Weill Medical College Research Articles

Participation of the 27kDa heat shock protein (hsp27) in mid-trimester amniotic fluid: Ethnic variability and association with anti-inflammatory immunity

AMNIOTIC FLUID: ETHNIC VARIABILITY AND ASSOCIATION WITH ANTIINFLAMMATORY IMMUNITY SRIRAM C. PERNI, EMRE KARASAHIN, ROBIN B. KALISH, STEPHEN T. CHASEN, STEVEN S. WITKIN, Weill Medical College of Cornell University, Obstetrics and Gynecology, New York, New York OBJECTIVE: Modulation of pro-inflammatory immune responses during gestation is essential for pregnancy prolongation. The extracellular release of the 27 kDa heat shock protein (hsp27) induces anti-inflammatory immunity. However, the possible presence of hsp27 in amniotic fluid (AF) and its interaction with other AF components has not been determined. We investigated whether hsp27 was present in mid-trimester amniotic fluid and determined its relationship with other AF immuno-modulating components and with maternal ethnicity. STUDY DESIGN: 278 pregnant women with singleton gestations who presented for genetic amniocentesis were enrolled. Clara cell protein 16 (CCP16) and cortisol, two anti-inflammatory components of AF, as well as the cytokines interleukin (IL)-1b, IL-1 receptor antagonist (IL-1ra), IL-6, IL-13, and hsp27 were measured by ELISA. Mann-Whitney U tests and linear regression analysis were used for statistical analysis. RESULTS: Hsp27 was detected in all samples with a median (range) of 5.8 ng/ mL (0.2-43.3). Median AF hsp27 concentrations were higher in blacks (6.3 ng/ mL) than in whites (4.5 ng/mL) (P = .04). IL-1b was identified in 67.8% of the AFs with a median concentration of 13.8 pg/mL (1.0-92.8). AF concentrations of hsp27 were strongly negatively correlated with AF IL-1b concentrations (r = .4360, P ! .0001) and positively correlated with CCP16 (r = .2199, P = .0012) and cortisol (r = 0.1396, P = .04) levels. CCP16 concentrations were also negatively associated with IL-1b (r = .1753, P = .006), but not as strongly as hsp27. There was no relationship between cortisol and IL-1 b levels. There was no relationship between hsp27 levels and IL-1ra, IL-6, IL-13 concentrations or neonatal gender. CONCLUSION: Hsp27 is present in AF and contributes to the down-regulation of IL-1b-induced pro-inflammatory immunity during the mid-trimester. Whether differences in baseline hsp27 levels between blacks and whites contribute to observed ethnic variations in rates of preterm birth and neonatal morbidities remains to be determined. Supported by NIH HD41676. 568 UNEXPLAINED INTRAUTERINE FETAL DEATH IS ACCOMPANIED BY ACTIVATION OF COMPLEMENT KARINA RICHANI, ELEAZAR SOTO, JIMMY ESPINOZA, JYH KAE NIEN, TINNAKORN CHAIWORAPONGSA, JERRIE REFUERZO, SEAN BLACKWELL, SAMUEL EDWIN, MOSHE MAZOR, ROBERTO ROMERO, Wayne State University School of Medicine, Detroit, Michigan, Perinatology Research Branch, NICHD, NIH, DHHS, Bethesda, Maryland, Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, Michigan, Soroka University Medical Center, Beer Sheva, Israel, Israel OBJECTIVE: The complement system has recently been implicated in the mechanisms of fetal loss in the anti-phospholipid antibody syndrome (JCI 2003; 112:1644). We propose that complement activation may also be involved in other causes of intrauterine fetal death (IUFD) in the second and third trimesters of pregnancy. This study was conducted to determine if IUFD is associated with changes in maternal plasma C5a concentration, the most biologically relevant product generated during complement activation. STUDY DESIGN: A cross-sectional study was designed to include normal pregnant women (n = 60) and patients with IUFD (n = 60). The IUFD group was classified according to the cause of fetal death into: (a) unexplained (n = 44); (b) associated with preeclampsia (n = 8); and (c) chromosomal abnormality or major malformation (n = 8). The plasma concentration of C5a was measured by ELISA. Non-parametric statistics were used for analysis. RESULTS: (1) The median plasma concentration of C5a in patients with IUFD was significantly higher than that of normal pregnant women (median 16.05 ng/mL, range 4.59–402.52 ng/mL vs. median 11.64 ng/mL, range 1.22– 87.13 ng/mL, respectively; P! .001); (2) Among patients with IUFD, those with unexplained fetal death and fetal death with preeclampsia had a median plasma C5a concentration higher than that of normal pregnant women (P = .002 and P ! .001, respectively); (3) There was no significant difference in median plasma concentration of C5a between IUFD with congenital anomalies and normal pregnancy. CONCLUSION: Unexplained IUFD is accompanied by complement activation.

Ultrasound evaluation of abnormal umbilical cord coiling in second trimester of gestation as a predictor of adverse pregnancy outcome

TRIMESTER OF GESTATION AS A PREDICTOR OF ADVERSE PREGNANCY OUTCOME MLADEN PREDANIC, SRIRAM C. PERNI, STEPHEN T. CHASEN, REBECCA N. BAERGEN, FRANK A. CHERVENAK, Cornell University, Obstetrics and Gynecology, New York, New York, Weill Medical College of Cornell University, Obstetrics and Gynecology, New York, New York, Weill Medical College of Cornell University, Pathology and Laboratory Medicine, New York, New York OBJECTIVE: To evaluate the antenatal umbilical cord coiling index (aUCI) obtained during the fetal anatomical survey in the second trimester as a predictor of adverse antenatal and perinatal events. STUDY DESIGN: Four hundred and twenty-five consecutive women who had a routine fetal anatomical survey in second trimeseter were evaluated for umbilical cord coiling index. aUCI was correlated with adverse antenatal and perinatal events, such as: small for gestational age (SGA), mode of delivery (interventional vs noninterventional), presence of meconium stained amniotic fluid, presence of non-reassuring fetal status (NRFS) in labor, and low Apgar scores (6 or less) at 1 and 5 minutes. RESULTS: A total of 294 patients had adequate ultrasound images and all antenatal and labor data to meet the study inclusion criteria. The aUCI above 90%ile and below 10%ile were recognized as hyperand hypocoiled umbilical cords in 10.5% and 9.2% of cases, respectively. Abnormal coiling was significantly associated with SGA neonates at birth (P = .043) and NRFS in labor (P = .007), whereas a trend toward a higher incidence of interventional deliveries and meconium stained amniotic fluid in labor was observed, but statistically nonsignificant (Table). No statistical difference for low Apgar scores between compared groups was noted. CONCLUSION: Abnormal umbilical cord coiling, detected at the fetal ultrasound anatomical survey in the second trimester, can be potentially employed as a predictor of adverse antenatal or perinatal events.

Phase I trial of yttrium-90—labeled anti—prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer: Milowsky MI, Nanus DM, Kostakoglu L, Vallabhajosula S, Goldsmith SJ, Bander NH, Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY. J Clin Oncol 2004;22:2522–31

To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90–labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (90Y-J591) in patients with androgen-independent prostate cancer (PC). Patients with androgen-independent PC and evidence of disease progression received indium-111-J591 for pharmacokinetic and biodistribution determinations followed 1 week later by 90Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m2. Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory. Twenty-nine patients with androgen-independent PC received 90Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m2, with two patients experiencing thrombocytopenia with non-life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m2 dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization. The recommended dose for 90Y-J591 is 17.5 mCi/m2. Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of 90Y-J591 in the treatment of patients with PC.

Letters

Back to table of contents Previous article Next article LettersFull AccessRobert B. Millman, M.D.Robert B. MillmanSearch for more papers by this author, M.D.Published Online:1 Oct 2004https://doi.org/10.1176/appi.ps.55.10.1183-aAboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: At the outset of my psychiatric training, John Talbott was the first faculty member I met who was committed to the principles and practices of community psychiatry. At the Payne Whitney Clinic, at that time, there were not many others who shared those interests. John was deeply interested in the provision of reasonable care to patients who were chronically mentally ill, often impoverished, and generally underserved. He was even interested in patients who had drug and alcohol abuse and dependence problems. Whereas organized psychiatry and psychiatrists were often reluctant to accept responsibility for the care of these apparently unattractive and perhaps incurable patients, John recognized that the drug use disorders were inextricably intertwined with other acute and chronic psychiatric conditions. He well understood the remarkable prevalence of comorbid disorders and actively sought interventions that might be effective on a large scale.And John is unique in the way he communicates his interests and enthusiasms. He is a charismatic, generous, and powerful leader and teacher. He brought me and many others in, and encouraged my involvement in committees, in the journal, and in our peerless board examiner group. That examiner group was a thing of beauty—responsible, incredibly hard working, and really fun, just like John.I believe that John Talbott has significantly influenced the care of underserved patient populations and enhanced the pool of interested academic and clinical psychiatrists who care for these individuals.Dr. Millman is the Saul P. Steinberg distinguished professor of psychiatry and public health and chief of the division of community and public health programs at Cornell University's Joan and Sanford I. Weill Medical College in New York City. FiguresReferencesCited byDetailsCited ByNone Volume 55Issue 10 October 2004Pages 1183-a-1183 Metrics History Published online 1 October 2004 Published in print 1 October 2004

Letters

Back to table of contents Previous article Next article LettersFull AccessArnold M. Cooper, M.D.Arnold M. CooperSearch for more papers by this author, M.D.Published Online:1 Oct 2004https://doi.org/10.1176/appi.ps.55.10.1182-aAboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: There are many reasons to celebrate and honor John Talbott. I will mention only a few. His contributions to psychiatry and public health mark him as one of a small number in our field who have understood our mission as basically social—the attempt to alleviate suffering, especially for those who are unable to make their needs heard in the public arena.As a teacher, researcher, editor, leader, and advocate, John has been guided by a profound social conscience to use his gifts in the service of those who are less fortunate.This sense of moral commitment that has guided John's professional career has also guided aspects of his personal life.John's devotion to good food, good wine, French culture, good literature, jogging, friendship—to mention just a few of his deep interests—are pursued with the same diligence, intelligence, and striving for excellence as are his more obvious contributions to the well-being of society. Being around John is pretty much a guarantee of a good time.His laugh and warmth are infectious, and his intellect sparkles.John is one of those rare few of us who is leaving an enduring legacy. Psychiatric Services, which thrived during John's tenure, has become a guide for investigation and the generation of new ideas in an arena that is often neglected by many of us.While John is giving up a title, it is unlikely that we will miss him, because his large presence, ebullience, wit, and endless gush of ideas will continue to be a part of our personal and professional lives.Dr. Cooper is the Stephen P. Tobin and Dr. Arnold M. Cooper professor emeritus in consultation-liaison psychiatry at Weill Medical College of Cornell University in New York City. FiguresReferencesCited byDetailsCited ByNone Volume 55Issue 10 October 2004Pages 1182-a-1182 Metrics History Published online 1 October 2004 Published in print 1 October 2004

The Effects of Age and Obesity on Patient Discharge Disposition Following Total Hip Arthroplasty

Robert Wood Johnson Medical School, New Brunswick, NJ (Rocchetti); and Hospital for Special Surgery, New York, NY (Fritzsche and Ganz). This research was supported by American Federation for Aging/ Samuels/Hartford Foundation Medical Student Summer Scholars Program, Weill Medical College of Cornell University, Division of Geriatrics.

Immune thrombocytopenic purpura: investigation of the role of cytomegalovirus infection

There are several reports of thrombocytopenia temporally associated with cytomegalovirus (CMV) infection in both immunocompetent and immunosuppressed patients (Crapnell et al, 2000; Yenicesu et al, 2002). While these anecdotal and brief reports raise the question of CMV causing immune thrombocytopenic purpura (ITP), the role of CMV infection in typical acute, self-limited or persistent ITP in children and adults remains unclear. There are several theoretical reasons why CMV infection may cause thrombocytopenia: direct cytotoxicity of CMV to haematopoietic cells; immune-mediated destruction of infected cells; or impairment of bone marrow stromal function by CMV (Crapnell et al, 2000). It is also possible that CMV infection induces non-specific autoantibodies that somehow result in antibody-mediated destruction of platelets (Toyoda et al, 1999). It has been shown that human CMV can infect megakaryocytes and their precursors in vitro, suggesting that infection of haematopoietic progenitor cells in vivo may contribute to thrombocytopenia in patients with CMV infection (Crapnell et al, 2000). In a study of CMV infection in a primate model, one of eight subjects exhibited marked thrombocytopenia that was also associated with transient leucocytosis (Lockridge et al, 1999). To investigate the association between CMV infection and thrombocytopenia, we screened a series of 80 adult and 28 paediatric patients who presented to the Platelet Disorders Center of the New York Presbyterian Hospital–Weill Medical College of Cornell University for the management and evaluation of thrombocytopenia. All patients attending the centre with a diagnosis of ITP were screened during a 6-month period in 1999. Urine was tested for CMV by shell vial assay. Of the 28 paediatric patients presenting with thrombocytopenia, three (11%) were positive for CMV in the urine by shell vial assay. Of these, two patients were diagnosed as having ‘routine’ ITP and one patient had Evan's syndrome. All were human immunodeficiency virus (HIV) negative. Of the 80 adult patients, three (4%) were CMV positive in the urine. Two of these patients were HIV positive with ITP. One patient had chronic ITP and an abnormally decreased lymphoproliferative response to phytohaemagglutinin. The mean nadir platelet count for patients who tested positive for CMV at any time was 12·4 × 109/l compared with 14·7 × 109/l for patients that were never positive for CMV (P = 0·799). There were no statistically significant differences in other blood cell indices between CMV-positive and -negative patients. There was no statistically significant difference between clinical course based on CMV status. We screened a total of 108 patients who presented to clinic with thrombocytopenia for CMV infection by performing shell vial assays on urine samples. Shell vial assay for the detection of CMV has been shown to be more reliable than serological testing in immunocompromised subjects and neonates (Weber et al, 1992), and more sensitive in asymptomatic patients and patients receiving antiviral therapy (Manez et al, 1994). Based on our findings, CMV infection does not appear to be involved with routine ITP. Of 108 patients, only six had CMV-positive urine results. While HIV+ patients with thrombocytopenia have improved platelet counts when HIV viral load is controlled, there were no similar findings with regard to CMV. There was no apparent correlation between CMV clearance and resolution of thrombocytopenia. The patients who did not receive anti-viral therapy still cleared the CMV. While we did not have a control group of patients who were screened for CMV, based on the historical understanding of CMV infection and detection, it seems unlikely that CMV infection is a common cause of profound thrombocytopenia. It does not, therefore, seem merited to routinely test patients with otherwise typical ITP for CMV infection. However, screening of highly refractory patients still remains as a possible strategy, and exploration of immune function of patients infected with CMV may be appropriate.

‘Depression Care Managers’ Help Reduce Suicidal Thoughts

‘Depression Care Managers’ Help Reduce Suicidal Thoughts

Pruritus of ILVEN relieved by topical pimecrolimus cream

PRURITUS OF ILVEN RELIEVED BY TOPICAL PIMECROLIMUS CREAM Noah S Gratch, MD, New York Prebyterian, Weill Medical College of Cornell University, NY, NY, United States, Deng Liang, MD, PhD, New York Prebyterian, Weill Medical College of Cornell University, NY, NY, United States, Rachelle Scott, MD, New York Prebyterian, Weill Medical College of Cornell University, NY, NY, United States, Pai Lao, MD, PhD, New York Prebyterian, Weill Medical College of Cornell University, NY, NY, United States

Parathyroid hormone.

Ms. Madore is a Medical Student, Weill Medical College of Cornell University, New York, NY. Dr. Sherman is Assistant Scientist, Research, Hospital for Special Surgery, New York, NY, and Orthopaedic Surgeon, Piedmont Orthopaedic Surgery, Lynchburg, VA. Dr. Lane is Professor of Orthopaedic Surgery, Weill Medical College of Cornell University, and Chief, Metabolic Bone Disease Clinic, Hospital for Special Surgery. None of the following authors or the departments with which they are affiliated has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article: Ms. Madore, Dr. Sherman, and Dr. Lane. Reprint requests: Dr. Sherman, Piedmont Orthopaedic Surgery, 1914 Thomson Drive, Lynchburg, VA 24503.

Teaching about the changing U.S. health care system: an innovative clerkship.

Changes in the U.S. health care system have necessitated modifying the scope and content of existing courses in the medical school curricula. In 1996, the Weill Medical College of Cornell University created a new, integrated public health curriculum to reflect the changes in the ways that medical care is organized, financed, and delivered. Teaching medical students to understand the constantly changing health care system is a primary objective of the new curriculum. As part of this curriculum, the medical college instituted a required public health clerkship that focused on the health care system, to be taken in either the third or fourth year. Students are prepared for the clerkship by taking courses in epidemiology, biostatistics, and evidence-based medicine in the first year and an introduction to the health system in the second year. The two-week clerkship, which may be unique in U.S. medical education, seeks to present an in-depth exposure to issues in health care financing and delivery by means of lectures, panel discussions with experts in the field, seminars, and field assignments to health care organizations and agencies.

Psychosurgery Evolves Into New Neurosurgery Approaches

Psychosurgery Evolves Into New Neurosurgery Approaches

Attachment Disorganization: The Reunion of Attachment Theory and Psychoanalysis.

City College and The Graduate School and University Center of the City University ofNew York, New York Presbyterian Hospital—Weill Medical College of CornellUniversity, and New York UniversityThe author investigates the psychoanalytic implications of recent attachmentresearch on the disorganized attachment categoryin infants and theunresolvedfor trauma and loss adult attachment classification with which it has beenassociated. The author first reviews empirical findings on attachment disorga-nization and then explores the ways in which they are consistent with andilluminated by psychoanalytic concepts. The focus is on linkages between dis-organized attachment and Freud’s theoryof strain trauma and traumatic anxiety,Klein’s theoryof projective identification and the interplaybetween paranoid–schizoid and depressive anxieties in development, and Blatt’s theoryof psy-chological development as resulting from the interplayof anaclitic and intro-jective developmental lines. In so doing, this article contributes to the reunionbetween attachment theory and psychoanalysis.Manyof the ideas in this article have their roots in a series of dialogues that SidneyBlattand I had with attachment researchers while we were editing two issues of PsychoanalyticInquiry on the implications of recent attachment research for psychoanalysis. Much to our

Unexplained polyhydramnios and perinatal outcomes

SRIRAM C. PERNI, JENNIFER E. CHO, ROBIN B. KALISH, MLADEN PREDANIC, STEPHEN T. CHASEN, Weill Medical College of Cornell University, Obstetrics & Gynecology, New York, NY OBJECTIVE: The relationship between polyhydramnios and poor neonatal outcomes has been inconsistent in the literature. The aim of our study was to determine the correlation between unexplained polyhydramnios and adverse perinatal outcomes. STUDY DESIGN: Over a 6-year period, 363 singleton pregnancies with polyhydramnios were identified from our ultrasound database. Patients with pregnancies complicated by diabetes or known fetal anomalies were excluded. Patients with polyhydramnios, defined as an amniotic fluid index (AFI) greater than 20 centimeters (cm), were stratified into categories of mild (AFI 20-24 cm), moderate (AFI 25-29 cm), and severe (AFI >30 cm). Perinatal outcome data were retrieved frommedical records. Chi-square, Fisher’s exact, andMann-WhitneyU tests were used for statistical analysis where appropriate. A P value < 0.05 was considered statistically significant. RESULTS: 304 pregnanciesmet inclusion criteria. Polyhydramnios wasmild in 190 cases (62%), moderate in 84 cases (28%), and severe in 30 cases (10%). There was a trend towards higher rates of malpresentation (15.4% vs 5.5%, P = 0.056) and cesarean section (74.1% vs 55.8%, P = 0.052) in cases with severe polyhydramnios, compared to mild and moderate. There was no association with fetal gender, birth weight, gestational age at delivery, incidence of preeclampsia, or NICU admission between pregnancies with severe polyhydramnios and those with mild/moderate polyhydramnios. While no neurological abnormalities were detected in neonates from the mild or moderate polyhydramnios groups, 2 of 30 neonates (6.7%) from the severe polyhydramnios group were neurologically abnormal (P < 0.001). One neonate experienced intractable seizures, and the other had dysmorphic features. CONCLUSION: In singleton pregnancies not complicated by diabetes or known fetal anomalies, polyhydramnios is associated with favorable outcomes in most cases. Severe polyhydramnios may indicate fetal neurological dysfunction, even in the absence of any apparent fetal abnormalities.

The association of birth weight discordance and ponderal index in triplet gestations

AL INDEX IN TRIPLET GESTATIONS ROBIN B. KALISH, GEETA SHARMA, LOUIS G. KEITH, DEBBIE J. RHEA, ISAAC BLICKSTEIN, Weill Medical College of Cornell University, Obstetrics and Gynecology, New York, NY Northwestern University, Gynecology, Chicago, IL Matria Healthcare Inc., Department of Clinical Research, Marietta, GA Kaplan Medical Center, Obstetrics and Gynecology, Rehovot, Israel OBJECTIVE: Our objective was to determine the association of the ponderal index with birth weight discordance in triplets. STUDY DESIGN: We analyzed data from triplets delivered at 28-37 weeks for birth weight discordance (> 25%difference between the heaviest and lightest triplet). Three categories of discordance (low skew, symmetrical, and high skew) were classified according to the relative position of the middle triplet. Birth weights and the ponderal index (birth weight/length 3) of all concordant and discordant triplet groups were compared. RESULTS: Of 752 triplet sets included, 184 (24.5%) were discordant. Total triplet birth weight was higher in the concordant compared to all discordant categories. As opposed to birth weight, where only the middle triplet differed according to discordance pattern, the ponderal index for the largest triplet was significantly higher in the low skew discordant group compared to the concordant and other discordant triplet groups. In contrast, the ponderal indexes for the smallest and middle triplets were similar among the discordant groups. CONCLUSION: Discordance in triplet pregnancies exhibits different patterns of mass (birth weight) versus size (ponderal index). Our findings suggest that it may be the size of the largest triplet that determines the presence or absence of discordance in triplet gestations.

Comparison of multifetal pregnancies resulting from in vitro fertilization and spontaneous conception: differences in maternal interleukin-1 receptor antagonist genotype distribution

233 234 COMPARISON OF MULTIFETAL PREGNANCIES RESULTING FROM IN VITRO FERTILIZATION AND SPONTANEOUS CONCEPTION: DIFFERENCES IN MATERNAL INTERLEUKIN-1 RECEPTOR ANTAGONIST GENOTYPE DISTRIBUTION ROBIN B. KALISH, SANTOSH VARDHANA, MERUKA GUPTA, SRIRAM C. PERNI, STEVEN WITKIN, Weill Medical College of Cornell University, Obstetrics and Gynecology, New York, NY OBJECTIVE: To determine whether genotype frequencies of polymorphic genes associated with inflammation differed between women who conceived following in vitro fertilization (IVF) and women with spontaneously conceived multifetal pregnancies. STUDY DESIGN: Buccal swabs were obtained from 101 women with twin (98) or triplet (3) pregnancies. DNA was assayed by polymerase chain reaction for a length polymorphism in intron 2 of the IL-1ra gene and polymorphisms at position +3953 in the IL-1b gene, -590 in the IL-4 promoter, -1082 in the IL-10 promoter, and -308 in the TNF-a promoter. Patient charts were reviewed to obtain pregnancy outcomes. RESULTS: Multifetal pregnancies resulting from IVF occurred in 58 women; 43 women had spontaneous conceptions. IL-1ra homozygotes (IL1RN*1/IL1RN*1) were identified in 31.6% of women who underwent IVF as opposed to 52.5% with spontaneous conceptions (P = .06; OR = 0.42, 95% CI = 0.2-1.0). Conversely, the IL1RN*1/IL1RN*2 heterozygote genotype was present in 54.4% of women who underwent IVF as opposed to 27.5% of those with spontaneous conceptions (P = .01; OR = 3.14, 95% CI = 1.2-8.2). The IL-1ra genotype distribution was similar to that found in non-pregnant women only in the women with spontaneous conceptions. There were no differences in IL-1b, IL-4, IL-10, or TNF-a genotypes between the two groups. Similarly, the rate of spontaneous preterm birth was comparable in both groups. Volume 189, Number 6 Am J Obstet Gynecol SMFM Abstracts S127

First-trimester screening for trisomy 21 in pregnancies conceived by in vitro fertilization

CONCEIVED BY IN VITRO FERTILIZATION SRIRAM C. PERNI, ROBIN B. KALISH, GEETA SHARMA, MERUKA GUPTA, JENNIFER E. CHO, STEPHEN T. CHASEN, Weill Medical College of Cornell University, Obstetrics & Gynecology, New York, NY OBJECTIVE: The aim of our study was to examine the effect of in vitro fertilization (IVF) on first-trimester levels of pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin (b-hCG), and nuchal translucency (NT) measurements used in aneuploidy screening. STUDY DESIGN: We compared the first-trimester maternal dried whole blood specimens for PAPP-A and b-hCG of 31 singleton pregnancies conceived by IVF with 135 pregnancies conceived spontaneously. Maternal serum biochemistry analysis was performed by NTD Laboratories and was reported as multiples of the median (MoM). NT was measured using the Fetal Medicine Foundation protocol from 11-14 weeks of gestation. Pregnancies conceived by IVF were matched with four spontaneous conception controls. Subgroups were stratified based on gestational age. Free b-hCG, PAPP-A, and NT levels were compared between the IVF and control groups using the Mann-Whitney U statistical test. A P value < 0.05 was considered statistically significant. RESULTS: PAPP-A levels were 6.6% lower and free b-hCG levels were 2.8% higher in pregnancies conceived by IVF compared to spontaneous conceptions, although this did not reach statistical significance. Among the patients presenting at the earliest gestational age range, median PAPP-A was significantly lower (0.82 MoM versus 1.68 MoM, P = 0.036) in the IVF pregnancies. b-hCG and NTmeasurements did not differ significantly between the two groups at any gestational age. However, there was a trend towards increased median NT measurements in IVF pregnancies from 11.5 12.5 weeks of gestation (1.55 mm versus 1.45 mm, P = 0.09) compared to the controls at the same gestational age. CONCLUSION: In singleton pregnancies conceived by IVF, PAPP-A levels appear to be lower early in gestation. Larger studies are necessary to explore the possibility of using appropriate adjustment factors to correct for IVF gestations.

Polymorphisms in the tumor necrosis factor alpha and heat shock protein HSP70-2 genes and preterm premature rupture of the membranes in multifetal gestations

To determine the relationship between preterm premature rupture of the membranes (PPROM) and polymorphisms in genes involved in pro-inflammatory immunity (TNF) and cell viability under conditions of stress (hsp70) in multifetal gestations. Buccal swabs from 101 mother-neonate pairs of multifetal pregnancies were tested for nucleotide polymorphisms at position 308 of the TNF gene and position 1267 of the hsp70-2 gene. Pregnancy outcome data were subsequently obtained. Carriage of allele 2 of the TNF gene (TNF∗2) by the firstborn was associated with PPROM. Fetus A carried TNF∗2 in 37.0% of cases with PPROM as opposed to 9.0% without PPROM (P = .002; OR = 5.98, 95% CI = 1.7-22.1). Conversely, the first fetus was TNF∗1-homozygous in 91.0% of cases without PPROM as opposed to 63.0% with PPROM (P = .002; OR = .17, 95% CI = .1-.6). Homozygous carriage of hsp70 allele 2 (HSP70∗2) by the firstborn was also associated with PPROM. Fetus A was HSP70∗2 homozygous in 23.1% of PPROM cases as opposed to 6.3% without PPROM (P = .06; OR = 4.43, 95% CI = .97-21.3). There was no relation between TNF∗2 or HSP70∗2 carriage by the second fetus or the mother and PPROM. In pregnancies with PPROM, the firstborn was positive for both TNF∗2 and HSP70∗2 homozygosity in 15.4% as opposed to 0% of cases without PPROM (P = .006; OR = 24.32, 95% CI = 1.3-469.6). The rate of PPROM in multifetal pregnancies is related to carriage of the TNF∗2 allele and/or HSP70∗2 homozygosity in the firstborn. TNF∗2 is associated with increased TNF production as compared to TNF∗1. HSP70∗2 homozygosity is associated with decreased messenger RNA levels compared to HSP70∗1 homozygotes and heterozygotes. Hyper-TNF production by the fetus nearest the chorioamnion in response to stressful stimuli, coupled with a decreased level of protection against cell death due to reduced hsp70 production, may increase susceptibility to PPROM.

Practice patterns among urologic surgeons treating localized renal cell carcinoma in the laparoscopic age: technology versus oncology

Objectives To evaluate the effect of laparoscopy on practice patterns at a single institution in the treatment of renal cell carcinoma. Many now regard laparoscopic radical nephrectomy (LRN) as a standard of care in the management of localized renal cell carcinoma. As laparoscopy becomes more prevalent in the urologic community, practice patterns are changing. Methods We analyzed the renal cancer surgical database at the Weill Medical College of Cornell University from 1997 to 2002. We compared three groups, including open radical nephrectomy (ORN), open partial nephrectomy (OPN), and LRN. Results A total of 222 consecutive renal surgeries done for presumed malignancy were performed from 1997 to 2002. A total of 194 were assessable. Of these, 63 were OPNs, 51 were ORNs, and 80 were LRNs. When analyzed over time, during the latter half of 2000, 89% of all LRNs were performed on tumors less than 4 cm in size. More recently, in 2002, only 42% of LRNs were performed for tumors 4 cm or less in size. From 1997 to 2000, 30% of all OPNs were done on tumors greater than 4 cm compared with 28% from 2000 to 2002. Of 30 OPNs performed from 1997 to 2000, 21 (70%) were performed on small (4 cm or less) tumors compared with 24 (73%) of 33 from 2000 to 2002. Conclusions From 2000 to 2002, the percentage of tumors less than 4 cm that were treated with LRN has increased with time. In the ORN cohort, the percentage of nephrectomies performed on small tumors (less than 4 cm) has decreased with time, and the trends in the OPN group have remained relatively stable. As an institution becomes more comfortable with laparoscopic techniques, technological concerns are likely to play less of a role in determining treatment algorithms among treating urologists.

Model for a merger: New York-Presbyterian's use of service lines to bring two academic medical centers together.

NewYork-Presbyterian Hospital is the result of the 1998 merger of two large New York City academic medical centers, the former New York and Presbyterian Hospitals, and is affiliated with two independent medical schools, the Columbia University College of Physicians and Surgeons and the Joan and Sanford J. Weill Medical College of Cornell University. At the time of the merger, the hospital faced a number of significant challenges, chief among them the clinical integration of the two medical centers. Size, separate medical schools, geography, and different histories and cultures all presented barriers to collaboration. To bring about the needed clinical alignment, the hospital turned to service lines as a way to realize the benefits of clinical integration without forcing the consolidation of departments. In this article, members of the hospital's senior management review the thinking behind the hospital's use of the service lines, their development and operation, and the significant, positive effects they have had on volume, clinical quality, clinical efficiency, best practices, and revenue management. They discuss how the service lines were used to bring together the two clinical cultures, the impact they have had on the way the hospital is operated and managed, and why service lines have worked at NewYork-Presbyterian in contrast to other hospitals that tried and abandoned them. Service lines play an increasingly central role in the hospital's clinical and business strategies, and are being extended into the NewYork-Presbyterian health care system.