Effects of mixed chimeric bone marrow repopulation on platelet storage pool-associated bleeding defects in mouse mutants

We have previously shown mouse platelet storage pool deficiency (SPD) to be associated with lesions at eight different genetic loci, each of which is sufficient to produce murine SPD. We have also shown that normal bleeding times and normal platelet functions are restored when mice with SPD are transplanted with marrow from normal mice. Conversely, when normal mice are transplanted with mutant marrow, they present symptoms of SPD. In order to determine the amount of normal platelets needed to prevent the prolonged bleeding times associated with SPD, we established stable mixed chimeric mice by transplanting various ratios of normal and mutant marrow into lethally irradiated host animals. The proportion of normal input marrow correlated well with the proportion of normal peripheral red blood cells and platelets determined in chimerae 100 days after transplantation using direct morphology and electrophoretic variants of glucose phosphate isomerase to identify normal and mutant cell populations. The proportions of normal input marrow were also reflected in the proportions of platelets with normal and mutant platelet morphology in the chimerae. This confirms that the platelet abnormality in SPD is intrinsic to the stem cell population from which the platelets are derived. When bleeding times were determined in the mixed chimeric mice, a surprisingly high percentage of normal platelets (greater than 50% and sometimes greater than 75%) were needed to stop bleeding. These results suggest that the mutant platelets in the mixed chimeric mice may interfere with normal platelet aggregation patterns. They also raise some important considerations in devising treatment for SPD. Bleeding episodes in human SPD are normally treated by platelet transfusion. The results suggest that, at least in some cases, transfusions may not be effective. Also, in future gene therapy of this disease, it is like that a functional gene will have to be present in greater than 50% of stem cells for therapy to be effective.     

Lymphangiomas in children: MR imaging

Seventeen lymphangiomas in 15 patients were imaged with magnetic resonance (MR) to define the nature, extent, and anatomic relationships of these lesions. The MR and pathologic findings were then compared to determine the histologic basis for the signal-intensity characteristics of these lesions. The signal intensity of 13 lesions was similar to or slightly less than that of muscle on T1-weighted images and greater than that of fat on T2-weighted images. This appearance correlated with the presence of ectatic lymphatic channels containing clear fluid on histologic section. Four lymphangiomas had high signal intensity, approximately equal to that of fat, on T1-weighted images, reflecting the presence of clotted blood or small cystic spaces with a higher ratio of fat to fluid. Sixteen of 17 lesions had visible septations on MR images. The authors' experience suggests that most lymphangiomas have a characteristic appearance on MR images. The information obtained with MR imaging can help in providing a preoperative diagnosis, in planning surgical resection, and in defining recurrence.     

Image-directed percutaneous biopsies with a biopsy gun

Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method.     

The Slc35d3 gene, encoding an orphan nucleotide sugar transporter, regulates platelet-dense granules

Platelet dense granules are lysosome-related organelles which contain high concentrations of several biologically important low-molecular-weight molecules. These include calcium, serotonin, adenine nucleotides, pyrophosphate, and polyphosphate, which are necessary for normal blood hemostasis. The synthesis of dense granules and other lysosome-related organelles is defective in inherited diseases such as Hermansky-Pudlak syndrome (HPS) and Chediak-Higashi syndrome (CHS). HPS and CHS mutations in 8 human and at least 16 murine genes have been identified. Previous studies produced contradictory findings for the function of the murine ashen (Rab27a) gene in platelet-dense granules. We have used a positional cloning approach with one line of ashen mutants to establish that a new mutation in a second gene, Slc35d3, on mouse chromosome 10 is the basis of this discrepancy. The platelet-dense granule defect is rescued in BAC transgenic mice containing the normal Slc35d3 gene. Thus, Slc35d3, an orphan member of a nucleotide sugar transporter family, specifically regulates the contents of platelet-dense granules. Unlike HPS or CHS genes, it has no apparent effect on other lysosome-related organelles such as melanosomes or lysosomes. The ash-Roswell mouse mutant is an appropriate model for human congenital-isolated delta-storage pool deficiency.     

Red cell distribution width is associated with mortality in kidney transplant recipients

Background

Red cell distribution width (RDW), a parameter routinely reported as part of the complete blood count, is associated with increased morbidity and mortality risk in different patient populations. No published data are available about the association between RDW and mortality in kidney transplant recipients.

Methods

We collected socio-demographic, clinical parameters, medical and transplant history and laboratory data at baseline in 723 prevalent kidney transplant recipients between June and October 2008 [mean age 51 ± 13 (SD) years, 56 % men, 21 % diabetics]. Associations between baseline RDW values and all-cause mortality over 3 years were examined in unadjusted and adjusted models.

Results

Increasing RDW was associated with increased mortality in both unadjusted [(HR_{1 % increase} = 1.63; 95 % CI 1.41–1.89) and (HR_>median = 2.74; 95 % CI 1.68–4.48)] and fully adjusted models [(HR_{1 % increase} = 1.60; 95 % CI 1.27–1.89) and (HR_>median = 1.33; 95 % CI 0.76–2.35)]. In reclassification analyses, RDW improved the predictive value of all-cause mortality prediction models [the net reclassification improvement (NRI) was 0.189; p < 0.001].

Conclusions

RDW, a cheap and readily available but largely neglected parameter independently, predicts mortality in prevalent kidney transplant recipients and could potentially been used in everyday risk assessment of kidney transplant recipients.     

Improved visualization of tubes and lines in portable intensive care unit radiographs: a study comparing a new approach to the standard approach

Tube and line interpretation in portable chest radiographs was assessed using a new visualization method. When using the new method, radiologists' interpretation time was reduced by 30% vs. standard modality processing and window and level (23 vs. 33 s). For pulmonary ICU physicians, reading time was essentially unchanged. There was more than a 50% reduction in the use of inferential language in the dictation for both reader groups when using the new method, suggesting greater interpretation confidence.     

Transplantation of cryopreserved osteochondral Dowel allografts for repair of focal articular defects in an ovine model.

The purpose of this study was to test whether successful cryopreservation of osteochondral tissue is possible and whether, with the appropriate surgical procedure, it can be used for the successful repair of focal articular defects within joints. Fresh (nonfrozen) and snap-frozen (plunged in liquid nitrogen and thawed in a water bath at 37 degrees C, repeated three times) autografts were used as positive and negative controls, respectively. Snap-frozen, frozen (fresh tissue placed in a freezer at -80 degrees C), and cryopreserved (immersed in 10% dimethyl sulfoxide for 30 minutes and then frozen at 1 degrees C/min to -80 degrees C) allografts were transplanted into the knees of adult sheep. Outcomes were evaluated 3, 6, and 12 months after transplantation. The morphological, histological, biochemical, and biomechanical behaviors and characteristics of the graft cartilage, the host cartilage adjacent to the grafts, and the opposing tibial cartilage were assessed. Freezing protocols that yielded poor chondrocyte recovery after thawing (frozen and snap-frozen) resulted in poor overall graft outcome. The cryopreservation protocol, however, resulted in intermediate recovery (50%) of chondrocytes and in intermediate overall graft outcome compared with fresh autografts. The membrane integrity of the allograft chondrocytes immediately following cryopreservation was identified as the most reliable predictor of long-term outcome of the graft. Further improvements in cryopreservation technique may lead to an effective method of banking osteochondral tissue for successful transplantation for the repair of focal defects and larger joint reconstructions.     

The unrecognized epidemic of blunt carotid arterial injuries: early diagnosis improves neurologic outcome.

OBJECTIVE: To determine the benefit of screening for blunt carotid arterial injuries (BCI) in patients who are asymptomatic. SUMMARY BACKGROUND DATA: Blunt carotid arterial injuries have the potential for devastating complications. Published studies report 23% to 28% mortality rates, with 48% to 58% of survivors having permanent severe neurologic deficits. Most patients have neurologic deficits when the injury is diagnosed. The authors hypothesized that screening patients who are asymptomatic and instituting early therapy would improve neurologic outcome. METHODS: The Trauma Registry of the author's Level I Trauma Center identified patients with BCI from 1990 through 1997. Beginning in August 1996, the authors implemented a screening for BCI. Arteriography was used for diagnosis. Patients without specific contraindications were anticoagulated. Endovascular stents were deployed in the setting of pseudoaneurysms. RESULTS: Thirty-seven patients with BCI were identified among 15,331 blunt-trauma victims (0.24%). During the screening period, 25 patients were diagnosed with BCI among 2902 admissions (0.86%); 13 (52%) were asymptomatic. Overall, eight patients died, and seven of the survivors had permanent severe neurologic deficits. Excluding those dying of massive brain injury and patients admitted with coma and brain injury, mortality associated with BCI was 15%, with severe neurologic morbidity in 16% of survivors. The patients who were asymptomatic at diagnosis had a better neurologic outcome than those who were symptomatic. Symptomatic patients who were anticoagulated showed a trend toward greater neurologic improvement at the time of discharge than those who were not anticoagulated. CONCLUSIONS: Screening allows the identification of asymptomatic BCI and thereby facilitates early systemic anticoagulation, which is associated with improved neurologic outcome. The role of endovascular stents in the treatment of blunt traumatic pseudoaneurysms remains to be defined.     

Treatment of a proximal accessory nerve injury with nerve transfer

OBJECTIVE AND HYPOTHESIS: This study presents a case report of a patient who sustained an iatrogenic proximal accessory nerve injury that was treated with a medial pectoral to accessory nerve transfer. STUDY DESIGN: Case study. MATERIALS AND METHODS: Chart of one patient who was treated with a medial pectoral to accessory nerve transfer was reviewed. RESULTS: Five months after excision of a branchial cyst that resulted in a very proximal injury to the accessory nerve, this patient underwent a medial pectoral to accessory nerve transfer. At final follow-up, 3 years after surgery, the patient had full abduction overhead with some residual shoulder/scapular discomfort and mild scapular winging. CONCLUSION: The medial pectoral to accessory nerve transfer provides a viable surgical option with good reinnervation of the trapezius muscle in patients with a proximal accessory nerve injury where standard nerve repair or graft techniques are not feasible.