Prospective evaluation of combined local bupivacaine and steroid injections for the management of chronic vaginal and perineal pain

Purpose  

Vaginal/perineal pain is common following obstetric trauma or vaginal surgery for prolapse and may have a serious impact on sexual function and quality of life. Local injections of corticosteroids, local anaesthetic and hyaluronidase are treatment options for chronic pain; however, there are no published studies to support their efficacy. The objective of this study was to evaluate prospectively the efficacy of perineal/vaginal injections for chronic localised pain following childbirth or vaginal surgery.     

FEM assisted evaluation of PMMA and Ti6Al4V as materials for cranioplasty resulting mechanical behaviour and the neurocranial protection

Recent advances in Computer Aided Design and Manufacturing techniques (CAD/CAM) have facilitated the rapid and precise construction of customized implants used for craniofacial reconstruction. Data of the patients' trauma, acquired through Computer Topographies (CT), provide sufficient information with regard to the defect contour profile, thus allowing a thorough preoperative evaluation whilst ensuring excellent implant precision. During the selection, however, of a suitable implant material for the specific trauma, the mechanical aspects of the implant have to be considered. This investigation aims to assess the mechanical strength, the shock resistance and the critical deflection of cranial implants manufactured with two commonly used materials, Polymethylmethacrylate (PMMA) and Ti6Al4V. Even though the strength properties of Ti-alloys are far superior to those of PMMA, there are several aspects that may act in advantage of PMMA, e.g., it is known that discontinuities in the elastic modulus of adjoined parts (bone-implant) lead to bone resorption thus loosening the fixation of the implant over time.The implant design and fixation was the same in both cases allowing a direct comparison of the implant behavior for various loads. Finite Element Methods (FEM) assisted procedures were employed, providing a valuable insight to the neurocranial protection granted by these implants.     

Mixed Hyperbranched/Triblock Copolymer Micelle Assemblies: Physicochemical Properties and Potential for Drug Encapsulation

Mixed micelles have numerous advantages while requiring little to no effort in preparation. This study aims to produce mixed micelle nanostructures from a linear triblock copolymer and a hyperbranched random copolymer, and is able to be loaded with the weakly water-soluble drugs curcumin and indomethacin. Different preparation techniques are employed to produce mixed micelles comprised of Pluronic F127 block copolymer, and hyperbranched poly[(ethylene glycol) methyl ether methacrylate-co-lauryl methacrylate], H-[P(OEGMA-co-LMA)], copolymer. Few studies have dabbled in these types of coassemblies, which provides insight into how structural differences of each copolymer can affect the formation of micelles. To determine the properties of the emerging nanostructures in aqueous environments, including their size, homogeneity, and surface charge, different physicochemical techniques are used, such as light scattering and spectroscopic methods. The results reveal that the copolymers combine, and spontaneously self-assemble into mixed micelle-like nanostructures in aqueous environments, whereas both systems of neat and drug-loaded nanostructures exhibit desirable properties such as small average micelle hydrodynamic radii and low size polydispersity indices. The nanostructures that result from the effective encapsulation of curcumin exhibit outstanding stability over 169 days. The fluorescent qualities of curcumin persist after encapsulation, making the novel nanostructures excellent candidates for bioimaging applications.     

Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease

There is increasing evidence for bone-liver interplay. The main aim of this study was to determine serum sclerostin and Dickkopf (DKK)-1 levels in patients with nonalcoholic fatty liver disease (NAFLD) and their association with the disease severity. Patients with biopsy-proven NAFLD, 13 with nonalcoholic simple steatosis (SS) and 14 with steatohepatitis (NASH), and 20 gender-, age-, body mass index- and waist circumference-matched controls were enrolled. Serum sclerostin, DKK-1, bone turnover markers, vitamin D, insulin and standard biochemical and hematologic parameters were measured; lumbar spinal dual-energy X-ray absorptiometry was performed. We observed that there was a progressive decline in serum sclerostin levels from the controls (76.1 ± 6.8) to SS (53.5 ± 6.4) and NASH (46.0 ± 8.1 pmol/l) patients (p = 0.009); in adjusted pairwise comparisons, sclerostin was significantly higher in the controls than in NASH patients (p = 0.012). Although serum DKK-1 did not differ between groups (p = 0.135), there was a trend toward U-shaped distribution (controls 35.8 ± 2.8; SS 27.3 ± 2.9; NASH 36.8 ± 4.4 pmol/l). Higher DKK-1 levels were independently associated with NASH. Regarding specific histological lesions, DKK-1 levels were marginally lower in NAFLD patients with lower (≤33 %) than higher (>33 %) steatosis grade (27.7 ± 3.1 and 38.8 ± 4.7 pmol/l, respectively; p = 0.049). No other significant difference was observed within histological lesions. In conclusion, serum sclerostin levels were lower in NASH patients than in controls. DKK-1 levels were independently associated with NASH in NAFLD patients. The potential importance of these findings indicates a possible bone-liver interaction and warrants further investigation.     

Polyacrylamide hydrogel (Bulkamid®) for stress urinary incontinence in women: a systematic review of the literature

Introduction and hypothesis

Polyacrylamide hydrogel (PAHG, Bulkamid®) is one of several injectable agents currently used for the treatment of women with urinary stress incontinence. Although bulking agents appear to have lower efficacy rates compared to other surgical treatments, current evidence based on large prospective or comparative studies as well as systematic reviews is limited. The purpose of this study was to conduct a systematic review on the efficacy of PAHG in the treatment of female patients with stress urinary incontinence with regard to reproducibility, feasibility, safety and clinical outcome.

Methods

We searched MEDLINE (1966–2015), Scopus (2004–2015), POPLINE (1974–2015) and ClinicalTrials.gov (2008–2015) along with reference lists of electronically retrieved studies. Observational studies, prospective, retrospective and randomized controlled studies were included. Two reviewers independently selected studies, assessed the risk of bias and tabulated data to structured forms.

Results

We included 8 studies, which enrolled a total of 767 patients who received treatment with PAHG. We found that 186 of 767 women (24.3 %, range 12–35 %) required reinjection in order to achieve adequate efficacy. The most frequent adverse effects were pain at the site of injection (4–14 %) and urinary tract infections (3–7 %). Both the number of incontinence episodes/24 h and the number of ml/24 h were significantly reduced 1 year following treatment and the quality of life of patients was significantly improved.

Conclusions

PAHG is a safe intervention for treating women with stress urinary incontinence, but repeat injections are often required. Further research is mandated in the field in order to compare its efficacy to other bulking agents.

     

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.     

Are bony pelvis dimensions associated with levator ani defects? A case–control study

Introduction and hypothesis

Bony pelvis dimensions have been shown to differ in women with and without pelvic floor dysfunction. The goal of this study was to determine whether bony pelvis dimensions are different when comparing women with severe bilateral levator ani defects (LAD) with those with normal muscles.

Methods

This is a secondary analysis of a case–control study comparing women with and those without pelvic organ prolapse. Subjects underwent pelvic organ prolapse quantification (POP-Q) examination and were classified as either having prolapse or being normal. All underwent pelvic magnetic resonance imaging (MRI). Levator defects were assessed based on the muscles’ appearance on imaging and subjects were stratified into two groups—women with normal muscles (n?=?99) and women with severe bilateral LAD (n?=?50). Bony pelvis dimensions were measured via MRI pelvimetry. The subpubic angle, interspinous and intertuberous diameters, and the sacrococcygeal joint-to-infrapubic point (SCIPP) lengths were compared.

Results

Both groups had similar demographics. The SCIPP length was 2.5 % (3 mm) shorter in women with severe LAD than in those without defects (P?=?0.02). The SCIPP measured 4 % (5 mm) less in women with prolapse and severe LAD than in subjects with prolapse but normal muscles (P?=?0.01). Logistic regression identified SCIPP length and history of forceps delivery as being independent predictors of severe bilateral LAD.

Conclusions

Severe bilateral LAD are associated with shorter SCIPP length and forceps-assisted vaginal delivery.     

Different effects of chronic THC on the neuroadaptive response of dopamine D2/3 receptor‐mediated signaling in roman high‐ and roman low‐avoidance rats

The Roman high (RHA)‐ and low (RLA)‐avoidance rat sublines have been identified as an addiction‐prone and addiction‐resistant phenotype based on their high vs. low locomotor responsiveness to novelty and high vs. low ability to develop neurochemical and behavioral sensitization to psychostimulants, respectively. Most studies though have focused on psychostimulants and little is known about the neuroadaptive response of these two lines to cannabinoids. This study investigated the effects of chronic exposure to Δ⁹‐tetrahydrocannabinol (THC) on dopamine D_2/3 receptor (D_2/3R) availabilities and functional sensitivity in the mesostriatal system of RHA and RLA rats. At baseline, RLA rats exhibited higher densities of mesostriatal D2/3R but lower levels of striatal CB₁R mRNA and displayed a lower locomotor response to acute THC as compared to RHAs. Following chronic THC treatment, striking changes in D_2/3R signaling were observed in RLA but not in RHA rats, namely an increased availability and functional supersensitivity of striatal D_2/3R, as evidenced by a supersensitive psychomotor response to the D_2/3R agonist quinpirole. Moreover, in RLA rats, the lower was the locomotor response to acute THC, the higher was the psychomotor response to quinpirole following chronic THC. These results showing a greater neuroadaptive response of RLA vs. RHA rats to chronic THC thus contrast with previous studies showing a resistance to neuroadaptive response of RLAs to psychostimulants, This suggests that, contrasting with their low proneness to psychostimulant drug‐seeking, RLAs may exhibit a heightened proneness to cannabinoid drug‐seeking as compared to RHA rats.     

Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays

Merkel cell polyomavirus (MCV) is a newly‐discovered human tumor virus found in ～80% of Merkel cell carcinoma (MCC). The rate of MCV infection among persons without MCC is unknown. We developed a MCV virus‐like particle (VLP) enzyme‐linked immunoassay (EIA) that does not cross‐react with human BK or murine polyomaviruses. Peptide mapping of the MCV VP1 gene and immunoblotting with denatured MCV VLP are less sensitive than the MCV EIA in detecting MCV antibodies suggesting antibody reactivity in this assay primarily targets conformational but not linear epitopes. Among MCC patients, all 21 (100%) patients tested with MCV‐positive tumors had high serum MCV IgG but not high MCV IgM levels. Only 3 of 6 (50%) MCC patients with MCV‐negative tumors were positive for MCV antibodies. Sera from most adults, including 107 of 166 (64%) blood donors, 63 of 100 (63%) commercial donors and 37 of 50 (74%) systemic lupus erythematosus patients, show evidence for prior MCV exposure. Age‐specific MCV prevalence was determined by examining a cross‐sectional distribution of 150 Langerhans cell histiocytosis (an unrelated neoplasm) patient sera. MCV prevalence increases from 50% among children age 15 years or younger to 80% among persons older than 50 years. We did not find evidence for vertical transmission among infants. Although past exposure to MCV is common among all adult groups, MCC patients have a markedly elevated MCV IgG response compared with control patients. Our study demonstrates that MCV is a widespread but previously unrecognized human infection. © 2009 UICC