Barry S. Block

Intrauterine asphyxia and the breakdown of physiologic circulatory compensation in fetal sheep

In response to acute hypoxemia, the fetus invokes physiologic compensatory mechanisms that cause a preferential redistribution of the circulation to sustain the brain, heart, and adrenal gland and maintain blood flow to the placenta. These mechanisms are available for a limited time and eventually the fetus is no longer able to maintain preferential perfusion and decompensation occurs. To identify the relationship between hypoxemia with severe acidemia and the breakdown of circulatory compensation, we decreased uterine blood flow in 10 chronically instrumented pregnant sheep. We measured fetal blood gases and pH, arterial and central venous pressures, heart rate, combined ventricular output, and regional blood flow distribution during hypoxemia with severe acidemia and when a fixed-baseline sustained bradycardia (agonal) heart rate pattern developed. Hypoxemia with severe acidemia was characterized by markedly decreased blood flow to most organs; however, the preferential perfusion of the brain, heart, adrenal gland, and placenta was still present. An agonal heart rate pattern was characterized by complete cardiovascular collapse. This study demonstrates that circulatory compensation is present in fetal sheep affected by deficiency of oxygen delivery despite hypoxemia with severe acidemia.

Clostridium difficile-associated diarrhea follows perioperative prophylaxis with cefoxitin

Clostridium difficile-associated diarrhea during prolonged therapy of obstetric and gynecologic infections is known to occur with use of all classes of antibiotics except vancomycin and the aminoglycosides. We present 11 cases of C. difficile-associated diarrhea which followed a short course of perioperative prophylaxis with cefoxitin during a 1-year period. Nine of the cases of C. difficile-associated diarrhea were among 162 women who received cefoxitin perioperative prophylaxis for cesarean section or hysterectomy, but none occurred in 85 women who received one of four other antibiotics for perioperative prophylaxis (p = 0.024, Fishers exact test). The two other occurrences of C. difficile-associated diarrhea following perioperative prophylaxis with cefoxitin were in women who underwent exploratory laparotomy. We conclude that C. difficile-associated diarrhea is related to perioperative prophylaxis with cefoxitin.

Intrauterine growth retardation and the circulatory responses to acute hypoxemia in fetal sheep

Intrauterine growth retardation has been produced experimentally by umbilical placental embolization for 9 days (early intrauterine growth retardation) in pregnant sheep. Fetuses with early intrauterine growth retardation had a 20% decrease in mean body weight and 33% decrease in placental blood flow. However, the regional blood flow distribution was not significantly different at rest between the embolized and normally grown fetuses despite the 39% decrease in fetal arterial oxygen content. The purpose of this study was to determine the circulatory responses to acute hypoxemic stress in the early development of intrauterine growth retardation. We found that the regional blood flow distribution was not significantly different during imposed acute hypoxemia between the seven fetuses with early intrauterine growth retardation and seven nonembolized normally grown fetuses. We conclude that growth-retarded fetuses are able to meet basal metabolic oxygen requirements and to respond normally to imposed acute hypoxemia until the placental circulatory reserve capacity is depleted.

Comparison of human chorionic gonadotropin regression in molar pregnancies and post-molar nonmetastatic gestational trophoblastic neoplasia☆

The rate of regression of the beta subunit of human chorionic gonadotropin in patients successfully treated by single-agent chemotherapy with methotrexate (MTX) for postmolar nonmetastatic gestational trophoblastic neoplasia (NMGTN) has not previously been described. In 21 patients with NMGTN treated with MTX, the rate of regression was determined. Nineteen patients had a log-exponential disappearance of serum beta-hCG titers within 100 days. There was a 50% probability of a negative titer at 50 days. Two patients had plateauing titers within 63 days after therapy. There was no difference in beta-hCG disappearance whether MTX with citrovorum factor or MTX alone was administered. Also, the regression rate of beta-hCG titer in the treated patients was compared to 63 patients with spontaneous decline of titers postevacuation of trophoblastic disease. In the postevacuation group there was a 50% probability at 49 days of negative serum titers. All 63 patients had negative titers within 105 days after evacuation.

The effect of the α-emitting radionuclide lead-212 on human ovarian carcinoma: A potential new form of therapy

To improve response and survival of patients with ovarian carcinoma noncross-resistant forms of therapy must be developed. alpha-emitting radionuclides may be therapeutically useful since they can directly ionize with energies of 5 to 9 MeV, penetrate only a few cell diameters, and transfer a high amount of energy. The purpose of this study was to determine the effect of the alpha-emitter, lead-212 (212Pb), complexed to sulfur in a nude athymic mouse model (NIH:OVCAR-3) containing human ascites and solid epithelial ovarian carcinoma. Thirty-six nude mice 28 to 32 days old were injected with 10(7) to 10(8) carcinoma cells from donor mice. After 4 weeks, six groups of six nu/nu athymic BALB-C mice were intraperitoneally injected with 70, 50, 20, 5 microCi of 212Pb sulfur colloid, sulfur colloid, or saline. Tumor necrosis with a decrease in ascites and a dose-related survival were noted with doses of 50, 20, and 5 microCi. With 70 microCi acute gastrointestinal toxicity developed. These experiments form the basis for further investigations and the development of alpha-emitting radiocolloids which may be of therapeutic efficacy in the treatment of intraperitoneal ovarian carcinoma.

Abortion hysterectomy for gynecologic pathology

Abortion hysterectomy has been discredited as the method of performing simultaneous pregnancy termination and elective sterilization for women with undesired pregnancies who simultaneously wish to end their child-bearing potential. The procedure continues to be advocated, however, for cases in which there is an underlying gynecologic pathologic condition. The morbidity of this procedure has not been directly compared with that for indicated hysterectomy in nonpregnant women. Between January 1976 and January 1987, 50 patients underwent abortion hysterectomy at The University of Chicago. The morbidity and mortality rates of these patients were compared with those of 50 premenopausal nonpregnant women undergoing abdominal hysterectomy for gynecologic pathologic status. There was no statistically significant different between the groups in the duration of surgery, estimated blood loss, or infectious morbidity. No operative site infections or other adverse sequelae were noted at the time of final postoperative examination. These data support the relative safety of abdominal abortion hysterectomy for women with undesired pregnancy in whom hysterectomy is indicated for an underlying gynecologic pathologic condition.

Understanding and eliminating errors in perinatal research

Research studies published in the scientific literature have had a rapid impact on medical practice, especially in clinical obstetrics. Recently, incentives to control medical costs without sacrificing the quality of care have placed increased importance on studies that truly demonstrate clinical effectiveness. In addition, there are ethical concerns that improperly designed or conducted studies adversely affect medical practice and place patients at unnecessary risk. This article summarizes potential sources of error and encourages the valid interpretation of the results and conclusions of experimental studies by making four suggestions: (1) the errors and limitations that may be present in the methodology should be described and explanations given how the errors might have affected the results and why the limitations are acceptable; (2) the methods selected should allow an answer to the question proposed; (3) the investigator should verify that the appropriate statistical test is used; and (4) when unexpected or hard to explain results are found, verification before publication should be undertaken.