Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia

The purpose of this report was to evaluate scintigraphy analysis of Southern blot hybridization as a method to quantify the breakpoint cluster region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic myelogenous leukemia (CML). Cytogenetic and molecular studies performed simultaneously on 474 bone marrow and/or blood samples from 300 patients treated with alpha-interferon-based therapy were compared. Molecular results were expressed as the percentage of rearranged BCR bands versus the total scintigraphic signal. The percentage of Ph+ metaphases was calculated on 25 metaphases. The results of molecular studies obtained on both peripheral blood and bone marrow samples were identical. The rank correlation between the BCR quantification and the percentage of Ph positivity in 465 samples was excellent (r = .78). However, of 99 samples with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR rearrangement. In samples with a minor or no cytogenetic response (Ph+ metaphases, > 34%), BCR analysis overestimated the degree of response in 73 of 326 samples (22%). Nevertheless, survival analysis by BCR quantification level showed statistically better outcome for patients in complete or partial molecular response (P < .01). Molecular quantification of BCR was useful in monitoring the course of Ph+ CML. This method, which can be used on peripheral blood, detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression.     

Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia

The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to- moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan.     

Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity

We have compared multiple assays for the P-glycoprotein (Pgp/MDR1) phenotype in fresh and thawed adult acute leukemia to validate and quantitate measures for the expression and function of Pgp. The results are related to the Pgp-expressing KB8 and KB8-5 call lines. The most sensitive assay was the measurement of modulation of the rhodamine 123 (R123) fluorescence by 2 micromol/L PSC833, followed by the modulation of the probe calcein-AM. We also found a good intralaboratory and interlaboratory correlation between the values of the R123/PSC833 assay for fresh as well as thawed samples. In addition, the affects of PSC833 on 3H-daunorubicin (DNR) accumulation, DNR fluorescence, and 3H- vincristine accumulation were very similar. The correlation between the DNR/PSC833 and R123/PSC833 test was r = .86 (N = 51). The modulation of drug accumulation by 8 micromol/L verapamil was the some as the PSC833 effect for DNR (117%, N = 21), but was higher for vincristine in every single case (161% v 121%, N = 22; P< .001), indicating additional verapamil effects, not related to Pgp. The correlation of the staining of viable cells for Pgp with the monoclonal antibody MRK16 was r = .77 (N = 52) for the R123/PSC833 functional test and r = .84 (N = 50) for the DNR/PSC833 test. From these results it could be calculated that a maximal increase of the mean DNR accumulation of about 50% can be achieved by blocking Pgp pump activity with PSC833 in leukemic blast samples with the highest mean Pgp expression. Subpopulations of blast calls with higher Pgp activity are likely to be present. Their relevance has to be studied further. The methods outlined here allow the reliable, quantitative monitoring of the Pgp/MDR1 phenotype in leukemias in multicentered, clinical Pgp modulation studies.     

Minimal invasive para-rectus approach for limited open reduction and percutaneous fixation of displaced acetabular fractures

Introduction

Minimal invasive fixation has been reported as an alternative option for treatment of acetabular fractures to avoid blood loss and complications of extensive approaches. Closed reduction and percutaneous lag screw fixation can be done in minimally displaced acetabular fractures. Open reduction is indicated, if there is wide displacement. In this study, we report the use of a mini-open anterior approach to manipulate and reduce anteriorly displaced transverse acetabular fractures combined with percutaneous lag screw fixation.

Methods

This report included eight patients. All had anterior displaced simple transverse acetabular fractures. An oblique mini-incision was made above and medial to the mid-inguinal point, and lateral to the lateral border of rectus abdominis muscle. The external abdominal oblique aponeurosis was incised along its fibres. The arched fibres of internal abdominal oblique were displaced medially above the inguinal ligament to expose and incise the fascia transversalis. Care was taken to avoid injury of ilioinguinal nerve, inferior epigastric vessels, and spermatic cord. The external iliac vessels were palpated and protected laterally. A blunt long bone impactor was introduced through this small incision to manipulate and reduce the fracture under fluoroscopic control. Fluoroscopic guided percutaneous lag screw fixation was done in all patients.

Results

The average time to operation was 4 days. Average blood loss was 110 mL. Operative time averaged 95 min. Maximum fracture displacement averaged 10 mm preoperatively and 1.3 mm postoperatively. According to Matta score, anatomical reduction of the fracture was achieved in five patients and imperfect in three. Follow up averaged 27 months. Wound healing occurred without complications and fracture union was achieved without secondary displacement in all patients. Average time to fracture healing was 14 weeks. According to the modified Merle d’Aubigné score, functional outcome was good to excellent in all patients.

Discussion and conclusion

Limited open reduction can solve the problem of fracture reduction, which is the main concern in minimal invasive fixation of acetabular fractures. It may help the inclusion of displaced acetabular fractures for percutaneous lag screw fixation. This mini-para-rectus approach has the advantages of minimal soft tissue dissection with the possible anatomical reduction of simple transverse displaced acetabular fractures.     

Surgical management of epilepsy due to cerebral cavernomas using neuronavigation and intraoperative MR imaging

OBJECTIVES： Cure from seizures due to cavernomas might be surgically achieved dependent on both, the complete removal of the cavernoma as well as its surrounding hemosiderin rim. High field intraoperative MRI imaging （iopMRI） and neuronavigation might play a crucial role to achieve both goals. We retrospectively investigated the long-term results and impact of intraoperative 1.5T MRI （iopMRI） and neuronavigation on the completeness of surgical removal of a cavernous malformation （CM） and its perilesional hemosiderin rim as well as reduction of surgical morbidity.     

Mandibular symphysis morphology and dimensions in different anteroposterior jaw relationships

Objective:To assess the morphology and dimensions of mandibular symphysis (MS) in different anteroposterior jaw relationships and to investigate whether craniofacial parameters have any correlation with its shape and/or dimensions.Materials and Methods:Lateral cephalograms of subjects with Class I, Class II, and Class III skeletal relationships were traced. Several craniofacial and MS parameters were measured. MS parameters were compared between the three groups using analysis of variance and were correlated with the craniofacial parameters using the Pearson correlation coefficient.Results:Larger angle of concavity of the chin, more inclination of the alveolar bone toward the mandibular plane, and larger MS dimensions and area (P < .001) were found with a Class III skeletal relationship compared to Class I and Class II relationships. The Pearson correlation coefficient between Id-Me and AFH was r  =  0.83 and between Id-Me and LAFH it was r  =  0.81.Conclusions:The dimensions and configuration of MS in the Class III relationship were different than those in Class I and Class II relationships; the alveolar part of MS compensated for the skeletal relationship in the Class III pattern. MS dimensions were strongly correlated to anterior facial dimensions.     

Effect of socioeconomic status on normative and perceived orthodontic treatment need

Objective:To determine the influence of socioeconomic status (SES) on normative and perceived orthodontic treatment need, satisfaction with dental appearance, and regularity of dental attendance.Materials and Methods:The sample consisted of 550 adolescents (232 boys, 318 girls) aged 13 to 17 years who were categorized according to SES into three groups: low, middle, and high SES. Normative treatment need was assessed by using the Index of Orthodontic Treatment Need. Data were collected by clinical examination and face-to-face interview. The χ² test and logistic regression analysis were used for statistical analyses.Results:Approximately 34.0% of the untreated subjects had a definite dental need for treatment and 24.5% had a moderate need; among those, 53.5% were of low SES (P  =  .017). One-third of the sample had a moderate to definite esthetic need, most of whom had a low SES (P  =  .009). Of the subjects who were dissatisfied with their dental appearance and reported a self-perceived need for treatment, around one-third had a low SES. Most subjects with low SES were irregular dental attenders (P < .001). Subjects of low SES, those who had a self-perceived need for treatment, and those who were dissatisfied with their dental appearance were more likely to have a definite normative esthetic need.Conclusions:Subjects of low SES exhibited greater normative and perceived treatment needs than subjects of higher SES. They were less satisfied with their dental appearance and visited a dentist less frequently.