Charles O. A. Omwandho

Role of TGF-βs in normal human endometrium and endometriosis

Endometriosis is characterized by presence of endometrial tissue outside the uterus. Prevalence is estimated at 6-10% in the general female population and many patients experience pain and/or infertility. Diagnosis is achieved by laparoscopic intervention followed by histological confirmation of viable endometriotic tissue. Mild cases are managed medically with contraceptive steroids and non-steroidal anti-inflammatory agents. Surgery provides relief to women in pain but symptoms recur in 75% of cases within 2 years. Starting with menstruation, we have categorized endometriosis into six stages, namely (1) shedding of cells, (2) cell survival, (3) escape from immune surveillance, (4) adhesion to peritoneum, (5) angiogenesis and (6) bleeding. In most of these biological processes, which resemble metastasis, transforming growth factor-beta (TGF-betas) and their high-affinity receptors are involved directly or indirectly. TGF-betas are abundantly and differentially expressed in the endometrium under hormonal control. Although they are preferentially synthesized in the stroma, glands and macrophages also secrete TGF-betas into the uterine fluid, where interaction with preimplantation embryos is suspected. Because mRNA and protein expression of all three TGF-betas is increased around menstruation, we suggest that TGF-betas might be involved in initiation of menstruation. Furthermore, because of high postmenstrual TGF-beta3 levels, we suppose that it might participate in scarless postmenstrual regeneration of endometrium. Our suggestions pave the way to novel routes of investigation into the roles of TGF-betas during menstruation and endometriosis.

Impact of endometriosis on quality of life: A pilot study

Endometriosis affects 6–10% of women in reproductive age, 35–50% of whom experience pain, infertility or both. Mild cases are managed medically but surgery provides relief to women in pain. However, symptoms recur in 75% of cases within 2 years. We investigated the impact of endometriosis on quality of life among 65 women aged 18–60 years working at a city supermarket in Giessen, Germany. Of the 65 women, 12 had undergone surgeries, 22 had dysmenorrhoea, 24 dyspareunia and 3 were infertile. Of the 22 women with dysmenorrhoea, 10 had difficulties performing gardening, housework, sports and leisure activities. Five of these 10 women experienced social isolation, 6 professional setbacks; 6 declined efficiency at work and 3 had taken time off work. Of the 24 women with dyspareunia, 7 experienced minimal, 12 light and 5 moderate to strong pain. Only 16 of these 24 women discussed the problem with their partners. This study demonstrates that pain is a major cause of physical, psycho-social, emotional and professional or work related impairment among women with endometriosis. Because endometriosis is likely to impose emotional and financial burdens, we suggest that future studies should be extended to include interviews with family members.

Management of stage I cervical sarcoma botryoides in childhood and adolescence

Rhabdomyosarcomas are the most common soft tissue sarcomas in childhood. The botryoid variant arises in infancy from the vagina or urinary bladder and extremely rarely from the uterine cervix. Treatment regimes range from local excision of the tumour to radical hysterectomy with adjuvant multidrug therapy and/or radiotherapy. In cases of minimal cervical invasion, the less invasive local excision in combination with adjuvant chemotherapy has resulted in excellent survival rates with complete functional preservation of the bladder, rectum, vagina, and ovaries. We present here a 30-year literature review and a case report of a cervical sarcoma botryoides in a 5-year-old girl. Conclusion:based on the literature review and our own observation, we recommend minor surgical approaches in combination with chemotherapy as the treatment of choice for early stage I cervical rhabdomyosarcoma.

Recurrent pregnancy losses and the role of immunotherapy

Abstract Post implantation pregnancy losses are psychologically and economically stressful to the childbearing population. The etiology in the vast majority of cases is unknown but is partly thought to result from a breakdown of the maternal tolerance to the fetoplacental unit. Immunologically based therapy remains controversial but no alternative therapy is available at the moment. This article reviews the conceived immunological basis of recurrent pregnancy losses, discussing the controversies arising, and recommending the use of intravenous immunoglobulin, IVIg, in well controlled experiments for further clinical trials.

Early pregnancy loss and neonatal deaths associated with Klebsiella pneumonia infection: a mini review of possible occupational health risk

Recurrent pregnancy loss is a disease of grave psychological and economic concern. The etiology in the vast majority of the cases is unknown or at best poorly understood. Although Klebsiella pneumonia infections have been reported in humans and animals during pregnancy, there is hardly any information to indicate whether or not these infections may be responsible for early pregnancy loss. We present a review of literature and report for the first time in humans, Klebsiella pneumonia infection in placenta of a 38-year-old secondary recurrent aborter (parity 2+3).

Elution and partial characterization of immunoglobulins bound to ovine placenta

Immunoglobulins were eluted from ovine placentae and characterized by immunoprecipitation, electrophoresis, western blotting and ELISA. IgG was shown to comprise the bulk of placental‐bound immunoglobulins while smaller amounts of IgM and only trace amounts of IgA were demonstrated. Results suggest that ovine placental IgG eluted by surgical cannulation of the uterine blood vessels in situ is similar to that eluted from postpartum placentae in vitro, implying that there may be some transfer of antibodies across the maternal side of the placental barrier to the trophoblast. These antibodies are rich in IgG, and IgG2, have a relative molecular weight of 158 kDa, and bind to an 80 kDa peptide prepared from pre‐acidified ovine placental cotyledons.

Defects in resting metabolic rates and mitochondrial respiration in Kwashiorkor and dietary obese rats

SummaryResting metabolic rates have been measured and compared with hepatic mitochondrial respiration in Kwashiorkor and diet-induced obese weaned rats. In Kwashiorkor, resting metabolic rate was 21% lower than the value of controls, while that of the obese rats was 14% higher than in control animals. The resting metabolic rate for Kwashiorkor animals was 50% of the predicted basal metabolic rate (BMR), whereas that of the obese rats was 23% higher than the predicted BMR. The mitochondrial oxygen consumption patterns, using malate plus glutamate or succinate as respiratory substrates, revealed that the resting respiration (state 4) was 23.9% higher in Kwashiorkor and 29.1% higher in obese animals, while the active (state 3) respiration was 34.8% lower in Kwashiorkor and 43.3% lower in obese rats compared to controls. The respiratory control ratios (RCR) were 51.1% and 43.8% in Kwashiorkor and obese rats, respectively, relative to the values in control rats. It is concluded from these studies that Kwashiorkor disease and diet-induced obesity appear to interfere with oxygen utilization at the level of state 3 mitochondrial respiration, which is markedly decreased when compared to the values for control animals.

Doppler measurements in fetal descending aorta and umbilical artery can predict borderline oxygenation in pre-eclampsia and HELLP syndrome

Objective: To determine diagnostic utility of Doppler measurements in fetal descending aorta and umbilical arteries in predicting intrauterine growth retarded (IUGR) fetuses at risk in pregnancies complicated by preeclampsia and/or HELLP syndrome. Methods: Doppler measurements were taken in fetal descending aorta and umbilical arteries of 53 patients with pre-eclampsia, 10 of whom had HELLP syndrome using fetometry (ACUSON 128XP/10, 3.5 MHz probe). These values were compared with those of 44 appropriate-for-gestational age singleton pregnancies (AGA). Doppler Indices (Resistance Index (RI), Systolic/Diastolic (S/D) ratio) and end-diastolic flows were related to fetal heart rate (FHR) during contraction stress test, to cord blood parameters (pH, Base Excess) and to Apgar Scores. Results: In contrast to AGA fetuses, IUGR fetuses had decreased end-diastolic flow and an increase of Doppler Indices significantly earlier in the descending aorta (p < 0.05), compared to umbilical artery. Increased RI’s, S/D ratios and a decrease of end-diastolic flow in fetal aorta were significantly correlated to frequency of FHR decelerations during contraction stress tests, pH, Base Excess (p < 0.01) and Apgar Scores in IUGR fetuses. Conclusion: A decrease in end-diastolic flow paralleled with an increase in Doppler indices in fetal descending aorta reflect oxygen deprivation in IUGR fetuses during pre-eclamptic pregnancies with or without HELLP syndrome. While ductus venosus and umbilical artery are more frequently used nowadays to determine fetal oxygen deprivation, Doppler measurements in fetal descending aorta provide additional information for early detection of fetuses at risk for IUGR in pregnancies complicated with pre-eclampsia and/or HELLP syndrome

P10.40: Cerebro- and cardiovascular responses and oxygen consumption during prolonged hypoxia in fetal sheep

was 28% and 78% for the first trimester scan and 42% and 84% for the second trimester scan, while the values for predicting FGR was 22% and 84%, and 33% and 88% respectively. Conclusion: The performance of both first and second trimester RI values were better for pregnancy hypertension than fetal growth restriction. While there was good correlation between first and second trimester values, the performance appear to be better for second trimester values. A larger database would be needed to evaluate a combined first/second trimester index.