Diploidy in second trimester prostaglandin E2 induced abortuses

Second trimester abortuses induced by prostaglandin E₂ were karyotyped. Twenty (11.9%) had chromosomal aberrations. These were diploid aberrations except for one case of double Y male. Twelve, however, were genetically balanced chromosomal rearrangements, and two had deletions of acrocentric G group chromosome short arms which should have no phenotypic effects. Only 5 cases out of 20 or 2.98% of 168 karyotyped could be classified as having serious chromosomal defects. These were all structural lesions, suggesting a shift from aneuploidy in first trimester abortuses to diploidy in second trimester induced abortuses. The decline In fetal deaths In the second trimester of pregnancy might therefore be associated not so much with a decline in the frequency of chromosomal aberrations but apparently with a limitation of the more extreme variations through selection and greater maturity.     

Severe aphthous stomatitis associated with oral calcineurin and mTOR inhibitors

Background Aphthous stomatitis, a common mucocutaneous disorder, is a well accepted complication of sirolimus therapy. This association has been reported less frequently with tacrolimus. Case We present an 11‐year old male with Budd‐Chiari syndrome who experienced profound worsening of chronic aphthous ulcers after immunosuppressive therapy was changed from tacrolimus to sirolimus. Conclusion Since these drugs are used widely in the pediatric transplantation population, this report serves to heighten awareness of this debilitating phenomenon, and to stress the importance of exercising caution when sirolimus and tacrolimus are administered in combination to pediatric patients.     

Incisional wound healing in transforming growth factor-β1 null mice

Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure.     

Community‐Based Practice Experience of Unsuspected Breast Magnetic Resonance Imaging Abnormalities Evaluated With Second‐Look Sonography

Objective. The purpose of this study was to assess the utility and efficacy of second‐look breast sonography in the evaluation of abnormalities identified on presurgical breast magnetic resonance imaging (MRI) examinations. Methods. A retrospective review was performed of 152 presurgical breast MRI examinations having 196 unsuspected abnormalities to identify findings that underwent subsequent breast sonography. Eligible examinations had a suspicious abnormality identified on presurgical MRI and documentation of the location and size of the finding on MRI and subsequent second‐look sonography. Fourteen examinations not meeting the criteria were excluded, with 182 abnormalities remaining. Patient medical records were reviewed. Results. Seventy percent (128 of 182) of breast MRI lesions were visible at second‐look sonography; 30% (54 of 182) were sonographically occult. Ninety‐five percent (121 of 128) of sonographically visible abnormalities underwent breast biopsy. Pathologic examinations of sampled sonographically visible lesions revealed 39 cancers, 9 high‐risk lesions, 72 benign lesions, and 1 lesion not specified at surgery; 23% (9 of 128) of cancers were in the contralateral breast. Fifty‐four lesions were sonographically occult. Needle biopsy was performed for 93% (50 of 54) of occult lesions, revealing 8 cancers, 1 high‐risk lesion, and 41 benign lesions; 3 of the benign lesions did not have sufficient pathologic specimens but were benign at follow‐up. Magnetic resonance imaging guidance was used in 86% (43 of 50) of these biopsies. One contralateral cancer was identified in the sonographically occult subset. Of the 182 lesions that underwent second‐look sonography, 20% (36 of 182) had a change in management. Conclusions. Second‐look sonography has value in the evaluation of abnormalities found on breast MRI. We found enhancements in 70% (128 of 182), yielding 39 cancers.     

Assessment of methotrexate as a potential immunosuppressive agent in baboons

Methotrexate is an anti-proliferative agent that affects both T-cell and B-cell immunity, and therefore might be expected to suppress antibody (Ab) production. Although it has been used in xenotransplantation studies to suppress anti-pig Ab production, it has always been used in combination with other immunosuppressants. The purpose of this study was to measure its effect as a single immunosuppressant on anti-Gal Ab production in baboons (n=4). Pharmacokinetic studies showed that methotrexate was not detected in the blood when administered per os. Prolonged daily IV or IM administration (i) reduced T-cell and B-cell numbers by 50% to 70% and modestly reduced responsiveness on mixed lymphocyte reaction (but only at toxic doses) and (ii) did not result in lowered anti-Gal Ab levels, only marginally reducing the rate of return of Ab after extracorporeal immunoadsorption. Our observations would suggest that methotrexate will not contribute significantly to immunosuppressive regimens in the baboon at non-toxic doses.