Giant cell tumor of bone

Giant cell tumor is a locally aggressive tumor with a high recurrence rate if not completely excised. The condition is more common among Asians than whites. During a 10-year period 44 patients, ranging in age from 12 to 51 years, were treated. The most common sites were the proximal femur and the distal radius. The aim of treatment was to excise the tumor completely. Because the tumor usually occurred at the juxtaarticular region of the bone, difficult reconstruction was expected. The authors' method of choice for filling large defects resulting from resection was to use a large vascularized bone graft from the iliac crest to enhance bone to bone corporation. The recurrence rate was low (4.5%), with only 2 recurrences: 1 at the proximal femur and the other at the proximal tibia. The functional results were highly satisfactory, with excellent stability of the joint, although in the case of the distal radius there was some degree of subluxation of the wrist joint. By applying microsurgical technique for the reconstruction, one was able to be more aggressive with excision of this locally aggressive tumor while maintaining excellent functional results. In the case of the knee, as long as 1 tibial condyle was intact, reconstruction of the other condyle using a vascularized iliac crest block maintained the joint integrity perfectly or created a pseudojoint component that was perfectly stable.     

Does blood flow through holmium:YAG transmyocardial laser channels?

BACKGROUND: Early reports indicate that transmyocardial laser revascularization improves symptoms in patients with refractory angina. However, there is little experimental evidence of whether blood flow through channels is the mechanism of action. METHODS: Endocardial channels were made in the distribution of the left anterior descending coronary artery in canine hearts (n = 5) using a holmium:yttrium-aluminum garnet laser. Hearts were excised acutely while perfused in a retrograde fashion from a second dog so that the aortic valve always remained closed. The proximal left anterior descending coronary artery was ligated. To measure direct transmyocardial blood flow, colored microspheres were injected into the left ventricular chamber. RESULTS: The number of spheres per gram of tissue in the channel region was significantly higher than in the control region (low load, 302.5 +/- 169.0 versus 41.8 +/- 59.4; high load, 208.4 +/- 138.3 versus 5.8 +/- 11.7; both, p < 0.05). However, the estimated regional blood flow through the channels was extremely low (<0.01 mL/g/min. In the chronic setting (n = 4) (2-week survival), no flow as detected through the channels, and the endocardial entry points were closed. CONCLUSIONS: Transmyocardial blood flow does not appear to occur through channels made with the holmium:yttrium-aluminum garnet laser. It remains to be determined whether this is the case with other types of lasers.     

Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: interaction with low dose acetylsalicylic acid

1. Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases. 2. We investigated the effects of captopril (2 x 25 mg day-1), or ASA (1 x 100 mg day-1), or the combination of both drugs for 7 days, on blood pressure, prostanoid and NO formation rates in a double-blind, double dummy, randomized crossover study in 13 healthy female subjects. The urinary metabolites of thromboxane A2 (2,3-dinor-TXB2) and prostacyclin (2,3-dinor-6-keto-PGF1 alpha), and PGE2 were measured by gas chromatography/tandem mass spectrometry in urine on days 1, 6 and 7 of each medication. NO formation was assessed using urinary NO3- and cyclic GMP as indicators. 3. Urinary 2,3-dinor-6-keto-PGF1 alpha excretion was not significantly changed by either captopril, ASA, or their combination. Urinary 2,3-dinor-TXB2 excretion was inhibited by > 80% by ASA alone or in combination with captopril (each P < 0.05), but was not affected by captopril alone. Urinary PGE2 excretion was not significantly changed by either of the treatments. Urinary NO3- and cyclic GMP excretion rates were not significantly changed by captopril, ASA, or their combination. 4. Blood pressure was slightly reduced by captopril. ASA had no effect on blood pressure when given alone, nor did it modulate the effect of captopril on blood pressure during co-administration. Angiotensin II/angiotensin I ratio (index of ACE activity) was significantly decreased by captopril alone or in combination with ASA, but was unaffected by ASA alone. 5. Captopril does not stimulate prostacyclin formation in healthy human subjects in a dose sufficient to substantially inhibit ACE activity. Co-administration of ASA significantly inhibits 2,3-dinor-TXB2 excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects.     

Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa

Sputum isolation of Pseudomonas aeruginosa (PA) is associated with extensive disease in bronchiectasis. It is not known, however, whether infection with P. aeruginosa is the result or the cause of severe disease. We compared spirometry in patients with bronchiectasis before and after infection with P. aeruginosa, with that of patients infected by other organisms. All patients (n=12) with chronic colonization by P. aeruginosa (PA group) were studied. These were compared with other patients with bronchiectasis with no isolations of P. aeruginosa (n=37, non-PA group). In the PA group, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were lower than in the non-PA group. The PA group, however, also had lower values at the time of initial colonization with P. aeruginosa than the current values for the non-PA group. Change in FEV1 and FVC over time was faster in the PA group than in the non-PA group. Reduction of FEV1 and FVC over time in the PA group prior to P. aeruginosa colonization was intermediate, not being statistically different from either value above. Our results confirm the association of chronic P. aeruginosa colonization with poor lung function, but conclude that patients with bronchiectasis who become colonized by P. aeruginosa have poorer lung function when first colonized than those colonized by other organisms. Decline in lung function is faster in those chronically colonized by P. aeruginosa than in those colonized by other organisms. It is not clear whether chronic P. aeruginosa colonization causes an accelerated decline in lung function or whether it is simply a marker of those whose lung function is already declining rapidly.     

Regulation of ornithine decarboxylase gene expression by the Wilms' tumor suppressor WT1

The importance of ornithine decarboxylase (ODC) to cell proliferation is underscored by the complex array of cell-specific mechanisms invoked to regulate its synthesis and activity. Misregulation of ODC has severe negative consequences on normal cell function, including the acquisition of tumorigenic growth properties by cells overexpressing ODC. We hypothesize that ODC gene expression is a candidate target for the anti-proliferative function of certain tumor suppressors. Here we show that the Wilms' tumor suppressor WT1 binds to multiple sites within the human ODC promoter, as determined by DNase I protection and methylation interference assays. The expression of WT1 in transfected HCT 116, NIH/3T3 and HepG2 cells represses activity of the ODC promoter controlling expression of a luciferase reporter gene. In contrast WT1 expression enhances ODC promoter activity in SV40-transfected HepG2 cells. Both the extent of modulation of ODC gene expression and the mediating WT1 binding elements are cell specific. Constructs expressing WT1 deletion mutants implicate two regions required for repressor function, as well as an intrinsic activation domain. Understanding the regulation of ODC gene expression by WT1 may provide valuable insights into the roles of both WT1 and ODC in development and tumorigenesis.     

Familial paraganglioma

Non-secreting paragangliomas are rare tumours usually present in the head and neck. We describe an unusual case of familial paraganglioma with cranial nerve palsies. After exhaustive investigation, a vagal paraganglioma, was found and excised. The positive family history of paraganglioma was of significance, although this was only present in one of five generations. The diagnosis and management of non-secreting paragangliomas is discussed.