The effects of human herpesvirus 8 infection and interferon-gamma response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals

Background Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV-8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary. Objectives To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS). Methods We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART). Results CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS. Conclusions. Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.

Quantitative parameters of facial motor evoked potential during vestibular schwannoma surgery predict postoperative facial nerve function

Background Facial motor evoked potential (FMEP) amplitude ratio reduction at the end of the surgery has been identified as a good predictor for postoperative facial nerve outcome. We sought to investigate variations in FMEP amplitude and waveform morphology during vestibular schwannoma (VS) resection and to correlate these measures with postoperative facial function immediately after surgery and at the last follow-up. Methods Intraoperative orbicularis oculi and oris muscles FMEP data from 35 patients undergoing surgery for VS resection were collected, then analysed by surgical stage: initial, dural opening, tumour dissection (TuDis), tumour resection (TuRes) and final. Findings Immediately after surgery, postoperative facial function correlated significantly with the FMEP amplitude ratio during TuDis, TuRes and final stages in both the orbicularis oculi (p = 0.003, 0.055 and 0.028, respectively) and oris muscles (p = 0.002, 0.104 and 0.014, respectively). At the last follow-up, however, facial function correlated significantly with the FMEP amplitude ratio only during the TuDis (p = 0.005) and final (p = 0.102) stages for the orbicularis oris muscle. At both time points, postoperative facial paresis correlated significantly with FMEP waveform deterioration in orbicularis oculi during the final stage (immediate, p = 0.023; follow-up, p = 0.116) and in orbicularis oris during the TuDis, TuRes and final stages (immediate, p = 0.071, 0.000 and 0.001, respectively; follow-up, p = 0.015, 0.001 and 0.01, respectively). Conclusions FMEP amplitude ratio and waveform morphology during VS resection seem to represent independent quantitative parameters that can be used to predict postoperative facial function. Event-to-baseline FMEP monitoring is quite useful to dictate when intraoperative changes in surgical strategy are warranted to reduce the chances of facial nerve injury.

Scanning laser polarimetry with enhanced corneal compensation for detection of axonal loss in band atrophy of the optic nerve

PURPOSE: To compare the abilities of scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) and variable corneal compensation (VCC) modes for detection of retinal nerve fiber layer (RNFL) loss in eyes with band atrophy (BA) of the optic nerve. DESIGN. Cross-sectional study. METHODS: Thirty-seven eyes from 37 patients with BA and temporal visual field defect from chiasmal compression and 40 eyes from 40 healthy subjects were studied. Subjects underwent standard automated perimetry and RNFL measurements using an SLP device equipped with VCC and ECC. Receiver operating characteristic (ROC) curves were calculated for each parameter. Pearson correlation coefficients were obtained to evaluate the relationship between RNFL thickness parameters and severity of visual field loss, as assessed by the temporal mean defect. RESULTS: All RNFL thickness parameters were significantly lower in eyes with BA compared with normal eyes with both compensation modes. However, no statistically significant differences were observed in the areas under the ROC curves for the different parameters between GDx VCC and ECC (Carl Zeiss Meditec, Inc, Dublin, California, USA). Structure-function relationships also were similar for both compensation modes. CONCLUSIONS: No significant differences were found between the diagnostic accuracy of GDx ECC and that of VCC for detection of BA of the optic nerve. The use of GDx ECC does not seem to provide a better evaluation of RNFL loss on the temporal and nasal sectors of the peripapillary retina in subjects with BA of the optic nerve.

Paracoccidioidomycosis: Cells expressing IL17 and Foxp3 in cutaneous and mucosal lesions

We demonstrated and quantified by immunohistochemistry the population of cells expressing IL17 and Foxp3 in cutaneous and mucosal paracoccidioidomycosis lesions, associating these populations of cells with different presentations of granulomatous response. For this purpose, 61 skin biopsies and 55 oral mucosal biopsies were evaluated. Cells expressing IL17 were distributed in the inflammatory infiltrate in both groups of lesions and were found in the vessels` wall too. Foxp3+ expression was limited to the nuclei of lymphocytes in the inflammatory infiltrate. The distribution of IL17 was similar among the groups; however, Foxp3+ cells were increased in mucosal lesions that displayed compact granulomas. The results suggest that IL17 seems to play a role in paracoccidioidomycosis cutaneous and mucosal lesions, probably as secondary cells in the clearance of the fungal antigens. The presence of Foxp3+ cells both in skin and mucosa corroborates some previous researches that suggest the role of this group of cells in the modulation of local immune response. (C) 2011 Elsevier Ltd. All rights reserved.

Comparative effects of wavelengths of low-power laser in regeneration of sciatic nerve in rats following crushing lesion

Peripheral nerves are structures that, when damaged, can result in significant motor and sensory disabilities. Several studies have used therapeutic resources with the aim of promoting early nerve regeneration, such as the use of low-power laser. However, this laser therapy does not represent a consensus regarding the methodology, thus yielding controversial conclusions. The objective of our study was to investigate, by functional evaluation, the comparative effects of low-power laser (660 nm and 830 nm) on sciatic nerve regeneration following crushing injuries. Twenty-seven Wistar rats subjected to sciatic nerve injury were divided into three groups: group sham, consisting of rats undergoing simulated irradiation; a group consisting of rats subjected to gallium-aluminum-arsenide (GaAlAs) laser at 660 nm (10 J/cm(2), 30 mW and 0.06 cm(2) beam), and another one consisting of rats subjected to GaAlAs laser at 830 nm (10 J/cm(2), 30 mW and 0.116 cm(2)). Laser was applied to the lesion for 21 days. A sciatic functional index (SFI) was used for functional evaluation prior to surgery and on days 7, 14, and 21 after surgery. Differences in SFI were found between group 660 nm and the other ones at the 14th day. One can observe that laser application at 660 nm with the parameters and methods utilised was effective in promoting early functional recovery, as indicated by the SFI, over the period evaluated.

Temporomandibular disorders and cutaneous allodynia are associated in individuals with migraine

The objective of this study was to estimate and contrast the occurrence of ictal and interictal cutaneous allodynia (CA) in individuals with migraine with and without temporomandibular disorders (TMD). Both TMD and CA are common in migraine and may be associated with migraine transformation from episodic into a chronic form. Herein we hypothesize that TMD contributes to the development of CA and to more severe headaches. In a clinic-based sample of individuals with episodic migraine, the presence of TMD was assessed using the research diagnostic criteria for myofascial or mixed (myofascial and arthralgic) TMD. Ictal CA was quantified using the validated Allodynia Symptom Checklist (ASC-12). The ASC-12 measures CA over the preceding month by asking 12 questions about the frequency of allodynia symptoms during headaches. Interictal CA was assessed in the domains of heat, cold and mechanical static allodynia using quantitative sensory testing. Our sample consists of 55 individuals; 40 (73%) had TMD (23 with myofascial TMD and 17 with the mixed type). CA of any severity (as assessed by ASC-12) occurred in 40% of those without TMD (reference group), 86.9% of those with myofascial TMD (P = 0.041, RR = 3.2, 95% CI = 1.5-7.0) and in 82.3% of those with mixed TMD (P = 0.02, RR = 2.5, 95% CI = 1.2-5.3). Individuals with TMD were more likely to have moderate or severe CA associated with their headaches. Interictally (quantitative sensory testing), thresholds for heat and mechanical nociception were significantly lower in individuals with TMD. Cold nociceptive thresholds were not significantly different in migraine patients with and without TMD. TMDs were also associated with change in extra-cephalic pain thresholds. In logistical regression, TMD remained associated with CA after adjusting for aura, gender and age. TMD and CA are associated in individuals with migraine.

LOCAL LOW POWER LASER IRRADIATION ACCELERATES THE REGENERATION OF THE FIBULAR NERVE IN RATS

Objective: To study the influence of low power GaAsAl laser irradiation on the regeneration of a peripheral nerve, following a controlled crush injury. Material and methods: The right common fibular nerve of 30 Wistar rats was submitted to a crush injury with an adjustable load forceps (5 000 g, 10 minutes of application). The animals were divided into three groups (n=10), according to the postoperative procedure (no irradiation; sham irradiation; effective irradiation). Laser irradiation (830 nm wave-length; 100 mW emission power; continuous mode; 140 J/cm(2)) was started on the first postoperative day and continued over 21 consecutive days. Body mass, time spent on the walking track and functional peroneal index (PFI) were analyzed based on the hind footprints, both preoperatively and on the 21st postoperative day. Results: Walking time and PFI significantly improved in the group that received effective laser irradiation, despite the significant gain in body mass between the pre- and post-operative periods. Conclusion: Low Power GaAsAl laser irradiation, with the parameters used in our study, accelerated and improved fibular nerve regeneration in rats.

A NEW ADJUSTABLE PINCH DESIGNED FOR PRODUCING CRUSH NERVE INJURIES IN THE SCIATIC NERVE OF RATS

Objective: A new adjustable pinch has been developed for producing a crush injury, with a previously known load of 5 kg, on a 5 mm-long segment of the nerve. Methods: Stainless steel was the material selected for building the pinch due its durability and possibility of sterilization with anti-septic substances, which are often corrosive. The crushing load of the pinch is adjustable by increasing or decreasing the tension of the spring by means of a screw used for calibration, which is performed by a load cell. Result: This pinch has been used in a few experimental investigations and was shown to be as efficient as both the universal testing machine and the dead weight machine, previously used. Conclusion: The developed pinch has the advantages of being portable and user-friendly. In addition, the pinch is cheap and allows for the standardization of the applied load.

INFLUENCE OF LASER RADIATION IN NERVE REGENERATION IN DIFFERENT TREATMENT SITES

Objective: This study seeks to determine, through functional gait assessment in different irradiation sites, the influence of a low-intensity GaAsAl laser beam on an injury caused by crushing the peroneal nerve in rats. Methods: 53 rats were used, which were divided into six groups: normal, injured and untreated, injured and treated using placebo, injured and treated in the bone marrow, injured and treated in the nerve, and injured and treated in both (nerve and bone marrow). The peroneal nerve was crushed using a pair of tweezers, and subsequently treated with laser for 28 consecutive days. The functional gait evaluation analyzed the footprints, which were recorded with a video camera on an acrylic bridge in the preoperative period, and on postoperative days 14, 21 and 28, and assessed using PFI formula software. Results: In the functional gait evaluation, significant differences were found only on postoperative day 14. Conclusion: Based on the functional gait evaluation, low-intensity GaAs AI irradiation was able to accelerate and reinforce the process of peripheral nerve regeneration in rats on postoperative day 14, both in the bone marrow- and in the nerve-treated groups.

Morphologic and morphometric evaluation of experimental acute crush injuries of the sciatic nerve of rats

In order to qualify and quantify nerve fiber lesion following an acute crush injury, a morphologic and morphometric study was carried out in 25 Wistar rats divided into live groups of five animals each according to the crushing load applied, i.e., 500,1000, 5000, 10 000, and 15 000 g. The injury was produced under general anesthesia on a 5 mm-long intermediate segment of the right sciatic nerve for 10 min using a dead-weight machine. The animals were killed with an excessive dose of anesthetics 72 h later and submitted to perfusion with a fixing solution through the abdominal aorta immediately after death. Both the right and left sciatic nerves were removed and prepared for histologic and morphometric examinations: 5 mu m-thick sections stained with 1% Toluidine blue were examined under a light microscope equipped with a video camera linked to a computer loaded with a graphic program (KS 400). The morphometric studies included measuring total number of fibers, fiber density, fiber diameter, myelin fiber area, axon diameter, axon area and G ratio. The results showed that damage to the nerve fibers began to appear as early as with the 500g load and was similar in all groups despite the load applied, increasing with the 10000 and 15000g loads, although the external supporting tissues and small diameter fibers were preserved. The predominant type of lesion produced was axonotmesis. (c) 2008 Elsevier B.V. All rights reserved.

Modulation of cutaneous inflammation induced by ticks in contrasting phenotypes of infestation in bovines

Tick saliva contains molecules that are inoculated at the site of attachment on their hosts in order to modulate local immune responses and facilitate a successful blood meal. Bovines express heritable, contrasting phenotypes of infestations with the cattle tick, Rhipicephalus (Boophilus) microplus: breeds of Bos taurus indicus are significantly note resistant than those of Bos taurus taurus. Tick saliva may contain molecules that interfere with adhesion of leukocytes to endothelium and resistant hosts may mount an inflammatory profile that is more efficient to hamper the tick`s blood meal. We show in vitro that adhesion of peripheral blood mononuclear cells to monolayers of cytokine-activated bovine umbilical endothelial cells was significantly inhibited by tick saliva. The inflammatory response to bites of adults of R. microplus mounted by genetically resistant and susceptible bovine hosts managed in the same pasture was investigated in vivo. The inflammatory infiltrates and levels of message coding for adhesion molecules were measured in biopsies of tick-bitten and control skin taken when animals of both breeds were exposed to low and high tick infestations. Histological studies reveal that cutaneous reactions of resistant hosts to bites of adult ticks contained significantly more basophils and eosinophils compared with reactions of the susceptible breed. Expression of the adhesion molecules - intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin - was higher in adult-infested skin of susceptible hosts undergoing low infestations compared to resistant hosts; when host was exposed to high infestations expression of these adhesion molecules was down-regulated in both phenotypes of infestations. Expression of leukocyte adhesion glycoprotein-1 (LFA-1) was higher in skin from susceptible hosts undergoing low or high infestations compared to resistant hosts. Conversely, higher levels of E-selectin, which promotes adhesion of memory T cells, were expressed in skin of resistant animals. This finding may explain the resistant host`s ability to mount more rapid and efficient secondary responses that limit hematophagy and infestations. The expression profiles observed for adhesion molecules indicate that there are differences in the kinetics of the inflammatory reactions mounted by resistant and susceptible hosts and the balance between tick and host is affected by the number of tick bites a host receives. We show that the contrasting phenotypes of infestations seen in bovines infested with R. microplus are correlated with differences in the cellular and molecular composition of inflammatory infiltrates elicited by bites with adult ticks. (C) 2009 Published by Elsevier B.V.

Surgical management of glomus jugulare tumors: a proposal for approach selection based on tumor relationships with the facial nerve Clinical article

Object. The goal of this paper is to analyze the extension and relationships of glomus jugulare tumor with the temporal bone and the results of its surgical treatment aiming at preservation of the facial nerve. Based on the tumor extension and its relationships with the facial nerve, new criteria to be used in the selection of different surgical approaches are proposed. Methods. Between December 1997 and December 2007, 34 patients (22 female and 12 male) with glomus jugulare tumors were treated. Their mean age was 48 years. The mean follow-up was 52.5 months. Clinical findings included hearing loss in 88%, swallowing disturbance in 50%, and facial nerve palsy in 41%. Magnetic resonance imaging demonstrated a mass in the jugular foramen in all cases, a mass in the middle ear in 97%, a cervical mass in 85%, and an intradural mass in 41%. The tumor was supplied by the external carotid artery in all cases, the internal carotid artery in 44%, and the vertebral artery in 32%. Preoperative embolization was performed in 15 cases. The approach was tailored to each patient, and 4 types of approaches were designed. The infralabyrinthine retrofacial approach (Type A) was used in 32.5%; infralabyrinthine pre- and retrofacial approach without occlusion of the external acoustic meatus (Type B) in 20.5%; infralabyrinthine pre- and retrofacial approach with occlusion of the external acoustic meatus (Type C) in 41 W. and the infralabyrinthine approach with transposition of the facial nerve and removal of the middle ear structures (Type D) in 6% of the patients. Results. Radical removal was achieved in 91% of the cases and partial removal in 9%. Among 20 patients without preoperative facial nerve dysfunction, the nerve was kept in anatomical position in 19 (95%), and facial nerve function was normal during the immediate postoperative period in 17 (85%). Six patients (17.6%) had a new lower cranial nerve deficit, but recovery of swallowing function was adequate in all cases. Voice disturbance remained in all 6 cases. Cerebrospinal fluid leakage occurred in 6 patients (17.6%), with no need for reoperation in any of them. One patient died in the postoperative period due to pulmonary complications. The global recovery, based on the Karnofsky Performance Scale (KPS), was 100% in 15% of the patients, 90% in 45%, 80% in 33%, and 70% in 6%. Conclusions. Radical removal of glomus jugulare tumor can be achieved without anterior transposition of the facial nerve. The extension of dissection, however, should be tailored to each case based on tumor blood supply, preoperative symptoms, and tumor extension. The operative field provided by the retrofacial infralabyrinthine approach, or the pre- and retrofacial approaches. with or without Closure of the external acoustic meatus, allows a wide exposure of the jugular foramen area. Global functional recovery based on the KPS is acceptable in 94% of the patients. (DOI: 10.3171/2008.10.JNS08612)

High-voltage electrical burn injuries: Functional upper extremity assessment

High-voltage electric injuries have many manifestations, and an important complication is the damage of the central/peripheral nervous system. The purpose of this work was to assess the upper limb dysfunction in patients injured by high-voltage current. The evaluation consisted of analysis of patients` records, cutaneous-sensibility threshold, handgrip and pinch strength and a specific questionnaire about upper limb dysfunctions (DASH) in 18 subjects. All subjects were men; the average age at the time of the injury was 38 years. Of these, 72% changed job/retired after the injury. The current entrance was the hand in 94% and grounding in the lower limb in 78%. The average burned surface area (BSA) was 8.6%. The handgrip strength of the injured limb was reduced (p < 0.05) and so also that of the three pinch types. The relationship between the handgrip strength and the DASH was statistically significant (p < 0.001) as well as the relationship between the three pinch types (p <= 0.02) to the injured limb. The ability to perceive cutaneous touch/pressure was decreased in the burnt hand, principally in the median nerve area. These data indicate a reduction of the hand muscular strength and sensibility, reducing the function of the upper limb in patients who received high-voltage electrical shock. (C) 2008 Elsevier Ltd and ISBI. All rights reserved.

Phrenic nerve diabetic neuropathy in rats: unmyelinated fibers morphometry

We have demonstrated that phrenic nerves` large myelinated fibers in streptozotocin (STZ)-induced diabetic rats show axonal atrophy, which is reversed by insulin treatment. However, studies on structural abnormalities of the small myelinated and the unmyelinated fibers in the STZ-model of neuropathy are limited. Also, structural changes in the endoneural vasculature are not clearly described in this model and require detailed study. We have undertaken morphometric studies of the phrenic nerve in insulin-treated and untreated STZ-diabetic rats and non-diabetic control animals over a 12-week period. The presence of neuropathy was assessed by means of transmission electron microscopy, and morphometry of the unmyelinated fibers was performed. The most striking finding was the morphological evidence of small myelinated fiber neuropathy due to the STZ injection, which was not protected or reversed by conventional insulin treatment. This neuropathy was clearly associated with severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment. The STZ-diabetes model is widely used to investigate experimental diabetic neuropathies, but few studies have performed a detailed assessment of either unmyelinated fibers or capillary morphology in this animal model. The present study adds useful information for further investigations on the ultrastructural basis of nerve function in diabetes.

A morphometric study on the longitudinal and lateral symmetry of the sural nerve in mature and aging female rats

Aging affects peripheral nerve function and regeneration in experimental models but few literature reports deal with animals aged more than one year. We investigated morphological and morphometric aspects of the sural nerve in aging rats. Female Wistar rats 360, 640 and 720 days old were killed, proximal and distal segments of the right and left sural nerves were prepared for light microscopy and computerized morphometry. No morphometric differences between proximal and distal segments or between right and left sides at the same levels were found in all experimental groups. No increase in fiber and axon sizes was observed from 360 to 720 days. Likewise, no difference in total myelinated fiber number was observed between groups. Myelinated fiber population distribution was bimodal, being the 720-days old animals` distribution shifted to the left, indicating a reduction of the fiber diameters. The 9 ratio distribution of the 720-days old animals` myelinated fiber was also shifted to the left, which suggests axonal atrophy. Morphological alterations due to aging were observed, mainly related to the myelin sheath, which suggests demyelination. Large fibers were more affected than the smaller ones. Axon abnormalities were not as common or as obvious as the myelin changes and Wallerian degeneration was rarely found. These alterations were observed in all experimental groups but were much less pronounced in rats 360 days old and their severity increased with aging. in conclusion, the present study indicates that the aging neuropathy present in the sural nerve of female rats is both axonal and demyelinating. (C) 2008 Elsevier B.V. All rights reserved.