A Longitudinal Comparison of Arm Morbidity in Stage I–II Breast Cancer Patients Treated with Sentinel Lymph Node Biopsy,Sentinel Lymph Node Biopsy Followed by Completion Lymph Node Dissection,or Axillary Lymph Node Dissection

Background  

Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and ALND in stage I/II breast cancer patients.     

Electron beam sterilization does not have a detrimental effect on the ability of extracellular matrix scaffolds to support in vivo ligament healing

Extracellular matrix (ECM) scaffolds have been used to enhance anterior cruciate ligament (ACL) repair in large animal models. To translate this technology to clinical care, identifying a method which effectively sterilizes the material without significantly impairing in vivo function is desirable. Sixteen Yorkshire pigs underwent ACL transection and were randomly assigned to bridge‐enhanced ACL repair—primary suture repair of the ACL with addition of autologous blood soaked ECM scaffold—with either (i) an aseptically processed ECM scaffold, or (ii) an electron beam irradiated ECM scaffold. Primary outcome measures included sterility of the scaffold and biomechanical properties of the scaffold itself and the repaired ligament at 8 weeks after surgery. Scaffolds treated with 15 kGy electron beam irradiation had no bacterial or fungal growth noted, while aseptically processed scaffolds had bacterial growth in all tested samples. The mean biomechanical properties of the scaffold and healing ligament were lower in the electron beam group; however, differences were not statistically significant. Electron beam irradiation was able to effectively sterilize the scaffolds. In addition, this technique had only a minimal impact on the in vivo function of the scaffolds when used for ligament healing in the porcine model. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1015–1023, 2015.     

Repair of superficial osteochondral defects with an autologous scaffold-free cartilage construct in a caprine model: implantation method and short-term results

OBJECTIVE: To compare four different implantation modalities for the repair of superficial osteochondral defects in a caprine model using autologous, scaffold-free, engineered cartilage constructs, and to describe the short-term outcome of successfully implanted constructs. METHODS: Scaffold-free, autologous cartilage constructs were implanted within superficial osteochondral defects created in the stifle joints of nine adult goats. The implants were distributed between four 6-mm-diameter superficial osteochondral defects created in the trochlea femoris and secured in the defect using a covering periosteal flap (PF) alone or in combination with adhesives (platelet-rich plasma (PRP) or fibrin), or using PRP alone. Eight weeks after implantation surgery, the animals were killed. The defect sites were excised and subjected to macroscopic and histopathologic analyses. RESULTS: At 8 weeks, implants that had been held in place exclusively with a PF were well integrated both laterally and basally. The repair tissue manifested an architecture similar to that of hyaline articular cartilage. However, most of the implants that had been glued in place in the absence of a PF were lost during the initial 4-week phase of restricted joint movement. The use of human fibrin glue (FG) led to massive cell infiltration of the subchondral bone. CONCLUSIONS: The implantation of autologous, scaffold-free, engineered cartilage constructs might best be performed beneath a PF without the use of tissue adhesives. Successfully implanted constructs showed hyaline-like characteristics in adult goats within 2 months. Long-term animal studies and pilot clinical trials are now needed to evaluate the efficacy of this treatment strategy.     

Transdermal nicotine patch enhances type I collagen synthesis in abstinent smokers

Cigarette smokers deposit less collagen, expressed as hydroxyproline, in granulation tissue than nonsmokers. We studied the effect of abstinence from smoking and transdermal nicotine patches on deposition of hydroxyproline, proline, type I procollagen, and total proteins. Fifty-four healthy smokers were studied during 10 days of smoking and again from days 10 to 20 following smoking cessation. After the first 10 days of abstinence they were randomized to double-blind treatment with transdermal nicotine patches of 25 mg/day or placebo for a period of 10 days. During this period and during smoking, an expanded polytetrafluoroethylene tube was implanted into the subcutis. Following removal of the implant, total amino acids and peptides were extracted. Hydroxyproline and proline were analyzed by high-pressure liquid chromatography, type I procollagen was analyzed by enzyme-linked immunoassay, and total proteins were determined colorimetrically. In the 39 subjects who complied with the study protocol, abstinence from smoking did not affect the deposition of hydroxyproline, proline, type I procollagen, or total protein in the implants. During abstinence, the type I procollagen level increased by 18% in the transdermal nicotine patches group and decreased by 10% in the placebo group (p<0.05). We conclude that 20 days of abstinence from smoking does not affect collagen deposition in granulation tissue. However, in abstinent smokers, transdermal nicotine patches appears to increase type I collagen synthesis.     

First clinical experience and 1-year follow-up with the sutureless 3F-Enable aortic valve prosthesis.

BACKGROUND: Aortic valve replacement (AVR) with extracorporeal circulation (ECC) is currently the treatment of choice for symptomatic aortic stenosis. However, patients with multiple high-risk comorbid conditions may benefit from reduced ECC time and thus, reduced myocardial ischemia, by the use of sutureless AVR. We describe the initial experience and 1-year results of our first 3F-Enable AVR implants. METHODS: Between 09/05 and 12/05, six patients (age 74+/-1.8 years; three females) with symptomatic aortic stenosis (NYHA III) underwent AVR with an equine pericardial and nitinol-stented sutureless prosthesis. For additional safety up to three stay sutures were placed. Echocardiography was performed preoperatively, intraoperatively, at 6- and 12-month follow-up. Clinical data, adverse events and patient outcome were recorded prospectively. RESULTS: Prosthesis sizes were 27 mm (n=3), 25 mm (n=1), 23 mm (n=1) and 21 mm (n=1). ECC time was 87+/-32 min; aortic clamp time was 56+/-24 min. Prosthesis deployment time was 148 +/- 173 s. There were no intraoperative deaths or complications. At 12-month follow-up mean pressure gradients (MPG) were 6.8+/-3.5 mmHg and aortic valve area (AVA) was 2.2 +/- 0.5 cm(2). One patient underwent successful redo AVR after 8 months due to severe paravalvular leakage (PVL), and one patient died due to lung cancer 10 months after surgery. At 12 months follow-up four out of six patients are alive and asymptotic (NYHA I) with the 3F-Enable aortic valve prosthesis, however, one patient showed mild paravalvular leakage. CONCLUSIONS: These first 1-year follow-up data suggest the feasibility of this new concept of sutureless aortic valve implantation. However, severe aortic insufficiency at 8 months and paravalvular leakage at 1-year follow-up should prompt further procedural and device enhancements.     

Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term

Background. Radial artery bypass conduits are prone to early vasospasm or “string sign” with use of vasopressor therapy intraoperatively and postoperatively, causing increased resistance in coronary artery grafts. Current intraoperative treatment with papaverine fails to provide sustained inhibition of vasoconstriction. We tested the hypothesis that a 30-minute pretreatment of radial artery segments with the -adrenergic antagonist phenoxybenzamine (PB) or the putative protein phosphatase 2,3-butadione monoxime (BDM) attenuates vasoconstriction induced by the vasopressors phenylephrine or norepinephrine for as long as 48 hours compared with papaverine.

Methods. Canine radial arteries were harvested, incubated in control buffer or solutions of papaverine 10⁻⁶ M, BDM 10⁻⁶ M or phenoxybenzamine 10⁻⁶ M for 30 minutes, washed, and stored in drug-free culture medium for 2, 24, or 48 hours. After storage, constriction was induced by norepinephrine at incremental concentrations ranging from 0.7 to 3.5 μmol/L or by phenylephrine (0.300 to 1.5 μmol/L) with or without the inhibitors, and the degree of vasoconstriction was quantified in organ chambers. Responses to norepinephrine or phenylephrine were compared to constriction with receptor-independent potassium chloride KC1 (30 mmol/L).

Results. Maximum responses to phenylephrine and norepinephrine were comparable at 2, 24, and 48 hours after harvest in the control group (phenylephrine: 67% ± 4%, 62% ± 6%, 65% ± 6% of KC1 response; norepinephrine: 75% ± 4%, 62% ± 1%, 58% ± 7%, respectively). Papaverine failed to attenuate constriction to phenylephrine and norepinephrine 2, 24, or 48 hours posttreatment. Pretreatment with BDM did not reduce vasoconstriction responses to phenylephrine or norepinephrine 2 hours after incubation but did reduce constriction responses thereafter. In contrast, phenoxybenzamine completely attenuated constriction to both phenylephrine (19% ± 8%, 1% ± 4%, −12% ± 4%) and norepinephrine (7.1% ± 1%, −5% ± 5%, −20% ± 5%) at 2, 24, and 48 hours posttreatment, respectively. Phenoxybenzamine did not alter endothelial function relative to controls at any time point.

Conclusions. Thirty-minute pretreatment of RA conduits with 10⁻⁶ M phenoxybenzamine completely inhibits vasoconstriction to phenylephrine and norepinephrine for as long as 48 hours. Soaking radial artery grafts briefly in phenoxybenzamine solution before implantation may be effective in preventing postoperative vasospasm caused by two common -adrenergic agonists used in postoperative hemodynamic management.     

Proinflammatory effects of Staphylococcus aureus exotoxin B on nasal epithelial cells.

OBJECTIVE: The aim of this study was to evaluate the effects of Staphylococcus aureus exotoxin B (SE-B) on proinflammatory cytokine/chemokine releases in primary nasal epithelial cell cultures (NECC) of subjects with and without chronic rhinosinusitis (CRS). STUDY DESIGN AND SETTING: NECC (CRS: n = 14; Controls: n = 11) were stimulated with SE-B. Protein concentrations of interleukin-(IL)-1beta, IL-6, and IL-8 levels were measured in NECC supernatants by ELISA before (T0) and after 24 hr stimulation with SE-B (T1). RESULTS: T0: supernatants of the NECC of CRS patients contained significant lower levels of IL-8 (2.1 ng/ml) compared to Controls (IL-8: 6.2 ng/ml; P < 0.01). T1: SE-B induced a significant increase of IL-6 in NECC (P < 0.001). IL-1beta was not detectable. CONCLUSIONS: This is the first study evaluating the effects of exotoxins on NECC. SE-B showed proinflammatory effects on NECC. SIGNIFICANCE: Our data suggest that resident NECC are involved in immunological responses to Staphylococcus aureus toxins, supplementing the so-called "superantigen hypothesis" in CRS.     

Chaperone domains convert prolyl isomerases into generic catalysts of protein folding

The cis/trans isomerization of peptide bonds before proline (prolyl bonds) is a rate-limiting step in many protein folding reactions, and it is used to switch between alternate functional states of folded proteins. Several prolyl isomerases of the FK506-binding protein family, such as trigger factor, SlyD, and FkpA, contain chaperone domains and are assumed to assist protein folding in vivo. The prolyl isomerase activity of FK506-binding proteins strongly depends on the nature of residue Xaa of the Xaa-Pro bond. We confirmed this in assays with a library of tetrapeptides in which position Xaa was occupied by all 20 aa. A high sequence specificity seems inconsistent with a generic function of prolyl isomerases in protein folding. Accordingly, we constructed a library of protein variants with all 20 aa at position Xaa before a rate-limiting cis proline and used it to investigate the performance of trigger factor and SlyD as catalysts of proline-limited folding. The efficiencies of both prolyl isomerases were higher than in the tetrapeptide assays, and, intriguingly, this high activity was almost independent of the nature of the residue before the proline. Apparently, the almost indiscriminate binding of the chaperone domain to the refolding protein chain overrides the inherently high sequence specificity of the prolyl isomerase site. The catalytic performance of these folding enzymes is thus determined by generic substrate recognition at the chaperone domain and efficient transfer to the active site in the prolyl isomerase domain.