Management of Darier disease: A review of the literature and update.

Darier disease (DD) is a rare type of inherited keratinizing disorder with no definitive therapeutic approach. The objective of this study is to provide a detailed literature review of all the available treatment modalities of Darier disease, including those that are both surgical and non surgical, to compare their efficacies and to propose a novel therapeutic approach. A complete search of the literature for all articles describing the different treatments of Darier disease, with no restrictions on patients' ages, gender or nationalities, was performed with the use of PubMed. A total of 68 articles were included in the study: 3 prospective studies, 44 case reports/case series and 21 letters/correspondences/clinical images. The treatments described were topical, oral or physical. Retinoids (isotretinoin, tazarotene and adapalene) and fluorouracil were the two most effective topical treatments. Oral retinoids were the most effective oral therapy and were prescribed in the cases of generalized Darier disease. For localized and resistant skin lesions, physical therapies including surgical excision, dermabrasion and CO2 laser ablation were the first line choices. Limitations of this article include the inability to verify the accuracy of the published data, the relatively small sample size, the absence of randomized controlled clinical trials and possible unidentified confounding factors in various studies. In every therapeutic approach to Darier disease, consideration of patient comorbidities, disease distribution, severity and treatment accessibility is essential. Large and randomized clinical trials are necessary for the comparison of the efficacy and the safety of all the treatments of Darier disease and settling a consensus for management.

Optimizing Q-switched lasers for melasma and acquired dermal melanoses.

The Q-switched Nd:YAG laser is an established modality of treatment for epidermal and dermal pigmented lesions. The dual wavelengths of 1064nm and 532nm are suited for the darker skin tones encountered in India. Though this laser has become the one of choice for conditions such as nevus of Ota, Hori's nevus and tattoos, its role in the management of melasma and other acquired dermal melanoses is not clear. Despite several studies having been done on the Q-switched Nd:YAG laser in melasma, there is no consensus on the protocol or number of sessions required. Acquired dermal melanoses are heterogenous entities with the common features of pigment incontinence and dermal melanophages resulting in greyish macular hyperpigmentation. This article reviews the current literature on laser toning in melasma and the role of the Q-switched Nd:YAG laser in stubborn pigmentary disorders such as lichen planus pigmentosus. As the pathology is primarily dermal or mixed epidermal-dermal in these conditions, the longer wavelength of 1064nm is preferred due to its deeper penetration. Generally multiple sessions are needed for successful outcomes. Low fluence Q-switched Nd:YAG laser at 1064nm utilizing the multi-pass technique with a large spot size has been suggested as a modality to treat melasma. Varying degrees of success have been reported but recurrences are common on discontinuing laser therapy. Adverse effects such as mottled hypopigmentation have been reported following laser toning; these can be minimized by using larger spot sizes of 8 to 10mm with longer intervals (2 weeks) between sessions.

Fractional lasers in dermatology--current status and recommendations.

INTRODUCTION: Fractional laser technology is a new emerging technology to improve scars, fine lines, dyspigmentation, striae and wrinkles. The technique is easy, safe to use and has been used effectively for several clinical and cosmetic indications in Indian skin. DEVICES: Different fractional laser machines, with different wavelengths, both ablative and non-ablative, are now available in India. A detailed understanding of the device being used is recommended. INDICATIONS: Common indications include resurfacing for acne, chickenpox and surgical scars, periorbital and perioral wrinkles, photoageing changes, facial dyschromias. The use of fractional lasers in stretch marks, melasma and other pigmentary conditions, dermatological conditions such as granuloma annulare has been reported. But further data are needed before adopting them for routine use in such conditions. PHYSICIAN QUALIFICATION: Any qualified dermatologist may administer fractional laser treatment. He/ she should possess a Master's degree or diploma in dermatology and should have had specific hands-on training in lasers, either during postgraduation or later at a facility which routinely performs laser procedures under a competent dermatologist or plastic surgeon with experience and training in using lasers. Since parameters may vary with different systems, specific training tailored towards the concerned device at either the manufacturer's facility or at another center using the machine is recommended. FACILITY: Fractional lasers can be used in the dermatologist's minor procedure room for the above indications. PREOPERATIVE COUNSELING AND INFORMED CONSENT: Detailed counseling with respect to the treatment, desired effects and possible postoperative complications should be provided to the patient. The patient should be provided brochures to study and also adequate opportunity to seek information. A detailed consent form needs to be completed by the patient. Consent form should include information on the machine, possible postoperative course expected and postoperative complications. Preoperative photography should be carried out in all cases of resurfacing. A close-up front and 45-degree lateral photographs of both sides must be taken. LASER PARAMETERS: There are different machines based on different technologies available. Choice parameters depend on the type of machine, location and type of lesion, and skin color. Physician needs to be familiar with these requirements before using the machine. ANESTHESIA: Fractional laser treatment can be carried out under topical anesthesia with eutectic mixture of lidocaine and prilocaine. Some machines can be used without any anesthesia or only with topical cooling or cryospray. But for maximal patient comfort, a topical anesthetic prior to the procedure is recommended. POSTOPERATIVE CARE: Proper postoperative care is important in avoiding complications. Post-treatment edema and redness settle in a few hours to a few days. A sunscreen is mandatory, and emollients may be prescribed for the dryness and peeling that could occur.

Nonablative lasers and nonlaser systems in dermatology: current status.

Nonablative lasers and nonlaser systems are newer systems used for skin rejuvenation, tightening, body sculpting, and scar remodeling. DEVICES: Different technologies such as lasers, Intense Pulsed Light (IPL), and radiofrequency have been introduced. Most nonablative laser systems emit light within the infrared portion of the electromagnetic spectrum (1000-1500 nm). At these wavelengths, absorption by superficial water containing tissue is relatively weak, thereby effecting deeper tissue penetration. A detailed understanding of the device being used is recommended. INDICATIONS: Nonablative technology have been used for several indications such as skin tightening, periorbital tissue tightening, treatment of nasolabial lines and jowl, body sculpting/remodeling, cellulite reduction, scar revision and remodeling and for the treatment of photodamaged skin. FACILITY: Nonablative laser and light modalities can be carried out in a physician treatment room or hospital setting or a nursing home with a small operation theater. PREOPERATIVE COUNSELING AND INFORMED CONSENT: The dermatologic consultation should include detailed assessment of the patient's skin condition and skin type. An informed consent is mandatory to protect the rights of the patient as well as the practitioner. All patients must have carefully taken preoperative and postoperative pictures. CHOICE OF THE DEVICE AND PARAMETERS: Depends on the indication, the area to be treated, the acceptable downtime for the desired correction, and to an extent the skin color. ANESTHESIA: These lasers are mostly pain-free and tolerated well by patients but may require topical anesthesia. In most cases, topical cooling and numbing using icepacks is sufficient, even in an apprehensive patient. POSTOPERATIVE CARE: The nonablative lasers, light sources and radiofrequency systems are safe, even in darker skin types, and postoperative care is minimal. Proper postoperative care is important in avoiding complications. Post-treatment edema and redness settle in a few hours to a few days. Postoperative sun avoidance and use of sunscreen is mandatory.

Standard guidelines of care: laser and IPL hair reduction.

UNLABELLED: Laser-assisted hair removal, Laser hair removal, Laser and light-assisted hair removal, Laser and light-assisted, long-term hair reduction, IPL photodepilation, LHE photodepilation; all these are acceptable synonyms. Laser (Ruby, Nd Yag, Alexandrite, Diode), intense pulse light, light and heat energy system are the different light-/Laser-based systems used for hair removal; each have its advantages and disadvantages. The word "LONG-TERM HAIR REDUCTION" should be used rather than permanent hair removal. Patient counseling is essential about the need for multiple sessions. PHYSICIANS' QUALIFICATIONS: Laser hair removal may be practiced by any dermatologist, who has received adequate background training during postgraduation or later at a centre that provides education and training in Lasers or in focused workshops providing such training. The dermatologist should have adequate knowledge of the machines, the parameters and aftercare. The physician may allow the actual procedure to be performed under his/her direct supervision by a trained nurse assistant/junior doctor. However, the final responsibility for the procedure would lie with the physician. FACILITY: The procedure may be performed in the physician's minor procedure room. Investigations to rule out any underlying cause for hair growth are important; concurrent drug therapy may be needed. Laser parameters vary with area, type of hair, and the machine used. Full knowledge about the machine and cooling system is important. Future maintenance treatments may be needed.

Characterization of three glycosyltransferases involved in the biosynthesis of the phenolic glycolipid antigens from the Mycobacterium tuberculosis complex.

Mycobacterium tuberculosis and Mycobacterium leprae, the two main mycobacterial pathogens in humans, produce highly specific long chain beta-diols, the dimycocerosates of phthiocerol, and structurally related phenolic glycolipid (PGL) antigens, which are important virulence factors. In addition, M. tuberculosis also secretes glycosylated p-hydroxybenzoic acid methyl esters (p-HBAD) that contain the same carbohydrate moiety as the species-specific PGL of M. tuberculosis (PGL-tb). The genes involved in the biosynthesis of these compounds in M. tuberculosis are grouped on a 70-kilobase chromosomal fragment containing three genes encoding putative glycosyltransferases: Rv2957, Rv2958c, and Rv2962c. To determine the functions of these genes, three recombinant M. tuberculosis strains, in which these genes were individually inactivated, were constructed and biochemically characterized. Our results demonstrated that (i) the biosynthesis of PGL-tb and p-HBAD involves common enzymatic steps, (ii) the Rv2957, Rv2958c, and Rv2962c genes are involved in the formation of the glycosyl moiety of the two classes of molecules, and (iii) the product of Rv2962c catalyzes the transfer of a rhamnosyl residue onto p-hydroxybenzoic acid ethyl ester or phenolphthiocerol dimycocerosates, whereas the products of Rv2958c and Rv2957 add a second rhamnosyl unit and a fucosyl residue to form the species-specific triglycosyl appendage of PGL-tb and p-HBAD. The recombinant strains produced provide the tools to study the role of the carbohydrate domain of PGL-tb and p-HBAD in M. tuberculosis pathogenesis.

Lasers in dermatology: four decades of progress

Advances in laser technology have progressed so rapidly during the past decade that successful treatment of many cutaneous concerns and congenital defects, including vascular and pigmented lesions, tattoos, scars, and unwanted hair-can be achieved. The demand for laser surgery has increased substantially by patients and dermatologists alike as a result of the relative ease with which many of these lesions can be removed, combined with a low incidence of adverse postoperative sequelae. Refinements in laser technology and technique have provided patients and practitioners with more therapeutic choices and improved clinical results. In this review, the currently available laser systems with cutaneous applications are outlined, with primary focus placed on recent advancements and modifications in laser technology that have greatly expanded the cutaneous laser surgeon's armamentarium and improved overall treatment efficacy and safety.

Cytotoxic cell granule-mediated apoptosis. Characterization of the macromolecular complex of granzyme B with serglycin.

We have recently shown that the physiological mediator of granule-mediated apoptosis is a macromolecular complex of granzymes and perforin complexed with the chondroitin-sulfate proteoglycan, serglycin (Metkar, S. S., Wang, B., Aguilar-Santelises, M., Raja, S. M., Uhlin-Hansen, L., Podack, E., Trapani, J. A., and Froelich, C. J. (2002) Immunity 16, 417-428). We now report our biophysical studies establishing the nature of granzyme B-serglycin (GrB.SG) complex. Dynamic laser light scattering studies establish that SG has a hydrodynamic radius of approximately 140 +/- 23 nm, comparable to some viral particles. Agarose mobility shift gels and surface plasmon resonance (SPR), show that SG binds tightly to GrB and has the capacity to hold 30-60 GrB molecules. SPR studies also indicate equivalent binding affinities (K(d) approximately 0.8 microm), under acidic (granule pH) and neutral isotonic conditions (extra-cytoplasmic pH), for GrB.SG interaction. Finally, characterization of GrB.SG interactions within granules revealed complexes of two distinct molecular sizes, one held approximately 4-8 molecules of GrB, whereas the other contained as many as 32 molecules of GrB or other granule proteins. These studies provide a firm biophysical basis for our earlier reported observations that the proapoptotic granzyme is exocytosed predominantly as a macromolecular complex with SG.

Promovendo a cicatrizaçäo de úlceras hansênicas e näo hansênicas com laserterapia: ensaio clínico em unidades ambulatoriais do Sistema Único de Saúde / Laser therapy applied to leprous and non-leprous ulcers healing: a clinical trial in out-patient units of Public Health Service

A hanseníase apresenta, como incapacidade decorrente muito comum, a ulceraçäo plantar. Tendo em vista a necessidade de implantaçäo de programas de açäo de controle da doença e melhora da qualidade de vida dos portadores desta nos serviços básicos de saúde, este projeto viabilizou, comparativamente a afetados pela mesma lesäo, porém de outras etiologias, a utilizaçäo da laserterapia de baixa intensidade para cicatrizaçäo das úlceras hansênicas de membros inferiores. Na sua adoçäo, uma vez claramente definidos populaçäo de referência, bem como respectivos critérios de inclusäo e exclusäo, a normalizaçäo ética vigente no país prevista foi rigorosamente cumprida. Promoveram-se procedimentos adequados para padronizaçäo de condutas de mensuraçäo, avaliaçäo, aplicaçäo e acompanhamento da evoluçäo clínica e documental. Operou-se conjunto de indicadores em escalas de variáveis quantitativas e qualitativas. No primeiro caso, lidou-se com propriedades dimensionais de profundidade, comprimento, largura e volume, monitoradas pelo tempo; investigaram-se e notificaram-se padröes de secreçäo e demais sinais semiológicos pertinentes. Inferências paramédicas foram analisadas aos níveis correntes de significância, após aplicaçäo das provas de Goodman para variaçöes intra e inter populaçöes multinomiais, Anova e Wilcoxon. Desaparecimento lesional predominou estatisticamente sobre reduçäo e piora entre hansenianos 66,7(por cento); 16,7(por cento) e 16,7(por cento respectivamente) e näo hansenianos 55,3(por cento); 20,0(por cento) e 26,7(por cento) apontando näo só para aumento de repertório terapêutico, para a condiçäo estudada em unidades ambulatoriais do Sistem Único de Saúde, mas também para o sucesso de seu emprego em tais situaçöes

Sequential analysis of erythrocyte aggregation in health and diseases.

Aggregation of erythrocytes requires prolonged interaction of cellular and plasma constituents similar to in vivo conditions. To achieve this and then to analyse this process in various clinical and laboratory conditions, a PC-AT based system is developed. The erythrocyte suspension at 5% hematocrit in plasma is placed in a glass chamber, and the changes in laser transmitted intensity due to movement of the aggregates and erythrocytes in the path of the beam are sequentially recorded. From these data, aggregate size index, aggregate sedimentation time index, time required for completion of process and total number of fluctuations are calculated. From these, two additional parameters - effective number of cells and effective sedimentation duration - are calculated. The results show that in leprosy the aggregation of erythrocytes is reduced. In in vitro studies due to the cholesterol-enrichment of the erythrocyte membrane and treatment with pentoxifylline the aggregation of cells is increased whereas in disprin treated cells this is reduced compared to that of normal erythrocytes.

Aggregation and deformability of erythrocytes in leprosy.

The hemorheological parameters, erythrocyte aggregation and deformability are determined in leprotic patients and are compared with that of healthy subjects. The aggregation is determined by sequential analysis of the He-Ne laser transmission data through erythrocyte suspension at hematocrit 5%. The erythrocyte deformability is determined by measurement of passage time (reciprocal of deformability) of erythrocyte suspension in PBS at hematocrit 6% through cellulose membrane. The observations show that in leprosy the aggregation of erythrocyte is marginally reduced and the deformability is significantly increased. These parameters in combination with low hemoglobin and hematocrit levels in these patients lowers the blood viscosity to maintain the transport of material across the capillary wall.

Laser de diodo no tratamento da retinopatia diabética proliferativa / Diode laser in treatment of proliferative diabetic retinopathy

Foram encontrados 207 pacientes portadores de hanseníase, em hospital colônia, sendo 195 (94,2 por cento) da forma Virchowiana e 12 (5,8 por cento) tuberculóide. Cento e quarenta e sete (71,0 por cento) eram do sexo masculino e 60 (28.9 por cento) do sexo feminino. Setenta e sete (39,5 por cento) pacientes apresentaram alteraçöes dos anexos oculares e 89 (45,6 por cento) apresentaram alteraçöes do bulbo ocular, na forma Virchowiana. Madarose parcial de supercílio foi a alteraçäo dos anexos oculares mais frequente (58 casos; 29,7 por cento) e a alteraçäo do bulbo ocular mais frequente foi a diminuiçäo da sensibilidade corneana (72 casos; 36,9 por cento). Cegueira unilateral ocorreu em 30 (15,4 por cento) pacientes e bilateral em 13 (6,6 por cento) na forma Virchowiana

Study of intracellular deposition of the anti-leprosy drug clofazimine in mouse spleen using laser microprobe mass analysis.

Laser microprobe mass analysis (LAMMA) was used to study the composition of the brick-red crystalline material which had accumulated in the spleen of mice that had received the anti-leprosy drug Clofazimine in their diet for several months. The crystalline deposits light-microscopically resembled pure Clofazimine crystals. The presence of the drug in the crystals was indicated by LAMMA by the appearance of the chloride mass peaks in the negative mass spectra. More specific information was obtained from the positive mass spectra. A mass signal for the protonated molecule was present.

Fluorescent probes as tools to assess the receptor for the urokinase-type plasminogen activator on tumor cells.

Flow cytofluorometric protocols (FACScan) are described for the rapid and quantitative real-time analysis of binding of FITC-pro-u-PA to cell surface receptors (u-PAR) on living, resting, and also on PMA-stimulated human monocytic U937 cells. Binding of pro-u-PA was visualized by CLSM. This fairly new technique is superior over conventional fluorescence microscopy and is an alternative to electron microscopic approaches. Both flow cytofluorometry and confocal laser scanning microscopy allow the analysis quantitatively and with high-sensitivity binding of FITC-pro-u-PA to single suspended or adherent cells. By CLSM u-PA/u-PAR were found to be located in heterogeneously distributed discrete patches at the cell surface on U937 and not inside the cell. This is in agreement with previous studies by Hansen et al, who applied radioiodinated u-PA and electron microscopy to locate u-PAR on microvilli of fixed U937 cells. By flow cytofluorometry, it was possible to quantify the time-dependent and temperature-dependent binding of FITC-pro-u-PA to living single U937. Apparent saturation of u-PAR was achieved at 5 nM FITC-pro-u-PA for both nonstimulated and PMA-stimulated U937 cells. Half saturation of u-PAR was also determined. Nonstimulated U937 was 0.7 nM, and PMA-stimulated U937 was 1.1 nM of FITC-pro-u-PA. This increase in half-saturation concentration in PMA-stimulated cells is paralleled by a steep increase in binding sites (3.6-fold). The use of fluoresceinated reference beads is recommended to verify changes in affinity and binding sites. Using CLSM or flow cytofluorometry, it is also possible to study the structure relationship of u-PA/u-PAR in the presence of competitive binding analogues or inhibitors. Fluorescence techniques will also permit the identification of u-PAR-positive cells in blood, ascitic fluid, or biopsies obtained from cancer patients.