First report of donor cell-derived acute leukemia as a complication of umbilical cord blood transplantation

Donor cell leukemia is a rare complication after allogeneic hematopoietic stem cell transplantation. A 12-month-old boy underwent unrelated donor umbilical cord blood transplant (UCBT) for refractory Langerhan's cell histiocytosis. Forty months after transplantation, he developed acute myeloid leukemia. Cytogenetic and molecular analysis confirmed donor cell origin. The Cord Blood Bank (CBB) contacted the donor's family and established that the child, now 7 years old, was healthy. This represents the first reported case of donor cell leukemia following UCBT. This case illustrates that donor cell leukemia is a rare but real event after UCBT as with other stem cell sources and highlights the need for CBBs to maintain linkage data between donors and recipients.     

Effectiveness of a Locking Plate in Preserving Midcalcaneal Length and Positional Outcome after Evans Calcaneal Osteotomy: A Retrospective Pilot Study

When using the Evans calcaneal osteotomy for repair of a calcaneovalgus deformity, lengthening of the lateral column of the foot is the method by which the procedure acts to correct the deformity. Therefore, maintaining the length is a priority. In our experience, substantial length is lost soon after surgery using the traditional nonfixated procedure. To test this hypothesis, a retrospective study was undertaken in which we compared the calcaneal length before and after the Evans procedures in 22 patients treated without fixation and 13 patients in whom the graft was fixated with a small locking plate to bridge the osteotomy and reduce the compressive forces on the graft. Within the first 10 days after surgery, the increase in calcaneal length from the preoperative length was 6.3 mm in the nonfixated group and 6.8 mm in the fixated group (p = .54 for the 0.5-mm difference). At 12 weeks after surgery, the mean amount of shortening from the value observed at 1 week was 2.45 (range 0 to 6) mm in the nonfixated group and 1.0 (range 0 to 3) mm in the internal fixation group (p = .48). Also, at 12 weeks, distal calcaneal migration or dorsal anterior calcaneal displacement of more than 3 mm occurred in 5 patients (23%) in the nonfixated group and 1 patient (8%) in the fixated group (p = .04). Our results suggest that locking plates do preserve the correction obtained with the Evans calcaneal osteotomy.     

Relationship of coccidial lesion scores and weight gain in infections of Eimeria acervulina, E. maxima and E. tenella in broilers

A relationship was estimated between weight gains and coccidial lesion scores measured on individual male broiler chicks experimentally infected with different field isolates of Eimeria acervulina (seven tests), E. maxima (five tests) or E. tenella (eight tests). There was a small decrease in weight gain as lesion scores increased in E. acervulina infections, and a modest reduction in weight gain with increasing lesion scores in E. maxima and E. tenella infections. This relationship was observed in both nonmedicated birds and birds fed on diets containing 60 mg salinomycin/kg. The weight gains for birds fed 60 mg/kg with lesion scores of 2, 3 and 4 for E. acervulina. 1,2,3 and 4 for E. maxima and 2 and 3 for E. tenella were significantly greater than the weight gains of nonmedicated birds with the same lesion scores. The results demonstrated that lesion scoring does not fully reflect the degree of disease severity in induced infection. High lesion scores caused by the three species studied were associated with small changes in weight gain in medicated birds when compared with nonmedicated birds.     

Serosal mast cells maintain their viability and promote the metabolism of cartilage proteoglycans when cocultured with chondrocytes.

OBJECTIVE. To determine the consequences of mast cell (MC)-chondrocyte interactions. METHODS. Cocultured cells were analyzed histochemically, morphologically, biochemically, and functionally. RESULTS. Cocultured MC adhered to the chondrocytes and remained viable. Chondrocytes cocultured with nonactivated MC produced more proteoglycans than did chondrocytes cultured alone, and these proteoglycans possessed an intact hyaluronic acid-binding region. In contrast, most of the proteoglycans produced by chondrocytes cocultured with activated MC were degraded. CONCLUSION. These studies indicate that a complex interaction occurs in which the nonactivated MC stimulates biosynthesis and the activated MC degrades cartilage proteoglycans.     

Impact of journal articles and grand rounds on practice: CT scanning in appendicitis

The purpose of this study was to determine whether a report in a high-impact journal published in January 1998 changed practice patterns and to further explore the impact of a review of the subject in a department of surgery grand rounds (January 2000). Charts from all patients undergoing appendectomy at our institution during three time periods (January to December 1997, January to December 1999, and January to June 2000) were reviewed. Rates of CT scanning, negative appendectomy, and perforated/ gangrenous appendicitis were compared for the three periods to determine the impact of the journal article and the subject review during grand rounds on practice patterns and outcomes. Charts from 230 (88%) of 262 patients who underwent appendectomy during the time periods were available for review. Age, percentage of male patients, temperature on admission, and white blood cell count did not differ among the groups. The rate of CT scanning increased significantly from 1997 to 1999 and again in 2000 (6.7%, 43%, and 70%, respectively; P < 0.001), whereas the proportion of perforated/gangrenous appendicitis decreased significantly from 33% in 1997 and 31% in 1999 to 13% in 2000 (P = 0.012). The use of CT scanning in appendicitis increased both after publication of a report in a high-impact journal and after review during grand rounds. A rate of CT scanning above 45 % appeared to affect outcomes as well. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001 (poster presentation).     

First-in-Human Study of Acoustic Angiography in the Breast and Peripheral Vasculature

Screening with mammography has been found to increase breast cancer survival rates by about 20%. However, the current system in which mammography is used to direct patients toward biopsy or surgical excision also results in relatively high rates of unnecessary biopsy, as 66.8% of biopsies are benign. A non-ionizing radiation imaging approach with increased specificity might reduce the rate of unnecessary biopsies. Quantifying the vascular characteristics within and surrounding lesions represents one potential target for assessing likelihood of malignancy via imaging. In this clinical note, we describe the translation of a contrast-enhanced ultrasound technique, acoustic angiography, to human imaging. We illustrate the feasibility of this technique with initial studies in imaging the hand, wrist and breast using Definity microbubble contrast agent and a mechanically steered prototype dual-frequency transducer in healthy volunteers. Finally, this approach was used to image pre-biopsy Breast Imaging Reporting and Data System (BI-RADS) 4 and 5 lesions <2?cm in depth in 11 patients. Results indicate that sensitivity and spatial resolution are sufficient to image vessels as small as 0.2?mm in diameter at depths of ~15?mm in the human breast. Challenges observed include motion artifacts, as well as limited depth of field and sensitivity, which could be improved by correction algorithms and improved transducer technologies.     

Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates

Purpose

ABT-888 inhibits poly(ADP-ribose) polymerase (PARP) and may enhance the efficacy of chemotherapy and radiation in CNS tumors. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of ABT-888 in a non-human primate (NHP) model that is highly predictive of human CSF penetration.

Methods

ABT-888, 5 mg/kg, was administered orally to three NHPs. Serial blood and CSF samples were obtained. Plasma and CSF concentrations of ABT-888 were measured using LC/MS/MS, and the resulting concentration versus time data were evaluated using non-compartmental and compartmental PK methods.

Results

The CSF penetration of ABT-888 was 57 ± 7% (mean ± SD). The peak ABT-888 concentration in the plasma was 0.62 ± 0.18 μM. Plasma and CSF AUC_0–∞ were 3.7 ± 1.7 and 2.1 ± 0.8 μM h. PARP inhibition in peripheral blood mononuclear cells was evident 2 h after ABT-888 administration.

Conclusion

The CSF penetration of ABT-888 after oral administration was 57%. Plasma and CSF concentrations were in the range that has been shown to inhibit PARP activity in vivo in humans.     

Cellular uptake,retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties

Curcumin, a naturally-occurring compound found in the rhizome of Curcuma longa plant, is known for its antitumor activities. However, its clinical efficacy is limited due to poor bioabsorption. A new class of synthetic analogs of curcumin, namely diarylidenylpiperidone (DAP), has been developed with substantially higher anticancer activity than curcumin. However, its cellular uptake and bioabsorption have not been evaluated. In this study we have determined the absorption of a representative DAP compound, HO-3867, using optical and electron paramagnetic resonance spectrometry. The cellular uptake of HO-3867 was measured in a variety of cancer cell lines. HO-3867 was taken in cells within 15 minutes of exposure and its uptake was more than 100-fold higher than curcumin. HO-3867 was also retained in cells in an active form for 72 hours and possibly longer. HO-3867 was substantially cytotoxic to all the cancer cells tested. However, there was no direct correlation between cellular uptake and cytotoxicity suggesting that the cytotoxic mechanisms could be cell-type specific. When administered to rats by intraperitoneal injection, significantly high levels of HO-3867 were found in the liver, kidney, stomach and blood after 3 hours. Also, significant accumulation of HO-3867 was found in murine tumor xenografts with a dose-dependent inhibition of tumor growth. The results suggest that the curcumin analog has substantially higher bioabsorption when compared to curcumin.Key words: curcumin, ovarian cancer, bioabsorption, HO-3867