Haematological Effects of Betamethasone Treatment in Late Pregnancy

Summary: To assess the maternal haematological effects of betamethasone administered in late pregnancy, an automated full blood count was performed before and daily for 5 days after betamethasone in 25 women with a singleton pregnancy between 23 and 33 weeks' gestation. From a mean (±SD) baseline level of 11.0 ± 2.2 ± 10⁹/L, the total white cell count increased significantly to 13.2 ± 2.9 ± 10⁹/L and 13.5 ± 3.1 ± 10⁹/L on the first and second day after treatment respectively, returning to baseline on day 3 (p < 0.0001, ANOVA). These changes represented a mean increase in the neutrophil count of 35% and a mean decrease in the lymphocyte count of 23%. While there was considerable intersubject variation in the extent of the changes, this study has quantified the leucocytosis induced by betamethasone in late pregnancy, information that may assist with the clinical evaluation of a woman at risk of preterm delivery.     

Epidermal growth factor receptor status in four carcinoma of the cervix cell lines

We have evaluated aspects of the EGF receptor content of four human cell lines derived from patients with previously untreated carcinoma of the cervix. Scatchard analysis revealed that three of the lines possessed approximately 2×10⁵ low-affinity and 2×10⁴ high-affinity receptors, whereas the fourth line had approximately 9×10⁴ low-affinity receptors and 9×10³ high-affinity receptors. Immunocytochemical staining using the monoclonal antibody EGFR1 showed wide intra- and inter-line variation in staining intensity. Flow cytometric analysis of EGFR1 demonstrated a fivefold difference in staining intensity between lines. Thirteen cloned derivatives of one of the lines exhibited a 200% variation in EGFR1 staining intensity. There were no differences in radiosensitivity in four of the cloned lines with different EGF receptor levels. Southern blotting analysis did not reveal any rearrangement or amplication of the EGF receptor gene. These three different methods for determining receptor content produced variations in the ranking of receptor number across the four cell lines. These studies with cervix carcinoma cell lines demonstrate the presence of varied levels of EGF receptors according to the methodology used. This may reflect differences in biological characteristics of the cell lines evaluated.     

Paclitaxel in combination with cisplatin is less effective for peripheral blood progenitor cell mobilization

Abstract. Kurata H, Takakuwa K, Tsuneki I, Aoki Y, Tanaka K. Paclitaxel in combination with cisplatin is less effective for peripheral blood progenitor cell mobilization.
The purpose of this study was to determine the efficacy of paclitaxel in combination with cisplatin and granulocyte-colony stimulating factor (G-CSF) for mobilization of peripheral blood progenitor cells (PBPC). Twenty-seven patients with gynecological cancer received paclitaxel and cisplatin (TP, n = 9) or other platinum-based chemotherapy ( n = 18) (etoposide and cisplatin [ n = 5]; cyclophosphamide, adriamycin, and cisplatin [ n = 8]; or pepleomycin, etoposide, and cysplatin [ n = 5]). Each combination was followed by G-CSF. The mean number of colony-forming unit granulocyte macrophage (CFU-GM)/kg and CD34⁺ cells/kg collected per cycle was 1.2 × 10⁵ and 0.8 × 10⁶ after the TP regimen, compared with 2.6 × 10⁵ ( P < 0.05) and 2.0 × 10⁶ for patients who received other platinum-based chemotherapy. The CFU-GM target yield (≥1.0 × 10⁵/kg) was achieved in 56% and 83% patients in the TP and comparison group, respectively. With the TP regimen, a younger age (≤50 years of age) and fewer prior chemotherapy cycles (≤2) were associated with the CFU-GM targeted yield (<0.05). In conclusion, TP mobilized PBPC less effectively than other platinum-based chemotherapy. Therefore, the TP regimen may need to be changed to another appropriate regimen when PBPC mobilization is planned for high-dose chemotherapy in gynecological cancer patients.     

The serum pregnancy-specific β1-glycoprotein to betahuman chorionic gonadotrophin ratio as an index of prognosis in patients with choriocarcinoma

Summary. The ratio of serum pregnancy-specific β₁-glycoprotein (SP1) to the β-subunit of human chorionic gonadotrophin (β-hCG) before and after chemotherapy was measured in 12 patients with metastatic choriocarcinoma. The ratios before chemotherapy ranged between 0^.03 and 0^.75, with a mean value of 0^.34 (SD 0^.21). The ratio increased to over 1^.0 (1^.05–53^.3) after one or two courses of chemotherapy in seven of the 12 patients. These women achieved complete remission. In the other five patients who died of the disease due to drug resistance of the tumour, the ratio after chemotherapy was low (0^.04–0^.74) and tended to decline. These data suggest that the serum SPl/β-hCG ratio can be used to predict the prognosis of patients with choriocarcinoma.     

Thrombocythaemia and recurrent miscarriage

The incidence of thrombocythaemia (a platelet count >600×l0⁹/l) in a 10-year survey was 7 per 10⁶ population per year (R. M. Pettit, personal communication). It is generally a disease of late middle age, but a second population of young and mainly female patients has been described (Hoagland & Silverstein 1978). An increased platelet count can be secondary (after splenec-tomy, associated with inflammation, malignancy or iron deficiency) or due to a primary myeloproliferative disorder. We describe four patients in whom a series of miscarriages before 20 weeks gestation appears associated with thrombocythaemia and estimate the prevalence of this association in patients with unexplained repeated miscarriage.     

Reduced in-vitro fertilization of human oocytes from patients with raised basal luteinizing hormone levels during the follicular phase

Summary. A series of 62 women were managed in the University of Western Australia/PIVET Laboratory in-vitro fertilization programme. In 60 of them follicle growth was stimulated with clomiphene citrate' with or without additional human menopausal gonadotrophin (hMG) and in two with hMG alone. Follicles were aspirated at laparoscopy following an hCG trigger injection and occasionally following a spontaneous luteinizing hormone (LH) surge. Oocytes were inseminated with 0·5×10⁵−10⁵ sperm/ml 3–6 h later. A significant reduction ( P <0·001) in the fertilization rate of mature oocytes was observed in those patients whose basal serum LH values were >1 SD above the mean. Fifty-nine women subsequently had embryo transfer and of 10 clinical pregnancies, none occurred in those with elevated LH values. Reduced fertilization may be a reflection of premature oocyte maturation or ageing. This may have clinical implications in the management of some patients with unexplained infertility.     

Advances in the management of advanced and recurrent uterine papillary serous carcinoma

Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer that accounts for 5–10% of all cases. Over 50% of the patients with UPSC present with advanced stage disease ⁽¹⁾ . Among patients with noninvasive uterine disease, 40% have advanced stage UPSC ⁽¹⁾ ; therefore, complete surgical staging is crucial to determine prognosis and treatment ⁽²⁾ . Optimal tumor debulking (<1cm) is associated with a better prognosis and improved overall survival ⁽³⁾ . After initial surgical staging, patients with high stage UPSC have an improved overall survival if treated with chemotherapy (platinum-based or paclitaxel-based therapy) ⁽¹⁾ . Even with chemotherapy, the disease free interval is approximately 1 year ^(4–6) . The role of radiation in these patients is unclear. Up to 30% of recurrences occur outside of the abdomen and pelvis (unpublished data). While the response rate to chemotherapy in the recurrent setting is up to 80%, the duration of response is approximately 7 months ^(4–6) . Because the disease free interval in the adjuvant setting and the duration of response in patients with recurrent disease is limited, better strategies are needed to treat patients with this disease. We have recently evaluated Her-2/neu overexpression and amplification in a series of patients with UPSC. Her-2/neu overexpression was independently associated with a poor prognosis, however the rate of specific gene amplification was only 3% ⁽⁷⁾ . We have found that imatinib-targeted kinases are overexpressed in UPSC ⁽⁸⁾ . We currently are evaluating imatinib (Gleevec, Novartis) and paclitaxel for the treatment of UPSC in patients with advanced or recurrent disease.     

Standard dose cisplatin with rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer

We have investigated the feasibility of a program of autologous peripheral blood stem cell (PBSC) harvesting and transplantation in patients with ovarian cancer. From four patients, PBSC was collected during hematopoietic recovery following aplasia induced by standard dose cisplatin 70 mg m⁻² with etoposide 500 mg m⁻² or adriamycin 40 mg m⁻² and cyclophosphamide 500 mg m⁻² plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) at a dose of 75 µg day⁻¹ given intracutaneously. In apheresed patients, we harvested an average of 2.31 × 10⁵ kg⁻¹ colony-forming unit granulocyte/macrophage (range 0–5.22) per cycle. Low hematologic toxicity was observed during the hematopoietic reconstitution of the four patients subjected to PBSC support with G-CSF (5 µg kg⁻¹ day⁻¹ given by continuous infusion) after high-dose chemotherapy (carboplatin 900 mg m⁻² and etoposide 900 mg m⁻²). The patients were not evaluable for a response because we performed consolidated high-dose chemotherapy. However, no evidence of recurrence has been observed 11.8 months (range 2–19) after high-dose chemotherapy. We can conclude that standard dose cisplatin in combination with etoposide or adriamycin and cyclophosphamide plus rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer.     

Histologic and immunohistochemical analysis of tissue response to adenovirus-mediated herpes simplex thymidine kinase gene therapy of ovarian cancer

Abstract. Hasenburg A, Fischer DC, Tong X-W, Rojas-Martinez A, Nyberg-Hoffman C, Orlowska-Volk M, Kohlberger P, Kaufman RH, Ramzy I, Aguilar-Cordova E, Kieback DG. Histologic and immunohistochemical analysis of tissue response to adenovirus-mediated herpes simplex thymidine kinase gene therapy of ovarian cancer.
Herpes simplex virus (HSV) thymidine kinase (tk) gene incorporated into adenovirus was delivered intraperitoneally (ip) followed by an antiherpetic prodrug and topotecan in patients with recurrent epithelial ovarian cancer. Tissue response was evaluated. Ten patients underwent secondary debulking with subsequent delivery of ADV-HSV-tk therapy. Two patients each were treated at dose level 1 (2 × 10¹⁰ vector particles = VP), 2 (2 × 10¹¹ VP), and 3 (2 × 10¹² VP); four patients were treated at dose level 4 (2 × 10¹³ VP). Five patients underwent second-look surgery about one month after gene therapy (GT). Treatment response, presence of vector DNA, protein expression of steroid hormone receptors, p53, c-erbB2 and Ki67 protein were analyzed.   At second-look, two out of five patients were tumor-free and none of their peritoneal biopsies showed vector DNA. After GT, the vital tumor mass was smaller, desmoplastic reaction had increased, and tumors were less differentiated with an increase of Ki67 expression. There was no change in expression of hormone receptors, p53, or c-erbB2. ADV-HSV-tk GT appears to eliminate cells with higher differentiation first and might induce fibrosis. Dedifferentiation might render residual cells more sensitive to chemotherapy secondary to their subsequent higher mitotic activity.     

Intracardiac injection of potassium chloride as method for feticide: experience from a single UK tertiary centre

We report our experience with intracardiac administration of potassium chloride as safe and effective method for late termination of pregnancy (TOP) and to document the indications for feticide in a major tertiary unit. During the study period (January 2000 and December 2005), 239 late terminations of pregnancy were performed at a median gestational age of 22⁺⁶ weeks (range 20⁺⁶ to 36⁺³ weeks). The most frequent indication was represented by aneuploidy (24.3%), followed by brain abnormalities (17.6%). Maternal indications were responsible for 2.9% of the total number of terminations. No maternal complications occurred and complete asystole was achieved in all cases with a median volume of potassium chloride of 4.7 ml (range 2–10 ml). Potassium chloride injected directly in the left ventricle induces immediate asystole, and it is a safe and effective method of TOP. Interestingly, despite the widespread introduction of aneuploidy screening, chromosomal abnormalities, particularly trisomy 21, still represent the major indication for late TOP.     

Platelet angiotensin II binding sites in normotensive and hypertensive women

Summary. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10⁹ cells) when compared with the non-pregnant women (9.0 fmol/10⁹ cells   P <0.001  ). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10⁹ cells) when compared with the 25 normotensive pregnant women (   P <0.001  ). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10⁹ cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10⁹ cells) although the difference was not statistically significant (   P <0.04  ). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy.     

Impact of the malaria parasite on reproductive indices of male mice

Aim:  To investigate the impact and possible mechanism of action of the rodent malarial parasite on reproduction.
Methods:  Male albino mice were infected with 15, 30 and 45% Plasmodium berghei berghei through inoculation with 10⁷ parasitized red blood cells. Each experiment had its own control that was not infected with P. berghei berghei . Mice infected with 15% P. berghei berghei were killed on days 0, 5, 10 and 15; those infected with 30% P. berghei berghei were killed on days 0, 3, 6 and 10; and those infected with 45% P. berghei berghei were killed on days 1–7 after infection. Caudal epididymal sperm motility, counts and morphology, body and wet organ weights and hematological indices were determined.
Results:  The results showed a progressive duration dependent decrease in sperm motility, sperm count and viability ( P  < 0.01) in parasitized mice. There were significant decreases in serum testosterone and increases in cortisol levels ( P  < 0.05) in the infected mice compared with the controls. There was also a progressive decrease ( P  < 0.05) in red blood cell count and packed cell volume. However, there was a progressive increase ( P  < 0.01) in white blood cell count and weight of the spleen and liver. There was no significant change in weight of the testis and epididymides.
Conclusion:  The results suggest that the malaria parasite could depress male fertility indices. (Reprod Med Biol 2006; 5 : 201–209)     

A Review of Eclampsia in Melbourne: 1978–1992

Summary: A retrospective review of all cases of eclampsia diagnosed at 3 obstetric teaching hospitals in Melbourne from January, 1978 to December, 1992 was undertaken. Ninety cases were identified; there were 5 maternal deaths and 17 perinatal deaths. Severe maternal morbidity such as pulmonary oedema, acute renal failure or HELLP syndrome was found in 26%. Significant maternal thrombocytopenia (<100 × 10⁹/L) was found in 50% and 35% had abnormal maternal liver function tests. Forty six women received magnesium sulphate for treatment of eclampsia and of these 3 had further seizures compared to 4 of 18 who received phenytoin (odds ratio 0.24 (0.04-1.52) X², p=0.09). Eclampsia remains a significant complication of pregnancy with high maternal and perinatal mortality and morbidity. Results of this study show a trend that is in agreement with recent randomized controlled trials which demonstrate a reduced incidence of seizures and maternal and fetal complications with tbe use of magnesium sulphate. The results of these recent trials suggest that magnesium sulphate should be the drug of choice in the prevention and treatment of eclampsia.     

妊娠合并急性阑尾炎81例临床分析

目的探讨妊娠合并急性阑尾炎临床特征、诊断及治疗。 方法对2008年1月至2015年12月就诊于广州医科大学附属第三医院妇产科的81例妊娠合并急性阑尾炎住院患者的临床资料进行回顾性分析。 结果(1)临床症状和体征：81例妊娠合并急性阑尾炎,93.83%的患者以腹痛来就诊,具有典型的转移性右下腹痛占28.39%;患者入院平均体温为(37.17±0.70)℃。(2)辅助检查：白细胞(13.82±4.84)×10⁹个/L,中性粒细胞数为(11.72±4.88)×10⁹个/L,中性粒细胞百分比为82.89%,C-反应蛋白为(92.49±61.31)mg/L,降钙素原为(0.20±0.28)ng/ml。(3)治疗：手术治疗者35例,使用抗生素非手术治疗者46例。孕中期行腹式阑尾切除术17例,孕晚期行剖宫产加阑尾切除术18例,术后病理报告类型以急性化脓性阑尾炎(15例)为主。 结论掌握妊娠合并急性阑尾炎的临床特点,做到早期诊断和正确处理对妊娠结局有重要影响。     

Incidence of urinary incontinence and constipation during pregnancy and postpartum: survey of current findings at the Rotunda Lying-in Hospital

Objective To assess the impact of pregnancy upon continence and constipation.
Design A questionnaire survey.
Setting Maternity wards in the Rotunda Lying In Hospital, Dublin, Republic of Ireland.
Population 7771 women who were delivered of liveborn infants.
Methods Questionnaires were delivered and collected by physiotherapy staff as part of routine postnatal care.
Results Analysis of data using χ² tests showed significant differences between three parity groups [primigravidae, multigravidae (2–4) and multigravidae (5+)] for symptoms of both urinary incontinence (  χ²= 119.54  , df = 2, P = 0.000) and constipation (  χ²= 12.53  , df = 3, P = 0.002); the incidence of both constipation and urinary incontinence increased with parity.
Conclusion The results of this survey have emphasised the relation between parity and postpartum incontinence which stresses the importance of early diagnosis and intervention.     

Neonatal alloimmune thrombocytopenia due to anti-HPA 1a antibodies; the level of maternal antibodies predicts the severity of thrombocytopenia in the newborn

Eleven thousand one hundred pregnant women were genotyped for human platelet antigen HPA 1, and 198 HPA 1bb women were followed in the pregnancy with quantitative assay for anti-HPA 1a antibodies. Antibodies were detected in 24 women, and nine children were born with severe thrombocytopenia (< 50×10⁹/L). All mothers with high levels of antibodies were delivered of children with severe thrombocytopenia. None of the newborn infants had clinical signs of intra-cranial haemorrhage. The level of maternal anti-HPA 1a antibodies is predictive for fetal thrombocytopenia and may be used in decisions related to time and mode of delivery.     

Colposcopic differential diagnosis of dysplasia, carcinoma in situ and microinvasive carcinoma of the cervix

Summary: Two hundred and twenty-eight patients with cervical neoplasia, detected in routine uterine cancer screening at the Center for Adult Diseases, Osaka, from 1973 through 1977 were selected. The histological diagnosis was as follows: dysplasia, 69; carcinoma in situ, 102; and microinvasive carcinoma, 57. A retrospective study of this material was made with the aid of adequate colposcopic colour photographs, and features likely to be useful in differential diagnosis were determined.
Atypical vessels were seen in 24 of 36 patients (67%) with Stage la¹ lesions, but only in a few of those with Stage 0² lesions. Punctation, mosaic and white epithelium were less evident in stage la² than in Stage 0¹ and Stage 0². Punctation, mosaic and white epithelium in patients with dysplasia were less formed, and their borders were less distinct than in patients with Stage 0 lesions. These characteristic changes are of value in accurate colposcopic diagnosis.     

Oral etoposide in elderly previously untreated ovarian cancer patients with residual disease

As etoposide had shown activity as second-line therapy and is a well-tolerated drug, a phase II study was performed to test the efficacy and side effects of intermittent oral etoposide in elderly untreated patients with residual ovarian cancer after primary laparotomy. Twenty-seven patients were treated with etoposide 170 mg m⁻² day⁻¹ p.o. for 5 days every 3 weeks for a maximum of 10 cycles. There was a high proportion of patients with stage IV disease (45.5%) and bulky residual disease greater than 5 cm (81.8%). The overall clinical response rate (CR+PR) in 21 assessable patients was 47.6% (95% CI: 26–70%). The median survival for all patients was 10 months (range 0.5–61+) and the median time to treatment failure 6.5 months (range 0.5–31). The overall toxicity was moderate and manageable, and consisted mainly of bone marrow suppression with 54% and 14% of the patients developing white blood cell (WBC) and platelet values corresponding to WHO grades 3–4, respectively. In conclusion, the results of our study confirm that etoposide has activity in previously untreated ovarian cancer patients and is well tolerated.     

Carboplatin and etoposide as first-line chemotherapy in advanced epithelial ovarian cancer

Carboplatin and etoposide are chemotherapeutic agents active in ovarian cancer, previously proved to have a synergistic activity in animal models. The objective of this phase II study was to determine the feasibility and the efficacy of the combination of carboplatin and etoposide in previously untreated patients with advanced epithelial ovarian cancer.
Carboplatin, 400 mg m⁻² day 1, and etoposide, 100 mg m⁻² days 1–3 every 4 weeks were administered to 28 patients with advanced stage (III–IV) ovarian cancer and a performance status 0–2 (ECOG scale), as a firstline chemotherapy.
Twenty-three patients were evaluable for response; 15 (65%) (95% CI: 45–81%) responded, 10 (43%) (95% CI: 25–63%) with clinical complete response. Pathologic complete response demonstrated during postchemotherapy laparotomy was noted in 5/23 (22%) (95% CI: 9–42%) patients. The median progression-free interval was 8.5 months, and median survival was 19.5 months. Toxicity, mainly hematologic, was severe. Nine (32%) patients experienced at least one episode of leucopenic fever, which consequently led to toxic deaths in two (7%) patients.
The relatively low response and survival rates with increased toxicity rate are disappointing.     

Liver function following pregnancy complicated by the HELLP syndrome

Serum levels of aminotransferases, lactate dehydrogenase, gammaglutamyl transferase, alkaline phosphatase, albumin and conjugated bilirubin, measured in 54 women at a median of 31 months (range 3–101) after pregnancies complicated by the HELLP syndrome, were not elevated. Total bilirubin levels, however, were elevated in 20'1/0 of these women; this represents a significant difference from the prevalence in 151 women with a previous normal pregnancy (  χ²= 12.23  ,   P < 0.001  ), or in the normal female population (  χ²= 22.34  ,   P < 0.00001  ). This raises the possibility that a dysfunction of the bilirubin-conjugating mechanism represents a risk factor for the development of the HELLP syndrome.