Simulated pulmonary nodules: detection with dual-energy digital versus conventional radiography

Performance of a prototype dual-energy digital chest radiography unit in detecting calcified and noncalcified simulated pulmonary nodules was compared with that of a highly optimized, conventional system. Nodules ranging in size (0.5, 1.0, and 1.6 cm), in number (five to 11), and in calcium content (0-25 mg) were superimposed over the lungs of a frozen, unembalmed, human chest phantom. For each technique, six observers examined 50 posteroanterior projections with different randomized nodule locations. Detection consisted of locating and assigning a level of confidence to each perceived nodular opacity. The resulting plots of the true-positive fraction versus the mean number of false-positive calls per projection indicate that for both calcified and noncalcified nodules, the digital unit performed significantly better (P less than .01).     

The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases

Numerous inositol polyphosphate 5-phosphatases catalyze the degradation of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P(2)) to phosphatidylinositol-4-phosphate (PtdIns-4-P). An alternative pathway to degrade PtdIns-4,5-P(2) is the hydrolysis of PtdIns-4,5-P(2) by a 4-phosphatase, leading to the production of PtdIns-5-P. Whereas the bacterial IpgD enzyme is known to catalyze this reaction, no such mammalian enzyme has been found. We have identified and characterized two previously undescribed human enzymes, PtdIns-4,5-P(2) 4-phosphatase type I and type II, which catalyze the hydrolysis of PtdIns-4,5-P(2) to phosphatidylinositol-5-phosphate (PtdIns-5-P). Both enzymes are ubiquitously expressed and localize to late endosomal/lysosomal membranes in epithelial cells. Overexpression of either enzyme in HeLa cells increases EGF-receptor degradation upon EGF stimulation.     

The effect of cartilage and bone density of mushroom-shaped,photooxidized, osteochondral transplants: an experimental study on graft performance in sheep using transplants originating from different species

Background  

Differences in overall performance of osteochondral photooxidized grafts were studied in accordance of their species origin and a new, more rigorous cleansing procedure using alcohol during preparation.     

Hyperpigmentation mimicking Laugier syndrome, levodopa therapy and Addison''s disease

The Laugier-Hunziker syndrome is an acquired, idiopathic, benign mucocutaneous hypermelanosis that usually occurs on the lips and oral mucosa, although it may appear at other sites. Nails are frequently involved, mainly forming longitudinal hyperpigmented bands. We report the case of a patient that presented a typical picture of this entity, nearly 1 year after the beginning of treatment with levodopa. Two years after the first lesions occurred, she developed Addison's disease. The patient suffered from a diffuse discrete hyperpigmentation (it was more remarkable on exposed areas) and an intensification of the melanotic macules that were previously noticeable before in oral and genital mucosa, fingers, toes and nails. Hormonal replacement treatment enabled the control of laboratory and general manifestations and to decrease the degree of mucocutaneous hyperpigmentation considerably, despite initial hyperpigmented lesions persisting in described areas.     

Acute spinal cord injury: MR imaging at 1.5 T

Thirty-seven magnetic resonance (MR) imaging studies were performed with a 1.5-T magnet and surface coils in 27 patients with suspected spinal cord injuries. Imaging was performed 1 day to 6 weeks after injury. Cord abnormalities were seen with MR in 19 patients, while skeletal and/or ligamentous injuries were seen in 21 (78%). Three types of MR signal patterns were seen in association with cord injuries. Acute intraspinal hemorrhage was seen in five patients with cord injuries and demonstrated decreased signal intensity on T2-weighted images obtained within 24 hours of injury. Cord edema and contusion had high signal intensity on T2-weighted images and were observed in 12 cases with cord injury. Neurologic recovery, determined in 16 patients, was insignificant in patients with intraspinal hemorrhage; however, patients with cord edema or contusion recovered significant neurologic function. MR at 1.5 T is extremely useful in the diagnosis of acute cord injury and also demonstrates potential in predicting neurologic recovery.     

Invasive pulmonary aspergillosis caused by Aspergillus versicolor in a patient on mechanical ventilation

Aspergillus spp. often colonise the respiratory tract of critically ill patients in intensive care units and subsequently cause invasive disease. The risk of developing invasive disease is more in immunocompromised patients. Here we report a case of fatal invasive pulmonary aspergillosis caused by Aspergillus versicolor in a post-operative patient on mechanical ventilation, who did not respond to intravenous itraconazole. We then discuss the challenges involved in the accurate diagnosis of this condition and appropriate management.     

VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression

T-cell defects and premature thymic atrophy occur in cancer patients and tumor-bearing animals. We demonstrate that exposure of mice to recombinant vascular endothelial growth factor (VEGF) at concentrations similar to those observed in advanced stage cancer patients reproduces this profound thymic atrophy and is highlighted by a dramatic reduction in CD4+/CD8+ thymocytes. We find that VEGF does not induce thymocyte apoptosis, but instead rapidly decreases the number of the earliest observable progenitors in the thymus. VEGF does not inhibit thymocyte development in fetal thymic organ culture, further suggesting a prethymic effect. We also demonstrate that bone marrow progenitors from animals infused with recombinant VEGF and transferred to irradiated untreated animals recolonize the thymus more efficiently than progenitors from control animals. This suggests that VEGF exposure is associated with an increased population of thymus-committed progenitors in the bone marrow. We hypothesize that pathophysiologically relevant concentrations of VEGF may block the differentiation and/or emigration of these progenitors resulting in the observed thymic atrophy. Removal of VEGF via cessation of infusion or adoptive transfer of progenitors to a congenic host induces a preferential commitment of lymphoid progenitors to the T lineage and results in a restoration of the normal composition and cellularity of the thymus. These data demonstrate that at pathophysiologic concentrations, VEGF interferes with the development of T cells from early hematopoetic progenitor cells and this may contribute to tumor-associated immune deficiencies.     

Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia

Folylpolyglutamate synthetase (FPGS) is responsible for the metabolism of natural folates and a broad range of folate antagonists to polyglutamate derivatives. Recent studies indicated increased accumulation of methotrexate (MTX) polyglutamates (MTX-PG) in blast cells as a predictor of favorable treatment outcome in childhood acute lymphoblastic leukemia (ALL). We determined the expression of FPGS activity in blasts from children with ALL at diagnosis and after treatment with MTX as a single agent, before conventional remission induction therapy. The levels of enzyme activity in ALL blasts at diagnosis (median of 689 pmol/h/mg protein) were significantly higher (P = .003) than those found in acute nonlymphoblastic leukemia (ANLL) blasts (median of 181 pmol/h/mg protein). Comparable lineage differences in normal lymphoid versus nonlymphoid cells suggest a lineage-specific control of FPGS expression, FPGS activity increased in ALL blasts after in vivo exposure to MTX. The median increase in FPGS activity was significantly higher (P = .003) in B-lineage ALL (188%) than in T-lineage ALL (37%). Likewise, the percentage of intracellular long chain MTX-PG (Glu3-6) was significantly higher (P = .02) in B- lineage ALL (92%) than in T-lineage ALL (65%), consistent with higher FPGS activity in B-lineage blasts. This finding could explain, at least in part, the superior outcome in children with B-lineage ALL treated with antimetabolite therapy.