Differential uptake and catabolism of prostaglandin (PG)E(2) versus PGF(2alpha) in the sheep choroid plexus during development

The early postnatal decrease in prostaglandin (PG)E(2) levels in cerebrospinal fluid (CSF) likely contributes to the establishment of continuous breathing. To elucidate mechanisms underlying this event, choroid plexuses from lateral (L-CP) and third/fourth (III/IV-CP) ventricles were incubated with [3H]-PGE(2) and label uptake (tissue-to-medium ratio for radioactivity, T/M) and catabolism (%radioactivity associated with metabolites, PGM) were measured. [3H]-PGF(2alpha) was a reference. Uptake of [3H]-PGE(2) was lower than [3H]-PGF(2alpha) in the term fetus (L-CP: 5.9+/-0.5 vs. 9.6+/-0. 9, n=11; III/IV-CP: 2.7+/-0.4 vs. 7.7+/-1.0, n=5) and 17 d lamb (L-CP: 5.3+/-0.8 vs. 11.0+/-1.2, n=7; III/IV-CP: 3.1+/-0.2 vs. 11. 6+/-2.8, n=3 and 4, respectively). This difference was not significant in the pregnant adult. Release of the two compounds was similar and did not change with age. [3H]-PGE(2) uptake was reduced by probenecid (1 mM) and excess PG (60 microM PGE(2) or PGF(2alpha)). Excess PG also reduced catabolism in the fetus, which was extensive for [3H]-PGE(2) and [3H]-PGF(2alpha)60%). In the lamb, catabolism remained high for [3H]-PGE(2) (L-CP: 64+/-4%, n=7; III/IV-CP: 41+/-4%, n=3), but not [3H]-PGF(2alpha) (L-CP: 26+/-4%, n=7; III/IV-CP: 4+/-1%, n=4). In the pregnant adult, catabolism was above background only for [3H]-PGE(2) in the L-CP (26+/-5%, n=11). Unlike the perinatal animal, this catabolism was reduced by probenecid. In conclusion, PGE(2) uptake and catabolism operate independently in the choroid plexus from perinatal sheep. Differences between PGE(2) and PGF(2alpha) are developmentally-regulated for both mechanisms. While neither process explains the postnatal decrease in CSF PGE(2), both may help keep CSF levels low during early postnatal development.     

Moderate varus/valgus malalignment after total knee arthroplasty has little effect on knee function or muscle strength: 91 patients assessed after 1 year

Background and purpose — Postoperative muscle strength and component alignment are important factors affecting functional results after total knee arthroplasty (TKA). We are not aware of any studies that have investigated the relationship between them. We therefore investigated whether coronal malalignment of the mechanical axis and/or of individual implant components would affect knee muscle strength and function 1 year after TKA surgery.Patients and methods — We included 120 consecutive osteoarthritis (OA) patients admitted for TKA. Preoperative active range of motion (ROM) of the knee, patient age, sex, and BMI were recorded and the Knee Society score (KSS) and knee joint extensor/flexor muscle strength were assessed. At 1-year follow-up, the mechanical and coronal component alignment was measured from a postoperative long standing radiograph, and ROM, KSS, and muscle strength measurements were taken in 91 patients. Functional outcome and muscle strength measurements were compared between normally aligned and malaligned TKA groups.Results — 29 of 91 TKAs were malaligned, i.e. they deviated more than 3° from the neutral mechanical axis. 18 femoral components and 15 tibial components were malaligned. Before surgery, the malaligned and normally aligned groups were similar regarding sex distribution, BMI, ROM, KSS, and muscle strength. At the 1-year follow-up, the differences between the groups regarding knee joint function and muscle strength were small, not statistically significant, and barely clinically relevant.Interpretation — Moderate varus/valgus malalignment of the mechanical axis or of individual components has no relevant clinical effect on function or muscle strength 1 year after TKA surgery.Failure to restore limb alignment in total knee arthroplasty (TKA) increases the risk of revision (Jeffery et al. 1991, Ritter et al. 1994 and 2011, Berend et al. 2004), but the effect of accurate postoperative alignment on TKA function is controversial (Lotke and Ecker 1977, Choong et al. 2009, Fang et al. 2009, Longstaff et al. 2009, Huang et al. 2012).Huang et al. (2012) reported that TKAs with a coronal alignment within 3° from the neutral axis had better function and quality of life at 5-year follow-up than TKAs that deviated more than 3° from neutral alignment. Other studies comparing computer-assisted TKA with conventional TKA surgery have not been able to correlate malalignment with inferior functional outcomes (Spencer et al. 2007, Kamat et al. 2009, Kim et al. 2009, Burnett and Barrack 2013).Patients with greater preoperative muscle strength have been reported to have faster recovery and better functional outcome after TKA (Mizner et al. 2005, Yoshida et al. 2008). However, full recovery of muscle strength after TKA is uncommon (Berth et al. 2002, Valtonen et al. 2009, Maffiuletti et al. 2010, Vahtrik et al. 2012).It is plausible that failure to restore the mechanical axis restoration results in inferior muscle function. Sogabe et al. (2009) found different cross-sectional areas in the quadriceps muscles with different knee alignments. They suggested that knees with varus or valgus deformation should have poorer muscle function compared to normally aligned knees. However, we have not been able find any studies investigating muscle strength after TKA in relation to component alignment and mechanical axis restoration.We investigated whether coronal malalignment of the mechanical axis and/or of individual implant components would affect knee muscle strength and function 1 year after TKA surgery.     

Treatment of hemorrhagic lymphatic malformation of the tongue with a pulsed-dye laser

Hemorrhagic lymphatic malformation (formerly called hemolymphangioma) of the tongue is an uncommon malformation that may pose both functional and cosmetic problems for the patient. The challenge has been to find a conservative treatment with low morbidity and better results than those achieved with surgical excision, which has been the mainstay of therapy. We report a case of successful treatment of a hemorrhagic lymphatic malformation of the tongue with a variable-pulse 595-nm pulsed-dye laser (Vbeam; Candela Corp, Wayland, Mass). In this patient, pulsed-dye laser treatment of the hemorrhagic lymphatic malformation achieved satisfactory functional and cosmetic outcomes. Its use in superficial vascular lesions of the mucosa should be considered.     

Degeneration of mammalian PNS and CNS axons is accelerated by incubation with protein synthesis inhibitors

Protein synthesis inhibitors (PSIs) increase the rate of degeneration, as measured by compound action potential (CAP) conduction, in segments of rat PNS and CNS axons. Sciatic axonal segments maintained in vitro in Krebs at 37-38 degrees C generate CAPs for 24 h compared to 8 h for axons exposed to Krebs containing two PSIs, 100 microM anisomycin and/or 35 microM cycloheximide. Spinal axonal segments at 37-38 degrees C generate CAPs for 3 h compared to 2 h for axons exposed to Krebs containing PSIs. While cooling (6-9 degrees C) slows degeneration rate, cooled sciatic axons exposed to PSIs exhibit lower peak CAPs compared to cooled control segments (P<0.005).     

The Rheometric Analysis of the Polymer Modifier’s Properties in the Environment of Hydrated Cement

This paper investigates the effect of polymer modifiers (re-dispersible powder, multifunctional additives, methylhydroxyethylcellulose) on the rheological behavior of emulsions, saturated of calcium hydrosilicates to simulate a hydrating cement structure. The subjects of the study were modified emulsions which had varied concentrations of each additive and they were examined comparatively to a base emulsion. Tests were performed with a CR-rheometer (“Himpribor-1”, Tula, Russia) applying the Searle measuring principle at various shear rates to characterize viscosity properties. The performance of modified mixtures within the operating period was analyzed by using two parameters—effective viscosity (η) and the proportion of structural failure (|m|). The test results showed that the most important factor influencing rheological characteristics is the addition of methylhydroxyethylcellulose additive—the higher additive amount in the emulsion, the higher the viscosity. Furthermore it was noted in the work that adding olefin sulfonate sodium salt causes reduced viscosities as well as lower shear moduli. If ethylhydroxyethylcellulose and ethylene vinyl acetate additives are used in the same mixture together, the rate of structural failure |m| can be relatively similar and low regardless of whether the mixture has large or small viscosity values.     

A perivascular niche in the bone marrow hosts quiescent and proliferating tumorigenic colorectal cancer cells

Disseminated tumor cells (dTCs) can frequently be detected in the bone marrow (BM) of colorectal cancer (CRC) patients, raising the possibility that the BM serves as a reservoir for metastatic tumor cells. Identification of dTCs in BM aspirates harbors the potential of assessing therapeutic outcome and directing therapy intensity with limited risk and effort. Still, the functional and prognostic relevance of dTCs is not fully established. We have previously shown that CRC cell clones can be traced to the BM of mice carrying patient-derived xenografts. However, cellular interactions, proliferative state and tumorigenicity of dTCs remain largely unknown. Here, we applied a coculture system modeling the microvascular niche and used immunofluorescence imaging of the murine BM to show that primary CRC cells migrate toward endothelial tubes. dTCs in the BM were rare, but detectable in mice with xenografts from most patient samples (8/10) predominantly at perivascular sites. Comparable to primary tumors, a substantial fraction of proliferating dTCs was detected in the BM. However, most dTCs were found as isolated cells, indicating that dividing dTCs rather separate than aggregate to metastatic clones—a phenomenon frequently observed in the microvascular niche model. Clonal tracking identified subsets of self-renewing tumor-initiating cells in the BM that formed tumors out of BM transplants, including one subset that did not drive primary tumor growth. Our results indicate an important role of the perivascular BM niche for CRC cell dissemination and show that dTCs can be a potential source for tumor relapse and tumor heterogeneity.     

Multiple clustered dermatofibroma: case report and review of the literature

The presence of multiple dermatofibromas is rare and is defined as more than 15 lesions. Multiple clustered dermatofibroma (MCDF) is a distinct entity with only 12 reported cases in the literature. MCDF occurs in healthy individuals of both sexes in the first to third decades on the lower half of the body and portends an excellent prognosis. On histology, MCDF is consistent with benign dermatofibromas. We report a 31‐year‐old healthy Hispanic woman with a 14‐year history of slowly progressive MCDF located on her right hip initially misdiagnosed as dermatofibrosarcoma protuberans. We believe this case represents the 13th report of MCDF in the literature and the second from North America. Gershtenson PC, Krunic AL, Chen HM. Multiple clustered dermatofibroma: case report and review of the literature.