Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP‐8 activity from 2 to 6 weeks post‐injury, with peak increases in activity occurring at 4 weeks post‐injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96 h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP‐8 activity in situ. Our findings suggest that inhibition of MMP‐8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:500–506, 2014.     

Nephron-sparing surgery is superior to radical nephrectomy in preserving renal function benefit even when expanding indications beyond the traditional 4-cm cutoff

ObjectivesTo analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in preserving renal function outcome in relation to tumor size indication.Methods and materialsClinical data from 973 patients operated at 9 academic institutions were retrospectively analyzed. Glomerular filtration rate (GFR) before and after surgery was calculated with the abbreviated Modification of the Diet in Renal Disease equation. For a fair comparison between the 2 techniques, all imperative indications for PN were excluded. A shift to a less favorable GFR group following surgery was considered clinically significant.ResultsMedian age at diagnosis was 60 years (19–91). Tumor size was smaller than 4 cm in 665 (68.3%) cases and larger than 4 cm in 308 (31.7%) cases. PN and RN were performed in 663 (68.1%) and 310 (31.9%) patients, respectively. In univariate analysis, patients undergoing PN had a smaller risk for developing significant GFR change following surgery than those undergoing RN did. This was true for tumors≤4 cm (P = 0.0001) and for tumors>4 cm (P = 0.0001). In multivariate analysis, the following criteria were independent predictive factors for developing significant postoperative GFR loss: the use of RN (P = 0.0001), preoperative GFR<60 ml/min (P = 0.0001), tumor size≥4 cm (P = 0.0001), and older age at diagnosis (P = 0.0001).ConclusionsThe renal function benefit carried out by elective PN over RN persists even when expanding nephron-sparing surgery indications beyond the traditional 4-cm cutoff.     

Gram-negative sepsis treated with neutrophils collected exclusively by intermittent flow centrifugation leukapheresis

The effectiveness of neutrophils prepared for transfusion by intermittent flow centrifugation leukapheresis (IFCL) as treatment for serious bacterial infections in neutropenic patients has not been documented in the literature. Their value, in fact, has been questioned. We report that IFCL neutrophils are similar to cells prepared by other techniques in the ability to support neutropenic patients with culture-proven, gram-negative sepsis unresponsive to antibiotics.     

Differential reactivity in the pulmonary circulation

A new method for relating regional intravascular resistance to pulmonary arterial, capillary, and venous pressure and volume was used to evaluate local differences of reactivity in the pulmonary blood vessels in the isolated lung lobe of the dog.Intravascular infusion of isoproterenol caused active dilatation of pulmonary arteries and veins. Capillary conductance (1/resistance) and volume increased, possibly as a result of the opening of previously closed capillaries. Serotonin infusion caused active constriction of both the pulmonary arteries and veins. A low dose of serotonin (1.5 mug/min per kg) caused predominant constriction of whichever vessels were upstream (arteries during forward perfusion, veins during reverse perfusion). A high dose of serotonin (4.5-5.0 mug/min per kg) caused constriction of both upstream and downstream vessels. Metabolic inactivation of serotonin by the lung is suggested as an explanation for these observations. Histamine infusion caused predominant venous constriction whether veins were upstream or downstream. Capillary volume and conductance decreased during forward and reverse perfusion, perhaps as a result of pericapillary edema formation. Large arterial vessels constricted slightly, whereas small arterial vessels appeared to be passively dilated.     

ArF excimer laser debrides burns without destruction of viable tissue: A pilot study

Introduction

Recent evidence indicates that early removal of eschar by tangential debridement can promote healing. Laser debridement can be used for debridement of areas that prove challenging for debridement using tangential excision. In particular, irradiation with an ArF excimer laser ablates desiccated eschar and is self-terminating, preserving hydrated or viable tissue.