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1.
Genes Immun ; 17(4): 228-38, 2016 06.
Article in English | MEDLINE | ID: mdl-27029527

ABSTRACT

RGS1 (regulator of G-protein signaling 1) has been associated with multiple autoimmune disorders including type I diabetes. RGS1 desensitizes the chemokine receptors CCR7 and CXCR4 that are critical to the localization of T and B cells in lymphoid organs. To explore how RGS1 variation contributes to autoimmunity, we generated Rgs1 knockdown (KD) mice in the nonobese diabetic (NOD) model for type I diabetes. We found that Rgs1 KD increased the size of germinal centers, but decreased the frequency of T follicular helper (TFH) cells. We show that loss of Rgs1 in T cells had both a T cell-intrinsic effect on migration and TFH cell frequency, and an indirect effect on B-cell migration and germinal center formation. Notably, several recent publications described an increase in circulating TFH cells in patients with type I diabetes, suggesting this cell population is involved in pathogenesis. Though Rgs1 KD was insufficient to alter diabetes frequency in the NOD model, our findings raise the possibility that RGS1 plays a role in autoimmunity owing to its function in TFH cells. This mechanistic link, although speculative at this time, would lend support to the notion that TFH cells are key participants in autoimmunity and could explain the association of RGS1 with several immune-mediated diseases.


Subject(s)
Diabetes Mellitus, Type 1/genetics , Germinal Center/pathology , RGS Proteins/genetics , T-Lymphocytes, Helper-Inducer/pathology , Animals , Autoimmunity/genetics , Diabetes Mellitus, Type 1/immunology , HEK293 Cells , Humans , Mice , Mice, Inbred NOD , RGS Proteins/metabolism
2.
J Theor Biol ; 359: 101-11, 2014 Oct 21.
Article in English | MEDLINE | ID: mdl-24931673

ABSTRACT

Diabetes cases worldwide have risen steadily over the past few decades, lending urgency to the search for more efficient, effective, and personalized ways to treat the disease. Current treatment strategies, however, may fail to maintain oscillations in blood glucose concentration that naturally occur multiple times per day, an important element of normal human physiology. Building upon recent successes in mathematical modeling of the human glucose-insulin system, we show that both food intake and insulin therapy likely demand increasingly precise control over insulin sensitivity if oscillations at a healthy average glucose concentration are to be maintained. We then model and describe personalized treatment options for patients with diabetes that maintain these oscillations. We predict that for a person with type II diabetes, both blood glucose levels can be controlled and healthy oscillations maintained when the patient gets an hour of daily exercise and is placed on a combination of Metformin and sulfonylurea drugs. We note that insulin therapy and an additional hour of exercise will reduce the patient׳s need for sulfonylureas. Results of a modeling analysis suggest that, with constant nutrition and controlled exercise, the blood glucose levels of a person with type I diabetes can be properly controlled with insulin infusion between 0.45 and 0.7µU/mlmin. Lastly, we note that all suggested strategies rely on existing clinical techniques and established treatment measures, and so could potentially be of immediate use in the design of an artificial pancreas.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus/blood , Diabetes Mellitus/drug therapy , Patient-Specific Modeling , Precision Medicine/methods , Biological Clocks/physiology , Humans , Insulin/administration & dosage , Insulin/blood , Metformin/administration & dosage , Sulfonylurea Compounds/administration & dosage , Time Factors
3.
Eur J Obstet Gynecol Reprod Biol ; 158(2): 285-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21664027

ABSTRACT

OBJECTIVE: Endometriosis is one of the most frequent gynaecological disorders being associated with infertility. Hence, the early detection of endometriosis in infertility patients is of importance for the treatment modalities in infertility. Transvaginal hydrolaparoscopy (THL) offers an accurate, safe and quick diagnostic tool, not only for the evaluation of the fallopian tubes but also for the detection of very subtle endometriotic lesions in the early stages of endometriosis. STUDY DESIGN: Between January 2008 and January 2010, we conducted a study in order to evaluate the prevalence, extent and localisation of endometriosis via the new technique of THL in infertility patients. 239 patients with a mean age of 33.9 years underwent THL after having given informed consent. RESULTS: In 237 patients, access to the cul-de-sac was successfully achieved. Endometriosis was detected in 77 of 237 cases (32.5%). In 85.7% of cases, the endometriotic lesions were classified as very small (ASRM stage I°). Predominantly, the small lesions were found merely on the left side of the patient's peritoneal cavity: in 43 cases (55.8%), endometriosis was detected strictly on the left side, whereas the disease was detected on the right side in only 5 patients (6.5%). In 29 patients, endometriosis could be detected in both sides of the pelvis (37.7%). The differences in the side-dependent distribution were statistically highly significant (p<0.0001). In most of the cases, the subtle endometriotic lesions affected the ovarian surface superficially (53.5%) or the peritoneum of the lateral pelvic wall (25.6%). CONCLUSIONS: These data clearly indicate that there is a high prevalence of endometriosis in patients with infertility. THL is an accurate, safe and quick method for a thorough examination of the female pelvis besides the patency of the fallopian tubes. The high prevalence of left-sided subtle endometriotic lesions must be interpreted that during THL a very early process in the development of endometriosis can be observed. Even minimal to mild endometriosis might lead to a significant restriction in uterotubal transport capacity whose integrity is directly correlated to normal pregnancy rates. The extent of the accompanying adenomyosis is directly correlated to the loss of intact uterotubal transport capacity.


Subject(s)
Endometriosis/diagnosis , Adult , Disease Susceptibility , Endometriosis/complications , Female , Humans , Infertility, Female/etiology , Laparoscopy
4.
Z Gerontol Geriatr ; 43(4): 254-8, 2010 Aug.
Article in German | MEDLINE | ID: mdl-20237932

ABSTRACT

Many studies have shown that the number of new dementia diagnoses in Germany is increasing yearly. Thus, two social tasks are important: the adequate support and care of dementia patients, now and in the future, as well as covering the costs thereof. The survival period of dementia patients has a central meaning - especially for health policy planning. Therefore, the question of our 8-year follow-up study was whether living conditions affect the survival period of dementia patients? A total of 173 dementia outpatients (ICD-10 numbers F00 and F01) were screened for survival time and living conditions. For deceased patients, a close reference person was interviewed, and the exact date of death was recorded. For statistical evaluation, the Cox proportional hazard model was used and dying risks were determined. Our investigation shows that a clear difference exists in the survival period of dementia patients, according to whether they have lived at home or in a senior citizen's home. Patients in senior citizen's homes had a higher relative dying risk of around 53.1% (hazard ratio), than for those cared for at home (p=0.047). Prospective research is needed to gain more evidence about the impact of social factors, e.g., living conditions, on the survival time of demented patients.


Subject(s)
Alzheimer Disease/mortality , Dementia, Vascular/mortality , Homes for the Aged/statistics & numerical data , Independent Living , Nursing Homes/statistics & numerical data , Aged , Aged, 80 and over , Child , Follow-Up Studies , Germany , Home Care Services/statistics & numerical data , Humans , Infant , Proportional Hazards Models , Survival Analysis
5.
Z Gerontol Geriatr ; 41(1): 51-5, 2008 Feb.
Article in German | MEDLINE | ID: mdl-18286327

ABSTRACT

Alzheimer's disease and vascular dementia still may be looked upon as distinct nosologic entities, representing the two main etiologic categories of senile dementia. However, rather recent findings suggest a comorbidity of neurodegenerative and ischemic pathology in a majority of dementia cases in later life. The effect of the vascular pathology on the survival time was studied in 173 dementia outpatients. For 147 patients with complete datasets, we were able to gain information concerning their survival time. As an indicator of cerebrovascular morbidity the 18-point ischemic scale of Hachinski (HIS) was correlated with the survival time. Thus, we did not use the HIS for its original purpose to differentiate between degenerative and vascular dementia, but to roughly evaluate the cerebrovascular impact in a continuum model. Using the Cox model we calculated mortality risks for every point on the HIS. We found a Cox hazard ratio of 1.038 for each supplementary point on the HIS, which equals a 3.8% higher relative mortality risk. The result misses significance (p=0.092), but indicates a clear tendency towards a shortening of survival time by vascular comorbidity. Future prospective studies should integrate brain imaging to further corroborate our findings.


Subject(s)
Alzheimer Disease/mortality , Brain Ischemia/mortality , Dementia, Vascular/mortality , Dementia/mortality , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Brain Ischemia/diagnosis , Cohort Studies , Comorbidity , Dementia/diagnosis , Dementia, Vascular/diagnosis , Female , Germany , Humans , Male , Proportional Hazards Models , Retrospective Studies , Survival Analysis
6.
Eur J Obstet Gynecol Reprod Biol ; 137(2): 204-9, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17397990

ABSTRACT

OBJECTIVE: Enlargement of the junctional zone (JZ) on T2-weighted resonance imaging of the uterus has recently been established as the major criterion for adenomyosis in patients with endometriosis. This study was conducted to analyse the extent of adenomyosis using magnetic resonance imaging (MRI) and relate it to the duration of dysmenorrhoea. STUDY DESIGN: This was a prospective study of 70 patients presenting with the complaint of severe dysmenorrhoea. Forty patients (57%) reported dysmenorrhoea as their major complaint and 30 patients (43%) suffered additionally from infertility. Group I (n=40) consisted of patients with dysmenorrhoea of between 1 and 10 years' duration, group II (n=30) consisted of patients with dysmenorrhoea of longer than 11 years' duration. All patients underwent laparoscopy to detect the presence and degree of endometriosis, and all patients underwent T2-weighted resonance imaging of the uterus to detect the extent of adenomyosis by measurement of the "junctional zone". RESULTS: In group I, adenomyosis could be detected via MRI in 21 patients (52.5%), while 19 patients (47.5%) showed no signs of adenomyosis. By contrast, in group II a distinct enlargement of the JZ, as the major radiological criterion of adenomyosis, could be observed in 26 patients (87%), while only 4 patients (13%) revealed no signs of adenomyosis (p=0.04). The mean thickness of the JZ was significantly enlarged in group II (11.07 mm) compared with group I (6.38 mm; p<0.0001). The prevalence of adenomyosis in endometriosis after dysmenorrhoea of more than 11 years' duration was 87%. CONCLUSIONS: In deep infiltrating endometriosis, a correlation between a specific localisation and dysmenorrhoea can often not be found. Recently, endometriosis and adenomyosis have been believed to result from a common uterine disease, the dislocation of the basal endometrium. Our data clearly show that dysmenorrhoea of long duration in patients who have had endometriosis for over a threshold value of 11 years is significantly related to adenomyosis of the uterus. Hence, evaluation of adenomyosis using MRI should become a standard procedure in cases of dysmenorrhoea and endometriosis. Severe dysmenorrhoea of long duration should always focus clinical interest on adenomyosis of the uterus.


Subject(s)
Dysmenorrhea/pathology , Endometriosis/pathology , Magnetic Resonance Imaging , Adult , Disease Progression , Dysmenorrhea/diagnosis , Dysmenorrhea/etiology , Endometriosis/complications , Endometriosis/diagnosis , Endometrium/pathology , Female , Humans , Prospective Studies , Time Factors
7.
Ann N Y Acad Sci ; 1101: 1-20, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17416925

ABSTRACT

The uterus and fallopian tubes represent a functionally united peristaltic pump under the endocrine control of ipsilateral ovary. We have examined this function by using hysterosalpingoscintigraphy (HSS), recording of intrauterine pressure, electrohysterography, and Doppler sonography of the fallopian tubes. An uptake of labeled particles into the uterus was observed during the follicular and luteal phases of the cycle after application into the vagina. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Furthermore, the predominant transport was into the tube ipsilateral to the ovary containing the dominant follicle. The pregnancy rate following spontaneous intercourse or insemination was higher in those women in whom ipsilateral transport could be demonstrated. The amount of material transported to the ipsilateral tube was increased after oxytocin administration, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. An increase in the basal tone and amplitude of contractions was observed after oxytocin administration. These results support the idea that the uterus and fallopian tubes act as a peristaltic pump, which increases transport of sperm into the oviduct ipsilateral to the ovary bearing the dominant follicle. Oxytocin appears to play a critical role in this peristaltic pump. A failure of the peristaltic mechanism is possibly responsible for infertility. We propose the term tubal transport disorder (TTD) as a nosological entity. Results from HSS could be a useful adjunct for choosing treatment modalities in patients with patent fallopian tubes suffering from infertility. These patients may be better served with in vitro fertilization (IVF).


Subject(s)
Fallopian Tubes/physiology , Sperm Transport/physiology , Spermatozoa/physiology , Uterus/physiology , Adult , Female , Humans , Hysterosalpingography , Male , Microspheres , Middle Aged , Retrospective Studies , Uterine Contraction/physiology , Uterus/anatomy & histology
8.
Breast ; 16(3): 235-40, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17449250

ABSTRACT

Gene expression profiling using Affymetrix HG-U133 Arrays (22,500 genes) was performed on fresh frozen pretherapeutic core biopsies from 50 patients undergoing neoadjuvant chemotherapy (NAC) with docetaxel, adriamycin, cyclophosphamide (TAC) within the GEPARTRIO trial. The Sorlie classification based on the "intrinsic gene set" revealed four different subgroups in our cohort (normal-like: 14%, basal-like: 20%, erbB2+: 22% and luminal: 44%), which is in line with the original description. High genomic grade but not histopathological grading was statistically different within the four subgroups (P<0.001). About 45.5% of tumors classified according to erbB2+ cluster showed a pathological complete response compared to 0% in the normal-like, 10.0% in the basal-like and 9.1% in the luminal subgroup (P=0.024). There was a trend to less tumor relapses in the erbB2+ subgroup (0%) compared to the normal-like (28.6%), basal-like (30.0%) and luminal (13.6%) cluster (P=0.215). Our data suggest that the molecular tumor subtypes based on the "intrinsic gene set" can be used to predict tumor response according to NAC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/genetics , Genes, erbB-2 , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cyclophosphamide/administration & dosage , Docetaxel , Doxorubicin/administration & dosage , Female , Gene Expression Profiling , Humans , Middle Aged , Neoadjuvant Therapy , Taxoids/administration & dosage
9.
Breast ; 16(1): 86-93, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17010609

ABSTRACT

Gene expression analysis in breast cancer patients undergoing neoadjuvant chemotherapy is an interesting tool for identification of gene signatures and new markers to predict tumor response. However, the detection of predictive markers strongly depends on the drugs used in the specific therapeutic setting. There is growing evidence that topoisomerase II-alpha (TOPO IIalpha) is a marker for anthracycline-, and microtubule-associated protein tau (MAPT) for taxane sensitivity. HER-2 has been described as a marker of both anthracycline and taxane sensitivity. We performed gene expression profiling of 50 patients within the GEPARTRIO study, an anthracycline and taxane neoadjuvant chemotherapy trial. Here we investigate the predictive value of TOPO IIalpha, MAPT and HER-2 mRNA expression for pathological complete response (pCR) in this setting. Interestingly, HER-2 gene expression was strongly predictive of pCR (P=0.017) as well as overall response (P=0.037) and clinical complete response (cCR, P=0.050). In contrast, for both TOPO IIalpha and MAPT no correlation with pCR was observed in our sample group.


Subject(s)
Antigens, Neoplasm/genetics , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Carcinoma, Ductal, Breast/genetics , Carcinoma, Lobular/genetics , DNA Topoisomerases, Type II/genetics , DNA-Binding Proteins/genetics , Gene Expression Profiling , Genes, erbB-2/genetics , Oligonucleotide Array Sequence Analysis , tau Proteins/genetics , Adult , Aged , Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Docetaxel , Doxorubicin/administration & dosage , Female , Humans , Middle Aged , Neoadjuvant Therapy , Predictive Value of Tests , Taxoids/administration & dosage
10.
Zentralbl Gynakol ; 128(5): 242-5, 2006 Oct.
Article in German | MEDLINE | ID: mdl-17001558

ABSTRACT

OBJECTIVE: Cervical cancer screening guidelines stated recently that the screening interval of healthy women can be extended up to 3 years. Can those recommendations be applied for high risk populations? MATERIAL AND METHODS: In a prospective setting 305 HIV-positive women have been enrolled in this analysis between September 2000 and December 2003. Patients have been characterized according to HPV (human papilloma virus) prevalence, CIN (cervical intraepithelial neoplasia) incidence and CD4 cell count. RESULTS: 41 % of all HIV-positive women were HPV positive (oncogene subtypes). In patients with diminished CD4 cells the HPV prevalence increased to 60 % (54/90). CIN was found in 27 % (83/305) women. CIN was more frequent by HPV-positive women with a CD4 cell count < 200 mm (3) (52 %, 38/72). The CIN incidence was also high in HIV-positive women with negative HPV infection and diminished CD4 cell count (39 %, 7/18 vs.7 %, 11/161). CONCLUSIONS: The current cervical cancer screening guidelines are not helpful in HIV-positive women. The CIN incidence is significantly higher as in the HIV-positive population. For this reason this high risk population as e. g. HIV-infected women need an intensive care of diagnostic tools and short screening intervals to detect CIN.


Subject(s)
HIV Seropositivity/complications , Mass Screening/methods , Papillomavirus Infections/epidemiology , Uterine Cervical Neoplasms/prevention & control , Adolescent , Adult , Alphapapillomavirus/isolation & purification , Female , HIV Seropositivity/epidemiology , Humans , Middle Aged , Prevalence , Prospective Studies , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/virology , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/virology
11.
Zentralbl Gynakol ; 128(3): 135-7, 2006 Jun.
Article in German | MEDLINE | ID: mdl-16758379

ABSTRACT

The significance of retrograde menstruation as a risk factor for endometriosis has been confirmed by numerous clinical observations. Integrins mediate both cell-cell and cell-matrix adhesion, and it is therefore suspected that integrins are involved in the development of endometriosis. Using immunohistochemistry, integrin expression in eutopic and ectopic endometrium is examined in endometriosis patients and control individuals. In nearly all cases, the glandular epithelial cells in the endometrium showed expression of alpha (2-), alpha (3)-, alpha (6)- and alpha (v)- integrin and a low percentage of expression of alpha (1)-, alpha (4)-, and alpha (5)-integrin. In comparison with eutopic endometrium, ectopic endometrium shows reduced expression of alpha (2)- and alpha (v)-integrin. Since no differences in alpha (2)- and alpha (v)-integrin expression were observed in eutopic endometrium between endometriosis patients and control individuals, it may be suspected that the reduced expression of these in ectopic endometrium is explained by influences in the altered environment -- e. g., in the peritoneal fluid -- on the ectopic endometrium.


Subject(s)
Endometriosis/genetics , Endometrium/cytology , Integrins/genetics , Biopsy , Choristoma/genetics , Choristoma/pathology , Endometrium/pathology , Female , Humans
12.
BJOG ; 113(8): 902-8, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16753046

ABSTRACT

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.


Subject(s)
Adenomyoma/complications , Endometriosis/complications , Fallopian Tube Diseases/complications , Infertility, Female/etiology , Uterine Neoplasms/complications , Adenomyoma/physiopathology , Adult , Endometriosis/physiopathology , Fallopian Tube Diseases/physiopathology , Female , Humans , Infertility, Female/physiopathology , Magnetic Resonance Imaging , Prospective Studies , Uterine Neoplasms/physiopathology
13.
Zentralbl Gynakol ; 128(2): 87-9, 2006 Apr.
Article in German | MEDLINE | ID: mdl-16673251

ABSTRACT

The seldom occurring androgen insensitivity syndrome is characterised by male karyotype in a phenotypical women. We report on a complete androgen insensitivity syndrome with the rare coincidence of bilateral Fallopian tubes and a testicular intraepithelial neoplasia. Additionally we discuss aspects of incidence, molecular background, characteristics, diagnostic pitfalls and therapy against the background of the current literature.


Subject(s)
Androgen-Insensitivity Syndrome/diagnosis , Carcinoma in Situ/diagnosis , Testicular Neoplasms/diagnosis , Adolescent , Androgen-Insensitivity Syndrome/pathology , Androgen-Insensitivity Syndrome/surgery , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/pathology , Breast Neoplasms, Male/surgery , Carcinoma in Situ/pathology , Carcinoma in Situ/surgery , Fallopian Tubes/pathology , Fallopian Tubes/surgery , Female , Fibroadenoma/diagnosis , Fibroadenoma/pathology , Fibroadenoma/surgery , Humans , Karyotyping , Laparoscopy , Male , Mastectomy, Segmental , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/surgery , Orchiectomy , Phenotype , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery
14.
Zentralbl Gynakol ; 128(6): 347-51, 2006 Dec.
Article in German | MEDLINE | ID: mdl-17213974

ABSTRACT

OBJECTIVE: The incidence of vulvar intraepithelial neoplasia (VIN) has increased in the last decades. The therapy of VIN is the in toto resection. Still some patients develop VIN recurrence. The aim of this retrospective study is the identification of risk factors for VIN recurrence. MATERIAL AND METHODS: 68 Patients with VIN III has been examined in an univariate and multivariate analysis for the following parameters (follow-up: median 27 months): age, HPV, HIV, multicentricity, resection margins (1-4 mm, 5-9 mm, > or = 10 mm). RESULTS: In the univariate analysis positive HPV and HIV status correlated with VIN recurrence. Also resection margins < 5 mm showed a significant correlation with VIN recurrence. Multivariate analysis demonstrated that HPV, HIV and resection margins < 5 mm are independent risk factors. No statistically association was found for age and multicentricity. CONCLUSION: The aim of VIN therapy must be the total resection with a negative resection margin of > or = 5 mm. HPV- and/or HIV-positive patients have a significantly higher risk for VIN recurrence and need therefore an intensive follow up.


Subject(s)
Carcinoma in Situ/epidemiology , Vulvar Neoplasms/epidemiology , Adult , Alphapapillomavirus/isolation & purification , Analysis of Variance , Carcinoma in Situ/pathology , Carcinoma in Situ/surgery , Female , Humans , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local , Reoperation/statistics & numerical data , Risk Factors , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgery
15.
Zentralbl Gynakol ; 127(6): 395-9, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16341984

ABSTRACT

INTRODUCTION: We observed the congruity of bacteria found in urine and cervix of pregnant women with amniotic fluid infection (AFI) compared to healthy controls. PATIENTS AND METHODS: Over three years, we prospectively analysed urine and cervical swabs cultures in 120 pregnant women in gestational week 16-20. The patient population was divided in two groups: group I patients had clinical symptoms of AFI. The rest of the patients were designated as healthy controls (group II). Congruity between findings in both groups was observed. In patients with bacterial growth, antibiotic treatment was initiated as recommended and once ended - culture probes were repeated. RESULTS: The rates of nonsignificant and significant bacteriuria were doubled in group I. Fifty-five percent (n = 33) of patients in group I had identical bacteria cultured both from the urine sample and cervical swab, in contrast to only 13.3 % in group II. Congruity was most pronounced for Klebsiella species and E. coli, the later being single most dominant isolate in regards to both cultures. After antimicrobial treatment, microbial eradication occurred in 15 patients (45.5 %). The observed incidences of abortions and preterm deliveries were significantly lower in patients with microbial eradication versus patients with microbial persistence. CONCLUSION: Patients with clinical symptoms of AFI have high risk for bacteriuria identical to bacterial culture from cervical swab. Antimicrobial treatment was effective only partially where indicated. Screening for eradication is recommended and consensus on the most appropriate therapy is needed.


Subject(s)
Amniotic Fluid/microbiology , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/urine , Vaginal Smears , Amniotic Fluid/virology , Bacterial Infections/diagnosis , Bacterial Infections/urine , Female , Humans , Pregnancy
16.
Endocr Relat Cancer ; 12(4): 903-16, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16322330

ABSTRACT

The function of estrogen receptor beta (ER-beta) in mammary tissue is not completely understood. While early observations were often conflicting, more recent data suggest an important role as a tumor-suppressor gene. A decrease of ER-beta expression has been observed in ductal carcinoma in situ and invasive carcinoma as compared with benign mammary epithelial cells. The loss of ER-beta resulted in abnormal growth of mammary epithelial cells. We have previously shown that the mRNA expression of the ER-beta gene is almost totally suppressed in breast carcinomas from patients with a poor prognosis. Here we analyzed whether methylation changes in the different promoters of ER-beta are responsible for the loss of expression of the gene. A methylation assay with high specificity and sensitivity was developed, and a panel of breast tissue samples (n = 175) was characterized for methylation status. In contrast to benign breast, more than two-thirds of invasive breast cancers showed a high degree of methylation. Importantly, increased methylation was also detectable in numerous premalignant lesions. By analysis of breast tumors, previously characterized by gene-expression profiling, methylation was predominantly detected in a subgroup of patients with an unfavorable prognosis, suggesting a possible prognostic value of the ER-beta methylation status. We also investigated the structural characteristics of the two ER-beta promoters, which were both found to be closely associated with a second, downstream, localized and opposite-oriented promoter. However, we could not detect endogenous antisense RNA transcribed from these promoters, which may be involved in epigenetic gene silencing. We also failed to induce ER-beta promoter methylation by expressing siRNAs in cell lines. Interestingly, by comparing the promoter sequences of ER-beta with other genes known to be epigenetically inactivated in breast cancers, we identified a sequence motif possibly involved in promoter methylation.


Subject(s)
Breast Neoplasms/genetics , Carcinoma/genetics , DNA Methylation , Estrogen Receptor beta/genetics , Precancerous Conditions/diagnosis , Promoter Regions, Genetic/genetics , Base Sequence , Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Carcinoma/diagnosis , DNA, Neoplasm/metabolism , Epigenesis, Genetic , Estrogen Receptor beta/metabolism , Female , Gene Expression Profiling , Humans , Molecular Sequence Data , Precancerous Conditions/genetics , Prognosis , RNA, Small Interfering/genetics
17.
BJOG ; 112(10): 1391-6, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16167942

ABSTRACT

OBJECTIVE: To investigate uterotubal transport by means of hysterosalpingoscintigraphy (HSSG) in women with and without endometriosis. DESIGN: A prospective observational study. SETTING: University Hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 350 in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles and 400 intrauterine insemination (IUI) cycles/year. POPULATION: Cases included 56 infertile women with laparoscopic proven endometriosis and patent fallopian tubes. Twenty-two women with partners suffering from male factor infertility served as controls. METHODS: A diagnostic cycle incorporating HSSG was performed. Subsequently, patients underwent either four cycles of timed intercourse (TI) or IUI in order to achieve pregnancy. If pregnancy did not occur, IVF or ICSI was performed. MAIN OUTCOME MEASURES: Evaluation of uterotubal transport capacity in women with endometriosis and healthy controls. RESULTS: Patients suffering from endometriosis (group I) showed a significant reduction in physiologic uterotubal transport function: While 20 patients (36%) had ipsi- or bilateral uterotubal transport, there was pathological uterotubal transport contralateral to the dominant follicle or a complete failure of transport capacity (negative HSSG) in 36 patients (64%). In the controls (group II), transport function was significantly different: 15 of 22 patients (68%) revealed ipsi- and bilateral tubal demonstration, while 5 patients (22%) showed contralateral transport and 2 patients (10%) showed negative HSSG (P= 0.01). Twenty-three pregnancies were observed (pregnancy rate: 29%). Eleven out of 14 (79%) women with ipsi- or bilateral tubal transport function fell pregnant by means of TI or IUI. In seven of nine patients (78%) with a failure in tubal transport, pregnancy was achieved by IVF/ICSI, despite acceptable semen parameters (P= 0.01). CONCLUSIONS: Endometriosis is significantly associated with a reduction in physiologic uterotubal transport capacity compared with controls. This resulted in diminished pregnancy rates even in women with normozoospermic partners. Therefore, IVF/ICSI may be required even when fallopian tubes are patent or semen quality is normal.


Subject(s)
Endometriosis/physiopathology , Fallopian Tube Diseases/physiopathology , Infertility, Female/physiopathology , Ovum Transport/physiology , Pregnancy Rate , Uterus/physiology , Adult , Fallopian Tube Diseases/diagnostic imaging , Female , Fertilization in Vitro , Humans , Hysterosalpingography/methods , Infertility, Female/diagnostic imaging , Infertility, Female/etiology , Infertility, Male/therapy , Male , Pregnancy , Prospective Studies , Sperm Injections, Intracytoplasmic
18.
Zentralbl Gynakol ; 127(4): 242-7, 2005 Aug.
Article in German | MEDLINE | ID: mdl-16037906

ABSTRACT

OBJECTIVE: The management of HIV-positive pregnancies was investigated in conjunction to pre-, peri and postpartal complications and the HIV transmission rate. PATIENTS AND METHODS: Retrospective study of 88 HIV-positive patients who were delivered at the Dept. of Obstetrics and Gynaecology during 1.1.1997-31.12.2001. RESULTS: HIV-positive patients showed significantly more prepartal complications, compared to control group. Low CD4-cell count (< or = 200/microl) or high viral load (> 10 000 HIV-copies/ml) was not associated with increased risk for transmission relevant complications. The overall HIV-transmission rate was 3.4 % (3/89 newborns; with ART 2.5 % [2/85], without ART 33.3 % [1/3]). The transmission rate increased with complications during pregnancy (7.7 % [2/26] vs. 1.6 % [1/61]). Newborns delivered < or = 35 (th) week of gestation showed a transmission rate of 5.3 % compared to 2.9 % of newborns delivered after the 35 (th) week of gestation. 98 % of the patients were delivered by cesarean section (primary: n = 71, prior: n = 15), spontaneously: n = 2). 97 % of patients (85/88) were treated with antiretroviral therapy (ART). No differences were found in the postpartal complication rate of HIV-positive to -negative patients. None of the newborns was breast fed. CONCLUSIONS: Treatment of this risk-pregnancies in HIV experienced centers significantly reduces the risk of HIV transmission.


Subject(s)
HIV Seropositivity/transmission , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/virology , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Retrospective Studies
19.
Hum Reprod ; 20(8): 2309-16, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15919780

ABSTRACT

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.


Subject(s)
Endometriosis/epidemiology , Endometriosis/pathology , Infertility, Female/epidemiology , Infertility, Female/pathology , Magnetic Resonance Imaging , Adolescent , Adult , Endometrium/pathology , Female , Fertility , Humans , Male , Middle Aged , Prevalence , Sperm Count
20.
Rofo ; 176(11): 1641-7, 2004 Nov.
Article in German | MEDLINE | ID: mdl-15497083

ABSTRACT

PURPOSE: To evaluate the clinical value of magnetic resonance imaging (MRI) of the uterus and the pelvis in infertile female with symptomatic endometriosis for the assessment of uterine morphology and function. MATERIALS AND METHODS: Forty-one infertile women (mean age: 33.2 years) with symptomatic endometriosis documented by laparoscopy were evaluated with high-field MRI (Sonata, Siemens) using T2- and T1-weighted sequences. In addition, the patients underwent hysterosalpingoscintigraphy (HSSG) for evaluation of the uterotubal transport capacity. Pathologic findings of the uterine junction zone were correlated with the laparoscopic results, clinical symptoms and uterotubal transport capacity. RESULTS: Adenomyosis was diagnosed on T2-weigthed MR-images in 35 (85.4 %) patients (focal adenomatosis in 26 patients and diffuse adenomatosis in 9). Patients showing signs of adenomyosis tended to be older than patients without adenomyosis (mean age 34.1 years vs. 30.1 years) and showed a longer history of symptomatic endometriosis. A positive transport capacity in HSSG was observed in 73.1 % (19/26) of the patients with focal adenomyosis and in only 22.2 % (2/9) of patients with diffuse adenomyosis. In 83.3 % (5/6) of the patients without signs of adenomyosis, a positive uterotubal transport was documented. CONCLUSION: MRI of the uterus is a helpful diagnostic tool for the diagnosis of adenomyosis and for planning further therapies. Patients with the diagnosis of adenomyosis showed a reduced uterotubal transport capacity that depended on the severity of adenomyotic changes and might be a possible cause of infertility.


Subject(s)
Endometriosis/diagnosis , Infertility, Female/etiology , Magnetic Resonance Imaging , Uterine Diseases/diagnosis , Adult , Age Factors , Endometriosis/complications , Endometriosis/diagnostic imaging , Female , Humans , Infertility, Female/diagnosis , Laparoscopy , Radionuclide Imaging , Time Factors , Uterine Diseases/complications , Uterine Diseases/diagnostic imaging
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