Contralateral Site Research Articles

Possible inflammatory pain biomarkers in postamputation pain.

Although chronic pain after amputation is frequent, the underlying mechanisms are still not well understood. It is widely accepted that the pathogenesis of postamputation pain is multifactorial, with both peripheral and central mechanisms playing an essential role. However, recent studies suggest that the immune system plays an important role in different neuropathic pain conditions, including postamputation pain. Eleven amputees were included in this clinical study. Information on the type and intensity of spontaneous postamputation pain was obtained and evoked pain responses for brush, cold, and warm allodynia and pinprick hyperalgesia were determined. In addition, skin biopsies were taken from the amputated site and a contralateral control site and analysed for possible markers of pain: IbA1 (macrophages), calcitonin gene-related peptide (CGRP), and substance P (SP). Irrespectively of the type and intensity of postamputation pain, no differences were found in IbA1, CGRP, and SP levels between the amputated site and the control site. Although no differences between the sites were seen in this study, this new method seems promising for our understanding of skin changes in amputees. In future studies, staining for other cytokines and inflammatory mediators in skin biopsies could provide new insight into the mechanisms of postamputation pain.

Evaluation of topically applied probiotic treatment on localized aggressive periodontitis patients: A split mouth study

Aim: This study aims to evaluate clinically the effect of probiotic treatment on localized aggressive periodontitis patients. Subjects and methods: This study was designed as a randomized, controlled, split mouth clinical trial, carried out on localized aggressive periodontitis (LAP) which having almost two identical sites with clinical probing depth of ≥ 5 mm. Two contralateral sites were randomly divided into two groups, Group I: received conventional periodontal treatment, scaling and root planning combined with topical application of probiotic. Group II: received conventional periodontal treatment, scaling and root planning only. Patients were evaluated clinically using the following parameters: plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL) and radiographically by radiographic bone density (pixel) at baseline, 3, 6, and 9 months. Results: Clinical and radiographic results of this study showed that: there were a significant reduction for assessed variables (Plaque Index, gingival index, probing pocket depth and clinical attachment level and significant increase in radiographic bone density in probiotic group compared to group II. Conclusion: Adjunctive use of topically applied probiotic appeared to be beneficial effect in localized aggressive periodontitis patients when compared with scaling and root planning alone.

Gingival Crevicular Fluid Levels of RANKL and OPG After Placement of Collagen Membrane With Simvastatin in the Treatment of Intrabony Defects in Chronic Periodontitis.

Purpose:The aim of this study was to estimate the Receptor activator of nuclear factor kappa-B ligand (RANKL) and Osteoprotegrin (OPG) levels in gingival crevicular fluid (GCF) after placement of collagen membrane with simvastatin in intrabony defects.Materials and Methods:Sixty subjects were grouped according to the treatment plan as Group I and Group II. Group I included patients with intrabony defects treated with collagen membrane. Group II included patients with intrabony defects treated with simvastatin of 1.5 mg concentration incorporated into the collagen membrane. A split-mouth design was planned, in which two contralateral sites with >5 mm probing pocket depth and radiographic evidence of bone loss at baseline were chosen. Probing pocket depth was standardized with acrylic stent in all the selected areas. GCF samples were collected at baseline and 21 days. The amount of RANKL and OPG in the samples was determined by commercial ELISA kits (Biomedica Medizinprodukte, Austria).Results:When comparing both the groups, Group II had more statistically significant (P < 0.001**) decrease in the levels of RANKL than Group I. In contrast to RANKL, the OPG levels were significantly increased in patients (Group II) having intrabony defects treated with collagen membrane along with simvastatin.Conclusion:Simvastatin-loaded collagen membrane expressed increased OPG and decreased RANKL levels, which could have a potential role in periodontal regeneration.

The Impact of Stochastic Perturbations upon the Hydrodynamic Relationship between the Activity of Human Cardiac Ventricles and Low-Frequency Blood Flow Oscillations in the Microcirculatory Bed

Abstract—The experimentally revealed high phase coherence between low-frequency oscillations in the cutaneous blood perfusion signal at the contralateral skin sites indicates the existence of a central mechanism of its regulation. The vascular bed can be such a regulatory mechanism because it is a closed hydrodynamic system. It has been shown in this study using a mathematical model of the human cardiovascular system that the impact of low-intensity stochastic perturbations on the stiffness of the cardiac ventricles leads to the formation of low-frequency oscillations in microvascular blood flow. The results show that there is a relationship between the activity of the heart and low-frequency oscillations of microcirculatory skin blood flow, which is due to the hydrodynamic properties of the vascular bed without the involvement of autonomous control from autonomic nervous system.

Somatosensory profiles in acute herpes zoster and predictors of postherpetic neuralgia.

This prospective cohort study aimed to characterize the sensory profile during acute herpes zoster (AHZ) and to explore sensory signs as well as physical and psychosocial health as predictors for postherpetic neuralgia (PHN). Results of quantitative sensory testing of 74 patients with AHZ at the affected site and at the distant contralateral control site were compared to a healthy control group. Pain characteristics (Neuropathic Pain and Symptom Inventory and SES), physical functioning, and psychosocial health aspects (Pain Disability Index, SF-36, and STAI) were assessed by questionnaires. Patients with PHN (n = 13) at 6-month follow-up were compared to those without PHN (n = 45). Sensory signs at the affected site were thermal and vibratory hypesthesia, dynamic mechanical allodynia (DMA), pressure hyperalgesia, and high wind-up (18%-29%), as well as paradoxical heat sensations and pinprick hypalgesia (13.5%). The unaffected control site exhibited thermal and vibratory hypesthesia, DMA, and pressure hyperalgesia. Dynamic mechanical allodynia and pinprick hypalgesia were mutually exclusive. Postherpetic neuralgia was associated with DMA (38.5% vs 6.7%; P = 0.010) and vibratory hypesthesia (38.5% vs 11.1%; P = 0.036) at the control site, with mechanical gain and/or loss combined with normal thermal detection (affected site: 69.2% vs 31.1%; P = 0.023; control site: 53.8% vs 15.5%; P = 0.009). Pain Disability Index (P = 0.036) and SES affective pain perception scores (P = 0.031) were over 50% higher, and 6 of 8 SF-36 subscores were over 50% lower (P < 0.045) in PHN. Sensory profiles in AHZ indicate deafferentation and central but not peripheral sensitization. Sensory signs at distant body sites, strong affective pain perception, as well as reduced quality of life and physical functioning in the acute phase may reflect risk factors for the transition to PHN.

Characteristics and relative factors of headache caused by cervicocerebral artery dissection.

To analyze the characteristics and relative factors of headache and neck pain due to cervicocerebral artery dissection (CAD). A total of 146 consecutive patients with CAD in Zhengzhou, China (2010-2017) were observed and registered prospectively. There were 60 (60/146) cases who complained of headache and neck pain, and we analyzed the characteristics of pain according to their clinical features. For the 130 (130/146) patients with complete clinical laboratory data, they were divided into two groups according to pain, and the relative factors of pain were analyzed. The headache and neck pain in 60 CAD patients was mostly acute onset (98.3%), 70.6% (12/17) of patients with anterior circulation dissection and 88.4% (38/43) of patients with posterior circulation dissection complained of moderate to severe pain. 41.2% (7/17) of patients with anterior circulation dissection had temporal pain, while 46.5% (20/43) of the patients with posterior circulation dissection had occipital pain. There were 23.5% (4/17) and 32.6% (14/43) of patients with anterior and posterior circulation dissection complained of throbbing pain, respectively, 23.5% (4/17) and 20.9% (9/43) of patients with anterior and posterior circulation dissection complained of pulsating pain. The pain could occur in the ipsilateral (40.0%), bilateral (52.7%), or contralateral (7.3%) sites of the dissection. In the 130 patients, there were 56 cases (43.1%) in the pain group, and 74 cases (56.9%) in the non-pain group. Multivariate logistic regression analysis showed that female gender (OR 4.01, 95% CI 1.63-9.85, P = 0.002), posterior circulation (OR 3.18, 95% CI 1.39-7.28, P = 0.006), history of headache (OR 4.72, 95% CI 1.08-20.52, P = 0.039), and low-density lipoprotein less than 1.8mmol/L (OR 2.90, 95% CI 1.15-7.34, P = 0.025) were risk factors of the occurrence of the pain related to CAD. The headache and neck pain caused by CAD is a moderate to severe pain occurring suddenly. The pain nature may be diverse but mostly like throbbing and pulsating. When the dissected artery is located in the posterior circulation, the pain is mostly in the occipital region, and mostly in the temporal region when the dissected artery is located in the anterior circulation. The pain can occur in ipsilateral, bilateral, or contralateral of the dissection. In addition, several factors might contribute to the occurrence of headache and neck pain.

Effects of Coil Orientation on Motor Evoked Potentials From Orbicularis Oris.

This study aimed to characterize effects of coil orientation on the size of Motor Evoked Potentials (MEPs) from both sides of Orbicularis Oris (OO) and both First Dorsal Interosseous (FDI) muscles, following stimulation to left lip and left hand Primary Motor Cortex. Using a 70 mm figure-of-eight coil, we collected MEPs from eight different orientations while recording from contralateral and ipsilateral OO and FDI using a monophasic pulse delivered at 120% active motor threshold. MEPs from OO were evoked consistently for six orientations for contralateral and ipsilateral sites. Contralateral orientations 0°, 45°, 90°, and 315° were found to best elicit OO MEPs with a likely cortical origin. The largest FDI MEPs were recorded for contralateral 45°, invoking a posterior–anterior (PA) current flow. Orientations traditionally used for FDI were also found to be suitable for eliciting OO MEPs. Individuals vary more in their optimal orientation for OO than for FDI. It is recommended that researchers iteratively probe several orientations when eliciting MEPs from OO. Several orientations likely induced direct activation of facial muscles.

Histological and inflammatory analysis to diagnostic method of proximal gingivitis by flossing.

The aim of this study was to assess with histological and inflammatory analysis the use of flossing as a diagnostic method for detecting proximal gingivitis. This is a diagnostic accuracy paper composed of two different studies. In the first study, three groups were identified based on papilla status: bleeding (+) with both methods (N = 26); bleeding (+) with dental floss, but no bleeding (-) with probing (N = 26); and no bleeding (-) with either method (N = 26). One papilla from all 78 participants was biopsied and analyzed for the determination of inflammatory infiltrate and percentage of collagen fibers. Sensibility, specificity, positive and negative predictive, and accuracy values were analyzed. In the second study, the volume of gingival crevicular fluid (GCF) was analyzed in 49 participants with flossing+/probing- and flossing-/probing- at contralateral proximal sites. The GCF volume was compared between these sites (n = 172). Significantly greater frequencies of moderate/intense inflammation were found in the flossing+/probing+ (100%) and flossing+/probing- (92.3%) groups compared to those in the flossing-/probing- (0%) group. Significantly different percentages of collagen fibers were found among the three groups (flossing+/probing+ (40.90 ± 3.68); flossing+/probing- (45.78 ± 4.55); flossing-/probing- (60.01 ± 36.66)) (P < 0.001). Dental floss increased the balance between sensitivity and specificity values and showed highest positive predictive (100%) and accuracy (97%) values. Among the 172 sites evaluated, positive bleeding sites had a significantly greater volume of GCF (38 (27-68)) than negative sites (25 (16-51)) (P < 0.001). The findings suggest that flossing can be used as a diagnostic method for proximal gingivitis in subjects with no history of periodontitis. Dental floss can be used as a complementary diagnostic method for proximal gingivitis in adults without clinical attachment loss in clinical practice as well as epidemiology studies.

Radiographic and histologic observations of sequential healing processes following ridge augmentation after tooth extraction in buccal-bone-deficient extraction sockets in beagle dogs.

To evaluate dimensional ridge alterations and sequential healing processes following ridge augmentation after tooth extraction in damaged extraction sockets with buccal-bone-deficiency. Bilateral dental roots of three mandibular premolars were extracted with entire removal of the buccal-bone plate in eight beagle dogs. Unilateral sites were grafted with biomaterials (test group) and contralateral sites were healed without grafting (control group). Observations were made after 1, 2, 4, and 8weeks, and all sites were distributed evenly (n=6 for each group and period). Radiographic/histomorphometric analyses were performed. In spontaneous healing of damaged extraction sockets, the dimension of regenerated alveolar ridge gradually increased until 4weeks and then remained stable, but radiographic/histomorphometric analyses revealed evident dimensional shrinkage compared to the pristine tissue at 8weeks in the coronal and middle areas. Bone grafting retained the pristine dimension of alveolar ridge, and newly formed bone area within the augmented space continuously expanded during the observational period to the outermost border of the space. Spontaneous healing of damaged extraction sockets caused substantial dimensional shrinkage. However, ridge augmentation can provide space into which new bone may grow continuously, resulting in the final dimensions comparable to those of the pristine alveolar ridge.

Percutaneous ultrasound-guided balloon-assisted embolization of iatrogenic femoral artery pseudoaneurysms with Glubran®2 cyanoacrylate glue: safety, efficacy and outcomes.

Femoral pseudoaneurysm (PA) is a frequent complication of arterial access for endovascular procedures. Surgery has traditionally been considered as the gold standard of therapy. We aimed to report our experience of percutaneous ultrasound (US)-guided balloon-assisted embolization with cyanoacrylate glue for the treatment of iatrogenic femoral PAs. Retrospective two-center study of patients with femoral iatrogenic PAs treated by N-butyl cyanoacrylate-methacryloxy sulfolane (NBCA-MS) Glubran®2 glue embolization between July 2013 and November 2017. All patients underwent contralateral arterial access with balloon placement of an appropriate size in front of the PA neck before glue/lipiodol embolization in a 1:1 ratio by percutaneous US-guided puncture of the aneurysmal sac under fluoroscopy control. Twenty-three patients (12 females, 11 males; median age, 79 years; range, 18-93 years) were included. Median PA size was 34 mm (range, 17-60 mm). The median time to treatment was 5 days (range, 1-30 days). Twenty patients (86.9%) were successfully treated by glue injection alone. The three remaining patients (13.1%) with persistent PA or associated arterial-venous fistula were immediately treated during the same procedure by additional stent-graft. Then, overall immediate and 1-month clinical success rates were 100%. No surgical conversion was necessary. No recurrence was reported during the median follow-up of 11 months (range, 2-73 months). Two (8.7%) puncture-related complications occurred at the contralateral arterial access site, which spontaneously resolved. No non-target glue embolization occurred. US-guided balloon-assisted glue embolization is safe and effective to treat iatrogenic femoral PAs in most cases, offering complete exclusion of the PA and avoiding the morbidity of open surgery.

Transfer of Topical Testosterone to Subcutaneous Microdialysate, Blood and Saliva in Healthy Young Men.

We evaluated percutaneous penetration of topical testosterone and subsequent transfer to subcutaneous tissue, blood and saliva. This microdialysis trial involved eight healthy male volunteers. Five participants received a single dose of 50 mg testosterone gel on the abdominal skin and three untreated participants served as controls. Two microdialysis probes were inserted percutaneously into the abdominal subcutaneous adipose tissue. On the skin above one probe, testosterone gel was applied (ipsilateral side). A second control probe was inserted on the contralateral side. For the determination of total and free testosterone, samples of subcutaneous microdialysate, serum, and saliva were collected over six hours, frozen, and analysed using ELISA procedures. Testosterone values in the ipsilateral microdialysate of treated subjects increased significantly within 6 h after gel application compared to controls. Salivary testosterone levels showed a rapid increase within 20 min after transdermal application followed by a plateau phase with tenfold increased testosterone levels. Microdialysate testosterone of the contralateral site started to rise moderately within the normal range 1 h after administration of testosterone gel whereas total and free testosterone serum concentrations increased within 2 h in each case followed by a plateau phase. Single topical administration of testosterone gel leads to a continuous increase of testosterone in the subcutaneous ipsilateral microdialysate. Rapid salivary testosterone increase happens after gel administration followed by tenfold increased testosterone plateau values. Despite continuous influx, testosterone concentrations in serum, saliva, and contralateral microdialysate show a plateau formation thus avoiding testosterone excess.

Cdk5-mediated CRMP2 phosphorylation is necessary and sufficient for peripheral neuropathic pain

Neuropathic pain results from nerve injuries that cause ectopic firing and increased nociceptive signal transmission due to activation of key membrane receptors and channels. The dysregulation of trafficking of voltage-gated ion channels is an emerging mechanism in the etiology of neuropathic pain. We identify increased phosphorylation of collapsin response mediator protein 2 (CRMP2), a protein reported to regulate presynaptic voltage-gated calcium and sodium channels. A spared nerve injury (SNI) increased expression of a cyclin dependent kinase 5 (Cdk5)-phosphorylated form of CRMP2 in the dorsal horn of the spinal cord and the dorsal root ganglia (DRG) in the ipsilateral (injured) versus the contralateral (non-injured) sites. Biochemical fractionation of spinal cord from SNI rats revealed the increase in Cdk5-mediated CRMP2 phosphorylation to be enriched to pre-synaptic sites. CRMP2 has emerged as a central node in assembling nociceptive signaling complexes. Knockdown of CRMP2 using a small interfering RNA (siRNA) reversed SNI-induced mechanical allodynia implicating CRMP2 expression as necessary for neuropathic pain. Intrathecal expression of a CRMP2 resistant to phosphorylation by Cdk5 normalized SNI-induced mechanical allodynia, whereas mimicking constitutive phosphorylation of CRMP2 resulted in induction of mechanical allodynia in naïve rats. Collectively, these results demonstrate that Cdk5-mediated CRMP2 phosphorylation is both necessary and sufficient for peripheral neuropathic pain.

Time dependent loss of trabecular bone in human tibial plateau fractures.

We investigated if time between injury and surgery affects cancellous bone properties in patients suffering tibial plateau fractures (TPF), in terms of structural integrity and gene expression controlling bone loss. A cohort of 29 TPF, operated 1-17 days post-injury, had biopsies from the fracture and an equivalent contralateral limb site, at surgery. Samples were assessed using micro-computed tomography and real-time RT-PCR analysis for the expression of genes known to be involved in bone remodeling and fracture healing. Significant decreases in the injured vs control side were observed for bone volume fraction (BV/TV, -13.5 ± 6.0%, p = 0.011), trabecular number (Tb.N, -10.5 ± 5.9%, p = 0.041) and trabecular thickness (Tb.Th, -4.6 ± 2.5%, p = 0.033). Changes in these parameters were more evident in patients operated 5-17 days post-injury, compared to those operated in the first 4 days post-injury. A significant negative association was found between Tb.Th (r = -0.54, p < 0.01) and BV/TV (r = -0.39, p < 0.05) in relation to time post-injury in the injured limb. Both BV/TV and Tb.Th were negatively associated with expression of key molecular markers of bone resorption, CTSK, ACP5, and the ratio of RANKL:OPG mRNA. These structure/gene expression relationships did not exist in the contralateral tibial plateau of these patients. This study demonstrated that there is a significant early time-dependent bone loss in the proximal tibia after TPF. This bone loss was significantly associated with altered expression of genes typically involved in the process of osteoclastic bone resorption but possibly also bone resorption by osteocytes. The mechanism of early bone loss in such fractures should be a subject of further investigation. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2865-2875, 2018.

Blocking neuromuscular junctions to impair muscle overactivity enhances neurological heterotopic ossifications (NHO) development in a mouse model of spinal cord injury

To ascertain a role for muscle spasticity in the development of NHO, by blocking neuromuscular signalling using botulinum toxin during spinal cord injury-induced NHO formation in a murine model. Spinal Cord Injury (SCI) was performed on 5–6-week-old C57BL/6 mice. To promote NHO development, cardiotoxin (CDTX) dose injections were administered at the time of the surgery to the right and left hamstring muscles. Botulinum toxin A (BTA) injections were administered at the site of NHO formation in the right hamstrings to block neuromuscular signalling, and mock equivalent volume of PBS was injected in the contralateral site 4 days prior to SCI, and weekly for 3 weeks. Twenty-one days post SCI, quantitative assessment of NHO volume and density within each hamstrings muscle were performed using Micro-computed tomography scan. μCTscan analysis revealed the development of NHO in 100% of mice in both hamstrings. NHO volume average was 1.6 mm 3 (± 1.0) in the left hamstrings injected with PBS in contrast to 3.3 mm 3 (± 1.4) in the right hamstrings with BTA. This doubling of NHO volume in BTA-treated hamstrings was statistically significant (Wilcoxon matched-pairs signed rank test, P = 0.013). Furthermore, NHO were more compact in muscles injected with BTA with a density of 1244.6 mg/cm 3 (± 10.4) and was significantly denser compared to NHO in the PBS-treated contralateral side density of 1231.2 mg/cm 3 (± 20.1) (Wilcoxon matched-pairs signed rank test, P = 0.027). In our murine model of SCI-induced NHO, we demonstrated a doubling of the NHO volume, and increased density burden when treated locally with BTA. These results demonstrate that local administration of BTA exacerbates NHO development leading to an overall increase in bone formation. The outcome suggests that in contrast to risk spasticity, resulting from defective neuromuscular signalling, may be an inhibitor of local NHO development.

Flapless Postextraction Socket Implant Placement, Part 3: The Effects of Bone Grafting and Provisional Restoration on Soft Tissue Color Change-A Retrospective Pilot Study.

This article presents the results of a soft tissue color study on flapless immediate implant therapy from a sample of 23 patients who received either a provisional restoration alone or with bone grafting. The gingival color in clinical photographs was measured for the implant and for the contralateral tooth site at 2.0 and 5.0 mm below the free gingival margin using Photoshop software (Lightroom CC, Adobe). The average color difference (ΔE) values for the two groups were 2.6 and 2.4 at 2.0 mm and 1.9 and 2.5 at 5.0 mm from the free gingival margin, respectively. Approximately 80% of the sites were below the visibly perceptible threshold (ΔE = 3.1 ± 1.5) and not detectable by the human eye. The use of provisional restorations has shown positive outcomes on the stability of peri-implant soft tissue thickness and lower ΔE values. Further research is required to assess esthetic outcomes inclusive of color change relative to the clinical treatment rendered.

Sinus augmentation using rhBMP-2/ACS in a mini-pig model: Influence of an adjunctive ceramic bone biomaterial.

Recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support significant bone formation when used to augment the maxillary sinus for implant dentistry. Nevertheless, bone biomaterials have been suggested to extend rhBMP-2/ACS with limited support of the merits of such approaches. To evaluate local bone formation/dental implant osseointegration following implantation of rhBMP-2/ACS combined with a ceramic bone biomaterial using a mini-pig sinus augmentation model. Twelve adult Göttingen mini-pigs received rhBMP-2/ACS (rhBMP-2 adjusted to 0.43mg/cc) alone or combined with an off-the-shelf biphasic ceramic (15%/85% HA/ß-TCP) biomaterial at 3:1, 1:1 and 1:3 ratios randomized to contra-lateral maxillary sinus sites yielding rhBMP-2/ACS fractions of 100%, 75%, 50% and 25%, respectively. A 4-cc implant volume was used for all sites. Two threaded dental implants (ø4.0×11.5mm) were placed at each site. The animals were euthanized at 8weeks for histologic analysis. Surgical execution and healing were generally uneventful, infraorbital local swelling was observed in all animals until suture removal. rhBMP-2/ACS combined with the ceramic biomaterial did not significantly enhance local bone formation (range 9.0±1.5 to 9.7±2.1mm) compared with rhBMP-2/ACS alone (8.6±1.1mm; p>0.05). Variations in rhBMP-2/ACS to ceramic matrix ratios yielding rhBMP-2 doses approximating 0.4, 0.9, 1.3 and 1.7mg/sinus did not appreciably influence bone formation/osseointegration. Whereas rhBMP-2/ACS supports significant bone formation/osseointegration in the mini-pig sinus augmentation model and thus appears an effective alternative for sinus augmentation procedures, adding a ceramic biomaterial to rhBMP-2/ACS does not produce meaningful biological advantages.

Cerebral Microcirculation and Histological Mapping After Severe Head Injury: A Contusion and Acceleration Experimental Model.

Cerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow. This study assesses the changes of cerebral microcirculation blood flow over time after an experimental brain injury model in sheep and contrasts these findings with the histological analysis of the same regions with the aim of mapping cerebral flow and tissue changes after injury. Microcirculation was quantified using flow cytometry of color microspheres injected under intracardiac ultrasound to ensure systemic and homogeneous distribution. Histological analysis used amyloid precursor protein staining as a marker of axonal injury. A mapping of microcirculation and axonal staining was performed using adjacent layers of tissue from the same anatomical area, allowing flow and tissue data to be available from the same anatomical region. A mixed effect regression model assessed microcirculation during 4 h after injury, and those results were then contrasted to the amyloid staining qualitative score. Microcirculation values for each subject and tissue region over time, including baseline, ranged between 20 and 80 ml/100 g/min with means that did not differ statistically from baseline flows. However, microcirculation values for each subject and tissue region were reduced from baseline, although their confidence intervals crossing the horizontal ratio of 1 indicated that such reduction was not statistically significant. Histological analysis demonstrated the presence of moderate and severe score on the amyloid staining throughout both hemispheres. Microcirculation at the ipsilateral and contralateral site of a contusion and the ipsilateral thalamus and medulla showed a consistent decline over time. Our data suggest that after severe head injury, microcirculation in predefined areas of the brain is reduced from baseline with amyloid staining in those areas reflecting the early establishment of axonal injury.

Assessment of Paraspinal Muscle Atrophy Percentage after Minimally Invasive Transforaminal Lumbar Interbody Fusion and Unilateral Instrumentation Using a Novel Contralateral Intact Muscle-Controlled Model.

Study DesignRetrospective comparative clinical study.PurposeThis study aimed to assess paraspinal muscle atrophy in patients who underwent minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) and unilateral pedicle screw fixation using a novel contralateral intact muscle-controlled model.Overview of LiteratureThe increased incidence of paravertebral lumbar muscle injuries after open techniques has raised the importance of implementing minimally invasive spine surgical techniques using tubular retractors and minimally invasive screw placement. The functional cross-sectional area (FCSA) represents the lean muscle mass; furthermore, FCSA is a useful marker of the contractile ability of a muscle following a spine surgery. However, the benefits of unilateral fixation and MI-TLIF on paraspinal muscles have not been defined.MethodsWe performed a retrospective imagenological review on eleven patients who underwent unilateral MI-TLIF and unilateral transpedicular screw lumbar placement. FCSAs of the multifidus and erector spinae were measured 1 year after surgery at adjacent levels and were compared to the contralateral intact muscles. Measurement differences between the surgical and nonsurgical sites were compared. The interobserver reliability was calculated using an intraclass correlation coefficient.ResultsThe mean FCSA at the surgical site was 20.97±5.07 cm2 at the superior level and 8.89±2.87 cm2 at the inferior level. The mean FCSA at the contralateral nonsurgical site was 20.15±5.95 cm2 at the superior level and 9.20±2.66 cm2 at the inferior level was. The superior and inferior FCSA measurements showed no significant difference between the surgical and nonsurgical sites (p=0.5, p=0.922, respectively).ConclusionsUsing a mini-open tubular approach through the sulcus between the longissimus and iliocostalis, MI-TLIF and unilateral pedicle screw instrumentation produced minimal paraspinal muscle damage at the superior and inferior adjacent levels.

Somatosensory changes at forearm donor sites following three different surgical flap techniques

BackgroundThe aim of this study was to investigate the somatosensory changes at the forearm donor region after using different types of modified flap surgical techniques. MethodsThirty-one patients, who underwent oral and maxillofacial reconstructive surgery involving the use of a traditional radial forearm flap (TRFF) or two modified radial forearm flap techniques (MRFF-I; MRFF-II), participated in the study. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), pressure pain threshold (PPT), mechanical detection threshold (MDT), and mechanical pain threshold (MPT) were assessed at four sites of the forearms corresponding to the middle of the vascular pedicle (VP) area, the middle of the forearm flap area, and the corresponding contralateral sites (cVP and cFF) at about 5.0 ± 1.9 months after the surgery. Data were analysed with one-way ANOVA, and post-hoc tests were performed using Tukey's Honest Significant Difference test. ResultsSignificant differences between the VP and cVP sites were detected for WDT (P < 0.001) in TRFF and for WDT (P < 0.001) and MDT (P = 0.006) in MRFF-I. Significant differences among TRFF, MRFF-I, and MRFF-II at the VP site were detected for CDT (P = 0.022), WDT (P < 0.001), and MDT (P = 0.015). MRFF-II was associated with significantly higher sensitivity compared to that of TRFF for WDT (P = 0.017) and higher sensitivity compared to that of MRFF-I for CDT (P = 0.017), WDT (P < 0.001), and MDT (P = 0.013). ConclusionsSignificant sensory loss was detected for all types of surgical procedures with free forearm flaps. However, the MRFF-II was associated with a better sensory recovery at short follow-up after surgery. These results suggest that a longer follow-up period and larger sample size should be included in future studies.

Using in vivo fluorescence lifetime imaging to detect HER2-positive tumors

BackgroundAssessment of the status of tumor biomarkers in individual patients would facilitate personalizing treatment strategy, and continuous monitoring of those biomarkers and their binding process to the therapeutic drugs would provide a means for early evaluation of the efficacy of therapeutic intervention. Fluorescent probes can accumulate inside the tumor region due to the leakiness of its vascularization and this can make it difficult to distinguish if the measured fluorescence intensity is from probes bound to target receptors or just accumulated unbound probes inside the tumor. In this paper, we have studied the fluorescence lifetime as a means to distinguish bound HER2 specific affibody probes to HER2 receptors.Our imaging system is a time-resolved fluorescence system using a Ti-Sapphire femtosecond pulse laser as source and Time correlated Single photon Counting (TCSPC) system as detector for calculating the lifetime of the contrast agent. HER2-specific Affibody (His6-ZHER2:GS-Cys) (Affibody, Stockholm, Sweden) conjugated with a Dylight750 fluorescent probe (Thermo-Fisher-Scientific, Waltham, Massachusetts) was used as contrast agent and six human cancer cell lines, BT-474, SKOV-3, NCI-N87, MDA-MB-361, MCF-7, and MDA-MB-468, known to express different levels of HER2/neu, are used in athymic mice xenografts.ResultsBy comparing the lifetime of unbound contrast agent (at the contralateral site) to the fluorescence lifetime at the tumor site, our results show that the fluorescence lifetime decreases as HER2 specific Affibody probes bind to the tumor receptors. A decrease of ~15% (100ps) in tumor fluorescence lifetime was observed in tumors with mid to high HER2 expression. Smaller decreases were observed in tumors with low-level of HER2 receptors and no change was observed in the non-HER2-expressing tumors.ConclusionsUsing HER2-specific Affibody conjugated with the Dylight750 fluorescent probe as contrast agent, we demonstrated in live animals that change in fluorescence lifetime of the bound contrast agent can be used to assess the high to mid-level expression of HER2 expressing tumors in-vivo in only one measurement. The rationale is that the fluorescence lifetime of our specific probe is sensitive to affinity to, and specific interaction with, other molecules.