Catherine M. Craven

Decidual spiral artery remodelling begins before cellular interaction with cytotrophoblasts

Endometrial arteries undergo structural alterations during pregnancy to increase blood flow to the intervillous space. It is hypothesized that physiologic change in decidual arteries is similar to vascular remodelling seen in other organs. Histologic features of spiral arteries in secretory endometrial biopsies were compared blindly to decidual arteries from elective abortions. Similar sections were stained for trophoblastic and vascular antigens. Spiral arteries in endometrium from ectopic (tubal) and intrauterine pregnancies were compared also. Evidence of decidual endothelial activation was sought using antibodies to vascular cell adhesion molecule (VCAM-1). As expected, decidual arteries were significantly different than arteries in secretory endometrium: there was more endothelial basophilia, vacuolation, and arterial dilation in early pregnancy. Some vessels had disorganized or hypertrophied smooth muscle layers. Similar structural alterations were seen in endometrium of ectopic pregnancies, and in the decidua parietalis of intrauterine pregnancies. Immunohistochemical studies confirmed that these alterations occurred in the absence of cellular interaction with extravillous cytotrophoblasts. Independently of trophoblasts, decidual endothelial cells expressed VCAM-1. It is concluded that the initial stages of physiologic change are characterized by vascular remodelling, which occur in the absence of trophoblast invasion of the spiral arteries. Arterial modifications in decidua begin as a maternal response to pregnancy.

Angiotensinogen T235 expression is elevated in decidual spiral arteries.

Preeclampsia is associated with a common molecular variant of angiotensinogen (Met235Thr). This variant is in tight linkage disequilibrium with a mutation in the angiotensinogen promoter, G(-6)A, which leads to elevated expression in vitro. Since angiotensin II levels could play a role in atherotic changes of the uterine spiral arteries associated with preeclampsia, we investigated angiotensinogen expression in the first trimester uterus. We localized angiotensinogen transcription in uterine decidua using in situ reverse transcription PCR. We then compared decidual T235 expression levels to M235 levels in heterozygous women using an allele-specific ligation assay and a single nucleotide primer extension assay. In human decidua, angiotensinogen is expressed only in spiral artery smooth muscle cells. Heterozygous women have significantly elevated expression of the T235 allele compared to the M235 allele (P < 0.0001). These observations suggest that elevated expression of the T235 allele in decidual spiral arteries may cause first trimester atherotic changes leading to preeclampsia.

The effect of combined immunosuppression with systemic low-dose cyclosporin and topical fluocinolone acetonide on the survival of rat hind- limb allografts

Sixty rat hind-limb allotransplantations across strong histocompatibility barriers were performed. Group I (isograft controls), (Lewis-Brown-Norway [LBN] to LBN) limb transplantations were performed; Group II (rejection controls), LBN limbs transplanted to Lewis rat LEW recipients with no immunosuppressive treatment; Group III (steroid group), fluocinolone acetonide (50 muml;/ml) was applied topically; Group IV (cyclosporine group), 4 mg/kg of cyclosporine was administered subcutaneously daily; Group V (combination group), combined systemic cyclosporine with topical fluocinolone acetonide was administered daily. Group II: Limb rejection was present on the fourth day. Group III: Limb survival was extended for 3 weeks with no signs of skin rejection in 75% of animals. Group IV: Rejection was complete at 3 weeks. Group V: Limbs survived to 6 weeks. Topical steroid prevented skin rejection and delayed rejection of other components of the composite allograft. Combined treatment of topical steroid and low cyclosporine doses significantly extended survival rate of limb allografts.Inceoglu S, Siemionow M, Chick L, Craven CM, Lister GD. The effect of combined immunosuppression with systemic low-dose cyclosporin and topical fluocinolone acetonide on the survival of rat hind-limb allografts. Ann Plast Surg 1994;33:57–65

Vascular rejection in cardiac transplantation: Histologic, immunopathologic, and ultrastructural features

Although the majority of rejection found in cardiac transplant biopsies is cellular in type, a variety of vascular alterations occur in cardiac biopsies, constituting different forms of rejection that can be recognized using light microscopic and immunopathologic criteria. In this report, pathologic aspects of the vascular alterations associated with vascular and mixed rejection of cardiac allografts are described in detail. Methods and controls used in this report are identical to those previously reported. The histologic, immunopathologic, and ultrastructural findings associated with vascular rejection and other vascular processes in cardiac allografts are discussed. The relationship of these findings to chronic allograft rejection and potential pathogenetic mechanisms of these vascular changes are also detailed.

Maternal Smoking, Intrauterine Growth Restriction, and Placental Apoptosis

AbstractPregnant women who smoke are at greater risk of delivering a growth-restricted infant than nonsmoking mothers. We wanted to see if apoptosis could be involved in the mechanisms behind smoke-induced growth restriction, and our aim was to compare apoptosis in the placenta of smoking mothers giving birth to growth-restricted infants and nonsmoking mothers with infants of appropriate weight. The project was conducted at the Magee—Womens Hospital and Magee—Womens Research Institute, University of Pittsburgh, PA. Histological sections from 20 placentas were selected from smoking mothers who had given birth to small-for-gestational-age infants (birth weight ≤ 2 SD). The controls were gestational-age matched nonsmoking mothers with infants having appropriate-for-gestational-age weight. The TUNEL method was used to demonstrate DNA fragmentation in nuclei, and a monoclonal antibody M30, specific for a neo-epitope on cytokeratin 18, was used to identify apoptotic epithelial cells. The positive nuclei (TUNEL) and positive cells (M30-positive cytoplasm) were counted blindly both in villous tissue and in decidual/basal plate tissue. M30-positive cells in villous tissues were significantly increased in placentas from smoking mothers compared to nonsmoking mothers. When evaluated by the TUNEL method, the difference between the two groups of women was not significant. Our study shows that apoptosis was increased in the placentas of smoking mothers with growth-restricted infants. The difference between the two groups was mainly in the syncytiotrophoblast layer and in connection with perivillous fibrin deposition. Cigarette smoke with reduction in blood flow has previously been shown to increase apoptosis, and it is possible that this could be one of the mechanisms playing a role in the growth restriction.

Syncytiotrophoblastic fragments in first-trimester decidual veins: Evidence of placental perfusion by the maternal circulation early in pregnancy

OBJECTIVE To determine whether maternal placental perfusion occurs in the first trimester, this study compared veins in endometrium with those in decidua. We hypothesize that veins draining the placenta become dilated and contain syncytiotrophoblastic fragments. STUDY DESIGN Normal late-secretory endometrial biopsy specimens (n = 10) were compared with elective abortion decidua at 7 to 11 weeks (n = 100). Tissue sections were processed by routine staining and immunohistochemical studies. The cross sections of veins and glands were counted in 25 decidual biopsy specimens, and the number of syncytiotrophoblastic fragments in veins or glands was determined. Statistical significance by chi(2) or linear regression analysis was P <.05. RESULTS All sets of decidua had dilated veins; no secretory endometrium did. Intravenous syncytiotrophoblastic fragments were seen in 91 of 100 sets of decidua. There were more syncytial elements in veins (572/6845, 8.4%) than in glands (13/23,310, 0.06%) (P <.001). CONCLUSION Decidual veins were distended and contained syncytiotrophoblastic fragments, consistent with maternal intervillous perfusion in the first trimester.

Granulocytic sarcoma of the prostate. Two cases causing urinary obstruction

Two cases of patients with prostatic granulocytic sarcoma in whom urinary obstruction occurred are presented. The diagnosis was made by tissue examination with hematoxylin and eosin and specific esterase stains. One patient had a myelodysplastic syndrome and the other patient had acute myeloblastic leukemia. In both cases the diagnosis of prostatic granulocytic sarcoma was unexpected. Granulocytic sarcomas should be considered in the differential diagnosis of urinary obstruction in patients with myeloperoliferative or myelodysplastic syndromes. Cancer 59:142–146, 1987.

Fetal endothelial cells express vascular cell adhesion molecule in the setting of chorioamnionitis.

PROBLEM: In intrauterine infection, inflammatory mediators may be released into the fetal circulation prior to fetal infection. We hypothesize that, in chorioamnionitis, inflammation alters fetal blood vessels. To test this, fetal endothelial cells were examined for vascular cell adhesion molecule (VCAM).
 METHOD OF STUDY: Umbilical cords (n=9) from placentas with chorioamnionitis were immunostained for VCAM. Controls from preterm preeclamptic pregnancies (n=7) without histologic inflammation were selected, and matched for gestational age and method of delivery. VCAM sections were reviewed by a pathologist blinded to clinical diagnoses.
 RESULTS: All endothelial cells from each of the nine cords from placentas with chorioamnionitis had strong VCAM staining. Two of nine samples also had acute cord vasculitis. No cord endothelial cells from preeclamptic placentas demonstrated similar VCAM staining (p<0.01).
 CONCLUSION: Histologic chorioamnionitis was associated with VCAM expression of the umbilical cord vessels. In chorioamnionitis, inflammatory mediators may have entered the fetal circulation to activate endothelial cells. Intrauterine inflammation was not restricted to the chorioamnion, but also involved the fetal circulation.

Monitoring normal and aberrant electrocardiographic activity from an endotracheal tube: Comparison of the surface, esophageal, and tracheal electrocardiograms

Introduction. We designed an endotracheal (ET) tube with orthogonally spaced ECG cuff electrodes. This ET tube was evaluated in dogs and sheep to determine (1) whether ECGs recorded from our tube were sufficient to make accurate clinical decisions concerning heart rate and rhythm; and (2) whether metallic cuff electrodes in direct contact with the trachea could induce mucosal burn injury during episodes of defibrillation.Methods. Using experimental animals, we obtained ECGs from their tracheae and compared our findings with ECGs obtained from surface and esophageal electrodes. The electrical activity of the heart was modified by increasing the depth of anesthesia, occluding the left coronary artery, and administering beta-adrenergic drugs. Before the dogs were euthanized, they were subjected to episodes of transthoracic and intrathoracic defibrillation at energy levels of 200 to 400 J. A postmortem pathological examination of the trachea was performed to determine the incidence of mucosal burn injury.Results. Tracheal electrocardiography provided valid information on heart-rate monitoring and certain morphology profiles. The R-R, PR, QRS, and QT intervals measured from the trachea had a correlation of 1.0, 0.96, 0.83, and 0.98, respectively, when compared with the same intervals obtained from surface electrodes. Two tracheae subjected to intrathoracic defibrillation at >300 J revealed evidence of minor burn injury. Some localized epithelium loss was displayed in all tracheae; we attributed this to tracheal intubation.Conclusion. Tracheal electrocardiography may be useful in trauma patients who require intubation where injury precludes placement of chest ECG electrodes.AbstraktZiel. Wir entwarfen einen Endotrachealtubus (ET) mit rechtwinklig angeordneten EKG-Cuffelektroden. Dieser ET wurde bei Hunden und Schafen getestet, um zu bestimmen, Ob 1) die von unserem Tubus aufgenommenen EKG-Daten ausreichten, um exakte klinische Entscheidungen beziiglich Herzfrequenz und Rhythmus treffen zu konnen; 2) wahrend der Defibrillation metallische Cuffelektroden in direktem Kontakt mit der Trachea Verbrennungsschaden der Schleimhaut verursachen konnten.Methoden. Bei unseren Versuchstieren leiteten wir die EKGs von der Trachea ab und verglichen unsere Ergebnisse mit EKGs, die mit Oberflächen-und Ösophaguselektroden abgeleitet wurden. Wir modifizierten die elektrische Aktivitat des Herzens durch Narkosevertiefung, Verschluβ der linken Koronararterie und Gabe von etasympathomimetika. Vor ihrer Totung wurden die Hunde transthorakal und intrathorakal mit Energien von 200 bis 400 Joule defibrilliert. Postmortal untersuchten wir die Trachea histologisch, um die Inzidenz von Verbrennungsschaden der Schleimhaut zu bestimmen.Ergebnisse. Die tracheale Elektrokardiographie lieferte valide Informationen iiber die Herzfrequenz und gewisse morphologische Profile. Die RR-, PR-, QRS- und QT-Intervalle der Trachealableitung korrelierten mit den entsprechenden Intervallen der Oberflächenableitungen mit Koeffizienten von 1.0, 0.96, 0.83 und 0.98. Die Tracheae zweier Versuchstiere, die intrathorakaler Defibrillation mit >300 Joule unterworfen worden waren, zeigten geringe Verbrennungsschaden. Ortlich begrenzter Verlust von Trachealepithel trat in alien Tracheae auf; wir schrieben dies der Intubation zu.SchluBfolgerung. Die tracheale Elektrokardiographie konnte bei intubationspflichtigen Unfallpatienten, deren Verletzungen die Anlage von Brustelektroden ausschlieβen, nützlich sein.ResumenObjetivo. Disenamos un tubo endotraqueal (ET) con electrodos de ECG en manguito espaciados ortogonalmente. Este tubo ET fue evaluado en perros y ovejas para determinar (1) si los ECG obtenidos desde nuestro tubo eran suficientes para efectuar decisiones clinicas en relacion a la frecuencia y ritmo cardiacos; y (2) si los electrodos metalicos en manguito en contacto directo con la tràquea pudiesen inducir quemaduras de la mucosa durante episodios de defibrilacion.Mètodos. Usando animales experimentales, obtuvimos ECG a partir de sus tràqueas y los comparamos con ECG obtenidos desde electrodos de superficie y desde electrodos esofagicos. La actividad elèctrica cardiaca fue modificada cambiando la profundidad de la anestesia, ocluyendo la arteria coronaria izquierda, y administrando drogas betaadrenèrgicas. Antes de sacrificar los perros, ellos fueron objeto de episodios de defibrilacion transtroràcica e intratoracica con niveles de energia entre 200 y 400 joules. Se realizò examen patològico de la tràquea para determinar la incidencia de quemadura de la mucosa.Resultados. La electrocardiografia traqueal proporcionò informatiòn vàlida en relaciòn a monitorizaciòn de frecuencia cardiaca y algunos perfiles morfo`ogicos. Los intervalos R-R, PR, QRS, y QT medidos en la tràquea tuvieron correlaciones de 1.0, 0.96, 0.83, y 0.98, respectivamente, al ser comparados con los mismos intervalos medidos con electrodos de superficie. Dos traqueas sometidas a defibrilacion intratoracica con energia de 300 joules revelaron evidencia de quemaduras menores. Algun grado de `erdida localizada de epitelio fue observado en todas las traqueas; nosotros atribuimos esto a la intubatiòn traqueal.Conclusion. La electrocardiografia traqueal puede ser ùtil en pacientes traumatizados que requieran intubatiòn en quienes, debido a la injuria, sea poco factible la colocacion de electrodos de ECG en el tòrax.

Sudden death in a young athlete: a case report

A 19-year-old man had been recruited to play football for a university during his freshman year. He flew from his home at sea level to the campus, located at an altitude of more than 1500 meters. He then registered in the school’s athletic program and took the athletic department’s medical examination. The examination, performed by a team of physicians, included measurements of his height, weight, and blood pressure, with examination of his ears, nose, throat, cardiorespiratory systems, abdomen, urogenital system, nervous system, joints, and extremities. He was passed as &dquo;OK for contact sports&dquo; on each of the systems examined. Laboratory tests included a dipstick urinalysis, which was trace positive for protein, and a urine screen for substances of abuse and anabolic steroids, which was negative. The next morning, during a timed mile run with a group of teammates, he was unable to complete the final lap. He complained of being unable to catch his breath and of having leg cramps. He was dyspneic and appeared exhausted. The temperature on the field was in the mid-70s and the humidity was low. He was assisted into the training room where he collapsed with a cardiopulmonary arrest. Cardiopulmonary resuscitation was immediately begun and paramedics were summoned. Approximately 4 minutes later, when the paramedics arrived, he was still unresponsive, with an irregular cardiac rhythm. He was transported to the emergency department of a nearby hospital and was found to have a pulse of 136 beats per minute, with occasional premature ventricular contractions. His respiratory rate was 48 breaths per minute, blood pressure 122/54 mm Hg, and rectal temperature 37.8°C. He responded to painful stimuli with eye motion, but had no withdrawal response. His Glascow coma scorel9 was 4. Arterial blood gases, on 10 liters of oxygen administered through a facial mask, showed a pH of 6.78; pC02, 35.0 mm Hg; p02, 133.0 mm HG; HC03, 4.8 mmol/L. He was anemic: hemoglobin, 12.0 g/dL and hematocrit, 0.37 L/L. His white blood cell count was 38.2 x 10’/L with a left shift. A second