a 245-amino-acid polypeptide of 26,022 Da with the potential to form six transmembrane helices and with a 48 to 51% similarity to proteins involved in redox transport in cytochrome c biogenesis. ORF3 could encode a periplasmic polypeptide of 186 amino acids of 20,638 Da with a similarity to thioredoxin-like proteins and with a putative signal peptide of 21 amino acids. Purified SoxXA, SoxYZ, and SoxB are essential for thiosulfate or sulfite-dependent cytochrome c reduction in vitro. N-terminal and internal amino acid sequences identified SoxX, SoxY, SoxZ, and SoxA to be coded by the respective genes. The molecular masses of the mature proteins determined by electrospray ionization spectroscopy (SoxX, 14,834 Da; SoxY, 11,094 Da; SoxZ, 11,717 Da; and SoxA, 30,452 Da) were identical or close to those deduced from the nucleotide sequence with differences for the covalent heme moieties. SoxXA represents a novel type of periplasmic c-type cytochromes, with SoxX as a monoheme and SoxA as a hybrid diheme cytochrome c. SoxYZ is an as-yet-unprecedented soluble protein. SoxY has a putative signal peptide with a twin arginine motif and possibly cotransports SoxZ to the periplasm. SoxYZ neither contains a metal nor a complex redox center, as proposed for proteins likely to be transported via the Tat system.

[Design of a multicenter study for assessing the effectiveness of extracorporeal shockwave therapy in epicondylitis humeri radialis]. / Design einer Multizenterstudie zum Wirksamkeitsnachweis der Extrakorporalen Stosswellentherapie (ESTW) bei Epicondylitis humeri radialis.

INTRODUCTION: Previously published studies concerning, extracorporeal shock-wave therapy (ESWT) in the treatment of lateral epicondylitis do not fulfil the biometric standards of modern clinical research. The objective of the trial is to show that ESWT is effective in the treatment of chronic LE. METHOD: A prospective, randomized, placebo-controlled, single-blinded, multicenter trial with an independent blinded observer was designed. The effectiveness of ESWT is evaluated by comparison with a control group in which sham-ESWT is performed, both under local anaesthesia. Outcome is determined on the basis of the Roles/Maudsley-Score. Inclusion criteria are a history of at least 6 months of LE and failure of conventional treatment. The therapy includes 3 sessions of low energy ESWT with 2000 impulses (energy flux density 0.07-0.09 mJ/mm2). Sample size is 272 patients. STATUS: Randomisation started in October 1998 and is planned over a period of two and a half years. CONCLUSION: Only a randomised clinical trial with adequate control of placebo effects and observer bias can provide the required evidence for the efficiency of ESWT in the treatment of lateral epicondylitis of the elbow.

Drosophila ACT88F indirect flight muscle-specific actin is not N-terminally acetylated: a mutation in N-terminal processing affects actin function.

Many eukaryotic proteins are co and post-translationally modified at their N termini by removal of one or two amino acid residues and N(alpha)-acetylation. Actins show two different forms of N-terminal processing dependent on their N-terminal sequence. In class II actins, which include muscle actins, the common primary sequence of Met-Cys-Asp-actin is processed to acetyl-Asp-actin. The functional significance of this in vivo is unknown. We have studied the indirect flight muscle-specific actin, ACT88F, of Drosophila melanogaster. Our results show that ACT88F is N-terminally processed in vivo as a class II actin by removal of the first two amino acid residues (Met and Cys), but that uniquely the N terminus is not acetylated. In addition we show that ACT88F is methylated, probably at His73. Flies carrying the mod(-) mutation fail to complete post-translational processing of ACT88F. We propose that the mod gene product is normally responsible for removing N-acetyl-cysteine from actin. The biological significance of this process is demonstrated by observations that retention of the N-acetyl-cysteine in ACT88F affects the flight muscle function of mod(-) flies. This suggests that the extreme N terminus affects actomyosin interactions in vivo, a proposal we have examined by in vitro motility assays of ACT88F F-actin from mod(-) flies. The mod(-) actin only moves in the presence of methylcellulose, a viscosity-enhancing agent, where it moves at velocities slightly, but significantly, reduced compared to wild-type. These data confirm that N-acetyl-cysteine at the N terminus affects actomyosin interactions, probably by reducing formation of the initial actomyosin collision complex, a process known to involve the actin N terminus.

Binding of nucleotides to guanylate kinase, p21(ras), and nucleoside-diphosphate kinase studied by nano-electrospray mass spectrometry.

The binding of nucleotides to three different nucleotide-binding proteins and to a control protein was studied by means of nano-electrospray mass spectrometry applied to aqueous nondenaturing solutions. The method leads to unambiguous identification of enzyme complexes with substrates and products but does not allow the determination of dissociation constants or even stoichiometries relevant to the binding in solution. For guanylate kinase (EC 2.7.4. 8), the transfer of HPO(3) between nucleotides was observed whenever a ternary complex with adenylate or guanylate nucleotides was formed. Guanosine 5'-tetraphosphate was generated after prolonged incubation with GDP or GTP. Mg(2+) binding was considerably enhanced in functional high affinity complexes, such as observed between guanylate kinase and its bisubstrate inhibitor P(1)-(5'-guanosyl)-P(5)-(5'-adenosyl) pentaphosphate or with the tight nucleotide-binding protein p21(ras) and GDP. Nucleoside-diphosphate kinase (EC 2.7.4.6) itself was phosphorylated in accordance to its known ping-pong mechanism. All nucleotide-binding proteins were shown to bind sulfate (SO(4)(2-)) with presumably high affinity and slow exchange rate. The binding of phosphate (PO(4)(3-)) could be inferred indirectly from competition with SO(4)(2-).

The Ras mutant D119N is both dominant negative and activated.

The introduction of mutation D119N (or its homolog) in the NKxD nucleotide binding motif of various Ras-like proteins produces constitutively activated or dominant-negative effects, depending on the system and assay. Here we show that Ras(D119N) has an inhibitory effect at a cell-specific concentration in PC12 and NIH 3T3 cells. Biochemical data strongly suggest that the predominant effect of mutation D119N in Ras-a strong decrease in nucleotide affinity-enables this mutant (i) to sequester its guanine nucleotide exchange factor, as well as (ii) to rapidly bind GTP, independent of the regulatory action of the exchange factor. Since mutation D119N does not affect the interaction between Ras and effector molecules, the latter effect causes Ras(D119N) to act as an activated Ras protein at concentrations higher than that of the exchange factor. In comparison, Ras(S17N), which also shows a strongly decreased nucleotide affinity, does not bind to effector molecules. These results point to two important prerequisites of dominant-negative Ras mutants: an increased relative affinity of the mutated Ras for the exchange factor over that for the nucleotide and an inability to interact with the effector or effectors. Remarkably, the introduction of a second, partial-loss-of-function, mutation turns Ras(D119N) into a strong dominant-negative mutant even at high concentrations, as demonstrated by the inhibitory effects of Ras(E37G/D119N) on nerve growth factor-mediated neurite outgrowth in PC12 cells and Ras(T35S/D119N) on fetal calf serum-mediated DNA synthesis in NIH 3T3 cells. Interpretations of these results are discussed.

[Intrarenal doppler flow analysis in patients with kidney transplantation and stable transplant function]. / Intrarenale Dopplerflussanalysen bei nierentransplantierten Patienten mit stabiler Transplantatfunktion.

AIM OF THE STUDY: Intrarenal arterial Doppler sonography is used in noninvasive monitoring of transplant kidneys with controversial results. With the application of the method on renal transplants with stable function normal values should be generated and pitfalls should be identified. METHOD AND STUDY SUBJECTS: In a prospective study doppler findings in 61 renal transplant patients with stable graft function were compared with measurements in native kidneys of 60 healthy controls. In all kidneys duplex Doppler studies of arcuate/interlobar intrarenal arteries were performed and both the resistance index (RI) as well as the pulsatility index (PI) was determined. RESULTS: The results of our study are summarized: 1. Transplanted kidneys have significantly higher intrarenal arterial flow indices in comparison to native kidneys: RI = 67 +/- 5% in allografts vs. RI = 57 +/- 5% in native kidneys; and PI = 123 +/- 21% in allografts vs. PI = 91 +/- 15% in native kidneys, respectively. 2. RI and PI increase with age in both the native kidneys and the allografts. However, the increase in the transplanted kidney correlates with the age of the recipient but not with the age of the donor. 3. Corresponding to the increase in RI and PI the blood pressure is significantly elevated in the elderly. 4. The degree of external pressure with the transducer on the graft has an impact on the intrarenal arterial Doppler findings and measurements obtained. CONCLUSION: The intrarenal arterial Doppler findings dependent on various extrarenal factors. Using arterial Doppler sonography to evaluate transplant kidneys it is mandatory to take into account factors such as recipient's age and hemodynamic situation. External pressure with the transducer on the graft must be avoided. Once these factors were considered the intrarenal arterial Doppler sonography of kidney transplant is a valuable diagnostic tool.

cAPK-phosphorylation controls the interaction of the regulatory domain of cardiac myosin binding protein C with myosin-S2 in an on-off fashion.

Myosin binding protein C is a protein of the myosin filaments of striated muscle which is expressed in isoforms specific for cardiac and skeletal muscle. The cardiac isoform is phosphorylated rapidly upon adrenergic stimulation of myocardium by cAMP-dependent protein kinase, and together with the phosphorylation of troponin-I and phospholamban contributes to the positive inotropy that results from adrenergic stimulation of the heart. Cardiac myosin binding protein C is phosphorylated by cAMP-dependent protein kinase on three sites in a myosin binding protein C specific N-terminal domain which binds to myosin-S2. This interaction with myosin close to the motor domain is likely to mediate the regulatory function of the protein. Cardiac myosin binding protein C is a common target gene of familial hypertrophic cardiomyopathy and most mutations encode N-terminal subfragments of myosin binding protein C. The understanding of the signalling interactions of the N-terminal region is therefore important for understanding the pathophysiology of myosin binding protein C associated cardiomyopathy. We demonstrate here by cosedimentation assays and isothermal titration calorimetry that the myosin-S2 binding properties of the myosin binding protein C motif are abolished by cAMP-dependent protein kinase-mediated tris-phosphorylation, decreasing the S2 affinity from a Kd of approximately 5 microM to undetectable levels. We show that the slow and fast skeletal muscle isoforms are no cAMP-dependent protein kinase substrates and that the S2 interaction of these myosin binding protein C isoforms is therefore constitutively on. The regulation of cardiac contractility by myosin binding protein C therefore appears to be a 'brake-off' mechanism that will free a specific subset of myosin heads from sterical constraints imposed by the binding to the myosin binding protein C motif.

Molecular basis of drug interaction with L-type Ca2+ channels.

Different types of voltage-gated Ca2+ channels exist in the plasma membrane of electrically excitable cells. By controlling depolarization-induced Ca2+ entry into cells they serve important physiological functions, such as excitation-contraction coupling, neurotransmitter and hormone secretion, and neuronal plasticity. Their function is fine-tuned by a variety of modulators, such as enzymes and G-proteins. Block of so-called L-type Ca2+ channels by drugs is exploited as a therapeutic principle to treat cardiovascular disorders, such as hypertension. More recently, block of so-called non-L-type Ca2+ channels was found to exert therapeutic effects in the treatment of severe pain and ischemic stroke. As the subunits of different Ca2+ channel types have been cloned, the modulatory sites for enzymes, G-proteins, and drugs can now be determined using molecular engineering and heterologous expression. Here we summarize recent work that has allowed us to determine the sites of action of L-type Ca2+ channel modulators. Together with previous biochemical, electrophysiological, and drug binding data these results provide exciting insight into the molecular pharmacology of this voltage-gated Ca2+ channel family.

Kinetic analysis by fluorescence of the interaction between Ras and the catalytic domain of the guanine nucleotide exchange factor Cdc25Mm.

Guanine nucleotide exchange factors (GEFs) activate Ras proteins by stimulating the exchange of GTP for GDP in a multistep mechanism which involves binary and ternary complexes between Ras, guanine nucleotide, and GEF. We present fluorescence measurements to define the kinetic constants that characterize the interactions between Ras, GEF, and nucleotides, similar to the characterization of the action of RCC1 on Ran [Klebe et al. (1995) Biochemistry 34, 12543-12552]. The dissociation constant for the binary complex between nucleotide-free Ras and the catalytic domain of mouse Cdc25, Cdc25(Mm285), was 4.6 nM, i.e., a 500-fold lower affinity than the Ras.GDP interaction. The affinities defining the ternary complex Ras. nucleotide.Cdc25(Mm285) are several orders of magnitude lower. The maximum acceleration by Cdc25(Mm285) of the GDP dissociation from Ras was more than 10(5)-fold. Kinetic measurements of the association of nucleotide to nucleotide-free Ras and to the binary complex Ras. Cdc25(Mm285) show that these reactions are practically identical: a fast binding step is followed by a reaction of the first order which becomes rate limiting at high nucleotide concentrations. The second reaction is thought to be a conformational change from a low- to a high-affinity nucleotide binding conformation in Ras. Taking into consideration all experimental data, the reverse isomerization reaction from a high- to a low-affinity binding conformation in the ternary complex Ras. GDP.Cdc25(Mm285) is postulated to be the rate-limiting step of the GEF-catalyzed exchange. Furthermore, we demonstrate that the disruption of the Mg2+-binding site is not the only factor in the mechanism of GEF-catalyzed nucleotide exchange on Ras.

Simple analogues of anthralin: unusual specificity of structure and antiproliferative activity.

Fifty-nine simple analogues of the antipsoriatic agent, anthralin, have been prepared by modifying the positions of the 1,8-hydroxyl groups, replacement of the hydroxyl groups, substitution at the oxygen functions, introduction of additional functional groups into various positions of the anthracenone nucleus, or removal of particular structural elements. The compounds were evaluated for their antiproliferative action against human keratinocytes and inhibition of the generation of leukotriene B4 in polymorphonuclear leukocytes, which may be useful to resolve the proliferative and inflammatory aspects of psoriasis, respectively. Even though many anthracenones were more potent inhibitors of leukotriene biosynthesis than anthralin, none of the compounds was substantially more effective as this drug in suppressing keratinocyte cell growth. There is an absolute requirement for two hydroxyl groups peri to a hydrogen bond acceptor such as a keto or an imino group for high potency. In addition to further delineating the nature of the pharmacophore for this class of compounds, also naphthalenedione with a peri hydroxyl group was identified as a pharmacophore with antiproliferative activity against keratinocyte growth.

Antipsoriatic anthrones with modulated redox properties. 4. Synthesis and biological activity of novel 9,10-dihydro-1,8-dihydroxy-9-oxo-2-anthracenecarboxylic and -hydroxamic acids.

A novel series of carboxylic and hydroxamic acids based on 1,8-dihydroxy-9(10H)-anthracenone were synthesized from 8-hydroxy-1-methoxy-9,10-anthracenedione as the key intermediate and evaluated both in the bovine polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay and in the HaCaT keratinocyte proliferation assay for their enzyme inhibitory and antiproliferative activity, respectively. The most potent inhibitors in both assays were the N-methylated hydroxamic acids 5d-8d with straight chain alkyl spacers. Incorporation of these structural features on the anthracenone pharmacophore resulted in increased inhibitory activity against 5-LO while the antiproliferative activity was retained. In addition, prooxidant properties as measured by deoxyribose degradation and cytotoxicity as assessed by LDH release were largely reduced as compared with the antipsoriatic anthralin. Contrary to anthralin, antioxidant properties were observed as documented by the reactivity of the novel compounds against free radicals and inhibition of lipid peroxidation in model membranes.

L-type calcium channels: binding domains for dihydropyridines and benzothiazepines are located in close proximity to each other.

We investigated the binding of a fluorescent diltiazem analogue (3R,4S)-cis-1-[2-[[3-[[3-[4,4-difluoro-3a,4-dihydro-5,7-dimethyl-4-bo ra-3a,4a-diaza-s-indacen-3-yl]propionyl]amino]propyl]amin o]ethy]-1,3,4,5-tetrahydro-3-hydroxy-4-(4-methoxyphenyl)-6-(triflu oromethyl)-2H-1-benzazepin-2-one (DMBODIPY-BAZ) to L-type Ca2+ channels in the presence of different 1,4-dihydropyridines (DHPs) by using fluorescence resonance energy transfer (FRET) [Brauns, T., Cai, Z.-W., Kimball, S. D., Kang, H.-C., Haugland, R. P., Berger, W., Berjukov, S., Hering, S., Glossmann, H., & Striessnig, J. (1995) Biochemistry 34, 3461]. When channels are occupied with DMBODIPY-BAZ, a rapid fluorescence change occurred upon addition of different DHPs. The direction of this intensity modulation was found to be only dependent on the chemical composition of the dihydropyridine employed. DHPs containing a nitro group decreased, whereas others (e.g., isradipine) enhanced the fluorescence signal. In addition, all DHPs markedly decreased the association rate constant for DMBODIPY-BAZ without affecting equilibrium binding. Both observations together are best explained by a steric model where the DHP binding site is located in close proximity to the accession pathway of DMBODIPY-BAZ.

Attitudes to current oral contraceptive use and future developments: the women's perspective.

OBJECTIVES: The study was planned to determine current trends in contraceptive usage and to examine the attitudes, needs and preferences of women with respect to oral contraceptives. METHODS: Semi-structured interviews were carried out with women (n = 1201, aged 16-45 years) in Germany, the UK and France. RESULTS: The study revealed that oral contraceptives were the most popular method of contraception employed, followed by condoms, and that the majority of respondents were aged 16-19 years when they first used an oral contraceptive. An important finding of the study was that an oral contraceptive was first used only after having sexual intercourse for the first time (within 1 year), emphasizing the importance of effective contraceptive information and education for adolescents. Regarding non-contraceptive health benefits, protection from ovarian and endometrial cancer was perceived by respondents to be of the greatest importance; however, few women were spontaneously aware of this benefit. When given a number of different oral contraceptive intake options to assess, the established 'once daily for 21 consecutive days' option remained the most popular, although a 'once weekly' alternative was cited by many women. When asked about the preferred frequency of menstrual bleeding, there was a polarization between women favoring the normal monthly bleed and those wanting a 'no-bleed' regimen. CONCLUSION: Women are poorly informed about oral contraceptive use, and are largely unaware of the important long-term non-contraceptive benefits. Many women would prefer alternative pill intake options and a significant number would favor a 'no-bleed' regimen.

[Clinical and chemical laboratory course of HELLP syndrome--a retrospective analysis]. / Klinischer und laborchemischer Verlauf des HELLP-Syndroms--eine retrospektive Analyse.

The HELLP-Syndrom (hemolysis, elevated liver enzymes, low platelet count) is considered as a severe complication of eclampsia with unpredictable development of pregnancy including high maternal and fetal risk. The result of retrospective analysis of all deliveries of the years 1986-1991 at the UFK Marburg were 28 cases of proved HELLP-Syndrom. Medical history, correlation of clinical and laboratory findings as well as the development of the disease and the neonatal dates were evaluated by computerized documentation. The incidence of HELLP-Syndrom was 28 of 8111 deliveries at all (0,34%). 82% of the women with HELLP-Syndrom were primiparae. The leading symptom was right upper abdominal pain in 75%, which lasted already 5,7 days before presentation in the clinic. Hypertonus, edema and proteinuria were present in 71%, 61% and 89% of the cases. The diagnosis indicating laboratory finding was the thrombocytopenia (mean 62 G/l). In comparison to the thrombocytes, which were at the 4.-7. day pp in 89% within the normal range, the liver function tests normalized just between the 9. and 13. day pp (SGOT 89%, SGPT 77%). The shortening of the prepartal hospitalization from 6 days in 1986/87 to 8 hours in 1990/91 decreases the periand postnatal complication rate from 43% to 23%. 26/28 patients (92%) were delivered by caesarean section from healthy babies through which were 75% premature infants and in 27% of the cases small for gestational age additionally. We conclude that the decrease of the diagnosis-delivery interval and the intensive medical care are responsible for the diminution of the maternal and neonatal mortality rate to 0%.

2-Anthracenonyl acetic acids as 5-lipoxygenase inhibitors.

The synthesis of 2-substituted anthracenonyl acetic acid (2-AA) derivatives is described. The key step is the Marschalk reaction of 1-hydroxy-8-methoxy-anthracenedione with glycolic acid. After protection of the resulting 2-anthracenonyl acetic acid derivative, the 2-monoalkylated derivatives are selectively obtained by direct alkylation. The methodology proves quite general and allows for the introduction of various substituents onto the 2-position of the carboxylic side chain. Reduction of the anthracenediones proceeds with concomitant protecting group removal and provides final 2-AA products in good yields. The results of initial biological studies demonstrate enhanced 5-lipoxygenase inhibition compared to anthralin.