Late-Onset Posttransplant Lymphoproliferative Disorders after Solid Organ Transplantation in Adults: A Case Series and Review of the Literature.

The posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of neoplasms that have wide variety of clinical and histological presentations. The management of PTLDs is challenging due to variety of involvement sites and histological types. The length and type of immunosuppression are correlated with the emergence of PTLDs, and most of the cases appear within the first two years after transplant. This case series describes five late-onset PTLDs with rare histological features and multiorgan involvement.

Using Kinesthetic and Tactile Cues to Maintain Exercise Intensity.

Haptic cues may be able to assist an individual who is engaged in a manual control task, freeing visual and auditory attention for other mental tasks. We describe an experiment in which subjects attempted to step at a consistent pace on a stair climber exercise machine which was modified for haptic cuing through the legs. Subjects' visual attention was engaged by a video game. Five different haptic cues for consistent pacing were investigated, two of them more kinesthetic in nature and three that were more tactile. Results showed that haptic cues could indeed improve the manual control task performance without diminishing the visual attention task performance. The tactile cues generally outperformed the kinesthetic ones.

Is severe macrosomia manifested at 11-14 weeks of gestation?

OBJECTIVE: To determine the association between fetal biometry in the first or early second trimester and severe macrosomia at delivery. METHODS: This case-control study included 30 term severely macrosomic neonates; 90 appropriate-for-gestational age (AGA) neonates served as controls. All pregnancies underwent nuchal translucency (NT) screening at 11-14 weeks' gestation. Pregnancies were dated by accurate last menstrual period consistent with crown-rump length (CRL) measurements at the time of screening, early pregnancy CRL or date of fertilization. The association between birth weight and the difference between the measured and the expected CRL at the time of NT screening was analyzed. RESULTS: The difference between measured and expected CRL, expressed both in mm and in days of gestation, was statistically greater in the severely macrosomic neonates compared with controls (mean, 6.66 +/- 4.78 mm vs. 1.17 +/- 4.6 mm, P < 0.0001 and 3 +/- 2.2 days vs. 0.5 +/- 2.3 days, P < 0.0001, respectively). Furthermore, there were significant correlations between the extent of macrosomia and the discrepancy between expected and measured fetal size at the time of NT screening (r = 0.47, P < 0.01 and r = 0.48, P < 0.01, respectively). CONCLUSION: Severe macrosomia apparently manifests as early as 11-14 weeks' gestation.

Does the availability of maternal HbA1c results improve the accuracy of sonographic diagnosis of macrosomia?

OBJECTIVE: To determine whether measuring maternal glycosylated hemoglobin (HbA1c) can improve the accuracy of sonographic estimation of fetal macrosomia. METHODS: Sonographic estimation of fetal weight (EFW) and maternal HbA1c were obtained in term, non-diabetic patients within 1 week before delivery. Neonatal birth weights were recorded at delivery and compared with both sonographic estimations and HbA1c. Macrosomia was defined as birth weight of >or=4000 g. The absolute error of the sonographic EFW was calculated. Receiver-operating characteristics (ROC) curve analysis was used to evaluate sonographic EFW and HbA1c as predictors of birth weight >or=4000 g. Variables were tested using regression analysis and student's t-test. RESULTS: One hundred and sixty two patients were evaluated between July and December 2002. Twenty-eight patients (17.3%) delivered macrosomic infants. Sonographic EFW >or=4000 g predicted macrosomia with sensitivity, specificity and positive and negative predictive values of 66.6%, 88.8%, 54.5% and 93.0%, respectively. Its overall accuracy was 85.5%. The area under the ROC curve of sonographic EFW in the prediction of macrosomia was 0.9 (P < 0.001). HbA1c levels in women delivering macrosomic and non-macrosomic neonates were 5.3 +/- 0.7% and 5.2 +/- 0.5%, respectively (P = 0.27). The area under the ROC curve of HbA1c in the prediction of macrosomia was 0.53 (P = 0.27). CONCLUSIONS: Maternal HbA1c is not a useful test in the prediction of birth weight. It therefore cannot be used to improve the accuracy of sonographic EFW.

Inferior vena cava thrombosis presenting as non-immune hydrops in the fetus of a woman with diabetes.

We present a rare case of non-immune hydrops fetalis (NIHF) caused by a thrombus in the inferior vena cava in a neonate with low levels of anti-thrombin III. The diagnosis of (NIHF) was made in utero in a 43-year-old woman with poorly controlled gestational diabetes who subsequently developed pre-eclampsia. Cesarean section was performed due to fetal compromise and worsening pre-eclampsia. The thrombus resolved after neonatal treatment with heparin.

Nucleated red blood cells in human fetal scalp capillary blood samples: a feasibility study.

OBJECTIVE: Elevated umbilical cord nucleated red blood cell (NRBC) counts have been suggested as a predictor of adverse perinatal outcome. We sought to evaluate the feasibility of obtaining fetal scalp capillary blood NRBC counts during labor and to assess their correlation with umbilical cord NRBC counts. METHODS: Fetal scalp capillary blood specimens were prospectively collected in laboring patients who underwent scalp sampling because of the presence of an abnormal fetal heart rate pattern. Matched umbilical cord blood samples were collected immediately after birth. Outcome measures were the feasibility of obtaining fetal scalp NRBC counts and their correlation with umbilical cord NRBC counts. RESULTS: Thirteen term singleton pregnancies formed the study population. In four patients, fetal scalp capillary blood sampling was performed twice. Of the attempts to evaluate fetal scalp capillary samples for NRBC counts, 16 out of 17 (94.1%) were successful. The mean fetal scalp capillary blood NRBC count per 100 white blood cells was 12.6 +/- 7.6 (+/- SD). Umbilical cord mixed, venous and arterial NRBC counts were 15.5 +/- 8.8, 13.4 +/- 10.7 and 12.6 +/- 10.7, with p = 0.09, p = 0.59 and p = 0.68, respectively, when compared to the corresponding scalp sample. The Spearman rank correlation between fetal scalp capillary samples and umbilical cord mixed, venous and arterial NRBC counts were r = 0.86, r = 0.92 and r = 0.95, respectively, with all p values < 0.001. CONCLUSION: Previous studies have established the clinical utility of umbilical cord NRBC counts. Our study demonstrated that it was possible to obtain NRBC counts from a fetal scalp capillary sample and that these counts correlated highly with umbilical cord NRBC counts. Future studies are needed to evaluate fetal scalp NRBC counts as a predictor of perinatal outcome.

The association between fetal and maternal sleep patterns in third-trimester pregnancies.

OBJECTIVE: We sought to investigate the association between fetal heart rate and maternal electroencephalogram patterns during overnight sleep. STUDY DESIGN: Data were collected prospectively between December 1, 1999, and June 30, 2001. Initially, the participating patients were asked to complete a 66-question survey for the assessment of maternal perception of sleep quality that was referred to as the sleep disturbance score: a continuous score from 0 (no evidence of sleep disturbance) to 110 (extreme sleep disturbance). Second, a subgroup of patients was monitored overnight by concomitant fetal heart rate and maternal electroencephalogram tracings. Statistical analysis included the Student t test, chi2 test, logistic regression, and Cramer's V contingency correlation. RESULTS: One hundred two singleton pregnancies formed the study population. The mean sleep disturbance score was 26.7 +/- 9.9. Maternal age was the only variable that correlated with sleep disturbance score. A subgroup of 11 patients was studied overnight. A significant correlation between active fetal sleep and maternal wakefulness was demonstrated in 6 patients. The mean sleep disturbance score for these patients was significantly higher than for patients without such correlation (P =.04). CONCLUSION: This study establishes an association between fetal activity and maternal wakefulness, which explains many of the maternal awakenings during sleep in the third trimester.

Maternal pain and anxiety in genetic amniocentesis: expectation versus reality.

OBJECTIVE: To investigate maternal perceptions of both pain and anxiety before and after genetic amniocentesis. STUDY DESIGN: This prospective study of midtrimester, singleton pregnancies was conducted between March 2000 and July 2000. Study variables included patient demographics, medical and obstetric histories, indication for amniocentesis and a description of the source of information used by the patient regarding the procedure and technical degree of difficulty. Maternal pain and anxiety associated with performing amniocentesis were subjectively quantified with the use of the visual analog scale (VAS). Statistical analysis included Wilcoxon signed rank test, anova, and simple and stepwise regression analyses. RESULTS: One hundred and eighty-three women participated in the study. Perception of pain before amniocentesis was significantly higher compared to that expressed immediately after the procedure, with a mean VAS score of 3.7 +/- 2.5 vs. 2.1 +/- 2.0 (P < 0.0001). Similarly, perception of anxiety was significantly greater prior to the procedure, with a mean VAS score of 4.6 +/- 2.8 vs. 2.8 +/- 2.4 after the amniocentesis (P < 0.0001). Perceptions of pain and anxiety were significantly and positively correlated to each other both before and after the procedure (P < 0.0001). History of a prior amniocentesis was the only variable associated with reducing expected pain and anxiety (negative correlation, P < 0.001), whereas the technical degree of difficulty was the only significant variable impacting on the actual pain and anxiety (positive correlation, P < 0.005). CONCLUSIONS: Preamniocentesis counseling should emphasize the fact that, for most women, the actual pain and anxiety experienced during the procedure are significantly lower than expected. In fact, on a scale of 0-10, the mean level of pain was only 2.1, with a slightly higher mean level of anxiety.

Reported exposure to chickenpox: a predictor of positive anti-varicella-zoster antibodies in parturient women.

OBJECTIVE: To determine the positive and negative predictive values of recalled exposure to chickenpox for identifying anti-varicella-zoster virus (VZV) seropositive parturient women. METHODS: Blood samples were taken from laboring women during February 1998: All women completed questionnaires concerning a history of chickenpox in themselves and their children. Anti-VZV antibodies were determined by the immunofluorescent antibodies to membrane antigen (IFAMA) technique. RESULTS: Three hundred and twenty-seven women formed the study population; 239 women (73.1%) recalled chickenpox in themselves or their children, of which 229 (95.8%) were seropositive for anti-VZV antibodies. Of the 88 women who gave a negative/uncertain history of chickenpox 82 (93.2%) were seropositive and 6 (6.8%) were seronegative. All 87 mothers who were certain their children had had chickenpox were seropositive, including all 16 mothers who had a negative personal history. Thus, a woman with a history of chickenpox had a positive predictive value of 95.8%, and a woman with a lack of history had a negative predictive value of 6.8% (sensitivity 73.6%, specificity 37.5%), while a positive history of chickenpox in a child had a positive predictive value of 100%. CONCLUSIONS: Most women with no known history of VZV infection have evidence of prior exposure by serologic testing. Moreover, 100% of women with a negative history who were exposed to VZV in their children were protected from the disease. Therefore, mothers exposed to VZV during pregnancy can be reassured that most likely they are protected. However, the practice of testing all pregnant women exposed to the disease should be continued.

Interaction of fibrin with VE-cadherin.

The conversion of fibrinogen into fibrin and the association of fibrin(ogen) with activated platelets play a fundamental role in hemostasis because their interaction with the injured vessel prevents blood extravasation. Platelet aggregates and fibrin also participate in the occlusion of the vascular lumen in pathological conditions. Fibrin II also promotes the formation of new blood vessels, for example, during wound healing and tumor growth. Using an in vitro assay, we have studied the mechanism by which fibrin II induces formation of capillaries. Generation of fibrin II on top of an endothelial cell monolayer rapidly rearranged the ECs into a capillary network. In contrast, neither fibrin I nor fibrin 325 induced these morphogenetic changes, indicating that exposure of the N-terminal peptide beta 15-42 is involved in this process. Binding studies, using the N-terminal fragment of fibrin (NDSK II), showed that NDSK II binds to EC with high affinity, but neither NDSK nor NDSK325 bound specifically. Binding of NDSK II to endothelial cells was blocked with an antibody to VE-cadherin. Direct association of NDSK II and VE-cadherin was also demonstrated in a VE-cadherin antibody capture assay. NDSK II bound specifically with the captured VE-cadherin but NDSK or NDSK 325 did not associate with VE-cadherin. Moreover, fibrin II associated with EC VE-cadherin and this interaction triggered the formation of capillary-like structures. A better understanding of the cellular responses to fibrin, identification of the fibrin binding site within VE-cadherin and the intracellular signaling that follows this interaction, could yield important information that may translate into better control of the angiogenic process.

Hysteroscopy may be the method of choice for management of residual trophoblastic tissue.

STUDY OBJECTIVE: To assess the efficacy of and reproductive outcome after selective curettage of residual trophoblastic tissue directed by hysteroscopy compared with conventional, nonselective, blind curettage. DESIGN: Retrospective analysis (Canadian Task Force classification II-1). SETTING: Tertiary care medical center. PATIENTS: Seventy patients after curettage or delivery, with clinical and ultrasonographic signs of suspected residual trophoblastic tissue. MEASUREMENTS AND MAIN RESULTS: Twenty-four women underwent traditional curettage and 46 underwent hysteroscopic selective curettage. Five (20.8%) patients who underwent traditional curettage later required operative hysteroscopy due to persistent residual tissue. None of those who underwent hysteroscopic selective curettage needed a second operation. No patient in either group experienced anesthetic complications, perforation of the uterus, fluid overload, or other surgical complication. Reproductive outcome was similar in both groups, with tendency to conceive earlier in the hysteroscopy group, but no difference in overall pregnancy rates. CONCLUSION: Operative hysteroscopy for selective curettage of residual trophoblastic tissue should be considered an alternative to nonselective, blind curettage.

Umbilical artery Doppler velocimetry--an update.

Doppler ultrasonography was introduced into clinical obstetric practice over 20 years ago. It is also accepted that a variety of common obstetrical complications such as preeclampsia and intrauterine growth restriction have their origin in abnormal development of the placental vasculature and this could be reflected in abnormal Doppler velocimetry. Doppler velocimetry of the umbilical artery has been the subject of multiple clinical studies but results have often been disputed due to differences in study populations and methodologies. In recent years, meta-analysis of randomized clinical trials have shown that incorporation of Doppler velocimetry into clinical practice will reduce perinatal mortality in high-risk patients. This article reviews the data of the meta-analyses as it pertains to the management of high-risk pregnant patients.

Nonmyeloablative conditioning allows for more rapid T-cell repertoire reconstitution following allogeneic matched unrelated bone marrow transplantation compared to myeloablative approaches.

Nonmyeloablative pretransplantation conditioning regimens have resulted in durable engraftment of allogeneic hematopoietic stem cells. In contrast to conventional fully myeloablative approaches, nonmyeloablative regimens are associated with a marked reduction of morbidity and mortality in the early posttransplantation period. Consequently, such reduced-intensity transplantation approaches can be used in older and frailer patients who would not tolerate fully ablative regimens. However, it is currently unclear how this radically different transplantation strategy affects immunological reconstitution. To address this important issue, we used T-cell receptor Vbeta spectratype analysis to examine the distribution of complementarity-determining region 3 (CDR3)-size bands as a measure of the complexity of the redeveloping T-cell repertoire. For this study, we evaluated the T-cell repertoire of 9 patients receiving T-cell replete, matched unrelated donor transplants following fully ablative or nonmyeloablative conditioning regimens. All 4 of the myeloablative and 2 of the nonmyeloablative patients received bone marrow, whereas 3 other nonmyeloablative patients received peripheral blood stem cells. The results of the spectratype analysis demonstrated that the patients who received nonmyeloablative conditioning together with either bone marrow or peripheral blood stem cells exhibited more rapid reconstitution of T-cell repertoire complexity.

Natural-cycle in vitro fertilization in women aged over 44 years.

Women who are 44 years of age or more are usually denied infertility treatment because of their low response to ovarian stimulation and the extremely low pregnancy rate that can be achieved. The object of this study was to assess the place of natural-cycle in vitro fertilization (IVF) in this population. From January 1996 to September 1997, all consecutive women aged 44-47 years who approached our unit seeking infertility treatment with their own oocytes were enrolled in the study. After a counselling session in which the advantage of egg donation was discussed, women who still wished to try to conceive by utilizing their own oocytes were treated according to the following protocol. Ultrasound and hormonal surveillance was carried out starting 5 days prior to the presumed ovulation day, based on previous menstrual history. Ovum pick-up was timed either by detection of the luteinizing hormone surge or by human chorionic gonadotropin administration. In total, 48 treatment cycles were conducted in 20 women. Oocyte retrieval was successful in 22 cycles. Fertilization and cleavage rates of 48% and 100%, respectively, were detected. Nine of the 12 embryos transferred were defined as grade A. One chemical and one ongoing pregnancy were achieved. We conclude that, despite the fact that high-quality embryos can be obtained in this population, the likelihood of pregnancy is low.

Gonadotropin stimulation following GnRH-a priming for poor responders in in vitro fertilization-embryo transfer programs.

The effect of gonadotropin-releasing hormone agonist (GnRH-a) administration before gonadotropin superovulation on the stimulation characteristics of poor responder patients was assessed in an in vitro fertilization (IVF) program. Thirty consecutive patients who had exhibited low ovarian response (fewer than four retrieved oocytes) in at least two previous IVF cycles (control cycles, n = 60), were eligible for the study. GnRH-a (nafarelin) was administered daily for 7-10 days from the mid-luteal phase of the previous cycle until the first day of menstruation. Menotropin treatment was commenced on cycle day 3 (with no additional GnRH-a) (study cycles, n = 39). A significantly higher number of oocytes was retrieved (p < 0.0002) and a higher number of embryos transferred (p < 0.003) in the study cycles than in the control cycles. No cases of premature luteinizing hormone surge were recorded. Pregnancy rates per embryo transfer and per cycle were 10.4% and 7.7% for the study cycles and 2.8% and 1.6% for the control cycles, respectively. GnRH-a, administered prior to gonadotropin treatment, should be an additional option of ovulation induction protocol for poor responders in IVF programs.

Budd-Chiari syndrome complicating restorative proctocolectomy for ulcerative colitis: report of a case.

PURPOSE: This is a case of hepatic vein thrombosis presenting in a delayed fashion after proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Search for a causative thrombotic condition resulted in the diagnosis of polycythemia vera, a myeloproliferative disorder associated with hypercoagulability. The polycythemia was masked by an iron deficiency associated with the ulcerative colitis. METHODS: The history, physical, diagnostic modalities, and treatment for this patient are described, and the literature of Budd-Chiari syndrome associated with ulcerative colitis is reviewed. RESULTS: Six cases of Budd-Chiari syndrome in the setting of ulcerative colitis are reported in the literature from 1945 to 1997. CONCLUSIONS: Hepatic vein thrombosis is a rare complication of ulcerative colitis. The diagnosis of Budd-Chiari syndrome demands a thorough search for a hematologic condition predisposing to thrombosis. Our patient had a myeloproliferative disorder, polycythemia vera, that is associated with a hypercoagulable state. The disorder was masked by an iron deficiency associated with the ulcerative colitis. Recognition of the entity will permit successful treatment.

Standard in vitro fertilization or intracytoplasmic sperm injection in advanced female age--what may be expected?

This study was conducted to evaluate the current results of standard in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the elderly (> or = 40 years of age) female population. Oocyte recovery, fertilization, embryo transfer, pregnancy and cumulative pregnancy rates were assessed. The results were analyzed for: the entire elderly population; the standard IVF group (group 1); all those in the ICSI group (group 2); and ICSI for severe male-factor category (group 3). A total of 330 IVF and 158 ICSI treatment cycles were carried out in 249 women. Forty-five (9.2%) clinical pregnancies were achieved. This rate was not statistically different from those achieved for groups 1, 2 and 3 (9.1%, 9.5% and 6.8%, respectively). The cumulative pregnancy rate for a total of five cycles was 19.2% and 26.4% for groups 1 and 2, respectively. For those who started their treatments at > or = 40 years, the cumulative pregnancy rate for three cycles was 26.5% and 36.5% in groups 1 and 2, respectively. These results clearly demonstrate that female age is a major success determinant, with similar influence on both standard IVF and ICSI therapy modalities.