New approaches to the laser treatment of vascular lesions

The pulsed dye laser (PDL) was developed based on the concept of selective photothermolysis. Using a wavelength of light well absorbed by the target and a pulse duration short enough to spatially confine thermal injury, specific vascular injury could be produced. While the PDL revolutionized the treatment of port wine stains (PWS) and a variety of other vascular lesions, the mathematical model predicted that the ideal thermal relaxation time for the vessels in PWS is actually 1-10 msec, not 450 microseconds. These original theoretical calculations have been proved correct recently in a study using both an animal vessel model and in human PWS. Longer wavelengths of light within the visible spectrum penetrate deeper into the skin and are more suitable for deeper vessels; while longer pulse duration is required for larger calibre vessels. A variety of lasers have been developed recently for the treatment of vascular lesions that incorporate these concepts into their design, including PDL at 1.5 msec, a filtered flash-lamp pulsed light source with pulse durations of 1-20 msec, several 532 nm pulsed lasers with pulse durations of 1 to as high as 100 msec, long pulsed alexandrite lasers at 755 nm with pulse durations up to 20 msec, pulsed diode lasers in the 800-900 nm range, and long pulsed 1064 Nd:YAG sources. Preliminary results are encouraging.     

Synopsis of laser assisted hair removal systems

Conventional treatment options for hypertrichosis and hirsutism are tedious and time consuming. Laser hair removal offers an efficient way to permanently reduce excessive hair growth. Hair is damaged using the principle of selective photothermolysis with wavelengths of light well absorbed by follicular melanin and pulse durations that selectively thermally damage the target without damaging surrounding tissue. Patients with dark hair and light skin are ideal candidates. Multiple treatments (3 to 6) performed every 6-8 weeks are necessary to achieve a permanent reduction of hair growth. As the field develops, a better sense of the effectiveness of laser hair removal will evolve and reasonable expectations will be determined.     

A comparison of two passive agglutination procedures with enzyme-linked immunosorbent assay for rubella antibody status

A total of 293 sera, submitted for rubella immune status, were tested by enzyme-linked immunosorbent assay (ELISA) and two passive agglutination procedures. The Rubascan Kit showed a higher agreement (97.6%) with ELISA than the Rubaquick Kit (95.2%). Rubascan was also easier to read, especially low-positive sera.     

Intranuclear rodlets and associated true intranuclear bodies in normal cultured human dermal papilla cells

The dermal papilla is believed to exert controlling influences on hair growth. This report documents, for the first time, the occurrence of intranuclear rodlets in normal cultured human dermal papilla cells. Intranuclear rodlets have been observed predominantly in normal neurons, neural neoplasms, and paraneuromas. Whereas intranuclear rodlets and complex intranuclear bodies have not been identified in dermal papilla cells in vivo, they were observed, by light microscopy and transmission electron microscopy, in primary and subsequent passaged cultures in all 10 individuals examined. Intranuclear rodlets and bodies were not found, however, in parallel cultures of scalp dermal fibroblasts from the same individuals. Rodlet ultrastructure in cultured dermal papilla cells exhibited many features in common with previous reports on rodlets in neuronal and paraneuronal cells. Features that differentiated the rodlets in this study, however, included: doublet/triplet rodlets in the same nucleus; rodlets or crystalline filament bundles within complex nuclear inclusions; close relationship with the nuclear membrane, and their frequent intimate association with intranuclear bodies; and nucleoli and fine chromatin-distinct fibrillar material. Although the function of these true intranuclear inclusions in dermal papilla cells is unknown, it is noteworthy that they were present in these highly metabolically active fibroblasts while absent in comparatively less active dermal fibroblasts, and may indeed be a marker for this fibroblast cell type.     

Mechanism of thioamide drug action against tuberculosis and leprosy

Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically effective in the treatment of Mycobacterium tuberculosis, M. leprae, and M. avium complex infections. Although generally considered second-line drugs for tuberculosis, their use has increased considerably as the number of multidrug resistant and extensively drug resistant tuberculosis cases continues to rise. Despite the widespread use of thioamide drugs to treat tuberculosis and leprosy, their precise mechanisms of action remain unknown. Using a cell-based activation method, we now have definitive evidence that both thioamides form covalent adducts with nicotinamide adenine dinucleotide (NAD) and that these adducts are tight-binding inhibitors of M. tuberculosis and M. leprae InhA. The crystal structures of the inhibited M. leprae and M. tuberculosis InhA complexes provide the molecular details of target–drug interactions. The purified ETH-NAD and PTH-NAD adducts both showed nanomolar K_is against M. tuberculosis and M. leprae InhA. Knowledge of the precise structures and mechanisms of action of these drugs provides insights into designing new drugs that can overcome drug resistance.     

Intravascular glucocorticoid metabolism during inflammation and injury in mice

11beta-hydroxysteroid dehydrogenases (11betaHSDs) catalyze interconversion of 11-hydroxy-glucocorticoids with inactive 11-keto metabolites. In blood vessel walls, loss of 11betaHSD1 is thought to reduce local glucocorticoid concentrations, reducing the progression of atheroma and enhancing angiogenesis. Conversely, on the basis that 11betaHSD1 is up-regulated approximately 5-fold by inflammatory cytokines in cultured human vascular smooth muscle cells, it has been proposed that increased 11betaHSD1 during vascular inflammation provides negative feedback suppression of inflammation. We aimed to determine whether inflammation and injury selectively up-regulate 11betaHSD1 reductase activity in vitro and in vivo in intact vascular tissue in mice. In isolated mouse aortae and femoral arteries, reductase activity (converting 11-dehydrocorticosterone to corticosterone) was approximately 10-fold higher than dehydrogenase activity and was entirely accounted for by 11betaHSD1 because it was abolished in vessels from 11betaHSD1(-/-) mice. Although 11betaHSD1 activity was up-regulated by proinflammatory cytokines in cultured murine aortic smooth muscle cells, no such effect was evident in intact aortic rings in vitro. Moreover, after systemic inflammation induced by ip lipopolysaccharide injection, there was only a modest (18%) increase in 11beta-reductase activity in the aorta and no increase in the perfused hindlimb. Furthermore, in femoral arteries in which neointimal proliferation was induced by intraluminal injury, there was no change in basal 11betaHSD1 activity or the sensitivity of 11betaHSD1 to cytokine up-regulation. We conclude that increased generation of glucocorticoids by 11betaHSD1 in the murine vessel wall is unlikely to contribute to feedback regulation of inflammation.     

The "hybrid flip-over" technique for anterior leaflet prolapse repair

Repair of the anterior mitral leaflet or bi-leaflet prolapse is technically more demanding than repair of the posterior mitral leaflet. Although several techniques have been proposed for the repair of anterior mitral leaflet prolapse during bi-leaflet repair, practical challenges remain, including the determination of the appropriate length for artificial chords. Herein we describe a novel and reproducible technique for bi-leaflet mitral valve repair, including those with extensive anterior mitral leaflet prolapse.