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[Development of laser systems in the treatment of hyperpigmented skin lesions].

Laser beams have been in common use for the treatment of hyperpigmented skin lesions. However, therapeutic efficacy has been limited mainly because the output is circular with a Gaussian distribution of intensity, which makes it difficult to apply a uniformly distributed dose to the lesions. We have developed a technique whereby a laser beam is converted to have a square and uniform output intensity distribution. The principle of this technique is that the divergent laser beam enters a glass square pillar, propagates through the pillar repeating the total reflection and emerges with a uniform intensity distribution over the cross-section at the end of the pillar. The device applied this technique is incorporated in a hand-piece and both ruby and argon laser systems have been developed. The ruby laser has been used for the treatment of the melanistic skin lesions such as nevus cell nevus and nevus spilus. In clinical application, 36 of 67 cases have shown remarkably effective results with an improvement rate of 53.7%. The argon laser has been used for the treatment of vasogenic skin lesions such as portwine stain. In clinical application, 44 of 66 cases have shown effective results and the improvement rate is 66.7%. These results are excellent when compared with the other methods of treatment and with laser therapy previously used.

Humans↗

[Automatic grinding of undecalcified bone sections with exact adjustment of thickness].

A new grinding machine for preparing thin undecalcified bone sections after methylmethacrylate embedding is described. About 20 rather small bone sections can be ground at the same time; bigger specimens, up to 8 cm of length, are allowed. Bone sections are mounted on a cylindrical specimen holder by an adhesive film. Then the final thickness of the sections is exactly adjusted by screwing three rubies out of the holder's bottom. Now the prepared holder is set in a guide ring on a turntable carrying a rough ended glass plate. The desired thickness of the sections is reached as soon as the three rubies touch the glass surface. The variation in the thickness of the sections is less than +/- 3 micron. The machine is simply constructed, easily to handle and rapidly to clean.

Animals↗

[Improving the quality of glass ocular prostheses].

A critical analysis has been attempted of the current state-of-the-art in studying seleno-cadmium ruby glasses applicable for glass ocular prosthesis production. Better quality of these prostheses can be achieved by both the refinement of the ruby glass composition and by its strengthening (hardening) through proper methods.

Eye, Artificial↗

Treatment of cafe au lait macules with lasers. A clinicopathologic correlation.

BACKGROUND: Cafe au lait macules (CALMs) respond variably to treatment with different lasers. This study was done to determine whether the type of laser and the individual histologic features of the CALMs could predict clinical response to treatment. Nine CALMs were treated with both the frequency-doubled Q-switched neodymium: YAG laser (wavelength, 532 nm; beam diameter, 2.0 mm) and the Q-switched ruby laser (wavelength, 694 nm; beam diameter, 5.0 mm). Both lasers were used at a fluence of 6.0 J/cm2. Biopsy specimens of the CALMs were obtained before and after treatment. Clinical follow-up was done at 1-, 3-, and 6-month intervals. OBSERVATIONS: Both lasers yielded variable responses to treatment. Two histologic subtypes of CALMs were identified, but these different subtypes did not predict clinical outcome after laser treatment. CONCLUSIONS: Cafe au lait macules respond variably to treatment with both the Q-switched ruby laser and the frequency-doubled Q-switched neodymium:YAG laser. Further research might address the effect of using multiple treatments. In view of these results, clinicians using lasers to treat CALMs should inform their patients of the potential for recurrence or darkening of CALMs.

Adult↗

The Q-switched Nd:YAG laser effectively treats tattoos. A controlled, dose-response study.

BACKGROUND AND DESIGN: The Q-switched ruby laser was recently shown to remove tattoos without scarring. The Q-switched neodymium: yttrium aluminum garnet (Nd:YAG) laser, which targets black ink with a longer wavelength that has less absorption by melanin, should effectively treat tattoos with fewer pigmentary alterations. A prospective, blinded, controlled study was conducted to assess the ability of the Q-switched Nd:YAG laser (1064 nm, 10 ns, 5 Hz) to remove tattoos. Twenty-five patients with 39 blue-black or multicolored tattoos (14 previously untreated, 25 Q-switched ruby laser-resistant) were exposed in randomly derived quadrants with 6, 8, 10, or 12 J/cm2 at 3 to 4 week intervals for a total of four treatment sessions. RESULTS: An excellent response (> 75% ink removal) was seen in 77% of the black tattoos and more than 95% of the black ink cleared in 11 (28%) of 39 tattoos at 10 to 12 J/cm2 after four treatment sessions. Colored inks were not as effectively removed. Response was related to fluence with greatest improvement noted in the quadrants treated with 10 and 12 J/cm2. No significant side effects, including pigmentary changes or scarring, were noted. Histopathologic examination demonstrated persistence of tattoo ink in clinically clear areas and confirmed the absence of fibrosis and granulomatous changes. CONCLUSION: The Q-switched Nd:YAG laser (1064 nm) effectively treats black tattoos with an excellent cosmetic outcome. Bright colors were minimally responsive to treatment. Higher doses were more effective and equally well tolerated.

Adult↗

Treatment of traumatic tattoos with the Q-switched neodymium:YAG laser.

BACKGROUND: Treatment for traumatic tattoos often results in incomplete removal of the pigment or produces unacceptable scars or textural changes. Successful results using Q-switched ruby lasers have been reported. The Q-switched neodymium:YAG laser, with a wavelength of 1064 nm and a pulse duration of 5 to 7 nanoseconds, penetrates deeper into the skin and has less interaction with melanin than the Q-switched ruby laser. OBSERVATIONS: The present study documents 32 cases of traumatic tattoos involving 51 sites of the face, trunk, and extremities in patients ranging in age from 6 to 58 years. All patients were treated with the Q-switched neodymium:YAG laser. Excellent results were noted for 50 of 51 treated tattoos. The number of treatments to achieve excellent results ranged from 1 to 6, with an average of 1.7. No scarring, atrophy, textural changes, or hypopigmentation was noted in any of the cases. Transient postinflammatory hyperpigmentation of 3 months' duration was noted in 1 patient. CONCLUSION: The Q-switched neodymium:YAG laser was effective in removing traumatic tattoos without any significant side effects.

Adolescent↗

Long-term renal and hearing toxicity of carboplatin in infants treated for localized and unresectable neuroblastoma: results of the SFOP NBL90 study.

BACKGROUND: A secondary end point of the NBL90 protocol (Rubie H et al. Pediatr Oncol 2001;36:247-250) was the concern in this infant population for possible carboplatin-(CBDCA) induced late side effects including impaired renal and hearing functions. PROCEDURE: Glomerular filtration rate (GFR), tubular function (TF), pure tone audiometry (PTA), high-frequency, and transient evoked-otoacoustic emission were prospectively assessed in 30 children alive and disease-free 6 years after the end of the treatment. RESULTS: Median age at diagnosis and at assessment was 4.7 months and 7 years, respectively. Blood pressure was < or =97.5 centile in all children. The mean estimated GFR was 114 +/- 13 ml/min/1.73 m(2) by Schwartz formula [range 87-145]. TF assessment failed to demonstrate any impairment. 29/30 children had grade 0 ototoxicity and all transient evoked otoacoustic emission were normal. CONCLUSIONS: With a 6-year follow-up the combination of VP16 and carboplatin given at conventional doses is safe on renal and hearing functions in infants with unresectable neuroblastomas treated according to SFOP NB90.

Antineoplastic Agents↗

A case for cytokines as effector molecules in the resolution of virus infection.

Some cytokines are known to have potent antiviral activity in vitro, and recent work shows that severely immunodeficient mice, which lack conventional effector T cells, can still recover from virus infection provided these factors are present at sites of virus replication. Here Alistair Ramsay, Janet Ruby and Ian Ramshaw discuss these findings and raise fundamental questions concerning the physiological role of cytotoxic T cells in the resolution of virus infection.

Animals↗

The development of guidelines for the treatment of vitiligo. Clinical Epidemiology Unit of the Istituto Dermopatico dell'Immacolata-Istituto di Recovero e Cura a Carattere Scientifico (IDI-IRCCS) and the Archives of Dermatology.

OBJECTIVE: To develop and introduce evidence-based guidelines for the treatment of vitiligo in children and in adults. PATIENTS AND SETTING: Patients, residents, and dermatologists from the Department of Dermatology, Academic Medical Center, University of Amsterdam, and the Netherlands Institute for Pigmentary Disorders in Amsterdam. DESIGN: Scientific evidence obtained from 3 systematic reviews of the literature was combined with the results of 2 questionnaires and interviews of potential users of the guidelines, 3 internal expert meetings, and 1 local expert meeting, during which preliminary guidelines were presented and commented on. A final version of the guidelines was synthesized and disseminated among potential users. Six months after the introduction of these guidelines, their use was evaluated. RESULTS: Before the development of the guidelines, there was no uniformity in treatment selection, and there was a variability in estimates of treatment outcome. The metaanalysis showed class 3 corticosteroids and narrowband UV-B to be the most effective and safest therapies for localized and for generalized vitiligo, respectively. From another systematic review, it could be concluded that patients with segmental, stable, or lip-tip vitiligo could be successfully treated with most autologous transplantation methods. For vitiligo universalis, results of the systematic review showed that depigmentation using monobenzone or a Q-switched ruby laser was equally effective. The final version of the guidelines consisted of a treatment scheme together with detailed treatment protocols. Implementation of the guidelines was evaluated in 5 physicians. After the introduction of these guidelines, they were followed in most adult cases with vitiligo (71% of patients with localized vitiligo, 82% with generalized vitiligo, 100% with stable or segmental vitiligo, and 80% with universal vitiligo). In children with vitiligo, the physicians adhered to the guidelines for 52% of the cases. CONCLUSIONS: Guidelines for the treatment of vitiligo can be successfully developed and disseminated for daily clinical practice. The results of the implementation of these guidelines should be confirmed in other centers involving more clinicians.

Adrenal Cortex Hormones↗

Laser iridotomy for aphakic pupillary block.

In six patients with aphakic pupillary block, argon laser produced full-thickness iridotomies that succeeded in restoring anterior chamber and intraocular pressure to normal. In one case, it was shown that location of iridotomy is important in determining whether or not iridotomy will succeed in relieving aphakic pupillary block. In two cases, pupillary block had resulted in shallowing of the anterior chamber without pressure elevation. Cases reported here show that continuous laser energy, such as from an argon laser, can produce a full-thickness opening, in contrast to the short duration pulse of the ruby, which will destroy only pigmented structures without producing a full-thickness iris opening. This need to produce some degree of spread of damage to unpigmented tissue elements in order to achieve and iris opening is a problem in phakic patients where injury to the lens must be avoided.

Aged↗

Future of laser dermatology.

BACKGROUND AND OBJECTIVE: Laser dermatology, a long-time model for laser tissue interactions, will play an important part in the future of research, diagnostics, and therapeutics. STUDY DESIGN/MATERIALS AND METHODS: Laser research continues in photobiology, especially in molecular reactions, and it continues at the cellular level in melanocyte and Langerhans cells. RESULTS: Laser diagnostics in the development of opto-electronics concern new developments in imagery. Some studies include new types of microscopes for living skin and vary from the portable illuminated skin microscopes, the current dermatoscopes, to the coaxial polarizing microscope and the new scanning confocal microscope of Gmitro for living tissues. The regular confocal microscope for fixed tissue slides will revolutionize dermatopathology. The other research microscopes include the ultrasonic biomedical microscope and the IR microscope and the holographic microscope of optical phase conjugation used for living tissues. CONCLUSION: New lasers for therapy include micromedical lasers, economical junction diode lasers alone and for pumping solid-state lasers, FEL of the future, and multiwavelength laser units. These later units include seven-wavelength units of barium, copper vapor and ruby, and are available for other heavy metal laser heads, ds gold-628 nm and lead-722 nm. Copper vapor can pump also Ti sapphire. The MOPO series (200 nm in the UV to > 4,500 in the IR) is the most extensive modern multiwavelength laser box type.

Dermatology↗

Laser ignition of traumatically embedded firework debris.

BACKGROUND AND OBJECTIVE: The Q-switched ruby laser (QSRL) has a good track record for traumatic tattoo removal. An unusual case of QSRL-treatment of a traumatic tattoo composed of firework debris is presented. STUDY DESIGN/PATIENT AND METHOD: A young man's traumatic tattoo, composed of firework debris, underwent QSRL ablation at 4-7 J/cm2 (pulse width 5 mm; duration 20 ns). RESULTS: Each test pulse produced visible sparks and focal projectile ejection of skin with pox-like scar formation. CONCLUSION: Caution is advised when using the QSRL for the treatment of traumatic tattoos composed of potentially combustible debris.

Adult↗

Mathematical modeling for the prediction and optimization of laser hair removal.

BACKGROUND AND OBJECTIVE: The study of hair removal is a slow, tedious process. Efficacy evaluations require test-site observation for at least one complete hair cycle, a minimum of 6-8 months. In addition, tracking and counting individual hairs is extremely labor intensive. The objective of this study was to develop and evaluate a mathematical model for hair removal that could significantly speed the entire process. STUDY DESIGN/MATERIALS AND METHODS: Generally accepted kinetic and statistical modeling methods were used to develop a mathematical description of hair growth. The anagen and telogen percentages and decay times were the variables used to predict the kinetics of untreated hair. In the case that the follicles were treated, it was necessary to additionally consider the possible outcomes after treatment, making the calculations much too complicated for simple mathematical formulations. Therefore, a computerized statistical model was developed that considered the probabilities of no, partial, or complete follicular damage in addition to the untreated model variables. These models were then evaluated by comparing them to data derived from the literature and a study center. RESULTS: Values derived from the mathematical model were capable of closely approximating the experimental results of untreated (shaving) and treated (plucking, electrolysis, ruby laser, Q-switched Nd:YAG laser) hair growth kinetics. The model was also shown to be useful for optimizing the number and interval of Q-switched Nd:YAG laser treatments. CONCLUSIONS: A mathematical model can be used to reliably predict results from a variety of hair removal techniques. It also appears to be useful for optimizing a particular treatment protocol. In addition, the development of new hair removal products may be aided by using this method.

Computer Simulation↗

Anatomical and functional evidence for lesion-specific sprouting of corticostriatal input in the adult rat.

Previous studies in our laboratory have shown that cortical lesions induced by thermocoagulation of pial blood vessels, but not by acute aspiration, result in 1) the preservation of control levels of the growth-associated protein (GAP)-43 and 2) a prolonged increase in neurotransmitter gene expression in the denervated dorsolateral striatum. We have examined whether corticostriatal projections from the spared homotypic contralateral cortex contribute to these effects. Adult rats received either a thermocoagulatory or aspiration lesion of the cerebral cortex and, after 30 days, received an injection of the anterograde tracer, Fluoro-Ruby, in the contralateral homotypic cortex. Rats were killed 7 days later, and labeled fibers were examined with fluorescence microscopy in the ipsilateral and contralateral striata. Ipsilateral corticostriatal projections were detected in lesioned and unlesioned rats. Numerous labeled fibers were detected in the contralateral striatum of thermocoagulatory-lesioned but not aspiration-lesioned or control animals, suggesting that contralateral cortical neurons may undergo axonal sprouting in the denervated striatum following a thermocoagulatory lesion of the cortex. To determine whether contralateral corticostriatal fibers play a role in the changes in striatal gene expression induced by the thermocoagulatory lesions, the effects of aspiration lesions, as well as unilateral and bilateral thermocoagulatory lesions of the cortex were compared. Confirming previous results, striatal enkephalin mRNA levels were increased after a unilateral thermocoagulatory lesion. However, they were unchanged after aspiration or bilateral thermocoagulatory lesions, suggesting that sprouting or overactivity of contralateral corticostriatal input contributes to the increase seen after unilateral thermocoagulatory lesions.

Animals↗

Topography of fibre organisation in the corticofugal pathways of rats.

The organisation of the long descending corticofugal pathways is poorly understood. We have examined these pathways to determine the fibre relationships along the extent of their course through the internal capsule, cerebral peduncle, longitudinal pontine fasciculus, pyramid, pyramidal decussation, and dorsal column of the spinal cord. Different cytoarchitectonic regions (e.g., lateral agranular and granular) of the rat's neocortex were injected with the axonal tracer biotinylated dextran. In other experiments, each animal had different-coloured fluorescent tracers (Fluoro Ruby and dextran-fluorescein) injected into separate cortical areas. Our results show that in the anterior and posterior limbs of the internal capsule, axons arising from spatially separate sites in rat neocortex occupy distinct regions of the cross-sectional area of the pathway. More caudally, within the cerebral peduncle and the longitudinal pontine fasciculus, axons from more distant cortical areas remain largely separate, but those from adjacent cortical areas begin to overlap. By the medullary pyramid, the pyramidal decussation, and the dorsal column of the spinal cord, the representations of all the cortical regions injected overlap completely; in these structures, the axons arising from each cortical area are widely intermingled. Thus, along the rostral-to-caudal course of the corticofugal pathways, there is a change in the organisation of axons. At rostral levels, the order corresponds roughly to the spatial distribution of the cells of origin, but more caudally, this changes to an arrangement of axons that has no readily apparent order. A similar change has been observed along the course of the retinofugal pathway, where a decrease of spatial order in the fibre distribution has been associated with a reordering of axons according to their temporal sequence of outgrowth.

Animals↗

Regulation of the polysialylated form of the neural cell adhesion molecule in the developing striatum: effects of cortical lesions.

Early in development, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is expressed by growth cones, neuronal processes, and neuronal cell bodies. In rat striatum, PSA-NCAM expression becomes progressively restricted to pre- and postsynaptic membranes and is undetectable by postnatal day 25 (P25), i.e., after corticostriatal synaptogenesis. This study examined the effects of cortical lesions performed on P14, when the corticostriatal projection is already primarily unilateral and cortical inputs have not yet formed asymmetric synapses on striatal neurons. Rats were killed on P25, and PSA-NCAM expression was examined by immunoblotting and immunohistochemistry with light and electron microscopy. In contrast to the case in controls, PSA-NCAM expression was maintained in the striatum of lesioned pups. Ultrastructural studies showed that PSA-NCAM was present 1) in growth cone-like structures and neuronal processes and 2) in striatal neurons. Together with the presence of growth cones, the observation that the number of asymmetric synapses was unchanged in the denervated striatum suggests that axonal sprouting occurred in response to the lesion. This was confirmed by axonal labeling in the denervated striatum after injection of Fluoro-Ruby in the contralateral cortex. The data indicate that P14 cortical lesions affect PSA-NCAM expression in the developing striatum 1) by inducing a robust axonal plasticity resulting in the presence of immature presynaptic elements that contain PSA-NCAM and 2) by delaying the loss of PSA-NCAM expression in striatal neurons, suggesting that the lesion affects the time course of striatal maturation.

Aging↗

Axonal regrowth upregulates beta-actin and Jun D mRNA expression.

When quiescent cells are perturbed, mRNAs encoding proteins that regulate gene transcription and the cell cycle are expressed at higher level. Jun and Fos are examples of proteins that mediate mitogenic signals and influence differentiation. In neurons, axon interruption (axotomy) increases the content of actin, tubulin, Jun D, and c-Jun proteins in association with increases in actin mRNA levels. Jun D protein binds to gene promoter regions, and its expression has been linked to several aspects of cell differentiation. Because Jun D and beta-actin messages have been described as "constitutive" in expression, we wanted to know whether these messages were responsive to axotomizing lesions of the sciatic motor nerve. We crushed the right sciatic nerve in Sprague-Dawley rats and extracted mRNA from the half spinal cord that serves each leg. At 4 days, Northern blots showed a 2.3-fold increase in beta-actin mRNA and a 2.5-fold increase in Jun D mRNA in the right hemicord. In situ hybridization showed either an undiminished or increased concentration of both mRNAs in motor neurons ipsilateral to the lesion at 4 days, even though many had enlarged two-to threefold. By introducing Fluoro-Ruby at the axotomy site, we were able to show that only the axotomized neurons have enlarged. We conclude that aspects of axonal regeneration resemble the embryonic program for neuronal differentiation and are reinitiated by axotomy.

Actins↗

Tracing of the entorhinal-hippocampal pathway in vitro.

In vitro tract tracing allowing for continuous observation of the perforant path is a crucial prerequisite for experimental studies on the entorhinal-hippocampal interaction in an organotypic slice culture containing the entorhinal cortex, the perforant path, and the dentate gyrus (OEHSC). We prepared horizontal slices of the temporal entorhinal-hippocampal region of the rat on a vibratome, and the perforant path axons were traced by application of the fluorescent tracer Mini Ruby on the entorhinal cortex. After 2 days in vitro (div), the perforant path became visible in most cultures. Entorhinal neurons and single perforant fibers could be followed to the outer molecular layers of the dentate gyrus by in vitro fluorescence microscopy and it was possible to monitor the perforant path directly over a period of 25 div. Moreover, ultrastructural analysis proved the existence of traced perforant path boutons forming synapses with spines and dendritic shafts in the outer molecular layers of the dentate gyrus. Transsection of the prelabelled perforant path in vitro resulted in anterograde degeneration and subsequent phagocytosis of axonal material by activated microglial cells in the zone of denervation. In conclusion, in vitro tracing demonstrates the maintenance of the entorhinal-hippocampal pathway in OEHSCs and permits monitoring of dynamic changes in the prelabeled perforant path after various lesion paradigms, e.g., transsection or neurotoxin treatment. This approach permits further studies on the efficacy of neuroprotectants, cytokines, and growth factors in the treatment of lesion-induced neuronal degeneration.

Animals↗