Noelle C. Bowdler

Behavioral effects of aluminum ingestion on animal and human subjects.

Abnormally high brain aluminum concentrations have been detected in hemodialysis patients who died of an unexplained encephalopathy. As a result, this study was undertaken to examine whether the ingestion of aluminum produces behavioral aberrations in non-dialysed human subjects and rats with ostensibly normal renal function. Rats were fed AlCl3 by intubation in varying doses, and tests measuring learning ability, visual temporal acuity, motor coordination and activity were administered. It was found that orally ingested aluminum is absorbed by rats and deposited in the brain. High brain aluminum levels are associated with rapid general activity, decreased ability to maintain roto-rod activity, and increased sensitivity to flicker. Behavioral tests were also given to elderly human subjects and performance correlated with serum aluminum level. High serum levels of aluminum in elderly humans are associated with impaired visuo-motor coordination, poor long-term memory, and increased sensitivity to flicker.

The association between manual removal of the placenta and postpartum endometritis following vaginal delivery

Objective To determine whether manual removal of the placenta after vaginal delivery is a risk factor for postpartum endometritis. Methods A retrospective cohort study of vaginal deliveries compared 1052 patients who had manual removal of the placenta with 1085 patients whose placentas delivered spontaneously. Subjects were selected randomly from the 25,687 vaginal deliveries at the University of Iowa Hospitals during 1979–1992. The presence of endometritis was determined using information in medical records. The data were analyzed using odds ratios (OR) and multiple logistic regression. Results After controlling for confounding variables, manual removal of the placenta was associated with postpartum endometritis (adjusted OR 2.9, 95% confidence interval [CI] 1.7–4.9). Other risk factors for endometritis included maternal age less than 17 years (OR 3.3, 95% CI 1.5–7.2), postpartum anemia (OR 2.9, 95% CI 1.9–4.5), and membranes ruptured longer than 24 hours (OR 2.5, 95% CI 1.4–4.3). Conclusions Manual removal of the placenta is a risk factor for postpartum endometritis after vaginal delivery.

Predictors of neonatal resuscitation, low Apgar scores, and umbilical artery pH among growth-restricted neonates.

Objective To identify risk factors associated with poorer immediate neonatal outcomes among growth-restricted neonates. Methods Records of all 530 growth-restricted neonates born between January 1989 and February 1995 were reviewed. Outcomes included resuscitation measures, Apgar scores, and umbilical blood gas values. Neonates were assigned to one of six anesthetic groups, and outcomes were compared. Predictors of poorer outcomes were examined using logistic and linear regression. Results Neonates exposed to general anesthesia were more likely to be intubated (37.9% versus 4.1%, P < .001, Pearson χ2) and had lower mean 1- (4.0 versus 7.0) and 5-minute (6.5 versus 8.4) Apgar scores (P < .01, Scheffé) than those in all other anesthetic groups. They also had significantly lower umbilical artery (UA) pH values than neonates who received nalbuphine, epidural, or no anesthesia (7.21 versus 7.28, 7.26, 7.29, respectively; P < .01, Scheffé). Factors that significantly and independently predicted intubation among all neonates included exposure to general anesthesia (odds ratio [OR] 4.1; 95% confidence interval [CI] 1.9, 8.9) and lower infant weight (OR 10.1 per kg decrease; CI 5.1, 20). Factors predicting UA pH at most 7.15 included preeclampsia (OR 3.0; CI 1.5, 5.9) and older maternal age (OR 1.3 per 5 years; CI 1.02, 1.64); vertex delivery (OR 0.5; CI 0.2, 0.9) was protective. Factors predicting a 5-minute Apgar less than 7 were meconium (OR 1.5 per category going from none to terminal to light to heavy; CI 1.04, 2.3), general anesthesia (OR 6.9; CI 2.6, 18.2), lower infant weight (OR 16.5 per kg decrease; CI 7.8, 34.5), and vaginal breech delivery (OR 7.0; CI 1.8, 28.6); cesarean delivery (OR 0.2; CI 0.08, 0.66) was protective. Spontaneous vertex delivery raised the UA pH, and preeclampsia, amnioinfusion, breech delivery, and general anesthesia significantly and independently lowered the UA pH among all neonates. For infants delivered by cesarean, “fetal distress,” preeclampsia, previous spontaneous abortion, failed forceps use, and nalbuphine significantly and independently predicted lower UA pH. Conclusion Risk factors for poorer immediate neonatal outcomes among growth-restricted neonates include preeclampsia, fetal distress, breech delivery, forceps use, nalbuphine during labor, lower infant weight, and general anesthesia.

Age as a Factor Affecting Erythrocyte Osmotic Fragility in Males

Osmotic fragility and erythrocyte dimensions were measured in 40 normal males between the ages of 18 and 78 years. The principal independent variables correlating with osmotic fragility were mean cell haemoglobin concentration and the age of the donor. The age-related effect was shown to increase both the mean fragility of the cells and the variability of the fragilities of the cells within the individual blood sample. The physical basis for the change is an increase in the degree of isometric sphering of the erythrocytes at isotonicity. The change in shape does not appear sufficient to affect capillary perfusion significantly in normal subjects, but suggests that cell shape will increase the vulnerability of the elderly to abnormalities of the microvasculature.

Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise.

The maternal cardiovascular system undergoes hemodynamic changes during pregnancy via angiogenesis and vasodilation to ensure adequate perfusion of the placenta. Improper vascularization at the maternal-fetal interface can cause pregnancy complications and poor fetal outcomes. Recent evidence indicates that small conductance Ca(2+)-activated K(+) channel subtype 3 (SK3) contributes to vascular remodeling during pregnancy, and we hypothesized that abnormal SK3 channel expression would alter the ability of the maternal cardiovascular system to adapt to pregnancy demands and lead to poor fetal outcomes. We investigated this hypothesis using transgenic Kcnn3(tm1Jpad)/Kcnn3(tm1Jpad) (SK3(T/T)) mice that overexpress the channel. Isolated pressurized uterine arteries from nonpregnant transgenic SK3(T/T) mice had larger basal diameters and decreased agonist-induced constriction than those from their wild-type counterparts; however, non-receptor-mediated depolarization remained intact. In addition to vascular changes, heart rates and ejection fraction were increased, whereas end systolic volume was reduced in SK3(T/T) mice compared with their wild-type littermates. Uterine sonography of the fetuses on pregnancy day 14 showed a significant decrease in fetal size in SK3(T/T) compared with wild-type mice; thus, SK3(T/T) mice displayed an intrauterine growth-restricted phenotype. The SK3(T/T) mice showed decreased placental thicknesses and higher incidence of fetal loss, losing over half of their complement of pups by midgestation. These results establish that the SK3 channel contributes to both maternal and fetal outcomes during pregnancy and point to the importance of SK3 channel regulation in maintaining a healthy pregnancy.

Surgical site infections and cellulitis after abdominal hysterectomy

OBJECTIVES To identify risk factors for and outcomes of surgical site infections and cellulitis after abdominal hysterectomies. STUDY DESIGN We used logistic regression analysis to analyze data from a case-control study of 1104 patients undergoing abdominal hysterectomies at a university hospital between Jan. 1, 2007 and Dec. 30, 2010. RESULTS Factors significantly associated with surgical site infections and with cellulitis were: pulmonary disease, operations done in Main Operating Room East, and seroma. Body mass index >35, no private insurance, and fluid and electrolyte disorders were risk factors for surgical site infections. The mean prophylactic dose of cefazolin was significantly higher for controls than for patients with surgical site infections. Preoperative showers with Hibiclens (Molnlycke Health Care US, LLC, Norcross, GA) and cefazolin prophylaxis were associated with a significantly decreased cellulitis risk. Surgical site infections and cellulitis were significantly associated with readmissions and return visits and surgical site infections were associated with reoperations. CONCLUSION Preoperative showers, antimicrobial prophylaxis, surgical techniques preventing seromas, and the operating room environment may affect the risk of surgical site infections and cellulitis after abdominal hysterectomies.

Lipopolysaccharide-induced maternal inflammation induces direct placental injury without alteration in placental blood flow and induces a secondary fetal intestinal injury that persists into adulthood

Premature birth complicates 10%‐12% of deliveries. Infection and inflammation are the most common etiologies and are associated with increased offspring morbidity and mortality. We hypothesize that lipopolysaccharide (LPS)‐induced maternal inflammation causes direct placenta injury and subsequent injury to the fetal intestine.

Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice

Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated throughout human pregnancies complicated by preeclampsia (PE), and AVP infusion throughout gestation is sufficient to induce the major phenotypes of PE in mice. Thus, we hypothesized a role for AVP in the pathogenesis of PE. AVP infusion into pregnant C57BL/6J mice resulted in hypertension, renal glomerular endotheliosis, intrauterine growth restriction, decreased placental growth factor (PGF), altered placental morphology, placental oxidative stress, and placental gene expression consistent with human PE. Interestingly, these changes occurred despite a lack of placental hypoxia or elevations in placental fms-like tyrosine kinase-1 (FLT1). Coinfusion of AVP receptor antagonists and time-restricted infusion of AVP uncovered a mid-gestational role for the AVPR1A receptor in the observed renal pathologies, versus mid- and late-gestational roles for the AVPR2 receptor in the blood pressure and fetal phenotypes. These findings demonstrate that AVP is sufficient to initiate phenotypes of PE in the absence of placental hypoxia, and indicate that AVP may mechanistically (independently, and possibly synergistically with hypoxia) contribute to the development of clinical signs of PE in specific subtypes of human PE. Additionally, they identify divergent and gestational time-specific signaling mechanisms that mediate the development of PE phenotypes in response to AVP.

Does leptin predict successful induction of labor

Obesity in pregnancy is becoming increasingly common and is associated with many pregnancy-related complications such as failed induction of labor (IOL). Leptin, an adipocytokine important in energy homeostasis, is found in higher levels in obese individuals. Leptin has also been demonstrated to have an inhibitory effect on myometrial contractility in vitro. We hypothesize that leptin may play a part in the mechanism of dysfunctional labor. Thus, we sought to compare the maternal plasma leptin levels in women that had a successful vaginal delivery post-IOL vs. those who had a C-section post-IOL.

Importance of the physical exam and in-office tests in the evaluation of vulvovaginal irritation

Background: Vulvovaginal irritation is a common gynecologic complaint. A number of factors may lead to a trial of therapy without undertaking a physical exam or diagnostic testing. Case Report: A 45 year-old woman presented to our colposcopy clinic for evaluation of an abnormal Papanicolaou (Pap) test. She reported a one month history of vulvovaginal irritation, for which Premarin vaginal cream had been empirically prescribed. Examination of the external genitalia showed ulcers and erythema of the labia minora. Speculum exam was deferred because of the patient’s discomfort. Wet mount microscopy from a vaginal swab revealed evidence of Trichomonas vaginalis, bacterial vaginosis (BV), and yeast. A swab of the ulcers was sent for herpes simplex virus (HSV) polymerase chain reaction (PCR); this confirmed HSV-2. Treatment was initiated for each of these conditions, and the patient returned for colposcopy 21 days later. Conclusion: This case illustrates the importance of the physical exam when evaluating a complaint of vulvovaginal irritation. In many cases, the cause(s) of vulvovaginal irritation can be identified based on physical exam findings and in-office testing with wet mount microscopy, vaginal pH, and the amine “whiff” test. In some cases, additional testing may be required to establish or confirm a diagnosis. Accurate diagnosis is essential not only to initiate appropriate therapy, but also to prevent the transmission of sexually transmitted infections. In some cases, this may decrease the delay in diagnosing vulvar gynecologic malignancies.