Salivary gland botulinum toxin injections for drooling in children with cerebral palsy and neurodevelopmental disability: a systematic review

Aim The aim of this paper was to systematically review the efficacy and safety of botulinum toxin (BoNT) injections to the salivary glands to treat drooling in children with cerebral palsy and neurodevelopmental disability. Method A systematic search of The Cochrane Central Register of Controlled Trials, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and the Physiotherapy Evidence Database (PEDro) was conducted (up to 1 October 2011). Data sources included published randomized controlled trials (RCTs) and prospective studies. Results Sixteen studies met inclusion criteria. Three outcome measures support the effectiveness of BoNT for drooling. One RCT found an almost 30% reduction in the impact of drooling on patients’ lives, as measured by the Drooling Impact Scale (mean difference ?27.45; 95% confidence interval [CI] ?35.28 to ?19.62). There were sufficient data to pool results on one outcome measure, the Drooling Frequency and Severity Scale, which supports this result (mean difference ?2.71; 95% CI ?4.82 to ?0.60; p<0.001). There was a significant reduction in the observed number of bibs required per day. The incidence of adverse events ranged from 2 to 41%, but was inconsistently reported. One trial was terminated early because of adverse events. Interpretation BoNT is an effective, temporary treatment for sialorrhoea in children with cerebral palsy. Benefits need to be weighed against the potential for serious adverse events. More studies are needed to address the safety of BoNT and to compare BoNT with other treatment options for drooling.     

DETECTION OF ABNORMAL E-CADHERIN EXPRESSION BY SIMULATED PROSTATE BIOPSY

Purpose

Sampling error is an inherent problem of prostate biopsy. Consequently the determination of whether a given carcinoma is clinically significant based on biopsy results is problematic. We assess the dimensions of sampling error and, thereby, provide insight into the potential value of prognostic markers applied to needle biopsies.

Materials and Methods

We constructed 3-dimensional computer models of 21 prostatectomy specimens, including outlines of carcinomas, regions of abnormal E-cadherin expression and individual Gleason patterns. The 6 random systematic core biopsy technique and modifications were simulated using a computer algorithm.

Results

In 6 of 21 cases the area of abnormal E-cadherin expression and/or high grade carcinoma was not sampled on 6 random systematic core biopsy. The areas missed were either small or inconsistently under sampled regions of the prostate. Modifying the placement of biopsy needles improved the detection of these features. In addition, percent tumor in the needle appeared to be well correlated to percent tumor in the prostate (r = 0.891, r (²) = 0.642).

Conclusions

To avoid underestimating the aggressiveness of prostatic carcinoma at least 6 biopsies should be taken from each patient. A more extensive sampling is probably not warranted in all patients but it may prove useful in those in whom extent of disease is unclear or whose general health makes treatment decisions difficult. A reliable estimate of tumor volume in the prostatectomy specimen can be made based on relative amount of tumor in the biopsy specimen on an individual basis.     

Inhibition of tissue factor pathway inhibitor by the aptamer BAX499 improves clotting of hemophilic blood and plasma

Summary. Background: Tissue factor pathway inhibitor (TFPI) is the major inhibitor of tissue factor‐initiated coagulation, making it an interesting and novel therapeutic target in hemophilia treatment. The aptamer BAX499 (formerly ARC19499) is designed to improve hemostasis by specifically inhibiting TFPI. Objectives: The aim of the study was to examine the concentration‐dependent augmentation of clotting by BAX499. Methods: Whole blood clot formation was quantified by rotational thromboelastometry and thromboelastography, and thrombin generation in platelet‐poor plasma was assessed with the calibrated automated thrombogram, in samples from patients with congenital hemophilia A (N = 55) and B (N = 11), patients with acquired hemophilia A (N = 1), and healthy controls (N = 37). Results: BAX499 significantly improved clotting of samples from hemophilic patients in a concentration‐dependent manner, resulting in clotting profiles in samples from patients with severe hemophilia that were similar to those of healthy controls. Conclusion: BAX499 improved ex vivo clotting parameters in blood and plasma from patients with hemophilia A and B with different severity of disease, and also in a patient with acquired hemophilia. These results further support the contention that anti TFPI strategies may be an effective treatment for hemophilic patients.     

被动超声冲洗对弯曲根管的碎屑清理能力和根管形态的影响

目的: 评价被动超声冲洗在弯曲根管内碎屑清理能力和根管偏移量。方法: 选取下颌磨牙近中弯曲根管36个,弯曲度在25°以上,以机用 XP-endo Shaper根管锉预备根管。根据弯曲长度（curved length,CL）和冲洗方式分为A1组（CL>3 mm,注射器冲洗）、B1组（CL>3 mm,超声K锉冲洗）、C1组（CL>3 mm,irrisafe超声锉冲洗）、A2组（CL<3 mm,注射器冲洗）、B2组（CL<3 mm,超声K锉冲洗）和C2组（CL<3 mm,irrisafe超声锉冲洗）,每组6个样本。对所有样本冲洗前、后进行Micro-CT扫描,计算冲洗后根管内体积增加量和根管偏移量。采用SPSS 22.0软件包对数据进行统计学分析。结果: 在CL>3 mm的根管根尖区,PUI+irrisafe组的根管体积增量显著高于PUI+K锉和注射器冲洗（P<0.05）,并且在距离根尖孔5 mm处PUI+irrisafe形成的根管偏移量显著低于PUI+K锉（P<0.05）;与注射器冲洗相比无显著差异（P>0.05）。在CL<3 mm的根管中,PUI+irrisafe组和PUI+K锉组的根管体积增量均显著高于注射器冲洗（P<0.05）,但根管偏移量与注射器冲洗无显著差异（P<0.05）。结论: 在弯曲长度较大的根管中,被动超声冲洗结合预弯锉可获得更好的清理效果;而在弯曲长度较小的根管中,被动超声冲洗结合K锉和预弯锉均安全有效。     

COMPUTER MODELING OF PROSTATE BIOPSY: TUMOR SIZE AND LOCATION-NOT CLINICAL SIGNIFICANCE-DETERMINE CANCER DETECTION

Purpose

Sampling error is an inherent problem of prostate biopsy, and the determination of clinical significance based on biopsy results is problematic. We quantify the dimensions of these problems by computer simulation.

Materials and Methods

We constructed 3-dimensional solid computer models of 59 autopsy prostates containing clinically undetected prostate cancer, and performed simulations of the standard prostate biopsy method.

Results

Biopsy simulation detected 19 tumors from the 59 prostates, the majority of which were in the most accessible portion of the prostate, the posterior peripheral zone. Using 0.5 cc or greater tumor volume or less than 0.5 cc and Gleason sum 7 or greater as criteria of significance, the model detected 58% (11 of 19) significant tumors and 20% (8 of 40) insignificant tumors. With 0.25 cc or greater tumor volume or less than 0.25 cc and Gleason sum 7 or greater as criteria 15 of 29 significant (52%) and 4 of 30 insignificant (13%) tumors were detected. Among significant tumors defined by either volume criterion there was a statistical difference between detected and undetected tumors in terms of mean tumor volume and mean ratio of tumor volume-to-prostate volume. Among insignificant tumors defined by either criterion there was no such difference.

Conclusions

As much as 20 to 40% of currently detected prostate cancer may be histologically insignificant, as 4 of 19 cancers were detected when 0.25 cc was used as volume determinant of clinical significance and 8 of 19 were detected when 0.5 cc volume was used. These tumors are detected randomly. On the other hand, perhaps only one-half to three-fourths of clinically significant prostate cancers are being detected, and then only because the volume and anatomic location make them hard to miss.     

Natural Killer Cytotoxicity and Antibody-Dependent Cell Cytotoxicity to Herpes Simplex Virus-Infected Target Cells in Murine Pregnancy

ABSTRACT: In vitro natural killer cytotoxicity (NKC) and antibody-dependent cell cytotoxicity (ADCC) activity against herpes simplex virus (HSV)-infected cells were evaluated in a pregnant murine model (C₅₇B1₆inbred strain). Virgin (n = 16) and pregnant (late gestation) mice (n = 15) were infected intraperitoneally with HSV, type 1. After 18 hr, a 0.5-ml aliquot of the peritoneal wash was frozen for virus plaque assay, and the cells were cultured in the ⁵¹chromium release assay for NKC and ADCC. %NKC (mean ± S.E.) to HSV-infected targets was significantly suppressed (P < 0.05) in pregnant mice, 10.3% ± 1.9, compared to that of virgin mice, 32.5% ± 2.5. This suppression was abrogated with HSV-specific antisera (%ADCC); 53.9% ± 4.4 (pregnant) compared to 49.1% ± 3.6 (virgin). The diminished NKC activity in pregnant mice was reflected in an increased mean number of virus particles in the peritoneal wash, 266 + 66 PFU/ml, compared to 38 ± 11 PFU/ml in virgin mice (P < 0.05). We concluded that NKC, but not ADCC, to HSV-infected targets was suppressed and that HSV elimination was impaired in pregnant mice.     

Transplantation of endothelial cells corrects the phenotype in hemophilia A mice

BACKGROUND: The deficiency of factor VIII, a co-factor in the intrinsic coagulation pathway results in hemophilia A. Although FVIII is synthesized largely in the liver, the specific liver cell type(s) responsible for FVIII production is controversial. OBJECTIVE: This study aimed to determine the cellular origin of FVIII synthesis and release in mouse models. METHODS: We transplanted cells into the peritoneal cavity of hemophilia A knockout mice. Plasma FVIII activity was measured using a Chromogenix assay 2-7 days after cell transplantation, and phenotypic correction was determined with tail-clip challenge 7 days following cell transplantation. Transplanted cells were identified by histologic and molecular assays. RESULTS: Untreated hemophilia A mice, as well as mice treated with the hepatocyte-enriched fraction, showed extensive mortality following tail-clip challenge. In contrast, recipients of unfractionated liver cells (mixture of hepatocytes, liver sinusoidal endothelial cells (LSEC), Kupffer cells, and hepatic stellate cells) or of the cell fraction enriched in LSECs survived tail-clip challenge (P < 0.001). FVIII was secreted in the blood stream in recipients of unfractionated liver cells, LSECs and pancreatic islet-derived MILE SVEN 1 (MS1) endothelial cells. Although transplanted hepatocytes maintained functional integrity in the peritoneal cavity, these cells did not produce detectable plasma FVIII activity. CONCLUSIONS: The assay of cell transplantation in the peritoneal cavity showed that endothelial cells but not hepatocytes produced phenotypic correction in hemophilia A mice. Therefore, endothelial cells should be suitable additional targets for cell and gene therapy in hemophilia A.     

Novel Technique for Use of Cyanoacrylate in Mohs Surgery

BACKGROUND: Many Mohs procedures involve the handling and manipulating of thin, fragile skin tissue, particularly eyelid skin. After excision of such tissue, proper handling of the tissue becomes critical for tissue orientation and histologic processing. OBJECTIVE: The authors present a novel way to handle thin, friable tissue after excision in Mohs surgery with the direct application of cyanoacrylate onto freshly excised tissue. METHODS: Nonsterile generic cyanoacrylate can be applied along the epidermal surface edge to excised thin tissue sections before inking the margins, sectioning, and processing. CONCLUSIONS: The superglue increases tissue rigidity and provides for easier handling while staining and orienting the tissues. The added glue does not alter tissue integrity and shows minimal artifact upon histologic examination. This technique furthermore is inexpensive and adds little time to the Mohs procedure. Clinical photographs and histologic pictures are presented.