Correlation of intercentromeric distance, mosaicism, and sexual phenotype: molecular localization of breakpoints in isodicentric Y chromosomes.

Isodicentric chromosomes are among the structural abnormalities of the Y chromosome that are commonly identified in patients. The simultaneous 45,X cell line that is generated in cell division due to instability of the isodicentric Y chromosome [idic(Y)] has long been hypothesized to explain the variable sexual development of these patients, although gonads have been studied in only a subset of cases. We report here on the molecular localization of breakpoints in ten patients with an idic(Y). Breakpoints were mapped by FISH using BACs; gonads and fibroblasts were also analyzed when possible to evaluate the level of mosaicism. First, we demonstrate great tissue variability in the distribution of idic(Y). Second, palindromes and direct repeats were near the breakpoint of several idic(Y), suggesting that these sequences play a role in the formation of idic(Y). Finally, our data suggest that intercentromeric distance has a negative influence on the stability of idic(Y), as a greater proportion of cells with breakage or loss of the idic(Y) were found in idic(Y) with a greater intercentromeric distance. Females had a significantly greater intercentromeric distance on their idic(Y) than did males. In conclusion, our study indicates that the Y chromosome contains sequences that are more prone to formation of isodicentric chromosomes. We also demonstrate that patients with an intercentromeric distance greater than 20 Mb on their idic(Y) are at increased risk of having a female sexual phenotype.

Familial deletion 18p syndrome: case report.

BACKGROUND: Deletion 18p is a frequent deletion syndrome characterized by dysmorphic features, growth deficiencies, and mental retardation with a poorer verbal performance. Until now, five families have been described with limited clinical description. We report transmission of deletion 18p from a mother to her two daughters and review the previous cases. CASE PRESENTATION: The proband is 12 years old and has short stature, dysmorphic features and moderate mental retardation. Her sister is 9 years old and also has short stature and similar dysmorphic features. Her cognitive performance is within the borderline to mild mental retardation range. The mother also presents short stature. Psychological evaluation showed moderate mental retardation. Chromosome analysis from the sisters and their mother revealed the same chromosomal deletion: 46, XX, del(18)(p11.2). Previous familial cases were consistent regarding the transmission of mental retardation. Our family differs in this regard with variable cognitive impairment and does not display poorer verbal than non-verbal abilities. An exclusive maternal transmission is observed throughout those families. Women with del(18p) are fertile and seem to have a normal miscarriage rate. CONCLUSION: Genetic counseling for these patients should take into account a greater range of cognitive outcome than previously reported.

Genotoxic effects of chromium(VI) and cadmium(II) in human blood lymphocytes using the electron microscopy in situ end-labeling (EM-ISEL) assay.

Evaluation of genotoxic effects of potassium chromate (K2CrO4) and cadmium chloride (CdCl2) was carried out in human blood lymphocytes in vitro as measured by the electron microscopy in situ end-labeling (EM-ISEL). EM-ISEL was used to assess DNA single-strand breaks (SSBs) expressed as number of immunogold particles per microm2 of chromatin at both chromosomal and nuclear DNA levels. Human lymphocytes were cultured in supplemented RPMI medium for 72 h including treatment for 2 h with K2CrO4 (0-150 microM), CdCl2 (0-150 microM) or methyl methanesulfonate (500 microM) as a positive control. Quantification of SSBs by EM-ISEL showed that both compounds are genotoxic agents at non-cytotoxic concentrations. This study brings new information on the utility of EM-ISEL for the evaluation of genotoxicity and confirms the genotoxic effects induced by chromium and cadmium.

Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in nickel subsulfide-induced human lymphocyte death in vitro.

When isolated human lymphocytes were treated in vitro either with various concentrations (0-2 mM) of soluble form of nickel subsulfide (Ni3S2) at 37 degrees C for 4 h or at various times (0-240 min), both concentration- and time-dependent effects of Ni3S2 on lymphocyte death were observed. Increased generation of hydrogen peroxide (H2O2), and superoxide anion (O2-), lipid peroxidation and depletion of both nonprotein (NP-) and protein (P-) sulfhydryl (SH) contents were induced by 1 mM Ni3S2. Ni3S2-induced lymphocyte death was significantly prevented by pre-treatment with either catalase (a H2O2 scavenger), or superoxide dismutase (scavenger of O2- radical), or dimethylthiourea/mannitol (hydroxyl radical scavengers), or deferoxamine (iron-chelator), or glutathione/N-acetylcysteine. Co-treatment with cyclosporin A (a mitochondrial membrane potential' inhibitor) inhibited Ni3S2-induced disturbances in mitochondrial membrane potential, and significantly prevented Ni3S2-induced lymphocyte death. Ni3S2-induced lymphocyte death was also significantly prevented by modulating intracellular calcium fluxes using both Ca2+ channel blockers and intracellular Ca2+ antagonists. Thus, the mechanism of soluble Ni3S2-induced activation of lymphocyte death signalling pathways involves increasing generation of different types of oxidative stress, disturbances in mitochondrial membrane potential and cellular calcium homeostasis' destabilization.

Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in nickel sulfate-induced human lymphocyte death in vitro.

When isolated human lymphocytes were treated in vitro with various concentrations of nickel sulfate (NiSO4) (0-4 mM) at 37 degrees C for 4 h, both concentration- and time-dependent effects of NiSO4 on lymphocyte death were observed. Increased generation of hydrogen peroxide, depletion of both nonprotein and protein sulfhydryl contents, and lipid peroxidation were induced by NiSO4. NiSO4-induced lymphocyte death was significantly prevented by pre-treatment with either catalase, or dimethylthiourea/mannitol, or deferoxamine, or excess glutathione/N-acetylcysteine. Cotreatment with cyclosporin A (a specific inhibitor of mitochondrial membrane potential) not only inhibited NiSO4-induced mitochondrial membrane potential, but also significantly prevented Ni compound-induced lymphocyte death. NiSO4-induced lymphocyte death was also significantly prevented by modulating intracellular calcium fluxes using both Ca2+ channel blockers and intracellular Ca2+ antagonist. Thus, the mechanism of NiSO4-induced activation of lymphocyte death signalling pathways involves not only the excess generation of different types of oxidative stress but also NiSO4-induced loss of mitochondrial membrane potential and destabilization of cellular calcium homeostasis as well.

Nickel compound-induced DNA single-strand breaks in chromosomal and nuclear chromatin in human blood lymphocytes in vitro: role of oxidative stress and intracellular calcium.

The effects of nickel sulfate, and soluble forms of nickel carbonate hydroxide (NiCH), nickel subsulfide, and nickel oxide on delayed induction of DNA single-strand breaks (DNA SSBs) in chromosomal and nuclear chromatin of human blood lymphocytes in culture were studied. After 46 h of initial culture in supplemented RPMI-1640 media at 37 degrees C, human whole blood lymphocytes in culture were exposed to low concentrations (0-15 microM) of different nickel (Ni) compounds for 2 h, whereas only RPMI-1640 medium served as control. Immediately after 2 h of such exposure, both control and Ni-treated cells were washed with the same medium and incubated further in fresh complete RPMI-1640 culture medium for another 24h. After a total 70 h of incubation, cells were then arrested at metaphase. Two hours later, the induction of DNA SSBs involving both metaphase chromosomal and interphase nuclear chromatin was measured using the method of electron microscopy in situ end-labeling. The metaphase chromosomal chromatin showed significantly higher DNA SSBs (as measured by an increase in immunogold particles per microm2 chromatin) due to 15 microM NiCH and NiO when compared to the corresponding control value. Both NiCH and nickel oxide produced significantly higher induction of DNA SSBs than those of nickel subsulfide and nickel sulfate in chromosomal chromatin. The DNA SSBs in chromosomal chromatin were found to be significantly higher than those in nuclear chromatin due to different Ni compounds. Overall, the genotoxic potency seems to be decreased as follows: NiCH>nickel oxide>or=nickel subsulfide>nickel sulfate. Pretreatment of human blood lymphocytes with either catalase (a H2O2 scavenger), or superoxide dismutase (a scavenger of O2- radical) or dimethylthiourea (a hydroxyl radical scavenger), or N-acetylcysteine (GSH precursor) significantly reduced DNA SSBs in both chromosomal and nuclear chromatin induced by NiCH, suggesting the involvement of different types of oxidative stress in such genotoxicity. Deferoxamine (a highly specific iron chelator) pretreatment prevented NiCH-induced DNA SSBs in both chromosomal and nuclear chromatin suggesting a role of iron-mediated oxidative stress generating hydroxyl radical in such genotoxicity. Simultaneous treatment with either verapamil (an inhibitor of Ca 2+ through plasma membranes), or dantrolene (an inhibitor of mobilization of [Ca2+]i from endoplasmic reticulum), or BAPTA (a Ca2+ chelator) significantly reduced Ni compound-induced DNA SSBs in both chromosomal and nuclear chromatin, suggesting that Ni compound-induced destabilization of calcium homeostasis may also involved in the induction of such DNA SSBs.

Tetrasomy Y by structural rearrangement: clinical report.

Poly-Y karyotypes, except for 47,XYY, are rare events in humans. For instance, Y chromosome tetrasomy has been reported 10 times, 2 of which were by structural rearrangement. We present a 2-year-and-4-month-old boy who was referred for cytogenetic assessment because of global psychomotor delay. The GTG- and CBG-banded karyotypes on PHA-stimulated lymphocytes showed two cell populations, one of them contained two identical isodicentric Y chromosomes, which was seen in 93% of metaphases analyzed, and a 45,X cell line (7%). This was confirmed by FISH with probes DYZ3 (recognizing the centromeric region of the Y chromosome), 91H4.5 (recognizing Yp11.2), and DYZ1 (recognizing Y heterochromatin in Yq12). The breakpoint has occurred near the telomeric end of the heterochromatic region. Therefore, the karyotype is mos 47,X,idic(Y)(q12)x2[123]/45,X[9]. This is the second time that such a karyotype has been reported. This chromosomal anomaly was formed most likely by a U-type exchange. Clinical features included speech delay, short stature, brachycephaly, large ears, bilateral epicanthal folds, hypertelorism, delayed teeth eruption, bilateral radio-ulnar synostosis, bilateral fifth finger clinodactyly, normal external genitalia, and impulsive behavior. The father had normal phenotype and karyotype. A review of the tetrasomy Y patients is presented. All patients with Y chromosome tetrasomy exhibit some degree of mental retardation, various skeletal abnormalities, and facial dysmorphism. Nevertheless, the correlation between karyotype and phenotype is not yet well defined since few cases have been reported. This clinical report will be helpful in defining the phenotypic range associated with tetrasomy Y.

Rearrangement of the MLL gene and a region proximal to the RARalpha gene in a case of acute myelocytic leukemia M5 with a t(11;17)(q23;q21).

A case of acute myelocytic leukemia (AML) M5 subtype (French-American-British classification), in a 13-year-old girl showed the abnormal karyotype 46,XX,t(11;17)(q23;q21) in all bone marrow cells analyzed. Rearrangements involving 11q23 are frequent in cases of AML M5 and often involve the MLL gene. Nevertheless, t(11;17)(q23;q21) is very rare in this type of leukemia. In acute promyelocytic leukemia, the RARalpha gene, located at 17q21, is involved in almost all cases. Fluorescence in situ hybridization studies revealed a deletion of the C-terminal part of the MLL gene and a translocation of the RARalpha gene on the derivative chromosome 11, proximal to the remaining part of the MLL gene. However, hybridization with the LSI RARA dual color break-apart rearrangement probe showed that the RARalpha gene was not rearranged in this translocation. This is the first study reporting a t(11;17)(q23;q21) with a deletion distal to MLL gene exon 6 in a case of AML M5. Furthermore, this is the second study that strongly suggests the implication of a gene proximal and close to the RARalpha locus in a case of AML M5. According to these results, the discovery of new fusion partner genes of MLL and the precise characterization of t(11;17) will be important for the understanding of neoplastic cell differentiation in AML M5.

Impact of anemia on platelet response to clopidogrel in patients undergoing percutaneous coronary stenting.

High residual platelet reactivity (HRPR) on clopidogrel is a predictor of recurrent ischemic events in patients undergoing percutaneous coronary interventions (PCI). Significant intraindividual variability in platelet aggregation on repeat testing has been reported. To understand factors contributing to the variability in platelet aggregation testing, we examined clinical and laboratory elements linked to HRPR in 255 consecutive patients tested ≥12 hours after PCI using light transmission aggregometry (LTA) in response to adenosine diphosphate 5 µmol/L and VerifyNow P2Y12 assay (VNP2Y12; Accumetrics). HRPR was defined as >46% residual aggregation for LTA and >236 P2Y12 response units (PRUs) for VNP2Y12. On multivariate analysis the only variable independently associated with HRPR with both LTA and VNP2Y12 was laboratory-defined anemia. Prevalences of HRPR by LTA were 34.3% in anemic patients, 15.6% in patients with normal hemoglobin levels, and 59.8% versus 25.9% by VNP2Y12 (p <0.005 for the 2 comparisons). In a subgroup of 50 patients, testing was done before and after the clopidogrel loading dose. At baseline there were no differences in platelet aggregation with either assay; however, absolute decrease in reactivity after the clopidogrel load was significantly less in anemic patients compared to patients with normal hemoglobin (change in residual aggregation by LTA 15.8 ± 5.8% vs 28.8 ± 3.2%, p <0.05; change in PRU by VNP2Y12 56.5 ± 35.5 vs 145.0 ± 14.2 PRUs, p <0.05, respectively). In conclusion, anemia is an important contributor to apparent HRPR on clopidogrel and may explain some of the intraindividual variability of platelet aggregation testing.

Undifferentiated gonadal tissue, Y chromosome instability, and tumors in XY gonadal dysgenesis.

Patients with XY gonadal dysgenesis are at increased risk of developing gonadal tumors. The etiology of several cases of XY gonadal dysgenesis remains unknown, but X/XY gonadal mosaicism has been hypothesized to play a role. At the histologic level, the presence of persistent primitive sex cords containing immature germ cells in dysgenetic gonads (an entity called undifferentiated gonadal tissue, or UGT) was recently described, and these immature germ cells are thought to be at risk of neoplastic transformation. To further investigate both these aspects, we retrospectively studied the gonads from 30 patients with pure (22) and mixed (8) gonadal dysgenesis. Cytogenetic analyses performed on 35 gonads revealed that structurally abnormal Y chromosomes were lost in a majority of cells from the gonads, explaining the gonadal dysgenesis of patients bearing a rearranged Y chromosome. On the other hand, normal Y chromosomes were less often lost in gonads of patients with gonadal dysgenesis. At the histologic level, 43 of the 51 gonads presented areas characteristic of a streak; 13 of these streak gonads also presented areas of UGT. Structures resembling sex cords but without germ cells were found in many of the streaks not containing UGT, suggesting that UGT was initially present. Of the 13 gonads containing both UGT and a streak, 9 developed a tumor. The proximity of UGT with the tumors as well as the immunostaining patterns (PLAP+, OCT3/4+, and CD117/KIT+) suggests that germ cells found in UGT are a risk factor for gonadal tumors.

Coexistence of a choriocarcinoma and a gonadoblastoma in the gonad of a 46,XY female: a single nucleotide polymorphism array analysis.

Females with 46,XY complete gonadal dysgenesis are at significant risk of developing germ cell tumors, mostly gonadoblastomas. We present here the case of 2 half-sisters, sharing the same father, diagnosed with 46,XY complete gonadal dysgenesis. The 1st sister developed a gonadoblastoma and an invasive dysgerminoma, whereas the 2nd sister developed a gonadoblastoma and an invasive choriocarcinoma within the same gonad. No SRY mutation, chromosome abnormalities, or mosaicism were detected in blood. Single nucleotide polymorphism (SNP) profiling of the choriocarcinoma revealed a complex hyperdiploid pattern with gains of 1 to 4 copies of material from several autosomes, as well as the loss of the Y chromosome and a homozygous SNP profile without copy number change for the X chromosome. Our results are in agreement with the recurrent chromosome gains and losses previously published in germ cell tumors, and the coexistence of both tumors within the same gonad suggests that choriocarcinomas may derive from gonadoblastomas.

Comparison of the clinical application of the American College of Cardiology Foundation/American Society of Echocardiography Appropriateness Criteria for outpatient transthoracic echocardiography in academic and community practice settings.

BACKGROUND: We sought to compare the clinical application of the American College of Cardiology Foundation/American Society of Echocardiography Appropriateness Criteria (AC) for outpatient transthoracic echocardiography (TTE) in academic and community practice settings. METHODS: Indications for TTE ordered in both academic and community practice settings were determined by 2 reviewers and categorized according to the AC for TTE as Appropriate, Inappropriate, or Not Addressed. Patient characteristics, ordering physician specialty, and TTE findings were also recorded. RESULTS: Overall, 814 academic and 319 community TTEs were analyzed. Interobserver variability for indication determination was high and did not differ between studies ordered at the 2 practice settings. Compared with the academic practice, community practice TTE indications were more likely to be classified in the AC for TTE (88% vs 82%, P = .04), but were ordered for a similar frequency of Appropriate (71% vs 68%, P = not significant) and Inappropriate (17% vs 15%, P = not significant) indications. New important TTE abnormalities were more frequently found in Appropriate studies compared with Inappropriate studies in both academic (35% vs 16%, P < .001) and community practice (29% vs 15%, P = .04) settings. CONCLUSION: The clinical application of the AC for TTE is feasible, and the frequency of Appropriate and Inappropriate outpatient TTEs is similar in academic and community practice settings. However, limitations of the AC for TTE are identified that suggest revisions will be needed to fully encompass and stratify the broad clinical practice of echocardiography.

Prospective evaluation of the clinical application of the American College of Cardiology Foundation/American Society of Echocardiography Appropriateness Criteria for transthoracic echocardiography.

We sought to prospectively evaluate the clinical application of the American College of Cardiology Foundation/American Society of Echocardiography Appropriateness Criteria (AC) for transthoracic echocardiography in a single-center university hospital. Indications for transthoracic echocardiograms (TTE) were prospectively determined for consecutive studies by 2 reviewers and categorized, according to the AC for TTE, as appropriate (A) or inappropriate (I). The overall level of agreement in characterizing appropriateness between reviewers was high (kappa = 0.83). Among the 1,553 studies for which a primary indication was determined, 89% were covered in the AC for TTE. Of these studies, 89% were A, and 11% were I. New important TTE abnormalities were more common on A compared with I studies (40% vs. 17%, p < 0.001), and noncardiac specialists more frequently ordered I studies (13% vs. 9%, p = 0.04). In conclusion, the AC for TTE encompasses the majority of clinical indications for TTE and appears to reasonably stratify TTE ordering. However, revisions will be needed to fully capture and stratify appropriate clinical practice.

Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes.

Human peripheral lymphocytes from whole blood cultures were exposed to either soluble form of nickel carbonate hydroxide (NiCH) (0-60 microM), or of nickel subsulfide (Ni(3)S(2)) (0-120 microM), or of nickel oxide (NiO) (0-120 microM), or nickel sulfate (NiSO(4)) (0-120 microM) for a short duration of 2 h. The treatments occurred 46 h after the beginning of the cultures. The cultures were harvested after a total incubation of 72 h, and sister-chromatid exchange (SCE), replication index (RI), and mitotic index (MI) were measured for each nickel compound. The soluble form of NiCH at 30 microM but those of Ni(3)S(2) and NiO at 120 microM produced significant increase in the SCE per cell compared to the control value, whereas NiSO(4) failed to produce any such significant increase. Except NiSO(4), the soluble forms of NiCH, Ni(3)S(2), and NiO produced significant cell-cycle delay (as measured by the inhibition of RI) as well as significant inhibition of the MI at respective similar concentrations as mentioned above. Pretreatment of human blood lymphocytes with catalase (H(2)O(2) scavenger), or superoxide dismutase (superoxide anion scavenger), or dimethylthiourea (hydroxyl radical scavenger), or deferoxamine (iron chelator), or N-acetylcysteine (general antioxidant) inhibited NiCH-induced SCE, and changes in RI and MI. This suggests the participation of oxidative stress involving H(2)O(2), the superoxide anion radical, the hydroxyl radical, and iron in the NiCH-induced genotoxic responses. Cotreatment of NiCH with either verapamil (inhibitor of intracellular calcium ion ([Ca(2+)](i)) movement through plasma membranes), or dantrolene (inhibitor of [Ca(2+)](i) release from sarcoplasmic reticulum), or BAPTA (Ca(2+) chelator) also inhibited the NiCH-induced responses. These results suggest that [Ca(2+)](i) is also implicated in the genotoxicity of NiCH. Overall these data indicate that various types of oxidative stress including iron-mediated oxidative stress involving the Fenton-Haber/Weiss reaction, and alterations in calcium homeostasis are involved in the genetic damage produced by the soluble form of NiCH.

Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in human lymphocyte death induced by nickel carbonate hydroxide in vitro.

When isolated human lymphocytes were treated in vitro with various concentrations of soluble form of nickel carbonate hydroxide (NiCH) (0-1 mM), at 37 degrees C for 4 h, both concentration- and time-dependent effects of NiCH on lymphocyte death were observed. Increased generation of hydrogen peroxide (H(2)O(2)), superoxide anion (O(2)(-) ), depletion of both no protein (NP-) and protein (P-) sulfhydryl (SH) contents and lipid peroxidation (LPO) were induced by NiCH. Pretreatment of lymphocytes with either catalase (H(2)O(2) scavenger), or deferoxamine (DFO) (iron chelator), or excess glutathione (GSH) (an antioxidant) not only significantly reduced the NiCH-induced generation of H(2)O(2) and LPO, but also increased the NP-SH and P-SH contents initially reduced by NiCH. NiCH-induced generation of excess O(2)(-) but not excess LPO was significantly reduced by pretreatment with superoxide dismutase (SOD). NiCH-induced lymphocyte death was significantly prevented by pre-treatment with either catalase, or dimethylthiourea/mannitol (hydroxyl radical scavengers), or DFO, or excess GSH/N-acetylcysteine. NiCH-induced lymphocyte death was also significantly prevented by pretreatment with excess SOD. Thus, various types of oxidative stresses play an important role in NiCH-induced lymphocyte death. Cotreatment with cyclosporin A (a specific inhibitor of alteration in mitochondrial membrane potential (DeltaPsi(m)) not only inhibited NiCH-induced alteration in DeltaPsi(m), but also significantly prevented Ni-compound-induced lymphocyte death. Furthermore, NiCH-induced destabilization of cellular calcium homeostasis. As such, NiCH-induced lymphocyte death was significantly prevented by modulating intracellular calcium fluxes such as Ca(2+) channel blockers and intracellular Ca(2+) antagonist. Thus, the mechanism of NiCH (soluble form)-induced activation of lymphocyte death signalling pathways involves not only the excess generation of different types of oxidative stress, but also the induction of alteration in DeltaPsi(m) and destabilization of cellular calcium homeostasis as well.

Male pseudohermaphroditism and gonadal mosaicism in a 47,XY,+22 fetus.

Trisomy 22 syndrome manifestations include cranial and facial anomalies. Ambiguous genitalia have been described in some fetus, but histological examination of the gonads has been rarely provided. We report here the first case of a male pseudohermaphrodite fetus with non-mosaic full trisomy 22 in amniocytes and presenting with ambiguous external genitalia, testes, and a uterus. In this case, we have further analyzed cytogenetically gonadal and uterine tissues. FISH analyses on paraffin-embedded gonads and uterus indicated the presence of two cell lines: XY and monosomy X, with 22%-50% of uterine cells having monosomy X, while 85%-100% of right and 77%-96% of left testicular cells were XY. The distribution of sex chromosomes observed in these tissues could explain the sexual differentiation observed in this fetus. On the other hand, this phenotype could also have resulted from cryptic anomalies in one or several genes implicated in sexual differentiation. Further evidence is thus needed before identifying the true cause of pseudohermaphroditism in our patient.

The role of breastfeeding in postpartum disease activity in women with inflammatory bowel disease.

BACKGROUND: Women with inflammatory bowel disease (IBD) have an increased risk of experiencing a flare in the postpartum period. Work in other autoimmune disorders has found that breastfeeding may be associated with an increased risk for developing postpartum disease relapse. AIM: To assess the association between breastfeeding behavior and postpartum disease activity. METHODS: Women with IBD followed at a tertiary care center with a history of childbirth within the past 5 yr were recruited. Medical records were reviewed for disease type, disease activity during and after pregnancy, medication use, smoking, and breastfeeding behavior. The exposure of interest was breastfeeding prior to the onset of disease activity following a successful asymptomatic pregnancy. RESULTS: One hundred and twenty-two consecutive women who fit eligibility criteria were studied. Overall, only 44% (54/122) of the women had breastfed their infant. Reasons included physician recommendation, fear of medication interactions, and personal choice. Forty-three percent (23/54) of those who breastfed experienced a postpartum flare of their disease. The unadjusted odds ratio for disease activity with a history of breastfeeding was 2.2 (95% CI 1.2-3.9, p= 0.004). When stratified by disease type, the OR for ulcerative colitis was 0.89 (0.29-2.7, p > 0.05) and Crohn's disease 3.8 (1.9-7.4, p < 0.05). When adjusted for medication cessation, the OR became nonsignificant. CONCLUSIONS: A significant number of women with IBD do not breastfeed their children. Any relationship between breastfeeding and disease activity may be more a consequence of discontinuation of IBD therapies.