Embryonic Testicular Regression Syndrome Presenting as Primary Amenorrhea: A Case Report and Review of Disorders of Sexual Development.

BACKGROUND: Sex development depends on the synchronous interaction of complicated genetic and hormonal events. Sex differentiation begins with sex determination, which is the assignment of the embryonic bipotential gonads as either testes or ovaries on the basis of transcriptional regulation. Hormonal regulation then directs the development of the male or female phenotype. Disruptions of this intricate cascade of events result in disorders of sexual development. CASE: A 16-year-old female adolescent presented with primary amenorrhea. Evaluation revealed female external genitalia, XY karyotype, absent gonadal tissue, and rudimentary Müllerian structures. On the basis of her constellation of findings, the most logical diagnosis was the rare embryonic testicular regression syndrome. SUMMARY AND CONCLUSION: A careful understanding of embryonic sexual development is critical to the evaluation of patients with disorders of sexual development.

Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center.

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch-Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death ('primary refractoriness'). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

Contrast-enhancement techniques for particle-image velocimetry.

In video-based particle-image velocimetry (PIV) systems for fluid mechanics research, it is sometimes desirable to image seed particles to be smaller than a camera pixel. However, imaging to this size can lead to marginal image contrast such that significant numbers of erroneous velocity vectors can be computed, even for simple flow fields. A variety of image-enhancement techniques suitable for a low-cost PIV system that uses video cameras are examined and tested on three representative flows. Techniques such as linear contrast enhancement and histogram hyperbolization are shown to have good potential for improving the image contrast and hence the accuracy of the data-reduction process with only a 15% increase in the computational time. Some other schemes that were examined appear to be of little practical value in PIV applications. An automated shifting algorithm based on mass conservation is shown to be useful for displacing the second interrogation region in the direction of flow, which minimizes the number of uncorrelated particle images that contribute noise to the data-reduction process.

Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia.

PURPOSE: To evaluate the efficacy and safety of the combination of topotecan and cytarabine in patients with myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Fifty-nine patients with MDSs and 27 with CMML were enrolled. They were either previously untreated (66%) or had received only biologic agents (14%) or chemotherapy with or without biologic agents (20%). Treatment consisted of topotecan 1.25 mg/m(2) by continuous intravenous infusion daily for 5 days and cytarabine 1. 0 g/m(2) by infusion over 2 hours daily for 5 days. Prophylaxis included antibacterial, antifungal, and antiviral agents. At a median follow-up of 7 months, all 86 patients were assessable for response and toxicity. RESULTS: Complete remission (CR) was observed in 48 patients (56%; 61% with MDSs, 44% with CMML; P =.15). Similar CR rates were observed for patients with good-risk and poor-risk MDS (70% and 56%, respectively). The treatment effectively induced CR in patients with a poor-prognosis karyotype involving chromosomes 5 and 7 (CR, 71%) and secondary MDSs (CR, 72%). Fifty-four patients received one induction course, 25 patients received two, and the rest received more than two. The median number of continuation courses was two. The median overall duration of CR was 34 weeks (50 weeks for MDSs and 33 weeks for CMML). The median survival was 60 weeks for MDS and 44 weeks for CMML patients. CR and survival durations were longer in patients with refractory anemia with excess blasts (RAEB). Grade 3 or 4 mucositis or diarrhea was observed in three patients each. Fever was observed in 63%, and infections in 49% of patients. Six patients (7%) died during induction therapy. CONCLUSION: Topotecan and cytarabine induced high CR rates in unselected patients with MDSs and CMML, particularly among patients with poor-prognosis cytogenetics and secondary MDSs. Topotecan-cytarabine is an active induction regimen in MDS and CMML patients, is well tolerated, and is associated with a low mortality rate.

Hemolytic transfusion reaction due to anti-Tc(a).

BACKGROUND: Anti-Tc(a) detects a high-incidence antigen in the Cromer blood group system. Cromer system antibodies have not usually been associated with hemolytic transfusion reactions or hemolytic disease of the newborn. CASE REPORT: Anti-Tc(a) (initially identified in the patient's serum in 1982) was not detected when she was admitted to the hospital with upper gastrointestinal. bleeding. Three units of red cells were administered. The patient was discharged, but was readmitted to the hospital after her hemoglobin fell to 7.1 g per dL. Antibody detection tests remained negative and three additional units were transfused. Over the next 7 days, her hemoglobin steadily fell to 5.5 g per dL. The level of lactate dehydrogenase rose to 1257, the plasma hemoglobin rose to >16 mg per dL, and the haptoglobin decreased to <6 mg per dL. Five days after transfusion, her direct antiglobulin test was weakly reactive with complement-specific antiglobulin reagents. Eluates were nonreactive. Anti-Tc(a) was detected in her serum; no other antibodies were detected. Differential typing failed to detect any circulating Tc(a+) red cells. The antibody was strongly reactive in a monocyte monolayer assay. CONCLUSION: Although Cromer system antibodies have generally not been proven to be clinically significant in transfusion therapy, the destruction of red cells from six units of transfused Tc(a+) red cells in this patient indicates that anti-Tc(a) may have destructive potential in some patients.

Anti-Dob implicated as the cause of a delayed hemolytic transfusion reaction.

A 27-year-old, gravida 3, para 2 woman experienced a delayed hemolytic transfusion reaction. She had anti-Dob in both serum and eluate 8 days after infusion of 6 units of Do(b+) red cells. No antibody had been detected prior to transfusion. By the 15th day after transfusion, there was no evidence of survival of red cells from any of the 6 units. Anti-C and anti-M were demonstrated later, but 29 months after transfusion, no atypical antibodies were detectable. The evidence suggests anti-Dob should be considered an antibody of potential clinical significance until contrary evidence becomes available.

Example of a thimerosal-dependent antibody without apparent blood group specificity.

A third example of a thimerosal-dependent hemagglutinin is reported. The IgG antibody reacted by antiglobulin or ficin techniques with all cells incubated in the presence of thimerosal, including iadult cells and two examples of the Rhnull phenotype. Agglutination was inhibited by excess thimerosal (5 g/dl).

A modified capillary test using 4% ficin.

A capillary technique is described for economical Rh-phenotyping of large numbers of blood samples using diluted antisera and 4% ficin solution. This system is no more time consuming that conventional tube techniques, since enzyme premodification of the cells is not required.

Hemolytic disease of the newborn associated with anti-Jk3.

This report documents a mild case of hemolytic disease of the newborn (HDN) associated with anti-Jk3. The Filipino mother had previously had six children none of whom had been affected by HDN. She had been transfused at the time of her second pregnancy. Anti-Jkb and anti-Jk3 were detected in the maternal serum at the time of her seventh delivery. No prenatal serologic tests for blood group antibodies had been performed. The cord blood was found to have a positive direct antiglobulin test and anti-Jkb plus anti-Jk3 were eluted. The infant was treated with phototherapy.

Auto anti-Kpb associated with weakened antigenicity in the Kell blood group system: a second example.

An 84-year-old woman with intestinal bleeding had marked reduction of red blood cell antigenicity in the Kell system, and a positive direct antiglobulin test caused by auto-anti-Kpb. KX antigen activity of her cell was increased, an observation which supports the belief that KX marks a precursor structure utilized in the normal Kell biosynthetic pathway. It is postulated that reduced Kell antigenicity was an acquired change that resulted from enzymatic degradation, possibly of bacterial origin.

Coexistent Tk and VA polyagglutinability.

Serologic investigations of the red blood cells of two patients indicated polyagglutination as the cause of compatibility problems. Lectin studies to classify the variety of polyagglutination demonstrated the simultaneous exposure of two latent membrane receptors, Tk and VA. It is proposed that different bacterial enzymes were responsible.

Serologic activity of fatty acid dependent antibodies in albumin-free systems.

Fatty acid dependent agglutinin (FADA) refers to serum with the special ability to cause agglutination of red blood cells in the presence of certain fatty acids. The agglutinating mechanism is unclear. It has been proposed that the agglutinin reacts with albumin that has been conformationally altered by sodium caprylate and that the immune complex is passively adsorbed onto red blood cells. This report presents data that contradicts the proposal assigning a specific role to albumin in the agglutinating mechanism. FADA were isolated by column chromatography of resolubilized euglobulin preparations. No evidence of contamination with albumin was obtained in those IgM fractions possessing FADA activity. We propose, as an alternative explanation, that the serologic activity of FADA depends upon the interaction of IgM agglutinins with haptenic fatty acids.

Unexpected limitations in the use of commercial antiglobulin reagents.

The majority of antiglobulin sera used in blood banks in the USA are commercially prepared immune rabbit sera, designed to be reactive only with human red blood cells sensitized with immunoglobulins or complement components. Current manufacturing methods result in a product that gives reliable specific reactions provided that the test red blood cells are normal, particularly with respect to sialic acid levels. This report describes our findings of false positive antiglobulin tests caused by incompletely absorbed antiglobulin reagents when cells with low sialic acid levels were tested. An evaluation of nine commercially prepared antiglobulin reagents revealed, in many of them, the presence of anti-species antibody, anti-T, and anti-Tn. Blood bank personnel must be aware of these characteristics especially when testing either enzyme premodified or polyagglutinable cells. The use of incompletely absorbed reagents might account for positive direct antiglobulin tests that are encountered occasionally in apparently normal healthy individuals. Furthermore, recent protocols advocating the use of trypsinized cells for the evaluation of anti-C3d activity of antiglobulin sera are invalid if the reagent is inadequately absorbed of anti-species agglutinins.