Apoptosis of Merkel cells in neurotrophin-3 null mice

Postnatal mice lacking neurotrophin-3 (NT3) are deficient in Merkel cells of touch domes and whisker follicles. We examined the mechanism of Merkel cell loss by immunocytochemistry and electron microscopy. Merkel cell of whisker follicles of NT3 null newborns exhibited decreased immunoreactivity for cytokeratin 8 and contained apoptotic bodies that were positive for cleaved caspase-3, a marker of active apoptosis. By electron microscopy, the Merkel cells displayed aggregation of chromatin along the nuclear membrane, with the marginated chromatin forming caps at the periphery of the nucleus. Ribosomes aggregated in the cytoplasm, while dense core granules characteristic of Merkel cells were still discernible. Finally, the Merkel cells and their nuclei fragmented into apoptotic bodies. None of the apoptotic Merkel cells were contacted by nerve fibers, and their desmosomal contacts with surrounding keratinocytes disappeared. After postnatal day 6 apoptotic Merkel cells were no longer observed, and the number of surviving Merkel cells was severely reduced. They were flat and contained few osmiophilic granules. We conclude that perinatal apoptosis is responsible for the loss of Merkel cells lacking innervation in NT3 null mice.     

Angiomatoid change in polyps of the nasal and paranasal regions: an underrecognized and commonly misdiagnosed lesion—report of 45 cases

We present 45 patients with angiomatoid polyps of the nasal and paranasal regions (APNPRs), which are underrecognized lesions which may cause considerable diagnostic difficulties. There were 32 men and 13 women in our series. The average age at diagnosis was 49 years in men and 54.3 years in women. Locations were known in 41 cases and included the nasal septum (14), maxillary sinus (12), ethmoid sinuses (5), lateral wall of the nasal cavity (5), sphenoid sinus (1), and nasal cavity, not otherwise specified (4). X-ray or computed tomography was performed in 19 cases and revealed bone erosions/deviations in four cases. Initial misdiagnoses submitted by referring pathologists were reported in 20/32 of the consultation cases. Our study confirms that APNPRs are benign lesions which often recur and sometimes multiple recurrences are seen. APNPRs sometimes cause severe changes of the skeletal bones especially in recurrent lesions. Awareness of the above described features and familiarity with the clinical presentation of APNPRs is the best way to avoid a misdiagnosis.     

Comparison of an inhomogeneous orthotropic and isotropic material models used for FE analyses

Finite element (FE) analysis has been widely used to study the behaviour of bone or implants in many clinical applications. One of the main factors in analyses is the realistic behaviour of the bone model, because the behaviour of the bone is strongly dependent on a realistic bone material property assignment. The objective of this study was to compare isotropic and orthotropic inhomogeneous material models used for FE analyses of the "global" proximal femur and "small" specimens of the bone (cancellous and cortical). Our hypothesis was that realistic material property assignment (orthotropy) is very important for the FE analyses of small bone specimens, whereas in global FE analyses of the proximal femur, this assignment can be omitted, if the inhomogeneous material model was used. The three-dimensional geometry of the "global" proximal femur was reconstructed using CT scans of a cadaveric femur. This model was implemented into an FE simulation tool and various bone material properties, dependant on bone density, were assigned to each element in the models. The "small" specimens of cortical and cancellous bone were created in the same way as the model of the proximal femur. The results obtained from FE analyses support our above described hypothesis.     

Recurrent pregnancy loss and frequency of eight antiphospholipid antibodies and genetic thrombophilic factors in Czech women

PROBLEM: The aim of this study was to investigate frequencies of eight antiphospholipid antibodies (aPLs) in serum, four genetic thrombophilic factors and their mutual relation in 206 patients with repeated pregnancy loss (RPL). METHOD OF STUDY: Enzyme-linked immunosorbent assay was used for detection of aPLs against ph-serine, ph-ethanolamine, ph-inositol, DL-glycerol, phosphatidic acid, anti-annexin V, cardiolipin, and beta2-GPI. FV 1691G>A (Leiden mutation), FII 20210G>A mutation, MTHFR 677C>T and MTHFR 1298A>C variant genotypes were determined using a melting curve analysis of the PCR amplification product detected by the fluorescence resonance energy transfer. Genotypic distribution and allelic frequencies were calculated. Correlation between aPLs and thrombophilic factors was tested by chi-square and Fisher exact test. RESULTS: Our results show significantly increased prevalence of aPLs against ph-inositol (17-19.6% dependent on number of spontaneous miscarriages) and against ph-serine (18-25%). aPLs in IgG prevail. In 96% of the studied group, at least one risk factor was found (either aPLs positivity or thrombophilic factor). Both aPLs and thrombophilic factors were present in 43%. In the group of women with three or more RPLs, strong positive correlation of aPLs positivity and thrombophilic risk factors was observed. CONCLUSION: Antiphospholipide antibodies and genetic thrombophilic factors are important risk factors in the pathogenesis of RPL. Both autoantibodies against various kinds of phospholipides and genetic thrombophilic factors must be studied together in diagnosis of RPL for appropriate treatment.     

Strong expression of kinase insert domain-containing receptor, a vascular permeability factor/vascular endothelial growth factor receptor in AIDS-associated Kaposi's sarcoma and cutaneous angiosarcoma.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the angiogenesis associated with the growth of many human and animal tumors. VPF/VEGF stimulates endothelial cell growth and increases microvascular permeability by interacting with two endothelial cell tyrosine kinase receptors, KDR and flt-1. We studied 16 cases of AIDS-associated Kaposi's sarcoma (KS), 2 cases of cutaneous angiosarcoma, and 6 cases of capillary hemangioma by in situ hybridization for expression of VPF/VEGF, KDR, and flt-1 mRNAs. We also performed immunohistochemical staining for VPF/VEGF protein in 15 cases. Tumor cells in KS and angiosarcoma strongly expressed KDR but not flt-1 mRNA. Endothelial cells in small stromal vessels in and around these tumors strongly expressed both KDR and flt-1 mRNAs. Tumor cells expressed VPF/VEGF mRNA strongly in only one case of KS, adjacent to an area of necrosis. This was also the only case in which the tumor cells stained substantially for VPF/VEGF protein. VPF/VEGF mRNA and protein were, however, strongly expressed by squamous epithelium in areas of hyperplasia and near areas of ulceration overlying tumors. VPF/VEGF mRNA was also expressed focally at lower levels by infiltrating inflammatory cells, probably macrophages. The strong expression of both KDR and flt-1 in small stromal vessels in and around tumors suggests that VPF/VEGF may be an important regulator of the edema and angiogenesis seen in these tumors. The strong expression of KDR by tumor cells in KS and angiosarcoma implies that VPF/VEGF may also have a direct effect on tumor cells. Tumor cells in four of six capillary hemangiomas strongly expressed both KDR and flt-1 mRNAs in contrast to the high level expression of only KDR observed in the malignant vascular tumors studied. Neither VPF/VEGF mRNA or protein were strongly expressed in capillary hemangiomas. VPF/VEGF and its receptors may play an important but as yet incompletely understood role in the pathogenesis of both benign and malignant vascular tumors.     

Anal incontinence severity assessment tools used worldwide

Objective

To conduct an international survey of anal incontinence assessment tools and the need to evaluate frequency of occurrence of fecal urgency.

Methods

A questionnaire on the use of anal incontinence assessment tools was distributed between May and December 2012 among clinicians and researchers dealing with anal incontinence, primarily in North America, Europe, and Asia.

Results

A total of 143 responses were collected from 56 (39.2%) obstetricians, gynecologists, and urogynecologists; 71 (49.7%) colorectal surgeons, proctologists, and general surgeons; and 16 (11.2%) physiotherapists, theoretical scientists, and gastroenterologists. Fourteen different tools were reported—most commonly Wexner score (n = 78; 48.8%) and St Mark’s score (n = 29; 18.1%). No scoring system was used by 24 (16.8%) respondents. Thirty-four (28.6%) used multiple tools. There was variation in the reasons given for scoring the frequency of fecal urgency as 4 points when using St Mark’s score. Of 96 respondents responding to a query about modifying the St Mark’s score, 88 (91.7%) agreed that fecal urgency should be scored according to the frequency of occurrence.

Conclusion

Although the Wexner score neglects fecal urgency, it is the most commonly used scoring system. The study contributes to the standardization of terminology and reproducibility of results in research and clinical management of anal incontinence.     

Clinical evaluation of early postpartum pain and healing outcomes after mediolateral versus lateral episiotomy

Objective

To evaluate short-term perineal pain among primiparous women after mediolateral episiotomy (MLE) and lateral episiotomy (LE).

Methods

The prospective randomized study was conducted in the Czech Republic during 2010–2012. Consecutive primiparous women who gave birth at or after 37 weeks of pregnancy and had indications for an episiotomy were enrolled and randomly assigned to undergo MLE or LE. Patients were unaware of the episiotomy type performed. The primary outcomes were pain at 24 hours, 72 hours, and 10 days post partum, measured by a visual analog scale, verbal rating scale, interference with activities of daily living, and amount of analgesic use.

Results

The analysis included 266 women who underwent MLE and 297 women who underwent LE. Complete relief of pain was observed in 6 (2.3%) of 266 women after 24 hours, 21 (8.0%) of 264 after 72 hours, and 77 (29.1%) of 265 after 10 days in the MLE group, and in 11 (3.9%) of 285, 23 (7.7%) of 297, and 78 (26.4%) of 295 in the LE group, respectively (P = 0.36). There were no significant differences in overall pain scores from any rating system or in the amount of analgesics used.

Conclusion

Incidence and extent of pain in the first 10 days after LE correspond to those after adequately performed MLE.     

Lumbar degenerative spondylolisthesis: factors associated with the decision to fuse

BACKGROUND CONTEXTThe indication to perform a fusion and decompression surgery as opposed to decompression alone for lumbar degenerative spondylolisthesis (LDS) remains controversial. A variety of factors are considered when deciding on whether to fuse, including patient demographics, radiographic parameters, and symptom presentation. Likely surgeon preference has an important influence as well.PURPOSEThe aim of this study was to assess factors associated with the decision of a Canadian academic spine surgeon to perform a fusion for LDS.STUDY DESIGN/SETTINGThis study is a retrospective analysis of patients prospectively enrolled in a multicenter Canadian study that was designed to evaluate the assessment and surgical management of LDS.PATIENT SAMPLEInclusion criteria were patients with: radiographic evidence of LDS and neurogenic claudication or radicular pain, undergoing posterior decompression alone or posterior decompression and fusion, performed in one of seven, participating academic centers from 2015 to 2019.OUTCOME MEASURESPatient demographics, patient-rated outcome measures (Oswestry Disability Index [ODI], numberical rating scale back pain and leg pain, SF-12), and imaging parameters were recorded in the Canadian Spine Outcomes Research Network (CSORN) database. Surgeon factors were retrieved by survey of each participating surgeon and then linked to their specific patients within the database.METHODSUnivariate analysis was used to compare patient characteristics, imaging measures, and surgeon variables between those that had a fusion and those that had decompression alone. Multivariate backward logistic regression was used to identify the best combination of factors associated with the decision to perform a fusion.RESULTSThis study includes 241 consecutively enrolled patients receiving surgery from 11 surgeons at 7 sites. Patients that had a fusion were younger (65.3±8.3 vs. 68.6±9.7 years, p=.012), had worse ODI scores (45.9±14.7 vs. 40.2±13.5, p=.007), a smaller average disc height (6.1±2.7 vs. 8.0±7.3 mm, p=.005), were more likely to have grade II spondylolisthesis (31% vs. 14%, p=.008), facet distraction (34% vs. 60%, p=.034), and a nonlordotic disc angle (26% vs. 17%, p=.038). The rate of fusion varied by individual surgeon and practice location (p<.001, respectively). Surgeons that were fellowship trained in Canada more frequently fused than those who fellowship trained outside of Canada (76% vs. 57%, p=.027). Surgeons on salary fused more frequently than surgeons remunerated by fee-for-service (80% vs. 64%, p=.004). In the multivariate analysis the clinical factors associated with an increased odds of fusion were decreasing age, decreasing disc height, and increasing ODI score; the radiographic factors were grade II spondylolisthesis and neutral or kyphotic standing disc type; and the surgeon factors were fellowship location, renumeration type and practice region. The odds of having a fusion surgery was more than two times greater for patients with a grade II spondylolisthesis or neutral and/or kyphotic standing disc type (opposed to lordotic standing disc type). Patients whose surgeon completed their fellowship in Canada, or whose surgeon was salaried (opposed to fee-for-service), or whose surgeon practiced in western Canada had twice the odds of having fusion surgery.CONCLUSIONSThe decision to perform a fusion in addition to decompression for LDS is multifactorial. Although patient and radiographic parameters are important in the decision-making process, multiple surgeon factors are associated with the preference of a Canadian spine surgeon to perform a fusion for LDS. Future work is necessary to decrease treatment variability between surgeons and help facilitate the implementation of evidence-based decision making.     

Gastrointestinal autonomic nerve (GAN) tumor. Ultrastructural evidence for a newly recognized entity

We describe three cases of spindle cell tumors arising in the gastrointestinal tract, each with ultrastructural features that recapitulate the ultrastructural morphology of the enteric autonomic nervous system. These features include the presence of small, dense core granules in the synthetic-secretory Golgi structures, sparsely distributed within the ample tumor-cell cytoplasm, near plasma-membrane surfaces and within axons. Tumor cells had elongated processes and axons contained small granular vesicles, clear vesicles, or large, dense vesicles. Specific features diagnostic for smooth-muscle cell, Schwann cell, or fibroblast cellular origin were absent.