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A broad spectrum of human papillomavirus types is present in the skin of Australian patients with non-melanoma skin cancers and solar keratosis.

BACKGROUND: Human papillomavirus (HPV) may play a role in the pathogenesis of non-melanoma skin cancer (NMSC) in epidermodysplasia verruciformis (EV) patients, but in the general population no specific HPV types have been associated with these lesions. Objectives To examine the spectrum of HPV types present in the skin and tumours of Australian patients with NMSC or solar keratosis (SK). METHODS: Biopsies from tumours, and cotton swab samples of perilesional skin and buttock skin from each of 59 Australian patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or SK were tested for HPV DNA by polymerase chain reaction (PCR) using HPV consensus (FAP) primers and by type-specific primers for HPV 38 and candidate HPV 92. The identification of HPV type from consensus PCR was performed by sequencing and comparison with GenBank. RESULTS: In total, 49 of 59 (83%) patients harboured HPV DNA, which was detected in 28 of 64 (44%) biopsies, 48 of 64 (75%; P < 0.001) perilesional swabs and 36 of 59 (61%; P = 0.04) buttock swabs. Forty-five different HPV types/putative types were detected: 15 were previously characterized HPV types, 17 were earlier described putative types and 13 were new putative types. In addition, six subtypes and four variants of HPV sequences were identified. HPV types within the B1 group (EV HPV types) were found in 26 of 64 (40%) lesions, 44 of 64 (69%) perilesional swabs and 35 of 59 (59%) buttock swabs. HPV 38 was detected in 23 of 59 (39%) patients, and was found in seven of 16 (43%) SKs, but was less common in SCCs [three of 23 (13%); P = 0.037] and BCCs [four of 25 (16%); P = 0.056]. Candidate HPV 92 was found in seven of 59 (12%) patients. CONCLUSIONS: A broad spectrum of HPV types, the majority from the B1 group, was found in skin of Australian patients with skin tumours. HPV 38 was found significantly more often in SK than in SCC. However, the role of cutaneous HPV infection in the pathogenesis of NMSC remains elusive.

Adult↗

Parameters related to oxygen free radicals in human skin: a study comparing healthy epidermis and skin cancer tissue.

In vitro studies with tumor cells have demonstrated that oxygen free radicals are involved in the development of skin cancers and that variations in the body's defense mechanisms can modify the course of the disease. To assess the validity of this hypothesis in spontaneous tumors, we determined glutathione S-transferase, superoxide dismutase, reduced and oxidized glutathione, and thiobarbituric acid reactive substances in healthy whole skin (n = 95), dermis (n = 73), and epidermis (n = 69). The values were compared with those obtained in three types of skin cancer: basal cell carcinoma (n = 16), squamous cell carcinoma (n = 6), and melanoma (n = 33). In healthy skin, glutathione S-transferase, superoxide dismutase, reduced glutathione, and oxidized glutathione were higher in epidermis than in dermis, whereas thiobarbituric acid reactive substances were higher in dermis than in epidermis; whole skin had intermediate values. These results suggest that there is an induction of some anti-oxygen free radicals mechanisms in epidermis as a result of increased oxygen free radicals production. Glutathione S-transferase and thiobarbituric acid reactive substances were higher in all types of tumor than in healthy epidermis but oxidized glutathione was lower. Reduced glutathione and superoxide dismutase activity were lower in basal cell carcinoma and squamous cell carcinoma samples. Glutathione S-transferase increased, whereas superoxide dismutase and thiobarbituric acid reactive substances decreased in melanoma samples in direct relation to the Clark levels. Higher glutathione S-transferase activity, particularly in the most invasive forms of melanoma, indicates that this type of cancer is more malignant. Similarly, a decrease in superoxide dismutase activity can also encourage progression of the tumor. These results are in accord with those from tumor cell cultures and could suggest new strategies (gene therapy) for managing skin cancer.

Acids↗

Differential time courses of skin blood flow and hyperalgesia in the human sunburn reaction following ultraviolet irradiation of the skin.

The response of skin to ultraviolet (UV) irradiation is an inflammation with pronounced vasodilation and hyperalgesia. Volunteers underwent UV irradiation of patches of forearm skin 3 cm in diameter. The intensity of the UV irradiation (290-320 nm) ranged between 133 mJ/cm2 and 400 mJ/cm2. Changes in skin blood flow were measured with laser Doppler technique at 3, 6, 9, 12, 24, 30, 36, 48, 60, 72, 96 and 216 h post UV irradiation. The alteration in pain threshold was measured for heat with a Peltier thermode and for pressure with a metal stylus. The effect of repeated topical pre-treatment 4 days prior to UV irradiation with 1.5 g of 0.04% capsaicin containing ointment was also investigated.UV irradiation resulted in a dose-dependent increase of skin blood flow for more than 96 h post-irradiation. There were two peaks of blood flow at 12 h and 36 h. Topical application of capsaicin prior to UV irradiation attenuated blood flow from 30 h to 45 h post UV irradiation. Enhanced blood flow was also present 5 mm outside the irradiated area (flare reaction). The control level of heat pain threshold was 44.5+/-0.7;C in normal skin. Heat pain thresholds were lowered by up to 7.761.2;C in UV-irradiated areas in a dose-dependent fashion. The control level of pressure pain threshold was 15.260.3N. Pressure pain thresholds were lowered by up to 6 N in irradiated areas. Maximal hyperalgesia coincided with the second peak of skin blood flow between 30 h and 60 h post UV irradiation. The effects of topical application of capsaicin suggests an involvement of neuropeptide mechanisms in the late phase of the human sunburn reaction.

Adult↗

Collagen degradation in rat skin but not in intestine during rapid growth: effect on collagen types I and III from skin.

Metabolic degradation of prelabeled collagen in whole body skin and whole intestine was compared to that of types I and III collagens from skin in young, rapidly growing rats. Pregnant rats were given [3H]proline during the last week of gestation; and after birth, littermates were compared. Between the second and sixth weeks of age, there was a 43% loss of radioactivity from dermal collagen but no significant loss of radioactivity from intestinal collagen. Pepsin treatment solubilized 90% of the dermal collagen but only 12% of intestinal collagen. Skin from 2- and 6-week-old rats yielded the same proportions of type I and type III collagens (type I, 82%; type III, 18%). The relative losses of total radioactivity from types I and III were similar to each other (50 and 44%, respectively) and to the loss from whole skin. Because types I and III collagens are known to be present in both skin and intestine, the marked degradation of both collagen types in skin but not in the intestine may be related to the amount and kind of intermolecular crosslinks present.

Aging↗

Cutaneous microdialysis in man: effects of needle insertion trauma and anaesthesia on skin perfusion, erythema and skin thickness.

Cutaneous microdialysis is a method of measuring endogenous and exogenous compounds in the dermal interstitial fluid. The microdialysis probe is inserted in the dermis using a guide cannula. The insertion trauma was studied in dorsal forearm skin in a total of 28 human healthy volunteers. Twenty-four volunteers received local anaesthesia (Xylocain 10 mg/ml) in both forearms and a microdialysis probe was inserted in one of the arms. In 12 volunteers the insertion trauma and the effect of anaesthesia on skin blood flow and erythema were studied by laser Doppler perfusion imaging, Minolta Chromameter CR 200 and Dermaspectrometer. In the other 12 subjects trauma-induced oedema and effects on skin thickness were studied by ultrasound imaging. In addition, a microdialysis probe was inserted without prior anaesthesia in 4 volunteers, and the effects on skin blood flow and erythema were investigated. Significant increases in skin blood flow, erythema and skin thickness were found after insertion of the microdialysis probe. Local anaesthesia prior to the insertion reduced the effects of trauma. Probe depth in dermis did not influence the effects of trauma. At least 90-120 min is required after insertion in order to allow the vascular reaction to needle trauma to return to the baseline range.

Administration, Cutaneous↗

Mother-infant skin-to-skin contact after delivery results in early recognition of own mother's milk odour.

AIM: To determine the effects of mother-infant skin-to-skin contact immediately after birth on infant recognition of their own mother's milk odour and breastfeeding duration until 1 y of age. METHODS: Sixty healthy, full-term neonates were randomly assigned to group A with skin-to-skin contact and group B without. One and 4 d after birth, infant responses to the following odour stimuli were observed: own mother's milk, another mother's milk, formula, orange juice and distilled water. Infant facial action was videotaped and the frequency of mouthing movements was evaluated for each stimulus. Nutritional assessment, focused particularly on breastfeeding, was performed every 3 mo on participating infants. Statistical analysis comparing the frequency of mouthing movements with the aforementioned five different odour exposures was performed by ANOVA with Fisher's PLSD. Kaplan-Meier analysis with a log-rank test was used to compare breastfeeding rates between groups. RESULTS: Infants in both groups responded differently to mother's milk odour (either their own or another mother's milk) compared to the other stimuli on days 1 and 4. However, infants in group A demonstrated a larger difference in mouthing movements between their own and another mother's milk odour at 4 d of age (2.6 +/- 1.6) compared to infants in group B (0.9 +/- 2.0, p = 0.01). Infants in group A were breastfed an average of 1.9 mo longer than the others. CONCLUSION: Our study provides evidence that mother-infant skin-to-skin contact for more than 50 min immediately after birth results in enhanced infant recognition of their own mother's milk odour and longer breastfeeding duration.

Adult↗

Porcine skin as a model system for studies of ultraviolet a effects in human skin.

The range of diagnostic and therapeutic applications of ultraviolet A (UVA) radiation has been continuously expanding. UVA radiation is a well-known mutagenic factor capable of damaging both cells and tissues. At the same time there is a very limited information on long-term consequences of irradiating the skin with different doses of UVA and long-wavelength ultraviolet B (UVB) radiation used in therapies of skin disorders. It was demonstrated that for UVA doses of 0.1 to 1000 mJ/cm2 the sensitivity of the porcine skin to the UVA-induced breaking of nuclear DNA is similar to that of the human skin. Results indicate that porcine skin may serve as a model system for population studies of the deleterious effects of UVA irradiation of the skin cells.

Animals↗

Directed expression of keratin 16 to the progenitor basal cells of transgenic mouse skin delays skin maturation.

We previously hypothesized that the type I keratin 16 (K16) plays a role in the process of keratinocyte activation that occurs in response to skin injury (Paladini, R.D., K. Takahashi, N.S. Bravo, and P.A. Coulombe. 1996. J. Cell Biol. 132:381-397). To further examine its properties in vivo, the human K16 cDNA was constitutively expressed in the progenitor basal layer of transgenic mouse skin using the K14 gene promoter. Mice that express approximately as much K16 protein as endogenous K14 display a dramatic postnatal phenotype that consists of skin that is hyperkeratotic, scaly, and essentially devoid of fur. Histologically, the epidermis is thickened because of hyperproliferation of transgenic basal cells, whereas the hair follicles are decreased in number, poorly developed, and hypoproliferative. Microscopically, the transgenic keratinocytes are hypertrophic and feature an altered keratin filament network and decreased cell-cell adhesion. The phenotype normalizes at approximately 5 wk after birth. In contrast, control mice expressing a K16-K14 chimeric protein to comparable levels are normal. The character and temporal evolution of the phenotype in the K16 transgenic mice are reminiscent of the activated EGF receptor- mediated signaling pathway in skin. In fact, tyrosine phosphorylation of the EGF receptor is increased in the newborn skin of K16 transgenic mice. We conclude that expression of K16 can significantly alter the response of skin keratinocytes to signaling cues, a distinctive property likely resulting from its unique COOH-terminal tail domain.

Animals↗

Regional variations in antigenic properties of skin. A possible cause for disease-specific distribution of skin lesions.

The possibility that the distribution of skin lesions in some cutaneous diseases is due to variations in the antigenic properties of skin was investigated by mapping the expression of the skin-specific pemphigus vulgaris and bullous pemphigoid antigens in different regions of the body. The expression of both antigens was relatively stable within the same region, but varied between regions in a pattern that was distinct for each antigen. For each antigen there was a correlation between regions of high expression and location of skin lesions in autoimmune diseases involving the antigen. The results indicate that there are marked regional differences in the antigenic properties of skin and suggest this may influence the distribution of cutaneous lesions in some skin diseases.

Antigens↗

In vitro activity of tigecycline against isolates from patients enrolled in phase 3 clinical trials of treatment for complicated skin and skin-structure infections and complicated intra-abdominal infections.

The in vitro activity of tigecycline was evaluated against 4913 baseline pathogens isolated from 1986 patients enrolled in 4 pivotal phase 3 clinical trials. The trials, which were conducted in 38 countries worldwide, involved patients with complicated skin and skin-structure infections or complicated intra-abdominal infections. Tigecycline was active against the most prevalent pathogens for each infection type, including gram-positive and gram-negative strains of both aerobic and anaerobic bacteria (MICs, < or =2 microg/mL for most pathogens). The spectrum of activity of tigecycline included important pathogens, such as Staphylococcus aureus (including methicillin-resistant S. aureus), Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis. A few genera, such as Pseudomonas aeruginosa and members of the tribe Proteeae, were generally less susceptible to tigecycline than were other gram-negative pathogens. The susceptibility of the pathogens to tigecycline was similar for isolates obtained from patients enrolled in the studies of complicated skin and skin-structure infection or of complicated intra-abdominal infection. For most pathogens, the susceptibility to tigecycline was similar across all geographic regions. The excellent expanded broad-spectrum activity of tigecycline demonstrated in vitro against clinical isolates confirmed its potential utility for pathogens associated with complicated skin and skin-structure infections or complicated intra-abdominal infections.

Anti-Bacterial Agents↗

A new technique for three-dimensional measurements of skin surface contours: evaluation of skin surface contours according to the ageing process using a stereo image optical topometer.

The evaluation of skin surface contours can be carried out by various techniques, including the use of a stylus profilometer, a laserprofilometer and a conventional optical profilometer (COP). But these methods have some drawbacks because their data are basically obtained from two-dimensional algorithms. So a new technique has been developed based on a new concept: a stereo image processing technique which is considered in this paper. Since a pair of stereo images contains depth information, the 'disparity', or the difference between the left and right images, enables the production of three-dimensional coordinates. This study was performed to evaluate the change of skin surface contours according to the ageing process. The stereo image optical topometer (SOT) is a new instrument used for the three-dimensional evaluation of skin surface contours. Thus. five new parameters have to be developed, such as mean surface roughness (S(a)), mean depth of roughness (S(z)), three-dimensional length (S(L)), three-dimensional area (S(A)), and three-dimensional volume (S(V)). S(a), S(L) and S(A) have shown a statistically significant increase in the seventies age group. S(z) has also shown a significant increase in the twenties and over-sixties age groups. The coefficient variation of the height of the skin surface using a COP varies between 14.76 and 6.57, but that using a SOT is between 2.18 and 2.69, according to age variation. In conclusion, the SOT system is a more reliable and useful method for evaluating skin surface contours than the COP system. Among the three-dimensional parameters which were made in this study, S(A), S(L) and S(a) seem to be useful as reliable parameters for evaluating skin surface contours in the ageing process.

Aging↗

Hydrolysis of bisphenol A diglycidylether by epoxide hydrolases in cytosolic and microsomal fractions of mouse liver and skin: inhibition by bis epoxycyclopentylether and the effects upon the covalent binding to mouse skin DNA.

Synergistic interactions have been reported in the carcinogenicity of two epoxy resin components to mouse skin. A mixture of bisphenol A diglycidylether and bis epoxycyclopentylether was highly carcinogenic, despite the fact that neither compound gave positive results when applied individually. To elucidate the mechanism of this synergistic interaction we have investigated the effects of bis epoxycyclopentylether upon the hydrolysis and DNA-binding of bisphenol A diglycidylether. This glycidylether was rapidly hydrolysed by microsomal and cytosolic fractions of mouse liver and skin. In three different mouse strains the specific epoxide hydrolase activities were 28.3-48.5; 33.0-38.8; 7.9-10.2 and 0.85-0.98 nmol/mg protein/min for liver microsomal and cytosolic and skin microsomal and cytosolic fractions respectively. This is the first demonstration of an epoxide hydrolase activity in skin cytosolic fractions. Bis epoxycyclopentylether inhibited the microsomal activities. This inhibition appeared to be slightly more effective with microsomal fractions from liver. The effect of this inhibition upon the binding of bisphenol A diglycidylether to mouse skin DNA was investigated using bisphenol A diglycidylether radiolabelled at two different positions. When high doses of bisphenol A diglycidylether were applied to the mouse skin one major DNA adduct was observed which was identified as a glycidaldehyde adduct. This adduct was not detectable at the lowest bisphenol A diglycidylether dose tested, unless bis epoxycyclopentylether was applied simultaneously. These findings suggest that glycidaldehyde may be formed from bisphenol A diglycidylether. At low doses, however, the epoxide groups are hydrolysed before glycidaldehyde can be formed, unless the epoxide hydrolase is inhibited. Such inhibition and the associated increased production of glycidaldehyde may account for the potentiation of the carcinogenic response in the epoxide mixture.

Animals↗

Evaluation of new anti-infective drugs for the treatment of selected infections of the skin and skin structure. Infectious Diseases Society of America and the Food and Drug Administration.

No method for classifying infections of the skin and skin structure is uniformly accepted. Therefore, each protocol for the evaluation of new anti-infective drugs must include definitions of the skin and skin-structure infections to be treated. Clinical findings may suggest the etiology. Cultures should be performed by the best available technique. Because the yield of pathogens from sites of skin and skin-structure infection is often low, monitoring of the clinical response to therapy is paramount. Randomized, double-blind, active-control comparative studies are needed, and maintenance of blinding is recommended, even with a change in the route of administration of the study and/or control drugs. The period of follow-up should be defined for each type of infection.

Anti-Infective Agents↗

Skin-to-skin contact as a method of body warmth for infants of low birth weight.

Skin-to-skin mother/infant contact as a means of warmth for newborns of low birth weight (less than or equal to 2500 g) was studied in 132 infants admitted consecutively during the cold season July/September at the Central Hospital in Maputo. The mean (+/- SD) birth weight was 1788 g (+/- 304 g) and the gestational age 34 weeks (+/- 2.7). Fifty-seven (43 per cent) infants were born outside the hospital and were referred. The ambient temperature ranged from less than 22 degrees C to 32 degrees C. Skin-to-skin contact as the principal means of warmth commenced in more than a third by age 3 days and in more than a half by age 5 days after periods of observation to exclude clinical problems. The infants were kept warm using conventional methods during observation. Re-admission to the intensive care unit was required in nine cases: four for diarrhoea; two for respiratory infection; two with jaundice; and one for poor suckling. Infants were discharged home at a mean (+/- SD) weight of 1864 g (+/- 227), and age 15.6 d (+/- 7.9). Skin-to-skin contact, either by itself or in combination with other methods of warmth, was reportedly followed at home by 67 per cent of the mothers who received home visits. No infant needed readmission for hypothermia either from the neonatal wards or after being discharged home. At follow-up, when body weight had reached greater than or equal to 2500 g, the outcome was graded as 'good' in 64; 'satisfactory' in 6; and 'poor' in 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Temperature↗

Cultured epithelial autografting on meshed skin graft scars: evaluation of skin elasticity.

Many patients with meshed skin graft scars complain of the scars' unsightly appearance and hardness. Since 1989 we have shaved away meshed skin graft scars and then resurfaced the area with autologous cultured epithelium in nine patients. This method improved the disfigurement of meshed skin graft scars, with minimal sacrifice of normal donor skin. Furthermore, autologous cultured epithelium grafted areas had high skin elasticity compared with meshed skin graft scars, as measured with a noninvasive suction device.

Adolescent↗

Comparative safety and efficacy of clarithromycin and cefadroxil suspensions in the treatment of mild to moderate skin and skin structure infections in children.

A prospective, randomized, single (investigator) blind multicenter study was performed to compare the safety and efficacy of clarithromycin and cefadroxil oral suspensions in the treatment of mild to moderate skin and skin structure infections in children. Male and female patients ages 6 months to 12 years were enrolled at 24 study centers in the United States. Patients had signs and symptoms consistent with mild to moderate skin or skin structure infections judged suitable for oral antimicrobial therapy. Clarithromycin oral suspension was given to 118 children in a dose of 7.5 mg/kg (maximum of 500 mg) twice daily; cefadroxil oral suspension was given to 113 children in a dose of 15 mg/kg (maximum of 1000 mg) twice daily. Among clinically evaluable patients clinical success rates (cure plus improvement) were 96% (71 of 74) for clarithromycin and 98% (83 of 85) for cefadroxil (P = 0.664). Bacteriologic cure rates in evaluable clarithromycin and cefadroxil patients were 96% (72 of 75) and 99% (89 of 90), respectively (P = 0.331). Pathogen eradication rates based on 204 evaluable pathogens were 97% in the clarithromycin group and 99% in the cefadroxil group (P = 0.326). Adverse events were mild or moderate and were reported in 25% of clarithromycin and 35% of cefadroxil patients (P = 0.085). In both groups adverse events involved primarily the digestive tract. No significant laboratory changes were noted. Clarithromycin oral suspension appears to be a safe and effective alternative to cefadroxil for the treatment of pediatric skin and skin structure infections.

Administration, Oral↗

Efficacy and safety of ampicillin/sulbactam and cefuroxime in the treatment of serious skin and skin structure infections in pediatric patients. UNASYN Pediatric Study Group.

BACKGROUND: Pediatric skin and skin structure infections are often polymicrobial and require empiric therapy effective against pathogens that may be resistant to many antimicrobial agents. The present study tested the efficacy and safety of a parenteral beta-lactam/beta-lactamase inhibitor combination, ampicillin/sulbactam, and a beta-lactamase-stable cephalosporin, cefuroxime, in serious pediatric skin and skin structure infections requiring hospitalization and parenteral antimicrobial therapy. METHODS: This was a multicenter, randomized, prospective, comparative open label trial that enrolled patients 3 months through 11 years of age. Patients received 150 to 300 mg/kg/day ampicillin/sulbactam in equally divided intravenous doses every 6 h. Cefuroxime was given in a dosage of 50 to 100 mg/kg/day either intravenously or intramuscularly in equally divided doses every 6 or 8 h. Maximum treatment was not to exceed 14 days. Patients could receive subsequent oral antimicrobial treatment at the investigator's discretion. RESULTS: At final evaluation for clinical efficacy, 78.0% (n = 46) of the 59 evaluable patients who received ampicillin/sulbactam were cured and 22.0% (n = 13) were improved. The respective values for the 39 evaluable patients treated with cefuroxime were 76.9% (n = 30) and 23.1% (n = 9). At the end of treatment all pathogens were eradicated from 93.2% (n = 55) of 59 patients treated with ampicillin/sulbactam and from 100% of 39 who received cefuroxime. There were no significant differences between treatments in clinical or bacteriologic efficacy. Both ampicillin/sulbactam and cefuroxime were well-tolerated. CONCLUSION: Both ampicillin/sulbactam and cefuroxime provide safe and effective parenteral antibiotic therapy in pediatric patients with serious skin and skin structure infections.

Ampicillin↗

Multicenter, randomized study comparing levofloxacin and ciprofloxacin for uncomplicated skin and skin structure infections.

BACKGROUND: The fluoroquinolone, levofloxacin, is active against most common pathogens in skin and skin structure infections. METHODS: The efficacy, tolerability, and safety of levofloxacin and ciprofloxacin were compared in a randomized, open-label, multicenter trial of patients with uncomplicated skin and skin structure infections. Of 469 patients treated, 231 received levofloxacin (500 mg qd) and 238 were given ciprofloxacin (500 mg bid). RESULTS: Overall clinical success rates (cured plus improved) for levofloxacin and ciprofloxacin were 98% and 94%, respectively (95% confidence interval [CI], -7.7, 0.7). Overall microbiologic eradication rates by patient were 98% in the levofloxacin group and 89% in the ciprofloxacin group (95% CI, -14.5, -2.7), whereas eradication rates by pathogen were 98% and 90%, respectively (95% CI, -12.6, -3.7). The eradication rate for Staphylococcus aureus was 100% in the levofloxacin group and 87% in the ciprofloxacin group (95% CI, -20.2, -5.1). Treatment-emergent adverse events were comparable, with drug-related adverse events reported in 6% of levofloxacin patients and 5% of ciprofloxacin patients. CONCLUSIONS: Levofloxacin is as effective and safe as ciprofloxacin in the treatment of uncomplicated skin and skin structure infections.

Administration, Oral↗