Hypercortisolism caused by ritonavir associated inhibition of CYP 3A4 under inhalative glucocorticoid therapy. 2 case reports and a review of the literature.

Recent in vitro and in vivo studies have shown a potent inhibition of cytochrome P450 CYP3A4 through human immune deficiency virus (HIV) protease inhibitors (PIs). The PI ritonavir is described as the most potent compound within these CYP3A4 inhibitors. We present 2 cases who developed the sequelae of glucocorticoid excess following ritonavir therapy and inhalative glucocorticoid treatment: A 60-year-old HIV positive man developed the typical symptoms of Cushing's syndrome and a 52-year-old HIV positive man developed severe osteoporosis.

An efficient approach to converting three-dimensional image data into highly accurate computational models.

Image-based meshing is opening up exciting new possibilities for the application of computational continuum mechanics methods (finite-element and computational fluid dynamics) to a wide range of biomechanical and biomedical problems that were previously intractable owing to the difficulty in obtaining suitably realistic models. Innovative surface and volume mesh generation techniques have recently been developed, which convert three-dimensional imaging data, as obtained from magnetic resonance imaging, computed tomography, micro-CT and ultrasound, for example, directly into meshes suitable for use in physics-based simulations. These techniques have several key advantages, including the ability to robustly generate meshes for topologies of arbitrary complexity (such as bioscaffolds or composite micro-architectures) and with any number of constituent materials (multi-part modelling), providing meshes in which the geometric accuracy of mesh domains is only dependent on the image accuracy (image-based accuracy) and the ability for certain problems to model material inhomogeneity by assigning the properties based on image signal strength. Commonly used mesh generation techniques will be compared with the proposed enhanced volumetric marching cubes (EVoMaCs) approach and some issues specific to simulations based on three-dimensional image data will be discussed. A number of case studies will be presented to illustrate how these techniques can be used effectively across a wide range of problems from characterization of micro-scaffolds through to head impact modelling.

Two large liver abscesses complicating Crohn's disease.

A 20-year-old woman with active Crohn's disease had an abrupt onset of high fever accompanied by an elevation of serum gamma-glutamyltransferase and alkaline phosphatase. Her past medical history included a course of corticosteroid therapy for 7.5 months and a resection of the terminal ileum and the cecum 2 months before admission. At that time an ileoascendostomy had been performed, revealing a walled-off perforation of the colon into the retroperitoneal space. Sonography revealed 2 large abscesses in the right lobe of the liver. After beginning antibiotics, ultrasound-guided percutaneous aspiration and drainage with a pigtail catheter were performed for both abscesses leading to a rapid reduction of their size and an improvement in the patients general condition. Liver abscess represents a rare complication of Crohn's disease. A review of the literature is presented.

Human-derived and new synthetic injectable materials for soft-tissue augmentation: current status and role in cosmetic surgery.

The recent development of human-derived and new synthetic filling agents heralds a new era in soft-tissue augmentation. Many of the disadvantages of xenogenic and prior exogenous materials have been overcome with the advent of these autologous, allogeneic, and inert synthetic alternatives. Early reports using human-derived and inert exogenous filling agents have demonstrated good results and prolonged correction. It is too early, however, to assess the long-term efficacy of these agents. Future investigations should include histologic examination after facial implantation to document long-term safety and efficacy.

Severe iron deficiency anemia in young children.

We retrospectively characterized clinical features of 55 patients with severe nutritional iron deficiency anemia. Anemia was commonly discovered in the absence of related complaints. Forty percent of patients were of Southeast Asian ancestry. Most were treated successfully with iron therapy alone; 8 required transfusion.

Effect of botulinum toxin type A on movement-associated rhytides following CO2 laser resurfacing.

BACKGROUND: Many patients who undergo CO2 laser resurfacing for correction of rhytides experience recurrence of movement-associated wrinkles within 6 to 12 months following the laser procedure. OBJECTIVE: The purpose of this study was to evaluate the effect of botulinum toxin type A (Botox) injections on movement-associated rhytides following cutaneous laser resurfacing. METHODS: Forty patients who had received full face CO2 laser resurfacing for the treatment of facial rhytides were randomized to receive Botox injections to the glabella, forehead or lateral canthal regions or to receive no additional treatment (control group). Clinical and photographic assessments were performed at baseline and at 3, 6 and 9 months. RESULTS: Enhanced and more prolonged correction of forehead, glabellar and/or lateral canthal rhytides was observed in patients treated with Botox injections postoperatively compared to non-Botox treated control patients. CONCLUSION: The use of botulinum toxin type A following cutaneous CO2 laser resurfacing results in prolonged correction of movement-associated rhytides. It is advised that patients receive information regarding the benefits of maintenance therapy with botulinum toxin as part of their routine preoperative education.

Effect of pretreatment on the incidence of hyperpigmentation following cutaneous CO2 laser resurfacing.

BACKGROUND: Transient hyperpigmentation is the most common complication seen following cutaneous carbon dioxide (CO2) laser resurfacing. OBJECTIVE: The purpose of this study was to determine whether the use of a topical skin lightening regimen prior to cutaneous laser resurfacing reduces the incidence of post-laser resurfacing hyperpigmentation. METHODS: One hundred consecutive CO2 laser resurfacing patients (skin types I-III) were randomized to receive preoperative treatment with 10% glycolic acid cream twice daily (n=25), hydroquinone 4% cream qHS and tretinoin 0.025% cream twice daily (n=25) or no pretreatment (n=50, control) for at least 2 weeks. Clinical and photographic assessments were performed prior to laser resurfacing and at 4 and 12 weeks following treatment. RESULTS: There was no significant difference in the incidence of post-CO2 laser resurfacing hyperpigmentation between subjects who received pretreatment with either topical glycolic acid cream or combination tretinoin/hydroquinone creams and those who received no pretreatment regimen. CONCLUSION: It is postulated that reepithelialization after cutaneous laser resurfacing includes follicular melanocytes that have not been affected by topical pretreatment. When instituted as a component of the skin care regimen postoperatively, topical hydroquinone, tretinoin and/or glycolic acid preparations may be helpful in reducing post-laser resurfacing hyperpigmentation.

Improvement of infraorbital hyperpigmentation following carbon dioxide laser resurfacing.

BACKGROUND: Many patients who request cutaneous carbon dioxide (CO2) laser resurfacing for correction of periorbital rhytides also complain of "dark circles" under their eyes. OBJECTIVE: This study was conducted in order to determine the effectiveness of high-energy pulsed CO2 laser treatment in reducing infraorbital hyperpigmentation. RESULTS: Significant lightening of infraorbital hyperpigmentation was observed 9 weeks following CO2 laser resurfacing. Melanin reflectance spectrometry readings did not correlate with clinical findings. CONCLUSIONS: This study represents the first report of the successful use of a non-pigment-specific laser system for the treatment of infraorbital dark circles. The lack of correlation of melanin spectrometry readings with clinical assessment likely represents an insufficient follow-up time period.

Autologous human collagen and dermal fibroblasts for soft tissue augmentation.

BACKGROUND: Augmentation of soft tissue defects can be achieved through intradermal injection of silicone, animal collagen, plasma-gelatin mixture, and fat. Due to their rapid degradation in vivo, however, clinical effects are typically transient. The use of autologous human collagen could conceivably result in sustained clinical improvement due to decreased collagen degradation. OBJECTIVE: The purpose of this study was to determine whether prolonged dermal correction could be achieved through injection of autologous human fibroblasts. RESULTS: Significant sustained clinical improvement was observed in two of the original 12 patients entered into the study. The nasolabial fold region was shown to be the most responsive facial area to treatment. CONCLUSIONS: The use of injectable autologous human collagen for soft tissue correction remains an intriguing prospect. While the findings of this study indicate possible sustained clinical improvement using this autologous system in some patients, it remains difficult to predict the degree and duration of individual response in various areas.

Effect of topical vitamin C on postoperative carbon dioxide laser resurfacing erythema.

BACKGROUND: Postoperative erythema of several months duration is a universal and problematic side effect of cutaneous carbon dioxide (CO2) laser resurfacing. OBJECTIVE: This study was conducted in order to determine the effectiveness of two formulations of topical ascorbic acid in reducing the degree and duration of post-CO2 laser resurfacing erythema. RESULTS: The application of topical L-ascorbic acid in an aqueous formulation resulted in a significant decrease in post-CO2 laser resurfacing erythema by the eighth postoperative week when compared with laser-irradiated skin that had not received topical vitamin C. The application of topical ascorbic acid in a cream formulation did not result in a significant reduction in post-CO2 laser resurfacing erythema. CONCLUSION: Topical L-ascorbic acid, when used in an appropriate vehicle and when initiated at an appropriate postoperative period, may decrease the degree and duration of erythema after cutaneous CO2 laser resurfacing. It is presumed that the anti-inflammatory effect of vitamin C is responsible for the clinical changes observed in this study.

Comparison of the long-pulse dye (590-595 nm) and KTP (532 nm) lasers in the treatment of facial and leg telangiectasias.

BACKGROUND: Telangiectasias develop on the face secondary to genetic predisposition, chronic actinic damage, collagen vascular disease, topical steroid application, and disorders of vascular regulation including acne rosacea. Linear and "spider" telangiectasias develop on the legs, especially in women beginning in the second to third decade, secondary to multiple factors including genetic predisposition, gravity, pregnancy, and trauma. OBJECTIVE: The purpose of this investigation was to compare the 590- and 595-nm long-pulse (1.5 msec) dye laser and KTP (532 nm) laser in the treatment of facial and leg telangiectasias. RESULTS: For both facial and lower extremity telangiectasias, the difference in improvement ratings between the two lasers following both one and two treatment sessions was statistically significant. CONCLUSION: Both the flashlamp-pumped long-pulse dye laser and the KTP laser may play a role in the treatment of facial and leg telangiectasias. However, when used to treat vessels on the lower extremities, both of these laser systems are probably best used in conjunction with sclerotherapy of the larger "feeding" reticular veins. While long-pulse dye laser irradiation achieves superior vessel clearance, patients may prefer multiple treatments with the KTP laser due to its low side effect profile and decreased associated pain.

Treatment of scars: a review.

Hypertrophic scars and keloids occur as the result of an exaggerated wound healing response of the skin following injury. In addition to presenting a cosmetic concern, hypertrophic scars and keloids may be painful or pruritic and may restrict range of motion. There is no universally accepted treatment modality resulting in permanent hypertrophic or keloid scar ablation. Atrophic scars secondary to surgery, trauma, and common conditions such as acne vulgaris and varicella may also be disfiguring. This review discusses the etiology and clinical course of hypertrophic, keloid, and atrophic scars. The vast array of treatment modalities which have been implemented in an effort to eradicate scars are reviewed. The advent and development of laser technology represents perhaps the most promising treatment modality for the cosmetic and functional improvement of cutaneous scars.

Laser resurfacing of atrophic scars.

Many patients seek treatment for the disfigurement caused by obvious variations in skin texture secondary to atrophic scarring. Many different procedures, including dermabrasion, chemical peels, punch grafting, and augmentation with filling materials, have been implemented for the treatment of atrophic scars. With the advent of high-energy, pulsed and scanned CO2 laser technology, precisely controlled, layer-by-layer tissue vaporization may be achieved with minimal thermal damage to adjacent skin. Atrophic scars resulting from acne, surgery, or trauma respond more favorably to laser resurfacing than to other, more conventional forms of treatment when proper techniques are employed.

Resurfacing of atrophic facial acne scars with a high-energy, pulsed carbon dioxide laser.

BACKGROUND: Treatment of atrophic acne scars has been limited to the use of such traditional treatments as dermabrasion and chemical peels for many years. Recently, the addition of high-energy, pulsed carbon dioxide (CO2) lasers to the treatment armentarium has created renewed enthusiasm for cutaneous resurfacing due to their ability to create specific thermal injury with limited side effects. OBJECTIVE: To determine the effectiveness of a high-energy, pulsed CO2 laser in eliminating atrophic facial scars and to observe for side effects. METHODS: Fifty patients with skin phototypes I-V and moderate to severe atrophic facial acne scars were included in the study. Each patient received one high-energy, pulsed CO2 laser treatment using identical laser parameters by the same experienced laser surgeon. Baseline and 1-, 4-, 8-, 12-, and 24-week postoperative photographs and clinical assessments were obtained in all patients. Textural analysis of skin before and after laser irradiation were obtained in 10 patients to confirm clinical impressions. Clinical evaluations were conducted independently by two blinded assessors. RESULTS: There was an 81.4% average clinical improvement observed in acne scars following laser treatment. Skin texture measurements of laser-irradiated scars were comparable to those obtained in normal adjacent skin. Side effects were limited to transient hyperpigmentation lasting an average of 3 months in 36% of patients. Prolonged erythema (2 months average) was usual and considered to be a normal healing response. No hypertrophic scarring was observed following laser treatment. CONCLUSION: High-energy, pulsed CO2 laser treatment can safely and effectively improve or even eliminate atrophic facial scars and provides many benefits over traditional treatment methods.

The presentation, frequency, and outcome of bacteremia among children with sickle cell disease and fever.

All patients with positive blood cultures who were admitted to our children's hospital for sickle cell disease and fever over a 27-month period underwent chart review. Of 517 admissions, there were 10 (1.9%) positive blood cultures. These occurred more frequently in children less than two years old and in children with indwelling central venous catheters. All but one would have been considered at high risk for bacteremia at admission owing to an ill appearance, a focus of infection, or a central venous catheter in place. The one patient with a positive blood culture who did not have one of these three criteria had a benign hospital course on parenteral antibiotics with blood cultures turning negative within one day of presentation. Outpatient management strategies with antibiotics in selected children with sickle cell disease and fever merit further study.

Erythroid progenitors in the peripheral blood of children with sickle cell disease.

PURPOSE: The goals of this study were (a) to determine the number of peripheral blood burst forming units-erythroid (BFU-E); (b) to define the relationship between circulating BFU-E number and fetal hemoglobin (HbF) level; and (c) to define the relationship between BFU-E number and age in pediatric sickle cell disease (SCD) patients. PATIENTS AND METHODS: Fetal hemoglobin (HbF) level and peripheral blood BFU-E number were determined in children < 18 years of age with SCD in a steady state of their disease. These data were compared with those of normal children. RESULTS: An increased number of BFU-E was observed in the peripheral blood of children with SCD compared with normals (30.7 vs. 15.7 per 10(5) mononuclear cells, respectively; p = 0.009). Overall there was the suggestion of a direct relationship between HbF level and peripheral blood BFU-E number (regression coefficient = 0.445; p = 0.06). Additionally, a strong inverse relationship between BFU-E number and age (regression coefficient = -0.671; p < 0.0001) was observed. CONCLUSIONS: In children with SCD (a) there are an increased number of peripheral blood BFU-E compared with normal children; (b) the inverse relationship between HbF level and BFU-E number observed in adult SCD patients is not seen in children; and (c) there is a strong inverse relationship between age and BFU-E number. This information may help to further clarify the relationship between peripheral blood BFU-E and erythropoietic stress.

Effects of lead and benzene on the developmental stability of Drosophila melanogaster.

: Fluctuating asymmetry has been proposed as a general and sensitive indicator of developmental instability. Although there have been many field studies of fluctuating asymmetry in populations exposed to toxic chemicals, there have been few laboratory studies. To test the hypothesis that stress from toxic chemicals causes an increase in fluctuating asymmetry, we exposed larval Drosophila melanogaster to six concentrations of lead and benzene in their food. Lead and benzene caused neither a significant reduction in the number of emerging adult flies, nor a significant difference in the average number of sternopleural bristles. Flies exposed to lead at 10mg kg(-1) and benzene at 1000 mg kg(-1), however, showed increased fluctuating asymmetry of sternopleural bristles. Higher concentrations (10,000 mg kg(-1)) of benzene caused a transition from fluctuating asymmetry to directional asymmetry. Flies exposed to benzene at 10,000 mg kg(-1) also eclosed more than a day earlier than flies exposed to it at 0-1,000 mg kg(-1).

Influence of prostaglandins on electrolyte metabolism of human trabecular bone in vitro.

A procedure was developed to investigate the electrolyte metabolism of human trabecular bone and its regulation in vitro, in particular the influence of prostaglandins. Trabecular bone was prepared from femoral heads of patients who had undergone hip replacement surgery for coxarthrosis. 500 mg samples were incubated in modified EAGLE's minimal essential medium. Net electrolyte movements between bone and incubation medium were measured. During 6 hours of incubation PGE2 caused an increase in the release of calcium and magnesium from bone into incubation medium as compared to controls. The effect of PGE2 was dose-dependent and comparable to that of human parathyroid hormone 1-34 (hPTH 1-34) whereas hPTH 3-34 had no effect. Human calcitonin (hCT) caused a decrease in the release of calcium and magnesium. PGE2 was found to be the most potent prostaglandin. PGE1 and PGF2 alpha had about 50% and PGF1 alpha about 40% of the potency of PGE2. PGA1 and PGA2 had no effect. The effect of PGE2 could be completely inhibited by hCT and was not further enhanced by hPTH 1-34. Magnesium movement was affected in the same way as calcium movement, while phosphate movement and release of alkaline phosphatase and hydroxyproline from bone into incubation medium were not affected by prostaglandins.

Sternocostoclavicular hyperostosis: painful swelling of the sternum, clavicles, and upper ribs. Report of two new cases.

Five patients had persistent, pulling pain in the sternum, clavicles, and upper ribs that was exacerbated by cold and dampness. Clublike, symmetrical enlargement of the clavicles was seen and, in two patients, venous congestion of the upper half of the body. All patients had a constantly elevated erythrocyte sedimentation rate. Radiologically there was symmetrical hyperostosis of the sternal and middle portions of the clavicles, synostosis of the sternoclavicular joints, a widened and thickened sternum, and varying degrees of involvement of the upper ribs. X-ray findings did not change over several years. Phlebography showed bilateral subclavian vein occlusion in three patients and unilateral occlusion in one. Biopsies of the clavicles showed a characteristic hyperostotic sclerosis of the spongiosa. The cause of this sternocostoclavicular hyperostosis is unknown, but clinical, radiologic, and histologic findings indicate that it may represent a distinct, hitherto undescribed entity.