(A) clinical study on toxemia of pregnancy

의학과/석사[한글] [영문] This study was undertaken for clinical evaluation on the women with toxemia of pregnancy who was admitted to Yonsei University Medical Center from April, 1966 to December, 1970. By evaluating 583 cases of toxemia of pregnancy among total 8253 deliveries, following results were obtained. 1. The incidence of toxemia was 7.06% 2. According to the classification of American Committee on Maternal welfare, the incidence of toxemia were as follows; Mild pre-eclampsia : 33.9% Severe pre-eclampsia : 43.8% Eclampsia : 17.5% Chronic hypertensive vascular disease with superimposed acute toxemia : 3.9% Chronic hypertensive vascular disease without acute toxemia : 0.5% unclassified : 0.4% 3. Age distribution of toxemia was highest among 25-29 years range(42.5%). 4. 48.2% of toxemia was primipara and 51.8% of toxemia was multipara. 5. The numbers of toxemia were most spring time(28.66%), but no definits significance on seasonal variation. 6. The distribution between clinic xases and private cases was higher in clinic cases(71.5%). 7. Among the associated disease with toxemia of pregnancy were 28 cases(4.8%), and abruptio placentae were 23 cases(3.9%). Other diseases were essential hypertension, polyhydramnios and diabetes mellitus. 8. The total numbers of deliveries were increased yearly, but there was no remarkable change on rate of antenatal visit. There was a tendency of decrease on incidence of toxemia of pregnancy yearly. 9. The symptoms of toxemia of pregnancy disappeared on postpartum third day, in order of edema, hypertension, and proteinuria on each toxemic groups. 10. Perinatal mortality rate of toxemia was 121/1,000 live birth and it was very high value contrast to overall perinatal mortality rate(36.4/1,000 live births).restrictio

Morphologic alterations of the uterine cervix of rats induced by estrogen, progesterone and ortho-novum

의학과/박사[한글] 세계적으로 팽창되는 인구증가의 조절이 심각한 문제로 부각됨에 따라 여러 가지 피임방법이 연구되고 있으며 이중 경구피임약은 가장 안전하고 효율적인 방법으로서 널리 이용되고 있다. 경구피임제의 주 작용은 뇌하수체 전엽에서 성선자극호른몬의 분비를 억제하여 배란을 방해하는 것이지만 그 밖에 생식관 여러 부위에도 작용하여 불임을 초래하는 것으로 알려져 있다. 특히 Pincus 및 Chang(1958), Tyler(1964)등은 피임제에 의한 피임기전의 일부로서 자궁견관 점액 물질의 물리화학적 성상의 변화를 주장한 바 있으며 Rudel등(1075)도 피임제를 이용할 경우 난소로부터 배란은 되면서 피임이 되는 것을 관찰한 바 있다. 배란억제를 위하여 estrogen을 투여받은 사람의 경우 약 반수에서는 자궁경관의 점액내에 정자가 살아 움직이는 것을 관찰할 수 있으나(Jackson, 1961; Jackson, 1963), Guard(1960)와 Martinez-Manautous등(1966)은 estrogen과 progesterone을 복합투여하거나 소량 의 progesterone을 계속 투여할 경우에 자궁경관에서 분비되는 점액의 점도가 높아서 정자유입이 방해된다고 보고하였다. 그러나 경구피임제가 자궁경관에 미치는 영향에 대한 연구는 주로 점액물질의 물리화학적 변화와 이로 인한 정자의 점액 투과성의 변화에 불과하였으며(Moghissi, 1966; Carlborg등, 1969; Elstein등, 1976), 경관 상피세포의 점액 분비화현상을 관찰한 연구는 드물다. 본 실험에서는 estrogen 및 progesterone의 단독투여 및 혼합제인 경구피임약 Ortho-Novum을 투여한 후 백서 자궁경부 상피세포의 점액분비 상황을 조직화학적 및 전자현미경적 방법으로 비교 연구하였다. 실험동물로는 체중 200gm내외의 자성 백서를 사용하였으며 다음과 같이 2군으로 나누어 실험하였다. 제Ⅰ군: 정상대조군: 생리적 식염수 0.5cc/day(20마리) 제Ⅱ군: 실험군(90마리) a. Estrogen단독투여군: 0.15mg/kg/day(30마리) b. Progesterone단독투여군: 15mg/kg/day(30마리) c. Ortho-Novum투여군: 1.5mg/kg/day(30마리) 정상대조군은 질 도말검사를 시행하여 성 주기의 각 시기를 확인한 후 각 시기에 5마리씩 도살하였다. 약물은 5일에서 40일까지 매일 대퇴부 근육주사하였고, 투여시작후 5일, 10일, 15일, 20일, 30일 및 40일에 각 5마리씩 도살하였다. 도살 즉시 자궁 전체를 육안적으로 관찰한 후 자궁경부를 자궁체부 및 질경계부위를 포함하여 절제하여 10% 중성 formalin에 고정하고 paraffin에 포매한 후 7μ두께로 박절하여 hematoxylin-eosin, periodic acid-Schiff(PAS) 및 diastase-PAS, alcian blue염색을 시행하였다. 투시전자현미경적 검색을 위하여는 조직을 1mm**3 크기로 박절한 후 1% OsO^^4 에 고정하고 uranyl acetate와 lead citrate로 염색하여 Hitachi H-500전자현미경으로 관찰하였다. 주사전자현미경적 검색을 위하여는 자궁경관의 상피세포층을 노출시켜 3% glutaraldehype와 1% OsO^^4 에 고정한 후 critical point drier(Hitachi ICP^^2)로 건조시켜 gold palladium으로 표층을 입힌 다음 Hitachi S-450 주사전자현미경으로 관찰하였다. 연구결과는 다음과 같다. 1. 육안소견상 estrogen투여는 자궁경부 및 체부를 증대시키고 progesterone투여는 위축을 초래하였으며 Ortho-Novum투여는 다소의 위축을 일으켰다. 자궁 경관내의 점액은 estrogen투여군에서는 점도가 낮고 혼탁하였으며 progesterone과 Ortho-Novum투여군에서는 점도가 높고 투명하였다. 2. Estrogen단독투여는 자궁경부의 극세포를 증식시키고, 초기에는 점액형성을 일으키며 후기에는 각화현상을 초래하였다. 3. Progesterone단독투여는 극세표층의 심한 위축과 표층의 원주상피세포화를 초래하였고 점액형성이 주로 표증 원주상피세포에서 일어났다. 4. Ortho-Novum 투여는 표층 상피세포의 원주화와 극세포층의 증식을 함께 초래하였으며 점액도 표층 원주상피세포와 극세포층에서 공히 관찰할 수 있었다. 5. 질 상피세포의 점액형성은 progesterone투여군과 Ortho-Novum투여군에서만 현저하였으며 estrogen투여군에서는 각화현상이 현저하였다. 6. 특수염색소견상 극세포층과 원주상피세포에 초래된 낭포는 중성 및 산성 점액다당류의 생성 및 축적에 기인한 것을 알 수 있었으며, 염색의 강도로 보아 점액질의 농도는 Ortho-Novum투여군에서 가장 높았고 estrogen투여군에서 가장 낮았다. 7. 투시전자현미경적 검사상 낭포형성은 점액질 생성에 의한 것이었으며, 이러한 점액질은 처음에는 multivesicular body나 dense granule형태로 출현하다가 점액소낭으로 성숙되었다. Estrogen투여는 초기에 소수의 multivesicular body와 dense granule을, proge sterone투여는 투여기간의 증가에 따라 다수의 granule과 약간의 점액소낭을, 그리고 Ortho-Novum투여는 다수의 점액소낭을 형성하였다. Estrogen투여군은 상피표면의 microvilli가 길고 규칙적이며 조밀하였으나 progesterone투여군에서는 소수의 짧은 microvilli가 불규칙하게 관찰되었고, Ortho-Novum투여군의 microvilli는 초기에는 estrogen투여군과, 후기에는 progesterone투여군과 같은 모양이었다. 8. 주사전자현미경적 소견상 progesterone 및 Ortho-Novum투여군에서는 표층상피의 원주세포화를 확인할 수 있었으며 표면에 점액소낭의 돌출을 관찰할 수 있었다. 이상의 결과를 종합하면 estrogen은 극세포층을 증식시키고 투여초기에 점도가 낮은 점액을 분비하는 세포로 변형시키는 반면 progesterone은 표층 상피세포를 원주세포화 시켜 점도가 높은 점액분비를 초래하며, estrogen과 progesterone의 복합제인 Ortho-Novum투여가 자궁경부의 점액형성에 미치는 영향은 초기의 극세포증식과 후기의 점액분비화 때문이라고 생각되었다. [영문] Population control is a world wide problem, and various contraceptive measures are being sought to meet this problem. It is becoming clear that the oral contraceptives will be a choice of methods among various contraceptive means. The principal contraceptive action of the steroids is believed to be that of ovulation inhibition by inhibiting the secretion of gonadotropins from the anterior pituitary gland. However, changes in the cervical mucus have been considered as one of th possible contributors to the action of these drugs(Pincus and Chang, 1958; Tyler, 1964). Ovulation can occur on a random basis with all forms of treatment, but pregnancy does not ensue, presumably owing to cervical factors or endometrium which is not receptive to implantation(Rudel et al., 1965). The investigation of the cervical role in contraceptive action has been limited to the observation of the physical characteristics of cervical mucus(Mophissi,1966; Carlborg et al., 1969; Elstein et al., 1976), and the migration in vitro or vivo of spermatozoa subsequent to administration of a particular steroid. In patients receiving estrogen therapy for ovulation inhibition, the presence of live, mobile sperm has been demonstrated in the cervical mucus of about half of the treated individuals(Jackson, 1961; Jackson, 1963). However, the administration of either combined therapy or small doses of progestogens continuously causes inhibition of sperm transport due to production of viscus and "hostile" mucus(Guard, 1960; Martinez-Manautous et al., 1966). A few studes have been carried out on the morphologic alterations of the uterine cervix in mice to see the histogenesis of epidermidization, but not of the characteristic mucification of the cervical epithelium. The present investigation is aimed to study the morphologic basis of mucus changes in uterine cervix by histochemical and ultrastructural methods following the administration of oral contraceptive(Ortho-Novum) in comparison with the changes induced by progesterone or estrogen alone. Female albino rats weighing around 200gm were used for the experiment. They were divided into two groups and treated as followings. GroupⅠ. Normal control: Normal saline 0.5cc/day.(20 animals) GroupⅡ. Experimental(90 animals) a. Estrogen treated: 0.15mg/kg/day(30 animals) b. Progesterone treated: 15mg/kg/day(30 animals) c. Ortho-Novum treated: 1.5mg/kg/day(30 animals) Vaginal smears were performed on all of the twenty animals in the normal control group to see each phase of the estrous cycle and five animals were killed in each phase. Drugs are given by intramuscular injection every day for the period from five to forty days. Five animals from each group were killed at the 5th, 10th, 15th, 20th, 30th and 40th days. Uterine cervix including the margin of endometrium and vagina was dissected and examined especially on the characteristics of the mucin in the uterine cervical canal. The tissue was fixed in 10% neutral formalin for the light microscopic examination. Microsections were made from paraffin block and were stained by hematoxyline-osin, periodic acid-Schiff with and without diastase pre-treatment and alcian blue. For transmission electron microscopic examination, the tissue was cut in 1mm**3 size and fixed in 1% osmium tetraoxide. Sections were stained with uranyl acetate and lead citrate and examined under Hitachi H-500 electron microscope. Fro scanning electron microscopic examination, the uterine cervix was opened to expose the epithelial surface and fixed in 3% glutaraldehyde in phosphate buffer(pH 7.4) followed by 1% osmium tetraoxide. The tissue was dried with critical point drier(Hitachi ICP2), coated with gold palladium and examined under Hitachi S-450 scanning electron microscope. The results are as follows. 1. Estrogen induced hypertrophy of the uterine corpus and cervix, while progesterone and Ortho-Novum induced atrophy. The mucus in the uterine cervical canal was watery and turbid in estrogen treated group, while thick, tenaceous and clear in progesterone and Ortho-Novum treated groups. 2. Estrogen induced hyperplasia of the prickle cell layer of the cervix, and caused mucification at early stage but keratinization at latet stage. 3. Progesterone induced atrophy of the prickle cell layer of the cervix and mucification mainly in the superficial cells which had been columnarized by the drug. 4. Ortho-Novum induced superficial columnarization of the epithelium and hyperplasia of the prickle cell layer simultaneously. Mucification occurred not only in superficial columnar cells, but also in the prickle cell layer. 5. The mucification was prominent in vaginal epitheli7um in progesterone and Ortho-Novum treated groups, while the keratinization was conspicus only in estrogen treated group. 6. Special stains revealed the vacuolizations in superficial columnar cells and prickle cells were due to accumulation of acid and neutral mucopolysaccharides, the concentration of which was strongest in Ortho-Novum treated group, and weakest in estrogen treated group. 7. The transmission electron microscopic studies revealed the vacuolization was due to the accumulation of mucus material, which appeared as multivesicular bodies or dense granules, maturing into mucus droplets. A few multivesticular bodies and dense granules were observed in short term estrogen treatment, whereas many dense granules with a few mucus droplets, and numerous mucus droplets were produced respectively by the administration of progesterone and Ortho-Novum, especially in long term treatment. The microvilli on the cell surface were compact, long and regular in estrogen treated group, but by the administration of progesterone they became sparse, short and irregular. In animals of short term treatment of Ortho-Novum they were similar to those of estrogen treated group, but became as to those of progesterone treated one4 following long term therapy. 8. Scanning electron microscopic study also demonstrated superficial columnarization and mucus droplets on the surface in progesterone and Ortho-Novum treated groups. In Summary, estrogen induce hyperplasia of prickle cells and produce watery mucus, whereas progesterone induce columnarization of surface epithelial cells from which tenaceous, thick mucus is produced, The effect of the Ortho-Novum, a combined oral contraceptive, on the uterine cervix is throught to be the result of early hyperplasia of the prickle cells and later mucification.restrictio