Search PubMed⌕ Search

Biomedical subjects

N Weidner

Publications and source records attributed to N Weidner.

At least 19 recordsLinked to original sources

In vivo high-resolution MR imaging of neuropathologic changes in the injured rat spinal cord.

BACKGROUND AND PURPOSE: MR imaging is the most comprehensive noninvasive means to assess structural changes in injured central nervous system (CNS) tissue in humans over time. The few published in vivo MR imaging studies of spinal cord injury in rodent models by using field strengths < or = 7T suffer from low spatial resolution, flow, and motion artifacts. The aim of this study was to assess the capacity of a 17.6T imaging system to detect pathologic changes occurring in a rat spinal cord contusion injury model ex vivo and in vivo. METHODS: Seven adult female Fischer 344 rats received contusion injuries at thoracic level T10, which caused severe and reproducible lesions of the injured spinal cord parenchyma. Two to 58 days postinjury, high-resolution MR imaging was performed ex vivo (2) or in vivo in anesthetized rats (5 spinal cord injured + one intact control animal) by using 2D multisection spin- and gradient-echo imaging sequences, respectively, combined with electrocardiogram triggering and respiratory gating. RESULTS: The acquired images provided excellent resolution and gray/white matter differentiation without significant artifacts. Signal intensity changes, which were detected with ex vivo and in vivo MR imaging following spinal cord injury, could be correlated with histologically defined structural changes such as edema, fibroglial scar, and hemorrhage. CONCLUSIONS: These results demonstrate that MR imaging at 17.6T allows high-resolution structural analysis of spinal cord pathology after injury.

Animals↗

[Nerve repair strategies for restoration of erectile function after radical pelvic surgery].

Iatrogenic cavernous nerve lesions occurring during radical pelvic surgery often lead to irreversible erectile dysfunction. The nerve defects after excision of the neurovascular bundles must be reconstructed by interposition grafting to supply a permissive scaffold for oriented axonal regrowth. The use of autologous nerve grafts for the repair of human cavernous nerves during radical prostatectomy has been controversial regarding the limited success achieved with bilateral nerve grafting. Artificial nerve guides consisting of natural or synthetic materials have been successfully used for bridging peripheral nerve defects. The combination with Schwann cells, neurotrophic factors and extracellular matrix components has been shown to promote cavernous nerve regeneration.

Erectile Dysfunction↗

Nerve replacement strategies for cavernous nerves.

OBJECTIVE: This article reviews novel restorative therapies for cavernous nerves that may be used to replace resected cavernous nerves at the time of pelvic surgery. METHODS: A literature-based presentation (Medline search) on current nerve replacement strategies was conducted with emphasis on neurobiological factors contributing to the restoration of erectile function after cavernous nerve injuries. RESULTS: A promising alternative to autologous nerve grafts for extending the length of successful nerve regeneration are artificial nerve guides. The addition of neurotrophic factors, extracellular matrix components and Schwann cells has been shown to promote cavernous nerve regeneration. Neurotrophic factors can be incorporated in the scaffold or can be supplied by cells seeded into the stroma. The regenerative capacity of these cells can be further enhanced by genetic modification with neurotrophic factor encoding genes. CONCLUSIONS: Artificial nerve guides, especially biodegradable ones containing growth-promoting factors or cells, are a promising option for the repair of cavernous nerve lesions.

Erectile Dysfunction↗

High-resolution MR imaging of the rat spinal cord in vivo in a wide-bore magnet at 17.6 Tesla.

The objective was to demonstrate the feasibility and to evaluate the performance of high-resolution in vivo magnetic resonance (MR) imaging of the rat spinal cord in a 17.6-T vertical wide-bore magnet. A probehead consisting of a surface coil that offers enlarged sample volume suitable for rats up to a weight of 220 g was designed. ECG triggered and respiratory-gated gradient echo experiments were performed on a Bruker Avance 750 wide-bore spectrometer for high-resolution imaging. With T*2 values between 5 and 20 ms, good image contrast could be obtained using short echo times, which also minimizes motion artifacts. Anatomy of healthy spinal cords and pathomorphological changes in traumatically injured rat spinal cord in vivo could be visualized with microscopic detail. It was demonstrated that imaging of the rat spinal cord in vivo using a vertical wide-bore high-magnetic-field system is feasible. The potential to obtain high-resolution images in short scan times renders high-field imaging a powerful diagnostic tool.

Animals↗

[Tissue engineering of erectile nerves].

Dissection of the cavernous nerves eliminates spontaneous erections and may lead to irreversible erectile dysfunction due to degeneration of cavernous tissue. Novel procedures to reconstruct penile innervation include cavernous nerve interposition grafting and neurotrophic treatments to revitalize penile neural input, evaluated thus far in various preclinical models of cavernous nerve injury. Schwann cells crucially contribute to successful axonal regeneration by mechanical and paracrine mechanisms in the injured nerve, and Schwann cells seeded into guidance channels have been successfully employed to support regeneration in animal models of cavernous nerve injury. Gene therapy, tissue engineering, and reconstructive techniques have been combined to deliver neurotrophic factors and recover erectile function.

Absorbable Implants↗

Schwann cell seeded guidance tubes restore erectile function after ablation of cavernous nerves in rats.

PURPOSE: Dissection of the cavernous nerves eliminates spontaneous erections. We evaluated the ability of Schwann cell seeded nerve guidance tubes to restore erections after bilateral cavernous nerve resection in rats. MATERIALS AND METHODS: Sections (5 mm) of the cavernous nerve were excised bilaterally, followed by immediate bilateral microsurgical reconstruction. In 10 animals per group (20 study nerves) reconstruction was performed by genitofemoral nerve interposition, interposition of silicone tubes or interposition of silicone tubes seeded with homologous Schwann cells. As the control 10 animals (20 study nerves) underwent sham operation (positive control) and bilateral nerve ablation (without reconstruction) was performed in a further 10 (negative control). Erectile function was evaluated 3 months postoperatively by relaparotomy, electrical nerve stimulation and intracavernous pressure recording. RESULTS: After 3 months neurostimulation resulted in an intact erectile response in 90% (18 of 20) of Schwann cell grafts, while treatment with autologous nerves (30% or 6 of 20) or tubes only (50% or 10 of 20) was less successful (p <0.01). Whereas untreated ablated rats showed no inducible erections (0% or 0 of 20), all sham operated animals had an intact erectile response (100% or 20 of 20). Maximum intracavernous pressure upon electrostimulation was significantly elevated using Schwann cell grafts compared to results in the other treatment groups (p <0.001). Morphological evaluation revealed advanced regeneration within Schwann cell grafts. CONCLUSIONS: Schwann cell seeded guidance tubes restore erectile function after the ablation of cavernous nerves in rats and they are superior to autologous nerve grafts.

Animals↗

Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury.

Although it is believed that little recovery occurs after adult mammalian spinal cord injury, in fact significant spontaneous functional improvement commonly occurs after spinal cord injury in humans. To investigate potential mechanisms underlying spontaneous recovery, lesions of defined components of the corticospinal motor pathway were made in adult rats in the rostral cervical spinal cord or caudal medulla. Following complete lesions of the dorsal corticospinal motor pathway, which contains more than 95% of all corticospinal axons, spontaneous sprouting from the ventral corticospinal tract occurred onto medial motoneuron pools in the cervical spinal cord; this sprouting was paralleled by functional recovery. Combined lesions of both dorsal and ventral corticospinal tract components eliminated sprouting and functional recovery. In addition, functional recovery was also abolished if dorsal corticospinal tract lesions were followed 5 weeks later by ventral corticospinal tract lesions. We found extensive spontaneous structural plasticity as a mechanism correlating with functional recovery in motor systems in the adult central nervous system. Experimental enhancement of spontaneous plasticity may be useful to promote further recovery after adult central nervous system injury.

Animals↗

p53 immunoreactivity correlates with Ki-67 and bcl-2 expression in renal cell carcinoma.

This study assessed the relation of proliferation, inhibition of apoptosis, and the p53 tumor suppressor protein expression in clear renal cell carcinoma (RCC). Archival pathological specimens from 43 patients treated for RCC were obtained. Median follow-up for the patients was 52 months (range 2.5 months to 178 months). Immunostaining of paraffin tissue sections was carried out for four different markers: a) Ki-67, a marker for cellular proliferation; b) p53/DO7, c) p53/pAb240, antibodies for the p53 protein; and d) bcl-2, a marker for inhibition of apoptosis (programmed cell death). One thousand cells were counted per slide at 400x magnification. Staining of >/=10% of cells was considered positive and <10% negative. Fisher exact contingency tables were used for correlation between markers, tumor grade and stage. A significant correlation was found between Ki-67 and p53 immunoreactivity samples, P=0.0001. Interestingly, a significant association was found if Ki-67 and bcl-2 scores were combined and correlated with p53, P=0.009. Results showed no correlation between any of the immunohistochemical markers and grade or stage. In addition, Kaplan-Meier survival curves demonstrated no significant difference between patients' tumors that was scored immunoreactive negative vs. positive for Ki-67, p53, or bcl-2. This study indicates that p53 expression correlates with proliferation, and inhibition of programmed cell death in RCC.

Journal Article↗

Primary hepatic anaplastic large-cell lymphoma of T-cell phenotype in acquired immunodeficiency syndrome: a report of an autopsy case and review of the literature.

Anaplastic large-cell lymphomas (ALCL) were first described by Stein et al. in 1985 as large-cell neoplasms with a pleomorphic appearance, subtotal effacement of the lymph node structure, and expression of the lymphoid activation antigen CD-30 (Ki-l). Since their first description, these tumors have been documented in a variety of extranodal sites. We report a primary hepatic anaplastic large-cell lymphoma in a patient with advanced AIDS, who presented with hepatic failure and multiple nodules in the liver. A complete autopsy showed discrete tumor nodules throughout the entire liver without gross or microscopic involvement of lymph nodes or any other organs by the neoplastic process. The tumor cells showed typical histological and immunohistochemical features of ALCL and were strongly immunoreactive with the T-cell markers CD-3 and UCHL-1. Only one previous case of primary hepatic ALCL has been reported in the literature, and this tumor occurred in an immunocompetent patient and was not immunoreactive for B- or T-cell markers. To our knowledge, this study represents the first reported case of primary hepatic anaplastic large-cell lymphoma of T-cell phenotype. Additionally, this is the first case of primary hepatic ALCL reported in an AIDS patient.

Adult↗

Introduction. Vasculitis.

The vasculitides commonly create diagnostic and management problems, and a biopsy diagnosis of vasculitis usually does not stand alone in the proper medical management of a patient. Indeed, a conclusive diagnosis usually cannot be made without correlation with the patient's clinical history, physical findings, and/or angiographic findings. Nonetheless, a definitive diagnosis depends on histologic examination because few vasculitic syndromes have specific clinical and laboratory findings. Moreover, the histopathologic diagnosis depends on pathologist experience, tissue selection, sample size, chronologic age of the biopsied lesion(s), and effects of prior treatment. In this issue of Seminars in Diagnostic Pathology the important systemic vasculities are reviewed and updated. These include: polyarteritis nodosa, microscopic polyangiitis (microscopic polyarteritis), cutaneous leukocytoclastic vasculitis, Wegener's granulomatosis, giant-cell vasculitides, localized vasculitis, and angiocentric lymphomas (lymphomatous vasculitis).

Consensus Statements as Topic↗

Giant-cell vasculitides.

Although many of the vasculitides within the classification of the American College of Rheumatology can have a component of granulomatous inflammation with giant cells, two (ie, giant-cell [temporal] arteritis and Takayasu arteritis) are characterized by infiltrates that are dominated by granulomatous and/or giant-cell-containing inflammation. Furthermore, granulomatous and/or giant-cell dominant infiltrates can characterize disseminated giant-cell arteritis, granulomatous vasculitis of the central nervous system, localized giant-cell arteritis, mesenteric inflammatory veno-occlusive disease, primary cutaneous phlebitis, and giant-cell phlebitis of mesenteric veins and/or omentum. Like the other systemic vasculitides, there is considerable clinicopathologic overlap between these giant-cell vasculitides. Indeed, they are likely closely related, but how they specifically relate to each other is not clear. Their accurate diagnosis is important; because serious morbidity and even death may occur, if proper treatment is delayed or if excessive immunotherapy is given.

Aged↗

Primary anaplastic large cell lymphoma of the adrenal gland.

Primary adrenal lymphomas are rare. Most reported cases are of B-cell phenotype and follow an aggressive clinical course. We report a case of primary anaplastic large cell, CD30+ adrenal lymphoma developing in a 62-year-old woman. The patient presented with fatigue and vague right upper quadrant pressure. Computed tomography revealed bilateral adrenal masses. A right adrenalectomy was performed. Histologic evaluation showed islands of large atypical cells surrounded by eosinophilic acellular material. The tumor cells stained positive for CD45, CD45RO, CD43, and CD30. Epstein-Barr virus genome was identified in tumor cells using in situ hybridization. The patient was treated with chemotherapy and a 23-month follow-up examination showed no change in the size of the opposite adrenal gland and no other evidence of lymphoma.

Adrenal Gland Neoplasms↗

Endothelial-like cells derived from human CD14 positive monocytes.

In the present study, we show that endothelial-like cells (ELCs) can develop from human CD14-positive mononuclear cells (CD14 cells) in the presence of angiogenic growth factors. The CD14 cells became loosely adherent within 24 h of culture and subsequently underwent a distinct process of morphological transformation to caudated or oval cells with eccentric nuclei. After 1 week in culture the cells showed a clear expression of endothelial cell markers, including von Willebrand factor (vWF), CD144 (VE-cadherin), CD105 (endoglin), acetylated low-density lipoprotein (AC-LDL)-receptor, CD36 (thrombospondin receptor), FLT-1, which is vascular endothelial cell growth factor (VEGF) receptor-1, and, to a weaker extent, KDR (VEGF receptor-2). Furthermore, in these cells structures resembling Weibel-Palade bodies at different storage stages were identified by electron microscopy, and upon culturing on three-dimensional fibrin gels the cells build network-like structures. In addition, cell proliferation and vWF expression was stimulated by VEGF, and the endothelial cell adhesion molecules CD54 (ICAM-1), and CD106 (VCAM-1) became transiently inducible by tumor necrosis factor-alpha (TNF-alpha). In contrast, the dendritic markers CD1a, and CD83 were not expressed to any significant extent. The expression of CD68, CD80 (B7-1), CD86 (B7-2), HLA-DR and CD36 may also suggest that ELCs might be related to macrophages, sinus lining or microvascular endothelial cells. Taken together, our observations indicate that ELCs can differentiate from cells of the monocytic lineage, suggesting a closer relationship between the monocyte/macrophage- and the endothelial cell systems than previously supposed.

Antigens, Differentiation↗

Continuous epidural butorphanol relieves pruritus associated with epidural morphine infusions in children.

We examined the efficacy of epidural butorphanol to either prevent or relieve pruritus associated with epidural morphine infusion in children. Forty-six children were randomized to receive either epidural morphine (M) or epidural M with butorphanol (B) for postoperative analgesia. They received bupivacaine and either M 50 microg.kg-1 or the same dose of M plus B 10 microg.kg-1. Following surgery, a continuous infusion of 0.1% bupivacaine with either M 20 microg.ml-1 or M 20 microg.ml-1 + B 4 microg.ml-1 was given at a rate of 0.3 ml.kg-1.h-1. Pain scores and pruritus scores were recorded every 4 h during epidural infusion. Subjects with a pruritus score=2 received diphenhydramine 0.5 mg.kg-1 i.v. and were switched to an alternate epidural infusion; subjects receiving M (group M) were switched to M+B while subjects receiving M+B (group B) were switched to hydromorphone (H) 4 microg.ml-1. There was no difference in the initial incidence of pruritus (group M 11/18; group B 13/28). No subject in group M required a second change of epidural infusion because of continued pruritus after being switched to M+B; five of 13 subjects in group B continued to experience pruritus after being switched to H and required a second change of epidural infusion or an alternate analgesic modality (P=0.038). The median pruritus score in the first 24 h after changing epidural infusions was 0 in subjects in group MDelta (changed from M to M+B) and 1 in subjects in group BDelta (changed from M+B to H; P=0.012). While the median sedation score in the first 24 h was 1 in both groups, there was a greater incidence of sedation scores of 2 in group B than group M (28% vs 12.3%; P=0.021). B 10 microg.kg-1 was not effective in preventing pruritus associated with bolus epidural administration of M 50 microg.kg-1 in children. B 1.2 microg.kg-1. h-1 was effective in relieving pruritus associated with continuous epidural infusion of M 6 microg.kg-1.h-1.

Adolescent↗

Papillary and follicular neoplasms of the thyroid gland. Differential immunohistochemical staining with high-molecular-weight keratin and involucrin.

The morphologic distinction between papillary and follicular neoplasms of the thyroid gland can be difficult, especially on small biopsy specimens or in fine-needle aspirations. To determine whether immunohistochemistry could help in achieving the correct diagnosis, we characterized the staining pattern for a series of papillary and follicular neoplasms of the thyroid gland. A pilot study was performed using a panel of antibodies, including high-molecular-weight keratin (HMWK, 34 beta E12), cytokeratin (CK) 5/6, CK7, CK13, CK14, CK20, AE1/AE3, CAM5.2, involucrin, and villin. Of these antibodies, involucrin and HMWK showed strong differential staining between follicular and papillary neoplasms. HMWK stained 91% of papillary carcinomas, including follicular variants, with a median of 53% positive cells, and involucrin stained 72.5% of papillary neoplasms with a median of 45% positive cells. HMWK stained only 20% of follicular neoplasms, whereas involucrin stained 29% of cases. Papillary neoplasms showed strong, although patchy, staining with HMWK and involucrin, whereas those follicular neoplasms that did have staining showed a weak, diffuse pattern of staining. We believe that HMWK, and involucrin to a lesser degree, could be useful in differentiating papillary from follicular neoplasms, especially for cytologic cell block material or for cases in which the architectural pattern is follicular.

Adenocarcinoma, Follicular↗