Presentation, microsurgical therapy, and clinical outcomes in three cases of expanding melanonychia of the nail unit in children

The management of expanding melanonychia in childhood is controversial. Here, we present three cases and discuss their operating indications and reconstruction. Between January 1, 1995 and December 31, 2007, one boy and two girls, were operated for expanding melanonychia, involving the thumb, index finger or the middle finger. They were 2, 4, and 7 years at the time of surgery. A complete resection of the nail plate was performed followed by a direct finger reconstruction using a free short-pedicle vascularized nail flap of the toe. Histology showed a junctional nevus in all cases. The follow-ups were after 2, 3, and 5 years and without any complications or recurrence. Regarding reconstruction, the mean Foucher and Leclère score were, respectively, 17 and 16 points. It is concluded that for expanding melanonychia, in case of doubt, an examination of the entire lesion is necessary. Reconstruction of the nail unit after wide excision with nail plate ablation can be performed using microsurgery as discussed below. However, new guidelines on shave biopsy can make this microsurgical procedure obsolete.

Do Central Hypersensitivity and Altered Pain Modulation Predict the Course of Chronic Low Back and Neck Pain?

OBJECTIVES:: Widespread central hypersensitivity and altered conditioned pain modulation (CPM) have been documented in chronic pain conditions. Information on their prognostic values is limited. This study tested the hypothesis that widespread central hypersensitivity (WCH) and altered CPM, assessed during the chronic phase of low back and neck pain, predict poor outcome. METHODS:: A total of 169 consecutive patients with chronic low back or neck pain, referred to the pain clinic during 1 year, were analyzed. Pressure pain tolerance threshold at the second toe and tolerance time during cold pressor test at the hand assessed WCH. CPM was measured by the change in pressure pain tolerance threshold (test stimulus) after cold pressor test (conditioning stimulus). A structured telephone interview was performed 12 to 15 months after testing to record outcome parameters. Linear regression models were used, with average and maximum pain intensity of the last 24 hours at follow-up as endpoints. Multivariable analyses included sex, age, catastrophizing scale, Beck Depression Inventory, pain duration, intake of opioids, and type of pain syndrome. RESULTS:: Statistically significant reductions from baseline to follow-up were observed in pain intensity (P<0.001). No evidence for an association between the measures of WCH or CPM and intensity of chronic pain at follow-up was found. DISCUSSION:: A major predictive value of the measures that we used is unlikely. Future studies adopting other assessment modalities and possibly standardized treatments are needed to further elucidate the prognostic value of WCH and altered CPM in chronic pain.

Ultrasound-guided suprascapular nerve block, description of a novel supraclavicular approach

The suprascapular nerve (SSN) block is frequently performed for different shoulder pain conditions and for perioperative and postoperative pain control after shoulder surgery. Blind and image-guided techniques have been described, all of which target the nerve within the supraspinous fossa or at the suprascapular notch. This classic target point is not always ideal when ultrasound (US) is used because it is located deep under the muscles, and hence the nerve is not always visible. Blocking the nerve in the supraclavicular region, where it passes underneath the omohyoid muscle, could be an attractive alternative.

Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron.

Spectral waveform analysis of intranodal arterial blood flow in abnormally large superficial lymph nodes in dogs

Objective-To evaluate pulsed-wave Doppler spectral parameters as a method for distinguishing between neoplastic and inflammatory peripheral lymphadenopathy in dogs. Sample Population-40 superficial lymph nodes from 33 dogs with peripheral lymphadenopathy. Procedures-3 Doppler spectral tracings were recorded from each node. Spectral Doppler analysis including assessment of the resistive index, peak systolic velocity-to-end diastolic velocity (S:D) ratio, diastolic notch velocity-to-peak systolic velocity (N:S) ratio, and end diastolic velocity-to-diastolic notch velocity ratio was performed for each tracing. Several calculation methods were used to determine the Doppler indices for each lymph node. After the ultrasonographic examination, fine needle aspirates or excisional biopsy specimens of the examined lymph nodes were obtained, and lymphadenopathy was classified as either inflammatory or neoplastic (lymphomatous or metastatic) via cytologic or histologic examination. Results of Doppler analysis were compared with cytologic or histopathologic findings. Results-The Doppler index with the highest diagnostic accuracy was the S:D ratio calculated from the first recorded tracing; a cutoff value of 3.22 yielded sensitivity of 91%, specificity of 100%, and negative predictive value of 89% for detection of neoplasia. Overall diagnostic accuracy was 95%. At a sensitivity of 100%, the most accurate index was the N:S ratio calculated from the first recorded tracing; a cutoff value of 0.45 yielded specificity of 67%, positive predictive value of 81%, and overall diagnostic accuracy of 86.5%. Conclusions and Clinical Relevance-Results suggested that noninvasive Doppler spectral analysis may be useful in the diagnosis of neoplastic versus inflammatory peripheral lymphadenopathy in dogs.

Integrity of venoarteriolar reflex determines level of microvascular skin flow enhancement with intermittent pneumatic compression

OBJECTIVE: To investigate whether intermittent pneumatic compression (IPC) augments skin blood flow through transient suspension of local vasoregulation, the veno-arteriolar response (VAR), in healthy controls and in patients with peripheral arterial disease (PAD). METHODS: Nineteen healthy limbs and twenty-two limbs with PAD were examined. To assess VAR, skin blood flow (SBF) was measured using laser Doppler fluxmetry in the horizontal and sitting positions and was defined as percentage change with postural alteration [(horizontal SBF--sitting SBF)/horizontal SBF x 100]. On IPC application to the foot, the calf, or both, SBF was measured with laser Doppler fluxmetry, the probe being attached to the pulp of the big toe. RESULTS: Baseline VAR was higher in the controls 63.8 +/- 6.4% than in patients with PAD (31.7 +/- 13.4%, P = .0162). In both groups SBF was significantly higher with IPC than at rest (P < .0001). A higher percentage increase with IPC was demonstrated in the controls (242 +/- 85% to 788 +/- 318%) than in subjects with PAD, for each one of the three different IPC modes investigated (98 +/- 33% to 275 +/- 72%) with IPC was demonstrated. The SBF enhancement with IPC correlated with VAR for all three compression modes (r = 0.58, P = .002 for calf compression, r = 0.65, P < .0001 for foot compression alone, and r = 0.64, P = .0002 for combined foot and calf compression). CONCLUSION: The integrity of the veno-arteriolar response correlates with the level of skin blood flow augmentation generated with intermittent pneumatic compression, indicating that this may be associated with a transient suspension of the autoregulatory vasoconstriction both in healthy controls and in patients with PAD.

Reactivation of rheumatoid arthritis after pregnancy: increased phagocyte and recurring lymphocyte gene activity

OBJECTIVE: Pregnancy is associated with reduced disease activity in rheumatoid arthritis (RA) and frequently with disease exacerbation after delivery. This study was undertaken to generate a systematic overview of the molecular mechanisms related to disease remission and postpartum reactivation. METHODS: Transcriptomes of peripheral blood mononuclear cells (PBMCs) were generated from RA patients and healthy women by transcription profiling during the third trimester and 24 weeks after delivery. For functional interpretation, signatures of highly purified immune cells as well as Kyoto Encyclopedia of Genes and Genomes pathway annotations were used as a reference. RESULTS: Only minor differences in gene expression in PBMCs during pregnancy were found between RA patients and controls. In contrast, RA postpartum profiles presented the most dominant changes. Systematic comparison with expression signatures of monocytes, T cells, and B cells in healthy donors revealed reduced lymphocyte and elevated monocyte gene activity during pregnancy in patients with RA and in controls. Monocyte activity decreased after delivery in controls but persisted in RA patients. Furthermore, analysis of 32 immunologically relevant cellular pathways demonstrated a significant additional activation of genes related to adhesion, migration, defense of pathogens, and cell activation, including Notch, phosphatidylinositol, mTOR, Wnt, and MAPK signaling, in RA patients postpartum. CONCLUSION: Our findings indicate that innate immune functions play an important role in postpartum reactivation of arthritis. However, this may depend not only on the monocyte itself, but also on the recurrence of lymphocyte functions postpartum and thus on a critical interaction between both arms of the immune system.

Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis

INTRODUCTION: Recent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine the distribution of stem cell markers (Notch-1, Stro-1 and VCAM-1) and of molecules that modulate progenitor differentiation (Notch-1 and Sox9) in normal adult human articular cartilage and in osteoarthritis (OA) cartilage. METHODS: Expression of the markers was analyzed by immunohistochemistry (IHC) and flow cytometry. Hoechst 33342 dye was used to identify and sort the cartilage side population (SP). Multilineage differentiation assays including chondrogenesis, osteogenesis and adipogenesis were performed on SP and non-SP (NSP) cells. RESULTS: A surprisingly high number (>45%) of cells were positive for Notch-1, Stro-1 and VCAM-1 throughout normal cartilage. Expression of these markers was higher in the superficial zone (SZ) of normal cartilage as compared to the middle zone (MZ) and deep zone (DZ). Non-fibrillated OA cartilage SZ showed reduced Notch-1 and Sox9 staining frequency, while Notch-1, Stro-1 and VCAM-1 positive cells were increased in the MZ. Most cells in OA clusters were positive for each molecule tested. The frequency of SP cells in cartilage was 0.14 +/- 0.05% and no difference was found between normal and OA. SP cells displayed chondrogenic and osteogenic but not adipogenic differentiation potential. CONCLUSIONS: These results show a surprisingly high number of cells that express putative progenitor cell markers in human cartilage. In contrast, the percentage of SP cells is much lower and within the range of expected stem cell frequency. Thus, markers such as Notch-1, Stro-1 or VCAM-1 may not be useful to identify progenitors in cartilage. Instead, their increased expression in OA cartilage implicates involvement in the abnormal cell activation and differentiation process characteristic of OA.

Bailout revascularization of chronic femoral artery occlusions with the new outback catheter following failed conventional endovascular intervention

PURPOSE: To report the application of a true lumen re-entry device in the bailout treatment of chronic total occlusions (CTO) of the superficial femoral artery (SFA) after failed angioplasty. METHODS: Nineteen patients (12 men; mean age 81 years, range 61-97) with 20 SFA CTOs and Rutherford category 2 to 5 ischemia were prospectively evaluated. All CTOs had unsuccessful recanalization using conventional techniques and were subsequently treated with the Outback LTD catheter. Follow-up at 3, 6, and 12 months included ankle/toe pressure measurement and pulse volume recordings. Endpoints were revascularization rate, target lesion revascularization, and limb salvage. RESULTS: Revascularization was achieved in 95% of the cases. There were 2 (10%) periprocedural complications unrelated to the re-entry device, which were resolved by endovascular or surgical treatment. The target lesion revascularization rate was 10%, with the 2 events occurring at 3 and 6 months, respectively, in patients with Rutherford category 4-5 ischemia. There was one below-the-knee amputation in the patient with failed revascularization. CONCLUSION: The acute failure of endovascular treatment of SFA CTOs is most often due to an inability to re-enter the true lumen after the occlusion is crossed in a subintimal plane. Bailout revascularization with the Outback LTD catheter is highly successful and shows a low device-related complication rate. This needle- and fluoroscopic-based re-entry device increases the endovascular success rate and is therefore expanding the minimally invasive treatment options for surgically unfit patients.

Gait analysis in normal and spinal contused mice using the TreadScan system

Advances in spinal cord injury (SCI) research are dependent on quality animal models, which in turn rely on sensitive outcome measures able to detect functional differences in animals following injury. To date, most measurements of dysfunction following SCI rely either on the subjective rating of observers or the slow throughput of manual gait assessment. The present study compares the gait of normal and contusion-injured mice using the TreadScan system. TreadScan utilizes a transparent treadmill belt and a high-speed camera to capture the footprints of animals and automatically analyze gait characteristics. Adult female C57Bl/6 mice were introduced to the treadmill prior to receiving either a standardized mild, moderate, or sham contusion spinal cord injury. TreadScan gait analyses were performed weekly for 10 weeks and compared with scores on the Basso Mouse Scale (BMS). Results indicate that this software successfully differentiates sham animals from injured animals on a number of gait characteristics, including hindlimb swing time, stride length, toe spread, and track width. Differences were found between mild and moderate contusion injuries, indicating a high degree of sensitivity within the system. Rear track width, a measure of the animal's hindlimb base of support, correlated strongly both with spared white matter percentage and with terminal BMS. TreadScan allows for an objective and rapid behavioral assessment of locomotor function following mild-moderate contusive SCI, where the majority of mice still exhibit hindlimb weight support and plantar paw placement during stepping.

Cardiac c-kit+AT2+ cell population is increased in response to ischemic injury and supports cardiomyocyte performance

The expression pattern of angiotensin AT2 receptors with predominance during fetal life and upregulation under pathological conditions during tissue injury/repair process suggests that AT2 receptors may exert an important action in injury/repair adaptive mechanisms. Less is known about AT2 receptors in acute ischemia-induced cardiac injury. We aimed here to elucidate the role of AT2 receptors after acute myocardial infarction. Double immunofluorescence staining showed that cardiac AT2 receptors were mainly detected in clusters of small c-kit+ cells accumulating in peri-infarct zone and c-kit+AT2+ cells increased in response to acute cardiac injury. Further, we isolated cardiac c-kit+AT2+ cell population by modified magnetic activated cell sorting and fluorescence activated cell sorting. These cardiac c-kit+AT2+ cells, represented approximately 0.19% of total cardiac cells in infarcted heart, were characterized by upregulated transcription factors implicated in cardiogenic differentiation (Gata-4, Notch-2, Nkx-2.5) and genes required for self-renewal (Tbx-3, c-Myc, Akt). When adult cardiomyocytes and cardiac c-kit+AT2+ cells isolated from infarcted rat hearts were cocultured, AT2 receptor stimulation in vitro inhibited apoptosis of these cocultured cardiomyocytes. Moreover, in vivo AT2 receptor stimulation led to an increased c-kit+AT2+ cell population in the infarcted myocardium and reduced apoptosis of cardiomyocytes in rats with acute myocardial infarction. These data suggest that cardiac c-kit+AT2+ cell population exists and increases after acute ischemic injury. AT2 receptor activation supports performance of cardiomyocytes, thus contributing to cardioprotection via cardiac c-kit+AT2+ cell population.

Non-selective cutaneous sensory neurectomy as an alternative treatment for auto-mutilation lesion following arthrodesis in three dogs

OBJECTIVE: To describe an alternative method for the treatment of non-responsive self-mutilation injuries in three dogs after carpal/tarsal arthrodesis. STUDY DESIGN: Case series ANIMALS: Two dogs with carpal injury and one dog with tarsal injury treated by arthrodesis METHODS: All dogs developed self-mutilation injuries due to licking and/or chewing of the toes within 21-52 days of surgery. Clinical signs did not resolve within one week after conservative treatment with wound debridement and protective bandages. Following general anaesthesia, a deep horseshoe-shaped skin incision, including the subdermal tissue, was performed proximal to the self-mutilation injury transecting the sensory cutaneous afferent nerves. The skin incision was closed with simple interrupted sutures. RESULTS: All wounds healed without complication. Self-mutilation resolved completely within 24 hours after surgery in all dogs. No recurrence was observed (5 months to 3 years). CONCLUSION: Non-selective cutaneous sensory neurectomy may lead to resolution of self-mutilation following arthrodesis in dogs. CLINICAL RELEVANCE: Failure of conservative treatment in self-mutilation injuries often leads to toe or limb amputation as a last resort. The technique described in this case series is a simple procedure that should be considered prior to amputation. The outcome of this procedure in dogs self-multilating due to neurological or behavioral disturbances unrelated to carpal or tarsal arthrodesis is not known.

Estrogen receptor subtype beta2 is involved in neuromast development in zebrafish (Danio rerio) larvae

Estrogens are known to play a role in both reproductive and non-reproductive functions in mammals. Estrogens and their receptors are involved in the development of the central nervous system (brain development, neuronal survival and differentiation) as well as in the development of the peripheral nervous system (sensory-motor behaviors). In order to decipher possible functions of estrogens in early development of the zebrafish sensory system, we investigated the role of estrogen receptor beta(2) (ERbeta(2)) by using a morpholino (MO) approach blocking erbeta(2) RNA translation. We further investigated the development of lateral line organs by cell-specific labeling, which revealed a disrupted development of neuromasts in morphants. The supporting cells developed and migrated normally. Sensory hair cells, however, were absent in morphants' neuromasts. Microarray analysis and subsequent in situ hybridizations indicated an aberrant activation of the Notch signaling pathway in ERbeta(2) morphants. We conclude that signaling via ERbeta(2) is essential for hair cell development and may involve an interaction with the Notch signaling pathway during cell fate decision in the neuromast maturation process.

Histological evaluation of human intrabony periodontal defects treated with an unsintered nanocrystalline hydroxyapatite paste

OBJECTIVES The aim of the study was to clinically and histologically evaluate the healing of human intrabony defects treated with open flap surgery (OFD) and application of a new, resorbable, fully synthetic, unsintered, nanocrystalline, phase-pure hydroxyapatite (nano-HA). MATERIALS AND METHODS Six patients, each of them displaying very advanced intrabony defects around teeth scheduled for extraction due to advanced chronic periodontitis and further prosthodontic considerations, were included in the study. Following local anaesthesia, mucoperiosteal flaps were reflected; the granulation tissue was removed, and the roots were meticulously debrided by hand and ultrasonic instruments. A notch was placed at the most apical extent of the calculus present on the root surface or at the most apical part of the defect (if no calculus was present) in order to serve as a reference for the histological evaluation. Following defect fill with nano-HA, the flaps were sutured by means of mattress sutures to allow primary intention healing. At 7 months after regenerative surgery, the teeth were extracted together with some of their surrounding soft and hard tissues and processed for histological analysis. RESULTS The postoperative healing was uneventful in all cases. At 7 months following surgery, mean PPD reduction and mean CAL gain measured 4.0 ± 0.8 and 2.5 ± 0.8 mm, respectively. The histological analysis revealed a healing predominantly characterized by epithelial downgrowth. Limited formation of new cementum with inserting connective tissue fibers and bone regeneration occurred in three out of the six biopsies (i.e. 0-0.86 and 0-1.33 mm, respectively). Complete resorption of the nano-HA was found in four out of the six biopsies. A few remnants of the graft particles (either surrounded by newly formed mineralized tissue or encapsulated in connective tissue) were found in two out of the six biopsies. CONCLUSION Within their limits, the present results indicate that nano-HA has limited potential to promote periodontal regeneration in human intrabony defects. CLINICAL RELEVANCE The clinical outcomes obtained following surgery with OFD + nano-HA may not reflect true periodontal regeneration.

The prevalence of widespread central hypersensitivity in chronic pain patients

BACKGROUND Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. METHODS We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. RESULTS Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. CONCLUSIONS Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment.