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Biomedical subjects

R Winter

Publications and source records attributed to R Winter.

At least 73 records · Page 4Linked to original sources

Cervical intraepithelial neoplasia III: long-term outcome after cold-knife conization with clear margins.

OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia or squamous cell carcinoma in situ (CIN III) after cold-knife conization with clear margins. METHODS: A total of 4417 women (mean age 36, range 18-72 years) with histologically confirmed CIN III had cold-knife conization with clear margins at our institution between 1970 and 1994. All patients were followed up with colposcopy, cytology, and pelvic examination for a mean of 18 years (range 5-30years). RESULTS: New high-grade squamous intraepithelial lesions (SILs) (CIN II and III) developed in 15 (0.35%) patients (mean age 35, range 25-65 years) after a median of 107 (range 40-201) months. A total of 4402 (99.65%) patients (mean age 36, range 18-72 years) were free of high-grade SILs after a mean follow-up of 18 (range 5-30) years. High-grade glandular intraepithelial lesions developed in two (0.05%) patients 14 and 17 years after conization. Twelve (0.3%) patients had metachronous vulvar intraepithelial neoplasia (VIN) grade III or vaginal intraepithelial neoplasia (VAIN) grade III, and one (0.02%) patient had invasive vaginal carcinoma 10 years after conization. CONCLUSION: Cold-knife conization with clear margins was an adequate method to definitively treat CIN III.

Adolescent↗

Microinvasive carcinoma of the cervix: site of first focus of invasion.

OBJECTIVE: To evaluate the topography of the first invasive focus in microinvasive squamous cell carcinoma of the uterine cervix. METHODS: We studied 120 formalin-fixed and paraffin-embedded cold-knife conization specimens processed as step-serial sections. Four types of microinvasion were distinguished according to site: type I (ectocervical outside the last cervical gland), type II (ectocervical between the external os and the last gland and in connection with the surface epithelium), type III (ectocervical between the external os and the last gland but deep in cervical glands), and type IV (intracervical and in connection with the surface epithelium). RESULTS: A total of 142 early invasive foci were seen in the 120 cones. A single focus was seen in 106 (88%) specimens, whereas 14 (12%) had more than one focus. The foci were classified as type I in 16 (11%), type II in 31 (22%), type III in 70 (49%), and type IV in 25 (18%) cases. CONCLUSION: One half of the early invasive foci originated at the surface epithelium (types I, II, IV), either at the ectocervix (types I, II) or in the endocervix (type IV).

Carcinoma, Squamous Cell↗

A spectroscopic investigation of the binding interactions between 4,5-dihydroxyxanthone and heme.

In order to investigate one possible mechanism by which xanthones inhibit growth of malaria-causing Plasmodium parasites, optical and NMR spectroscopic studies were performed on a prototypic xanthone, 4,5-dihydroxyxanthone (45X2), upon its complexation to heme. The 45X2 x heme complex stoichiometry in aqueous solution was found to be 1:2; this interaction was non-cooperative, and exhibited a very similar heme complex dissociation constant (K(d)=5.1 x 10(-6)) as observed for the common antimalarial agents, chloroquine and quinine. The 45X2 x heme(2) complex formation was found to be both pH- and solvent-dependent, with clear evidence of the xanthone carbonyl moiety coordinating with the iron of heme. Hydrogen bonding between the hydroxyl groups of 45X2 and the propionate side chains of heme, as well as pi-pi stacking between both aromatic systems appeared to contribute to the overall stability of the 45X2 x heme(2) complex, as judged by 1H NMR. It was concluded that 45X2 forms a complex with a heme dimer in aqueous solution, and that this interaction can be generalized to account for its in vivo detrimental effect of parasite growth through an effective inhibition of hemozoin aggregate formation.

Animals↗

Grading of internal carotid artery stenosis: validation of Doppler/duplex ultrasound criteria and angiography against endarterectomy specimen.

OBJECTIVES: duplex ultrasound has replaced angiography prior to carotid endarterectomy (CEA) in many institutions. However, the indications for CEA are based on angiographically controlled studies and widely accepted ultrasound criteria do not exist. Consequently, the reliability of Doppler and/or duplex ultrasound to predict a high-grade ICA stenosis has to be proven. DESIGN: prospective validation study. MATERIALS: one hundred and fifty carotid bifurcations assessed by ultrasound and selective angiography and 68 acrylat outcasts of carotid specimen after eversion CEA. METHODS: ICA stenosis was measured angiographically according to the ECST criteria. Combined Doppler acoustic standard criteria (CDASC), peak systolic frequency (PSF), peak systolic velocity (PSV) and end-diastolic velocity (EDV) served as criteria for the ultrasound assessment. These criteria and the results of angiography were compared to the degree of ICA stenosis determined by specimen measurements. RESULTS: the median degree of ICA stenosis as assessed by angiography (82%, range 56-97%) and CDASC (83%, range 50-99%) corresponded well to the specimen measurements (80%, range 50-95%). The sensitivity of angiography and CDASC to predict a 70-90% ICA stenosis (ECST criteria) compared to the specimen measurements was 88% and 95%, respectively. The positive predictive value (PPV) reached 92% and 96%, respectively. CDASC were equivalent to angiography and were superior to the best single frequency or velocity parameters. If CDASC do not indicate a >/=70% ICA stenosis in spite of a PSV >/=180 cm/s and/or an EDV >/=50 cm/s, angiography may detect patients with a >70% ICA stenosis. CONCLUSIONS: CDASC are valid in the quantification of high-grade ICA stenosis. They are more reliable than single velocity and/or frequency measurements. However, if velocity criteria and CDASC do not agree, angiography should be performed.

Angiography↗

Left ventricular early diastolic inflow velocity and atrial ventricular plane downward velocity: useful parameters to test diastolic function in clinical practice? Diastolic parameters tested in a clinical setting.

AIMS: To study the clinical value of the colour-M-mode slope of the early diastolic left ventricular filling phase (Vp) and the early diastolic downward M-mode slope of the left atrioventricular plane displacement (EDS), compared with diastolic function assessed by traditional Doppler evaluation. METHODS AND RESULTS: In 65 consecutive patients EDS and Vp were compared with a four-degree traditional diastolic function classification, based on pulsed Doppler assessment of the early to atrial transmitral flow ratio (E/A), the E-wave deceleration time (Edt), and the systolic to diastolic (S/D) pulmonary venous inflow ratio. Vp (P=0.006) and EDS (P=0.045) were related to traditional diastolic function (Kruskal--Wallis analysis). EDS showed a trend brake between the moderate and severe diastolic dysfunction groups by traditional Doppler evaluation. Vp and EDS correlated weakly in simple linear regression analysis (r=0.33). Vp and EDS discriminated poorly between normal and highly abnormal diastolic function. CONCLUSIONS: Vp and EDS were significantly related to diastolic function by traditional Doppler evaluation. They were, however, not useful as single parameters of left ventricular diastolic function due to a small difference between normal and highly abnormal values, allowing for little between-measurement variability. Consequently, these methods for the evaluation of left ventricular diastolic function do not add significantly to traditional Doppler evaluation.

Adult↗

[Colposcopy of CIN and microinvasive cervical carcinoma].

The colposcopist must distinguish between two patterns: nonsuspicious findings and suspicious findings. With experience, the colposcopist will succeed more and more in distinguishing between the two, thereby markedly reducing the number of biopsies. Suspicious findings are not synonymous with abnormal findings because the latter are not always due to premalignant lesions. A number of features are of value in the different diagnosis of colposcopic findings: sharp borders, response to acetic acid (white epithelium), surface contour, appearance of blood vessels, surface extent (size), combinations of abnormalities, iodine uptake, and keratinization. The diagnostic features described above can be expressed to varying degrees, and can be found singly or in combination. The more distinct a feature is and the greater the variety of features seen in combination, the higher the index of suspicion. Attempting to differentiate between the various grades of CIN (SIL) colposcopically is more questionable, as these lesions are regarded now as forming a spectrum of the same biologic process.

Acetic Acid↗

Ontologies of developmental anatomy: their current and future roles.

A central problem in current biology is elucidating the molecular networks that drive developmental change and physiological function. Such knowledge is needed partly to understand these networks, partly to be able to manipulate them, and partly to understand and help treat those human congenital abnormalities that arise as a result of mutation. Thus far, bioinformatics technology has been of limited use in this enterprise, mainly because its core focus has been on sequence technology and data archiving. For bioinformatics to be of use in this next tier of investigations, genetic and protein data need to be both archived and searchable by tissue since this is the level at which these networks operate. The resulting databases in turn require ontologies of developmental anatomy that can provide the formal infrastructure for handling gene expression, microarray and other tissue-based data. Here, the progress in making such ontologies, particularly for the developing mouse, is reported and the uses to which they are and will be put, together with the resources and tools currently available for investigating molecular networks and the genetic basis of congenital abnormalities, are considered.

Anatomy↗

Impaired whole-blood polymorphonuclear leukocyte migration as a possible predictive marker for infections in preterm premature rupture of membranes.

OBJECTIVES: Steroids, used in preterm premature rupture of membranes (pPROM), to reduce the risk of morbidity and mortality of the preterm neonate, impair the maternal polymorphonuclear leukocyte (PMN)-based immune system. In spite of combination with antibiotics, prenatal and postnatal bacterial infections of mother and child are frequent. This pilot study focuses on the influence of steroids in pPROM on maternal PMN functional capacity and subsequent infections. METHODS: After opting for expectant management, eight women with pPROM and no signs of infection were treated by steroids (betamethasone 5.7 mg, i.m. every 24 hours, for three days) and antibiotic therapy with either amoxicillin and clavulanic acid, piperacillin or ampicillin i.v. up to delivery. The conventional inflammation parameters of PMN blood count and C-reactive protein (CRP) were measured daily in parallel with PMN migratory capacity towards N-formyl-methionyl-leucyl-phenylalanine stimulation and under blank conditions, estimated by a whole blood membrane filter assay. RESULTS: In all patients PMN migration decreased during the application of steroids. Three patients showed a decrease in PMN migration below critical values and in spite of antibiotic prophylaxis acute pyelonephritis developed 2-6 days later. PMN count and CRP were not predictive of maternal infection. CONCLUSION: Reduced PMN function, caused by steroid treatment in pPROM, is suggested to be a reason for serious bacterial infections in spite of antibiotic prophylaxis. PMN migration reflects individual PMN defensive capacity.

Antibiotic Prophylaxis↗

[Gynäkologisch-geburtshilfliche Rundschau -revisited, future directed and practice oriented].

After a long period of 15 years, the SGGG recognized the Gynäkologisch-geburtshilfliche Rundschau once again as their official organ. Herewith a sign is given for a more intense cooperation with the Austrian Society for Gynecology and Obstetrics. Eventually, the possibility that the Bavarian Society of Gynecology and Obstetrics will also join might be achieved. In a time of rapid developments in the field of print media, publishers and editors are now facing new and upcoming challenges. The concept of our journal will be adapted to the modern requirements of our readership. Besides the traditional original papers, important with regard to the impact factor, other topics will be published, e.g., medicine and law, management and health care, and congress reports. As recently introduced, articles in German as well as in English are welcome.

Austria↗

Effects of Psoroptes ovis infection and its control with an ivermectin controlled-release capsule on growing sheep. 2. Evaluation of wool production and leather value.

To evaluate the prophylactic and therapeutic effects of an ivermectin controlled-release capsule (IVM-CRC) on the productivity of growing sheep infested with Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed based on sex and Day 0 body weight. Within each replicate animals were randomly allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is designed to deliver ivermectin at a minimum dose of 20 microg/kg/day for 100 days. The lambs were infested with 50-60 P. ovis mites each on days 14 and 21. The animals were shorn on Day 126. After slaughter on Day 127 the quality of the leather produced from their skins was evaluated. The IVM-CRC treatment on Day 0 prevented the establishment of P. ovis. All untreated lambs became infested. The lambs treated with an IVM-CRC on Day 84 became mite-free from Day 112 onwards. The lambs which were treated on Day 0 had significantly (p<0.05) greater clean fleece weight (1.5 kg) and fleece yield (52.1%) than the untreated controls (0.9 kg and 34.1%, respectively) or than lambs treated on Day 84 (1.0 kg and 47.8%, respectively). Clean fleece weight and fleece yield were in the tendency (p=0.055) or significantly (p<0. 001) greater, respectively, for lambs treated on Day 84 than for the untreated controls. The chrome tanned dried crust leather of all untreated controls and six of the 16 lambs treated on Day 84 showed grain surface defects such as discolourations, indurations and coarse, pitted grain. The useful (defect-free) leather size was significantly (p<0.01) higher for the lambs treated on Day 0 (100%) than for the lambs treated on Day 84 (82.7%) and the untreated controls (7.8%). The physical testing revealed that the leather of sheep treated on Day 0 had significantly (p<0.05) higher thickness, elongation break and tear resistance than the leather of both untreated controls and sheep treated on Day 84. There were no significant differences in the physical characteristics of the leather of the untreated controls and the sheep treated on Day 84.

Animals↗

Effects of psoroptes ovis infection and its control with an ivermectin controlled-release capsule on growing sheep. 1. Evaluation of weight gain, feed consumption and carcass value.

To evaluate the prophylactic and therapeutic effects of an ivermectin controlled-release capsule (IVM-CRC) on the productivity of growing sheep infested with Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed based on sex and Day 0 body weight. Within each replicate animals were randomly allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is designed to deliver ivermectin at a minimum dose of 20 microg/kg per day for 100 days. The lambs were infested with 50-60 P. ovis mites each on Days 14 and 21. Mites in skin scrapings were counted on Days 70, 84, 98, 112 and 126. Body weight and feed consumption were measured every 2 weeks from Day 0 to 126. The animals were slaughtered on Day 127 and their carcasses evaluated. The IVM-CRC treatment on Day 0 prevented the establishment of P. ovis. All untreated lambs became infested. The lambs treated with an IVM-CRC on Day 84 became mite-free from Day 112 onwards. The lambs treated on Day 0 had significantly (p<0.05) greater body weight gain from Day 0 to 84 (13.9 kg) and Day 0 to 126 (20.9 kg) than the untreated controls (9.6 and 12.8 kg, respectively) and the sheep treated on Day 84 (8.4 and 14.9 kg, respectively). Feed consumption (Days 0-126) for sheep treated with the IVM-CRC on Day 0 was higher than for sheep treated on Day 84 (p<0.05) and for the untreated controls (p<0.1). The carcasses of sheep treated with the IVM-CRC on Day 0 had significantly (p<0.05) higher warm and cold weights, carcass yield, rib eye area and back fat thickness than the untreated control group and the sheep treated with the IVM-CRC on Day 84. The sheep treated with the ivermectin CRC on either Day 0 or 84 had significantly (p<0.05) better muscle scores and lower muscle pH 1h post-slaughter than the untreated controls. There was no significant (p>0.1) difference between warm and cold carcass weights, carcass yield and rib eye area between sheep treated on Day 84 and untreated controls.

Animals↗

Pnictides as symmetrically bridging ligands in novel neutral complexes

The reaction of [LWCl] (3) [L = N(CH2CH2NiPr)3] with LiE(SiMe3)2 (E = P, As, Sb) yields the novel, neutral pnictido-bridged complexes [LW = E = WL] (5-7). By following the reaction, which starts from the LiP-(SiMe3)2 derivative, by 31P NMR spectroscopy, the formation of an intermediate with a terminal pnictido ligand can be ruled out. The paramagnetic complexes 5-7 are comprehensively spectroscopically characterised. The X-ray structure analysis of the heterocumulenes 5-7 reveals a linear structure in which the two W-"tren" units bind to the central pnictido atom in a staggered conformation ["tren" = tren-based ligand; tren = tris(2-aminoethyl)-amine. When N2 is used as the inert gas in the synthesis of the starting material [N(CH2CH2NNp)3WCl] [Np = CH2C-(CH3)3], the complex [[N(CH2CH2NNp)3]W2(mu, eta 1: eta 1-N2)] (4) is formed as a side product. Complex 4 possesses a hydrazido(4-) (N2(4-)) ligand connected by two tungsten-"tren" moieties.

Journal Article↗

Efficacy of an ivermectin controlled-release capsule against some rarer nematode parasites of sheep.

A controlled trial was conducted to evaluate the efficacy of the intraruminal ivermectin controlled-release capsule (CRC) (IVOMEC Maximizer CR Capsule for Sheep, Merial Ltd.) against induced incoming third-stage larvae and established adult infections with some rarer gastrointestinal nematode parasites of sheep. Twenty-one worm-free lambs were allocated by restricted randomisation based on body weight within sex to one of the following treatments: unmedicated control, ivermectin CRC given on Day 0 prior to induced infection, and ivermectin CRC given on Day 70 after establishment of induced infection. The ivermectin CRC delivers ivermectin at a minimum dose rate of 20 microg/kg/day for 100 days. Infections were induced by daily administration of third-stage larvae for five consecutive days. Nematodes were counted on Day 84, 14 days after treatment of established infection. The treatment with the ivermectin CRC prevented the establishment of Ostertagia leptospicularis, O. ostertagi, Bunostomum trigonocephalum, Cooperia oncophora, C. punctata, C. surnabada, Nematodirus helvetianus, N. roscidus and Strongyloides papillosus by >99% as compared with the untreated controls (p < 0.01). The administration of the ivermectin CRC reduced established adult infections of O. ostertagi, B. trigonocephalum, C. oncophora, C. punctata, C. surnabada, N. roscidus and S. papillosus by >99% (p < 0.01), and reduced established adult infections of O. leptospicularis and N. helvetianus by 96.5 and 98.4% (p < 0.01), respectively.

Abomasum↗

A role for a helical connector between two receptor binding sites of a long-chain peptide hormone.

The conformational freedom of single-chain peptide hormones, such as the 41-amino acid hormone corticotropin releasing factor (CRF), is a major obstacle to the determination of their biologically relevant conformation, and thus hampers insights into the mechanism of ligand-receptor interaction. Since N- and C-terminal truncations of CRF lead to loss of biological activity, it has been thought that almost the entire peptide is essential for receptor activation. Here we show the existence of two segregated receptor binding sites at the N and C termini of CRF, connection of which is essential for receptor binding and activation. Connection of the two binding sites by highly flexible epsilon-aminocaproic acid residues resulted in CRF analogues that remained full, although weak agonists (EC(50): 100-300 nM) independent of linker length. Connection of the two sites by an appropriate helical peptide led to a very potent analogue, which adopted, in contrast to CRF itself, a stable, monomer conformation in aqueous solution. Analogues in which the two sites were connected by helical linkers of different lengths were potent agonists; their significantly different biopotencies (EC(50): 0.6-50 nM), however, suggest the relative orientation between the two binding sites rather than the maintenance of a distinct distance between them to be essential for a high potency.

Adrenocorticotropic Hormone↗

Pressure-induced unfolding/refolding of ribonuclease A: static and kinetic Fourier transform infrared spectroscopy study.

In this paper, we illustrate the use of high-pressure Fourier transform infrared (FT-IR) spectroscopy to study the reversible presssure-induced unfolding and refolding of ribonuclease A (RNase A) and compare it with the results obtained for the temperature-induced transition. FT-IR spectroscopy monitors changes in the secondary structural properties (amide I' band) or tertiary contacts (tyrosine band) of the protein upon pressurization or depressurization. Analysis of the amide I' spectral components reveals that the pressure-induced denaturation process sets in at 5. 5 kbar at 20 degrees C and pH 2.5. It is accompanied by an increase in disordered structures while the content of beta-sheets and alpha-helices drastically decreases. The denatured state above 7 kbar retains nonetheless some degree of beta-like secondary structure and the molecule cannot be described as an extended random coil. Increase of pH from 2.5 to 5.5 has no influence on the structure of the pressure-denatured state; it slightly changes the stability of the protein only. All experimental evidence indicates that the pressure-denatured states of monomeric proteins have more secondary structure than the temperature-denatured states. Different modes of denaturation, including pressure, may correlate differently with the roughness of the energy scale and slope of the folding funnel. For these reasons we have also carried out pressure-jump kinetic studies of the secondary structural evolution in the unfolding/refolding reaction of RNase A. In agreement with the theoretical model presented by Hummer et al. [(1998) Proc. Natl. Acad. Sci. U.S.A. 95, 1552-1555], the experimental data show that pressure slows down folding and unfolding kinetics (here 1-2 orders of magnitude), corresponding to an increasingly rough landscape. The kinetics remains non-two-state under pressure. Assuming a two-step folding scenario, the calculated relaxation times for unfolding of RNase A at 20 degrees C and pH 2.5 can be estimated to be tau(1) approximately 0.7 min and tau(2) approximately 17 min. The refolding process is considerably faster (tau(1) approximately 0.3 min, tau(2) approximately 4 min). Our data show that the pressure stability and pressure-induced unfolding/refolding kinetics of monomeric proteins, such as wild-type staphylococcal nuclease (WT SNase) and RNase A, may be significantly different. The differences are largely due to the four disulfide bonds in RNase A, which stabilize adjacent structures. They probably lead to the much higher denaturation pressure compared to SNase, and this might also explain why the volume change of WT SNase upon unfolding is about twice as large.

Amides↗