Transforming growth factor-beta opposes the stimulatory effects of interleukin-1 and tumor necrosis factor on amnion cell prostaglandin E2 production: implication for preterm labor.

In preterm labor increased concentrations of interleukin-1 and tumor necrosis factor are present in amniotic fluid. These cytokines may promote labor by stimulating the production of prostaglandins by intrauterine tissues. In many biologic processes, transforming growth factor-beta modifies the actions of cytokines. We studied the effect of transforming growth factor-beta on the cytokine-induced prostaglandin E2 production by amnion cells. Human amnion cells in monolayer culture were treated with interleukin-1, tumor necrosis factor, or vehicle in the presence or absence of transforming growth factor-beta. The prostaglandin E2 production was measured. Transforming growth factor-beta decreased the interleukin-1- or tumor necrosis factor-induced prostaglandin E2 production by 70% to 80% and the basal prostaglandin E2 synthesis by 27%. The synergistic stimulation of prostaglandin E2 production by the combination of interleukin-1 with tumor necrosis factor was inhibited by 80% in cells treated with transforming growth factor-beta. Transforming growth factor-beta 1, -beta 2, and -beta 1,2 were equipotent. Transforming growth factor-beta suppresses the cytokine-induced prostaglandin E2 production by amnion cells and may be an important factor in maintaining pregnancy in the face of labor-promoting cytokines.


Mutations of the Ki-ras oncogene in endometrial carcinoma.

The purpose of this study was to assess the extent of involvement of the ras oncogene in endometrial carcinoma. Genomic deoxyribonucleic acid from 30 samples of endometrial carcinoma was examined for point mutations in codons 12, 13, and 61 from the Ha-ras, Ki-ras, and N-ras genes by means of the polymerase chain reaction, slot-blotting, and deoxyribonucleic acid sequencing procedures. An apparent somatic mutation of Ki-ras codon 12 in one of 10 paraffin-embedded tumors was confirmed by deoxyribonucleic acid sequence analysis. Two of 20 frozen endometrial carcinoma specimens were also shown to contain a point mutation in Ki-ras codon 12. No correlation between ras mutation and a number of histologic or clinical parameters was observed. These data suggest a potential role for Ki-ras codon 12 mutations in the development of some (10%) endometrial cancers.


Effect of maternal oxygen administration on fetal oxygenation during graded reduction of umbilical or uterine blood flow in fetal sheep.

Effects of maternal oxygen administration on fetal blood gases and on oxygen delivery and consumption during reduced uterine and reduced umbilical blood flows were examined. In eight pregnant sheep (gestational age 133 +/- 4 days) flow transducers were applied to a uterine and the common umbilical artery. Graded reductions in uterine and umbilical blood flows were achieved by a hypogastric artery snare and a balloon cuff encircling the umbilical cord. Fetal femoral arterial and umbilical venous oxygen contents and flows were measured at varying flow reductions with the ewe breathing air or oxygen. During 75% reduction in umbilical blood flow maternal oxygen administration significantly increased fetal oxygen delivery (6.4 +/- 2.5 to 7.7 +/- 2.3 ml/min/kg) and oxygen consumption (4.3 +/- 1.2 to 5.0 +/- 0.8 ml/min/kg). With similar reduction of uterine flow oxygen administration increased oxygen delivery from 8.3 +/- 2.4 to 12.3 +/- 3.6 and oxygen consumption from 3.3 +/- 0.8 to 4.7 +/- 1.6 ml/min/kg. Maternal oxygen inhalation improves fetal oxygenation during umbilical but especially during uterine blood flow reduction.


Convulsions in pregnancy in related gorillas.

Two related gorillas, the second the granddaughter of the first, had pregnancies complicated by convulsions and edema. They may have suffered from eclampsia, indicating that this is not an exclusively human disease and that in gorillas, as in humans, there is a familial factor.


Messenger ribonucleic acid for transforming growth factor-alpha, but not for epidermal growth factor, is expressed in fetal and neonatal mouse brain.

Little is known concerning the presence of transforming growth factor-alpha in fetal and neonatal tissues. Our objective was to analyze messenger ribonucleic acid expression for transforming growth factor-alpha and epidermal growth factor, the structural and biochemical analog of transforming growth factor-alpha in fetal and neonatal murine brain. Messenger ribonucleic acid was prepared from whole brains of mice from these developmental stages: embryonic days 14, 15, and 17, postnatal days 0, 4, 10, and adult. Polymerase chain reaction was performed on the complementary deoxyribonucleic acid obtained from reverse transcription of messenger ribonucleic acid with transforming growth factor-alpha and epidermal growth factor primers. In addition, ribonuclease protection assay was used to identify transforming growth factor-alpha transcripts. We found messenger ribonucleic acid encoding transforming growth factor-alpha in all stages of development used. Epidermal growth factor messenger ribonucleic acid was not found in any stage. Ribonuclease protection assay confirmed transforming growth factor-alpha transcripts in these tissues. Transforming growth factor-alpha may play an autocrine or paracrine role in the differentiation or maintenance of murine fetal and neonatal brains.


Cardiac electromechanical dissociation in the hypoxic fetal sheep may have clinical implications.

Our purpose was to determine the sequence of fetal cardiac electrical and mechanical events associated with acute hypoxic acidemia and to correlate those events with terminal fetal heart rate patterns preceding fetal death. Eight acutely catheterized fetal sheep were rendered hypoxic by placental embolization with microspheres until fetal death occurred. The fetal electrocardiogram, Doppler cardiogram, left ventricular and aortic pressures, and fetal heart rate were continuously recorded. All eight fetuses showed a terminal bradycardia consisting of two phases: an initial phase of falling ventricular pressures, culminating in mechanical asystole, and a subsequent phase after asystole during which the electrocardiographic signal persisted for an average duration of 15.2 +/- 8.7 minutes (range 3.1 to 32.4) and triggered a Hewlett-Packard 8040A monitor to show a heart rate pattern. The phenomenon of cardiac electromechanical dissociation may be occurring during similar terminal bradycardias that are observed in human labor and explains the delivery of a fresh stillbirth in spite of the recording of an electrocardiographic signal from a scalp electrode.


The fetus as an allograft: immunobiologic role of human trophoblasts for fetal survival.

The hypothesis of this study is that trophoblasts contribute to the survival of the mammalian fetal allograft. Immunologic and molecular biologic studies were performed with human trophoblasts or trophoblastic tumor cells to investigate the expression of class I human leukocyte antigens, the susceptibility to natural killer and lymphokine-activated cells, the ontogeny of Fc gamma-receptors, and the production of immunosuppressive factors. Heterogeneous expression of class I human leukocyte antigens on trophoblasts was regulated at transcriptional level. Trophoblasts showed low susceptibility to natural killer and lymphokine-activated cells. Trophoblasts expressed natural killer cell-type Fc gamma-receptor III, which mediates phagocytosis. The trophoblast-derived immunosuppressive factor was very similar to transforming growth factor-beta. The trophoblasts, which ultimately form the fetoplacental interface, constitute a major immune barrier for the survival of the allogenic conceptus.


Suppression of natural killer cell activity by sera from patients with endometriosis.

We determined the effect of sera from patients who have endometriosis on natural killer cell activity. The natural killer cell activity of lymphocytes from healthy volunteers was examined after incubation with sera from patients who had endometriosis or from controls, with K562 cells used as targets. Lymphocytes treated with sera from patients who had endometriosis expressed significantly lower levels of cytotoxicity compared with lymphocytes treated with control sera. This suppression of cytotoxicity was dose dependent, and the degree of suppression was proportional to the incubation time of the effector cells with the sera. Decreased cytotoxicity after serum treatment was also observed with sera from patients who had been treated with danazol. These findings show that humoral factors that can inhibit natural killer cell activity in vitro are present in the peripheral blood of patients who have endometriosis; moreover, they suggest that the suppressed natural killer cell activity may allow the development of endometrial cells at ectopic sites.


A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies.

A prospective, controlled multicenter study was performed to estimate the obstetric risks of antiphospholipid antibodies (the lupus anticoagulant and anticardiolipin antibodies). In addition, the risks of prior thrombosis, obstetric history, systemic lupus erythematosus, and high-dose prednisone treatment were evaluated. After screening for antiphospholipid antibodies in patients with lupus erythematosus or women with prior fetal loss(es), 59 subsequent pregnancies with and 54 without these antibodies were followed. The presence of the lupus anticoagulant and a history of at least three spontaneous abortions could predict fetal loss (p = 0.032 and 0.001, respectively). In live born infants, a low birth weight could be predicted by the presence of anticardiolipin antibodies (p = 0.034), prior intrauterine fetal death (p = 0.025), and treatment with high-dose prednisone (p = 0.002). No relationships were seen between antiphospholipid antibodies and small-for-gestational-age newborns and pregnancy-induced hypertension or preeclampsia. The disappearance of antiphospholipid antibodies during pregnancy was not correlated with live birth. It is concluded that the presence of antiphospholipid antibodies is a risk factor for adverse pregnancy outcome.


Significance of peritoneal macrophages on fertility in mice.

To elucidate the role of peritoneal macrophages in infertility, we investigated how the presence of peritoneal macrophages would affect fecundity in mice. Moreover, we also studied the effects of interleukin-1 on embryonic development. Mice were administered OK-432 intraperitoneally to induce macrophage infiltration of the peritoneal cavity; ovulation was then induced and animals were mated. On day 13 of gestation, fetuses were counted. After injection of OK-432 or interleukin-1, the mice were mated. Three days later, embryos were collected and the stage of embryo development was determined. In mice given OK-432 (n = 33), four (12%) became pregnant and the mean litter number was 6.0 +/- 3.6, whereas in the control group 23 of 30 mice (77%; p < 0.01) became pregnant and the litter number was 14.1 +/- 5.3 (p < 0.01). OK-432 and interleukin-1 administered intraperitoneally significantly suppressed embryo development (p < 0.01). Increased numbers of peritoneal macrophages negatively affect fecundity, probably by suppressing embryonic development.


Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis.

Our aim was to examine the relationship between the levels of cytokines in peritoneal fluid and its embryo toxicity. The levels of interleukin-1 and tumor necrosis factor were measured in peritoneal fluid from infertile women who did not have endometriosis (n = 21), who had untreated endometriosis (n = 19), and who had undergone medical treatment for endometriosis (n = 10). Embryo toxicity was investigated in mouse two-cell embryos cocultured with the oviducts in culture media that contained various concentrations of peritoneal fluid. The levels of cytokines were significantly higher in the peritoneal fluid from women who had untreated endometriosis than in women who did not have endometriosis, but they were extremely low in women who had undergone medical treatment with either danazol or buserelin. The peritoneal fluid from women who had untreated endometriosis adversely affected the cleavage of mouse two-cell embryos. After medical treatment the embryo toxicity of the peritoneal fluid was almost undetectable. These results offer some theoretic bases in support of medical treatment to improve reproductive performance in infertile women who have endometriosis.


Luteinized unruptured follicle in the early stages of endometriosis as a cause of unexplained infertility.

We attempted to clarify the relationship between luteinized unruptured follicle, which occurs in the early stages of endometriosis, and unexplained infertility. Seventy patients who had unexplained infertility were reviewed. Laparoscopic examination showed that 47 patients (67%) had endometriosis; of these, 40 (85%) had minimal or mild disease. The incidence of luteinized unruptured follicle was higher (p < 0.05) in patients who had endometriosis (35%/patient and 25%/cycle) compared with patients who did not have endometriosis (11%/patient and 7%/cycle). Degenerated oocyte cumuli were collected in 6 (43%) of 14 luteinized unruptured follicles diagnosed by transvaginal ultrasound. These results show that luteinized unruptured follicle is common in patients who have mild or minimal endometriosis and that it may be one of the causes of endometriosis-associated infertility. Transvaginal ultrasound-guided follicular puncture of luteinized unruptured follicle during the mid luteal phase may be useful in establishing a definitive diagnosis of luteinized unruptured follicle.


Luteal function in infertile patients with endometriosis.

Our purpose was to determine whether infertile patients who have endometriosis show luteal phase defects. The luteal function in 24 infertile patients who had endometriosis was compared with the luteal function in 20 patients who had unexplained infertility and did not have endometriosis (control). In both groups serum luteinizing hormone, follicle-stimulating hormone, progesterone, and estradiol were assayed every day throughout the menstrual cycle. Endometrial biopsy specimens were obtained from eight patients of the endometriosis group for histologic dating of the endometrium. No significant differences in progesterone levels were observed between these two groups during the mid and late luteal phase. Seven of the eight patients who underwent histologic dating showed a luteal phase pattern, whereas only one patient was out of phase. Infertile patients who have endometriosis do not always have luteal phase defects.


The impact of endometriosis on the reproductive outcome of infertile patients.

We examined whether the presence and severity of endometriosis affect the reproductive outcome of infertile patients. The conception rates of 2080 infertile women, 1263 who had endometriosis and 817 who did not have endometriosis, were analyzed retrospectively by means of the chi 2 test. Depending on the stage of the disease patients who had endometriosis-associated infertility underwent expectant management, danazol therapy, or minor or major conservative surgery. The patients who failed to conceive after these conventional treatments were enrolled in the in vitro fertilization-embryo transfer program. The conception rates were virtually identical regardless of the presence or absence of endometriosis (30.7% vs 30.0%). The outcome of in vitro fertilization-embryo transfer was not affected either by the presence or the severity of the disease. Endometriosis had no impact on the reproductive outcome of infertile patients in this series unless the anatomy of the pelvic organs was heavily distorted, which can occur in the advanced stages of the disease.


Term birth after midtrimester hysterotomy and selective delivery of an acardiac twin.

Our aim was to determine whether hysterotomy and selective removal of an acardiac twin could improve the outcome of the "pump" twin. A literature and case review of the outcome of the acardiac twin malformation was performed. When an acardiac malformation was diagnosed at 19 weeks' gestation the patient was monitored with weekly ultrasonographic examinations. At 23 weeks' gestation, no blood flow could be demonstrated to the acardiac twin and it was thought that the continued presence of the acardiac twin posed a risk to the "pump" twin. A midtrimester hysterotomy was performed and the acardiac twin was delivered. After the midtrimester hysterotomy, the pregnancy progressed to term and a healthy female infant was delivered by elective cesarean section at 37 weeks' gestation. Midtrimester hysterotomy may be a useful intervention in cases of twinning when one fetus is a threat to the health of the other.


Idiopathic myelofibrosis in pregnancy: a case report and review of the literature.

Idiopathic myelofibrosis is a rare myeloproliferative disorder characterized by excessive accumulation of connective tissue in the bone marrow in association with anemia, splenomegaly, and extramedullary hematopoiesis. The cause of this disease is unknown, and the prognosis is generally poor. To our knowledge, this is the first case report of a patient with idiopathic myelofibrosis who carried a term pregnancy. In spite of the increased perinatal risks, a favorable outcome was possible with close antepartum surveillance.


Oral contraceptive use and the incidence of cervical intraepithelial neoplasia.

Our objective was to examine the relationship between oral contraceptive use and the incidence of cervical intraepithelial neoplasia. In a prospective follow-up study of 6622 women participating in the Second Tromsö Study conducted in 1979 and 1980 in Tromsö, Norway, women aged 20 to 49 years answered a questionnaire regarding their smoking history, dietary habits, alcohol consumption, and oral contraceptive use. They were then followed for 10 years with data from the Pathology Registry of the University Hospital. The age-adjusted incidence rate of cervical intraepithelial neoplasia was 897 per 100,000 person years among noncurrent and 1295 per 100,000 person years among current oral contraceptive users as of 1979. After adjusting for age, marital status, smoking, and frequency of alcohol intoxication the relative rate for current users was 1.5 (95% confidence interval 1.1 to 2.1), and the relative rate for past users was 1.4 (95% confidence interval 1.0 to 1.8), as compared with those who had never used oral contraceptives before 1979. These findings support the hypothesis that the occurrence of cervical intraepithelial neoplasia is increased by oral contraceptive use.


Calcium homeostasis in pregnant women receiving long-term magnesium sulfate therapy for preterm labor.

The hypothesis of this study is that calcium homeostasis and bone mineralization are altered in pregnant women receiving long-term therapy with magnesium sulfate as compared with similar women not receiving magnesium sulfate to control preterm labor. Thirty-nine women between 24 and 32 weeks' gestation, matched for age, race, and duration of bed rest, were enrolled. Indices of calcium homeostasis in serum and urine were measured serially, and bone mineralization of the distal radius was measured at 1 and 11 weeks post partum. Magnesium therapy was administered for a mean duration of 26 +/- 14 days and a cumulative dose of 1405 +/- 963 gm. Serum concentrations of magnesium, phosphorus, and parathyroid hormone increased and those of calcium decreased from baseline values in the magnesium sulfate group and remained uniform throughout the 3-week investigation. The serum magnesium, phosphorus, parathyroid hormone, and calcium concentrations in the control group were unchanged during the study and differed significantly from those in the magnesium sulfate group (p < 0.001). Urinary output of magnesium, calcium, and copper was significantly greater in the magnesium sulfate group than in the control group throughout the study. Urinary losses of calcium in the magnesium sulfate group, approximately 800 to 900 mg/day, were substantial. Although radius bone density 1 week post partum did not differ between groups, the change in bone density from 1 to 11 weeks post partum was significantly lower in the magnesium sulfate group than in controls. These data suggest that calcium homeostasis is altered during and after long-term magnesium sulfate therapy. The marked, prolonged urinary calcium losses may affect maternal bone mineralization.


Nifedipine for treatment of preterm labor: a historic prospective study.

The purpose of this study was to ascertain whether adverse fetal and/or neonatal effects occurred during nifedipine treatment of preterm labor and to assess maternal tolerance of nifedipine therapy in patients intolerant of a beta-sympathomimetic agent. We undertook historic prospective review of medical records of 102 women admitted to an antepartum ward for treatment of preterm labor who received nifedipine. Data were collected regarding maternal side effects, fetal surveillance, and neonatal outcome. The number and severity of reported maternal side effects were significantly reduced when patients were switched from terbutaline to nifedipine. No discontinuance of nifedipine occurred because of maternal side effects. Fetal surveillance testing and neonatal outcome data failed to reveal deleterious in utero effects of nifedipine. Nifedipine was a well-tolerated and safe tocolytic in this population and warrants further investigation.


Nonimmune hydrops fetalis associated with maternal infection with syphilis.

Intrauterine infection with syphilis was diagnosed by reactive maternal serologic studies, ultrasonographic findings, and exclusion of other causes in three hydropic fetuses at 31, 34, and 35 weeks' gestation. With penicillin therapy and preterm delivery all infants survived through the perinatal period. Intrauterine infection that follows syphilis is a potentially treatable cause of nonimmune hydrops.


Suppression of 24-hour cholecystokinin secretion by oral contraceptives.

Weight gain is a common side effect during oral contraceptive use. The secretion of the satiety hormone cholecystokinin was recorded for 24 hours in women before and during treatment with oral contraceptives. During treatment serum profiles of cholecystokinin were clearly suppressed, which might be related to increased appetite and weight gain.


Delayed endometrial maturation induced by daily administration of the antiprogestin RU 486: a potential new contraceptive strategy.

Our objective was to determine if a progesterone antagonist might interdict the development of a secretory endometrium. Eleven normally cycling women not at risk for pregnancy received RU 486 (1 mg/day orally) or placebo throughout one menstrual cycle in a randomized, double-blind, crossover fashion. Estradiol, progesterone, and placental protein 14 were measured every 3 days; luteinizing hormone was measured until the midcycle surge was detected. An endometrial biopsy was performed on luteal phase day 7 to 9 and interpreted with Noyes' criteria. Differences between treatment groups were analyzed by the Student t test. RU 486 delayed ovulation, retarded endometrial maturation, and reduced peak levels of placental protein 14 without affecting gonadal steroid production. The abnormalities in endometrial morphology and function are similar to those seen in infertile women with luteal phase defects. We hypothesize that this regimen of antiprogestin administration may prevent implantation and offer a novel strategy for fertility control.


Antenatal tests of fetal welfare and development at age 2 years.

Our objective was to examine the outcomes at 2 years of age of fetuses delivered electively before 34 weeks, studied antenatally with two tests of fetal well-being. Forty-two fetuses from high-risk pregnancies delivered electively by cesarean section before 34 weeks were stratified into normal versus abnormal subgroups with umbilical Doppler flow velocity waveform and fetal heart rate results. Developmental outcome was assessed at 2 years. Two comparison groups were also selected: 40 matched premature controls delivered spontaneously before 34 weeks and 67 normal babies delivered spontaneously at term. Frequency outcome data were tested with chi 2 analyses and the remainder with analyses of variance. Within the electively delivered study group poor cognitive progress at 2 years was more strongly associated with an abnormal fetal heart rate result than an abnormal Doppler result. Compared with the premature control and normal term groups, electively delivered fetuses were significantly delayed in growth, cognition, and motor development (p < 0.005). Adverse fetal welfare in a high-risk obstetric sample was associated with poorer outcome at 2 years. However, the whole of the group of fetuses from such high-risk pregnancies showed significant developmental delay compared with normal term children and, more importantly, matched premature infants delivered spontaneously from otherwise uncomplicated pregnancies.


Macrosomia in postdates pregnancies: the accuracy of routine ultrasonographic screening.

The purpose of this study was to assess the efficacy of routine ultrasonographic assessment of fetal weight in predicting fetal macrosomia in postdates pregnancies. A total of 519 pregnancies of > or = 41 weeks' duration were subjected to ultrasonographic estimation of fetal weight within 1 week of delivery. Estimated fetal weights were compared with birth weights. Linear regression analysis was performed and prediction limits for estimated fetal weights were generated. Twenty-three percent of infants had birth weights > or = 4000 gm and 4% had birth weights > or = 4500 gm. The mean percent absolute error was 7.7%. At a birth weight of > 3750 gm, the Hadlock model (which uses abdominal circumference and femur length) systematically overestimated the birth weight. The sensitivity, specificity, and positive and negative predictive values for the ultrasonographic diagnosis of macrosomia were 56%, 91%, 64%, and 87%, respectively. The prediction limits generated determine the range of birth weights predicted for a given estimated fetal weight. Routine ultrasonographic screening for macrosomia in postdates pregnancies is associated with a relatively low positive predictive value.


Retrospective maternal mortality case ascertainment in West Virginia, 1985 to 1989.

The death of women from pregnancy-related causes remains a threat to national maternal and child health. Maternal deaths as persistent, albeit rare occurrences are overlooked if vital registration systems are relied on to report such deaths. Live birth records were matched with death records for women of reproductive age to detect if a woman died within 1 year of delivery. The data for potential cases were reviewed by committee and classified as maternal and nonmaternal deaths. Of all linked birth-death records, 32% were related to pregnancy: 81% were directly related to pregnancy and 19% were indirectly related to pregnancy. The most frequent causes of death were hemorrhage and embolism. Thirty-eight percent of the women were transferred to tertiary hospitals before death. The case ascertainment through this study improved maternal death detection by 100% over official vital statistics. Enhanced maternal mortality surveillance increased the detection of maternal death in West Virginia. Case review of these deaths yielded important information useful in shaping the state's perinatal system.


Laparoscopic diagnosis and repair of spigelian hernia: report of a case and technique.

Spigelian hernia is an uncommon hernia of the abdominal wall. We report a case of acquired spigelian hernia diagnosed and treated by laparoscopy. With more extensive use of laparoscopy to evaluate abdominal pain, the diagnosis of spigelian hernia can be made and repair accomplished without need for open exploratory surgery.


Oligohydramnios and megacolon in a fetus with vesicorectal fistula and anal-urethral atresia: a case report.

Severe oligohydramnios and extremely dilated bowel filled with hyperechogenic material floating in fluid were the ultrasonographic findings in a fetus at 27 weeks' gestation. Vesicorectal communication and urethral-anal atresia permitted urine to empty into the colon, causing megacolon, oligohydramnios, and markedly increased intraabdominal pressure resulting in pulmonary hypoplasia.


Pathways to hysterectomy: insights from longitudinal twin research.

We hypothesized that genetic influences act on "liability" to hysterectomy, that secular influences might differentially affect relative importance of genetic and environmental influences, and that the sources of genetic influences could be identified from reported risk factors. Hysterectomy data from an Australia-wide volunteer sample of female adult monozygotic and dizygotic twins are reported. In 1980 through 1982 a mailed questionnaire was completed by 1232 monozygotic female twin pairs and 751 dizygotic female twin pairs (3966 women) from the Australian Twin Register (wave 1). The same twins were surveyed by questionnaire 8 years later (wave 2). A total of 366 had undergone hysterectomy by wave 1 and a further 198 at wave 2. The twin-pair correlations for liability to hysterectomy at wave 1 (0.61 +/- 0.06 for monozygotic and 0.20 +/- 0.11 for dizygotic) and wave 2 (0.65 +/- 0.05 for monozygotic and 0.32 +/- 0.09 for monozygotic) indicated a substantial genetic contribution. Reported risk factors accounted for only 15% of total variance. Genetic influences on liability to hysterectomy were substantial and stable across birth cohorts, but the important sources of genetic influence on liability to hysterectomy are yet to be identified.


Maternal and fetal hemodynamic effects of autologous blood donation during pregnancy.

Our objectives were to describe the maternal and fetal hemodynamic impact of a 1 U acute blood loss during pregnancy and to compare the hemodynamic responses of pregnant women with those of nonpregnant controls. With Doppler techniques cardiac output and total peripheral vascular resistance were determined in 16 pregnant women in the third trimester and in 16 nonpregnant volunteers before and during orthostatic stress, before and after donation of 450 ml of whole blood. In pregnant women the fetal umbilical artery systolic/diastolic ratio was also determined. Data were subjected to multiple logistic regression analysis. In both groups orthostasis provoked significant decreases in cardiac output and increases in total peripheral vascular resistance. The hemodynamic effects of blood loss were less pronounced and did not significantly change the hemodynamic response to orthostasis in either group. Neither orthostasis nor blood loss caused significant changes in the umbilical systolic/diastolic ratio. These data support the hemodynamic safety of uncomplicated autologous blood donation during late pregnancy.


First-trimester diagnosis of cystic hygroma--course and outcome.

We studied the outcomes of fetuses in whom cystic hygroma was diagnosed in the first trimester of pregnancy through the application of transvaginal ultrasonography. In the period 1990 to 1991 22 fetuses with cystic hygroma were found. All fetuses had karyotyping and a complete ultrasonographic search for associated anomalies. Aneuploidy was found in seven of 22 fetuses: four trisomy 21, two trisomy 18, and one translocation. Monosomy X was absent in this series. In 15 of 22 cases there was a normal karyotype. In 10 of 15 euploid fetuses the small nonseptated hygroma resolved spontaneously. In four of 15 euploid fetuses other malformations were detected with ultrasonography (i.e., polycystic kidneys, coarctation of the aorta, bladder outlet obstruction, and fetal hydrops). Whenever a cystic hygroma is suspected in the antenatal period, even if of small size, a structured and detailed ultrasonographic examination and fetal karyotyping are recommended.


Baking powder pica mimicking preeclampsia.

We report a case of baking powder pica during pregnancy that was associated with maternal hypertension, hypokalemia, and elevated liver function tests. After discontinuation of baking powder ingestion and correction of electrolyte abnormalities, the blood pressure and the liver function tests normalized.


Sterilization needs in the 1990s: the case for quinacrine nonsurgical female sterilization.

Much evidence suggests that demand for sterilization is a function of supply of surgical sterilization services in less-developed countries. If such services were greatly expanded, the number of procedures performed would grow dramatically. While the prevalence of sterilization is estimated to increase from 23.5% to 28.8% of married women of reproductive age in the 1990s, there will actually be 106,432,000 more couples of reproductive age at the end of this decade than at its beginning who use either no method or a far less effective method with much lower continuation rates than sterilization--nearly a 20% increase. To achieve a mean sterilization prevalence of 47% of married women of reproductive age in the less-developed world, as now seen in the Republic of Korea and Puerto Rico, the number of sterilizations would need to be more than double the current projection for the 1990s: 328,429,000 rather than 159,000,000. The quinacrine pellet method for nonsurgical female sterilization offers hope that this enormous shortfall in sterilization services can be overcome in this decade.


Predictors for live birth after unexplained spontaneous abortions: correlations between immunologic test results, obstetric histories, and outcome of next pregnancy without treatment.

Our objective was to determine whether results from tests for maternal serum antinuclear antibodies, cytotoxic antibodies to paternal lymphocytes, parental histocompatibility types, and blocking factors for maternal-paternal mixed lymphocyte reactions were predictive of pregnancy outcome without immunologic treatment. Pregnancy outcome data from 95 women with a history of unexplained recurrent spontaneous abortions who underwent immunologic tests at Jefferson Medical College were evaluated with multiple logistic regression analyses. The number of prior spontaneous abortions, history of another relevant diagnosis, parental sharing of one histocompatibility antigen, and maternal age were related to the outcome of the next pregnancy in women given no immunologic treatment (p = 0.05). No significant correlation was found between results from the immunologic tests or other history characteristics evaluated and outcome of the next pregnancy. The immunologic tests evaluated were not clinically useful predictors of pregnancy outcome.


Cigarette smoking and urinary incontinence in women.

The goal of this case control study was to evaluate the relationship between smoking and female urinary incontinence. The study included 606 women whose smoking histories were known; 322 were incontinent and 284 were continent. The condition(s) causing each subject's incontinence was determined by urodynamic testing; 40% of the continent subjects had the same testing. There were highly significant overall differences (p = 0.000009) in the distribution of current, former, and never smokers between incontinent (35%, 16%, 49%) and continent (24%, 8%, 68%) groups. The odds ratio for genuine stress incontinence was 2.20 for former (95% confidence interval 1.18 to 4.11) and 2.48 for current smokers (95% confidence interval 1.60 to 3.84); for motor incontinence it was 2.92 for former (95% confidence interval 1.58 to 5.39) and 1.89 (95% confidence interval 1.19 to 3.02) for current smokers. Increasing daily and lifetime cigarette consumption was associated with an increasing odds ratio for genuine stress incontinence but not for motor incontinence. The increased risk for incontinence was not due to differences in age, parity, weight, or hypoestrogenic status. The data establish a strong statistical relationship between current and former cigarette smoking and both stress and motor urinary incontinence in women.


Natural history of chronic proteinuria complicating pregnancy.

Although the significance of proteinuria is well-documented for pregnancy complicated by preeclampsia or diabetes, protein excretion of up to 300 mg per day is considered normal for uncomplicated pregnancy. Our purpose was to determine the significance of otherwise "asymptomatic" proteinuria identified during pregnancy. We reviewed the perinatal outcome of 65 pregnancies in 53 women with the following criteria: (1) proteinuria exceeding 500 mg per day, (2) no previously known renal disease, (3) no reversible renal dysfunction, and (4) no evidence for preeclampsia at discovery. Renal insufficiency coexisted in 62% of women, and 40% had chronic hypertension. Excluding 8 abortions, 53 (93%) of 57 pregnancies resulted in live infants; 45% of infants were delivered preterm and 23% had growth retardation. Of these 57 women, 62% demonstrated clinical evidence compatible with superimposed preeclampsia, and although the incidence of preeclampsia was increased with isolated proteinuria (29%), it was increased even more when there was associated chronic hypertension (incidence 100%) or renal insufficiency (incidence 58%). All 21 women who eventually underwent renal biopsy had histologic evidence of renal disease. To date, with only a limited follow-up of these 53 women, 11 (20%) have progressed to end-stage renal disease. "Asymptomatic" proteinuria is associated with a number of adverse pregnancy outcomes and serious long-term maternal morbidity.


Selective pelvic and periaortic lymphadenectomy does not increase morbidity in surgical staging of endometrial carcinoma.

The objective of this study was to retrospectively assess whether there was increased morbidity associated with the addition of selective pelvic and periaortic lymphadenectomy to hysterectomy in patients with endometrial carcinoma. From 1977 through 1988, 196 patients undergoing selective pelvic and periaortic lymphadenectomy plus hysterectomy were compared with 104 patients who underwent hysterectomy alone for endometrial adenocarcinoma. Only after adjusting for covariates was selective pelvic and periaortic lymphadenectomy associated with a higher estimated blood loss, which increased linearly with weight and was higher for black than for white women. The transfusion rate was similar for the two groups (selective pelvic and periaortic lymphadenectomy 6%, hysterectomy 10%). The mean blood loss was significantly different among the four gynecologic oncology surgeons (range 343 to 652 ml). The operating time primarily depended on patient weight and race, surgeon, and estimated blood loss. Postoperative hospital stay increased significantly with age, surgeon, wound infections, thrombotic events, and serious complications. Selective pelvic and periaortic lymphadenectomy had no effect on wound infections, which were directly related to operating time. Seventy-five (38%) of the selective pelvic and periaortic lymphadenectomy group and 19 (18%) of the hysterectomy group (p < 0.01) received whole-pelvic radiation with no difference in bowel complications (selective pelvic and periaortic lymphadenectomy 2/75, hysterectomy 1/19). The risk of serious complications was associated only with increasing age. Selective pelvic and periaortic lymphadenectomy in patients with endometrial carcinoma does not significantly add to morbidity from hysterectomy, which is related primarily to other factors such as patient weight, age, and race; operating time; and surgeon.


Does DeLee suction at the perineum prevent meconium aspiration syndrome?

We attempted to determine the impact of "early" (before delivery of the chest) oronasopharyngeal DeLee suctioning at the perineum in the prevention of meconium aspiration syndrome and to confirm that meconium aspiration syndrome is a postnatal event. We compared infants with meconium-stained fluid who underwent "early" oronasopharyngeal DeLee suctioning with a similar group of infants whose airways were suctioned "late" (after chest delivery). Practicing obstetricians did not know the study was being conducted by the pediatric staff, and an independent observer documented whether obstetricians performed "early" or "late" oronasopharyngeal DeLee suctioning. Immediate postnatal tracheal suctioning was performed in both groups. The study was conducted in a private tertiary care center averaging 5800 deliveries annually. A consecutive sample of 438 infants with meconium-stained fluid was analyzed. Of these infants, 221 received "early" oronasopharyngeal DeLee suctioning, while 217 infants were suctioned "late". Of the 438 infants with meconium-stained fluid, meconium aspiration syndrome developed in 38 (9%). These infants had higher rates of fetal distress (i.e., abnormal fetal heart rates) and lower Apgar scores (< or = 6) than infants without meconium aspiration syndrome (58% vs 17% and 65% vs 13%, respectively; p < 0.001). Forty-five percent of the infants with meconium aspiration syndrome had renal failure during the first 20 hours of life. In spite of "early" oronasopharyngeal DeLee suctioning, 53% of the infants in this group had meconium below the vocal cords and meconium aspiration syndrome developed in 7%. The time of oronasopharyngeal DeLee suctioning did not affect the rate of meconium aspiration syndrome or the presence of meconium below the vocal cords. We concluded that "early" oronasopharyngeal DeLee suctioning at the perineum does not affect the rate of meconium aspiration syndrome. We speculate that meconium aspiration syndrome is predominantly an intrauterine event associated with fetal distress and that meconium in the airways is merely a "marker" of previous fetal hypoxia.


Assessment of the renal circulation during pregnancy with color Doppler ultrasonography.

A non-invasive method of assessing the renal vasculature during pregnancy would be useful in the management of patients with renal dysfunction resulting from preeclampsia or chronic renal disease. The objectives of this study were to determine (1) whether color ultrasonography during pregnancy facilitates Doppler interrogation of renal and intrarenal arteries, allowing (2) the assessment of differences between waveforms from nonpregnant and pregnant women and (3) the analysis of waveform variability throughout the kidney and between the right and left kidneys. In a cross-sectional study renal and intrarenal artery flow waveforms were obtained from women in early (12 to 19 weeks; n = 8), mid (20 to 29 weeks; n = 11), and late (30 to 37 weeks; n = 14) pregnancy with eight age-matched, nonpregnant women acting as controls. Waveforms were analyzed for pulsatility index, resistive index, and systolic/diastolic ratio. Left or right renal and upper- and lower-pole interlobar artery waveforms were obtained from all women. The mean pulsatility index values for the nonpregnant women were not significantly different from those women in early, mid, or late pregnancy. In the nonpregnant women, the left renal artery pulsatility index (1.13 +/- 0.13) was greater than the left lower interlobular artery pulsatility index (0.91 +/- 0.08; p < 0.05). During pregnancy renal and interlobar artery pulsatility index values were greater than those for the corresponding interlobular arteries, but the differences were not significant. Mean renal and intrarenal artery pulsatility index values were greater on the right, but the difference was significant only for the lower interlobular artery in midpregnancy. Pregnancy does not significantly affect renal and intrarenal artery flow waveforms, nor are there significant differences between waveforms from the renal and interlobar arteries.


Sleep quality in preeclampsia.

Our goal was to study the sleep quality in women with preeclampsia with a special reference to nocturnal body movement activity. Sleep quality was evaluated in nine women with preeclampsia and eight women with normal term pregnancy by means of questionnaires and by recording the nocturnal body movement activity with the static charge-sensitive bed. Subjective sleep complaints were similar in both groups. The total movement time and the total frequency of body movements in bed were, however, significantly increased in the preeclamptic group. The study suggests that sleep is impaired in preeclamptic subjects.


Reversal of fetal distress by emergency in utero decompression of hydrothorax.

The purpose of our study was to determine whether in utero pleural decompression can improve abnormal cardiotocograms resulting from compressive fetal hydrothorax. We reviewed all cases of fetal hydrothorax referred to our level 3 fetal medicine unit. Highly pathologic cardiotocographic findings were observed in four third-trimester patients. All had mediastinal compression that resulted in skin edema on the upper part of the body. Prenatal therapy was performed on an emergency basis, two with thoracocentesis and two with pleuroamniotic catheters. One patient went into intractable bradycardia on arrival in the department and died in spite of immediate thoracocentesis. The other three recovered, with normal heart rate patterns after pleural decompression. Emergency prenatal therapy may reverse fetal distress in utero, allowing time for delivery of uncompromised infants if possible after a complete evaluation of nonimmune hydrops.


Changes in coagulation and anticoagulation in women taking low-dose triphasic oral contraceptives: a controlled comparative 12-month clinical trial.

The effects of two triphasic oral contraceptives on coagulation and anticoagulation factors were compared in a 12-month open-label study. Fifty-two women (mean age 26 years) were enrolled in and completed the study; 20 had been randomly assigned to receive levonorgestrel plus ethinyl estradiol, 24 had been randomly assigned to receive norethindrone plus ethinyl estradiol, and eight surgically sterile women acted as untreated controls. Coagulation and anticoagulation factors were measured at baseline and during the sixth and twelfth months. Both oral contraceptives produced significant decreases from baseline in prothrombin time and partial thromboplastin time; there were also significant changes in laboratory control times. Factor XII was significantly increased in both oral contraceptive groups after 6 and 12 months. Fibrinogen antigen was significantly increased for norethindrone plus ethinyl estradiol after 6 and 12 months and for levonorgestrel plus ethinyl estradiol after 12 months. Platelet counts were unchanged. There was a significant increase in antithrombin III activity with norethindrone plus ethinyl estradiol at 12 months. Antithrombin III antigen was unchanged with the oral contraceptives; however, significant increases existed for alpha 1-antitrypsin antigen and plasminogen antigen and activity after 6 and 12 months and for alpha 2-macroglobulin antigen after 12 months for both oral contraceptives. alpha 2-Antiplasmin antigen was significantly increased for norethindrone plus ethinyl estradiol at the 12-month evaluation. There were no significant differences between the oral contraceptives for any coagulation or anticoagulation factor, and mean values generally remained within reference ranges. Levonorgestrel plus ethinyl estradiol and norethindrone plus ethinyl estradiol had equivalent, minimal effects on hemostasis, and changes in coagulation factors appeared to be balanced by changes in anticoagulation factors.


Serum collagenase levels in relation to the state of the human cervix during pregnancy and labor.

The purpose of our study was to investigate the role of collagenase in the cervical ripening and dilatation process in term pregnancy. Serum samples were obtained from nonpregnant women (n = 5) and term-pregnant women. The term-pregnant women were either admitted for elective cesarean section or labor induction (unfavorable cervix, n = 19; favorable cervix, n = 12) or in spontaneous, active labor (stiff and inelastic cervix, n = 7; soft compliant cervix, n = 8). Statistical analysis was performed with the Student t test. The nonpregnant women had low serum collagenase levels (5.2 +/- 0.7 micrograms collagen digested per minute per 100 ml serum, mean +/- SEM). At term but before labor, women with unripe cervices had higher collagenase levels (10.3 +/- 0.9). The women with ripe cervices had even higher serum collagenase levels (22.9 +/- 4.2; p < 0.001). During labor, women with stiff and inelastic cervices had lower serum collagenase levels compared with women with soft and compliant cervices (12.9 +/- 1.7 vs 28.0 +/- 4.2; p < 0.01). Serum collagenase during ripening at term and in active labor increases, supporting its active role in the ripening process.


Genetic offspring in patients with vaginal agenesis: specific medical and legal issues.

There are new options for genetic offspring in patients with vaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome). The reported world experience to date with genetic offspring of patients with vaginal agenesis consists of five pregnancies (including two reported here and two frozen embryos). The specifics of these cases are presented for discussion. We present a retrospective description of two women with vaginal agenesis and their matched gestational carriers with positive outcome of two live births. Care was delivered in a private in vitro fertilization and gamete intrafallopian transfer program. In vitro fertilization of oocytes gathered from the genetic mother with vaginal agenesis and sperm from the genetic father were transferred to a gestational carrier. Two live births and one blighted ovum pregnancy resulted. Until recently, treatment for patients with vaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome) has centered on the creation of a functional vagina. The technology of in vitro fertilization and embryo transfer, allowing for collection of oocytes from the genetic mother, fertilization by the genetic father, and placement into a gestational carrier, enables a woman without a uterus to have her own genetic children. The specific medical and legal issues involved in facilitating genetic offspring in these instances must be considered; these include the initial matching of the genetic parents with the gestational carrier, cycle synchronization for in vitro fertilization and embryo transfer, anatomic difficulties of oocyte retrieval, birth certificate documentation, and the current legal status of a gestational carrier.


Fetal plasma erythropoietin concentration in red blood cell-isoimmunized pregnancies.

The aim of this study was to investigate the relationship between fetal anemia, plasma erythropoietin concentration, and erythroblastosis in red blood cell-isoimmunized pregnancies. Fetal plasma erythropoietin concentration in umbilical venous blood samples from 68 red blood cell-isoimmunized pregnancies at 18 to 35 weeks' gestation was measured. Measurements were compared with the appropriate reference range with gestation, and associations with blood pH, erythroblast count, and hemoglobin concentration were examined. The mean fetal plasma erythropoietin concentration and erythroblast count in red blood cell-isoimmunized pregnancies were significantly increased only in severe fetal anemia (hemoglobin deficit > 7 gm/dl). Furthermore, some severely anemic fetuses were hydropic and acidemic. The degree of increase in plasma erythropoietin was significantly associated with both fetal acidemia and, more strongly, fetal erythroblastosis. These findings suggest that in fetuses from red blood cell-isoimmunized pregnancies the ability to prevent tissue hypoxia is present until anemia becomes severe, presumably by an increase in cardiac output and tissue perfusion. In severe anemia tissue hypoxia occurs, and the data indicate that fetuses respond by increasing erythropoietin production from at least 20 weeks' gestation. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.


Doppler velocimetry and fetal heart rate studies in nephropathic diabetics.

Our objectives were to determine in pregnancies complicated by diabetic nephropathy (1) if impedance to flow in the uterine and umbilical arteries is normal and (2) if these fetuses are hypoxemic and acidemic and if they have decreased fetal heart rate variation and Doppler blood flow redistribution. In a cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London, serial assessment of fetal heart rate variation and Doppler velocimetry of the placental and fetal circulations was undertaken in six pregnancies complicated by diabetic nephropathy. In all cases cordocentesis was performed within 24 hours before delivery for the measurement of umbilical venous blood gases. Cordocentesis demonstrated these fetuses to be hypoxemic and acidemic. The fetal heart rate variation was decreased; however, impedance to flow in the uterine artery was normal, and increased impedance to flow in the umbilical artery with evidence of blood flow redistribution was observed in only one case. Fetal hypoxemia and acidemia in pregnancies complicated by diabetic nephropathy is not a consequence of impaired placental perfusion, and the degree of metabolic derangement may be obscured by the apparent normal growth and failure of these fetuses to demonstrate blood flow redistribution.


Renal pyelectasis in pregnancy: correlative evaluation of fetal and maternal collecting systems.

The current study is aimed at assessing the possibility of a statistical relationship between fetal and maternal collecting system dilatation during pregnancy. Two hundred thirty consecutive pregnant women and their fetuses (20 to 40 weeks' gestation) were simultaneously examined by ultrasonography. The renal collecting systems were measured, and the frequency of dilatation was subjected to chi 2 analysis. The temporal incidence of fetal pyelectasis was compared with the maternal incidence. Dilatation of maternal collecting systems was detected in 91 of 230 patients (40%) and fetal pyelectasis occurred in 60 of 230 (26%). Fetal pyelectasis was 5.6 times more likely to occur in fetuses of mothers with dilated collecting systems. Furthermore, the temporal incidence of fetal pyelectasis throughout pregnancy appeared similar to that of maternal pyelectasis. This study points out the existence of a statistically significant association between maternal and fetal collecting system dilatation during pregnancy.


Umbilical venous pressure in nonimmune hydrops fetalis: correlation with cardiac size.

Our objectives were to examine the relationship between umbilical venous pressure and cardiac size in nonimmune hydrops fetalis and to assess the role of cardiac failure in the pathogenesis of the disease. Fourteen fetuses with nonimmune hydrops fetalis were investigated in a tertiary referral unit with high-resolution ultrasonography, echocardiography, and fetal blood sampling. Fetal heart size was assessed by measurement of the cardiothoracic ratio. Umbilical venous pressure was measured at the time of fetal blood sampling with a fluid-filled system. The 10 fetuses with elevated umbilical venous pressures had significantly increased cardiothoracic ratios (p = 0.02). These fetuses also had ascites. Four other fetuses had normal-sized hearts, normal umbilical venous pressures, and no ascites. There was a linear relationship between cardiothoracic ratio and umbilical venous pressure (r = 0.75, p = 0.003). Measurement of umbilical venous pressure validates cardiothoracic ratio as a noninvasive assessment of cardiac function in nonimmune hydrops.


Monitoring of intravascular fetal transfusions with Doppler velocimetry.

Intravascular fetal transfusions are occasionally complicated by extravascular deposition of transfused blood or by fetal bradycardia on penetration of the needle into the umbilical cord. It is desirable therefore to continuously monitor the intravascular location of the needle and the fetal heart rate. This can be achieved by Doppler velocimetry of the umbilical vein and artery during the procedure. The technique is easily performed, does not require moving of the ultrasonography transducer, and appears to be time efficient.


Reproductive, menstrual, and medical risk factors for endometrial cancer: results from a case-control study.

Our objective was to evaluate the risk for endometrial cancer in relation to reproductive, menstrual, and medical factors. A case-control study of 405 endometrial cancer cases and 297 population controls in five areas of the United States enabled risk to be evaluated. A major risk factor was the absence of a prior pregnancy (relative risk 2.8, 95% confidence interval 1.7 to 4.6). The protective effect of pregnancy appeared to reflect the influence of term births, because spontaneous and induced abortions were unrelated to risk. Among nulliparous women infertility was a significant risk factor, with women having sought medical advice having nearly eight times the risk of those without difficulty conceiving. After adjustment for other reproductive characteristics, age at first birth and duration of breast-feeding were not related to risk. Elevated risks were found for subjects reporting early ages at menarche (relative risk 2.4 for ages < 12 vs > or = 15) and longer days of flow (relative risk 1.9 for > or = 7 vs < 4 days), but there was no relationship with late ages at natural menopause. Height was not associated with risk, but there was a significant relation to weight, with the risk for 200 versus < 125 pounds being 7.2 (95% confidence interval 3.9 to 13.3). After adjustment for weight and other factors, histories of hypertension and gallbladder disease were not significantly related to risk, but an effect of diabetes persisted (relative risk 2.0, 95% confidence interval 1.1 to 3.6). Hirsutism developing at older ages was also significantly related (relative risk 2.0, 95% confidence interval 1.2 to 3.4).


Randomized trial of human versus animal species insulin in diabetic pregnant women: improved glycemic control, not fewer antibodies to insulin, influences birth weight.

Macrosomia occurs in infants of diabetic mothers in spite of "nearly normal maternal blood glucose levels" with insulin treatment. Insulin antibodies may carry bound insulin into the fetal blood and thus may be associated with fetal hyperinsulinemia and macrosomia in these infants. Our objective was to test the hypothesis that human insulin is associated with lower insulin antibody levels and less macrosomia than is animal species insulin. Forty-three insulin-requiring pregnant (< 20 weeks' gestation) women, previously treated with animal insulin, were randomized to human and animal insulins and studied at weeks 10 through 20, 24, 28, 32, 36, and 38, at delivery, and at 3 months post partum. Infant blood was drawn at delivery (cord) and at 1 day and 3 months post partum 1 hour after a glucose-amino acid challenge. Women receiving human insulin required significantly less insulin per kilogram of body weight and showed significant dampening of glucose excursions (p < 0.05 for each comparison). Infants born to mothers receiving human insulin weighed 2880 +/- 877 gm compared with 3340 +/- 598 gm for infants of women treated with animal insulin (p < 0.05). There was no difference in insulin antibody levels between groups for either mothers or infants. Infants born to mothers receiving human insulin had a 1 hour C-peptide level after the glucose-amino acid challenge at 3 months of age of 0.21 +/- 0.13 pmol/ml compared with 0.32 +/- 0.13 pmol/ml (p = 0.01). Administration of human insulin to pregnant diabetic women has a therapeutic advantage over animal insulin, with less maternal hyperglycemia or hypoglycemia, fewer larger-for-gestational-age infants, and less neonatal hyperinsulinemia. Our data do not support the hypothesis that maternal antibodies to insulin influence infant birth weight.


Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: correlations with stage and other clinicopathologic features.

This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay and immunohistochemical analysis were used. The immunohistochemical analysis receptor content was estimated semiquantitatively by a total and a cancer immunohistochemical histologic score. Multiple regression analysis was used in testing independence of established correlations. Estrogen and progesterone receptor dextran-coated charcoal values and immunohistochemical histologic scores correlated inversely (p < 0.001) with International Federation of Gynecology and Obstetrics grade of tumor. An inverse correlation (p < 0.0001) between clinical stage and dextran-coated charcoal values was independent of International Federation of Gynecology and Obstetrics grade. Age of patient, years since menopause, and previous estrogen treatment were not related to receptor content. In adenomatous hyperplasia high progesterone receptor levels were seen. The inverse correlation between clinical stage of endometrial carcinoma and content of estrogen and progesterone receptors may reflect tumor biologic behavior.


Effect of fat and fat-free mass deposition during pregnancy on birth weight.

The purposes of our study were to describe the patterns and location of fat and fat-free mass deposition during pregnancy and to evaluate their effects on fetal growth. Our study is a prospective follow-up of 105 healthy pregnant women who were delivered of term infants. Body composition was evaluated eight times during gestation with anthropometric measures and bioimpedance techniques. Body fat and fat-free mass were calculated with equations specifically developed for this population. Total weight gain was 10.0 +/- 3.5 kg; net weight gain was 3.7 +/- 0.31 kg; birth weight was 3211 +/- 467 gm (values are mean +/- SEM). In these women fat was deposited mostly in the thigh and subscapular region for a total of 6.23 +/- 0.19 kg at term. The period of pregnancy of the largest maternal fat deposition per week is between the twentieth and thirtieth weeks. After adjusting by prepregnancy weight, birth weight is associated with maternal changes in thigh skin folds and fat gain before the thirtieth week of gestation. Infants born to mothers with low fat gain before the thirtieth week were 204 gm lighter than infants born to mothers with fat gain > or = 25th percentile of this population. Maternal nutritional status at the beginning of gestation and the rate of fat gain early in pregnancy are the two nutritional indicators most strongly associated with fetal growth in this population.


Maternal ventricular tachycardia associated with hypomagnesemia.

We present a rare case of recurrent sustained maternal ventricular tachycardia associated with hypomagnesemia. The frequency of this arrhythmia was markedly reduced with magnesium sulfate therapy. Both maternal and fetal outcomes were good. To the best of our knowledge this is the first description of maternal ventricular tachycardia that was associated with hypomagnesemia and did not require treatment with conventional antiarrhythmic medications. We discuss the possible underlying pathophysiologic causes of this condition.


Maternal floor infarction: relationship to X cells, major basic protein, and adverse perinatal outcome.

Maternal floor infarction of the placenta is characterized by gross placental abnormalities and histologic evidence of X-cell proliferation. Previously, pregnancy-associated major basic protein has been localized to the placental X cell and identified at elevated levels in serum and amniotic fluid in all normal pregnancies. Here we test the hypothesis that pregnancy-associated major basic protein is localized to the X cells in maternal floor infarction and that it contributes to the pathophysiologic features of pregnancies complicated by maternal floor infarction. Seven patients with eight pregnancies complicated by maternal floor infarction were evaluated. We analyzed placental tissue, serum, amniotic fluid, and placental cyst fluid for pregnancy-associated major basic protein. Placental tissue from pregnancies complicated by maternal floor infarction had increased numbers of X cells and fibrinoid material that occupied or surrounded degenerating villi and that stained intensely for pregnancy-associated major basic protein. Serum pregnancy-associated major basic protein levels were variable and likely cannot be used to predict the occurrence of maternal floor infarction. Pregnancy-associated major basic protein, a potent cytotoxin, is localized to X cells and is deposited in close proximity to chorionic villi in maternal floor infarction and may contribute to the pathophysiology of this disorder.


The effect of placental management at cesarean delivery on operative blood loss.

The effect of alternative methods of placental delivery at cesarean section on blood loss has not been reported. The hypothesis of this study was that spontaneous expulsion of the placenta would reduce operative blood loss, compared with that of manual extraction during cesarean delivery. We prospectively randomized and compared outcomes of 62 gravid women with manual (n = 31) or spontaneous (n = 31) placental delivery at cesarean section. Operative blood loss was measured directly. Blood loss measured at cesarean delivery was greater in the manually delivered group (967 +/- 248 ml) than in the spontaneously delivered group (666 +/- 271 ml, p < 0.0001). The incidence of postpartum endometritis was sevenfold greater in the manual than the spontaneous group (23% vs 3%, respectively; p < 0.05). We conclude that spontaneous expulsion of the placenta at cesarean delivery results in less operative blood loss and a lower incidence of postoperative endometritis.


Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis. I. Efficacy results.

We aimed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis. A double-blind randomized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis. Pretreatment and posttreatment endometriosis symptoms and signs were assessed with standardized methods. When compared with danazol, leuprolide depot caused a more rapid and profound suppression of estradiol. Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis, as well as the pain and tenderness associated with endometriosis. Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain.


Glycated hemoglobin of fractionated erythrocytes, glycated albumin, and plasma fructosamine during pregnancy.

To evaluate glucose metabolism during pregnancy, we measured plasma fructosamine, glycated albumin, and the stable glycated hemoglobin of the light and dense erythrocytes. The abnormal glucose tolerance group comprised patients with gestational diabetes and those with one abnormal value on a 75 gm oral glucose tolerance test. Erythrocyte fractionation was performed by capillary centrifugation. In normal pregnancy glycated hemoglobin of the light erythrocytes was reduced in the second and third trimesters (3.42% +/- 0.62% [mean +/- SD] [n = 306] in the first trimester, 2.15% +/- 0.48% [n = 353] in the second, and 2.06% +/- 0.58% [n = 300] in the third), and dense erythrocytes were higher in the third trimester (first 4.59% +/- 0.46%, second 4.70% +/- 0.49%, third 5.29% +/- 0.73%). Glycated albumin and fructosamine followed a pattern similar to the light erythrocytes. The group with abnormal glucose tolerance had significantly higher levels of glycated hemoglobin of the light erythrocytes in the first and third trimesters and glycated hemoglobin of the dense erythrocytes and glycated albumin in all trimesters. The biphasic change in nonfractionated glycated hemoglobin is the sum of the lower glycated hemoglobin of the light erythrocytes and the higher glycated hemoglobin of the dense erythrocytes in late pregnancy. The stable glycated hemoglobin of fractionated erythrocytes and the glycated albumin accurately reflect maternal glucose metabolism during pregnancy.


The effect of the menstrual cycle on serum CA 125 levels: a population study.

Our objective was to assess the effect of the menstrual cycle on CA 125 levels in a population study. Serum CA 125 was measured in 1478 women, with day of menstrual cycle noted in 574 women. Repeat examination was performed in women with elevated results, and 40 of these women were tracked by weekly examination of CA 125 levels. A significant difference was demonstrated when midcycle samples were compared with day 1 and day 28 samples (p < 0.05). In spite of this significance the difference was not clinically useful. Elevated serum CA 125 (> 35 U/ml) levels were present in 77 (5.2%) of the premenopausal women. A significant variation was demonstrable with higher CA 125 levels about the time of menstruation in 29 of the 40 women tracked. This study suggests that in the population as a whole the effect of the menstrual cycle on serum CA 125 is not clinically significant, but single elevated levels in an individual may represent menstrual fluctuation.


The fetal recoil test.

A reassuring fetal recoil test has positive and negative predictive values of 98% and 8%, respectively, for a reactive nonstress test (sensitivity 89%, specificity 33%). Among 21 of 30 subjects in whom recoil was present immediately before delivery, none had umbilical arterial pH values < or = 7.20 versus 5 of 9 (56%) with nonreassuring recoil (p = 0.005). We concluded that a reassuring fetal recoil test is a reliable marker for fetal well-being.


Recurrent squamous carcinoma of the vulva.

This study reviews experience at Indiana University with recurrent squamous carcinoma of the vulva over an 18-year period from 1971 to 1989. The pattern of recurrence, time interval to recurrence, and efficacy of salvage therapy are evaluated in the context of the primary tumor. This is a retrospective study of 40 patients, 21 of whom underwent primary therapy for invasive squamous carcinoma of the vulva at Indiana University. Vulvar recurrences were observed in 17 patients (43%), the groin was involved in 12 (30%), whereas pelvic and distant recurrences were observed in 2 (5%) and 9 (22.5%) patients, respectively. Salvage surgery and/or radiotherapy were successful in 25 patients (62.5%) alive from 1 to 144 months (median 8 months) from secondary therapy. Survival after retreatment varied significantly by site of recurrence (p = 0.002), tumor grade (p = 0.009), and interval to recurrence (p < 0.001). Best outcomes were in patients with initial stage I or II disease (International Federation of Gynecology and Obstetrics), grade 1 tumors, local failure, and interval to relapse of > 16 months' duration. Two of 12 patients with groin recurrences were salvaged with surgery and radiotherapy. Long-term follow-up of patients with vulvar cancer and careful restaging at the time of recurrence are mandatory. Although local and nodal recurrences may be controlled with surgery and/or radiotherapy, regional recurrences are usually fatal.


Contraction monitoring with a manager calculator.

A simple manager calculator was used as a contraction monitor, and external parallel registrations were performed on 10 pregnant women in labor with the Psion and other kinds of tocodynamometers. A 94% correlation was found between the simultaneously registered data.


Mechanisms of relaxation induced by prostaglandins in isolated canine uterine arteries.

Prostaglandins liberated from the uterus in response to chemical and physical stimuli would be important modulators of uterine arterial tone and blood flow. This study was aimed at analyzing mechanisms of vasodilator action of prostaglandins in uterine arteries. Canine uterine artery strips were suspended in Ringer-Locke solutions for isometric tension recording. Prostaglandin F2 alpha-induced relaxation was reversed to contraction by cyclooxygenase inhibitors and suppressed by tranylcypromine (prostaglandin I2 synthesis inhibitor) or diphloretin phosphate (an inhibitor of prostaglandin F2 alpha and prostaglandin I2 actions) but was unaffected by endothelium denudation. Prostaglandin E2-induced relaxation was not attenuated by indomethacin but was partially inhibited by a nitric oxide synthase inhibitor and endothelium denudation. Relaxation induced by beraprost (prostaglandin I2 analog) was suppressed by diphloretin phosphate but was not influenced by indomethacin and endothelium denudation. It appears that prostaglandin F2 alpha-induced relaxation is mediated by prostaglandin I2 released from subendothelial tissues, whereas prostaglandin E2-induced relaxation is caused by release of endothelium-derived nitric oxide and also by an endothelium-independent mechanism.


Chemotactic factor in the pregnant rabbit uterine cervix.

Neutrophil accumulation is one of the characteristic changes observed in uterine cervical stroma at term pregnancy, but chemotactic activity in the tissue is obscure. Our study examined the existence and production of chemotactic factor in the rabbit uterine cervix. Uterine cervical explants of rabbits at term pregnancy and nonpregnant rabbits were cultured with and without interleukin-1 alpha. Rat neutrophilic chemotaxis in culture media was evaluated with a Boyden chamber. Tissue extract from the pregnant rabbit uterine cervix at term pregnancy contained more chemoattractive activity than the nonpregnant cervix. Production of chemoattractant from cultured rabbit cervical explants at term pregnancy was also higher than that from nonpregnant explants. The addition of interleukin-1 alpha to the culture system promoted its production. This chemoattractant was characterized as a true chemotactic factor and heat-stable and trypsin-sensitive protein with an apparent relative molecular mass of 16,200. So far, these properties are very similar to those of the interleukin-8 family. Rabbit uterine cervical fibroblast is characterized as a chemotactic factor-producing cell in the rabbit uterine cervix. These results indicate that interleukin-8-like chemotactic factor participates in the cervical ripening at term pregnancy and that the production of this factor is controlled effectively by interleukin-1.


Transient umbilical cord occlusion causes hippocampal damage in the fetal sheep.

The purpose of our study was to examine the neuronal outcome after a standardized period of umbilical cord occlusion. The umbilical cord was clamped for 10 minutes in nine experimental and four control chronically instrumented fetal sheep. Three days later the animals were killed for histologic interpretation. Systemic, electrophysiologic, and neurohistologic effects were compared by analysis of variance. Clamping of the cord resulted in transient severe asphyxia, hypotension (24 +/- 5 mm Hg, p < 0.01), bradycardia (72 +/- 14 beats/min, p < 0.001), depressed electroencephalographic activity (-17 +/- 2 dB, p < 0.001), and an increase in cortical impedance. The electroencephalographic activity was depressed for 5 +/- 2 hours in spite of rapid recovery of arterial oxygen content. Neuronal loss was found in the hippocampus. Neither epileptiform electroencephalographic activity nor infarction were observed. Three animals with poor blood gas levels died during the occlusion. An isolated and brief period of umbilical cord occlusion in utero can cause predominantly hippocampal damage without persistent functional changes in cortical activity and with rapid recovery of other potential indicators of fetal asphyxia.


Secretion of prolactin and insulin-like growth factor I by decidual explant cultures from pregnancies complicated by intrauterine growth retardation.

Prolactin and insulin-like growth factor I secretion elsewhere in the uterus have been shown to decrease when tissue-specific growth is limited. We investigated their secretion by decidual explant cultures from pregnancies complicated by fetal intrauterine growth retardation. Explant cultures from 13 pregnancies complicated by intrauterine growth retardation and 12 control pregnancies were established in minimal essential medium and media was harvested after 24 hours of culture. Prolactin and insulin-like growth factor I concentrations were determined by radioimmunoassay. Total protein in the media was also measured. Data were analyzed by analyses of variance and linear regression. Decidual prolactin secretion in the pregnancies with intrauterine growth retardation was reduced to 109 +/- 31 ng/100 mg tissue per 24 hours compared with 254 +/- 51 ng in the controls (p = 0.01). Insulin-like growth factor I secretion was reduced to 1.9 +/- 0.6 ng/100 mg tissue per 24 hours from 7.1 +/- 0.9 ng/100 mg in the controls (p < 0.0001). Total protein secretion did not differ between the two groups. Decidual prolactin and insulin-like growth factor I secretion had a highly significant positive correlation (r = 0.71, p = 0.0001). Our data show that two protein hormones secreted by the maternal decidua are dramatically reduced in intrauterine growth retardation and warrant further investigation into their roles in the intrauterine environment.


Human ovarian surface epithelial cells are capable of physically restructuring extracellular matrix.

After ovulation the human ovarian surface epithelium proliferates at the wound edges, migrates over the ovulatory defect, and contributes to its repair primarily by the action of proteolytic enzymes and by the deposition of new matrix material. We examined the potential for human ovarian surface epithelial cells to physically remodel extracellular matrix in culture, similar to collagen gel lattice contraction by fibroblasts, a well-known culture model for wound repair, as an additional role of human ovarian surface epithelium in wound repair. Human ovarian surface epithelium cells from ovarian biopsies of 11 patients were grown in culture and plated onto a combination of collagen gel and rat ovarian surface epithelial-derived extracellular matrix. The degree of matrix contraction was measured as the percentage of the original culture diameter. Human ovarian surface epithelial cells surrounded and contracted the combination of matrices into a dense matrix organoid. The degree of organoid contraction was related to the number of human ovarian surface epithelial cells plated per organoid and to the inclusion of fibroblasts within the collagen gel but was not affected either by adding epidermal growth factor and hydrocortisone to the culture medium or by reducing the serum component of the medium. Human ovarian surface epithelial organoids may be useful for the study of normal and abnormal ovarian events such as ovulatory wound repair and cyst formation.


Autonomic and arginine vasopressin modulation of the hypoxia-induced atrial natriuretic factor release in immature and mature ovine fetuses.

This study investigated the maturational change in the atrial natriuretic factor response to hypoxia in ovine fetuses and the role of the autonomic nervous system and arginine vasopressin in modulating this response. Chronically catheterized ovine fetuses from 110 to 135 days' gestation were subjected to 30 minutes of hypoxia. The fetuses were either intact, treated with hexamethonium to block the autonomic nervous system, or treated with a pressor antagonist of arginine vasopressin. Hypoxia elevated plasma atrial natriuretic factor levels by 1635 +/- 265 pg/ml in immature fetuses; this response was greater than the increase of 748 +/- 189 pg/ml in mature fetuses (p < 0.0001). Blockade of the autonomic nervous system reduced the atrial natriuretic factor response and suppressed the vascular pressure changes to hypoxia in immature but not in mature fetuses. A vasopressin pressor antagonist suppressed the atrial natriuretic factor but not vascular pressure responses to hypoxia in mature fetuses. This study demonstrates that the immature fetus manifested a greater atrial natriuretic factor response to hypoxia than did the mature fetus. This enhanced response appeared to be dependent on the modulatory effects of the autonomic nervous system on vascular pressures during hypoxia. In addition, arginine vasopressin appeared to augment the atrial natriuretic factor response to hypoxia in the mature fetus independent of vascular pressure changes.


Acute intrauterine hypoxia increases amniotic fluid prostaglandin F metabolites in the pregnant sheep.

Amniotic fluid infection promotes cytokine release, prostaglandin production, and premature labor. In several tissues local hypoxia also activates the secretion of cytokines. Many patients initially seen in premature labor carry small-for-gestational-age fetuses, a condition associated with intrauterine hypoxia. The purpose of our study was to determine whether a reduction in placental blood flow and subsequent acute hypoxia affects prostaglandin secretion by the placenta. We chronically catheterized six pregnant sheep at 120 days of gestation. We placed catheters in the maternal and fetal femoral arteries and in the amniotic fluid cavity. A flow probe and snare were placed around the common uterine artery. A 30-minute uterine circulation occlusion of 30% of its control value produced an increase in prostaglandin F metabolite from 790 +/- 157 to 944 +/- 184 pg/ml within 10 minutes (p < 0.01). Additional uterine blood flow reduction to 60% of control increased the amniotic fluid prostaglandin F metabolites concentration to 894 +/- 202 (p < 0.05, analysis of variance). No increase in mean intrauterine pressure was detected (p > 0.1). We speculate that the prostaglandin increase in amniotic fluid in response to intrauterine hypoxia could eventually lead to premature labor. Whether the increase in prostaglandins is mediated by changes in cytokines is unknown at the present time.


Changes in pupillary diameter in relation to eye-movement and no-eye-movement periods in the human fetus at term.

The aim of our study was to reveal whether pupils dilate and constrict in a time sequence in the human fetus and to assess the relationship between changes in pupillary diameter and eye-movement-no-eye-movement periods. We simultaneously observed pupil and eye movement with real-time ultrasonography in 30 human fetuses at 36 to 41 weeks' gestation. Eighteen were excluded because of data loss. Statistical analysis of pupillary diameter changes were made on the remaining 12 fetuses with the least median of squares regression. Pupillary diameters were found to be differentiated with statistical significance into two groups: 9.7% for the dilated pupil (median 3.0 mm) and 90.3% for the constricted pupil (1.7 mm). The percentage of dilated pupils during the eye-movement period (14.3%) was significantly greater than that during the no-eye-movement period (2.3%; Wilcoxon rank sum test, p < 0.0001). These findings indicate a close relation between pupillary dilatation and eye-movement periods in the human term fetus.


Community care of corneal ulcers.

Because of increasing concern about the appropriate and cost-effective use of eye care services and procedures, several organizations have sought to arrive at practice guidelines or practice patterns from which physicians can draw guidance. To assess the potential effectiveness of such guidelines, we reviewed the care of patients with corneal ulcers. Corneal specialists recommend that cultures be obtained before initiation of treatment. We determined whether ophthalmologists implemented these guidelines by the following: (1) a review of records of 79 patients referred to a tertiary care corneal and external disease service for evaluation of keratitis, and (2) a survey by mail of practicing ophthalmologists. Antibiotic therapy without any cultures was observed in 38 of 79 referred patients with corneal ulcers (48.1%). Our survey of general ophthalmologists disclosed that 274 of 560 patients with corneal ulcers (48.7%) were treated with antibiotics without any cultures being obtained. Compliance with recommended practice in the care of corneal ulcers is poor, as measured with either method. This procedure provides insights into more effective implementation of future practice guidelines.


Lattice degeneration of the retina and the pigment dispersion syndrome.

Retinal detachment occurs more frequently in patients with pigment dispersion syndrome. We evaluated the incidence of peripheral retinal abnormalities known to predispose to rhegmatogenous retinal detachment in a consecutive series of 60 patients with pigment dispersion syndrome with or without glaucoma. Lattice degeneration was present in at least one eye of 12 patients (20%). Seven patients had bilateral lesions. Full-thickness retinal breaks were found in seven patients (11.7%) and two patients (3.3%) had asymptomatic rhegmatogenous retinal detachments that required scleral buckle procedures. The incidence of lattice degeneration and full-thickness retinal breaks appears to be increased in this group of patients, and may be responsible for the increased risk of rhegmatogenous detachment.


Changes in optic disk characteristics and number of nerve fibers in experimental glaucoma.

We compared the change in cup/disk ratio and neuroretinal rim area-to-disk area to estimated change in the number of optic nerve fibers in 12 cynomolgus monkeys with unilateral experimental glaucoma. Changes in the cup/disk ratios and neuroretinal rim area-to-disk area were estimated from stereoscopic optic disk photographs that were obtained before and after the development of increased intraocular pressure. Change in the number of optic nerve fibers in the glaucomatous nerves was estimated by comparing them to their fellow normal nerves. A significant linear correlation was present between change in the cup/disk ratios and neuroretinal rim area-to-disk area, and estimated change in the number of optic nerve fibers (r > or = .85; P < .0002). In optic disks with initial cup/disk ratios of 0.2 to 0.3 and neuroretinal rim area-to-disk area of 0.9, an increase in the cup/disk ratio of 0.1 and a decrease of 0.1 in the neuroretinal rim area-to-disk area is associated with a 10% and 9% loss of optic nerve fibers, respectively.


The influence of exposure duration in transscleral Nd:YAG laser cyclophotocoagulation.

Transscleral cyclophotocoagulation was performed in human autopsy eyes by using three Nd:YAG lasers with different durations of exposure: a pulsed, contact laser with a duration of 0.75 millisecond and a range of one to ten pulses per burst (GLase 106, Sunrise Technologies, Fremont, California); a pulsed, noncontact laser with a duration of 20 milliseconds (Microruptor 2, Lasag Medical Lasers, Thun, Switzerland); and a continuous-wave, contact laser with durations of 700 and 2,000 milliseconds (Microruptor 3, Lasag Medical Lasers, Thun, Switzerland). Tissue responses were observed with a high-magnification videographic recording technique to analyze the immediate, real-time laser effects, and by light microscopy to characterize the laser-induced lesions further. Videographically, both pulsed lasers were noted to cause mild whitening of the pigment epithelium with frequent vaporization and explosive tissue disintegration. Histologically, the 0.75-millisecond pulse typically produced the most marked epithelial disruption, referred to as an explosive-like lesion, whereas the 20-millisecond pulse more often caused moderate tissue disruption with elevation of the epithelial layers in a blister-like lesion. In contrast, the continuous-wave laser was observed videographically to produce prominent tissue whitening and puckering, seen histologically as convolution of the epithelium and coagulation of stroma, which was called a shrinkage-like lesion. Our study suggests that exposure duration influences in vitro tissue response to transscleral Nd:YAG cyclophotocoagulation, although in vivo studies and clinical trials are needed to determine which tissue response is optimum for clinical use.


Acquired oculomotor, trochlear, and abducent cranial nerve palsies in pediatric patients.

Between January 1966 and December 1988, 160 pediatric patients (age range, 0 to 17 years) were seen at the Mayo Clinic with an acquired oculomotor (35 patients), trochlear (19 patients), abducent (88 patients), or multiple (18 patients) cranial nerve palsy. The clinical findings in the 160 pediatric patients were compared with the results obtained in other reviews of cranial nerve palsies in the pediatric age group and with the adult Mayo Clinic patients with acquired cranial nerve palsies. Trauma was the most common reason for an acquired cranial nerve palsy in our pediatric group. The percentage of patients with an acquired cranial nerve palsy resulting from trauma was significantly greater in the pediatric group (42.5%) than in adults (15.4%) (P < .01). The difference between the percentage of adults (15.2%) and pediatric patients (16.9%) with a cranial nerve palsy secondary to a neoplasm was not statistically significant (P = .28).


Development of object vision in infants with permanent cortical visual impairment.

We examined 30 infants in whom cortical visual impairment was diagnosed during their first year of life to ascertain prognostic factors for the development of object vision, defined as the ability to recognize faces or hand-held toys. All patients were followed up for a minimum of 12 months. The most common causes of cortical visual impairment in the 30 infants were hydrocephalus in nine infants (30.0%), birth asphyxia or neonatal hypoxia in eight infants (26.7%), intracranial hemorrhage with or without hydrocephalus in seven infants (23.3%), and meningitis in five infants (16.7%). Lack of development of object vision was associated only with hypoxia (P = .013). Findings on ophthalmic examination, an abnormality in the visual pathway on computed tomographic or magnetic resonance scan, and seizures, hydrocephalus, intracranial hemorrhage, meningitis, cerebral palsy, developmental delay, prematurity, microcephaly, and hearing deficit, did not appear to be risk factors for the lack of development of object vision.


Ocular findings in Cockayne syndrome.

The ocular findings in eight patients with Cockayne syndrome included enophthalmos, hyperopia, poor pupillary dilation, and retinal dystrophy in all patients. Four patients had strabismus. Two patients had cataracts. Three patients had nystagmus. Visual acuity was relatively well preserved in six patients, including a 25-year-old man with a visual acuity of 20/60 in each eye despite advanced retinal pigmentary changes. Failure of DNA and RNA synthesis to recover after ultraviolet light exposure as well as selective loss of repair of transcriptionally active DNA may account for the ocular abnormality in this progeric syndrome.


Orbital cellulitis caused by Eikenella corrodens.

Eikenella corrodens is a gram-negative, facultative anaerobic bacillus with specific culture and growth requirements and unusual antibacterial susceptibilities. It has only recently been recognized as a human pathogen. Ocular and adnexal infections with this organism are rare especially in children. We treated two children with orbital cellulitis caused by E. corrodens. One was an 8-year-old boy; the other was an 11-year-old girl. Orbital cellulitis in both patients occurred after an upper respiratory tract infection. Sinusitis and a subperiosteal abscess were present in both patients. Eikenella corrodens and Streptococcus viridans were isolated from the boy; E. corrodens was the sole isolate in the girl. Intravenous ampicillin, prolonged hospitalization, and surgical drainage of the orbit were required to control the infection in both patients. Eikenella corrodens must be considered in the differential diagnosis of orbital cellulitis in children, and ophthalmologists must become familiar with the characteristics of this peculiar organism.


Diode laser photocoagulation for prethreshold, posterior retinopathy of prematurity.

Nine infants with posterior retinopathy of prematurity were treated by using the diode laser through an indirect ophthalmoscopic delivery system. Treatment was commenced as soon as plus disease (defined as tortuosity and dilation of posterior vessels) developed. We defined posterior retinopathy of prematurity as retinopathy of prematurity located in zone 1 (the limits of zone 1 are defined as twice the disk-fovea distance in all directions from the optic disk, that is, an arc of 60 degrees centered on the optic disk) or the posterior one half of zone 2 (zone 2 extends from the edge of zone 1 peripherally to a point tangential to the nasal ora serrata and around to an area near the temporal anatomic equator). Disease regressed in all eyes. These results are encouraging and represent an improvement over the results obtained by allowing these eyes to reach threshold (threshold disease is defined as 5 or more contiguous or 8 total clock hours of neovascularization in zone 1 or 2 in the presence of plus disease) before intervention.


Posterior segment changes in membranoproliferative glomerulonephritis.

Membranoproliferative glomerulonephritis is a renal disorder characterized by proliferation of cells and changes in the basement membrane of the glomerulus. The disease is divided into three subtypes: type I, characterized by the presence of subendothelial electrondense deposits; type II, characterized by deposition of electrondense material of unknown origin in the lamina densa of the glomerular basement membrane; and type III, characterized by lesions having both type I and type II qualities. Specific posterior segment changes have been reported with membranoproliferative glomerulonephritis type II. We examined three patients with membranoproliferative glomerulonephritis type II and two patients with type III disease. All three patients with type II disease had Bruch's membrane and retinal pigment epithelial changes, whereas both patients with type III disease had normal posterior segments.


Posterior capsulotomy as a complication of indirect laser photocoagulation.

Two pseudophakic patients with posterior chamber intraocular lens implants and intact posterior capsules underwent indirect laser photocoagulation during their immediate postoperative period (24 and 72 hours postoperatively, respectively). Laser treatment was indicated for a retinal break noted after vitrectomy and scleral buckling in one patient and after peribulbar perforation during cataract extraction in the other patient. Ocular media were hazy because of vitreous haze and hemorrhage in both eyes and higher power laser settings were required to produce adequate chorioretinal burns during photocoagulation. Inadvertent large posterior capsulotomy as a complication was noted in both eyes. High-power settings and hazy ocular media are risk factors toward this complication. We recommend that slit-lamp examination be performed before, during, and after indirect laser treatment, especially when higher power settings are required.


Retained lens fragments after phacoemulsification manifesting as marked intraocular inflammation with hypopyon.

We reviewed the medical records of four patients with marked intraocular inflammation and hypopyon as the initial manifestation of retained lens fragments after phacoemulsification. The severe inflammatory reaction occurred between one month and one year after the cataract extraction. All four patients underwent pars plana vitrectomy to remove the lens fragments. The vitreous specimens were cultured to rule out infectious endophthalmitis. In all patients, no organisms were isolated from the vitrectomy specimens placed on both aerobic and anaerobic media. All patients had improved vision and resolution of the marked intraocular inflammation after vitrectomy. Echography was useful in establishing the diagnosis in these uncommon cases.


Vogt-Koyanagi-Harada syndrome in patients with Cherokee Indian ancestry.

Eight patients with Vogt-Koyanagi-Harada syndrome who have Cherokee Indian ancestry ranged from 17 to 49 years of age. Five of the patients were black, three were white. Visual acuity at the time of initial examination ranged from 20/20 to counting fingers. Clinical findings included granulomatous iridocyclitis in six patients, vitreitis in seven patients, disk edema in five patients, exudative retinal detachment in six patients, and multifocal choroidal lesions in all eight patients. All of the patients were treated with systemic corticosteroids, and they recovered visual acuity of 20/40 or better. The seven patients assayed had the HLA-DRw52 haplotype, including five who were homozygous for this allele. This finding may add to the increasing evidence that a class II HLA antigen at a D-related locus may predispose carriers to the development of Vogt-Koyanagi-Harada syndrome.


Conjunctival involvement in paraneoplastic pemphigus.

Paraneoplastic pemphigus is a recently described autoimmune inflammatory mucocutaneous disease associated with an underlying neoplasm. Although histopathologic and direct immunofluorescence findings of involved skin and mucous membranes are consistent with pemphigus vulgaris, indirect immunofluorescence and immunoprecipitation study results are unique. We treated two patients with non-Hodgkin's lymphoma and paraneoplastic pemphigus. Both patients had bilateral bulbar conjunctival hyperemia and diffuse papillary tarsal conjunctival reactions. One patient had sloughing of conjunctival epithelium and the other had tarsal conjunctival cicatrization and forniceal shortening. Histopathologic findings of conjunctivae obtained from both patients were consistent with pemphigus vulgaris. Diffuse deposition of IgG and C3 in the intercellular substance of the conjunctival epithelium was demonstrated by direct immunofluorescence. Indirect immunofluorescence testing disclosed binding of autoantibodies to rodent bladder and intestinal epithelium. Immunoprecipitation disclosed antibodies reactive to Desmoplakin I (250 kd), bullous pemphigoid (230 kd), Desmoplakin II (210 kd) and 190-kd proteins. Ophthalmologists and pathologists should be aware of the conjunctival changes in paraneoplastic pemphigus.