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Biomedical subjects

G Kunz

Publications and source records attributed to G Kunz.

At least 19 recordsLinked to original sources

Oxytocin--a stimulator of directed sperm transport in humans.

Rhythmic peristaltic contractions of the muscular wall of the non-pregnant uterus, as well as rapid sperm transport from the vagina to the Fallopian tubes, have long been documented by means of vaginal sonography and hysterosalpingoscintigraphy. Uterine peristaltic activity reaches a maximum before ovulation and is controlled via oestradiol secretion from the dominant follicle systemically and into the utero-ovarian countercurrent system; it is also enhanced by oxytocin. In this study, the effect of oxytocin and its receptor antagonist atosiban on uterine peristalsis and thus directed sperm transport during the mid and late follicular phases was examined. Atosiban did not show any effect either on frequency or on pattern of the peristaltic contractions. However, oxytocin significantly increased the rapid and directed transport of radiolabelled particles representing spermatozoa from the vagina into the Fallopian tube ipsilateral to the site of the dominant follicle (P = 0.02, 0.04 and 0.02 after 1, 16 and 32 min of documentation respectively). It seems reasonable to assume that oxytocin plays an important, although not critical, role in the mechanisms governing rapid sperm ascension that, at least in humans, were developed to rapidly preserve an aliquot of spermatozoa following intercourse.

Adult↗

Uterotubal transport disorder in adenomyosis and endometriosis--a cause for infertility.

OBJECTIVE: Uterine hyperperistalsis and dysperistalsis are common phenomena in endometriosis and may be responsible for reduced fertility in cases of minimal or mild extent of disease. Since a high prevalence of adenomyosis uteri has been well documented in association with endometriosis, we designed a study to examine whether hyperperistalsis and dysperistalsis are caused by the endometriosis itself or by the adenomyotic component of the disease. DESIGN: A prospective observational study. SETTING: University hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 300 in vitro fertilisation/intracytoplasmatic sperm injection cycles and 350 intrauterine insemination cycles/year. POPULATION: Forty-one subjects with infertility and with laparoscopically proven endometriosis and patent fallopian tubes. Thirty-five subjects (85%) additionally showed signs of adenomyosis. METHODS: All subjects underwent T2-weighed magnetic resonance imaging (MRI) and hysterosalpingoscintigraphy (HSSG) during the subsequent menstrual cycle. MRI revealed the extent of the adenomyotic component of the disease and the integrity of uterotubal transport capacity was evaluated by HSSG. MAIN OUTCOME MEASURES: Influence of adenomyosis on uterotubal transport capacity in endometriosis. RESULTS: In 35 of the 41 subjects (85%) with endometriosis, signs of adenomyosis were detected using T2-weighed MRI. Two of six (33%) subjects with no adenomyosis (group I) showed dysperistalsis and hyperperistalsis, compared with 14 of 24 (58%) women with focal adenomyosis (group II) and 10 of 11 (91%) women with diffuse adenomyosis (seven showed a failure in transport capacity and two contralateral transport). CONCLUSIONS: Our data suggest that endometriosis is associated with impeded hyperperistaltic and dysperistaltic uterotubal transport capacity. However, adenomyosis is of even more importance, especially when diffuse adenomyosis is detected. Both forms of adenomyosis are commonly found in subjects with mild to moderate endometriosis. We suggest that the extent of the adenomyotic component in subjects with endometriosis explains much of the reduced fertility in subjects with intact tubo-ovarian anatomy.

Adenomyoma↗

IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients.

BACKGROUND: Preliminary very encouraging clinical results of intensity modulated radiation therapy (IMRT) in Head Neck Cancer (HNC) are available from several large centers. Tumor control rates seem to be kept at least at the level of conventional three-dimensional radiation therapy; the benefit of normal tissue preservation with IMRT is proven for salivary function. There is still only limited experience with IMRT using simultaneously integrated boost (SIB-IMRT) in the head and neck region in terms of normal tissue response.The aim of this work was (1) to establish tumor response in HNC patients treated with SIB-IMRT, and (2) to assess tissue tolerance following different SIB-IMRT schedules. RESULTS: Between 1/2002 and 12/2004, 115 HNC patients have been curatively treated with IMRT. 70% received definitive IMRT (dIMRT), 30% were postoperatively irradiated. In 78% concomitant chemotherapy was given. SIB radiation schedules with 5-6 x 2 Gy/week to 60-70 Gy, 5 x 2.2 Gy/week to 66-68.2 Gy (according to the RTOG protocol H-0022), or 5 x 2.11 Gy/week to 69.6 Gy were used. After mean 18 months (10-44), 77% of patients were alive with no disease. Actuarial 2-year local, nodal, and distant disease free survival was 77%, 87%, and 78%, respectively. 10% were alive with disease, 10% died of disease. 20/21 locoregional failures occurred inside the high dose area. Mean tumor volume was significantly larger in locally failed (63 cc) vs controlled tumors (32 cc, p <0.01), and in definitive (43 cc) vs postoperative IMRT (25 cc, p <0.05); the locoregional failure rate was twofold higher in definitively irradiated patients. Acute reactions were mild to moderate and limited to the boost area, the persisting grade 3/4 late toxicity rate was low with 6%. The two grade 4 reactions (dysphagia, laryngeal fibrosis) were observed following the SIB schedule with 2.2 Gy per session. CONCLUSION: SIB-IMRT in HNC using 2.0, 2.11 or 2.2 Gy per session is highly effective and safe with respect to tumor response and tolerance. SIB with 2.2 Gy is not recommended for large tumors involving laryngeal structures.

Adolescent↗

Control and function of uterine peristalsis during the human luteal phase.

Rhythmic peristaltic contractions of the muscular wall of the non-pregnant uterus can be demonstrated throughout the menstrual cycle, with a maximum just before ovulation. However, not only during the follicular phase but also during the luteal phase, the uterus shows remarkable contractile activity. The present study was conducted in order to examine uterine peristaltic activity and its function during the luteal phases of the human menstrual cycle. The results of vaginal sonography of uterine peristalsis, of hysterosalpingoscintigraphy and of the documentation of the sites of embryo implantation in natural and artificial cycles have shown that uterine peristalsis during the luteal phase is controlled by systemic and probably even more by local hormonal secretion from the fresh corpus luteum, and facilitates the fundal implantation of the blastocyst predominantly ipsilateral to the site of the dominant ovarian structure. Furthermore, this study suggests that the defence against the infiltration and inflammation of the upper genital tract, and thus the degradation of the implanted embryo, represents a further and phylogenetically old and genuine function of the archimetra, which in placentalia was modified in order to participate in the control of invasion of the endometrium by the trophoblast.

Abortion, Spontaneous↗

Adenomyosis in endometriosis--prevalence and impact on fertility. Evidence from magnetic resonance imaging.

BACKGROUND: The hypothesis is tested that there is a strong association between endometriosis and adenomyosis and that adenomyosis plays a role in causing infertility in women with endometriosis. METHODS. Magnetic resonance imaging of the uteri was performed in 160 women with and 67 women without endometriosis. The findings were correlated with the stage of the disease, the age of the women and the sperm count parameters of the respective partners. RESULTS: The posterior junctional zone (PJZ) was significantly thicker in women with endometriosis than in those without the disease (P<0.001). There was a positive correlation of the diameter of the PJZ with the stage of the disease and the age of the patients. The PJZ was thicker in patients with endometriosis with fertile than in patients with subfertile partners. The prevalence of adenomyotic lesions in all 160 women with endometriosis was 79%. In women with endometriosis below an age of 36 years and fertile partners, the prevalence of adenomyosis was 90% (P<0.01) CONCLUSIONS: With a prevalence of up to 90%, uterine adenomyosis is significantly associated with pelvic endometriosis and constitutes an important factor of sterility in endometriosis presumably by impairing uterine sperm transport.

Adolescent↗

[Endometriosis and adenomyosis].

Peristaltic activity of the non-pregnant uterus serves fundamental functions in the early process of reproduction. Hyperperistalsis of the uterus is significantly associated with the development of endometriosis and adenomyosis. In women with hyperperistalsis fragments of basal endometrium are detached during menstruation and transported into the peritoneal cavity. Fragments of basal endometrium have an increased potential of implantation and proliferation resulting in pelvic endometriosis. In addition, hyperperistalsis induces the proliferation of basal endometrium into myometrial dehiscencies. This results in endometriosis-associated adenomyosis with a prevalence of about 90%. Adenomyosis results in impaired directed sperm transport and thus constitutes an important cause of sterility in women with endometriosis. The principal mechanism of endometriosis/adenomyosis is the paracrine interference of endometrial estrogen with the cyclical endocrine control of archimyometrial peristalsis exerted by the ovary thus resulting in hyperperistalsis. Minimal endometriosis of the fertile women, endometriosis and adenomyosis of the infertile women and adenomyosis of the parous peri- and postmenopausal women are considered as phenotypes of a pathophysiological continuum with uterine peristalsis playing a prominent role.

Endometriosis↗

Endometriosis results from the dislocation of basal endometrium.

BACKGROUND: The hypothesis is tested that both adenomyotic and endometriotic lesions are derived from basal endometrium. METHODS: Normal uteri and uteri with adenomyosis obtained by hysterectomy, excised endometriotic lesions and menstrual blood of women with and without endometriosis were used. Estrogen receptor (ER), progesterone receptor (PR), progesterone receptor B isoform (PR(B)) and P450 aromatase (P450A) immunohistochemistry was performed with the use of specific monoclonal antibodies. RESULTS: With respect to the parameters studied there was a fundamental difference between the cyclical patterns of the basalis and the functionalis of the eutopic endometrium. The endometrium of endometriotic and adenomyotic lesions mimicked the cyclical pattern of the basalis. The peristromal muscular tissue of endometriotic and adenomyotic lesions displayed the same cyclical pattern of ER and PR expression as the archimyometrium. There was a significantly higher prevalence of fragments of shed basalis in menstrual blood of women with endometriosis than in healthy controls. CONCLUSIONS: These data suggest that ectopic endometrial lesions result from dislocation of basal endometrium. Dislocated basal endometrium has stem cell character resulting in the ectopic formation of all archimetrial components such as epithelial and stromal endometrium as well as peristromal muscular tissue.

Adult↗

[Influence of tandem optics and television tube of modern digital fluoroscopy equipment on image quality].

The influence of the tandem optics and the TV-tube to the image quality of 1k- and 2k-radiographs of a modern fluoroscopy equipment should be assessed on the basis of objective parameters and clinical requirements. Radiographs of different phantoms with 1k- and 2k-image matrix, different illumination point corrections (IPC) and signal gray levels were taken, examined and evaluated, in order to determine the objective image parameters and the clinical relevancy of these parameters. On the one hand, the digital images data could be used directly for evaluation; on the other hand, the radiographs could be visually evaluated by experienced radiologists within the framework of a blind study. The IPC is controlled by the aperture of the iris diaphragm and the insertion of a neutral gray filter in the tandem optics. The larger the aperture of the iris diaphragm (at constant image receiver dose) the higher were gradation, signal to noise ratio (SNR) and image homogeneity. Furthermore, the larger the aperture, the lower was the square wave response function (SWRF). The insertion of a gray filter in the tandem optics decreases gradation, SNR and homogeneity, and improves the SWRF.

Fluoroscopy↗

Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus.

A 64-year-old woman presented with bullous and ulcerating lichen sclerosus et atrophicus (LSA) on the neck, trunk, genital and perigenital area and the extremities. Histology of lesional skin showed the typical manifestations of LSA; in one of the biopsies spirochaetes were detected by silver staining. Despite treatment with four courses of ceftriaxone with or without methylprednisone for up to 20 days, progression of LSA was only stopped for a maximum of 1 year. Spirochaetes were isolated from skin cultures obtained from enlarging LSA lesions. These spirochaetes were identified as Borrelia afzelii by sodium dodecyl sulphate--polyacrylamide gel electrophoresis and polymerase chain reaction (PCR) analyses. However, serology for B. burgdorferi sensu lato was repeatedly negative. After one further 28-day course of ceftriaxone the lesions stopped expanding and sclerosis of the skin was diminished. At this time cultures for spirochaetes and PCR of lesional skin for B. afzelii DNA remained negative. These findings suggest a pathogenetic role for B. afzelii in the development of LSA and a beneficial effect of appropriate antibiotic treatment.

Borrelia↗

Identification and characterization of a thrombomodulin gene mutation coding for an elongated protein with reduced expression in a kindred with myocardial infarction.

Thrombomodulin is an endothelial cell receptor for thrombin. It functions as a natural anticoagulant by greatly accelerating activation of protein C by thrombin. Using a direct gene screening strategy we identified a frameshift insertion mutation, insT 1689, in the thrombomodulin gene of a patient with myocardial infarction. The mutation predicts an elongated gene product because of substitution of the 12 C-terminal amino acids by 61 abnormal residues. Pedigree analysis showed that the mutation was also likely to have been present in a sibling who had had fatal myocardial infarction. Carriers of the mutant allele express significantly lower amounts of thrombomodulin on the surface of their monocytes detected by flow cytometry and have lower levels of soluble thrombomodulin in plasma. Wild type and the mutant thrombomodulin were expressed in COS-7 cells. Cellular distribution of the expressed proteins was evaluated by immunofluorescence microscopy, which showed reduced cell surface expression and intense juxtanuclear localization of the abnormal protein. This suggests impaired translocation through the endoplasmic reticulum/Golgi apparatus. Cells expressing abnormal thrombomodulin had reduced ability ( approximately 2.5-fold) to accelerate the thrombin mediated activation of protein C. This is the first demonstration of reduced expression arising from a natural thrombomodulin gene mutation. The results provide support for the suggestion that gene mutation of thrombomodulin may be important in the pathogenesis of some cases of occlusive thrombotic disease. (Blood. 2000;95:569-576)

Adult↗

[Examination of the image quality from digital fluoroscopy equipment with 1k- and 2k-image matrix].

PURPOSE: The image quality of 1k- and 2k-radiographs from digital fluoroscopy equipments (Sireskop SX and Polystar SX--Siemens) are characterized by comparison with each other to evaluate the relevance of this technique in clinical routine. MATERIAL AND METHODS: We examined fabricated and evaluated images with 1k- and 2k-image matrix from several high and low contrast phantoms and from skeleton phantoms. On the one hand, the digital image values can be used directly for the evaluation, on the other hand the comparing evaluation by experienced radiologists resulted from a visual consideration in a blind study. RESULTS: The quality difference of the 1k- and 2k-images depends mainly on the distance of the investigated sector of the object to the image intensifier and on the scattering of the radiation in the object positioned between the investigated sector and the image intensifier. The nearer the investigated object is located to the intensifier and the smaller the radiation is scattered in the object, the more the image quality of a radiograph with a 2k-matrix is increasing in comparison to an image with 1k-matrix. The higher the tube voltage, the smaller are the differences. CONCLUSION: The image quality enhancement because of the more sensitive sampling of the Saticon target in the 2k-matrix is limited by the opening of the iris positioned in the light distributor. Therefore the image quality differences of medical 1k- and 2k-radiographs in many cases are small.

Bone and Bones↗

Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging.

In women with endometriosis, the peristaltic activity of the uterus is significantly enhanced and may even become dysperistaltic at midcycle. Since uterine peristalsis is confined to the endometrium and the subendometrial myometrium with its predominantly circular arrangement of muscular fibres it was assumed that this dysfunction might be associated with structural abnormalities that could be visualized by high resolution ultrasonography and magnetic resonance imaging (MRI). Therefore, the uteri of women with and without endometriosis were subjected to endovaginal sonography (EVS) and to MRI. In EVS, women with laparoscopically proven endometriosis and infertility exhibited an infiltrative expansion of the archimetra in that the halo surrounding the uterine endometrium and representing the subendometrial myometrium was significantly enlarged compared with controls. The expansion was more pronounced in older than in younger women. There was, however, no relationship between the width of the expansion and the severity of the endometriotic disease. Similar data were obtained by MRI in that the 'junctional zone' in women with endometriosis and infertility was expanded in comparison with controls. The results of this study provide further support to the notion that endometriosis is primarily a uterine disease.

Adult↗

The cyclic pattern of the immunocytochemical expression of oestrogen and progesterone receptors in human myometrial and endometrial layers: characterization of the endometrial-subendometrial unit.

Immunocytochemistry of oestrogen receptor (ER) and progesterone receptor (PR) expression of the whole uterine muscular wall and the endometrium was performed in order to obtain morphological and functional insights into the regulation of cyclic uterine peristalsis, which is confined to the endometrium and the subendometrial myometrium and serves functions such as rapid and sustained sperm transport. The study revealed that the subendometrial myometrium or stratum subvasculare with a predominantly circular arrangement of muscular fibres exhibits a cyclic pattern of ER and PR expression that parallels that of the endometrium, whereas the outer portion of the uterine wall composed of the stratum vasculare and supravasculare, which represents the bulk of the uterine musculature, does not exhibit a cyclic pattern of ER and PR expression. According to ontogenetic and phylogenetic data from the literature, the outer myometrium is of non-paramesonephric origin with functions confined to parturition, while the inner myometrial layer together with the glandular epithelium and the stroma of the endometrium is of paramesonephric origin with various functions during the cycle in addition to those during pregnancy and parturition. The inner quarter of the stratum vasculare adjacent to the stratum subvasculare constitutes a transitional zone in that the cyclicity of receptor staining becomes, in radial direction, gradually less expressed. Morphologically this zone corresponds to the inner part of the stratum vasculare where its muscular fibres blend with those of the stratum subvasculare.

Adult↗

A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and the risk of myocardial infarction in men.

Thrombomodulin is an endothelial cell surface receptor that transforms the procoagulant thrombin into an anticoagulant. A mutation in the thrombomodulin gene is a potential risk factor for venous and arterial thrombosis. We screened a region within the coding sequence of the thrombomodulin gene by single-strand conformation polymorphism analysis (SSCP) in a pilot study of 104 patients with myocardial infarction and 104 age, sex and race matched controls. We identified a 127G to A mutation in the gene, which predicts an Ala25Thr substitution, in 2 out of 104 patients (1 man and 1 woman) with myocardial infarction but in no controls. We assessed the risk of myocardial infarction associated with the mutation in a larger "Study of Myocardial Infarctions Leiden" (SMILE). Among 560 men with a first myocardial infarction before the age of 70, 12 were carriers of the Ala25Thr substitution. In a control group of 646 men, frequency-matched for age, seven were carriers of the Ala25Thr substitution. The allelic frequencies were 1.07% among patients and 0.54% among controls suggesting risk associated with the mutation [odds ratio (OR) 2.0, 95% confidence interval (CI) 0.8-5.1]. In patients aged below 50, the predicted risk was almost seven times increased (OR 6.5, CI 0.8-54.2). In the presence of additional risk factors, such as smoking and a metabolic risk factor, the predicted risk increased to 9-fold (OR 8.8. CI 1.8-42.2) and 4-fold (OR 4.4, CI 0.9-21.3), respectively. While not conclusive, these results strongly suggest that the Ala25Thr substitution is a risk factor for myocardial infarction, especially in young men, and when in the presence of additional risk factors.

Age Factors↗

Thrombomodulin gene mutations associated with myocardial infarction.

BACKGROUND: Thrombomodulin is an important receptor for thrombin on the endothelial cell surface of most blood vessels, including those of the heart. Thrombin-bound thrombomodulin activates protein C, which inhibits thrombin generation by degrading factors Va and VIIIa. The aim of this study was to analyze the 5' region of the thrombomodulin gene to determine whether mutations contribute a risk for myocardial infarction. METHODS AND RESULTS: We screened the promoter region of the thrombomodulin gene by single-stranded conformation polymorphism analysis in 104 patients with diagnosed myocardial infarction. Five mutations (three distinct) were identified (GG-9/-10AT, G-33A, and C-133A). The dinucleotide mutation GG-9/-10AT was identified in 3 individuals (2 heterozygous, 1 homozygous). Only one of the three different mutations was identified in 104 patient control subjects matched for age, sex, and race (G-33A in a single individual). All mutations identified were in close proximity to consensus sequences for transcription control elements within the thrombomodulin gene. In contrast, no difference was observed between patients and control subjects for the allelic frequency of a previously identified neutral polymorphism GCC/GTC coding for Ala/Val455, with 3 individuals homozygous for GTC (Val) in both groups. CONCLUSIONS: The findings suggest that mutations in the promoter region of the thrombomodulin gene may constitute a risk for arterial thrombosis.

Adult↗

After unification: gender and subjective health status in East and West Germany.

Results of a random survey of 2574 adults in East and West Germany in 1992 show virtually no differences in subjective health status for the populations of East versus West Germany and only slight differences for men versus women. A closer analysis via multiple regression indicates, however, that contrary to previous results from other countries West German women have a better health status than men. Of the four gender groups analyzed separately East German men are the best off, while owing to a number of socio-economic status discrepancies, East German women report the worst health status. Surprisingly, West German men show a poorer subjective health status than East German men, although a number of factors like participation in sport, better income and younger age would predict otherwise. It is suggested that their health situation is negatively influenced not only by their work situation but also by outside private commitments not accounted for in this analysis. Also difficult to explain from the present data is the relatively good health status of East German men. Despite an insecure job and a difficult work situation they may experience unification in sociopolitical terms and their present social status as something positive. Overall, conditions in the system of West Germany show a tendency to favor women, while those in East Germany clearly favor men.

Adult↗

The uterine peristaltic pump. Normal and impeded sperm transport within the female genital tract.

Rapid as well as sustained sperm transport from the cervical canal to the isthmical part of the fallopian tube is provided by cervico-fundal uterine peristaltic contractions that can be visualized by vaginal sonography. The peristaltic contractions increase in frequency and presumably also in intensity as the proliferative phase progresses. As shown by placement of labeled albumin macrospheres of sperm size at the external cervical os and serial hysterosalpingoscintigraphy (HSSG) sperm reach, following their vaginal deposition, the uterine cavity within minutes. In the early follicular phase a large proportion of the macrospheres remains at the site of application, while a smaller proportion enters the uterine cavity with even a smaller one reaching the isthmical part of the tubes. In the mid-follicular phase of the cycle with increased frequency and intensity of the uterine contractions the proportion of macrospheres entering the uterine cavity as well as the tubes has significantly increased. In the late follicular phase with maximum frequency and intensity of uterine peristalsis the proportion of macrospheres entering the tube increases further at the expense of those at the site of application as well as within the uterine cavity. The transport of the macrospheres into the tube is preferentially directed into the tube ipsilateral to the dominant follicle, which becomes apparent in the mid-follicular phase as soon as a dominant follicle can be identified by ultrasound. Since the macrosphere are inert particles the directed sperm transport into the tube ipsilateral to the dominant follicle is not functionally related to a mechanism such as chemotaxis but is rather provided by uterine contraction of which the direction may be controlled by a specific myometrial architecture in combination with an asymmetric distribution of myometrial oestradiol receptors. Women with infertility and mostly mild endometriosis display on VSUP a uterine hyperperistalsis with nearly double the frequency of contractions during the early and mid- as well as midluteal phase in comparison to the fertile and healthy controls. During midcycle these women display a considerable uterine dysperistalsis in that the normally long and regular cervico-fundal contractions during this phase of the cycle have become more or less undirected and convulsive in character. Hyperperistalsis results in the transport of inert particles from the cervix into the tubes within minutes already during the early follicular phase, and may therefore constitute the mechanical cause for the development of endometriosis in that it transports detached endometrial cells and tissue fragments via the tubes into the peritoneal cavity. Moreover, dysperistalsis may contribute to the infertility in these patients since it results in a break down of sperm transport within the female genital tract.

Animals↗