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In 50 patients with benign ovarian tumours, 39 malignant ovarian carcinoma patients and 39 age-matched healthy women, plasma levels of thrombin-antithrombin III complex and D-dimer were determined as well as CA 125. The coagulation activation marker thrombin-antithrombin III complex and D-dimer levels were elevated in the malignant group compared to the benign and control groups. The results suggest that coagulation and fibrinolysis must play a prominent role in ovarian cancer. Moreover, D-dimer and thrombin-antithrombin III were equally useful as CA 125 for the discrimination of patients with benign or malignant ovarian tumours as evidenced by receiver operating and likelihood ratio calculations.

Examination of a woman aged 17 years with primary amenorrhoea revealed normal breasts and external genital organs, hardly any axillary or pubic hair growth, a blind vaginal pouch and no palpable uterus or adnexa. At additional examination, uterus and adnexa proved to be absent, the serum testosterone concentration was substantially increased and the karyotype was 46,XY. The diagnosis was 'testicular feminization' (androgen insensitivity syndrome). The patient in childhood had undergone a bilateral inguinal hernia operation, at which 'ovaries' were found in the hernial sacs. It might have been interpreted as the first sign of the syndrome; such a finding necessitates further examination. Most patients with testicular feminization seek medical advice because of primary amenorrhoea. Early diagnosis is important because the risk of malignant degeneration of the intra-abdominal testes increases with advancing age (sometimes also in relatives). Also it makes it possible gradually to prepare the child for her future.

Objective: The purpose of the study was to determine whether ovarian cancer patients had haematological anomalies compared to patients with benign ovarian tumours., Study Design: Whole blood cell counts and leucocyte differentials were measured in 70 patients suspected of having ovarian tumours. Postoperatively, 20 patients had metastatic ovarian cancer and 50 patients had benign ovarian tumours. A control group consisted of 39 healthy women. Cell counting was performed by the Sysmex NE-8,000 system. The significance of differences was assessed by the Mann-Whitney U-test or the chi 2-test, where appropriate., Results: The median haemoglobin and haematocrit levels were significantly lower (P-values 0.004 and 0.02, respectively) and the platelet count was higher (P = 0.02) in the malignant group compared with the benign group. The leucocyte differentials revealed significantly lower values for lymphocytes in the malignant group in comparison to the design and control groups (P-values 0.02 and 0.00005, respectively). A significant increase in monocytes (P = 0.002) and decreases in eosinophils and basophils (P-values 0.04 and 0.02, respectively) were found in the malignant group compared to the benign group., Conclusion: These results demonstrate significant changes in whole blood cell counts and leucocyte differentials in patients with ovarian cancer. The low lymphocyte counts in the malignant group possibly indicate a primary immunodeficiency as a casual factor.

Objective: Our purpose was to determine the effect of smoking during pregnancy on neonatal hemostasis., Study Design: Venous blood samples of 26 newborns of smoking and 25 newborns of nonsmoking mothers were obtained from the clamped umbilical cord immediately after birth. Prothrombin fragment 1+2, thrombin-antithrombin III complex, plasmin-alpha2-antiplasmin complex, and D-dimer levels were determined to assess activation of coagulation and fibrinolysis. Cotinine was measured in all neonates to objectify cigarette smoke exposure. The Mann-Whitney U test was used to compare the differences between the values of the parameters of coagulation and fibrinolysis in the two groups at the p < 0.05 level., Results: The median values of prothrombin fragment 1+2 and thrombin-antithrombin III complex in newborns exposed to tobacco smoke in utero did not differ from values of newborns who were not exposed. Nor were the markers of fibrinolysis, plasmin-alpha2-antiplasmin complex and D-dimer levels, influenced by tobacco smoke exposure., Conclusion: The balance between the components of coagulation and fibrinolytic pathways in neonates is not disturbed by maternal smoking.

Human blood coagulation factor XIII is a transglutaminase zymogen. Two forms exist, an extracellular or plasma factor XIII and an intracellular form. Factor XIII occurs in platelets, blood, monocytes, megakaryocytes, the liver, the placenta, and the uterus. In obstetrics, factor XIII deficiency has been associated with fetal wastage. The interaction of smoking and the quantity of coagulation factor XIII during normal pregnancy was examined in 75 non-smoking and 118 smoking (> or = 20 cigarettes/day) women. A group of subjectively healthy, non-smoking, age-matched females served as a control group (n = 30). Smokers had a higher plasma concentration of factor XIII than non-smokers. Factor XIII declined during normal gestation. During the second half of gestation the plasma concentration of factor XIII was significantly higher in smokers than in non-smokers. In smokers the decline of factor XIII was less, possibly due to platelet activation and a relative polycythemia. The later decline of factor XIII in pregnant smokers remains unexplained. More extensive research with larger patient numbers is needed to address this matter.

Objectives: To assess the effects of smoking during pregnancy on coagulation and fibrinolysis., Design: A cross-sectional study., Setting: A teaching hospital in Heerlen, The Netherlands., Results: Parameters of coagulation activation increased significantly with gestational age. The values presented are median values. Prothrombin fragment 1 + 2 increased from 0.8 to 2.5 nmol/l in the nonsmoking group of pregnant women and from 1.0 to 1.8 nmol/l in the smoking group. Thrombin-antithrombin III (TAT) levels increased from 2.2 to 9.9 micrograms/l in the nonsmoking group and from 3.1 to 8.5 micrograms/l in the smoking group. Parameters of fibrinolysis showed a different picture. Plasminogen levels in both groups rose significantly in the first half of gestation reaching a plateau in the second half. The alpha 2-antiplasmin levels remained constant in both groups, although the smokers started with significantly higher levels: 119 versus 105% in the nonsmokers. The D-dimer levels rose significantly in both groups: from 278 to 847 micrograms/ml in the nonsmokers and from 215 to 520 micrograms/ml in the smokers. They were significantly lower in the smoking group from the 11th up to the 40th weeks. The D-dimer/TAT ratio was significantly higher in the nonsmokers., Conclusions: In smoking pregnant women the activated coagulation process was not counter balanced by an adequate increase of fibrinolysis which was the case in the nonsmokers.

In the Netherlands 30% of all women of reproductive age are habitual smokers. One third of these women continue to smoke during pregnancy. Tobacco smoke consists of more than 3600 different compounds. One of its chief pharmacologically active ingredients is nicotine of which 60% is metabolized to cotinine. Cotinine is the best available biochemical marker of nicotine consumption because it is specific for tobacco smoke exposure and it has a relatively long mean t1/2 of 15 hours. In the present study nicotine and cotinine concentrations were measured in 25 smoking and 25 non-smoking healthy pregnant women. In all 25 non-smoking pregnant women nicotine and cotinine levels were < 10 mg/l. Light smokers (< 10 cigarettes/day) were found to have nicotine blood concentrations < 10 mg/l and cotinine levels varying between 40 and 99 mg/l. Heavy smokers (> or = 10 cigarettes/day) had nicotine concentrations < 10 mg/l, but high cotinine levels varying from 115 to 199 mg/l. Cotinine was also determined in 25 neonates of non-smoking mothers and in 34 neonates of smoking mothers. In 9 of these 34 newborns the relationship between maternal and neonatal cotinine concentrations was investigated. Cotinine levels in neonates born to non-smokers and to women who smoked less than 10 cigarettes/day were below the detection limit of 10 mg/l. Cotinine values in neonates whose mothers smoked > or = 10 cigarettes/day were significantly higher than in those whose mothers smoked < 10 cigarettes/day, but significantly lower than in their mothers. The results of this study confirm that cotinine is more useful than nicotine in discriminating non-smokers, light and heavy smokers. Cotinine concentrations were significantly lower in the neonates than in their mothers, but there was a strong positive linear relationship between maternal and neonatal cotinine concentrations.

Smoking during pregnancy is associated with maternal and fetal complications. In the present study the effect of maternal smoking on neonatal cellular blood components was investigated. The values of whole blood cell count, leukocyte differential count, and thrombocyte and reticulocyte counts were determined and compared in cord blood of neonates of nonsmoking (n = 89) and smoking (n = 53) mothers. The variables of the erythrocyte and thrombocyte count were not different in cord blood of neonates who were exposed to smoke and in those who were not. In the reticulocyte range the reticulocyte count was significantly lower in the smoking group, while the reticulocyte subsets remained stable. The neutrophils were significantly lower in cord blood of neonates of smoking mothers (p < 0.05). The latter finding might be an explanation for the enhanced incidence of postnatal infection seen in children of smoking mothers.

Objective: To determine whether the anatomy of an obstetric brachial plexus lesion (OBPL) is causally related to the preceding obstetric history., Design: Anatomical classification of the OBPL during reconstructive neurosurgical treatment in consecutive infants who had surgery for OBPL between 1986 and 1994 and relating these findings with the characteristics of the preceding birth., Setting: De Wever Hospital, Heerlen, The Netherlands., Subjects: All infants who had surgical treatment for OBPL between 1 April 1986 and 1 January 1994 (n = 130)., Results: An Erb's C5-C6 injury was preceded more frequently by a difficult breech birth (19/26 cases or 73%). In contrast, the more extensive forms of Erb's palsy classified as a C5-C7 injury or a total palsy with a C5-T1 injury were observed more frequently after complicated cephalic birth (52/59 or 88%, and 43/45 or 96%, respectively). The extent of anatomical damage as expressed by the incidence of an avulsion of one or more spinal nerves was 18/26 (69%) in Erb C5-C6, 13/59 (22%) in Erb C5-C7 and 21/45 (47%) in total C5-T1 palsy., Conclusion: The Erb's C5-C6 palsy, occasionally bilateral and/or complicated by phrenic nerve injury, was the most frequent form of OBPL after a breech birth. The more extensive form of Erb's palsy and the total palsy were observed more frequently after delivery in a cephalic presentation. The pure form of Erb's palsy and the total palsy were characterised by a higher incidence of nerve avulsions than the extensive form of Erb's palsy.

Unlabelled: Our objective was to compare the platelet count and platelet indices of smoking and non-smoking women at different stages of normal pregnancy., Study Design: In 247 non-smoking and 123 smoking healthy pregnant women the platelet count, the mean platelet volume, the platelet distribution width and the plateletcrit were compared at 0-10, 11-20, 21-30 and 31-40 weeks of pregnancy. Exclusion criteria were a diastolic pressure > or = 90 mmHg, an endocrine disease, a coagulation disorder, acetylsalicylic acid or phenprocoumon use. A women was considered a smoker if she smoked more than 4 cigarettes a day. Non-smokers were defined as women reporting no smoking at all. Blood samples were run on the Sysmex NE-8000., Results: There was no significant difference between the platelet count in the two groups. In the non-smoking group, the platelet count showed a significant decrease with gestational age (287 x 10(9)/l to 258 x 10(9)/l). This was not the case in the smokers group. The mean platelet volume of the smokers was significantly lower than that of the non-smokers in the last ten weeks of pregnancy (10.4 fl versus 10.7 fl). The platelet distribution width and the plateletcrit did not change under the influence of cigarette smoking., Conclusion: Smoking during pregnancy does not significantly affect platelet count or platelet indices.

Unlabelled: Our objective was to compare the reticulocyte count and its subfractions in smoking and non-smoking women at different stages of normal pregnancy., Study Design: In 247 non-smoking and 123 smoking healthy pregnant women the reticulocyte count and its subfractions were compared at four different stages of pregnancy: 0-10, 11-20, 21-30 and 31-40 weeks. Exclusion criteria were a diastolic blood pressure > or = 90 mmHg, an endocrine disease or a coagulation disorder. Women in the smokers group smoked more than 4 cigarettes a day. Non-smokers were defined as women reporting no smoking at all. Blood samples were run on the Sysmex R-3000 reticulocyte counter., Results: The absolute reticulocyte count was lower in the smoking group throughout pregnancy, but this was only significant in the last ten weeks of gestation (71.9 x 10(9)/l versus 78.8 x 10(9)/l). There was no difference between the low fluorescence, the medium fluorescence and the high fluorescence proportions in the non-smoking and the smoking group. Both groups behaved similarly during pregnancy; there was a decrease of mature reticulocytes and a significant increase of more immature reticulocytes., Conclusion: These data show a moderate measurable effect of cigarette smoking on the reticulocyte count and the absence of an effect on the reticulocyte subsets.

Fifty postmenopausal women requiring hormone replacement therapy for the treatment of climacteric symptoms were recruited in six centers. All patients received a new combined norethisterone acetate (NETA)/oestradiol (E2)-TTS, (Estragest TTS, Ciba-Geigy Ltd), delivering 0.25 mg NETA and 50 micrograms E2 per day, continuously for 12 calendar months. Bleeding occurred in 38 (76%) of the 50 patients at any time during the 1 year treatment. The percentage of patients without bleeding increased gradually each month, from 24% in the second month to a relatively stable level of approximately 80% in month 7 and thereafter. Twenty-seven patients (54%) did not complete the whole trial period; 15 of which discontinued the treatment within the first few months due to irregular bleeding. In patients who remained in the trial, a clear decrease in the frequency and intensity of the bleeding was observed with time. Bleeding was mostly light or consisted of spotting only. None of the post-trial biopsies showed proliferation or hyperplasia of the endometrium. The treatment resulted in a substantial decrease of climacteric symptoms (Kupperman index) within 4 months and was well tolerated. It was concluded that the continuous NETA/E2-TTS treatment is an effective and safe alternative for the treatment of climacteric symptoms in selected patients.

The values of whole blood cell count, leucocyte differential, and platelet and reticulocyte counts were determined in cord blood of both male (n = 64) and female (n = 75) newborns of 87 non-smoking and 52 smoking mothers. Leucocytes and neutrophils in cord blood from the male newborns of smokers were significantly lower than those in their female counterparts and in male newborns of non-smokers. These results suggest that male newborns are more affected by cigarette exposure than females with regard to some haematological parameters.

Objective: To compare the erythrocyte count and the erythrocyte indices of smoking and non-smoking women at different stages of normal gestation., Study Design: In 247 non-smoking and 123 smoking healthy pregnant women the erythrocyte count and indices were compared at four different stages of pregnancy: 0-10, 10-20, 21-30 and 31-40 weeks. Exclusion criteria were a diastolic pressure > or = 90 mmHg, an endocrine disease or a coagulation disorder. A woman was considered a smoker if she smoked 4 or more cigarettes/day. Blood samples were run on the Sysmex NE-8000., Results: The erythrocyte count was significantly lower in smokers than in non-smokers (3.86 T/l versus 3.96 T/l in the last 10 weeks). Comparing the erythrocyte count during the beginning and the end of pregnancy there were significant lower values in both groups (4.32 T/l to 3.96 T/l in the non-smoking and 4.24 T/l to 3.86 T/l in the smoking group). The differences in the median Hb and Ht levels were neglectable. The MCV was significantly higher in women who smoked, as was the MCH (MCV 91 fl and MCH 1.90 fmol in the non-smoking versus MCV 94 fl and MCH 1.95 fmol in the smoking group in the last 10 weeks)., Conclusion: Smoking in pregnancy leads to a lower erythrocyte count and a higher MCV which might create a hypoxic condition of the fetus.

Fibrinogen and factor XIII were measured in sixty-four women with recently detected gynaecological tumours. Twenty-six of these tumours were benign and 32 were malignant: of the last group, nine patients had metastases. No patient showed clinical signs of bleeding or thrombosis. A reference group consisted of 31 age-matched healthy women. For fibrinogen, no significant deviation between the patient groups and the control group was found. The median values of factor XIII were higher in the benign tumour group than in the control group. In patients with a gynaecological tumour and metastases, factor XIII was significantly lower than in the non-metastasized malignancy group or in the benign tumour group.

Lipoprotein(a) (Lp(a)) levels were studied in 68 non-smoking and 118 smoking pregnant women and compared with a control group of 29 subjectively healthy, age matched non-smoking females. The median Lp(a) concentration of the total group of non-smoking pregnant women (123 mg l-1) surpassed significantly that of the pregnant smokers of comparable gestational age (64 mg l-1). The last group was not significantly different to the control group (67 mg l-1). Comparison of the smoking and non-smoking pregnant women showed significantly higher Lp(a) values during the last trimester of gestation (> or = 28 weeks) in non-smokers. The higher Lp(a) concentration in the plasma of non-smoking women during a normal pregnancy might be a physiological necessity. In that case lower levels of Lp(a), as seen in the last trimester of the smoking pregnant group, might be unfavourable for the normal development of the rapidly growing fetus in the last stage of the gestation.

The total leucocyte count was studied in 194 smoking and 518 non-smoking healthy pregnant women. Smoking in pregnancy appeared to have an additive enhancing effect on the already known total leucocyte increase in pregnancy. The leucocyte differential in 105 smoking and 288 non-smoking pregnant women showed that the eosinophil and basophil count was not involved in the white blood cell shift. The rise of the total leucocyte count was mainly due to an increase of neutrophils, monocytes and lymphocytes. The leucocytosis in the smoking pregnant women was dose-related: significant upward jumps of the percentages of leucocytosis were observed between 12 and 15 cigarettes/day as well as between 19 and 20 cigarettes/day. Further investigation as to the relevance of these observations for pregnancy and fetal well being has to be conducted.

The effect of two different regimens of hormone replacement therapy on coagulation and fibrinolysis was measured in 30 women taking Tibolone (Livial) and 30 taking oestradiol valerate, sequentially combined with cyproterone acetate (Climen). Blood samples were taken before the beginning of the medication, then six and twelve months afterwards. The Livial group showed a rise of fibrinolytic activity as measured by the alpha 2-antiplasmin-plasmin complexes. Tissue plasminogen activator antigen and plasminogen activator inhibitor-1 decreased simultaneously. No effect was seen in the coagulation variables. In the Climen group no significant alterations were noticed, either in the coagulation or in the fibrinolysis variables. In the direct comparison of both substances only factor VII appeared to be significantly higher in the Climen group after six months and one year of treatment.

Sex-related differences are known to exist in the haemostatic variables of adults. In the present study, three clotting factors were measured in cord blood of 191 newborns. A sex-related difference was found for clotting factor VII, with higher plasma levels in female newborns (p < 0.01). Factor VIII:c also tended to be higher in female newborns, compared with male newborns (p = 0.07). No difference in fibrinogen concentrations was found. The observed difference between the sexes for clotting factor VII is not easy to understand, but it is in line with studies showing higher concentrations of factor VII in females than in males throughout adult life.

Semen specimens from four groups of patients were evaluated for coagulation and fibrinolysis factors: a group of patients with infertile semen and involuntary childlessness (n = 35), a group with fertile semen and involuntary childlessness (n = 39), a group with fertile semen and proven fertility before vasectomy (n = 34) and a group with infertile semen after vasectomy (n = 147). The third patient group with proven fertility before vasectomy was considered as a control group. Only small amounts of fibrinogen, factor VIII:c, plasminogen, antithrombin III, fibrin monomers and plasminogen activator inhibitor-1 were detected in seminal plasma. The thrombin-antithrombin III, D-dimer and tissue plasminogen activator regular concentrations were measured and the D-dimer/thrombin-antithrombin III ratios calculated. The reference ranges were assessed and the quantities were compared in the different patient groups. Significant differences were demonstrated between the prevasectomy group (= control group) and both the postvasectomy and the infertility groups with respect to D-dimer and D-dimer/thrombin-antithrombin III ratio. We conclude that both coagulation and fibrinolysis play a part in coagulum formation and liquefaction of seminal plasma. The balance between coagulation and fibrinolysis (expressed as D-dimer/thrombin-antithrombin III ratio) was significantly different between the control group and the three patient groups. The coagulation/fibrinolysis balance was impaired in the semen from post vasectomy patients and from those with involuntary childlessness and the D-dimer/thrombin-antithrombin III ratios in both these patient groups were very similar.

The slide test method of Velaskar and Chitre for determining platelet aggregation in whole blood after induction of aggregation was modified for spontaneous platelet aggregation and evaluated. The reproducibility was satisfactory (CV 1-3%). The results obtained with this method and the method of Velaskar were not significantly different. The Spearman rank correlation was 0.75 (p less than 0.0001). We established reference values for the particle counter method and Velaskar's method in pregnant and non-pregnant women; no significant change in spontaneous platelet aggregation was seen throughout pregnancy. In order to estimate the clinical value of the test in pregnancy, we followed up a number of pregnant patients with primary enhanced spontaneous whole-blood platelet aggregation before and after treatment with low-dose acetylsalicylic acid. The test was found to be suited for the detection of spontaneous whole-blood platelet aggregation and for the follow-up after treatment with acetylsalicylic acid. Further studies are necessary, however, to assess the predictive value of an aberrant test result during pregnancy.

Two patients with primary squamous cell carcinoma of the uterus are described. In both patients, the disease was at an advanced stage when the diagnosis was made. Although endometrial malignancies with squamous elements account for 10-30% of endometrial carcinomas, primary squamous cell carcinoma of the uterus is extremely rare. Up to now fewer than 30 cases have been reported. The pathogenesis, morphogenesis and aetiology of squamous epithelium in the corpus uteri is discussed. Finally, some clinical aspects of the primary squamous cell carcinoma of the corpus uteri are reviewed.

Fifty-six pregnant women (gestational age 6-40 weeks) were evaluated for their coagulation activation (fibrin monomers and thrombin-antithrombin III complex) and for their fibrinolysis profile by determining tissue plasminogen activator, plasminogen activator inhibitor, plasminogen, alpha 2-antiplasmin and D-dimer. Fibrin monomers and thrombin-antithrombin III complexes were found to be significantly increasing with gestational age. All the fibrinolytic parameters showed a steady growth with the progress of the pregnancy, with the exception of tissue plasminogen activator which showed a significant decrease with gestational age, but mainly within the reference range. These results suggest a stimulation of the coagulation system and an activation of fibrinolysis with ongoing pregnancy, although the increasing alpha 2-antiplasmin and plasminogen levels and the decreasing tissue plasminogen activator concentrations do not conform to this trend.

The condition of the fetus during pregnancy was assessed by 1,763 antepartum cardiotocograms made in 386 patients with the use of fetal movements and physiologic uterine contractions. There appeared to be a significant correlation between the cardiotocograms and the obstetric outcome.

The effect of Bellergal Retard (BR) on climacteric complaints was evaluated versus a placebo in an 8-wk double-blind study, followed by a 4-wk open study in which only BR was used as medication. There was a marked decrease in complaints in both the BR and the placebo groups. Statistically significant differences were observed between the groups after 2 and 4 wk of treatment, indicating superior results with BR. After 8 wk of study however, these differences were no longer apparent. It was concluded that studies on medication for climacteric complaints should not only be placebo-controlled, but also be of at least 8 to 12 wk duration for proper evaluation.