Contralateral Control Site Research Articles

High-frequency electrical stimulation of cutaneous nociceptors differentially affects pain perception elicited by homotopic and heterotopic electrical stimuli.

Animal studies have shown that high-frequency electrical stimulation (HFS) of peripheral C-fiber nociceptors induces both homosynaptic and heterosynaptic long-term potentiation (LTP) within spinal nociceptive pathways. In humans, when HFS is applied onto the skin to activate nociceptors, single electrical stimuli are perceived more intense at the HFS site compared with a control site, a finding that was interpreted as a perceptual correlate of homosynaptic LTP. The present study aimed to investigate if after HFS the pain elicited by electrical stimuli delivered at the skin next to the HFS site is perceived as more intense compared with the pain at a control site (contralateral arm). To test this, HFS was applied to one of the two ventral forearms of 24 healthy participants. Before and after HFS, single electrical stimuli were delivered through the HFS electrode, through an identical electrode next to the HFS electrode and an identical electrode at the contralateral arm. After HFS, the pain elicited by the single electrical stimuli was reduced at all three sites, with the largest reduction at the HFS site. Nevertheless, electrical stimuli delivered to the skin next to the HFS site were perceived as more intense than control stimuli. This result indicates that higher pain ratings to electrical stimuli after HFS at the HFS site cannot solely be interpreted as a perceptual correlate of homosynaptic changes. Furthermore, we show for the first time, in humans, that HFS can reduce pain elicited by single electrical stimuli delivered through the same electrode.NEW & NOTEWORTHY High-frequency electrical stimulation (HFS) of cutaneous nociceptors can reduce pain perception to single electrical stimuli delivered through the same electrode. Moreover, single electrical stimuli delivered to the skin next to the site at which HFS was applied are perceived as more intense compared with that at the contralateral control site, indicating the presence of heterosynaptic effects for electrical stimuli.

Objective quantification of burn scar stiffness using shear-wave elastography: Initial evidence of validity

Shear-wave elastography (SWE) is an ultrasound based technology that can provide reliable measurements (velocity) of scar stiffness. The aim of this research was to evaluate the concurrent validity of using both the measured velocity and the calculated difference in velocity between scars and matched controls, in addition to evaluating potential patient factors that may influence the interpretation of the measurements. MethodsA cross-sectional study of 32 participants, with 48 burn scars and 48 matched contralateral control sites were evaluated with SWE, the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS) tactile sub-scores. ResultsSpearman’s rho demonstrated high correlations (r > 0.7) between the measured scar velocity and both the POSAS and VSS pliability sub-scores, whereas moderate correlations (r > 0.6) were found with the calculated difference in velocity. Regression analysis indicated that the association of increased velocity in scars, varied by length of time after burn injury and gender. Body location and Fitzpatrick skin type also demonstrated significant associations with velocity, whereas age did not. ConclusionSWE shows potential as a novel tool to quantify burn scar stiffness, however patient factors need to be considered when interpreting results. Further research is recommended on a larger variety of scars to support the findings.

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.

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.

Biomechanical properties of infantile hemangiomas: clinical stage and effect of age.

Infantile hemangiomas (IHs) are benign vascular neoplasms with rapid capillary proliferation shortly after birth and slow involution with diminishing capillary proliferative activity, fibrosis, and fatty replacement over 7-10 years. Hemangiomas and contralateral control sites in 88 subjects were measured using a suction device, 6-mm probe and 200 mbar negative pressure. Mechanical properties were assessed vs. controls and effects of body site, depth, clinical stage, histology diagnosis, and time. Biological elasticity, overall elasticity, net elasticity, total recovery, and elastic recovery were lower for IH vs. controls (P < 0.001). IH total deformation, elastic deformation, viscoelastic creep, and residual deformation were higher than controls (P < 0.001). Involuting IHs had lower viscoelasticity than proliferating and stable lesions (P < 0.001) and lower viscoelastic creep than stable IHs (P = 0.04). IH viscoelasticity was higher at 2.3 than 12.9, 23.7, and 61.0 months and at 4.9 and 8.1 than 61.0 months. IH elastic recovery varied by body site with larger differences vs. control for abdomen and leg. Elastic recovery differences from control were smaller at younger vs. older ages. Measurement of biomechanical properties may be useful to characterize IH progression and treatment response in clinical settings.

Clinical and Biochemical Effects of 810 nm Diode Laser as an Adjunct to Periodontal Therapy: A Randomized Split-Mouth Clinical Trial

The aim of this clinical trial was to determine the clinical and biochemical efficacy of an 810 nm diode laser as an adjunct to scaling and root planing (SRP). Lasers can achieve excellent tissue ablation with strong bactericidal and detoxification effects. The use of lasers is one of the most promising new technical modalities for nonsurgical periodontal treatment. However, the most effective wavelength and parameters for their use are still under investigation. This study was designed as a single-blinded, randomized-controlled, split-mouth clinical trial. Twenty-one patients (12 females and 9 males between 26 and 55 years of age), diagnosed with generalized chronic periodontitis, were included in the study. After initial periodontal therapy, which consisted of oral hygiene instructions and scaling, patients underwent two different treatment modalities. Test and control sites were chosen with coin toss randomization. At the test site, patients received SRP and laser treatment; at the contralateral control site, they received SRP treatment alone. Both treatment modalities resulted in significant improvements in all clinical and biochemical parameters. Sites irradiated with an 810 nm diode laser using the "hot tip" (∼ 760 °C) technique showed enhanced healing in all the registered periodontal variables and interleukin (IL)-1β levels, compared with SRP alone. Within the limitations of this study, the use of diode lasers as an adjunct to SRP produced significant improvements in clinical parameters as well as gingival crevicular fluid (GCF) IL-1β levels in the 6 month study period.

Effect of bosentan on intimal hyperplasia of carotid artery anastomoses in rabbits

We investigated the effect of bosentan on intimal hyperplasia of carotid artery anastomoses in rabbits. Eighteen New Zealand male rabbits were randomized into two groups, as drug (Group B) and non-drug (Group A). The right carotid artery of all the subjects was transected and anastomosed end-to-end with 10/0 polypropylene suture. The left carotid artery was left intact. Group B subjects received 30 mg/kg/day oral bosentan for 21 days, starting 3 days before the operation. Group A subjects did not receive any medication. After 28 days, the anastomoses site and the contralateral control site were removed, and samples were investigated histomorphometrically. Significant intimal hyperplasia was observed at all anastomoses compared to the non-anastomotic left side. Bosentan decreased significantly the intimal area [Group A: 48.3 µm(2) (37.1 µm(2)-65.7 µm(2)), Group B: 31.4 µm(2) (12.2 µm(2)-63.2 µm(2)), (p=0.04)] and intima/media area ratio [Group A: 0.49 (0.13-0.74), Group B: 0.22 (0.09-0.37), (p=0.024)] compared to the non-drug group. According to our investigation, bosentan decreased the intimal hyperplasia developed in a rabbit carotid artery model. Further investigations are needed to support the potential clinical utilization of bosentan after vascular interventions.

Microstructural remodeling of articular cartilage following defect repair by osteochondral autograft transfer

To assess collagen network alterations occurring with flow and other abnormalities of articular cartilage at medial femoral condyle (MFC) sites repaired with osteochondral autograft (OATS) after 6 and 12 months, using quantitative polarized light microscopy (qPLM) and other histopathological methods. The collagen network structure of articular cartilage of OATS-repaired defects and non-operated contralateral control sites were compared by qPLM analysis of parallelism index (PI), orientation angle (α) relative to the local tissue axes, and retardance (Γ) as a function of depth. qPLM parameter maps were also compared to ICRS and Modified O'Driscoll grades, and cell and matrix sub-scores, for sections stained with H&E and Safranin-O, and for Collagen-I and II. Relative to non-operated normal cartilage, OATS-repaired regions exhibited structural deterioration, with low PI and more horizontal α, and unique structural alteration in adjacent host cartilage: more aligned superficial zone, and reoriented deep zone lateral to the graft, and matrix disorganization in cartilage overhanging the graft. Shifts in α and PI from normal site-specific values were correlated with histochemical abnormalities and co-localized with changes in cell organization/orientation, cloning, or loss, indicative of cartilage flow, remodeling, and deterioration, respectively. qPLM reveals a number of unique localized alterations of the collagen network in both adjacent host and implanted cartilage in OATS-repaired defects, associated with abnormal chondrocyte organization. These alterations are consistent with mechanobiological processes and the direction and magnitude of cartilage strain.

Mapping biological to clinical phenotypes during the development (21 days) and resolution (21 days) of experimental gingivitis

To characterize and map temporal changes in the biological and clinical phenotype during a 21-day experimental gingivitis study. Experimental gingivitis was induced over 21 days in healthy human volunteers (n = 56), after which normal brushing was resumed (resolution phase). Gingival and plaque indices were assessed. Gingival crevicular fluid was collected from four paired test and contra-lateral control sites in each volunteer during induction (Days 0, 7, 14 and 21) and resolution (Days 28 and 42) of experimental gingivitis. Fluid volumes were measured and a single analyte was quantified from each site-specific, 30s sample. Data were evaluated by analysis of repeated measurements and paired sample tests. Clinical indices and gingival crevicular fluid volumes at test sites increased from Day 0, peaking at Day 21 (test/control differences all p < 0.0001) and decreased back to control levels by Day 28. Levels of four inflammatory markers showed similar patterns, with significant differences between test and control apparent at Day 7 (substance P, cathepsin G, interleukin-1β, elastase: all p < 0.03) and peaking at Day 21 (all p < 0.002). Levels of α-1-antitrypsin showed no pattern. Levels of substance P, cathepsin G, interleukin-1β and neutrophil elastase act as objective biomarkers of gingival inflammation induction and resolution that typically precede phenotypical changes.

A Clinical Investigation into the Relationship between Increased Periwound Skin Temperature and Local Wound Infection in Patients with Chronic Leg Ulcers

Increased local temperature is a classic sign of wound infection, and its quantitative measurement has the potential to assist with assessment and diagnosis of chronic deep wound and surrounding skin infection at the bedside. Evidence supporting such use in chronic wound care is very limited. This clinical pilot study was conducted in an attempt to quantify the relationship between increased periwound skin temperature and wound infection, as well as validate use of a handheld infrared thermometer for the wound care practitioner. Using a cross-sectional design, 2 groups of participants were recruited from a chronic wound clinic: without wounds (n = 20) and with chronic leg ulcers (n = 40). Participant and wound characteristics were documented. All skin temperatures were documented using a handheld infrared thermometer under consistent environmental conditions within the clinic. Data analysis was based on the difference (Delta) in skin temperature (in degrees Fahrenheit) between a target or wound site and an equivalent contralateral control site. Wound infection was identified using the combination of a validated assessment tool and clinical judgment. Supplemental semiquantitative bacterial swabs were collected from all wounds. Descriptive statistics were analyzed using the chi-squared calculation. A Pearson r calculation of test-retest skin temperature data collected from nonwounded participants initially determined reliability of the infrared thermometer. Correlation of increased periwound skin temperature to wound infection was determined by calculation of a 1-way analysis of variance. The infrared thermometer was found to be reliable (r = 0.939, P = .000 at a 95% confidence interval). A statistically significant relationship between increased periwound skin temperature and wound infection was identified (F = 44.238, P = .000 at a 95% confidence interval). Neither patient nor wound characteristics were significantly different between the participants with noninfected or infected wounds. The results of this study demonstrate that incorporating quantitative skin temperature measurement into routine wound assessment provides a timely and reliable method for a wound care practitioner to quantify the heat associated with deep and surrounding skin infection and to monitor ongoing wound status. Study limitations may reduce transferability of these findings to wound types other than chronic leg ulcers. Further research is needed to support and strengthen these results.

Assessment of changes in the oral tactile function of the soft tissues by implant placement in the anterior maxilla: a prospective study

The aim of the present study was to assess the somatosensory function in the peri-implant soft tissues in the anterior jaw bone by means of two psychophysical tests. Light-touch sensation (LTS) and two-point discrimination (2PD) were performed before, and at planned intervals until 18 months after the placement of one or two implants in the anterior maxilla. The same tests were used on the contralateral control sites. The psychophysical threshold was determined by performing the staircase method. The mean values and standard deviation of LTS and 2PD, pooled over the four sessions at each test area, were calculated. Despite a large intersubject variation in both the LTS and 2PD, significantly high intra-individual correlations were found (P < 0.005). For LTS, the thresholds were not significantly affected over time (P > 0.05) on both implant and control sites. The 2PD increased significantly after surgery and maintained the higher discriminatory sense for 1 year (P-value 0.005). The control sites remained stable over time. However, no correlation was revealed between LTS and 2PD perception (Pearson correlation test). In this prospective study, no major differences between the different sites and testing sessions were reported; except for the 2PD thresholds which were lowered after implant surgery. These findings suggest that the regenerated nerves may be responsible for the increased 2PD sensitivity in the peri-implant soft tissue. The unchanged LTS thresholds did not allow confirming this hypothesis.

Growth Factor–Mediated Treatment of Recession Defects: A Randomized Controlled Trial and Histologic and Microcomputed Tomography Examination

The primary aims of this two-part prospective study were: 1) to compare the safety and efficacy of beta-tricalcium phosphate (beta-TCP) + 0.3 mg/ml recombinant human platelet-derived growth factor-BB (rhPDGF-BB) with a bioabsorbable collagen wound-healing dressing and a coronally advanced flap (CAF) to a subepithelial connective tissue graft (CTG) in combination with a CAF in subjects with gingival recession defects using a randomized, controlled, split-mouth design; and 2) to compare, through histologic and microcomputed tomography (micro-CT) examination, the periodontal regenerative potential of these two therapies in surgically created gingival recession defects in restoring missing cementum, periodontal ligament (PDL), and supporting alveolar bone. In the randomized controlled trial (RCT), 30 patients with Miller Class II buccal gingival recession, > or = 3 mm deep and > or = 3 mm wide in contralateral quadrants of the same jaw were treated and followed for 6 months. Using a split-mouth design with similar bilateral recession defects, test sites were treated with 0.3 mg/ml rhPDGF-BB + beta-TCP + bioabsorbable collagen wound-healing dressing; contralateral control sites were treated with a CTG, each in combination with a CAF. In the histologic/micro-CT study segment, recession defects were created in six teeth, each requiring extraction for orthodontic therapy. These defects were created with a recession depth > or = 3 mm, the osseous crest 2 to 3 mm apical to the gingival margin, and with 2 to 3 mm of keratinized tissue. The defects were treated with a CTG (control) or rhPDGF-BB + beta-TCP + wound-healing dressing (test), plus CAF. Nine months after surgical correction, en bloc resections were obtained and examined histologically and with micro-CT. In the RCT, test and control treatments demonstrated clinically significant improvements from baseline through month 6. Statistically significant results favoring the CTG were found in recession depth reduction (-2.9 + 0.5 mm, test; -3.3 + 0.6 mm, control; P = 0.009), root coverage (90.8%, test; 98.6%, control; P = 0.013), and -3.9 +/- 0.7 mm, control, -3.3 +/- 1.3 mm, test, recession width reduction (P = 0.035), whereas mid-buccal probing depth (PD) and PD reduction (PDR) reduction favored the test group (1.4 +/- 0.4 mm, test; 1.8 +/- 0.1 mm, control; P < 0.001 PD and -0.0 mm test; +0.4 mm control PDR). For all other parameters, the two treatments were statistically equivalent, including increases in keratinized tissue, esthetic results, and subject satisfaction. In the histologic/micro-CT portion, all four sites treated with rhPDGF-BB + beta-TCP showed evidence of regeneration of cementum, PDL with inserting connective tissue fibers, and supporting alveolar bone, whereas neither CTG-treated site exhibited any signs of periodontal regeneration. CTG and rhPDGF-BB + beta-TCP + wound-healing dressing are effective treatment modalities for clinically correcting gingival recession defects. In addition, the current study demonstrated that regeneration of the periodontium in gingival recession defects was possible through a growth factor-mediated approach.

Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic dystrophy)

CRPS-I consists of post-traumatic limb pain and autonomic abnormalities that continue despite apparent healing of inciting injuries. The cause of symptoms is unknown and objective findings are few, making diagnosis and treatment controversial, and research difficult. We tested the hypotheses that CRPS-I is caused by persistent minimal distal nerve injury (MDNI), specifically distal degeneration of small-diameter axons. These subserve pain and autonomic function. We studied 18 adults with IASP-defined CRPS-I affecting their arms or legs. We studied three sites on subjects’ CRPS-affected and matching contralateral limb; the CRPS-affected site, and nearby unaffected ipsilateral and matching contralateral control sites. We performed quantitative mechanical and thermal sensory testing (QST) followed by quantitation of epidermal neurite densities within PGP9.5-immunolabeled skin biopsies. Seven adults with chronic leg pain, edema, disuse, and prior surgeries from trauma or osteoarthritis provided symptom-matched controls. CRPS-I subjects had representative histories and symptoms. Medical procedures were unexpectedly frequently associated with CRPS onset. QST revealed mechanical allodynia ( P < 0.03) and heat-pain hyperalgesia ( P < 0.04) at the CRPS-affected site. Axonal densities were highly correlated between subjects’ ipsilateral and contralateral control sites ( r = 0.97), but were diminished at the CRPS-affected sites of 17/18 subjects, on average by 29% ( P < 0.001). Overall, control subjects had no painful-site neurite reductions ( P = 1.00), suggesting that pain, disuse, or prior surgeries alone do not explain CRPS-associated neurite losses. These results support the hypothesis that CRPS-I is specifically associated with post-traumatic focal MDNI affecting nociceptive small-fibers. This type of nerve injury will remain undetected in most clinical settings.

Lack of Efficacy of Low-Intensity Pulsed Ultrasound on Prevention of Postmenopausal Bone Loss Evaluated at the Distal Radius in Older Chinese Women

A within-subject, randomized, and prospective intervention trial was done to evaluate the potential effect of low-intensity pulsed ultrasound on prevention of postmenopausal bone loss. Twenty healthy postmenopausal women between the ages of 51-81 years met the inclusion criteria. The treatment hand was randomly selected, and the contralateral site served as a control. Integral and trabecular bone mineral density were measured using highly precise multilayer peripheral quantitative computed tomography at the bilateral distal radius at baseline, 3 months after daily low-intensity pulsed ultrasound treatment, and 3 months after discontinuing treatment. Results showed that the rate of bone change (trabecular bone mineral density and integral bone mineral density) did not significantly differ between the site treated with low-intensity pulsed ultrasound and the contralateral control at either followup. Also, during the followup, bone mineral density did not change significantly in the contralateral control site. This was the first prospective and randomized study to show that low-intensity pulsed ultrasound at the current regime did not have significant effects on intact bone for prevention of postmenopausal bone loss in the distal radii of older Chinese women.

Collagen fibril diameters increase and fibril densities decrease in skin subjected to repetitive compressive and shear stresses

Understanding microstructural changes that occur in skin subjected to repetitive mechanical stress is crucial towards the development of therapies to enhance skin adaptation and load tolerance in patients at risk of skin breakdown (e.g. prosthesis users, wheelchair users). To determine if collagen fibril diameter, collagen fibril density, dermal thickness, epidermal thickness, basement membrane length, and dermal cell density changed in response to repetitive stress application, skin subjected to moderate cyclic compressive and shear stresses for 1 h/d, 5 d/week, for 4 week was compared with skin from an unstressed contralateral control. The lateral aspects of the hind limbs of 12 Landrace/Yorkshire pigs were used. Skin from under the stressed site and a contralateral control site was processed for electron microscopy and light microscopy analysis. Electron microscopy results demonstrated significant ( p<0.01) increases in collagen fibril diameter of 15.9%, 22.4%, and 22.9% for the upper, mid, and lower layers of the dermis, respectively, for the stressed skin compared with the control skin. Collagen fibril density (fibrils/unit cross-sectional area) decreased significantly for stressed vs. control by 19.8%, 29.2%, and 31.8% for the upper, mid, and lower layers, respectively. Light microscopy results demonstrated trends of a decrease in dermal thickness and an increase in cell density for stressed vs. control samples, but the differences were not significant. Differences in epidermal thickness and basement membrane length were not significant. These results demonstrate that quantifiable changes occur in collagen fibril architecture but not in the gross tissue morphology following in vivo cyclic loading of pig skin.

TGF-beta1 influences early gingival wound healing in rats: an immunohistochemical evaluation of stromal remodelling by extracellular matrix molecules and PCNA.

The effect of topically applied transforming growth factor beta1 (TGF-beta1) on the rat gingival wound healing process after flap surgery was evaluated by immunohistochemistry for extracellular matrix molecules (ECM), such as tenascin, heparan sulfate proteoglycan (HSPG) and type IV collagen, and for proliferating cell nuclear antigen (PCNA) in fibroblasts. TGF-beta1 solution was applied to the surgical wound experimental sites. Two microg/microl were applied at the time of the operation, and 1 microg/microl at days 1 and 2 after surgery, with contralateral control sites receiving the vehicle alone. Periodontal tissues were histologically examined at 3 and 7 days post-surgery. Tenascin was found to be more strongly stained in the granulation tissue from experimental sites at 3 days post-surgery. At 7 days postsurgery, HSPG-positive areas in granulation tissue had become smaller and there was a prominent proliferation of PCNA-positive fibroblast-like cells and type IV collagen-positive blood vessels. These results suggest that TGF-beta1 applied to surgical wounds influences early proliferation of gingival fibroblast-like cells, the formation of blood vessels, and ECM remodelling. In conclusion, TGF-beta1 application appears to promote granulation tissue formation in periodontal wound healing.

Ultrastructural analysis of human skin biopsy specimens from patients receiving recombinant human stem cell factor: Subcutaneous injection of rhSCF induces dermal mast cell degranulation and granulocyte recruitment at the injection site

We performed an ultrastructural analysis of 10 skin biopsy specimens that had been obtained from three women who were undergoing daily subcutaneous dosing with recombinant methionyl-human stem cell factor (rhSCF) as part of a phase I clinical trial. The biopsy specimens were obtained at sites of subcutaneous administration of rhSCF, within approximately 1 to 2 hours of rhSCF injection, and, at the same time, at contralateral control sites that had not been directly injected with rhSCF. We previously reported that subcutaneous dosing with rhSCF in these subjects induced the local development of a wheal and flare response, which was associated with evidence of mast cell degranulation, as well as a systemic increase in numbers of cutaneous mast cells. The present electron microscopic analysis revealed that all biopsies of swollen, erythematous rhSCF-injected sites exhibited anaphylactic degranulation of both mature and immature mast cells, an acute inflammatory response characterized by the migration of neutrophils, basophils (some of which exhibited evidence of piecemeal degranulation), and eosinophils through blood vessel walls into the perivascular and extravascular spaces, and edema and fibrin deposition within the interstitium. By contrast, the control biopsies contained no evidence of mast cell degranulation or acute inflammation. However, both control and rhSCF-injected sites exhibited mast cells that were undergoing granule building and maturation. Thus at the doses tested in these subjects, subcutaneous injection of rhSCF induced anaphylactic-type degranulation of dermal mast cells at the injection site, with an acute inflammatory response that was associated with the recruitment of granulocytes. By contrast, mast cells at sites distant from those directly injected with rhSCF exhibited no evidence of enhanced secretion. (J Allergy Clin Immunol 1998;101:793-806.)

Does lipid sampling with the Sebutape technique disturb the skin physiology?

Lipid sampling with the Sebutape technique takes at least 1 h in order to obtain a representative follicular pattern. Subsequent morphometric analysis reveals different parameters on the sebum excretion. However, application of Sebutape may disturb the normal skin physiology, and hence sebum excretion, due to an occlusive effect. The aim of the present study was to evaluate whether collection of skin surface lipids with Sebutape influences skin parameters such as TEWL, skin temperature and stratum corneum hydration. On the forehead, a comparison was made between skin sites covered with a Sebutape and contralateral control sites. Prior to removal of the Sebutape, skin temperature under the tape was measured. Immediately after removal of the tape, TEWL and skin capacitance were estimated. The same parameters were determined on the control sites. Furthermore, a comparison was made on the forearms between the occlusion effect of Sebutape application and a complete occlusion with a plastic tape. Hydration of the skin was measured as function of time after removal of both occlusive applications. We detected only a very weak influence of Sebutape application on TEWL and skin hydration. Skin temperature was not affected. A significant difference was detected between the application of Sebutape and the application of a plastic occlusion. Lipid sampling with Sebutape has only minor or no influence on the skin physiology as demonstrated by TEWL, skin temperature and stratum corneum capacitance measurements.

Cutaneous exposure to bis-(2-chloroethyl)sulfide results in neutrophil infiltration and increased solubility of 180,000 m r subepidermal collagens

Exposure to bis-(2-chloroethyl)sulfide (BCES; “sulfur mustard”) causes delayed formation of slowly healing skin blisters. Although the histopathology of BCES injury is well characterized [reviewed in Smith et al., J Am Acad Dermatol 32: 767–776, 1995], little is known of the cutaneous toxicity at the molecular level. To identify biological markers of exposure, epidermal and subepidermal extracts were prepared from 48 individual hairless guinea pigs (HGP) at successive 3-hr intervals following exposure to BCES vapor, and compared using gel electrophoresis, and lectin- and antisera-binding. Inflammation was assessed by measuring edema and myeloperoxidase activity. Edema reached peak levels at 15–18 hr and remained elevated above controls at 24 hr. Recruitment of neutrophils, deduced from increased myeloperoxidase, occurred as early as 3 hr after BCES exposure with maximum infiltration at 6–12 hr. Binding of concanavalin-A lectin revealed increased amounts, relative to contralateral control sites, of two approximately 180,000 M r polypeptides in subepidermal protein extracts from the BCES-exposed skin obtained ≥ 12 hr after exposure. This alteration was not found in epidermal protein extracts prepared from the same animals. Based upon the determined amino acid compositions, both polypeptides had significant collagenous triple helical content (> 75%). They could be distinguished immunologically from collagen types I, III, and IV by using polyclonal antisera. We conclude that exposure of HGP skin to BCES results in an early neutrophil infiltration that precedes epidermal-dermal separation and selective alterations of the subepidermal extracellular matrix.

Early diagnosis of upper aerodigestive tract cancer by autofluorescence.

To explore the potential of autofluorescence spectroscopy as a tool for early detection of upper aerodigestive tract cancer. Autofluorescence spectral characteristics of 19 untreated oral and oropharyngeal lesions in 13 patients were studied with excitation wavelengths of 370 and 410 nm generated by a nitrogen pumped dye laser. Ten healthy volunteers were recruited to characterize the fluorescence spectra of normal mucosa at different oral sites and to study individual variations. Fluorescence intensity and line shape of the spectra from lesions were compared with the same parameters from the contralateral control site in the same individual. Otolaryngology Research Center, Department of Otolaryngology-Head and Neck Surgery, New England Medical Center, Boston, Mass. The ratio of peak fluorescence intensities of the neoplastic lesions to contralateral normal control mucosa were consistently different compared with these ratios in benign lesions or normal mucosa. These differences were seen in 2 distinct regions of the fluorescence spectrum with both of the excitation wavelengths, but were more obvious with the excitation wavelength of 410 nm. Using these differences, we were able to correctly diagnose 17 of the 19 lesions studied, with 2 false-positive results. Neoplastic oral mucosa shows consistent differences in autofluorescence spectral intensity and line shape when compared with the normal mucosa in the same individual. These early results show that fluorescence spectroscopy may represent a useful technique for noninvasive early diagnosis of cancer of the upper aerodigestive tract.