Pattern recognition in menstrual bleeding diaries by statistical cluster analysis.

BACKGROUND: The aim of this paper is to empirically identify a treatment-independent statistical method to describe clinically relevant bleeding patterns by using bleeding diaries of clinical studies on various sex hormone containing drugs. METHODS: We used the four cluster analysis methods single, average and complete linkage as well as the method of Ward for the pattern recognition in menstrual bleeding diaries. The optimal number of clusters was determined using the semi-partial R2, the cubic cluster criterion, the pseudo-F- and the pseudo-t2-statistic. Finally, the interpretability of the results from a gynecological point of view was assessed. RESULTS: The method of Ward yielded distinct clusters of the bleeding diaries. The other methods successively chained the observations into one cluster. The optimal number of distinctive bleeding patterns was six. We found two desirable and four undesirable bleeding patterns. Cyclic and non cyclic bleeding patterns were well separated. CONCLUSION: Using this cluster analysis with the method of Ward medications and devices having an impact on bleeding can be easily compared and categorized.

Denial of pregnancy--characteristics of women at risk.

BACKGROUND: Denial of pregnancy is a woman's subjective lack of awareness of being pregnant. Denial throughout most of gestation or until delivery may be associated with significant risks for both mother and fetus. We wanted to investigate if maternal characteristics were useful in order to identify women at risk. METHODS: A 1-year prospective study was performed to recruit all women with denied pregnancies in Berlin, Germany. Maternal parameters were analysed and sociodemographic variables were compared with the regional birth register. RESULTS: Sixty-five women were recruited. Maternal age was between 15 and 44 years (median 27 years). Only 21 women had never been pregnant before. A large majority (83%) had a close partner. Three women had a psychiatric diagnosis of schizophrenia, and only one a current abuse of analgesics/tranquilizer. CONCLUSIONS: The group of women with denied pregnancy was heterogeneous, and a clear-cut typology of a 'pregnancy denier' could not be established.

Denial of pregnancy as a reproductive dysfunction: a proposal for international classification systems.

OBJECTIVE: To propose a new Diagnostic and Statistical Manual (DSM) and International Classification of Diseases (ICD) category concerning reproductive dysfunctions not caused by organic disorder. METHODS: Forensic (n=93) and obstetrical cases (n=78) of denied and concealed pregnancies are compared and discussed. RESULTS: Denied pregnancies occur with a ratio of 1:475 births. An overwhelming phenomenological agreement is demonstrated between obstetrical and forensic cases. The findings were similar for denial and concealment of pregnancy, probably representing two different types of reproductive dysfunction that can be classified psychosocially together under the heading "negated pregnancy". CONCLUSIONS: Analogous to the phenomenology of "sexual dysfunctions", "reproductive dysfunctions" could be distinguished by the extraordinariness of both reproductive experience and behavior (as part of human sexuality) and psycho-physiological changes, which characterize the reproductive course of events and cause obvious suffering and interpersonal complications. It is therefore suggested to include these entities as categories in their own right under the appropriate existing headings in DSM and ICD.

A 1-year study to compare the hemostatic effects of oral contraceptive containing 20 microg of ethinylestradiol and 100 microg of levonorgestrel with 30 microg of ethinylestradiol and 100 microg of levonorgestrel.

OBJECTIVES: To comparatively evaluate the impact of a balanced one-third dose-reduced oral contraceptive on hemostatic variables. METHODS: In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg of ethinylestradiol (EE) and 100 microg of levonorgestrel (LNG) was compared with a reference preparation containing 30 microg of EE and 150 microg of LNG. One-year data were obtained from 48 volunteers. RESULTS: The direction and magnitude of the changes (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. The majority of changes of all investigated variables remained within the reference ranges of variation. The procoagulatory variables increased to some extent from baseline to treatment cycle 13, while the anticoagulatory variables slightly decreased. In particular, thrombin turnover measured by prothrombin fragments 1+2 increased during treatment by 35% in the 20 microg of EE group and by 38% in the 30 microg of EE group. Statistically significant differences between the two treatment groups were found only for TAT. For the profibrinolytic variables, plasminogen was increased by 42% (20 microg of EE) and 49% (30 microg of EE). While the plasma levels of tPA antigen were reduced during treatment, the levels of its activity were increased by 54% (20 microg of EE) and 20% (30 microg of EE). For PAI, both antigen and activity were decreased, somewhat more pronounced with 20 microg of EE. D-Dimer remained virtually unchanged. Finally, the median FbDP levels were elevated by 30% (20 microg of EE) and 38% (30 microg of EE).

A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel.

OBJECTIVES: To evaluate the impact on lipid and carbohydrate variables of a combined one-third ethinyl estradiol (EE)/levonorgestrel (LNG) dose reduction in oral contraceptives. METHODS: In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg EE and 100 microg LNG (20 EE/100 LNG) was compared with a reference preparation containing 30 microg EE and 150 microg LNG (30 EE/150 LNG). One-year data from 48 volunteers were obtained. RESULTS: We found a decrease of HDL2 cholesterol and increases of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and total triglycerides in both treatment groups from baseline to the 13th treatment cycle. Although for four of six variables, the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant. The median values for the fasting levels of insulin, C-peptide and free fatty acids slightly increased or remained unchanged while the fasting glucose levels slightly decreased after 13 treatment cycles. While the glucose area under the curve (AUC) (0-3 h) was similar in both groups during the OGTT, the insulin AUC(0-3 h) was less increased in the 20 EE/100 LNG group compared with the 30 EE/150 LNG group. None of the differences between the treatment groups for any of the carbohydrate metabolism variables were statistically significant at any time point. Both study treatments were safe and well tolerated by the volunteers. CONCLUSION: Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new oral contraceptive caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.

Cyclic menstruation-like bleeding during denied pregnancy. Is there a particular hormonal cause?

OBJECTIVE: To investigate whether particular hormonal patterns could explain the persistence of cyclic menstruation-like bleeding during denied pregnancies. METHODS: Hormone measurements were performed immediately after delivery in a total of 28 subjects with denied pregnancies. The results were studied in three patient subgroups: subjects with any cyclic bleeding during pregnancy (n = 22), subjects with cyclic bleeding during pregnancy until the delivery date (n = 7) and subjects with amenorrhea (n = 6). These data were compared with those of a control group (n = 126). In some of the women who reported cyclic bleeding, hormone assessments were also done once the lactation period ended. RESULTS: For estradiol, free estriol and progesterone, no more than two values in each group were outside the 95% confidence interval of the control group. Several results for prolactin were remarkably lower. The findings for human chorionic gonadotropin, free testosterone, dehydroepiandrosterone sulfate, alpha-fetoprotein and thyroid-stimulating hormone were almost all within the 95% confidence interval. In seven subjects, abnormal results were obtained for the gondaotropin-releasing hormone/thyrotropin-releasing hormone test and the metoclopramid test after delivery and lactation. All of these subjects showed signs of corpus luteum insufficiency. In five subjects, evidence of hyperprolactinemia was found. CONCLUSION: Results revealed that hormonal patterns assessed immediately after delivery do not provide any causal explanation for the cyclic menstruation-like bleeding that occurs during denied pregnancies. Hormone assessments performed after the lactation period, i.e. during a normal menstrual cycle, showed a number of abnormalities. However, a causal relationship could not be drawn.

Vesicovaginal fistula after Irving sterilization: a case report.

BACKGROUND: Patients scheduled for gynecologic surgery must be informed about the development of urogenital fistulae as a possible complication. CASE: A 49-year-old woman underwent Irving sterilization with subsequent abdominal hysterectomy due to intraabdominal abscess formation. Inadvertent damage complication to the bladder during hysterectomy led to development of a vesicovaginal fistula despite intraoperative management. The fistula was repaired at once in a second session. As a sequela of bladder injury, the patient had recurrent vesical diverticula and urolithiasis with repeated removal of the diverticula and stones. A subsequent intervention performed laparoscopically led to development of a second vesicovaginal fistula. In addition, an anesthesia-induced complication resulted in cerebral hypoxia with postoperative development of Parkinson's disease. CONCLUSION: Retrospectively, there is doubt whether the proper surgical procedures were employed in this case. The fact that the patient had type 1 diabetes mellitus gives rise to the question of why no conservative method of contraception was chosen. The type of operative approach in elective surgery should always be planned on the basis of the individual patient's overall condition and in relation to the anatomic situation.

Elevation of interleukin-6 levels in cervical secretions as a predictor of preterm delivery.

BACKGROUND: The objective of this study was to evaluate the predictive value of interleukin-6 (IL-6) in cervical secretions for preterm delivery before 34+0 gestational weeks in patients with preterm labor. METHODS: In this prospective study, 31 patients were enrolled with preterm labor and intact membranes. Cervical swabs were taken on admission and the concentration of IL-6 was measured. The gestational age at the time of admission and delivery, as well as the time interval to delivery, were evaluated and compared with the concentration of IL-6 on admission. RESULTS: Cervical IL-6 was significantly elevated in the preterm delivery group (< 34+0 gestational weeks, p < 0.05). Choosing 20 pg/ml as a cut-off concentration, cervical IL-6 had a sensitivity and negative predictive value of 100%, a specificity of 67% and a positive predictive value of 47%. Concerning the time interval to delivery, the sensitivity of IL-6 was 100% and the specificity 57% for delivery within 2 days and 100% and 64% for delivery within 7 days. CONCLUSIONS: Cervical IL-6 is a new, promising diagnostic tool to identify patients at high risk of preterm delivery.

Elevated risk for neonatal outcome following denial of pregnancy: results of a one-year prospective study compared with control groups.

AIMS: Newborns following denied pregnancies are delivered after either late onset or total absence of antenatal care, with a presumed subsequently increased risk for neonatal outcome. For this specific group, several characteristic outcome parameters are investigated. METHODS: During the period July 1, 1995 to June 30, 1996, a prospective case sampling was performed for denied pregnancies in Berlin. Besides determination of the parameters' frequency, comparison with two control groups is performed: a normal group (BBR, all Berlin deliveries in 1995) and a high risk group (VIR, all deliveries at a perinatal center in 1996). RESULTS: Altogether 69 neonates occurred. For gestational age < 37 weeks, birth weight < 2500 g, small for gestational age, transferal rate of newborns to neonatal unit and surgical delivery, a statistically significant worse outcome is demonstrated for denied pregnancies versus BBR and VIR (p-level < 0.05). Neonatal mortality is 5.8% in all cases, the corrected rate is 1.5% (excluding three non-viable cases of 21st and 23rd week of gestation). CONCLUSIONS: The data underline the elevated fetal outcome risk for newborns after denial of pregnancy. In this group, total absence or late onset of antenatal care results in a manifestation of pregnancy dependent risks. Preterm births and small for gestational age newborns, together with deaths, may be classified as at least potentially avoidable.

Frequency of denial of pregnancy: results and epidemiological significance of a 1-year prospective study in Berlin.

BACKGROUND: There has been an increasing number of reports on denial of pregnancy. However, only very few studies have involved a large number of patients. To date, no reliable calculation of this condition's general frequency, also from an epidemiological perspective, has been available. METHODS: A prospective case sampling was performed between 1 July 1995 and 30 June 1996 in the metropolitan area of Berlin. All institutions in which deliveries have taken place were engaged. The lower limit for inclusion was the 20th week of gestation as the first physician's earliest diagnosis of pregnancy. Furthermore, the woman herself must not have had any subjective perception. RESULTS: Recruited women were divided into three groups. Altogether 62 cases and 29 462 deliveries within the 1-year study period were valid for the frequency calculation, leading to a ratio of 1 : 475 (all cases) and of 1 : 2455 for totally unexpected births with a viable newborn (intrapartal diagnosis of the pregnancy). CONCLUSIONS: This first prospective, population-based study has also certain epidemiological relevance. From projecting the ratio of 1 : 475 for all of Germany, approximately 1600 cases of denied pregnancies per year are diagnosed, at the earliest, from the 20th week of gestation. Totally unexpected deliveries of a viable fetus without any presumption of being pregnant with 300 projected yearly births would occur threefold more often than triplets. Occurrence of denied pregnancy seems yet to be similar across different socio-demographic conditions. The common view that denied pregnancies are exotic and rare events is no longer valid. More studies of similar design are needed.

Tris(dimethylamino)oxosulfonium difluorotrimethylsilicate, (Me(2)N)(3)SO(+)Me(3)SiF(2)(-) (TAOS Fluoride).

In the OSF(4)/Me(2)NSiMe(3) system besides the long known Me(2)NS(O)F(3) only the trisubstituted derivative is isolated as (Me(2)N)(3)SO(+)Me(3)SiF(2)(-) (3). Similar to (Me(2)N)(3)S(+)Me(3)SiF(2)(-) compound 3 is an excellent fluoride ion donor. With AsF(5) and HF the corresponding hexafluoroarsenate (Me(2)N)(3)SO(+)AsF(6)(-) (4) and the hydrogen bifluoride (Me(2)N)(3)SO(+)HF(2)(-) (5) are formed in almost quantitative yield. X-ray structure determinations of 3-5 surprisingly showed two different types of structures for the cation. In 3 and 5 this cation has C(3) symmetry, while in the hexafluoroarsenate 4 a (Me(2)N)(3)S(+)-like structure with C(s)() symmetry is determined. The experimental results for (Me(2)N)(3)SO(+) and (Me(2)N)(3)S(+) are compared with theoretical calculations for these cations and their isoelectronic neutral counterparts, the phosphorus amides (Me(2)N)(3)PO and (Me(2)N)(3)P, respectively.

Syntheses and Structures of Bis(azole)difluorosulfuranes.

Bis(imidazole)sulfur difluoride (4), bis(pyrazole)sulfur difluoride (6), and bis(1,2,4-triazole)sulfur difluoride (8) are formed in the reactions of N-(trimethylsilyl)imidazole, N-(trimethylsilyl)pyrazole, and 1-(trimethylsilyl)-1,2,4-triazole with SF(4), in high yield. The ring systems in these three molecules occupy equatorial positions in the pseudo-trigonal-bipyramidal coordination sphere of the central sulfur atoms. The angles between the planes of the ring substituents and the FSF axis for 4 and 6 are in the range 23.6-35.3 degrees, and in 8 the triazole rings are almost parallel (deviation 1.7 degrees ). The interaction between the heterocyclic substituents and the sulfur centers and their influence on the axial and equatorial bonds is discussed.