Array-comparative genomic hybridization analysis in patients with Müllerian fusion anomalies.

Fusion anomalies of the Müllerian ducts are associated with an increased risk for miscarriage and premature labor. In most cases polygenic-multifactorial inheritance can be assumed but autosomal-dominant inheritance with reduced penetrance and variable manifestation should be considered. We performed array-comparative genomic hybridization (CGH) analysis in a cohort of 103 patients with Müllerian fusion anomalies. In 8 patients we detected microdeletions and microduplications in chromosomal regions 17q12, 22q11.21, 9q33.1, 3q26.11 and 7q31.1. The rearrangement in 17q12 including LHX1 and HNF1ß as well as in 22q11.21 have already been observed in MRKHS (Mayer-Rokitansky-Küster-Hauser syndrome). In summary, we (1) detected causative micro-rearrangements in patients with Müllerian fusion anomalies, (2) show that Müllerian fusion anomalies and MRKHS may have a common etiology, and (3) identified new candidate genes for Müllerian fusion anomalies.

Mutations in WNT9B are associated with Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a well-known malformation pattern of the Müllerian ducts (MDs) characterized by congenital absence of the uterus and vagina. To date, most cases remain unexplained at molecular level. As female Wnt9b-/- mice show a MRKHS-like phenotype, WNT9B has emerged as a promising candidate gene for this disease. We performed retrospective sequence analyses of WNT9B in 226 female patients with disorders of the MDs, including 109 patients with MRKHS, as well as in 135 controls. One nonsense mutation and five likely pathogenic missense mutations were detected in WNT9B. Five of these mutations were found in cases with MRKHS accounting for 4.6% of the patients with this phenotype. No pathogenic mutations were detected in the control group (p = 0.017). Interestingly, all of the MRKHS patients with a WNT9B mutation were classified as MRKHS type 1, representing 8.5% of the cases from this subgroup. In previous studies, two of the patients with a WNT9B mutation were found to carry either an additional deletion of LHX1 or a missense mutation in TBX6. We conclude that mutations in WNT9B were frequently associated with MRKHS in our cohort and some cases may be explained by a digenic disease model.

A safety and efficacy study of a resorbable hydrogel for reduction of post-operative adhesions following myomectomy.

BACKGROUND: This multicenter, randomized, single-blind study assessed the safety and efficacy of a resorbable hydrogel ('Hydrogel') for the reduction of post-operative adhesion formation following myomectomy. METHODS: Women (n = 71) who were undergoing laparoscopic (67.6%) or laparotomic myomectomy were randomized (2:1) to Hydrogel (sprayed over surgically treated areas prior to wound closure, n = 48) or to control (standard care, n = 23). Patients (38 Hydrogel, 20 control) returned 8-10 weeks later for a second look. Adhesions were graded using a modified American Fertility Society (mAFS) scoring method. The primary efficacy measure was the posterior uterus mAFS score. RESULTS: For Hydrogel and control patients, respectively, mean +/- SD mAFS scores were 0.5 +/- 1.4 and 0.0 +/- 0.0 at baseline, and 1.1 +/- 1.9 and 2.6 +/- 2.2 at the second look. Similarly, mean changes from baseline were 0.8 +/- 2.0 and 2.6 +/- 2.2 (P = 0.01); 95% confidence intervals for these mean changes were (0.16-1.44) and (1.64-3.56). Adverse events were reported by 9.6 and 17.4% of Hydrogel and control patients, respectively. No intra-abdominal infections or post-operative site infections were reported. CONCLUSIONS: This 71-patient study provides the first clinical evidence of the safety and efficacy of Hydrogel for the reduction of adhesions following myomectomy. The ClinicalTrials.gov Identifier is NCT00562471.

Post-hoc analysis on the CD14 C(-260)T promoter polymorphism and coronary heart disease.

Functional C(-260)--> T polymorphism in the promoter of the CD14 gene has been reported to be associated with coronary heart disease (CHD). The functional role of the polymorphism, however, is still a matter of debate, since several studies have not proved its effect on clinical outcomes associated with atherosclerosis. Cardiovascular-related morbidity and mortality was assessed in a post-hoc approach four years after baseline characterization of patients (male/female n = 36/32) with angiographically proven coronary heart disease. CD14 C(-260)--> T promoter genotype was determined at baseline. Seventeen out of 20 CHD patients with non-lethal cardiovascular events carried at least one T-allele. CD14 T-260 allele carriers have a 3.59-fold (95 % confidence interval: 1.11-6.75) increased risk for non-lethal cardiovascular events (Kaplan-Meier plot: log rank test p = 0.029). All patients with lethal outcomes (n = 6) were also T-allele carriers. Multivariate logistic regression analysis among CHD patients including age, established risk factors and the C(-260)--> T polymorphism as covariates and non-lethal events as a dependent variable confirmed the independent prospective effect of the T-allele on cardiovascular outcomes in this subset. Further evidence is provided for the role of CD14 C(-260)--> T promoter polymorphism as a genetic susceptibility marker of atherosclerosis in patients with an advanced clinical course of the disease. Due to the small sample size and post-hoc character of the study large-scale prospective studies that monitor patients with proven CHD are needed to confirm these findings.

Hysteroscopic treatment of congenital uterine malformations causing hemihematometra: a report of three cases.

To our knowledge, this is the first case report of hysteroscopic treatment of congenital uterine malformations with one-sided occlusion causing hemihematometra. This rare form of uterine anomaly should be considered when symptoms such as increasing pelvic pain start with menarche. A 9-mm resectoscope was used for dissecting the way into the occluded part of the uterine body. There the endometrium was ablated for prevention of recurrence of hemihematometra. By this endoscopic approach the disadvantages of laparotomy could be avoided in three adolescent patients.

[Quinic acid lactone in coffee]. / Chinasäurelacton im Kaffee.

Quinic acid and its lactone (quinide) have been determined in coffee by capillary gas chromatography. No quinide could be detected in 14 green coffee's. After steaming of 4 green coffee's the content of quinic acid was always higher, but no quinide had been formed. During roasting, the latter can be detected when roasting loss exceed 6.5%. It increases approximately proportionally with quinic acid and amounts to 50% of the latter at 22% roasting loss. Both constituents decrease at unusual high roasting loss. In 13 commercial blends of roast coffee 2.4-6.4 g/kg quinide and 8.7-16.6 g/kg quinic acid were present. Especially high values were found in one Espresso type blend and high values in steamed and decaffeinated coffee's. In 11 commercial coffee extracts 2.0-23.2 g/kg quinide and 24.6-36.4 g/kg quinic acid were determined. At higher extraction yield, more quinic acid and quinide is formed, but at very high extraction yield the content of quinide is diminished. During holding of coffee brews at elevated temperature, quinide is slowly hydrolysed.

[Hematometra after hysteroscopic endometrium ablation--a case report]. / Hämatometra nach hysteroskopischer Endometriumablation--ein Fallbericht.

13 months after a hysteroscopic endometrial ablation a haematometra was diagnosed in a 44 year-old women as a source of recurrent pelvic pain. The cause of the haematometra was a complete obliteration of the ostium cervicae internum. This long-term complication of the endometrial ablation shows that all patients should have a regular clinical and sonographical follow up after endometrial ablation.

The prognostic value of salpingoscopy.

Salpingoscopy enables the visual inspection of the ampullary mucosa during either laparotomy or laparoscopy. This prospective study correlates the salpingoscopic results with the postoperative pregnancy rates and evaluates the value of salpingoscopy against already existing classification systems. A total of 226 women diagnosed as having pelvic inflammatory disease were treated by microsurgery. There were no other causes of infertility in these patients. The collective was divided into patients with pure adhesive disease and those with supplementary distal tubal occlusion. Salpingoscopy was performed at the end of a microsurgical laparotomy. All laparotomies were performed between 1989 and 1992. The occurrence of pregnancy was checked after 42 months follow-up. A correlation between salpingoscopy and the American Fertility Society classification for each tube is discussed. The crude and cumulative intrauterine pregnancy rates are reported for the two patient groups.

[Pregnancy after combined microsurgical and hysteroscopic surgical procedure in a patient with uterus septus and vagina septa]. / Schwangerschaft nach kombiniert mikrochirurgischem und operativ-hysteroskopischem Vorgehen bei einer Patientin mit Uterus septus und Vagina septa.

Disturbances in the development of the Müllerian duct system may cause different forms of genital anomalies. We report on a patient with uterus septus and vagina septa, undiagnosed for years, and consequently successfully treated for infertility, who became pregnant immediately after combined microsurgical and operative-hysteroscopic treatment. The pregnancy proceeded without any complications. The patient delivered a healthy girl in the 41st week of gestation.

Interstitial pregnancy treated with local and systemic methotrexate.

We present a case of an intact interstitial pregnancy at 6 postmenstrual weeks and 4 days, which was successfully treated by combined local and systemic methotrexate administration. The embryonic cardiac activity stopped within 1 min after uneventful ultrasound-guided puncture and methotrexate instillation of the chorionic sac. While the beta-hCG serum values returned to normal 59 days after local, and 52 days after systemic treatment, the echogenic lesion has reduced in size by 50%, but is still sonographically detectable 7 months after the procedure. This report shows that medical treatment of interstitial pregnancy may be an effective alternative to the surgical approach.

Hysteroscopy in infertility--diagnosis and treatment including falloposcopy.

Diagnostic hysteroscopy should be included routinely in the work-up of invasive examinations for infertility patients. Anyhow, one can rarely expect to find the definite underlying reason for infertility. In infertile patients about 20% of hysteroscopic examinations show some grade of intrauterine abnormalities. Congenital uterine malformations are the most frequently found disorders. In the group of patients with habitual abortions abnormalities are found much more often and can also be more often interpreted as the mainly underlying factor for the repeated abortions. Operative hysteroscopy has become the surgical method of first choice for the treatment of uterine septa, submucous myomas, polyps and synechia. After septum dissection results are excellent. Myoma removal also shows beneficial effects on fertility; nevertheless, cases are not too frequent among infertility patients. In cases of high-grade Asherman's syndrome, the prognosis after hysteroscopic surgery is still often poor.