Effect of tadalafil on blood flow,pain, and function in chronic cold Complex Regional Pain Syndrome: a randomized controlled trial

Background  

This double-blind, randomized, controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome (CRPS) in one lower extremity.     

Osteosarcoma: use of MR imaging and MR spectroscopy in clinical decision making

Magnetic resonance (MR) imaging was performed on 14 patients with histologically proved osteosarcoma (mean age, 14.4 years). There was excellent correlation of intramedullary tumor extent as determined with MR imaging and pathologic examination (r = 99%). This was facilitated by the presence of a chemical shift artifact at the tumor-marrow interface on the T1-weighted images. The correlation between CT and pathologic findings was not as good (r = 84%). In a single patient, however, a 10-cm length of sclerotic bone was incorrectly interpreted as being tumor. If this case is excluded, the correlation between CT and pathologic findings improves significantly (r = 96%). T2-weighted images were optimal in demonstrating soft-tissue bulk and breach of the epiphysis or cortex. Vascular involvement was also readily defined. The T2 value of the tumor soft-tissue component decreased in patients who were deemed to have responded well to therapy. Two patients with very high T2 values after chemotherapy developed wide-spread metastatic disease and died. Phosphorus-31 MR spectroscopy of five patients with osteosarcoma showed elevated levels of phosphomonoesters (PMEs), inorganic phosphate (Pi), and phosphodiesters (PDEs). PME and PDE peak areas decreased in three patients after chemotherapy, while Pi peak areas increased.     

Effects of Hydrophobicity on the Antifungal Activity of α‐Helical Antimicrobial Peptides

We utilized a series of analogs of D‐V13K (a 26‐residue amphipathic α‐helical antimicrobial peptide, denoted D1) to compare and contrast the role of hydrophobicity on antifungal and antibacterial activity to the results obtained previously with Pseudomonas aeruginosa strains. Antifungal activity for zygomycota fungi decreased with increasing hydrophobicity (D‐V13K/A12L/A20L/A23L, denoted D4, the most hydrophobic analog was sixfold less active than D1, the least hydrophobic analog). In contrast, antifungal activity for ascomycota fungi increased with increasing hydrophobicity (D4, the most hydrophobic analog was fivefold more active than D1). Hemolytic activity is dramatically affected by increasing hydrophobicity with peptide D4 being 286‐fold more hemolytic than peptide D1. The therapeutic index for peptide D1 is 1569‐fold and 62‐fold better for zygomycota fungi and ascomycota fungi, respectively, compared with peptide D4. To reduce the hemolytic activity of peptide D4 and improve/maintain the antifungal activity of D4, we substituted another lysine residue in the center of the non‐polar face (V16K) to generate D5 (D‐V13K/V16K/A12L/A20L/A23L). This analog D5 decreased hemolytic activity by 13‐fold, enhanced antifungal activity to zygomycota fungi by 16‐fold and improved the therapeutic index by 201‐fold compared with D4 and represents a unique approach to control specificity while maintaining high hydrophobicity in the two hydrophobic segments on the non‐polar face of D5.     

Aged venous thrombi: radioimmunoimaging with fibrin-specific monoclonal antibody

Radioimmunoimaging of fresh canine venous thrombi with a murine monoclonal antibody specific for human and dog fibrin has been reported. Successful imaging of canine deep venous thrombi 1, 3, and 5 days old at the time of antibody injection is reported. Images were positive in all dogs, and the uptake of fibrin-specific antibody was equivalent to that of fresh thrombi.     

Pro-inflammatory cytokines in patients with essential hypertension

BACKGROUND: It has been suggested that abnormalities in the immune response play a role in the pathogenesis of essential hypertension (EH). The aim of this study was to assess circulating concentrations and ex vivo production of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and of the anti-inflammatory cytokines IL-1 receptor antagonist (IL-1ra) and IL-6, in patients with EH and compare them with healthy volunteers. PATIENTS AND METHODS: Plasma cytokine concentrations were measured in EH patients and control volunteers by specific radioimmunoassays and ELISA. Ex vivo cytokine production was assessed after stimulation of whole-blood with lipopolysaccharide. RESULTS: Circulating concentrations of TNF, IL-1 and IL-6 did not differ between EH patients and controls. In contrast, IL-1ra circulating levels were higher in EH patients. Hypertensive patients had an increased IL-1 and IL-6 production capacity when whole blood was stimulated ex vivo with lipopolysaccharide, while TNF production was lower. IL-1ra production capacity did not differ between patients and controls. CONCLUSIONS: Patients with EH have an altered profile of pro-and anti-inflammatory cytokines, consistent with monocyte activation in the circulation. The importance of these changes for the pathogenesis of EH and/or its secondary complications remains to be elucidated.