Immunohistochemistry as a tool in the differential diagnosis of ovarian tumors: an update.

Immunohistochemistry has become an important tool in the diagnosis of ovarian tumors. This article reviews the role of immunohistochemistry in the differential diagnosis of the three main categories of ovarian tumors, with emphasis on recently developed antibodies. In the surface epithelial stromal category the most common problem is its discernment from metastasis. The use of differential cytokeratins, primarily CK7 and CK20, as well as Cdx-2, beta-catenin, and P504S in differentiating between metastatic adenocarcinoma, particularly of colorectal origin, and primary ovarian carcinoma is discussed. Dpc4 may be useful in distinguishing pancreatic from ovarian mucinous carcinomas, because up to 55% of pancreatic carcinomas lack Dpc4 expression, whereas the differential expression of mucin genes may be helpful in distinguishing between primary ovarian mucinous and metastatic tumors. Urothelial markers (thrombomodulin and uroplakin III) and renal cell carcinoma markers (CD10 and renal cell carcinoma marker) can be helpful in the diagnosis of metastatic urothelial and renal cell tumors to the ovary. The roles of inhibin, calretinin, CD99, and other recently described markers in the diagnosis of sex cord-stromal tumors are reviewed. The uses of OCT-4 (POU5F1) (a new highly sensitive and specific marker of dysgerminoma and embryonal carcinoma), CD30, and c-kit are also discussed.     

Ability to use duplex US to quantify internal carotid arterial stenoses: fact or fiction?

PURPOSE: To determine if duplex ultrasonography (US) can help predict the degree of internal carotid arterial (ICA) stenosis. MATERIALS AND METHODS: ICA peak systolic velocity (PSV) and the ratio of the PSV in the ICA to that in the ipsilateral common carotid artery (VICA/VCCA) were compared with the degree of arteriographically measured stenosis. ICAs were arteriographically subgrouped at 10% incremental levels of stenosis and broader ranges. Mean PSV, VICA/VCCA, and SDs were calculated for each category. Histograms showing the numbers of stenotic ICAs in subgroups and for vessels with stenoses of greater than or equal to or less than 70% narrowing were constructed. The number of vessels correctly subgrouped with typical Doppler US thresholds was calculated. RESULTS: Mean PSV and VICA/VCCA increased with stenosis level (P < .01); SDs were wide. Histograms showed Doppler US values in the central groups across all disease levels. Histograms differentiating at least or less than 70% stenosis showed minimal overlap. PSV and VICA/VCCA helped classify, respectively, 185 and 181 of 204 vessels with stenoses of less than 50%, 15 and 21 of 46 vessels with stenoses of 50%-69%, and 73 and 67 of 84 vessels with stenoses of 70% or greater. When classifying stenoses as 69% or less or 70% or more, PSV and VICA/VCCA were correct in 90.6% and 90.3% of vessels. CONCLUSION: Doppler US is excellent for classifying stenoses as above or below a single degree of severity but does not function well in stenosis subclassification.     

Quality-of-life and behavioral outcome measures in randomized controlled trials of antiepileptic drugs: a systematic review of methodology and reporting standards

PURPOSE: To review the methodology and use of quality-of-life and behavioral measures used in randomized controlled trials (RCTs) of antiepileptic drugs in patients with epilepsy. METHODS: Trial reports were found by searching a previously developed comprehensive database of epilepsy RCTs and searching through journals by hand. Inclusion and exclusion criteria were applied, and methodological and quality-of-life and behavioral measure data were extracted. RESULTS: There were 52 different measures used in 46 trials, with the Profile of Mood States, the Minnesota Multiphasic Personality Inventory, and the Washington Psychosocial Seizure Inventory being applied the most frequently. Overall, evidence of the reliability, validity, and sensitivity of measures used in populations of people with epilepsy was sparse. There was also little information on the clinical interpretation of the results. CONCLUSION: Our results highlight a consistent failure to apply quality-of-life and behavioral measures in RCTs in a systematic way. We found repeated evidence of researchers' failure to review the use of previous measures and selection of measures without evidence of their appropriateness for use in a population with epilepsy. We recommend the use of quality-of-life and behavioral measures in RCTs with proven psychometric properties in a population with epilepsy.     

A separated primary and scatter model for independent dose calculation of intensity modulated radiotherapy

BACKGROUND AND PURPOSE: Independent checking of beam monitor units is an essential step in the preparation of any radiotherapy plan. The present work describes a simple model for calculating a point dose from an arbitrary number of irregular, asymmetric fields, typical of beam segments used for IMRT. MATERIALS AND METHODS: Primary and scatter dose contributions were separated using a two-parameter exponential fit to measured beam data, from which differential scatter is determined. A total of 60 IMRT patient plans for a five-field prostate class solution were investigated to validate the model. RESULTS: The average difference between the model's prediction and direct measurement of reference dose was found to be -0.6% (ranging from -2.9% to +1.6%), with a standard deviation of 1.0%. This compares well with the observed average difference between treatment planning system prediction and direct measurement of +0.8% (SD 0.6%). CONCLUSIONS: The model is shown to provide a reliable and accurate independent check of planning system monitor units for the prostate IMRT plans studied. Implementation of the model could significantly reduce the time needed for point dose verification of IMRT plans currently performed by direct measurement.     

Caprine mucopolysaccharidosis IIID

Mucopolysaccharidosis type IIID (MPS IIID) is a lysosomal storage disorder resulting from lack of activity of the lysosomal hydrolase N-acetylglucosamine 6-sulfatase (6S) (EC 3.1.6.14). The syndrome is associated with systemic and central nervous system (CNS) heparan sulfate glycosaminoglycan (HS-GAG) accumulation, secondary storage of lipids, and severe, progressive dementia. In this investigation, caprine MPS IIID, established as a large animal model for the human disease, was used to evaluate the efficacy of enzyme replacement therapy (ERT). Recombinant caprine 6S (rc6S) (1 mg/kg/dose) was administered intravenously to one MPS IIID goat kid at 2, 3, and 4 wks of age. Five days after the last dose, the uronic acid (UA) content and the composition of uncatabolized HS-GAG fractions in the brain of the ERT-treated MPS IIID kid were similar to those from a control, untreated MPS IIID animal. However, hepatic uronic acid levels in the treated MPS IIID kid were approximately 90% lower than those in the untreated MPS IIID control; whereas the composition of the residual hepatic HS-GAG was identical to that in the untreated animal. Marked reduction of lysosomal storage vacuoles in hepatic cells of the treated MPS IIID kid was observed, but ERT had no effect on CNS lesions. No residual 6S activity was detected in brain or liver. This preliminary investigation indicates that other treatment regimens will be necessary to ameliorate MPS III-related CNS lesions.     

The human acrosome reaction

We developed tests of sperm-oocyte interaction: sperm-zona binding, zona-induced acrosome reaction, spermzona penetration and sperm-oolemma binding, using oocytes which failed to fertilise in clinical in vitro fertilization (IVF). Although oocyte defects contribute to failure of sperm oocyte interaction, rarely are all oocytes from one woman affected. Low or zero fertilization in standard IVFwas usually caused by sperm abnormalities. Poor sperm-zona pellucida binding was frequently associated with failure of standard IVF and obvious defects of sperm motility or morphology. The size and shape of the acrosome is particularly important for sperm binding to the oocyte. The proportion of acrosome intact sperm in the insemination medium was related to the IVF rate. Inducing the acrosome reaction with a calcium ionophore reduced sperm-zona binding. Blocking acrosome dispersal with an acrosin inhibitor prevented spermzona penetration. Sperm-zona penetration was even more highly related to IVF rates than was sperm-zona binding. Some patients had low or zero fertilization rates with standard IVF but normal sperm by conventional tests and normal sperm-zona binding. Few of their sperm underwent the acrosome reaction on the surface of the zona and none penetrated the zona. In contrast, fertilization and pregnancy rates were high with intracytoplasmic sperm injection. We call thiscondition defective zona pellucida induced acrosome reaction. Discovery of the nature of the abnormalities in the signal transduction and effector pathways of the human zona pellucida induced acrosome reaction should result in simpler tests and treatments for the patients and also provide new leads for contraceptive development.     

Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with refractory leukemia.

PURPOSE: To investigate the activity of a novel dioxolane L-nucleoside analog, troxacitabine (L-(-)-OddC, BCH-4556), in patients with refractory leukemia. PATIENTS AND METHODS: Study participants were patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP). Troxacitabine was provided as an intravenous infusion for more than 30 minutes daily for 5 days at a dose of 8.0 mg/m(2)/d (40 mg/m(2) per course). Courses were given every 3 to 4 weeks according to antileukemic efficacy. RESULTS: Forty-two patients (AML, 18 patients; MDS, one patient; ALL, six patients; CML-BP, 17 patients) were treated. Median age was 51 years (range, 23 to 80 years); 22 patients were male. Stomatitis was the most significant adverse event, with three patients (7%) and two patients (5%), respectively, experiencing grade 3 or 4 toxicity. Ten patients (24%) had grade 3 hand-foot syndrome, and two patients (5%) had grade 3 skin rash. One patient (2%) had grade 3 fatigue and anorexia. Marrow hypoplasia occurred between days 14 and 28 in 12 (75%) of 16 assessable patients with AML. Two complete remissions and one partial remission (18%) were observed in 16 assessable patients with AML. None of six patients with ALL responded. Six (37%) of 16 assessable patients with CML-BP experienced a return to chronic-phase disease. CONCLUSION: Troxacitabine has significant antileukemic activity in patients with AML and CML-BP.