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Biomedical subjects

O T Tan

Publications and source records attributed to O T Tan.

At least 19 recordsLinked to original sources

Mutations in a novel factor, glomulin, are responsible for glomuvenous malformations ("glomangiomas").

Glomuvenous malformations (GVMs) are cutaneous venous lesions characterized by the presence of smooth-muscle--like glomus cells in the media surrounding distended vascular lumens. We have shown that heritable GVMs link to a 4--6-cM region in chromosome 1p21-22. We also identified linkage disequilibrium that allowed a narrowing of this VMGLOM locus to 1.48 Mb. Herein, we report the identification of the mutated gene, glomulin, localized on the basis of the YAC and PAC maps. An incomplete cDNA sequence for glomulin had previously been designated "FAP48," for "FKBP-associated protein of 48 kD." The complete cDNA for glomulin contains an open reading frame of 1,785 nt encoding a predicted protein of 68 kD. The gene consists of 19 exons in which we identified 14 different germline mutations in patients with GVM. In addition, we found a somatic "second hit" mutation in affected tissue of a patient with an inherited genomic deletion. Since all but one of the mutations result in premature stop codons, and since the localized nature of the lesions could be explained by Knudson's two-hit model, GVMs are likely caused by complete loss of function of glomulin. The abnormal phenotype of vascular smooth-muscle cells (VSMCs) in GVMs suggests that glomulin plays an important role in differentiation of these cells--and, thereby, in vascular morphogenesis--especially in cutaneous veins.

Adaptor Proteins, Signal Transducing↗

Wavelengths for laser treatment of port wine stains and telangiectasia.

BACKGROUND AND OBJECTIVE: This report presents analytical modelling of the influence of wavelength on the amount of volumetric rate of heat produced in dermal blood vessels by millisecond laser radiation. STUDY DESIGN/MATERIALS AND METHODS: A new anatomical model is proposed that represents port wine stains as well as telangiectatic lesions. It consists of a target blood vessel, representing the deepest dermal blood vessel that requires irreversible injury, and a layer of whole blood, representing all other dermal blood vessels above the target vessel. The laser light that interacts with the blood vessels is assumed to be diffuse. Selective photothermolysis is the basis for the analysis. We consider wavelengths between 577 nm and 600 nm, the argon laser wavelengths at 488/515 nm, and the frequency doubled Nd:YAG laser wavelength at 532 nm. RESULTS: The rate of volumetric heat production of absorbed laser light in the target blood vessel is expressed analytically as a function of blood absorption, the concentration of additional dermal blood, and the depth of the target vessel. CONCLUSION: The model explains why 585 nm is a good compromise for treating port wine stains that vary widely in number of dermal blood vessels. It predicts that wavelengths between 577 nm and 582 nm are excellent for the treatment of port wine stains in young children, and it suggests a possible explanation as to why the argon laser is sometimes said to be capable of treating dark mature port wine stains. The copper vapour laser wavelength at 578 nm, and the frequency doubled Nd:YAG laser wavelength at 532 nm, are predicted to be suitable for the treatment of port wine stains that contain, respectively, a small to moderate and a moderate number of dermal blood vessels. When laser beam spotsize becomes smaller, the best wavelength for producing maximal rate of heat in the target vessel is predicted to shift to 577 nm.

Animals↗

Role of the Alexandrite laser for removal of tattoos.

BACKGROUND AND OBJECTIVE: The development of the Alexandrite laser for the removal of blue-black tattoos is described. STUDY DESIGN/MATERIALS AND METHODS: The responses of an animal study, using professionally tattooed skin and a human study involving 22 (professional and nonprofessional) blue-black tattoos, to the Alexandrite laser are reported. RESULTS: Histopathologic evaluation of tattooed pig skin biopsies demonstrated the method of removal of dermal tattoo pigment. An average 11.6 treatments were required to remove completely the ten human blue-black professional tattoos compared to an average of 10.3 treatments to reach the same endpoint in six subjects with nonprofessional tattoos. CONCLUSION: Of significance was the fact that unlike the Q-switched Ruby and Nd:YAG lasers where punctate bleeding and tissue splattering have been reported to occur during laser tattoo removal, epidermal integrity was maintained during exposure of tattooed skin to the Q-switched Alexandrite laser at therapeutic fluences used.

Adult↗

Removal of colored tattoos with the Q-switched alexandrite laser.

The Q-switched alexandrite laser at 760 nm and 50- to 100-ns pulse duration has been shown to effectively remove blue-black as well as green, red, and mauve in seven human subjects with colored tattoos. An average of 9.0 treatments were required to completely remove the green pigment at an average fluence of 5.80 J/cm2 compared with an average of 9.7 treatments at an average fluence of 6.10 J/cm2 for red and an average of 10 treatments at an average fluence of 6.20 J/cm2 for mauve. Orange and yellow were unaffected by the alexandrite laser over a range of fluences tested.

Animals↗

Pulsed dye laser treatment of recalcitrant verrucae: a preliminary report.

Patients with recalcitrant warts on the fingers and hands, periungual, and other parts of the body including verrucae plana and plantar surfaces were treated using the pulsed dye laser at 585 nm, 450 usec, and a spotsize of 5 mm diameter. Of the 39 patients treated, 28 (72%) were cleared of their warts after an average of 1.68 treatments at fluences of 6.25-7.5 J/cm2. Seven (18%) patients had a reduction of between 80-95% of their warts after 1.3 treatments, and verrucae reduced by 50% in four of the 39 patients after one treatment. The average follow-up period of the 28 cases cleared of their warts has been 5 months. Of this group, those with periungual warts have been followed for up to 6.4 months, compared to 4.8 months for those with warts on other parts of their body, 4.0 months for those with finger and hand warts, and 2.0 months for plantar warts. Only one of the 28 patients has had a recurrence after 3 months of clearance.

Adolescent↗

Alteration of argon laser-induced scars by the pulsed dye laser.

Ten patients with portwine stains (PWS) with test sites previously exposed to an argon laser were evaluated and subsequently treated with five pulsed dye (585 nm) laser treatments over a 10 month period. Clinical assessments, skin surface texture analyses using optical profilometry, and light microscopic histological evaluations were performed prior to commencement and at the end of the study in all ten patients. A change in the skin texture with return of skin markings approximating those of normal skin measured by optical profilometry was observed in the argon treated PWS skin following pulsed dye laser treatments.

Adolescent↗

Pulse duration effects on cutaneous pigment.

Melanin, an endogenous chromophore in pigment containing cells in skin, is being specifically altered by lasers using the principle of selective photothermolysis (SPT). This implies that a combination of specific laser parameters of wavelength, pulse duration, spotsize, and energy density are required to confine the delivered laser energy to the targeted cells alone. Because the bulk of cutaneous pigment is localized to epidermal basal cells, pigmentary incontinence has been found to occur in skin exposed to laser irradiation. This study demonstrates that pulse duration or exposure time of the laser affect the severity of pigmentary incontinence induced. Pigment granules are more abundant, aggregated, and located deeper in the dermis following exposure to 500 nsec pulse duration than 100 nsec at a wavelength of 504 nm. This relationship appears to be independent of the laser energy density used.

Animals↗

Pulsed dye laser treatment of benign cutaneous pigmented lesions.

Superficial benign cutaneous pigmented lesions that commonly present to the dermatologists and plastic surgeons have been treated by many conventional modalities such as dermabrasion, depigmenting creams as well as several types of lasers. Many of these treatment modalities lack specificity of injury, which has meant that normally pigmented and even non-pigment containing structures such as collagen as well as the hyperpigmented lesion itself have all been indiscriminately destroyed. This has resulted variously in hypopigmentation, hyperpigmentation, in addition to scar formation in some cases. A coaxial 504 nm laser with a pulse duration of 300 nsec was used to treat fifty two patients with superficial benign cutaneous pigmented lesions. Although the number of treatments required to clear the lesion varied according to the type of lesions being treated, on average, between 2 and 4 treatments were required to completely eradicate the superficial benign cutaneous pigmented lesions using 504 nm pulsed dye laser. The skin at the site successfully cleared of the pigmented lesion remained normal in skin color, texture, markings, and mobility.

Child, Preschool↗

EMLA for laser treatment of portwine stains in children.

Vascular-specific lasers with pulse durations of between 300 and 500 microseconds are the treatment of choice for portwine stains (PWS), particularly in children. Although the discomfort felt following laser irradiation from a single pulse is transient, these sensations are intensified when multiple pulses are delivered over a confined area of skin. Because 75-80% of PWS are located in the head and neck regions, laser treatment of these sites tends to be more painful than those located in most other parts of the body. A prospective double blind randomized study, assessing pain during laser irradiation on PWS skin occluded with either EMLA, placebo, or no cream (control) was performed in 73 PWS subjects between 5 and 16 years of age. Analysis of the data showed that the pain scores for EMLA-treated sites were the smallest, the control scores tended to be the highest, with the placebo scores in the middle. The differences between the treatments were significant (P < 0.0001).

Adolescent↗

Long-term neonatal rat aortic smooth muscle cell cultures: a model for the tunica media of a blood vessel.

Cultured neonatal rat aortic smooth muscle cells have been used to study the synthesis and accumulation of extracellular matrix components in many laboratories. These cells are capable of accumulating large amounts of insoluble elastin in the extracellular matrix and can be maintained in culture for long periods of time without subcultivation. This study examined the elastin and collagen contents of such cells in culture for 5, 21 and 43 weeks. The percent elastin and collagen observed in the 43-week cultures were strikingly similar to that seen in the intact neonatal rat aorta. It should be noted that the percent collagen varied significantly between 5 weeks and 43 weeks, whereas that for elastin remained relatively constant throughout the same time course. Histological examination demonstrated that the elastin fibers in the extracellular matrix of the cultures were arranged in a pattern similar to the elastic lamellae of the aortic tunica media. Data presented here suggest that these cells in culture mimic the donor tissue from which they were derived with respect to elastin and collagen content as well as elastic fiber arrangement, and possibly represent an organotypic culture of the medial layer of a blood vessel.

Animals↗

Treatment of ulcerated hemangiomas with the pulsed tunable dye laser.

Hemangiomas are the most common tumor of infancy and are characterized by rapid growth during the first 6 months of life. During the rapid growth phase, approximately 5% to 10% of the hemangiomas ulcerate. Ulcerated lesions are painful, may bleed, and are at risk for bacterial infection. Previous therapy has included daily local wound care, topical antibiotics, and local and systemic steroids. We treated nine infants (eight female and one male) with ulcerated hemangiomas by means of a vascular-specific (585-nm) pulsed (450-microsecond) tunable dye laser. Eight of the nine patients had a single ulceration, whereas one patient had two ulcerations within a large hemangioma. Six of the ulcerations healed with a single laser treatment. One ulceration required two treatments to heal, and the remaining two required three treatments. Pain was subjectively decreased within 2 to 3 days in all patients after a single treatment. The pulsed tunable dye laser should be considered in the treatment of all ulcerated hemangiomas.

Evaluation Studies as Topic↗

Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications.

Of 310 patients with port-wine stains, 68% had more than one dermatome involved; 85% had unilateral and 15% had a bilateral distribution of their port-wine stain. At the time of examination, 8% of all patients with trigeminal port-wine stains had evidence of eye and/or central nervous system (CNS) involvement. Extensive involvement, with port-wine stain over the trunk and extremities as well as the head and neck, was observed in 12%. Patients who did not have port-wine stains on the areas served by branches V1 and V2 of the trigeminal nerve had no signs or symptoms of eye and/or CNS involvement. Port-wine stains of the eyelids, bilateral distribution of the birthmark, and unilateral port-wine stains involving all three branches of the trigeminal nerve were associated with a significantly higher likelihood of having eye and/or CNS complications. Twenty-four percent of those with bilateral trigeminal nerve port-wine stains had eye and/or CNS involvement compared with 6% of those with unilateral lesions. All those who had eye and/or CNS complications had port-wine stain involvement of the eyelids; in 91% both upper and lower eyelids were involved, whereas in 9% only the lower eyelid was involved. None of those with upper eyelid port-wine stains alone had eye and/or CNS complications. In addition, 3 (75%) of the 4 subjects with seizures alone had bilateral port-wine stain involvement. A third group, these with unilateral V1, V2, and V3 port-wine stains, had eye and/or CNS complications in 3 (19%) of 16 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Laser treatment of benign cutaneous vascular lesions.

Benign cutaneous vascular lesions have been treated with a wide array of modalities. Lasers are a comparatively new form of treatment for cutaneous blood vessel abnormalities. Initially, results following laser treatment were disappointing, primarily because of widespread thermal injury to surrounding normal tissue. Recent developments in laser technology and the introduction of the tunable dye laser offer the ability to selectively target laser energy at specific chromophores such as oxyhemoglobin. The technique of selective photothermolysis provides successful treatment of benign vascular lesions with minimal damage to adjacent structures.

Adult↗

Laser treatment of congenital vascular birthmarks.

Congenital vascular birthmarks, classified as either hemangioma or vascular malformations (portwine stains), can now be cleared successfully using certain lasers. Since their introduction into medicine in the mid-1960s, several types of lasers including the argon, carbon dioxide, neodymium yttrium aluminum garnet (Nd:YAG) and pulsed tunable dye lasers have been used to treat benign cutaneous vascular lesions such as portwine stains. After extensive research examining the effects of specific laser parameters on tissue, a set of parameters was identified which together selectively destroyed blood vessels in the skin. Application of this laser technique for the treatment of benign cutaneous vascular lesions, such as portwine stains, meant that it was possible to destroy only the abnormally ectatic vessels which are inherent in these birthmarks. Because of the specificity of the laser injury, only the abnormal blood vessels are destroyed and healthy adjacent structures such as epidermal pigment and dermal collagen are left intact. Thus, unwanted adverse effects such as scar formation and pigmentary abnormalities at the laser-exposed site have been minimized. Skin treated using this combination of laser parameters normalizes in color, texture and its markings, and adnexae are maintained at the treated site. Not only has this new laser treatment provided a way of removing these disfiguring birthmarks with the return of normal-appearing skin at the treated site, but the lack of adverse effects following this treatment has meant that not only adults but children of all ages can now be treated using this technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Histologic comparison of the pulsed dye laser and copper vapor laser effects on pig skin.

Albino pig skin was exposed to the copper vapor (CVL) and flash-lamp pulsed dye (PDL) lasers at 578 nm with a 3 mm diameter spotsize over a range of fluences until purpura and whitening were first established. The total irradiation time was the parameter that was varied in order for the CVL to reach the desired fluence. The lowest fluence producing each clinical endpoint was designated the threshold fluence: 34 J/cm2 was required to produce purpura using the CVL compared to 7.5 J/cm2 with the PDL laser. Histologically, skin exposed to purpura fluences from the CVL revealed the presence of constricted, disrupted papillary dermal blood vessels with trapped RBC's within them which were unlike those exposed to PDL where the irradiated vessels were dilated and packed with masses of intravascular agglutinated RBC's. The whitening threshold fluences for the CVL and PDL lasers were 67 J/cm2 and 29 J/cm2, respectively. Streaming of epidermal cells and dermal collagen denaturation were observed in CVL irradiated skin, compared to occasional dyskeratotic epidermal cells and focal dermal collagen denaturation following PDL exposure. The mechanisms responsible for the clinical and histologic changes produced by the two laser systems are discussed.

Animals↗