Pacinian neuromas and neurofibromas of the hands and fingers: a systematic review.

Tumours involving Pacinian corpuscles are rare. The literature identifies two main pathological disorders: the Pacinian corpuscle neuroma or hyperplasia and the Pacinian corpuscle neurofibroma. Published data are confusing and at times conflicting. This systematic review summarizes the available data in order to support clinicians in the differential diagnosis with other tumours responsible for unclear symptoms in the hands and fingers. We identified 67 pertinent articles. Although some similarities have been described, the two tumours have relevant differences, specifically when comparing age of the patient, location, symptoms, characteristic of a mass, and aetiology. All these factors should be taken into account in order to improve diagnostic accuracy. Despite the low incidence of unsuccessful surgeries, extraordinary measures are occasionally necessary to achieve complete resolution of symptoms.

Delayed recognition of an ipsilateral femoral neck and shaft fracture leading to preventable subsequent complications: a case report.

BACKGROUND: Ipsilateral femoral shaft and neck fractures are rare injuries, affecting mostly young patients who sustained high-energy traumas. In 19-50% of cases, the femoral fracture is misdiagnosed or overlooked at the initial presentation, with reportedly increased risk of complications such as non-union and avascular necrosis. We present a case of an ipsilateral femoral neck and shaft fracture, which was missed at initial presentation despite radiographic and computed tomography (CT) scan evaluation. CASE PRESENTATION: A 56-year old female was admitted to our institution following a high-energy trauma (fall from 6 m). Initial radiographic and CT scan evaluation revealed a displaced femoral shaft fracture but no other femoral fractures were detected. Closed reduction and external fixation of the femoral shaft fracture was performed in the emergency setting. Follow-up radiologic evaluations revealed an ipsilateral laterally displaced femoral neck fracture. Despite cephalomedullary nail fixation of both fractures performed on the third day from the initial injury, the patient developed a non-union of the femoral neck fracture, which led to cut-out of the lag screw with associated varus failure of the femoral neck fracture requiring surgical revision and implant of a bipolar hemiarthroplasty at one year follow up. The postoperative course was uneventful and the patient had a full long-term recovery. CONCLUSION: This case report exemplifies the need to maintain the highest level of suspiciousness for the concomitant presence of an ipsilateral femoral neck fracture when treating polytraumatized patients who sustained a femoral shaft fracture as a consequence of a high-energy trauma. Furthermore, the pre-operative standardized radiological evaluation (plain x-ray and CT scan) might not always help in ruling out these fractures. It is therefore necessary to adopt additional standardized radiographic protocols not only in the pre-operative but also in the intra-operative and immediate post-operative settings.

A new animal model to assess angiogenesis and endocrine function of parathyroid heterografts in vivo.

BACKGROUND: It is still a matter of investigation how angiogenesis and restoration of gland perfusion determine graft function after free parathyroid autotransplantation. We provide a new animal model allowing simultaneous and repetitive in vivo assessment of angiogenesis and endocrine function of parathyroid transplants. METHODS: Fresh human parathyroid tissue from patients with secondary hyperparathyroidism was grafted into dorsal skinfold chamber preparations of athymic nude mice (CD1-nu; n=8). Equivalent pieces of the same human donor specimens were heat-inactivated and served as control grafts (n=7). RESULTS: In all animals receiving parathyroid transplants, intact human parathyroid hormone levels were detectable by species-specific enzyme-linked immunosorbent assay analysis of plasma samples on day 5 after transplantation and increased by 2.5-fold over the observation period (19 days) in contrast with controls. Plasma Ca levels revealed no differences between the groups. On day 5 after transplantation, intravital fluorescence microscopy revealed murine angiogenic microvessels sprouting along nonperfused human donor vessels, and 1 week later functional microvasculature was established in all parathyroid transplants. Histologic analysis revealed well-vascularized endocrine tissue. In contrast, control grafts were necrotic and partly resorbed; they exhibited no angiogenic activity or well-vascularized fat cells indicating fatty degeneration. In addition, species-specific Western blot analysis revealed vascular endothelial growth factor expression of parathyroid transplants rather than functional vessel density as the functional parameter of angiogenesis determining transplant function in vivo. CONCLUSION: This model may serve to understand mechanisms associated with specific parathyroid transplant angiogenesis and its significance for transplant function to optimize clinical success of autotransplantation in therapy-resistant patients.

Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy.

PURPOSE: Cationic liposomes have been shown to selectively target tumor endothelial cells. Therefore, the encapsulation of antineoplastic drugs into cationic liposomes is a promising tool to improve selective drug delivery by targeting tumor vasculature. It was the aim of our study to evaluate tumor selectivity and antitumoral efficacy of paclitaxel encapsulated in cationic liposomes in comparison with the free drug paclitaxel (Taxol(R)) in vivo. EXPERIMENTAL DESIGN: Experiments evaluating tumor selectivity were carried out in male Syrian golden hamsters bearing the amelanotic hamster melanoma A-Mel-3 in dorsal skinfold preparations. Growth of tumor cells was observed after s.c. inoculation (day 0). On days 5, 7, 9, 12, 14, and 16, animals were treated by continuous i.v. infusion over 90 min with 5% glucose, Taxol(R), unloaded cationic liposomes, or paclitaxel encapsulated into cationic liposomes (LipoPac), respectively (lipid dose, 150 mg/kg body weight; paclitaxel dose, 5 mg/kg body weight). Tumor volumes and presence of regional lymph node metastases were quantified. RESULTS: Vascular targeting of rhodamine-labeled cationic liposomes was maintained after encapsulation of paclitaxel as revealed by in vivo fluorescence microscopy (ratio of dye concentration, tumor:normal tissue = 3:1). The s.c. tumor growth revealed a remarkable retardation of tumor growth after treatment with LipoPac (1.7 +/- 0.3 cm(3)). In contrast, control tumors showed exponential tumor growth [tumor volume at the end of the observation period (mean +/- SE): 5% glucose, 17.7 +/- 1.9 cm(3); unloaded cationic liposomes, 10.0 +/- 1.6 cm(3); Taxol(R), 10.7 +/- 1.7 cm(3)]. In addition, the appearance of regional lymph node metastases was significantly delayed by treatment with paclitaxel encapsulated into cationic liposomes in comparison with all other groups. CONCLUSIONS: The data suggest that cationic liposomes are a powerful tool for selective and efficient drug delivery to tumor microvessels. This may serve as proof of the concept of neovascular tumor targeting therapy by cationic liposomes.

Fracture of the shoulder girdle in multiply injured patients - an imperative for a high level of suspicion for associated neurovascular injuries.

BACKGROUND: The combination of a bony injury to the shoulder girdle and damage to the brachial plexus and the subclavian vessels is a rare finding. The cases of this combined injury pattern described in the literature are most notably reported in multiply-injured patients after high velocity trauma. FINDINGS: Three cases were admitted to our hospital after motorcycle accidents resulting in a combination of severe bony injuries to the shoulder girdle, to the subclavian artery and a lesion to the brachial plexus. Based on these three clinical cases the patterns of injury, as well as primary and secondary treatment approaches are presented. CONCLUSION: The early detection of these injuries can be difficult in given acute, life threatening injuries addressed first in these multiply injured patients. A high level of suspicion, in conjunction with standardized ATLS based institutional protocols for secondary and tertiary survey, should increase the likelihood of a timely detection and early management of these rare but potentially devastating injuries.

Complement gene expression is regulated by pro-inflammatory cytokines and the anaphylatoxin C3a in human tenocytes.

Interplay between complement factors, regulatory proteins, anaphylatoxins and cytokines could be involved in tendon healing and scar formation. The expression and regulation of complement factors by cytokines or anaphylatoxins are completely unclear in tendon. Hence, the gene expression of the anaphylatoxin receptors C3aR, C5aR and cytoprotective complement regulatory proteins (CRPs) was analysed in human tendon, cultured primary tenocytes and to directly compare the general expression level, additionally in human leukocytes. Time-dependent regulation of complement by cytokines and the anaphylatoxin C3a was assessed in cultured tenocytes. Gene expression of the anaphylatoxin receptors C3aR, C5aR and the CRPs CD46, CD55 and CD59 was detected in tendon, cultured tenocytes and leukocytes, whereas CD35 could only be found in tendon and leukocytes. Compared with cultured tenocytes, complement expression was higher in tendon and compared with leukocytes C3aR, C5aR, CD35 and CD55, but not CD46 and CD59 gene expression levels were lower in tendon. C3aR mRNA was up-regulated by both TNFα and C3a in cultured tenocytes in a time-dependent manner whereby C5aR gene expression was only induced by C3a. IL-6 or C3a impaired the CRP gene expression. C3a stimulation lead to an up-regulation of TNFα and IL-1ß mRNA in tenocytes. Degenerated tendons revealed an increased C5aR and a reduced CD55 expression. The expression profile of the investigated complement components in tendon and cultured tenocytes clearly differed from that of leukocytes. Tenocytes respond to the complement split fragment C3a with CRP suppression and enhanced pro-inflammatory cytokine gene expression suggesting their sensitivity to complement activation.

Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels.

Recently, cationic liposomes have been shown to preferentially target the angiogenic endothelium of tumors. It was the aim of our study to investigate the influence of liposomal surface charge on the uptake and kinetics of liposomes into solid tumors and tumor vasculature. Experiments were performed in the amelanotic hamster melanoma A-Mel-3 growing in the dorsal skinfold chamber preparation of male Syrian golden hamsters. Fluorescently labeled liposomes with different surface charge were prepared. Accumulation of i.v. injected liposomes was assessed by quantitative intravital fluorescence microscopy of tumor and surrounding host tissue. The histological distribution of liposomes was analyzed by double-fluorescence microscopy 20 min after application of fluorescently labeled lectin as a vascular marker. After i.v. application of anionic and neutral liposomes, we observed an almost homogeneous distribution of liposome-induced fluorescence throughout the chamber preparation without specific targeting to tumor tissue. In contrast, cationic liposomes exhibited a significantly enhanced accumulation in tumor tissue and tumor vasculature up to 3-fold compared to surrounding tissue (p<0.05). The histological distribution of neutral and anionic liposomes revealed extravasation 20 min after i.v. injection, while cationic liposomes displayed a highly selective accumulation on the vascular endothelium. In conclusion, cationic liposomes exhibited a preferential uptake in angiogenic tumor vessels and therefore may provide an efficient tool for the selective delivery of diagnostic or therapeutic agents to angiogenic blood vessels of solid tumors. On the other hand, anionic and neutral liposomes may be used as carriers of drugs to the extravascular compartment of tumors due to their extravasation.