Controlled nail trephination for subungual hematoma

An injury to a finger or toe can result in a collection of blood under the nail plate that if unrelieved can cause extreme discomfort due to pressure. In this case, a 47-year-old man developed a subungual hematoma of the right thumb due to a crush injury. Controlled nail trephination was performed using a uniquely designed drill that penetrated the nail plate without breaching the nail bed. The subungual hematoma was successfully drained, and there was a substantial relief in pain over the subsequent 8 hours. This technique appears to be a quick and convenient method of evacuating subungual hematomas with minimal discomfort and minimal risk.     

Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice

Flk-1(+) endothelial progenitors contribute critically to the definitive onset of hematopoiesis during embryogenesis. Recent studies have suggested that adult sources of endothelial cells also possess hematopoietic activity. In this study, we sought to determine whether transplantation of primary vascular endothelial cells (ECs) could enhance the hematopoietic recovery and survival of irradiated mice. C57Bl6 mice were exposed to sublethal and lethal doses of irradiation and were subsequently given transplants of either primary murine brain-derived ECs (MBECs) or fetal blood-derived ECs (FBECs). Mice that received a transplant with MBECs alone demonstrated accelerated BM cellular recovery, radioprotection of BM c-kit(+)sca-1(-)lin(-) progenitors and enhanced regeneration of c-kit(+)sca-1(+)lin(-) (KSL) stem/progenitor cells following irradiation compared with controls. MBEC transplantation also facilitated the recovery of circulating white blood cell and platelet counts following radiation exposure. Remarkably, 57% of mice that received a transplant with MBECs alone survived long term following 1050 cGy exposure, which was 100% lethal in control mice. FBEC transplantation was also associated with increased survival compared with controls, although these mice did not survive in the long term. These data suggest that reestablishment of endothelial cell activity can improve the hematopoietic recovery and survival of irradiated mice.     

Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease

Cystic fibrosis is caused by impaired ion transport due to mutated cystic fibrosis transmembrane conductance regulator, accompanied by elevated activity of the amiloride-sensitive epithelial Na(+) channel (ENaC). Here we show that knockout of the ubiquitin ligase Nedd4L (Nedd4-2) specifically in lung epithelia (surfactant protein C-expressing type II and Clara cells) causes cystic fibrosis-like lung disease, with airway mucus obstruction, goblet cell hyperplasia, massive inflammation, fibrosis, and death by three weeks of age. These effects of Nedd4L loss are likely caused by enhanced ENaC function, as reflected by increased ENaC protein levels, increased lung dryness at birth, amiloride-sensitive dehydration of lung explants, and elevated ENaC currents in primary alveolar type II cells analyzed by patch clamp recordings. Moreover, the lung defects were rescued with administration of amiloride into the lungs of young knockout pups via nasal instillation. Our results therefore suggest that the ubiquitin ligase Nedd4L can suppress the onset of cystic fibrosis symptoms by inhibiting ENaC in lung epithelia.     

Expression of α and β subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads

OBJECTIVE—The objective of this study was to detail the topographical and zonal distribution of α and β subunits of the integrin superfamily in normal and osteoarthritic cartilage.
METHODS—Immunohistochemistry utilising antibodies towards α and β subunits was performed on cryostat sections of human articular cartilage from macroscopically normal (n = 6) and osteoarthritic (n = 6) femoral heads. Samples of articular cartilage were obtained from 12 topographically distinct sites from each femoral head. Each section was divided into zones (superficial, middle, deep) and staining scores were recorded.
RESULTS—Normal cartilage stained for integrin subunits α1, α5, αV, β1, β4, and β5, but not for α2, α3, α4, α6, β2, β3, and β6. Intact and non-intact residual cartilage from osteoarthritic femoral heads stained for α1, α2, α5, αV, β1, β4, and β5. Staining was occasionally seen for α4 and β2, but not for α3, α6, β3, and β6. There was no topographical variation in the staining for any of the subunits in either normal or osteoarthritic cartilage. The only subunit that displayed a zonal variation was αV; staining for this subunit was most pronounced in the superficial zone compared with the middle and deep zones.
CONCLUSION—Chondrocytes in normal and osteoarthritic cartilage express the integrin subunits α1, α5, αV, β1, β4, and β5. Chondrocytes in osteoarthritic cartilage, in addition, express the α2, α4, and β2 subunits. The αv subunit is expressed by more chondrocytes in the superficial zone in comparison with cells in the deeper zones. None of the subunits display topographical variation in expression.

Keywords: cartilage; integrins; immunohistochemistry; osteoarthritis     

Repositioning accuracy of a commercially available double-vacuum whole body immobilization system for stereotactic body radiation therapy

We evaluated the repositioning accuracy of a commercially available stereotactic whole body immobilization system (BodyFIX, Medical Intelligence, Schwabmuenchen, Germany) in 36 patients treated by hypofractionated stereotactic body radiation therapy. CT data were acquired for positional control of patient and tumor before each fraction of the treatment course. Those control CT datasets were compared with the original treatment planning CT simulation and analyzed with respect to positional misalignment of bony patient anatomy, and the respective position of the treated small lung or liver lesions. We assessed the stereotactic coordinates of distinct bony anatomical landmarks in the original CT and each control dataset. In addition, the target isocenter was recorded in the planning CT simulation dataset. An iterative optimization algorithm was implemented, utilizing a root mean square scoring function to determine the best-fit orientation of subsequent sets of anatomical landmark measurements relative to the original treatment planning CT data set. This allowed for the calculation of the x, y and z-components of translation of the patient's body and the target's center-of-mass for each control CT study, as well as rotation about the principal room axes in the respective CT data sets. In addition to absolute patient/target translation, the total magnitude vector of patient and target misalignment was calculated. A clinical assessment determined whether or not the assigned planning target volume safety margins would have provided the desired target coverage. To this end, each control CT study was co-registered with the original treatment planning study using immobilization system related fiducial markers, and the computed isodose calculation was superimposed. In 109 control setup CT scans available for comparison with their respective treatment planning CT simulation study (2-5 per patient, median 3), anatomical landmark analysis revealed a mean bony landmark translation of -0.4 +/- 3.9 (mean +/- SD), -0.1 +/- 1.6 and 0.3 +/- 3.6 mm in x, y and z-directions, respectively. Bony landmark setup deviations along one or more principal axis larger than 5 mm were observed in 32 control CT studies (29.4%). Body rotations about the x-, y- and z-axis were 0.9 +/- 0.7, 0.8 +/- 0.7 and 1.8 +/- 1.6 degrees, respectively. Assuming a rigid body relationship of target and bony anatomy, the mean computed absolute target translation was 2.9 +/- 3.3, 2.3 +/- 2.5 and 3.2 +/- 2.7 mm in x, y and z-directions, respectively. The median and mean magnitude vector of target isocenter displacement was computed to be 4.9 mm, and 5.7 +/- 3.7 mm. Clinical assessment of PTV/target volume coverage revealed 72 (66.1%), 23 (21.1%), and 14 (12.8%), of excellent (100% isodose coverage), good (>90% isodose coverage), and poor GTV/isodose alignment quality (less than 90% isodose coverage to some aspect of the GTV), respectively. Loss of target volume dose coverage was correlated with translations >5 mm along one or more axes (p<0.0001), rotations >3 degrees about the z-axis (p=0.0007) and body mass index >30 (p<0.0001). The analyzed BodyFIX whole body immobilization system performed favorably compared with other stereotactic body immobilization systems for which peer-reviewed repositioning data exist. While the measured variability in patient and target setup provided clinically acceptable setup accuracy in the vast majority of cases, larger setup deviations were occasional observed. Such deviations constitute a potential for partial target underdosing warranting, in our opinion, a pre-delivery positional assessment procedure (e.g., pre-treatment control CT scan).     

Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62 in head and neck or lung cancer.

The purpose of this study was to determine the effect of the first rat monoclonal antibody (MAb ICR62) to the epidermal growth factor receptor (EGFR) in a phase I clinical trial in patients with unresectable squamous cell carcinomas. This antibody effectively blocks the binding of EGF, transforming growth factor (TGF)-alpha and HB-EGF to the EGFR, inhibits the growth in vitro of tumour cell lines which overexpress the EGFR and eradicates such tumours when grown as xenografts in athymic mice. Eleven patients with squamous cell carcinoma of the head and neck and nine patients with squamous cell carcinoma of the lung, whose tumours expressed EGFR, were recruited. Groups of three patients were treated with 2.5 mg, 10 mg, 20 mg or 40 mg of ICR62 and a further eight patients received 100 mg. All patients were evaluated for toxicity using WHO criteria. Patients'' sera were tested for the clearance of MAb ICR62 and the development of human anti-rat antibodies (HARA). No serious (WHO Grade III-IV) toxicity was observed in patients treated with up to 100 mg of antibody ICR62. Antibody ICR62 could be detected at 4 h and 24 h in the sera of patients treated with 40 mg or 100 mg of ICR62. Only 4/20 patients showed HARA responses (one at 20 mg, one at 40 mg and two at 100 mg doses) and of these only the former two were anti-idiotypic responses. In four patients receiving doses of ICR62 at 40 mg or greater, biopsies were obtained from metastatic lesions 24 h later and examined for the localisation of ICR62 using anti-rat antibody reagent. In these patients we showed the localisation of MAb ICR62 to the membranes of tumour cells; this appeared to be more prominent at the higher dose of 100 mg. On the basis of these data we conclude that MAb ICR62 can be administered safely to patients with squamous cell carcinomas and that it can localise efficiently to metastases even at relatively low doses.     

A phase I study of prolonged infusion 5-fluorouracil and concomitant radiation therapy in patients with squamous cell cancer of the head and neck

The radiosensitization properties of 5-FU are well documented, and clinical trials have suggested improved local control and survival in head and neck cancer. Clinical trials to date have used bolus injection or short term (less than or equal to 5 days) 5-FU infusions. To determine the maximum tolerated dose (MTD) of 5-FU given as continuous intravenous infusion for 12 weeks concomitant with conventional radiation therapy, 18 patients with advanced inoperable head and neck cancers were treated with conventional irradiation and 100, 200, 250, or 300 mg/m2/day of 5-FU. A dose of 250 mg/m2/day was determined to be the maximum tolerated dose and is recommended for Phase II studies.