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Xanthelasma palpebrarum: treatment with the ultrapulsed CO2 laser.

BACKGROUND AND OBJECTIVE: Due to its delicate location near the eye and the high recurrence rate, the therapy of xanthelasma palpebrarum is a difficult surgical task. Besides chemical, physical, and surgical procedures, various laser systems have been used to treat these lesions (argon laser, pulsed dye laser, and CO2 laser). This study was designed to critically evaluate the use of the ultrapulsed CO2 laser for the treatment of xanthelasma palpebrarum. STUDY DESIGN/MATERIALS AND METHODS: We report about the standardized treatment of 23 patients (52 periorbital xanthelasmas) and the results obtained after one treatment with a new generation, ultrapulsed CO2 laser (COHERENT Ultrapulse 5000C, Palo Alto, CA; 250-500 mJ; 600-900 microsec; 10,600 nm). The followup time was 10 months. RESULTS: All lesions could be removed completely with a single laser treatment. As for side effects, only transient pigmental changes (4% hyperpigmentations, 13% hypopigmentations) and no visible scarring was observed. Three patients (13%) developed a recurrence of xanthelasma. CONCLUSIONS: The ultrapulsed CO2 laser is an effective and safe therapeutic alternative to the hitherto described approaches.

Adult↗

Clinical and histologic evaluation of six erbium:YAG lasers for cutaneous resurfacing.

BACKGROUND: Several erbium:YAG lasers are currently available for cutaneous laser resurfacing. Although different laser systems are purported to produce equivalent laser energies to produce similar laser-tissue interactions, no comparative clinical or histologic studies have been performed to objectively demonstrate their relative efficacies. OBJECTIVE: The purpose of the present study was to examine the in vivo clinical and histopathologic effects of six different erbium:YAG resurfacing lasers. METHODS: A blinded, prospective study using six different erbium lasers (Candela, Continuum Biomedical, HGM, MDLT, SEO, Sharplan/ESC) was performed. The facial halves of 12 patients were randomly resurfaced with one of the six laser systems by using an identical laser technique at 5.0 J/cm2. Intraoperative skin biopsies were obtained after each of three laser passes in two patients for blinded histologic determination of tissue ablation level and presence of residual thermal damage. Clinical assessments of reepithelialization rates, severity and duration of erythema, side effects, and degree of clinical improvement were made at 0.5, 1, 2, 4, 12, 26, and 52 weeks postoperatively. RESULTS: Irrespective of the erbium laser system used, complete reepithelialization typically occurred at 0.5 weeks and resolution of erythema was noted within 1-2 weeks postoperatively. A mean clinical improvement of 50% was observed, with photodamaged skin showing greater improvement than scarred skin. The most common postoperative side effect was hyperpigmentation, with all affected patients having either darker skin tones or preceding dermal inflammation. Three laser passes were needed to effect total epidermal ablation when using any one of the erbium:YAG systems. CONCLUSIONS: Equivalent clinical and histologic results were seen after each of the six erbium:YAG lasers studied. Erbium:YAG laser resurfacing can be used to significantly improve mild cutaneous photodamage and atrophic scars.

Adult↗

Long-pulsed alexandrite laser-assisted hair removal at 5, 10, and 20 millisecond pulse durations.

BACKGROUND: Several laser systems with varying wavelengths, pulse durations, and energy fluences are currently utilized for hair removal. However, the ideal laser parameters and treatment candidates for photoepilation remain largely unknown. The medical literature lacks a wealth of experimental data to sufficiently document the long-term safety and efficacy of laser-assisted hair removal. This study examines the clinical efficacy and side effect profile of long-pulsed alexandrite laser-assisted hair removal utilizing laser pulse durations of either 5, 10, or 20 milliseconds (ms). STUDY DESIGN/METHODS: Laser-assisted hair removal was performed on 36 subjects with a long-pulsed alexandrite laser. Areas of unwanted hair growth on the face, back, and legs were divided linearly into four 1 cm2 or 2 cm2 quadrants. Experimental regions included a control quadrant and three additional quadrants, which were treated with the alexandrite laser using an average fluence of 18 J/cm2, with a 10 mm spot size at either a 5, 10, or 20 ms pulse duration. Hair counts and photographs were obtained before treatment, immediately following irradiation, 1 week and 1, 3, and 6 months postoperatively. RESULTS: All laser-treated quadrants displayed a significant delay in hair regrowth compared to control nontreated quadrants at postoperative week 1 and months 1 and 3. Hair counts were reduced by 66% at 1 month, 27% at 3 months, and 4% at 6 months. No significant differences in clinical efficacy or side effect profiles were observed between treatment quadrants, yet a trend towards less post-treatment erythema and hyperpigmentation was noted with the 20 ms pulse duration. CONCLUSIONS: Equivalent long-term hair removal for up to 6 months was achieved with the long-pulsed alexandrite laser at 5, 10, and 20 ms pulse durations at an average fluence of 18 J/cm2. Side effects were limited and transient.

Adult↗

Treatment of venous malformations with an intense pulsed light source (IPLS) technology: A retrospective study.

BACKGROUND AND OBJECTIVE: The intense pulsed light source (IPLS) technology provides an innovative concept in the treatment of vascular lesions. We investigated the effectiveness of IPLS in the treatment of venous malformations. STUDY DESIGN/MATERIALS AND METHODS: A retrospective study of 11 patients with venous malformations (VMA) treated with IPLS was initiated. Clinical VMA characteristics recorded were size and location. Data collected included treatment parameters (filters, pulse duration, fluence, and pulse sequencing), % clearance, and side effects (e.g., swelling, blisters, crusting, pain, altered pigmentation, and scarring). RESULTS: Good and very good (70-100%) clearance was achieved in 8 malformations smaller than 100 cm(2). Especially small lesions needed only 2-3 treatments. Three VMA larger than 100 cm(2) could be cleared well in an average of 18 sessions. The most frequently used parameters were the 590 nm filter in long pulse mode, triple pulses, and fluences at an average of 80.4 J/cm(2). Side effects included prolonged erythema in 23.6, swelling in 17.9%, crusting in 4.7%. Bleeding, hypo-, hyperpigmentation, and scarring were rare (0.9% respectively). CONCLUSION: IPLS presents an effective method for treating VMA, especially small malformations, with a justifiable rate of side effects when optimal parameters are chosen.

Adolescent↗

Variable pulse erbium:YAG laser skin resurfacing of perioral rhytides and side-by-side comparison with carbon dioxide laser.

BACKGROUND AND OBJECTIVE: Laser resurfacing of facial rhytides has become a popular treatment option for many patients with wrinkles, photoaging, and acne scarring. Laser wavelength/pulse duration options and new techniques continue to shorten the healing phase associated with laser skin resurfacing while maintaining clinical efficacy. Variable pulse erbium:YAG (Er:YAG) laser systems are now available that offer the surgeon the ability to vary the Er:YAG pulse duration from a pulse that is primarily ablative to one that is more thermal. The objective of this study was to evaluate the histologic effects created with a variable pulse Er:YAG laser. To study prospectively the clinical effects on upper lip rhytides with a variable pulse Er:YAG laser when compared side by side with pulsed carbon dioxide (CO(2)) laser resurfacing. STUDY DESIGN/MATERIALS AND METHODS: Forty-two treatment sites on 21 patients were randomized and evaluated after treatment of the upper lip region with CO(2) laser resurfacing on one side and a variable pulse Er:YAG laser on the other. Patient diaries were maintained to assess erythema, crusting, pain, and pigmentary changes. Blinded objective grading of improvement was performed. Chromometer measurements were obtained to analyze erythema. RESULTS: The variable pulse Er:YAG laser treatment reduced the duration of crusting on average from 7.7 days with CO(2) to 3.4 days. Chromometer measurements noted decreased postoperative erythema. Grading by physicians in a blinded manner showed 63% improvement for the CO(2) treatment site and 48% improvement in the variable pulse Er:YAG site. No cases of permanent hyperpigmentation, hypopigmentation, or scarring occurred. CONCLUSION: The variable pulse Er:YAG laser resurfacing is a safe and effective resurfacing tool, which combines ablative and thermal modalities. The protocol used in this study approaches but does not equal the results we have traditionally seen with CO(2) laser resurfacing.

Carbon Dioxide↗

Percutaneous absorption of [3H]tretinoin and systemic exposure to mequinol after dermal application of 2% mequinol/0.01% [3H]tretinoin (Solagé) solution in healthy volunteers.

Solagé is a combination product composed of 2% mequinol (4-hydroxyanisole) and 0.01% tretinoin (all-trans-retinoic acid) in an ethanolic solution, which is being studied for its safety and efficacy as a topical treatment for disorders of skin hyperpigmentation. The purpose of this study was to evaluate the extent of percutaneous absorption of [3H]tretinoin and to estimate the systemic exposure to mequinol from this combination product when topically applied to the backs of healthy subjects. Eight subjects received bid topical applications of nonradiolabelled 2% mequinol/0.01% tretinoin solution on a 400 cm2 area of the back for 14 days. The subjects then received a single topical application of 2% mequinol/0.01% [3H]tretinoin solution. After 12 h, the radiolabelled dose was removed and bid treatment with nonradiolabelled 2% mequinol/0.01% tretinoin solution was continued for 7 days. Plasma, urine and faecal samples were analysed for total radioactivity and plasma was analysed for both mequinol and tretinoin by GC/MS procedure. Mean percutaneous absorption of [3H]tretinoin based on the cumulative recoveries of radioactivity in the urine and faeces was about 4.5% (median 2.18%). Tretinoin concentrations in plasma did not increase above endogenous levels. This was consistent with the concentrations of radioactivity in plasma, which showed an average Cmax of 91 pg-eq/mL (median 26 ng/mL). Average Cmax and AUC(0-12 h) values for mequinol were 10 ng/mL and 33 ng h/mL, respectively. Based on the results of this study, systemic toxicity from topical application of tretinoin in this formulation is unlikely, because percutaneous absorption of tretinoin is minimal and because endogenous levels of tretinoin are not increased following bid dosing with this combination formulation. The safety of mequinol in this combination formulation is supported by the low systemic exposures of the subjects in this study compared with the systemic exposures at the highest doses in the dermal toxicity studies in mice (16.6-fold) and rats (34.6-fold).

Administration, Topical↗

Analphoid 3qter markers.

Two cases of marker chromosomes derived from a non-centromeric location were studied to determine the characteristics of these markers with respect to the presence of functional centromeres and whether an associated phenotype could be described. The markers were characterized by fluorescence in situ hybridization and centromeric protein studies. Assessments were done to identify clinical features. Case 1 is a girl referred at age 1.5 years with swirly areas of hyperpigmentation, bilateral preauricular pits, hypotonia, developmental delay, and seizures. Case 2 is a male first evaluated as a newborn and then later during the first year of life. He had streaky hypopigmentation, right preauricular pit, accessory nipples, postaxial polydactyly, asymmetric cerebral ventricles, duplicated right kidney, a right pulmonary artery stenosis, and seizures. Mosaicism for an extra marker from the 3qter region was present in both cases. Both markers had a constriction near one end and were C-band negative. Centromeric protein studies indicated absence of CENP-B, presence of CENP-C (data for case 1 only), and presence of CENP-E. Marker chromosomes were thus identified with a chromosomal origin far from their usual centromeric region and yet appeared to have functional centromeres. These two cases did not permit a specific clinical phenotype to be ascribed to the presence of tetrasomy for 3q26.2 approximately 3q27.2-->3qter.

Autoantigens↗

Incontinentia pigmenti in a surviving male is accompanied by hypohidrotic ectodermal dysplasia and recurrent infection.

Familial Incontinentia pigmenti (IP) is a rare X-linked dominant condition. The affected cases have characteristic skin lesions, hair, eye, teeth and nail abnormalities and may also have neurological problems. The diagnosis has traditionally been made on clinical grounds. Segregation analysis has suggested that it is lethal in males. Only one liveborn male has been reported who died at one day of age. Female cases of IP survive because of the moderating effects of Lyonization. This child was the affected son of a female with IP. He had a novel phenotype consistent with hypohidrotic ectodermal dysplasia with immune deficiency (HED-ID) but with additional features: he had major problems with hematological disturbances, failure to thrive due to malabsorption, recurrent infections, generalized osteosclerosis and lymphedema of his lower limbs. He also demonstrated some typical features of IP with a generalized reticular skin hyperpigmentation, sparse hair and delayed eruption of teeth. The gene for NEMO (NF-kappa B Essential Modulator) has recently been shown to be mutated in cases of IP. Furthermore, most (80%) of patients possess a recurrent genomic rearrangement that deletes part of the gene resulting in an inactive NEMO protein. In the male case described here, a NEMO stop codon mutation has been identified that has arisen de novo in his affected mother. This mutation is likely to have a less severe effect on NEMO activity and may explain why this child survived for two years and 7 months.

Codon, Terminator↗

Further experience in treating patients with hepatocellular carcinoma in Uganda.

One hundred and thirty nine patients with histologically proven hepatocellular carcinoma (HC) were admitted to the Uganda Cancer Institute for treatment. The patients were considerably younger and seemed to have more advanced disease than HC patients in Europe and in North America. Of the 99 evaluable patients, 50 received Adriamycin intravenously; of these, 44% responded, with 10% achieving complete responses. Intraarterial Adriamycin tended to increase the response rate to 75%, but this may be merely a reflection of patient selection. Combination of Adriamycin with other drugs (dichloromethotrexate, 5-azacytidine, Rezoxane and cyclophosphamide) did not enhance its therapeutic effectiveness. The alphafetoprotein response curves observed when Adriamycin was combined with dichloromethotrexate suggested possible antagonisms between the two drugs. Hepatic artery ligation (HAL) is a good and simple palliative procedure with response rates similar to i.v. Adriamycin. However, the administration of Adriamycin after HAL tended to improve on response rates and survival. The toxicities observed were mainly myelosuppression, gastrointestinal disturbance, alopecia, and hyperpigmentation of the skin and mucous membranes.

Adolescent↗

Mucocutaneous side effects of Brequinar sodium. A new inhibitor of pyrimidine de novo biosynthesis.

Brequinar sodium (NSC 368390; DUP 785) is a new inhibitor of pyrimidine de novo biosynthesis which has completed Phase I clinical trials within the framework of the Early Clinical Trials Group of the European Organization for Research and Treatment of Cancer (EORTC). The main side effects of this compound are myelosuppression, nausea and vomiting, stomatitis and/or mucositis, and skin rash. In this report, the authors describe the pattern of mucocutaneous side effects of Brequinar sodium in patients who received the drug by four different schedules: (1) short-term intravenous (IV) infusion every 3 weeks; (2) weekly; (3) twice weekly; and (4) five times daily every 4 weeks. Mucocutaneous toxicities of Brequinar sodium included mainly cytotoxic reactions (stomatitis and/or mucositis and skin rash). However, rare episodes of local reactions (phlebitis at the site of injection), photosensitivity reactions (to sun light), angioneurotic edema, and localized secondary hyperpigmentation of the inflamed skin also occurred. Stomatitis and/or mucositis appeared to be dose-dependent and schedule-dependent. The skin rash consisted of a drug-induced toxic dermatitis which occurred mostly at the highest dose levels. Initial recommendations for the management of mucocutaneous toxicities of Brequinar sodium during Phase II trials are discussed.

Aged↗

Blue nevus and nevus of Ota associated with dural melanoma.

A 41-year-old woman with a complex congenital nevus that possessed features of both a blue nevus and a nevus of Ota is described. She was found to have melanotic hyperpigmentation of the underlying subcutaneous tissue and dura mater. Two separate melanomas developed in the tissues underlying her nevus (one in the subcutaneous tissue and another intracranially, arising from the dura).

Adult↗

A kindred with multiple endocrine neoplasia type 2A associated with pruritic skin lesions.

BACKGROUND: A kindred affected by multiple endocrine neoplasia type 2A (MEN 2A), associated with symmetric, bilateral, scapular pruritic skin lesions (PSL), is reported. METHODS: There were 21 members, including the propositus, in four generations. Screening of 10 family members showed a palpable thyroid tumor in 1 and positive results for a pentagastrin test in 7 others. Two of these patients had surgically confirmed pheochromocytoma. Two others had a biochemical diagnosis of pheochromocytoma but did not have surgery. RESULTS: Medullary thyroid carcinoma was confirmed in five patients and nodular C-cell hyperplasia in another. In five affected adults, PSL were observed in the interscapular region, crossing the midline in some. These lesions were characterized by hyperkeratosis and hyperpigmentation. In all the patients, the pruritus had been present long before the clinical or biochemical diagnosis. Skin biopsies were performed in two of these patients. No amyloid deposits were found (Congo red stain and electron microscopic examination were used). Two children (14 and 6 years old) in the fourth generation complained of scapular pruritus, although skin lesions were not apparent. CONCLUSIONS: Localized PSL must be sought when screening for MEN 2A.

Adolescent↗

Adrenocorticotropic hormone--producing thymic carcinoid in a teenager.

Carcinoid of the thymus rarely occurs during childhood. The authors identified eight cases in patients younger than 17 years of age. All were associated with Cushing syndrome. Adrenocorticotropic hormone (ACTH) produced by the tumor may be released intermittently, delaying the findings of Cushing syndrome. The authors describe a case of ectopic ACTH production in a teenaged boy who had longstanding hyperpigmentation, increased ACTH levels, and normal cortisol levels. Magnetic resonance imaging of the pituitary had normal findings. Subsequently, severe Cushing syndrome developed. Computed tomography (CT) scans of the chest showed a mediastinal mass that proved to be a thymic carcinoid. The lesion was inoperable. Radiation and chemotherapy were of limited benefit. Metyrapone was used to control hypercortisolism. The patient died with extensive metastases 6 years after initial presentation. CT scans of the chest should be performed in an attempt to localize ectopic ACTH-producing tumors. Surgical excision of the lesion is the treatment of choice. Control of hypercortisolism is essential.

Adolescent↗

Genetic heterogeneity in Peutz-Jeghers syndrome.

LKB1, the human gene encoding a serine threonine kinase, was recently identified as a susceptibility gene for Peutz-Jeghers syndrome (PJS), a disease characterized by the constellation of intestinal hamartomata, oral mucocutaneous hyperpigmentation, and an increased risk for gastrointestinal as well as extraintestinal malignancies. To date, the majority of individuals with PJS have been found to have genetic alterations in LKB1, most of which result in protein truncation. Additionally, linkage analyses have suggested a modicum of genetic heterogeneity, with the majority of PJS families showing linkage to the LKB1 locus. In this study, we evaluated five kindreds with greater than two affected family members, five PJS probands with only one other affected family member, as well as 23 individuals with sporadic PJS for mutations within the LKB1 gene. Conformation sensitive gel electrophoresis was utilized for the initial screen, followed by direct sequence analysis for characterization. Long-range PCR was used for the detection of larger genetic insertions or deletions. Mutation analysis revealed genetic alterations in LKB1 in two probands who had a family history of PJS. LKB1 mutations were detected in only four of the remaining 23 cases of sporadic PJS. These data suggest the presence of significant genetic heterogeneity for PJS and the involvement of other loci in this syndrome.

AMP-Activated Protein Kinase Kinases↗

Arsenic--state of the art.

Approximately 1.5 million workers in the United States are exposed to arsenic. Occupational exposure is primarily by inhalation. NIOSH recommends that time-integrated exposure to arsenic in air not exceed 2 micrograms/m3. Recent exposure is accurately measured by urine assay; urine arsenic concentrations above 50 micrograms/liter indicate increased absorption. Hair assay is a semiquantitative index of past exposure. Toxicity is associated primarily with the trivalent (3+) form of arsenic. Acute poisoning is caused most commonly by contaminated food or drink; it is rarely occupational. Chronic intoxication is characterized by dermatitis, hyperpigmentation, keratoses, peripheral neuropathy (primarily sensory), irritation of the upper and lower respiratory tract, and occasionally by hepatic toxicity and peripheral vasculopathy (blackfoot disease). Arsenic is not carcinogenic in animal species, but is mutagenic in Syrian hamster cells. In man, arsenic is known definitely to cause cancer of skin, lung, and liver (angiosarcoma) and possibly to cause lymphoma.

Animals↗

Fiberglass dermatitis from printed circuit boards.

Seven cases of fiberglass dermatitis among production operators in the electronics industry are reported. This was due to the repeated daily handling of printed circuit boards (PRCBs). The predominant complaint of the workers was itch of the lateral aspects of the fingers and finger webs. In six workers, unroofed vesicles, pinhead areas of postinflammatory hyperpigmentation, and excoriation marks were noted at these sites. Skin stripping of the affected sites confirmed the presence of fiberglass spicules in all cases. The glass fibers had diameters of 11-16 microns. Patch testing of six of the workers with the European Standard series of allergens revealed no relevant work-related contact sensitizers. Microscopic examination of the free edges and scrapings from the PRCBs showed glass fibers of similar fiber length and diameter to those found in the workers' skin. Fiberglass can be used as a reinforcement filling material in some types of PRCBs. Free edges of such PRCBs have easily detached fiberglass spicules. Workers in frequent contact with these PRCBs can have a fiberglass-induced irritant dermatitis. Preventive measures could include the use of PRCBs with less free fiberglass at its edges, vacuuming of the newly cut boards, use of dusting powder, protective devices and emollients, and improved personal hygiene of the workers.

Adult↗

Apparently new osteodysplastic and primordial short stature with severe microdontia, opalescent teeth, and rootless molars in two siblings.

A Thai man and his sister affected with a newly recognized syndrome of proportionate primordial short stature are reported. The patients had severe intrauterine and postnatal growth retardation, prominent nose and nasal bridge, small pinnae, large sella turcica, areas of hypo- and hyperpigmentation of skin, dry and thin scalp hair, and long and straight clavicles. Ivory epiphyses and cone-shaped epiphyses of the hands were found when they were young, but most of them disappeared as they grew up. Scaphoid and trapezium had angular appearance. The second toes were unusually long. Distal symphalangism of toes and barchymesophalangy of fingers were noted. The findings that appear to distinguish this syndrome from the previously reported syndromes are long second toes, opalescent and rootless teeth, severe microdontia, severely hypoplastic alveolar process, and unerupted tooth. The mode of inheritance is suspected to be autosomal recessive.

Abnormalities, Multiple↗

Pigmentary mosaicism of the hyperpigmented type in two half-brothers.

Pigmentary mosaicism is a heterogeneous cutaneous phenotype that is often associated with extracutaneous anomalies. It is widely accepted that these phenotypes arise de novo as a result of a postzygotic mutation, leading to a mosaic status of the embryo. In the vast majority of cases, the occurrence of pigmentary mosaicism is sporadic. We report two paternal half-brothers affected with pigmentary mosaicism of the hyperpigmented type. The hyperpigmentation in both patients is distributed along the lines of Blaschko. In addition, mental retardation, facial asymmetry, short stature, scoliosis, and short fingers with clinodactyly of the 5th digit were noted in one of them. Chromosome analysis in this 15-year-old patient demonstrated a mosaic 46,XY,dup(3)(p21.3;pter)/46,XY with 12% aberrant cells in lymphocytes and 2% in skin fibroblasts derived from a hyperpigmented area. His nine-year-old half-brother had similar systematized hyperpigmented skin lesions, macrocephaly, facial asymmetry, and clinodactyly of the 5th digit. Chromosome analysis of peripheral lymphocytes showed a normal karyotype 46,XY. A skin biopsy could not be obtained. So far, some familial cases of hypopigmentation along the lines of Blaschko have been reported, but familial occurrence of the hyperpigmented type of pigmentary mosaicism appears to be extremely unusual. It is difficult to establish a causal relationship with the chromosomal mosaicism as observed in patient 1. Paradominant transmission seems unlikely because this would likewise imply that the chromosomal mosaicism is an incidental finding.

Adolescent↗