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PubMed1978

Skin involvement in generalized amyloidosis. A study of clinically involved and uninvolved skin in 50 patients with primary and secondary amyloidosis.

A punch or excisional biopsy of the skin was done in 50 patients with generalized amyloidosis: In 46, clinically normal skin, usually the forearm, was biopsied and in four, only cutaneous lesions. Amyloid was seen in the skin of 21 of 38 patients with primary and multiple myeloma-associated amyloidosis. Sixteen of 34 biopsies from clinically uninvolved skin were positive. Five of 12 patients with secondary amyloidosis had amyloid deposits in clinically normal skin. Overall, amyloidosis was definitively diagnosed on skin biopsy examination in 26 patients. A punch biopsy of clinically involved or uninvolved skin is an innocuous, simple procedure with a high diagnostic yield and can be done in an office setting.

Amyloidosis↗
PubMed1999

Uptake of topically applied 5-aminolevulinic acid and production of protoporphyrin IX in normal mouse skin: dependence on skin temperature.

The temperature dependence of the uptake phase of 5-aminolevulinic acid (ALA) and the following production phase of protoporphyrin IX (PpIX) in normal mouse skin was investigated. A cream containing 20% ALA was topically applied on the skin for 10 min. The amount of ALA-induced PpIX was evaluated by measuring the fluorescence of PpIX from the treated skin. No measurable amount of PpIX was found in the skin immediately after 10 min application of ALA. The penetration of ALA into the skin was almost temperature independent while the following production of PpIX was found to be a strongly temperature-dependent process. Practically no PpIX was formed in the skin as long as skin temperature was kept low (12 degrees C).

Aminolevulinic Acid↗
PubMedDate not supplied

[The use of skin testing in the investigation of toxidermia: from pathophysiology to the results of skin testing].

Drug skin tests can be of value in investigating cutaneous adverse drug reactions (CADR). Guidelines have been recently published for drug skin tests to standardize the management of patients suffering from CADR in European dermatological departments. Three sorts of drug skin tests can be performed, each investigating specific immunological mechanisms: delayed cellular hypersensitivity with patch tests (PT), immediate hypersensitivity with prick tests and both immediate or delayed hypersensitivity with intradermal tests (IDT). The mechanisms involved in inducing CADR are not well elucidated. The results of the drug skin tests depend on the drug and the mechanisms i.e. the clinical features of the CADR. 164 patients developed a CADR that could be attributed to one drug. After a patch test and a negative prick and intradermal test, positive drug skin tests were nevertheless obtained in 72% of the cases. Some urticarias are due to an immediate IgE related hypersensitivity; in such cases prick tests and IDT performed with sequential dilutions can have immediate positive results. Vasculitis is related to circulating immune complexes and cannot be reproduced by skin tests. Delayed cellular hypersensitivity is involved in inducing maculopapular rashes, Baboon syndrome, localized or generalized eczema or acute generalized exanthematous pustulosis. In such CADR, drug PT or delayed positive reactions on IDT occur in more than 50% of the patients. Diluted drug patch tests can be positive in investigating drug rash with eosinophilia and systemic symptoms. As Stevens-Johnson and Lyell's syndromes are due to many both toxic and immunological mechanisms, drug skin tests are not of great value in investigating these severe CADR.

Drug Eruptions↗
PubMed1989

The relationship between postnatal skin maturation and electrical skin impedance.

Electrical impedance, which is the resistance to an alternating current, is a parameter that is used to determine the condition of the electrode-skin interface before evoked potentials are recorded. High electrical impedance can result in inaccurate interpretation of evoked potentials due to excessive artifacts. This study investigated the electrical skin impedance in 36 full-term infants who ranged from 0 to 1 year of age to delineate the temporal relationship between skin maturation and skin impedance. Correlation and regression analyses demonstrated a statistically significant inverse relationship between electrical skin impedance and age during the first year of life. This drop in skin impedance during the first few postnatal months was attributed to an increase in skin hydration as a result of the greater functional maturity of eccrine sweat glands.

Aging↗
PubMed1987

Avidin-biotin-peroxidase complex immunohistochemistry to detect immunoglobulin in formalin fixed skin biopsies in canine autoimmune skin disease.

Avidin-biotin-peroxidase complex immunohistochemistry was used on formalin fixed, paraffin embedded, trypsin digested, skin biopsies to detect immunoglobulin deposition in dogs with autoimmune skin disease. Immunostaining by the avidin-biotin-peroxidase complex technique revealed intercellular and/or basement membrane immunoglobulin deposits in 27 of 28 dogs considered to have autoimmune skin disease by clinical and histological evaluation and in six of 19 dogs considered to have autoimmune skin disease by clinical evaluation but without histological confirmation. Similar immunostaining was not evident in five biopsies of normal skin or in biopsies from four dogs with noninflammatory dermatoses, but was present in biopsies from one of ten dogs considered by clinical and histological criteria to have an inflammatory dermatosis other than autoimmune skin disease. Detection of immunoglobulin deposits in skin biopsies by avidin-biotin-peroxidase complex immunohistochemistry offers numerous advantages over conventional immunofluorescence methods including the opportunity to precisely compare histological and immunological findings.

Animals↗
PubMed1993

Prenatal diagnosis of genetic skin disease using fetal skin biopsy samples.

BACKGROUND: Understanding normal skin development and identifying markers of genetic skin disease expressed in postnatal skin have permitted the prenatal diagnosis of many severe genodermatoses: bullous diseases, keratinization diseases, pigment cell disorders, and disorders of the epidermal appendages (ectodermal dysplasias). Samples of 16 to 22 weeks' gestation fetal skin obtained by ultrasound-guided biopsy are evaluated using morphologic, immunohistochemical, and biochemical methods. OBSERVATIONS: The 12-year experience in evaluating samples from fetuses at risk of these disorders has allowed us to establish conditions that must be met before the samples are taken and the criteria for recognizing the disorder, to recommend the site(s) for sampling, and to be mindful of pitfalls that may be encountered in interpreting the tissue structure. CONCLUSIONS: Fetal skin biopsy is an important diagnostic tool that has permitted families in which members carry the abnormal gene for one of these severe skin diseases to undertake a pregnancy knowing that the condition of the fetus can be determined. Nonetheless, the ultimate goal is phase out this procedure when linkage of more of these disorders to specific genes is understood, specific mutations are characterized, and probes are available for molecular diagnoses using tissue obtained at earlier fetal ages. Until this is possible, fetal skin biopsy remains an important tool that can be used with reasonably high levels of safety and confidence.

Amniotic Fluid↗
PubMed1997

Hair cycle-dependent plasticity of skin and hair follicle innervation in normal murine skin.

The innervation of normal, mature mammalian skin is widely thought to be constant. However, the extensive skin remodeling accompanying the transformation of hair follicles from resting stage through growth and regression back to resting (telogen-anagen-catagen-telogen) may also be associated with alteration of skin innervation. We, therefore, have investigated the innervation of the back skin of adolescent C57BL/6 mice at various stages of the depilation-induced hair cycle. By using antisera against neuronal (protein gene product 9.5 [PGP 9.5], neurofilament 150) and Schwann cell (S-100, myelin basic protein) markers, as well as against neural cell adhesion molecule (NCAM) and growth-associated protein-43 (GAP-43), we found a dramatic increase of single fibers within the dermis and subcutis during early anagen. This was paralleled by an increase in the number of anastomoses between the cutaneous nerve plexuses and by distinct changes in the nerve fiber supply of anagen vs. telogen hair follicles. The follicular isthmus, including the bulge, the seat of epithelial follicle stem cells, was found to be the most densely innervated skin area. Here, a defined subpopulation of nerve fibers increased in number during anagen and declined during catagen, accompanied by dynamic alterations in the expression of NCAM and GAP-43. Thus, our study provides evidence for a surprising degree of plasticity of murine skin innervation. Because hair cycle-associated tissue remodeling evidently is associated with tightly regulated sprouting and regression of nerve fibers, hair cycle-dependent alterations in murine skin and hair follicle innervation offer an intriguing model for studying the controlled rearrangement of neuronal networks in peripheral tissues under physiological conditions.

Animals↗
PubMed2001

Evidence of 5-lipoxygenase overexpression in the skin of patients with systemic sclerosis: a newly identified pathway to skin inflammation in systemic sclerosis.

OBJECTIVE: Leukotrienes are a family of arachidonic acid derivatives with potent proinflammatory and profibrotic properties, and 5-lipoxygenase (5-LOX) catalyzes two key steps in the leukotriene biosynthetic pathway. Since inflammatory cell infiltrates and excessive fibrosis are hallmarks of systemic sclerosis (SSc) skin lesions, we undertook the present study to investigate the expression of 5-LOX in skin biopsy specimens from patients with SSc. METHODS: Expression of 5-LOX in skin sections from 10 SSc patients and 8 healthy controls was examined by in situ hybridization with specific riboprobes and by immunohistochemistry analysis with 5-LOX monoclonal antibodies. Synthesis of 5-LOX by cultured dermal fibroblasts from 7 patients with SSc and 4 controls was measured by fluorescence-activated cell sorter analysis. In addition, concentrations of leukotriene B4 (LTB4) and LTE4 in fibroblast supernatants after stimulation were determined using enzyme immunoassays. RESULTS: Expression of 5-LOX was found in all skin sections from SSc patients as well as from controls. However, the number and percentage of 5-LOX-positive cells were significantly higher in SSc skin sections compared with control sections. Expression of 5-LOX was seen in cells within perivascular inflammatory infiltrates as well as in fibroblasts throughout the skin. The experiments with cultured skin fibroblasts revealed that 5-LOX was constitutively expressed in these cells, which resulted in the production of leukotrienes after cell stimulation. Whereas no difference was found for LTE4, SSc fibroblasts produced significantly higher amounts of LTB4 after stimulation, compared with healthy control fibroblasts. CONCLUSION: The results of this study suggest that the 5-LOX pathway may be of significance in the pathogenesis of SSc and may represent a target for new treatment strategies.

Arachidonate 5-Lipoxygenase↗
PubMed1999

Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: A link to neurogenic skin disorders.

Many skin disorders, such as atopic dermatitis and psoriasis, worsen during stress and are associated with increased numbers and activation of mast cells which release vasoactive, nociceptive, and proinflammatory mediators. Nontraumatic acute psychological stress by immobilization has been shown to induce mast cell degranulation in the rat dura and colon. Moreover, intradermal injection of corticotropin-releasing hormone (CRH) or its analogue urocortin (10(-5)-10(-7) M) induced skin mast cell degranulation and increased vascular permeability. Here, we investigated the effect of acute immobilization stress on skin mast cell degranulation by light microscopy and electron microscopy. Immobilization for 30 min resulted (P < 0.05) in degranulation of 40.7 +/- 9.1% of skin mast cells compared to 22.2 +/- 7.3% in controls killed by CO(2) or 17.8 +/- 2.4% in controls killed by pentobarbital. Pretreatment intraperitoneally (ip) with antiserum to CRH for 60 min prior to stress reduced (P < 0.05) skin mast cell degranulation to 21.0 +/- 3. 3%. Pretreatment with the neurotensin (NT) receptor antagonist SR48692 reduced (P < 0.05) mast cell degranulation to 12.5 +/- 3.4%, which was significantly (P < 0.05) below control levels. In animals treated neonatally with capsaicin to deplete their sensory neurons of their neuropeptides, such as substance P (SP), mast cell degranulation due to immobilization stress was reduced to about 15%. This is the first time that stress has been shown to trigger skin mast cell degranulation, an action not only dependent on CRH, but apparently also involving NT and SP. These findings may have implications for the pathophysiology and possible therapy of neuroinflammatory skin disorders such as atopic dermatitis, neurogenic pruritus, or psoriasis, which are induced or exacerbated by stress.

Acute Disease↗
PubMed1999

An extended dorsal island skin flap with multiple vascular territories in the rat: A new skin flap model.

BACKGROUND: The use of various animal skin flap models can lead to difficulty in the interpretation of experimental findings. Establishment of an axial-pattern flap model with predictable necrosis is desirable for the study of the flap pathophysiology. MATERIALS AND METHODS: Twenty rats were injected with a lead oxide, gelatin, and water mixture through the carotid artery to investigate the cutaneous vascular anatomy. Each cutaneous perforator on the rat dorsum was dissected to its source artery. The skin was removed and radiographed to define its vascular architecture. On the basis of the initial angiographic data, an extended dorsal island skin flap (based on the unilateral deep circumflex iliac artery) measuring up to 8 x 9 cm was designed in 10 rats to assess the viability of the flap. The boundaries of the flap are defined by anatomical landmarks to standardize the flap for rats of different sizes. The upper margin was located at the level of the tip of the scapula and the lower margin at a level 2 cm below the iliac crest. All flaps were observed for 7 days postoperatively and the surviving flap area was calculated as a percentage of total flap dimensions using the paper template technique. RESULTS: Most of the skin of the rat dorsum is supplied by three arteries: the deep circumflex iliac artery (DCIA), the posterior intercostal arteries (PIA), and the lateral thoracic artery (LTA). The DCIA anastomoses with the ipsilateral PIA and the contralateral PIA and DCIA. The average percentage survival of the skin flap is 70.5 +/- 4.8% (mean +/- SD). CONCLUSIONS: The extended dorsal island skin flap has a consistent vasculature and has a predictable distal necrosis area. This new model is felt to be appropriate for skin flap physiological studies.

Animals↗
PubMed1985

Severity of asthma in skin test-negative and skin test-positive patients.

The standardized records of 144 asthmatic patients have been analyzed to determine whether the severity of their condition was correlated with the presence or absence of positive intradermal skin test reactions to a panel of seven allergen extracts (dust, feathers, Alternaria, Hormodendrum, mixed tree pollen, mixed grass pollen, and ragweed pollen). The skin tests were totally negative in 71 of the subjects, whereas in 73 subjects there was a strongly positive response to two or more allergens. The skin test-negative patients were older than the skin test-positive ones and had a shorter duration as well as a later onset of asthma. Also, they had lower serum-IgE levels and a lower frequency of a family history of atopic disease. Moreover, the skin test-negative group lost more time from their normal activities, required more visits to their doctor as a result of asthma, and were more frequently treated with oral corticosteroids. They additionally had greater air trapping on pulmonary function tests. However, when the groups were adjusted for the discordance in their age and duration of asthma, they tended to converge in the level of the variables that described the severity of their asthma. Thus the severity of asthma was found to be relatively similar in skin test-negative and skin test-positive patients.

Adult↗
PubMed1988

Immediate skin test reactivity to common aeroallergens in patients with respiratory allergies: a comparative analysis of allergen-induced skin reactions and their histamine controls.

The results of the immediate skin test response to a panel of 16 common aeroallergens performed in a group of 659 consecutive patients with symptoms suggestive of a respiratory allergy were analyzed. A group of 108 healthy individuals served as control subjects. Ninety-four percent of the patients and 87% of the control subjects had at least one allergen-induced reaction (wheal greater than or equal to 2 by 2 mm). The prevalence of positive skin reactions to each aeroallergen was equally high in both groups. However, if a skin reaction is considered as positive only when an allergen-induced wheal is equal or larger compared to the 50% of the wheal obtained with the histamine control in that individual, 70% of the patients had positive skin reactions and only 38% of the control subjects were positive (p less than 0.05). Similarly, the prevalence rates to five aeroallergens (pollen, Fusarium, Mucor, Pullularia, and Curvularia) in the patient group were reduced to those levels observed with the control group, suggesting they are clinically less important. The age and not the sex influenced both the prevalence rates (p less than 0.001) and the mean size (p less than 0.01) of allergen and histamine-induced skin reactions. Lower prevalence rates and mean size values were observed in the youngest group (0 to 9 years). Moreover, there was an inverse relationship between lower skin reactivity with more younger subjects in our patient population. These results indicate that patients and healthy individuals have similar mechanisms for skin reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Circadian variation of skin reactivity and allergy skin tests.

Previous investigations of the circadian variation in skin reactivity suggested that results of skin tests obtained in the afternoon could vary from the results obtained in the early morning and therefore could result in a differing assessment of patient sensitivity. To determine whether this was a practical concern in the normal clinical setting, we studied 20 adults and 20 children who had skin prick tests positive (3+ or more) to short ragweed. These patients were skin tested in duplicate at 8 AM and at 4 PM with fivefold serial dilutions of short ragweed extracts (1:20 to 1:12,500, wt/vol) and of histamine hydrochloride (10 to 0.016 mg/ml). Areas of wheal and flare were recorded and measured by computed planimetry. In addition, results were also read according to a conventional scoring system. Mean wheal and erythema areas with ragweed and histamine at each dilution were compared between morning and their corresponding evening values. Although there was a trend for the morning means to be larger than evening means, no significant differences between the two sessions were observed at any dilution. Mean morning skin index scores, as calculated from the combined mean wheal and erythema areas, were larger than mean evening scores for ragweed and histamine, but the differences were not of a degree to be clinically important. This observation was also true for conventional scores. Comparing the results from the two groups of children who had their first set of skin tests performed either in the morning or afternoon session indicated that there was no evidence of a refractory state of the skin during the second test sessions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1996

Relationship between the in vitro radiosensitivity of skin fibroblasts and the expression of subcutaneous fibrosis, telangiectasia, and skin erythema after radiotherapy.

OBJECTIVE: To investigate if the occurrence of subcutaneous fibrosis after radiotherapy in an unselected group of breast cancer patients is related to cellular radiosensitivity of skin fibroblasts as measured in a clonogenic assay. MATERIALS AND METHODS: An in vitro colony-forming assay of normal fibroblast radiosensitivity was applied to primary skin biopsies from 31 breast cancer patients who received post-mastectomy radiotherapy with large doses per fraction (2.7-3.9 Gy) more than 10 years earlier. Three clinical normal-tissue endpoints were assessed. Two late endpoints, subcutaneous fibrosis and telangiectasia, were evaluated in three treatment fields by a single experienced clinician. In addition, skin erythema had been assessed at the end of treatment by members of the staff and junior staff. From previous analyses of normal tissue response, individual clinical radiosensitivity could be assessed as "excess risk' of each of the three reactions. This was defined as the difference between the actual observed response in the patient and the expected response estimated from individual treatment characteristics in a linear quadratic (LQ) mixture model and, for the two late endpoints, with correction for the follow-up time. This clinical radioresponsiveness was compared with the in vitro radiosensitivity of the skin fibroblasts. To this end, the fractions of colony-forming cells after graded single doses were fitted by an LQ survival curve using non-linear regression from which the surviving fraction at 3.5 Gy (SF3.5) was estimated. Assessment at 3.5 Gy was chosen to reflect the fraction size during clinical radiotherapy. RESULTS: A statistically significant variability of in vitro radiosensitivity between patients could be detected for both SF2 (P = 0.0095) and SF3.5 (P = 0.0008). A significant correlation was observed between SF3.5 and excess risk of fibrosis (rs = -0.46, P = 0.009) while no association was found between fibroblast radiosensitivity and either the occurrence of severe skin telangiectasia or the acute endpoint skin erythema. CONCLUSION: These results suggest that variability in the occurrence of subcutaneous fibrosis, but not telangiectasia or erythema, after radiotherapy is partly accounted for by differences in cellular radiosensitivity of normal skin fibroblasts.

Adult↗
PubMed1986

Effects of skin storage conditions and concentration of applied dose on [3H]T-2 toxin penetration through excised human and monkey skin.

Penetration of [3H]T-2 toxin through excised human and monkey skin stored at -60 degrees C was faster than through human and monkey skin stored at 4 degrees C, respectively. The permeability of refrigerated human skin was 34% of the permeability of refrigerated monkey skin. Increasing the concentration of [3H]T-2 toxin applied to the refrigerated monkey skin increased the amount of [3H]T-2 toxin penetrating the skin and enhanced the efficiency of penetration. Metabolites of [3H]T-2 toxin were identified in the receptor fluid bathing the dermal side of the excised human and monkey skin.

Animals↗
PubMed1993

Evaluation of the contribution of chronic skin irritation and selected compositional parameters to the tumorigenicity of petroleum middle distillates in mouse skin.

Two-year skin carcinogenicity studies were conducted in C3H mice to assess the effects of irritation and selected compositional parameters on the carcinogenic potential of four petroleum liquids. Three samples (lightly refined paraffinic oil, LRPO; lightly hydrodesulfurized specialty oil, LHSO; jet fuel, JF) can be generically classified as middle distillates, i.e. distillation occurs between 350 and 700 degrees F (175-370 degrees C). The fourth sample was a Steam Cracked Gas Oil (SCGO) that distilled within the same range. In studies that assess the effects of irritation on tumorigenicity, LRPO was tested undiluted or was diluted to 50% and 25% in either mineral oil (which eliminated irritation of the skin) or toluene (which did not). Undiluted LRPO elicited tumors in 8% of the mice. Both dilution procedures eliminated tumorigenic potential. Thus, it was possible to maintain a visible level of skin irritation equivalent to that elicited by undiluted LRPO without inducing tumors. SCGO elicited a chronic irritant state grossly equivalent to LRPO but was not tumorigenic. Jet Fuel A (JF) was tested undiluted using both a standard skin painting protocol and an intermittent dosing schedule in which treatment was suspended periodically to allow skin irritation to resolve. The standard treatment protocol of JF resulted in both marked skin irritation and tumors in 44% of the mice. However, using the intermittent schedule, the tumor yield was reduced to 2%. Collectively these data demonstrate that tumor formation is not a necessary sequelae to chronic skin irritation. Conversely, prevention of a marked chronic irritant state was accompanied by decreased tumor yield. These data suggest that the chronic irritant state may be a necessary but not sufficient condition for tumor formation. In studies to assess the effects of compositional parameters, a lightly hydrodesulfurized specialty oil (LHSO) similar to LRPO but refined to have negligible levels of sulfur compounds (3 ppm), elicited chronic irritant and tumor responses (10%) similar to LRPO. Thus, the level of sulfur compounds does not appear to affect the tumorigenic activity for products in this boiling range. The SCGO which did not produce tumors contained only aromatic hydrocarbons, a finding consistent with previous reports that aromatics may not be the source of tumorigenic potential in petroleum fractions boiling between 350 and 700 degrees F (175-370 degrees C).

Animals↗
PubMed2004

The impact of skin banking and the use of its cadaveric skin allografts for severe burn victims in Singapore.

The skin banking programme was set-up in Singapore in 1998 to provide a ready source of allografts for patients with severe burns. The process and problems in establishing a local skin bank will be described together with a retrospective review of skin allograft recipients to determine the efficacy of the programme. For the skin bank set-up, pertinent issues related to legislation, methods, logistics, quality assurance and donation rate are discussed. In this retrospective review, a comparison between patients who had early complete excision with skin allograft transplantation and those who received conventional staged excision and coverage, was analysed in terms of clinical profile and outcome using statistical methods. The former group presented a significant reduction of mortality rate and hospital stay by 29% and 10 days, respectively. The establishment of the skin bank has helped in the management of severe burn patients by facilitating early excision and allografting. In a Burn Centre, therefore, it is essential to have an ample supply of skin allograft for burn victims in readiness for mass disaster situations.

Adolescent↗
PubMed2002

The presence of D-beta-aspartic acid-containing peptides in elastic fibers of sun-damaged skin: a potent marker for ultraviolet-induced skin aging.

Biologically uncommon d-aspartyl residues have been reported in proteins of various elderly tissues. We prepared a polyclonal antibody against d-beta-Asp-containing peptide and examined its immunoreactivity in the skin. The antibody recognized integrated or disintegrated elastic fibers in the sun-exposed skin but not in the sun-protected skin of the elderly donors. Western blot analysis of the proteins isolated from sun-damaged skin demonstrated that the 50 kDa protein was immunoreactive with both antibodies for d-beta-Asp-containing peptide and elastin. Ultraviolet (UV) irradiation on normal skin caused the appearance of d-beta-Asp-containing peptide-immunoreactive fibers in the dermis. These results suggest that UV irradiation is closely related to the formation of d-beta-Asp in the elastic fibers of skin. We propose that the antibody could be a useful indicator for sun damage of the skin.

Aged↗