Gestational diabetes insipidus, HELLP syndrome and eclampsia in a twin pregnancy: a case report.

We report a case of eclampsia in a twin pregnancy complicated by HELLP syndrome and diabetes insipidus. This confluence of disease processes suggests that a modification of common magnesium sulfate treatment protocols may be appropriate in a certain subset of patients.

Virtual simulation-enhanced triage training for Iraqi medical personnel.

Triage, establishing the priority of care among casualties in disaster management, is generally practiced using constructive tabletop or live exercises. Actual disasters involving multiple casualties occur rarely, offering little opportunity for gaining experience and competency assessment. When they do occur, response needs to be rapid and well-learned. In the Iraqi medical education environment where the need for triage is immediate, but the ability to stage practice is nearly impossible, blending didactic learning with simulation-based triage offers an alternative training methodology.

Normal fetal cardiac dimensions obtained by perpendicular imaging.

This study provides normal fetal cardiac dimensional data in a large patient group over a wide range of gestational ages. Perpendicular imaging decreased lateral resolution error, resulting in normal values with narrower confidence limits than in prior studies.

Human saturated steroid 6alpha-hydroxylase.

This study was conducted to evaluate further the reaction catalyzed by the saturated steroid 6alpha-hydroxylase of extrahepatic human tissues. Progesterone and 5alpha-dihydroprogesterone (5alpha-DHP) are plasma-borne precursors of 5alpha-pregnan-3alpha-ol-20-one, an anxiolytic/anesthetic steroid, and 5alpha-pregnan-3beta-ol-20-one in extrahepatic human tissues. These two steroids are metabolized further by a saturated steroid 6alpha-hydroxylase enzyme(s) that is distinct from the cytochrome P450 6alpha-hydroxylase that catalyzes the 6alpha-hydroxylation of delta4-3-ketosteroids such as progesterone, cortisol, and testosterone. Products of this saturated steroid 6alpha-hydroxylase, viz. 3beta/alpha,6alpha-dihydroxy-5alpha-pregnan-20-ones, are major radiolabeled urinary metabolites (excreted as glucuronosides) of i.v. administered tritium-labeled 5alpha-DHP in women and men. T47-D human breast cancer cells, which are rich in saturated steroid 6alpha-hydroxylase activity, were used as the enzyme source in this study. The greatest total and the highest specific activity of saturated steroid 6alpha-hydroxylase were localized in microsome-enriched preparations; enzyme activity was linear with incubation time up to 30 min and with microsome-enriched tissue protein concentrations between 0.05-0.5 mg/mL incubation mixture. The velocity of the reaction was similar in incubations in which the pH was varied from 6.0-8.0, and NADH and NADPH were equally effective in supporting the 6alpha-hydroxylation of 5alpha-pregnan-3beta-ol-20-one and 5alpha-pregnan-3alpha-ol-20-one. The more efficient substrates for this enzyme were 5alpha-pregnan-3beta-ol-20-one and 5alpha-pregnan-3alpha-ol-20-one, and the apparent Km (approximately 3.5 micromol/L) and maximum velocity (approximately 150 pmol/min x mg microsome-enriched protein) for these two substrates were indistinguishable. 5alpha-Androstane-3beta,17beta-diol was less efficiently 6alpha-hydroxylated, and 5alpha-androstane-3alpha,17beta-diol was an inefficient substrate. The addition of a variety of inhibitors of cytochrome P450 monooxygenases to the incubation mixtures did not diminish significantly the 6alpha-hydroxylation of 5alpha-pregnan-3beta-ol-20-one, findings consistent with those of other investigators who suggested that human saturated steroid 6alpha-hydroxylase (of human prostate) is not a cytochrome P450.

5-Alpha-dihydroprogesterone formation in human placenta from 5alpha-pregnan-3beta/alpha-ol-20-ones and 5-pregnan-3beta-yl-20-one sulfate.

5Alpha-dihydroprogesterone (5alpha-DHP) is the immediate precursor of 5alpha-pregnan-3alpha-ol-20-one, a potent anxiolytic/anesthetic agent in all vertebrate animals tested, including humans. The levels of 5alpha-DHP in the plasma of pregnant women are very high; and during the third trimester of pregnancy, the blood production rate of this steroid may exceed 100 mg/24 h. 5Alpha-DHP in maternal plasma, however, cannot be accounted for totally by the metabolism of maternal plasma progesterone. This study was conducted to evaluate the possibility that 5alpha-DHP is synthesized in placenta from 5alpha-pregnan-3alpha/beta-ol-20-ones delivered to the trophoblast via the fetal umbilical blood. In incubations of placental minces with radiolabelled 5alpha-pregnan-3alpha/beta-ol-20-ones, there is extensive epimerization and the intermediate, 5alpha-DHP, is the major product. In other incubations, 5alpha-pregnan-3beta-ol-20-one-sulfate was hydrolysed and the liberated 5alpha-pregnan-3beta-ol-20-one was converted to 5alpha-DHP by homogenates of placental tissue, but 5alpha-pregnan-3beta-ol-20-one-sulfate was not. The oxidation of 5alpha-pregnan-3alpha/beta-ol-20-ones was concentrated in microsome-enriched preparations of placental tissue and the apparent Kms for 5alpha-pregnan-3alpha-ol-20-one and 5alpha-pregnan-3beta-ol-20-one were 3.6 microM and 78 nM, respectively. The Vmaxs for 5alpha-DHP formation from 5alpha-pregnan-3alpha-ol-20-one and 5alpha-pregnan-3beta-ol-20-one were, respectively, 336 pmol/min/mg protein and 9.7 nmol/min/mg protein. These oxidation reactions were supported by both NAD+ and NADP+. We suggest that progesterone, which enters the umbilical circulation from its site of synthesis in the syncytiotrophoblast, is metabolized in the fetus to 5alpha-pregnan-3alpha/beta-ol-ones and to 5alpha-pregnan-3alpha/beta-yl-20-one sulfates. These metabolites of progesterone, 5alpha-pregnan-3alpha/beta-ol-20-one and 5alpha-pregnan-3beta-yl-20-one sulfate, formed in the fetus, serve as plasma-borne substrates for trophoblast formation of 5alpha-DHP. Because of the hemochorioendothelial nature of human placentation, 5alpha-DHP secreted from the trophoblast will preferentially enter the maternal compartment, thus constituting a maternal plasma progesterone-independent source of 5alpha-DHP.

Metabolism of 5 alpha-dihydroprogesterone in women and men: 3 beta- and 3 alpha-,6 alpha-dihydroxy-5 alpha-pregnan-20-ones are major urinary metabolites.

The metabolism of 5 alpha-dihydroprogesterone (5 alpha-DHP) in women and men was evaluated by defining the pattern and identity of selected metabolites excreted in urine after the iv infusion of radiolabeled 5 alpha-DHP. Virtually all of the radioactivity in urine (approximately 37% of the administered dose) was excreted within 72 h. Quantitatively, the 2 major urinary metabolites of 5 alpha-DHP in each of 13 studies conducted in 7 women and 2 men were 3 beta,6 alpha-dihydroxy-5 alpha-pregnan-20-one and 5 alpha-pregnane-3 alpha,20 alpha-diol, which could be extracted after beta-glucuronidase, but not solvolysis, treatment of the urine. Radiolabeled 3 alpha,6 alpha dihydroxy-5 alpha-pregnan-20-one (glucuronoside), in lesser amounts, also was identified in the urine of each subject. The 3 alpha/beta, 6 alpha-dihydroxy-5 alpha-pregnan-20-ones arise through specific extrahepatic pathways of progesterone/5 alpha-DHP metabolism. These metabolites are not the products of the enzyme reaction catalyzed by the cytochrome P450 steroid 6 alpha-hydroxylase of human liver (and other tissues), which affects the 6 alpha-hydroxylation of C19- and C21-delta 4-3-ketosteroids (e.g., progesterone, testosterone, and cortisol), but does not act upon 5 alpha-reduced steroids. Moreover, the steroid 5 alpha-reductases do not act upon 6 alpha-hydroxy-delta 4-3-ketosteroids. In addition, the 6 alpha-hydroxylation of 5 alpha-reduced-3 alpha/beta-hydroxysteroids is not demonstrable in adult liver tissue. Rather, the formation of 6 alpha-hydroxylated-5 alpha-pregnane-3 alpha/beta-ol-20-ones is indicative of an extrahepatic pathway of progesterone metabolism, viz. progesterone-->5 alpha-DHP-->5 alpha-pregnan-3 beta/alpha-ol-20-one(s)-->3 beta/alpha,6 alpha-dihydroxy-5 alpha-pregnan-20-one(s), in which 5 alpha-pregnan-3 alpha/beta-ol-20-ones are metabolized by an enzyme(s) that catalyzes the 6 alpha-hydroxylation of saturated substrates. There are important differences among mammalian species in the enzymes that catalyze the C-6-hydroxylation of 5 alpha-reduced C19- and C(21)-3 beta/alpha-hydroxysteroids, but in all species studied, these enzymatic reactions are the final steps in the extrahepatic inactivation of 5 alpha-reduced bioactive metabolites of progesterone (or testosterone).

The metabolic disposition of plasma 5 alpha-dihydroprogesterone (5 alpha-pregnane-3,20-dione) in women and men.

This study was conducted 1) to ascertain whether the high levels of plasma 5 alpha-dihydroprogesterone (5 alpha DHP) during the luteal phase of the human ovarian cycle and pregnancy are attributable to high rates of production or, alternatively, low rates of clearance, and 2) to estimate the relative distribution of the irreversible metabolism of 5 alpha DHP, i.e. hepatic compared with extrahepatic clearance of plasma 5 alpha DHP. The concentration of 5 alpha DHP in plasma of women during the luteal phase of the ovarian cycle and pregnancy is very high, viz. 12-40% that of progesterone. Thus, a potentially large source of steroid precursor is available for the formation of bioactive 5 alpha-pregnanolone metabolites. We found that the MCR of 5 alpha DHP in women and men is 4187 +/- 312 L plasma/24 h (range, 3181-5506; n = 6). The MCR of 5 alpha DHP as a function of body surface area was 2406 +/- 240 L/24 h.m2. The MCR of 5 alpha DHP, therefore, is the greatest of any steroid reported, except for that of the catechol estrogens, which are metabolized intravascularly by erythrocyte catechol-O-methyltransferase. Based on estimated rates of liver plasma flow (1500 L/24 h) and hepatic extraction (75-85%) of lipophilic steroids that are not specifically bound in plasma with high affinity to binding proteins as determined by other investigators (e.g. 5 alpha DHP), we estimate that approximately 1200 L plasma/24 h are cleared of 5 alpha DHP by liver and approximately 2800 L plasma/24 h are cleared of 5 alpha DHP (70%) by metabolism in extrahepatic tissues. Thus, 5 alpha DHP can serve as a precursor for bioactive 5 alpha-pregnanolone(s).

A rabbit model for bacteria-induced preterm pregnancy loss.

Bacterial infection has been implicated in premature labor in humans. To elucidate mechanisms and potential intervention strategies, we sought to develop a model of infection-induced pregnancy loss in rabbits. On day 21 (70% of gestation), each uterine horn was inoculated hysteroscopically with 0.2 ml containing saline solution of 10(6) cfu Escherichia coli or Bacteroides bivius or Fusobacterium necrophorum. Fetal viability was assessed. Animals were sacrificed at various times or as delivery occurred. Serum progesterone and amniotic fluid prostaglandins were measured. Cultures and histologic sections were prepared. Compared with the saline solution group, E coli and F. necrophorum-inoculated rabbits were significantly more likely to deliver (16 of 16 and six of seven with mean times of 31.9 +/- 10.7 and 28.3 +/- 11.5 hours, respectively for E. coli and F. necrophorum). Positive amniotic fluid cultures for the E. coli group were found in 11 of 12 (92%) and for the F. necrophorum group in three of three cases (100%). Histologic inflammation was seen heavily in both the E. coli and F. necrophorum groups, whereas it was absent in the saline solution group. Inoculation with B. bivius led to a much lower pregnancy loss rate (eight of 32) and less histologic inflammation despite positive uterine cultures in most animals. This model may provide an opportunity to determine mechanisms of clinical or subclinical intraamniotic infection and to test intervention strategies.

Reclosure of disrupted abdominal incisions.

We evaluated prospectively a technique of delayed reclosure of disrupted abdominal incisions. Forty-one consecutive postoperative obstetric and gynecologic patients with abdominal incisions that had opened because of infection, hematoma, or seroma and had intact fascia participated in the study. All wounds were first managed identically, with surgical drainage and debridement, for a minimum of 4 days. The patients then were randomized to either wound reclosure by a standardized en bloc technique (35) or healing by second intention (six). Reclosure was successful in 30 of 35 cases (85.7%). The mean time to complete healing was 15.8 days in successful cases, 67.2 days in failed cases, and 23.2 days for all patients who were reclosed. Failure to heal after reclosure was due to subcutaneous infection in two patients and seroma in three; these women were significantly heavier than those in whom reclosure was successful. There were no other major complications of wound reclosure. Patients randomized to healing by second intention required a mean of 71.8 days of wound care. The time to complete healing in the wound-reclosure group was significantly shorter compared with the group that healed by second intention (P = .002, log rank test). We conclude that en bloc reclosure of disrupted surgical incisions, compared with nonsurgical treatment, significantly decreases the time required for wound healing and has minimal morbidity.

Autoimmune disease in pregnancy.

Autoimmunity, whether present in a recognized syndrome such as systemic lupus erythematosus or represented by the production of subclasses of autoantibodies, adversely affects reproduction. While fertility of patients with autoimmune disorders is generally unimpaired, important exceptions exist. Recent data regarding the impact of intercurrent pregnancy upon women with SLE suggest that the overall course of this disorder is not affected. The impact of SLE and related autoimmune phenomena during pregnancy primarily relates to adverse fetal outcome. Pregnancy wastage is excessive, and premature delivery and poor fetal growth are commonly encountered. The occurrence of fetal complications correlates with the level of maternal disease activity and the presence of specific autoantibodies. Management of pregnancy complicated by SLE or the production of autoantibodies associated with poor reproductive outcome should be directed at maintaining maternal disease quiescence. The adverse effect of the maternal disorder on fetal growth and development far outweighs actual or theoretical risks attributable to maternal drug therapy.

Evaluation of the atypical Pap smear.

Two hundred thirty-six consecutively referred patients with "atypical" but not dysplastic Pap smears were evaluated by colposcopy and directed biopsies to assess the significance of this ambiguous result. Additionally the histologic diagnosis was compared with the results obtained by repetition of the Pap smear, interpretation of cervigrams, and the visual impression of the coloposcopist to evaluate the accuracy of these three modalities as intermediate screening procedures. Fifty-eight patients (25%) had biopsy-proved cervical intraepithelial neoplasia. Repeat Pap smears identified only 17% of these patients. Colposcopists noted atypical transformation zones in 97% of the patients with cervical intraepithelial neoplasia. Cervigrams identified 81% of the cervical intraepithelial neoplastic lesions but had a 15% method failure (uninterpretable). The time-honored tradition of repeating atypical smears before definitive diagnostic procedures are performed is to be condemned. Neither colposcopy nor cervicography was judged to be an ideal intermediate screening procedure, but both were superior to Pap smear repetition.

Cervical intraepithelial neoplasia in adolescents.

Three hundred and eleven adolescent patients with abnormal Pap smears were referred for evaluation. Two hundred and ninety-three were evaluated with colposcopy and directed biopsies. Fourteen percent had normal findings, 42% CIN I, 22% CIN II, and 22% CIN III. The distribution of pathologic findings was similar to that in an adult population in the same clinic except that no invasive carcinomas were found in our adolescents. Since there was a predominance of exocervical lesions, only 3% of the patients required diagnostic conization. Ninety-four percent of the adolescents were treated by cryotherapy as compared to 68% of the adults. Since adolescents have significant cervical intraepithelial neoplasia, an abnormal Pap smear should be evaluated and a tissue diagnosis obtained. Outpatient therapy is well suited for the majority of teenagers because the lesions are commonly confined to the exocervix.

Comparison of amniotic fluid lung maturity profiles in paired vaginal and amniocentesis specimens.

Amniotic fluid was obtained by transvaginal amniocentesis from 27 pregnant women in the third trimester. Subsequent to amniocentesis, membranes were ruptured and vaginal pool amniotic fluid was taken by bulb aspiration. The samples were analyzed for lung maturity profile, consisting of the lecithin/sphingomyelin (L/S) ratio and the percentages of phosphatidylinositol and phosphatidylglycerol. The L/S ratio was higher in the vaginal pool than in the amniotic sac in 22% of the paired samples. Similarly, the percentage of phosphatidylinositol was greater in the vaginal pool than in the amniotic sac in 48%. Phosphatidylglycerol, however, is invariably present in the amniotic sac when it is detected in the vaginal pool. The possible usefulness of these results in the management of patients with premature rupture of membranes is discussed.