Nail position has an influence on anterior knee pain after tibial intramedullary nailing

Our aim was to determine the possible relationship between anterior knee pain (AKP) and nail position marked as a distance from tip of nail to tibial plateau (NP) and to the tuberositas tibiae (NT). Nail position has an influence on anterior knee pain after tibial intramedullary nailing. We evaluated postoperative outcome results of 50 patients in the last 3 years with healed fractures initially treated with intramedullary (IM) reamed nails with 2 or 3 interlocking screws on both parts of the nail and with the use of medial paratendinous incision for nail entry portal. Patients marked a point on the visual analog scale (VAS) that corresponded to the level of postoperative AKP felt. Two groups of patients were formed on the basis of AKP (pain level was neglected): groups A and B, with and without pain, respectively. The difference between the two groups concerning NP measurements was statistically significant (p < 0.05), but not concerning NT measurements at the p < 0.05 level. Patients were classified by pain with high accuracy (98%) according to a classification tree. Symptoms of AKP did not appear if the tip of the nail position was more than 6.0 mm from the NP and more than 2.6 mm from the NT. However, for better evaluation of these results it will be necessary to examine a larger number of postoperative patients with AKP.     

Nail lengthening and fingertip amputations

Fingertip injuries can be treated in different ways, including shortening with primary closure, skin grafts, and local or distant flaps. Nail bed involvement complicates fingertip reconstruction and may influence the choice of treatment. Local flaps can usually replace the pulp and provide a satisfactory functional and aesthetic result, whereas reconstruction of the fingernail apparatus is more difficult. In the period between 1998 and 2001, 12 fingertip injuries with nail bed involvement were treated with a combination of local flaps (Tranquilli-Leali and Venkataswami flaps) and the eponychial flap. The eponychial flap described by Bakhach is a backward cutaneous translation flap that lengthens the nail plate and restores a good appearance of the nail apparatus. This technique is simple to use and can be used with different flaps for pulp reconstruction.     

Serous cutaneous glands in the South American horned frog Ceratophrys ornata (Leptodactylformes, Chthonobatrachia, Ceratophrydae): ultrastructural expression of poison biosynthesis and maturation

Serous cutaneous glands are described in newly metamorphosed and juvenile specimens of the horned frog Ceratophrys ornata using light and transmission electron microscopy. We report patterns of biosynthesis and maturation of the specific product of the gland secretory unit. The syncytial, secretory compartment possesses a complex of endoplasmic reticulum (predominantly smooth endoplasmic reticulum after metamorphosis) and Golgi stacks. The serous product is weak in density and is contained in vesicles involved in repeating merging processes. During this maturation activity, secondary lysosomes are observed, which derive from autophagic processes (crinophagy) involving the secretory materials. Ceratophrys ornata, a species representative of the type genus of the family Ceratophrydae, belongs to the heterogeneous group of anurans that, possibly as the result of convergence, all produce cutaneous poisons consisting of vesicles or faint density granules.     

The perception of painful and nonpainful stimuli during voluntary motor activity in man

Previous studies have shown that voluntary movement diminishes the transmission of cutaneous afferent input through the dorsal column-medial lemniscal system, and also raises the threshold for detecting nonpainful, cutaneous stimuli (electrical shocks). Although there is some evidence that pain elicited by electrical stimulation is diminished during movement, no studies have tested the effect of movement on the perception of pain produced by natural stimulation. For this reason, we tested the effects of voluntary motor activity on the perception of noxious thermal stimuli in human volunteers. We first developed a motor paradigm in which the thermal stimulation could be applied to the immobile limb (isometric elbow flexion-extension). Both isometric and isotonic muscle contractions about the elbow increased the threshold for detecting weak cutaneous stimuli (electrical shocks) applied to the forearm, and to a lesser extent the detection of stimuli applied to the dorsum of the hand. Afterwards, noxious and innocuous heat stimuli were applied to the forearm during isometric contractions and at rest. Magnitude estimates for the intensity of the pain, as well as latency measures of the onset of pain, were recorded. We found no evidence that isometric motor activity diminished either the threshold for pain or the subjective intensity of the noxious and innocuous thermal stimuli. Thus, motor activity decreases the ability to detect weak low-threshold cutaneous inputs, but has no effect on the perception of warmth and heat pain.     

Algesia and local responses induced by neurokinin A and substance P in human skin and temporal muscle

Neurokinin A (NKA), substance P (SP) and the two peptides combined (SP + NKA) were injected intracutaneously on the forearm and into the temporal muscle of healthy volunteers. Pain intensity, cutaneous wheal and flare responses and tenderness of the temporal muscle were quantitated. SP but not NKA induced cutaneous pain. This relates the algesic effect of SP to the specific N-terminal amino acid sequence of the peptide, not shared by NKA. NKA, however, potentiated the algesic effect of SP as SP + NKA induced a significantly prolonged cutaneous pain sensation. Both peptides induced wheals, but only SP induced flare. These results confirm previous studies relating wheal formation to the identical C-terminal amino acid sequence of the two peptides and flare reaction to the N-terminal part of SP. Injections into the temporal muscle did not cause pain or tenderness.     

A jury of none: an essay on the last acceptable form of civic banishment

Though many socio-legal scholars have criticized those measures that deny convicted felons the right to vote, few have challenged the statutes that withhold a convicted felon’s opportunity to sit on a jury. A majority of US jurisdictions bar felons from jury service permanently, creating a class of citizens defined and punished by the criminal justice system but unable to impact its function. This essay considers the invisibility of felon jury exclusion, notes its unlikely supporters, and asserts that by preventing convicted felons from taking part in civic processes, authorities work against reentry initiatives.     

Experimental and modeling investigation of the mechanism of synaptic vesicles recycling

Under the condition of microelectrode recording and fluorescence microscopy with dye FM 1-43 the research of exo-/endocytosis of synaptic vesicles in motor nerve terminals (NT) of frog cutaneous pectoris and white mice diaphragm muscles during high frequency stimulation (20 imp/s) was carried out. A mathematical modeling allowed us to conclude that the obtained experimental data can be explained in the following framework. Three pools of synaptic vesicles are involved in neurotransmitter release in the frog motor NT. Recovery of these pools is provided by endocytosis of two types: fast endocytosis with limited capacity and slow endocytosis. Fast-reconstructing vesicles refill the mobilization pool and slow endocytosis recovers the reserve pool. Our modeling investigation has revealed in frog NT independent recruiting of reserve and mobilization pools to the neurotransmitter secretion, i.e. this pools work concurrently. Experimental data, obtained on mice preparations, are well described with the framework of two-pools model including single type of endocytosis (fast endocytosis).     

Hereditary leukonychia, or porcelain nails, resulting from mutations in PLCD1

Hereditary leukonychia (porcelain nails or white nails) is a rare nail disorder with an unknown genetic basis. To identify variants in a gene underlying this phenotype, we identified four families of Pakistani origin showing features of hereditary leukonychia. All 20 nails of each affected individual were chalky and white in appearance, consistent with total leukonychia, with no other cutaneous, appendageal, or systemic findings. By using Affymetrix 10K chip, we established linkage to chromosome 3p21.3-p22 with a LOD score (Z) of 5.1. We identified pathogenic mutations in PLCD1 in all four families, which encodes phosphoinositide-specific phospholipase C delta 1 subunit, a key enzyme in phosphoinositide metabolism. We then identified localization of PLCD1 in the nail matrix. It was recently shown that PLCD1 is a component of the human nail plate by proteomic analysis and is localized in the matrix of human nails. Furthermore, mutations detected in PLCD1 resulted in reduced enzymatic activity in vitro. Our data show that mutations in PLCD1 underlie hereditary leukonychia, revealing a gene involved in molecular control of nail growth.     

Serous gland polymorphism in the skin of<Emphasis Type="Italic"> Phyllomedusa hypochondrialis azurea</Emphasis> (Anura,Hylidae): response by different gland types to norepinephrine stimulation

Stimulation by norepinephrine in physiological concentration was used on the dorsal skin of the Argentine tree-frog Phyllomedusa hypochondrialis azurea to trigger contraction of myoepithelial cells encircling the serous glands and provoke secretory release. This hylid species possesses two kinds of serous cutaneous glands, producing secretory granules or vesicles (type Ia and Ib serous units, respectively), along with serous-derived glands which synthesise lipids and store them in complex aggregates (type II units). Structural and ultrastructural observations on myoepithelia, secretory units and gland products collected in saline after discharge, revealed consistent but different responses in the three types investigated. Type Ia glands reacted intensely to treatment, with both contractile and secretory responses, type Ib glands were only mildly affected in their myoepithelia and glands of type II were not affected at all. According to data available in the literature, these findings suggest that: (a) the dense (type Ia) granules are expelled as a phasic response through bulk (holocrine) discharge, (b) the secretory (type Ib) vesicles are released as a tonic response through a merocrine mechanism and (c) lipid (type II) aggregates are exuded as a secretory component of a complex behavioural response which tends to reduce transcutaneous water loss. Furthermore, these findings indicate that the use of pharmacological modulation of myoepithelial activity allows selective collection of skin products in species characterised by serous gland polymorphism.     

Ectodermal dysplasia-cutaneous syndactyly syndrome maps to chromosome 7p21.1-p14.3

Ectodermal dysplasia syndromes are genetically heterogeneous group of disorders involving one or more of the classical ectodermal appendages (hair, nail, teeth, sweat glands) in association with anomalies of other organs or systems. In the present study a novel form of ectodermal dysplasia syndrome, ectodermal dysplasia cutaneous syndactyly (EDCS), segregating in an autosomal recessive pattern in a Pakistani family was investigated. The clinical features of the affected individuals included large prominent ear pinnae, tooth enamel hypoplasia, hypoplastic nails, bilateral partial cutaneous syndactyly, hypotrichosis, palmoplantar keratoderma and hyperhidrosis. Through genetic linkage study, EDCS syndrome was mapped on human chromosome 7p21.1-p14.3 flanked by markers D7S488 and D7S817. A maximum two-point LOD score of 2.94 (θ = 0.00) was obtained at marker D7S2496 while a maximum multipoint LOD score of 3.07 was obtained with several markers along the disease-interval. This interval spans 19.80-cM, which corresponds to 13.74-Mbp according to the sequence-based physical map (Build 36.1). Sequence analysis of 27 candidate genes, located in the candidate interval, did not reveal any functional sequence variant.     

Laser-evoked brain potentials in patients with dissociated loss of pain and temperature sensibility

Brief heat stimuli, elicited by a CO₂ laser (10.6 μm wave length), activate the most superficial cutaneous nerve terminals of the thin myelinated Aδ and unmyelinated C fibres which mediate heat and pain sensations. This paper investigates late cerebral potentials (SEPs) in response to laser pulses in comparison with those to conventional electrical stimulation in 18 patients with a dissociated sensory deficit (intact mechanosensibility and disturbed temperature and pain sensation). Patients were stimulated in the most disturbed limb (affected area) and in a corresponding control area.In all 18 patients the SEPs elicited by laser stimuli were able to identify the body site with heaviest disturbances in pain and thermosensibility: the SEPs from the affected area were reduced or delayed, compared to the control area. In contrast, no alterations in SEPs could be observed after conventional electrical nerve stimulation, in agreement with the normal mechanosensibility. However, the degree of SEP modulation in response to cutaneous heat stimuli did not correspond to the severity of the subjectively reported sensory deficit. Highest correlations between sensory deficits and abnormal SEPs were found in all those patients in whom computer tomography or MR imaging documented a localized destructive process in the CNS. All patients with the smallest SEP modulations despite a considerable sensory deficit had an inflammatory aetiology. Preliminary criteria to define a laser-evoked SEP as pathological are discussed.     

Development of serous cutaneous glands in Scinax nasica (Anura,Hylidae): patterns of poison biosynthesis and maturation in comparison with larval glands in specimens of other families

We examined the development of serous (poison) cutaneous glands in larval and juvenile Scinax nasica (Hylidae) at the ultrastructural level. We describe the biosynthesis and maturation of the cutaneous poison in comparison with the corresponding processes in representatives of Discoglossidae, Leptodactylidae, Pelobatidae and Pipidae. Serous biosynthesis in S. nasica starts in discrete adenoblasts and continues in the syncytial secretory unit. Biosynthetic processes involve rough endoplasmic reticulum and the Golgi apparatus, that releases membrane-bounded material, varying from fine grained to flocculent. During the post-Golgian secretory phase, this material undergoes initial maturation, and two products are formed: dense granules and larger vesicles holding a thin substance that will later be structured into a three-dimensional, honeycomb-like net. Both the secretory granules and vesicles change into glomerular-like aggregates of bowed, rod-shaped subunits (modules). In adult frogs, formation of dense granules is bypassed. The modular granule substructure seems to be related to the merocrine release of small amounts of poison, involved in regulating skin homeostasis. Comparison with maturational changes in larval glands of species representing four anuran families discloses similar patterns in the Leptodactylidae, but production of opaque homogeneous granules occurs in the Discoglossidae, clear vesicles in the Pelobatidae and aggregates of dense bars in the Pipidae.     

Respiratory responses induced by the activation of somatic nociceptive afferents in humans.

To further investigate the role of somatic nociceptive afferents in the neural control of breathing, we studied the respiratory effects of their activation by means of either electrical stimulation or ischemic pain in 14 healthy volunteers. Painful electrical cutaneous stimulation increased respiratory frequency (f), mean inspiratory flow (VT/TI), and rate of rise (XP/TI) of integrated electromyographic activity of diaphragm (IEMGdi). Painful muscular electrical stimulation caused similar but larger changes accompanied by increases in tidal volume (VT), peak XP of IEMGdi, and ventilation (VE); it also entrained respiratory rhythm. Ischemic pain, which was characterized by a progressively increasing intensity, caused augmentation in respiratory activity that displayed an increasing trend: VE, f, VT, XP, VT/TI, and XP/TI increased. In the light of available literature, it seems conceivable to suggest that respiratory responses to painful electrical stimulation are mediated through the activation of cutaneous (A delta) and muscular (group III) fine-myelinated afferents, and responses to ischemic pain are mediated by the activation of both fine myelinated (group III) and unmyelinated (group IV) muscular afferents. The input conveyed by these afferents may constitute an effective stimulus to respiration in humans.     

Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage

We characterised biological properties of novel formulations of two low-potency glucocorticosteroids, dexamethasone and hydrocortisone, which have an equivalent dose ratio of 1:50 in vasoconstriction tests. The rate of such carrier-mediated, mainly non-diffusive glucocorticosteroids transport with very deformable lipid vesicles (Transfersomes) through the skin, and the corresponding cutaneous drug biodistribution data, were complemented with the drug bio-efficacy studies. The minimum effective drug dose that reduces arachidonic acid-induced murine ear oedema by 50% was used as one bioactivity indicator. The minimum drug amount ensuring such an effect in mouse skin decreases appreciably when a corticosteroid is applied epicutaneously with very deformable vesicles rather than a lotion or a crème. Specifically, the minimum effective dose for hydrocortisone in very deformable carriers is 2-3 microg cm(-2) whereas for the crème- or lotion-like preparations at least 10 microg cm(-2) is required. Such three- to fivefold relative increase of hydrocortisone potency is accompanied by at least 13%, and more often >20%, absolute drug potency enhancement. The delivery of hydrocortisone with very deformable carriers moreover prolongs the suppression of the drug-induced oedema nearly 2-fold (to approximately 24 h per application). The effective dose of dexamethasone delivered with very deformable vesicles into murine skin is reduced >10 times compared with the crème- or lotion-based products. Specifically, less than 0.1 microg cm(-2) dexamethasone in very deformable vesicles suppresses the arachidonic acid-induced murine ear oedema >50%, on the average. Dexamethasone use on the skin in such vesicles extends the duration of drug action fourfold, compared with a commercial crème, i.e. to >48 h per application. Epicutaneous use of glucocorticosteroids in very deformable vesicles also diminishes such drug's abrasion sensitivity and may increase the general robustness of drug effect. Lower frequency of skin treatment, which ensures adequate biological response, is a result of this. Topical corticosteroid delivery with very deformable vesicles, Transfersomes, thus improves the therapeutic risk-benefit ratio, arguably due to better targeting into and longer drug presence in the skin.     

Ultrastructural study of the mental body of Hydromantes genei (Amphibia: Plethodontidae)

The mental glands of Hydromantes genei are considered a specialized form of the urodele serous cutaneous glands. Use of a variety of techniques of maceration and digestion as well as transmission electron microscopy (TEM) and scanning electron microscopy (SEM) has shown the three-dimensional morphology of secretory and myoepithelial cells. Secretory cells are pyramidal and rest on an almost continuous layer of myoepithelial cells. The latter have a long ribbon-like body from which branch off transversal and longitudinal processes with swallow-tailed ends. Cytoplasmic processes of secretory cells, containing irregular dense vesicles, squeeze through clefts between myoepithelial cells and may reach, at some points, the basal lamina. The interstices between myoepithelium and secretory cells are extraordinarily rich in nerve endings with clear vesicles. The glandular outlets appear as elliptical stomata in the superficial layer of the epidermis and are lined by horny cells, which invaginate to circumscribe the excretory duct. The morphological results indicate that the myoepithelium of Plethodontidae mental glands differ in some respects from that of amphibian serous cutaneous glands. A double polarity for the secretory cells is also suggested. © 1993 Wiley-Liss, Inc.     

Synaptic vesicles and microtubules in frog motor endplates.

Motor endplates of the cutaneous pectoris skeletal muscle of the frog have been examined by electron microscopy using a new technique. This involves pretreatment with an albumin solution, followed by fixation with 4% unbuffered tetroxide. A small proportion of the endplate axonal ramifications show microtubules clothed in synaptic vesicles and focused on the presynaptic membrane, in particular on the active zones. The microtubules run in the presynaptic cytoplasm either parallel to or across the active zones. These two sets of microtubules cross each other at the active zones, which lie opposite the dips in the post-junctional folds. The possibility that the microtubules are involved in the translocation of synaptic vesicles to the active zone is discussed.     

甲板甲床部分切除联合苯酚烧灼术治疗嵌甲症的临床研究

目的:探讨甲板甲床部分切除联合苯酚烧灼术治疗嵌甲症的临床疗效。方法:选择武汉市中心医院2004年10月至2013年5月收治的115例148趾拇趾嵌甲进行研究。以2004年10月至2007年12月的患者53例(67趾)作为对照组行单纯甲板甲床部分切除术治疗,2008年1月至2013年5月的患者62例(81趾)作为观察组行甲板甲床部分切除联合苯酚烧灼术治疗。对比两组患者的出血、疼痛缓解和康复时间,了解一年后患者复发情况及满意度。结果:148趾手术伤口均一期愈合,观察组病例术后出血时间、疼痛缓解时间(1.85±0.42天、13.25±2.17小时)较对照组(2.69±0.53天、21.54±2.56小时)低,但术后恢复时间(11.32±2.37天)较对照组(8.93±2.06天)长,差异均有统计学意义(P0.05),观察组和对照组的复发率及总体满意率分别为6.15%、12.5%及97.06%、91.07%,两组差异并无统计学意义(P0.05)。结论:甲板甲床部分切除联合苯酚烧灼术治疗嵌甲症与单纯甲板甲床部分切除术的疗效相当,但可显著减少患者痛苦。     

Influence of segmental and extra-segmental conditioning stimuli on cortical potentials evoked by painful electrical stimulation

This study evaluated the effects of two different types of segmental/extra-segmental conditioning stimuli (tonic muscle pain and non-painful vibration) on the subjective experience (perceived pain intensity) and on the cortical evoked potentials to standardized test stimuli (cutaneous electrical stimuli). Twelve subjects participated in two separate sessions to investigate the effects of tonic muscle pain or cutaneous vibration on experimental test stimuli. The experimental protocol contained a baseline registration (test stimuli only), a registration with the test stimuli in combination with the conditioning stimuli, followed by a registration with the test stimuli only. In addition, the effects of the conditioning stimuli were examined at two anatomically separated locations (segmental and extra-segmental). Compared with the test stimulus alone, the perceived pain intensity and peak-to-peak amplitudes of the evoked potentials were unchanged in the presence of non-painful conditioning stimuli at either location. In contrast, a significant decrease of the perceived pain intensity and peak-to-peak amplitudes was found in the presence of painful conditioning stimuli at the extra-segmental sites. Moreover, the topographic maps of the 32-channel recordings suggested that the distribution of the scalp evoked potentials was almost symmetrical around the vertex Cz in the baseline registration. The evoked potentials were generally decreased during hypertonic saline infusion at the extra-segmental sites, but the distribution of the topographic maps did not appear to change. Vibration has previously been shown to inhibit pain, but in the present study the perceived intensity of phasic painful electrical stimuli was unchanged. The reduced perceived pain intensity and the smaller peak-to-peak amplitude of the evoked potential in the presence of extra-segmental conditioning pain are in accordance with the concept of diffuse noxious inhibitory control.     

Activating the somatosensory system enhances net quadriceps moment during gait

Quadriceps muscle rehabilitation following knee injury or disease is often hampered by pain, proprioception deficits or instability associated with inhibition of quadriceps activation during walking. The cross-modal plasticity of the somatosensory system with common sensory pathways including pain, pressure and vibration offers a novel opportunity to enhance quadriceps function during walking. This study explores the effectiveness of an active knee brace that used intermittent cutaneous vibration during walking to enhance the peak knee flexion moment (KFM) during early stance phase as a surrogate for net quadriceps moment (balance between knee extensor and flexor muscle moments). The stimulus was turned on prior to heel strike and turned off at mid-stance of the gait cycle. Twenty-one subjects with knee pathologies known to inhibit quadriceps function were tested walking under three conditions: control (no brace), a passive brace, and an active brace. Findings show that compared to the control, subjects wearing an active brace during gait exhibited a significant (p < 0.001) increase in peak KFM and no significant difference when wearing a passive brace (p = 0.17). Furthermore, subjects with low KFM and knee flexion angle (KFA) in control exhibited the greatest increase in KFA at loading response in the active brace condition (R = 0.47, p < 0.05). Intermittent cutaneous stimulation during gait, therefore, provides an efficient method for increasing the KFM in patients with knee pathologies. This study’s results suggest that intermittent vibration stimulus can activate the cross-modalities of the somatosensory system in a manner that gates pain stimulus and possibly restores quadriceps function in patients with knee pain.     

Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

ABSTRACT: The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT) receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT), an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki = 44 uM). Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM) within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for beta2- and beta3-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions.