"Melanocytic Nests Arising in Lichenoid Inflammation": Reappraisal of the Terminology "Melanocytic Pseudonests".

Pseudonests or pseudomelanocytic nests represent aggregates of cells and cell fragments, including keratinocytes, macrophages, lymphocytes, and occasional melanocytes. Pseudomelanocytic nests in the setting of lichenoid inflammation can mimic atypical melanocytic proliferations. Several reports documented nonspecific staining of pseudonests with melanoma antigen recognized by T cells-1/Melan-A, which can be detected in the cytoplasm of nonmelanocytic cells. In contrast, nuclear stains, such as MITF and SOX10, avoid this nonmelanocyte cytoplasmic staining. The authors have previously proposed the term melanocytic pseudonests to describe junctional nests with numerous (>2) true melanoma antigen recognized by T cells-1/Melan-A, SOX10, and MITF in a nonmelanocytic lesion with lichenoid inflammation (unilateral lichen planus pigmentosus/erythema dyschromicum perstans). In this study, the authors report another case of this phenomenon arising in a different lichenoid inflammatory dermatitis (lichen planus). The immunophenotype and number of clustered true melanocytes indicate that these dermoepidermal aggregates represent true melanocytic nests and not pseudonests of any type. Therefore, the authors propose the revised terminology of "melanocytic nests arising in lichenoid inflammation" to describe this novel pattern of benign melanocytic reorganization or proliferation in a subset of lichenoid dermatitides. Because this phenomenon can mimic atypical melanocytic proliferations, clinicopathologic correlation is essential for the correct diagnosis.

Remission of refractory benign familial chronic pemphigus (hailey-hailey disease) with the addition of systemic cyclosporine.

BACKGROUND: Benign chronic familial pemphigus (BFCP) is an autosomal dominant dermatosis characterized by flares of painful and often debilitating blistering lesions in high friction areas of the body such as the groin, axillae, lateral neck, and intergluteal cleft. Limited knowledge of its pathophysiology has made treatment of BFCP a considerable challenge and efficacy with current first line therapies, topical corticosteroids and antibiotics, is variable. CASE REPORT: We present a case of this disease in a 52 year old woman that has responded dramatically to the addition of oral cyclosporine to her existing regimen of oral acitretin, with significant improvement of skin lesions, mobility, and quality of life. Cyclosporine's mechanism of action in BFCP is poorly understood, although it possibly acts through inhibition of proinflammatory cytokines in keratinocytes or modulation of intracellular calcium. BFCP, the use of cyclosporine for its treatment, and possible mechanisms of action of cyclosporine are reviewed.

Remission of refractory benign familial chronic pemphigus (hailey-hailey disease) with the addition of systemic cyclosporine.

BACKGROUND: Benign chronic familial pemphigus (BFCP) is an autosomal dominant dermatosis characterized by flares of painful and often debilitating blistering lesions in high friction areas of the body such as the groin, axillae, lateral neck, and intergluteal cleft. Limited knowledge of its pathophysiology has made treatment of BFCP a considerable challenge and efficacy with current first line therapies, topical corticosteroids and antibiotics, is variable. CASE REPORT: We present a case of this disease in a 52 year old woman that has responded dramatically to the addition of oral cyclosporine to her existing regimen of oral acitretin, with significant improvement of skin lesions, mobility, and quality of life. Cyclosporine's mechanism of action in BFCP is poorly understood, although it possibly acts through inhibition of proinflammatory cytokines in keratinocytes or modulation of intracellular calcium. BFCP, the use of cyclosporine for its treatment, and possible mechanisms of action of cyclosporine are reviewed.

Dynamic force distribution during level walking under the feet of patients with chronic ankle instability.

OBJECTIVES: To examine changes in the pattern of force transfer between the foot and the floor associated with chronically sprained ankles by measuring the peak forces and their timing under several regions of the feet during level walking. METHODS: Twelve young male subjects (mean (SD) age 21 (2) years) with recurrent ankle sprains were studied. Seven of them had unilateral and bilateral chronic instability and laxity, and five had bilateral instability. Twelve healthy men (without orthopaedic or medical disease) served as a control group. Subjects walked at their own pace along a 7 m walkway, which included a Mini-EMED pressure distribution measuring system. The variables measured were relative peak force (fraction of body weight) and relative timing (fraction of stance time). These variables were measured under six regions of interest in each foot print: heel, midfoot, medial, central, and lateral forefoot, and toes. RESULTS: (a) A significant delay to the time of peak force under the central and lateral forefoot and toes in subjects with chronic ankle instability. (b) A significant decrease in the relative forces under the heel and toes and an increase in the relative forces under the midfoot and lateral forefoot in subjects with chronic ankle instability. (c) In the patients with unilateral instability, there were no significant differences in any of the variables between the injured and non-injured foot. CONCLUSIONS: In patients with chronic ankle instability, there is a slowing down of weight transfer from heel strike to toe off, a reduced impact at the beginning and end of the stance phase, and a lateral shift of body weight.

The effect of shoe sole composition on in vivo tibial strains during walking.

To test the hypothesis that shoe sole composition can affect the level of bone strain and strain rates that contribute to the development of stress fractures, in vivo tibial strain measurements were made during treadmill walking while wearing four shoes which differed only in their sole composition. Soles of 65 Shore A polyurethane with an embedded heel air cell had significantly lower compression and shear strains and shear strain rates than soles of 65, 75 and a composite of 40/65 Shore A polyurethane with no embedded air cells. A sole composed of 65 Shore A polyurethane with an embedded air cell can potentially be protective against stress fracture in a walking shoe.

Optical processing of radiographic trabecular pattern versus bone mineral density of proximal femur as measures of bone strength.

The purpose of the present study was to evaluate a noninvasive method that utilizes optical processing to analyze the trabecular pattern on bone radiographs. The trabecular network on proximal femur radiographs of 17 intact cadaveric femora was analyzed by optical Fourier transform, yielding a trabecular bone index (TBI) at several locations. The bone mineral density (BMD) of the proximal femur was measured by dual X-ray absorptiometry. Dimensions of the proximal femur were obtained from the radiograph. The bones were fractured in a "fall configuration" to yield the fracture load. A multiple regression model, combining only radiograph- derived parameters-bone dimensions and the TBI at the intertrochanteric region and at the greater trochanter-yielded a correlation of 0.938 with the fracture load. A model combining the BMD at the greater trochanter and at the neck yielded a correlation of 0.928 with the fracture load. When all the variables were introduced into a combined analysis, the correlation with the fracture load was 0.973. The TBI obtained by optical processing of the trabecular bone pattern on femoral radiographs together with bone dimensions derived from these radiographs may serve as an effective estimate for hip fracture risk.

A home exercise program for tibial bone strengthening based on in vivo strain measurements.

OBJECTIVE: To compare the strain and strain rates generated during lower limb calisthenics with walking, an exercise that has been found to have only minimal effect on bone mass. Strengthening of bone, while it still has adaptive ability, can be achieved by exercise. Mechanical loading during physical activity produces strains and strain rates within the bones. It is thought that strain and strain rates higher than the usual provide the stimulus for the bones' adaptation. DESIGN: Three strain-gauged bone staples were inserted percutaneously in a 30 degrees rosette pattern in the medial aspect of the midtibial diaphysis of two volunteers. The principal compression, tension, shear strains, and strain rates were measured during various lower limb calisthenics and compared with those of jogging and walking. RESULTS: Zig-zag hopping was in the grouping of exercises with the highest principal compression, tension, and shear strains and compression strain rates, whereas walking was in the lowest or next-to-the-lowest grouping for all principal strain or strain rates. CONCLUSION: Zig-zag hopping, based on the high strain and strain rates that it produces, may be an optimal tibial bone-strengthening exercise.

In vitro and in situ inhibition of carotenoid biosynthesis in Capsicum annuum by bleaching herbicides.

Pepper leaves treated with the herbicide J852 show an accumulation of phytoene and zeta-carotene, whereas treatment with norflurazon led to an accumulation of only phytoene. The effects of these herbicides were examined in vitro after the expression of carotenoid desaturases in Escherichia coli. Whereas norflurazon is a potent inhibitor of phytoene desaturase (PDS) (I(50) = 0.12 microM) but not of zeta-carotene desaturase (ZDS) (I(50) = 144 microM), J852 inhibits both PDS (I(50) = 23 microM) and ZDS (I(50) = 49 microM). The influence of PDS/ZDS inhibition on gene expression was examined by comparative RT-PCR. None of the examined genes, namely, encoding phytoene synthase, PDS, ZDS, or the terminal oxidase associated with phytoene desaturation, were induced upon herbicide treatment in pepper leaves or seedlings. This was unexpected because inhibition of carotene desaturation led to an up-regulation of the carotenoid biosynthetic capacity (higher amounts of accumulating precursors plus remaining colored carotenoids are present in treated tissues versus control).

Plant genome complexity may be a factor limiting in situ the transfer of transgenic plant genes to the phytopathogen Ralstonia solanacearum.

The development of natural competence by bacteria in situ is considered one of the main factors limiting transformation-mediated gene exchanges in the environment. Ralstonia solanacearum is a plant pathogen that is also a naturally transformable bacterium that can develop the competence state during infection of its host. We have attempted to determine whether this bacterium could become the recipient of plant genes. We initially demonstrated that plant DNA was released close to the infecting bacteria. We constructed and tested various combinations of transgenic plants and recipient bacteria to show that the effectiveness of such transfers was directly related to the ratio of the complexity of the plant genome to the number of copies of the transgene.

A plastid terminal oxidase associated with carotenoid desaturation during chromoplast differentiation.

The Arabidopsis IMMUTANS gene encodes a plastid homolog of the mitochondrial alternative oxidase, which is associated with phytoene desaturation. Upon expression in Escherichia coli, this protein confers a detectable cyanide-resistant electron transport to isolated membranes. In this assay this activity is sensitive to n-propyl-gallate, an inhibitor of the alternative oxidase. This protein appears to be a plastid terminal oxidase (PTOX) that is functionally equivalent to a quinol:oxygen oxidoreductase. This protein was immunodetected in achlorophyllous pepper (Capsicum annuum) chromoplast membranes, and a corresponding cDNA was cloned from pepper and tomato (Lycopersicum esculentum) fruits. Genomic analysis suggests the presence of a single gene in these organisms, the expression of which parallels phytoene desaturase and zeta-carotene desaturase gene expression during fruit ripening. Furthermore, this PTOX gene is impaired in the tomato ghost mutant, which accumulates phytoene in leaves and fruits. These data show that PTOX also participates in carotenoid desaturation in chromoplasts in addition to its role during early chloroplast development.

Do high impact exercises produce higher tibial strains than running?

BACKGROUND: Bone must have sufficient strength to withstand both instantaneous forces and lower repetitive forces. Repetitive loading, especially when bone strain and/or strain rates are high, can create microdamage and result in stress fracture AIM: To measure in vivo strains and strain rates in human tibia during high impact and moderate impact exercises. METHODS: Three strain gauged bone staples were mounted percutaneously in a rosette pattern in the mid diaphysis of the medial tibia in six normal subjects, and in vivo tibial strains were measured during running at 17 km/h and drop jumping from heights of 26, 39, and 52 cm. RESULTS: Complete data for all three drop jumps were obtained for four of the six subjects. No statistically significant differences were found in compression, tension, or shear strains with increasing drop jump height, but, at the 52 cm height, shear strain rate was reduced by one third (p = 0.03). No relation was found between peak compression strain and calculated drop jump energy, indicating that subjects were able to dissipate part of the potential energy of successively higher drop jumps by increasing the range of motion of their knee and ankle joints and not transmitting the energy to their tibia. No statistically significant differences were found between the principal strains during running and drop jumping from 52 cm, but compression (p = 0.01) and tension (p = 0.004) strain rates were significantly higher during running. CONCLUSIONS: High impact exercises, as represented by drop jumping in this experiment, do not cause higher tibial strains and strain rates than running and therefore are unlikely to place an athlete who is accustomed to fast running at higher risk for bone fatigue.

In-vivo strain measurements to evaluate the strengthening potential of exercises on the tibial bone.

Mechanical loading during physical activity produces strains within bones. It is thought that these forces provide the stimulus for the adaptation of bone. Tibial strains and rates of strain were measured in vivo in six subjects during running, stationary bicycling, leg presses and stepping and were compared with those of walking, an activity which has been found to have only a minimal effect on bone mass. Running had a statistically significant higher principal tension, compression and shear strain and strain rates than walking. Stationary bicycling had significantly lower tension and shear strains than walking. If bone strains and/or strain rates higher than walking are needed for tibial bone strengthening, then running is an effective strengthening exercise for tibial bone.

Using bone's adaptation ability to lower the incidence of stress fractures.

In three prospective epidemiologic studies of the effect of pre-military-induction sport activities on the incidence of lower extremity stress fractures during infantry basic training, recruits who played ball sports (principally basketball) regularly for at least 2 years before basic training had a significantly lower incidence of stress fractures (13.2%, 16.7%, and 3.6% in the three studies, respectively) than recruits who did not play ball sports (28.9%, 27%, and 18.8%, respectively). Preinduction running was not related to the incidence of stress fracture. To assess the tibial strain environment during these sport activities, we made in vivo strain measurements on three male volunteers from the research team. Peak tibial compression and tension strain and strain rates during basketball reached levels 2 to 5.5 times higher than during walking and about 10% to 50% higher than during running. The high bone strain and strain rates that occurred in recruits while playing basketball in the years before military induction may have increased their bone stiffness, according to Wolff's Law. The stiffer bone could tolerate higher stresses better, resulting in lower strains for a given activity and a lower incidence of stress fractures during basic training.

Effect of microwave oven induced mild hyperthermia on bone viability and strength.

Extracorporeal hyperthermia treatment of bone followed by reimplantation may be an option for treating bone tumors. However, intensive heat treatment, such as autoclaving, causes a decline of mechanical and biologic functions of bone tissue. In the current study, a microwave oven was used for minimal hyperthermic treatment, and it was found that complete eradication of all viable cells in rat bone could be achieved with minimal reduction in mechanical function. When the cells were evaluated histologically by special lactate dehydrogenase activity staining, complete bone cell death occurred after 60 seconds of heating in an empty Petri dish and after 30 seconds when heated in a Petri dish containing normal saline. Mechanical stiffness and strength of the bones, tested in three-point bending, showed no decrease after this heating. Microwave oven induced hyperthermia eradication of viable cells without significant damage to the mechanical properties may have clinical relevance in limb salvage tumor surgery.

Do axial dynamic fixators really produce axial dynamization?

The use of dynamic external fixators for the treatment of long bone fracture is widespread and well accepted. It is claimed that dynamization, i.e. small micromovements of compression/distraction at the fracture site, can be produced by allowing sliding of an inner rod within an outer housing. However, as the forces on the fixator are not direct but transferred from the bone via bone pins, there is a bending moment on the fixator. This produces "self-locking" and effectively prevents axial movements. We have studied the effect of this moment on the binding properties of the Orthofix system. The amount of movement at a simulated fracture site allowed before this locking occurs was measured and its implications discussed. It would appear that true axial dynamization does not take place using this system.

Effect of cane use on tibial strain and strain rates.

The effect of cane ambulation on hip biomechanics has been well studied, but its effect on tibial strains and strain rates is not known. To test the hypothesis that cane use may lower tibial strain and strain rates during walking, percutaneous axial extensometers were mounted on the right medial cortex of the midtibial diaphysis in seven male volunteers. In vivo peak-to-peak axial tibial strains and strain rates were measured for ipsilateral and contralateral cane usage and compared with a no cane control. Cane-assisted ambulation was not found to significantly lower strain magnitudes; however, tibial strain rates were significantly lowered by both ipsilateral and contralateral cane usage. We conclude that either ipsilateral or contralateral cane usage may be beneficial when lowering tibial strain rate is desired, such as in the treatment of tibia stress fracture or osteoarthrosis of the knee.

Effect of fatiguing exercise on longitudinal bone strain as related to stress fracture in humans.

Muscular fatigue in the training athlete or military recruit has been hypothesized to cause increased bone strain that may contribute to the development of a stress fracture. Under normal circumstances, muscles exert a protective effect by contracting to reduce bending strains on cortical bone surfaces. In vivo strain studies in dogs show that muscle fatigue following strenuous exercise elevates bone strain and changes strain distribution. However, a similar experiment has yet to be performed in humans. The purpose of this work was to test the hypothesis in humans that strenuous fatiguing exercise causes an elevation in bone strain. It was also hypothesized that this elevation is greater in younger people than in older people due to the decline in muscle strength and endurance that normally occurs with age. To test these hypotheses, strain in the tibiae of seven human volunteers was measured during walking before and after a period of fatiguing exercise. Neither hypothesis was sustained. Post-hoc analysis of the strain data suggests that strain rate increases after fatigue with a greater increase in younger as opposed to older persons. Although not conclusive, this suggests that it is strain rate, rather than strain magnitude, that may be causal for stress fracture.

Effect of moderate bone hyperthermia on cell viability and mechanical function.

Extracorporeal hyperthermia treatment of bone followed by its reimplantation may be an optional treatment of bone tumors. In this study, the authors examined the minimal hyperthermic condition in which complete eradication of all viable cells in rat bone can be achieved and the mechanical effect of this treatment on the tested bone. When the results were evaluated histologically by special lactate dehydrogenase activity staining, it was found that complete bone cell death occurred after 30 minutes of heating at 60 degrees C. Cartilage cells, including those of the epiphysis, were more resistant to thermal damage. When the ability of the specimens to proliferate in cell cultures was tested, no growth was observed after heating at temperatures of 50 degrees C or greater. The mechanical stiffness tested in the Instron machine showed decreased bone stiffness at 70 degrees C but no change in the breaking load of the bones. Controlled hyperthermia's ability to eradicate viable cells without significant damage to the mechanical properties may have clinical relevance in limb salvage tumor surgery.