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Flashlamp-excited dye laser therapy of idiopathic vulvodynia is safe and efficacious.

OBJECTIVE: The management of chronic vulvovaginal pain, not explicable on specific histologic grounds, presents a major problem in referral centers for lower genital tract diseases. STUDY DESIGN: This article reports on a two-step protocol in a sample of 175 medical nonresponders, drawn from a 2-year cohort of 725 women with vulvovaginal pain. The first maneuver was the use of a flashlamp-excited dye laser to selectively photocoagulate symptomatic subepithelial blood vessels in 168 women; the second was the microsurgical removal of chronically painful Bartholin's glands in 52 women not responsive or not suited to flashlamp-excited dye laser photothermolysis. RESULTS: Dye laser response rates were independent of whether patients manifested macroscopic foci of painful erythema ("vestibular adenitis") or just colposcopically apparent hyperemia-ectasia of the individual blood vessels ("pruritic papillomatosis") (56% vs 45% after a single surgical procedure; 76% vs 65% after serial retreatment; p not significant). Conversely, response rates were much lower among women in whom pressure on the Bartholin's glands produced sharp, lancinating pain (15% vs 66% after a single surgical procedure; 22% vs 93% after serial retreatment; p < 0.001). Forty-two (85%) of 50 patients with flashlamp-excited dye laser failure had deep pain; however, the impasse to progress was broken by gland removal. Final response rates were 92.5% (complete response 62%; partial response 30%) in the "surface-only" group and 80.3% in the "surface-plus-deep" group (chi 2 = 14.9; p < 0.001). The major complication was acute bacterial cellulitis, occurring in the first postoperative week. Modification of the treatment protocol to include topical antibiotics with an occlusive dressing reduced the cellulitis rate from 17.2% to 2.5%. In four women (1.8%) Koebner-like exophytic condylomas also developed within 1 month of flashlamp-excited dye laser surgery. CONCLUSION: The availability of a safe, efficacious, and relatively noninvasive treatment should reduce the need for resective surgery in most patients with idiopathic vulvodynia.

Adolescent↗

Immunologic reactions in chronic wounds.

Although, healing is initiated by local inflammation, excessive or prolonged inflammation may delay healing and increase scar potential. Inflammatory cascades in the wound's microenvironment are triggered by complement degradation products; polymorphonuclear leukocyte products; oxygen free radicals; enzymes, particularly proteinases; and microbial products. Infection, ischemia, necrotic or severely damaged tissue, or foreign matter propel and prolong inflammation and challenge host defenses, leaving the patient susceptible to further microbial invasion. Occlusion dressings can minimize necrotic tissue by preventing desiccation, aiding debridement, and providing a barrier against exogenous pathogenic organisms, thus limiting the resulting inflammatory cascade.

Chronic Disease↗

Effect of topical recombinant TGF-beta on healing of partial thickness injuries.

Peptide growth factors produced by platelets, macrophages, epidermal, and dermal cells may play key roles in regulating healing of partial-thickness skin wounds. We examined the effects of recombinant transforming growth factor beta (TGF-beta) on cultures of epidermal and dermal cells in vitro and on healing of partial-thickness injuries in vivo. Increasing concentrations of TGF-beta (0.1, 1, and 10 ng/ml) progressively inhibited serum-stimulated DNA synthesis by up to 95% in cultures of adult human keratinocytes during 48 hr of exposure to TGF-beta. In contrast, TGF-beta (10 and 100 ng/ml) in serum-free media stimulated DNA synthesis by up to 80% compared to serum-free control cultures of adult human dermal fibroblasts. To evaluate the effects of TGF-beta on healing of partial-thickness injuries in vivo, wounds (20 x 20 x 0.6 mm) were created on the dorsal thoracolumbar region of adult pigs by an electrokeratome and were treated daily for 5 days after injury with vehicle or vehicle containing 0.1 or 1 microgram/ml TGF-beta and covered with occlusive dressing. Computerized planimetry of wound photographs demonstrated that TGF-beta treatment stimulated statistically significantly increases in the area of regenerated epidermis compared to wounds treated with saline vehicle on Days 3, 4, 5, and 7 after injury probably due to TGF-beta increasing the rate of epidermal cell migration. In addition, morphometry of biopsy specimens showed that TGF-beta treatment stimulated statistically significant increases in the cross-sectional depths of regenerated dermis compared to wounds treated with saline or Silvadene vehicles on Days 5, 6, and 8 after injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Radioimmunoassay for plasma betamethasone 17-benzoate.

A sensitive radioimmunoassay for plasma betamethasone 17-benzoate has been developed. The antiserum used was obtained by immunizing rabbits with betamethasone 17-benzoate-21-hemisuccinate-bovine-serum-albumin conjugate. All of the endogenous steroids tested cross reacted less than 0.10%. A standard curve was established with a useful range from 0.05-5 ng. Reliability criteria were satisfactory. Measurement of plasma concentrations of betamethasone 17-benzoate was performed in patients and in rabbits following occlusive dressing of betamethasone 17-benzoate cream and gel base.

Animals↗

Radioimmunoassay for dexamethasone 17,21-dipropionate and its metabolites in plasma and urine after topical application.

A sensitive radioimmunoassay for dexamethasone 17,21-dipropionate and its four metabolites in human plasma and urine has been developed using single anti-dexamethasone antiserum. The antiserum was obtained by immunizing rabbits with dexamethasone-3-oxime-bovine serum albumin conjugate. All of the endogenous steroids tested cross-reacted less than 0.07%. Before radioimmunoassay, dexamethasone 17,21-dipropionate and dexamethasone 17-propionate were hydrolyzed to dexamethasone, and 6 beta-OH-dexamethasone 17-propionate was hydrolyzed to 6 beta-OH-dexamethasone in 3% ammonia/methanol at 5 C for 16 h. A standard curve was established with a useful range between 0.005 and 2 ng in the case of dexamethasone, between 0.05 and 5 ng in the case of 6 beta-OH-dexamethasone. Measurement of plasma concentrations and percent urinary excretion of the metabolites in healthy men was performed following occlusive dressing of dexamethasone 17,21-dipropionate cream and ointment. The main metabolites in plasma were dexamethasone 17-propionate and dexamethasone, which increased gradually and reached maximum levels (160-200 pg/mL) at 24-32 h after application. The major metabolites observed in urine were 6 beta-OH-dexamethasone 17-propionate and 6 beta-OH-dexamethasone. Total percentage of their urinary excretions within 72 h after application amounted to 0.28-0.50% of the dose administered.

Administration, Topical↗

High efficiency induction of papillomas in vivo using recombinant cottontail rabbit papillomavirus DNA.

Plasmids containing cottontail rabbit papillomavirus (CRPV) DNA can induce papillomas in vivo, but efficiency has been low. The aim of the present investigation was to explore some of the technical variables involved in inoculation of rabbits with recombinant CRPV DNA in attempts to improve both yield and consistency of papilloma induction. It was found that induction of epidermal hyperplasia, with either a mixture of turpentine and acetone or phorbol esters, produced a marked increase in papilloma yield. An additional powerful factor was the use of very vigorous, cutaneous scarification, sufficient to penetrate the papillary dermis and produce bleeding. When used in combination, papilloma yields were consistent and often reached 90-100% of inoculated sites. A number of other variables which did not consistently affect papilloma yield were tested. These included bleb and puncture injections, plasmid dose, vector type, occlusive dressings, lipofection reagent, carrier DNA, and different methods for plasmid DNA extraction and purification. It is concluded that the most important variables in improving papilloma yields were prior induction of epidermal hyperplasia and vigorous cutaneous scarification.

Acetone↗

Human wound fluid from acute wounds stimulates fibroblast and endothelial cell growth.

One proposed mechanism for the beneficial effect of occlusive dressings on healing is the maintenance of contact between the wound bed and accumulated wound fluid, which is thought to contain growth stimulatory substances. We have examined the effect of human wound fluid on the in vitro growth of human dermal fibroblasts and umbilical vein endothelial cells. Acute wound fluid was collected from six patients undergoing split-thickness skin grafting. The acute wound fluid was sterilely collected daily from underneath a vapor-permeable membrane applied to the donor site and changed every 24 hours for 3 days postoperatively. After seeding in optimal growth media (control) on day 0, cultures of human dermal fibroblasts and umbilical vein endothelial cells were supplemented with or without acute wound fluid on the next day (day 1) and on day 3. As determined by cell counts, 2% acute wound fluid stimulated the growth of human dermal fibroblasts (p less than 0.05) and umbilical vein endothelial cells (p less than 0.01) when these cells were cultured in 2% fetal bovine serum and endothelial growth medium, respectively. Wound fluid from postoperative days 1 or 3 caused the same level of stimulation. The addition of an anti-platelet-derived growth factor antibody to wound fluid resulted in a 45% mean reduction in its stimulatory effect on fibroblast growth (p less than 0.02), suggesting that platelet-derived growth factor contributes to the observed effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Count↗

Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. An alternative treatment modality for solar keratoses, superficial squamous cell carcinomas, and basal cell carcinomas?

BACKGROUND: Topical photodynamic therapy with endogenous porphyrins consists of irradiation of a tumor with visible light after the application of exogenous 5-aminolevulinic acid. OBJECTIVE: To assess the effectiveness of this modality, patients with precancerous conditions and various skin cancers were treated. METHODS: Thirteen patients with 70 skin lesions were enrolled. Standard treatment involved the topical application of 20% 5-aminolevulinic acid in an oil-in-water emulsion. The emulsion was applied under an occlusive dressing for 4 to 8 hours before exposure to photoactivating light. RESULTS: We observed a complete response after a single treatment for all 9 solar keratoses, 5 of 6 early invasive squamous cell carcinomas, and 36 of 37 superficial basal cell carcinomas. Only 1 of 10 nodulo-ulcerative basal cell carcinomas completely resolved. Eight cutaneous metastases of malignant melanoma were therapeutic failures. CONCLUSION: Topical photodynamic therapy with endogenous porphyrins is effective for superficial epithelial skin tumors.

Administration, Cutaneous↗

The role of extracellular polysaccharide substance produced by Staphylococcus epidermidis in miliaria.

BACKGROUND: Previous studies have indicated that cutaneous bacteria, particularly coagulase-negative staphylococci, play a role in the pathogenesis of miliaria. An accumulation of periodic acid-Schiff (PAS)-positive material has been described as blocking the sweat duct in miliaria. Furthermore, a PAS-positive extracellular polysaccharide substance (EPS) has been identified as a product of some strains of Staphylococcus epidermidis. OBJECTIVE: We evaluated the relative ability of various species of coagulase-negative staphylococci to induce miliaria with particular reference to the potential role of EPS. METHODS: We inoculated various strains of coagulase-negative staphylococci on the volar forearms of subjects under an occlusive dressing coupled with thermal stimulation. Ability to induce miliaria as well as microbiologic, histologic, and immunostaining features were evaluated. RESULTS: Miliaria was induced only with strains of S. epidermidis; other species including S. haemolyticus, S. hominis, S. cohnii, S. saprophyticus, and S. simulans were not capable of inducing miliaria. Moreover, only S. epidermidis strains capable of producing EPS were capable of inducing miliaria. CONCLUSION: Our data indicate that EPS is the PAS-positive material that obstructs the delivery of sweat to the skin surface in miliaria and therefore demonstrate that the EPS produced by S. epidermidis plays a central role in the pathogenesis of miliaria. Furthermore, in a survey of staphylococcal flora isolated from 68 subjects, EPS-producing strains were found to be common.

Adolescent↗

Studies on benzyl acetate. III. The percutaneous absorption and disposition of [methylene-14C]benzyl acetate in the rat.

[methylene-14C]Benzyl acetate was applied over an area of 6.25, 12 or 18 cm2 to the shaved backs of male Fischer 344 rats under an occlusive dressing at dose levels of 100, 250 and 500 mg/kg. The compound was administered either as the neat substance or as a 50% (v/v) solution in ethanol. After 6 hr the dressing was removed, the shaven area was washed with ethanol and the dressing and washings were counted for 14C. Urine and faeces were collected for 72 hr from the start of treatment and urinary metabolites were assayed by radio-TLC and HPLC. Following administration of the neat compound, a significant proportion of the dose was recovered from the application site (28-48%) and a similar proportion (28-46%) was absorbed and excreted in the 0-24-hr urine. Excretion of 14C in the urine over 0-24 hr accounted for c. 95% of absorbed 14C in all cases, and total recovery of radioactivity was 79-84% with less than 2% of the dose present in the carcass at the end of the experiments. The extent of absorption of benzyl acetate per unit area of skin, as assessed by the recovery of its metabolites in urine, rose with increasing concentration (mg/cm2) of the test compound on the skin. The absorption of topically applied benzyl acetate was essentially the same when the dose was administered in a 50% ethanolic solution. In all cases, the major urinary metabolite was hippuric acid (c. 95% of urinary 14C), together with much smaller amounts of benzoyl glucuronide, benzoic acid and benzylmercapturic acid. The distribution of 14C in the tissues was examined 6 and 24 hr after the topical application of 5 mg [methylene-14C]benzyl acetate/kg as a 1% (v/v) solution in ethanol to rats. Radioactivity in all carcasses was less than 4% of the administered dose and levels in all the organs examined were lower at 24 than at 6 hr.

Animals↗

Staphylococcal toxic shock syndrome in a paediatric burn unit.

A case of staphylococcal toxic shock syndrome (TSS) in a 15-year-old patient undergoing reconstructive burn surgery is reported. This syndrome, first described in menstruating women using tampons, can also occur as a postsurgical complication. The epidemiology, microbiology, clinical presentation and management of non-menstrual TSS are discussed and correlated with the patient present. We advise caution in the use of occlusive dressings and recommend constant isolation of patients with open wounds colonized with a TSST-1 producing strain of Staph. aureus.

Adolescent↗

[Treatment of burns in infants].

Because of the potential severity of their residual deformities, burn injuries in infants justify an early management in specialized centres when they cover more than 5% of body surface and in every case when hands, face, or external genitalia are concerned. Cooling with cold water is the first aid treatment to be performed as early as possible after the injury. The treatment in specialized centres must be both general and surgical. General treatment includes fluid and electrolyte therapy, temperature control, appropriate nutrition and pain suppression. Pain suppression is a major part of the treatment and morphine must be largely used. Surgical treatment starts as soon as the patient arrives in the centre and is eventually performed under general anesthesia: all the burned areas are covered with occlusive dressings. Infections are prevented by systematic cultures and adjusted antibiotic therapy. A vigorous rehabilitation program must be instituted as soon as possible: massages, compressive clothes, splints, physical therapy, plastic surgery. Primary prevention by sustained parental education is important in order to reduce the frequency of burn injuries in infants.

Age Factors↗

A comparison of EMLA cream versus nitrous oxide for pediatric venous cannulation.

STUDY OBJECTIVE: To compare the analgesic and anxiolytic effects of nitrous oxide (N2O) when inhaled by face mask with those of a cutaneous application of a eutectic mixture of local anesthetics (EMLA) cream with lidocaine and prilocaine during pre-operative venous cannulation in children. DESIGN: Prospective, randomized study. SETTING: Outpatient presurgical area and operating rooms of a freestanding children's hospital. PATIENTS: 50 unpremedicated ASA status I and II outpatients, aged 6 to 12 years, undergoing an elective surgical procedure. INTERVENTIONS: Each patient received either 70% N2O in 30% oxygen (O2) administered by face mask for 120 seconds or an application of 2.5 g of EMLA cream under an occlusive dressing for a minimum of 60 minutes. All patients then underwent a single attempt at venous cannulation in the dorsum of the hand with a 22-gauge intravenous catheter. MEASUREMENTS AND MAIN RESULTS: A visual analog scale (VAS) pain score (0 to 100) was generated by the investigator and subsequently obtained from each patient immediately after the venous cannulation was completed. The pain scores generated by the investigator were significantly lower in the N2O group than the EMLA cream group (p = 0.001). When compared with the patients in the EMLA cream group, the patients in the N2O group also self-reported significantly lower VAS pain scores (p = 0.006). CONCLUSIONS: N2O administered by face mask appears to provide greater anxiolysis and attendant superior analgesia for pediatric venous cannulation than a cutaneous application of EMLA cream.

Administration, Topical↗

Repetitive photodynamic therapy with topical delta-aminolaevulinic acid as an appropriate approach to the routine treatment of superficial non-melanoma skin tumours.

Photodynamic therapy (PDT) with topical delta-aminolaevulinic acid (ALA) is considered as a valuable tool for treating non-melanoma skin tumours, but there is no consensus about the methods of treatment, where they should be used and the rates of complete responses. This study reports the treatment of 50 actinic keratoses (AKs), 23 superficial basal cell carcinomas (BCCs), 30 nodular BCCs, 4 pigmented BCCs, 12 superficial squamous cell carcinomas (SCCs), 6 nodular SCCs, 6 Bowen's diseases and 4 keratoacanthomas (KAs). A 20% ALA emulsion was applied under an occlusive dressing for 6-8 h and the skin was then irradiated with 630 nm light from a dye laser. Treatments were delivered every other day until complete clinical disappearance of the lesions was observed. ALA-PDT was interrupted in the case of a partial response if, after two additional treatments, no further improvement was observed. All AKs (50/50), superficial BCCs (23/23), Bowen's diseases (6/6) and KAs (4/4) showed a complete response. In addition, 91.6% (11/12) superficial SCCs, 80.0% (24/30) nodular BCCs and 66.7% (4/6) nodular SCCs responded completely to the treatment. All 4 pigmented BCCs were resistant to the therapy. Some (59) of the treated areas that appeared completely responsive were excised for serial histopathological examination and the remaining 63 were followed-up for 24-36 months (median value, 29 months). Comprehensively, the rates of complete responses decreased after taking into consideration the results of these histological examinations and the long-term follow-up. The final response rates are as follows: 84.0% (42/50) AKs, 86.9% (20/23) superficial BCCs, 50% (15/30) nodular BCCs, 83.3% (10/12) superficial SCCs and 33.3% (2/6) nodular SCCs. The rates of complete responses of Bowen's diseases and KAs remained at 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

One hundred percent fascial approximation with sequential abdominal closure of the open abdomen.

BACKGROUND: Damage-control surgery and the recognition of the abdominal compartment syndrome have improved patient outcomes but at the cost of an open abdomen. Multiple techniques have been introduced to obtain fascial closure for the open abdomen to minimize morbidity and cost of care. We performed a modification of the vacuum-assisted closure (VAC) technique that provided constant fascial tension, hypothesizing this would result in a higher rate of primary fascial closure. METHODS: After initial temporary closure of the abdomen after post-injury damage control or decompressive laparotomy for abdominal compartment syndrome, we began the sequential closure technique. The technique begins by covering the bowel with the multiple white sponges overlapped like patchwork, and the fascia is placed under moderate tension over the white sponges with #1-PDS sutures. Large black VAC sponges are placed on top of the white sponges and affixed with an occlusive dressing and standard suction tubing is placed. Patients are returned to the operating room for sequential fascial closure and replacement of the sponge sandwich every 2 days, with a resulting decrease in the fascial defect. RESULTS: Fourteen patients underwent sequential abdominal closure during the study period: 9 owing to damage control surgery and 5 owing to secondary abdominal compartment syndrome. Average time to closure was 7.5 +/- 1.0 days (range 4-16) and average number of laparotomies to closure was 4.6 +/- 0.5 (range 3-8). All patients attained primary fascial closure. CONCLUSION: We propose a modification of the previously described vacuum-assisted closure technique that achieves 100% fascial approximation in our limited experience. Further application and refinement of this technique may eliminate the need for delayed complex and costly reconstructive abdominal wall procedures for the open abdomen.

Abdominal Injuries↗

Mesenchymal-epithelial interactions in the skin: aiming for site-specific tissue regeneration.

Since trunk skin (or non-palmoplantar skin) is less durable under mechanical stress than sole skin (palm, plantar or palmoplantar skin), conventional trunk-derived skin grafts (including the trunk dermis) commonly result in erosion and ulceration when transplanted on to plantar wounds caused by various injuries including, diabetes mellitus or collagen diseases (including systemic sclerosis, polyarthritis nodosa and rheumatoid arthritis). However, trunk-derived epidermis can adopt a plantar phenotype, characterized by keratin 9 expression, hypopigmentation and thick suprabasal layers, through factors derived from plantar dermal fibroblasts in the wounds. Thus, intractable plantar wounds with exposed bones can be treated with the combination of bone marrow exposure, occlusive dressing and epidermal grafting. The higher expression of dickkopf 1 (DKK1), an inhibitor of canonical Wnt/beta-catenin signals, in the plantar dermis partly explains these phenomena. Thus, mesenchymal-epithelial interactions play important roles not only in embryogenesis (the embryonic development) but also in maintaining the homeostasis of adult tissue. The topographical (site-specific) interactions of growth factors and substances, including DKKs, fibroblast growth factors (FGFs) and transforming growth factor-beta (TGF-beta) family proteins including bone morphogenetic proteins (BMPs), may explain the site-specific differences in the skin in addition to the expression patterns of HOX genes and sonic hedgehogs (Shhs). We review the importance of dermal-epidermal interactions in tissue homeostasis and regeneration, especially in palms and soles.

Animals↗

EMLA-induced methemoglobinemia and systemic topical anesthetic toxicity.

This case report illustrates an adult presenting with the simultaneous occurrence of both methemoglobinemia (MetHb) and systemic toxicity from the topical application of local anesthetics while undergoing laser epilation therapy of the legs. The concurrent development of both is considered uncommon in this setting and may have been related to several factors, including her recent previous treatment, increased absorption secondary to abraded skin with the addition of occlusive dressing, and possible alteration of protein binding and drug metabolism due to the use of medications. The clinical manifestations and mechanisms of MetHb and systemic local anesthetic toxicity are discussed.

Adult↗

Adverse effects of EMLA (lidocaine/prilocaine) cream and efficacy for the placement of jugular catheters in hospitalized cats.

EMLA is a lidocaine/prilocaine cream used for topical analgesia in human pediatric patients. The purpose of this study was to establish the safety of EMLA in clinically ill cats, to measure systemic absorption and to determine whether EMLA reduced the need for sedation for the placement of jugular catheters. Thirty-one cats were randomized to either a placebo or EMLA cream group. Cream was applied to a 10 cm(2) area over the jugular vein, with 1h of occlusive dressing. Neither anesthetic was systemically absorbed in any cat, and no adverse clinical signs were observed. Struggling during catheter placement was less in the EMLA-treated cats compared to placebo, but did not reach significance (P = 0.06). Jugular catheters were successfully placed in 60% of EMLA-treated cats and 38% of placebo cats; this difference was not statistically significant and may not justify the added steps of EMLA cream administration for this purpose. However, EMLA does appear to be safe in clinically ill cats, and may be useful for other applications such as for skin mass removal or repeated venepuncture.

Analgesia↗