Unmasking dermatofibrosarcoma protuberans: Case report of an atypical presentation complicated by post-surgical excision.

INTRODUCTION: Dermatofibrosarcoma Protuberans (DFSP) is a rare type of malignant tumor of the cutaneous soft tissue that typically involves the dermis and surrounding structures. The typical clinical presentation involves an asymptomatic, slowly enlarging, indurated plaque, usually found on the trunk. PRESENTATION OF CASE: Here we present an atypical presentation of DFSP in a patient with a recurrent mass that was initially diagnosed as a lipoma, with supporting literature and clinical considerations for post-surgical management DISCUSSION: In its earlier stages, DFSP can mimic other benign or malignant dermatological pathologies, which can complicate diagnosis purely via history and physical exam. Atypical features such as prior surgical management, morphology, and location can complicate the clinical diagnosis of DFSP. Immunohistochemistry is often required for definitive diagnosis as DFSP is CD34+ and is histologically described as spindle-cells in whorled or storiform pattern, with uniform, small elongated cells. CONCLUSION: DFSP is a rare tumor of the skin and subcutaneous tissue. Though it commonly presents with induration, skin discoloration, and telangiectasias, it is important to keep DFSP as a differential in new masses found on previous surgical sites, especially if the previous mass had a possibility of recurrence.

Transformation of Mental Health Care for U.S. Soldiers and Families During the Iraq and Afghanistan Wars: Where Science and Politics Intersect.

The cumulative strain of 14 years of war on service members, veterans, and their families, together with continuing global threats and the unique stresses of military service, are likely to be felt for years to come. Scientific as well as political factors have influenced how the military has addressed the mental health needs resulting from these wars. Two important differences between mental health care delivered during the Iraq and Afghanistan wars and previous wars are the degree to which research has directly informed care and the consolidated management of services. The U.S. Army Medical Command implemented programmatic changes to ensure delivery of high-quality standardized mental health services, including centralized workload management; consolidation of psychiatry, psychology, psychiatric nursing, and social work services under integrated behavioral health departments; creation of satellite mental health clinics embedded within brigade work areas; incorporation of mental health providers into primary care; routine mental health screening throughout soldiers' careers; standardization of clinical outcome measures; and improved services for family members. This transformation has been accompanied by reduction in psychiatric hospitalizations and improved continuity of care. Challenges remain, however, including continued underutilization of services by those most in need, problems with treatment of substance use disorders, overuse of opioid medications, concerns with the structure of care for chronic postdeployment (including postconcussion) symptoms, and ongoing questions concerning the causes of historically high suicide rates, efficacy of resilience training initiatives, and research priorities. It is critical to ensure that remaining gaps are addressed and that knowledge gained during these wars is retained and further evolved.

Conservation of leukocyte cell surface proteins: implications for the generation of monoclonal antibodies against newly identified leukocyte cell surface proteins.

The availability of mouse monoclonal antibodies has been integral to the classification of human leukocyte cell surface proteins under the "Cluster of Differentiation" or "CD" nomenclature system. The sequencing of the human genome has identified many more proteins that have characteristics similar to the known leukocyte cell surface proteins, but which have not so far been identified using monoclonal antibodies. One factor that may have limited the generation of monoclonal antibodies to some of these proteins is the high level of sequence conservation between the mouse and human proteins, in particular in the extracellular regions that are recognized by most of the widely used antibodies. An alternative approach is to use a more distant species, such as chickens, for the generation of antibody reagents. Here we compare the extent of amino acid differences in the protein CD molecules expressed by human leukocytes and their mouse and chicken homologs. The analysis confirms that the human proteins are more similar to the mouse homologs than the chicken homologs. The results indicate that chicken antibodies have the potential to be used as an alternative to mouse reagents where human-mouse sequence conservation is high.

Improved antigen binding by a CD20-specific single-chain antibody fragment with a mutation in CDRH1.

We have prepared single-chain immunoglobulin Fv fragments from the CD20-specific hybridoma HB13d. One scFv clone demonstrated strong binding to a CD20-derived peptide by ELISA and to CD20-positive cells by flow cytometry, a second had reduced binding, and a third clone did not bind the target antigen. Sequence analysis showed that all three constructs contained shared and unique amino acid changes when compared to the nearest germline match. Molecular modelling of the scFv variants revealed that several of the mutations are located in regions predicted to contact antigen, including a mutation in the heavy chain CDR1 of the strongest binding scFv construct. No similar mutation is present in the highly conserved protein sequences of a number of CD20-specific monoclonal antibodies. BIACORE analysis demonstrated that the mutated scFv had approximately three-fold greater antigen-binding activity than another clone. Competition studies showed that the scFv is able to compete with intact CD20 monoclonal antibody for binding to the target antigen. The improved antigen binding of this scFv will permit the construction of novel CD20-specific reagents for the therapy of lymphomas.

Improved psychomotor performance in aged mice fed diet high in antioxidants is associated with reduced ex vivo brain interleukin-6 production.

Psychomotor performance is decreased in the aged. This study investigated the relationship between brain oxidative stress, interleukin-6 (IL-6) production by brain tissue ex vivo and psychomotor deficits during aging, and the effects of feeding an antioxidant-rich diet on ex vivo brain IL-6 production and motor function in aged mice. Male BALBc mice reared in SPF conditions and ranging in age from 3 to 24 months were studied. There was a precipitous decline in motor function after 12 months of age and an increase in brain lipid peroxidation and IL-6 production by coronal brain slices ex vivo. In another study, 12-month-old mice were fed diets formulated to provide a disparate range of antioxidants. At 18 months of age psychomotor coordination, motor learning, and ex vivo brain IL-6 production were evaluated. Mice fed an antioxidant-rich diet had improved psychomotor coordination compared to mice fed diet adequate or low in antioxidants. When mice were tested on successive days, only those fed adequate and high antioxidants exhibited motor learning. Analysis of IL-6 production by coronal brain slices indicated that as dietary antioxidants increased, IL-6 production decreased. Collectively, these data indicate that antioxidants improve psychomotor performance in aged mice, and suggest antioxidants may be useful for reducing brain IL-6 production, which has been shown to increase in aged mice.

Increased yield and activity of soluble single-chain antibody fragments by combining high-level expression and the Skp periplasmic chaperonin.

The success of recombinant antibody fragments as diagnostic reagents and therapeutic agents depends on the availability of sufficient functional material. We have produced a bacterial expression vector that combines high-level expression driven by a modified Shine-Dalgarno sequence with the periplasmic chaperonin Skp. Using this vector, we are able to obtain higher yields of soluble antibody fragments from cultures without the need for supplementation of the culture medium during expression. The fragments produced in the presence of the Skp show improved antigen binding activity compared to when the chaperonin is absent.

Renaut bodies in the sciatic nerve of beagle dogs.

182 control Beagle dogs from 23 historical studies (14 chronic, 9 subchronic) were reviewed histologically for the presence of Renaut bodies in the sciatic nerve. Renaut bodies were found in 36.1 percent of the subchronic-study dogs and in 46.4 percent of the chronic-study dogs. The Renaut bodies most often resided in the distal sections of the sciatic nerve, specifically in the tibial branch as it traversed the knee joint in situ. There was no sex predilection. Renaut bodies were located predominately in the endoneurium, in the center of the nerve sections. There was no associated axonal degeneration, reactive gliosis, or encapsulation. The Renaut bodies were characterized as large (20 to 500 microns diameter in cross section), well-demarcated elliptical structures with an onion-skin arrangement of loosely textured, filamentous strands intermixed with sparse numbers of dark spindle-shaped nuclei. Occasionally the core displayed a more dense, intensely eosinophilic arrangement of fibers. Histochemical results included: positive acidic alcian blue, Gomori's trichrome, and Verhoeff Van Gieson's; and negative Periodic-acid Schiff, Congo Red, and Luxol fast blue/cresyl violet. Immunohistochemical results included: positive vimentin and collagen (subtypes I, II, and VI); and negative NSE, S-100, GFAP, amyloid A component, desmin, alpha-sarcomeric actin, pancytokeratin, EMA, and von Willebrand factor. Transmission electron microscopy revealed loosely arrayed, circumferentially oriented collagen fibers intermixed with varying amounts of amorphous substance and finely fibrillar material. Most of the cells comprising the Renaut body were identified as fibroblasts. No nerve fibers entered or left the Renaut body, and nearby nerves appeared to be normal structurally. Based on this characterization of Renaut bodies and in conjunction with the past literature, Renaut bodies appear to have little or no pathological significance, but rather are suggestive of a physiological adaptation in response to mechanical stress imposed on nerves.

Tumors in long-term rat studies associated with microchip animal identification devices.

Tumors surrounding implanted microchip animal identification devices were noted in two separate chronic toxicity/oncogenicity studies using F344 rats. The tumors occurred at a low incidence rate (approximately 1 percent), but did result in the early sacrifice of most affected animals, due to tumor size and occasional metastases. No sex-related trends were noted. All tumors occurred during the second year of the studies, were located in the subcutaneous dorsal thoracic area (the site of microchip implantation) and contained embedded microchip devices. All were mesenchymal in origin and consisted of the following types, listed in order of frequency: malignant schwannoma, fibrosarcoma, anaplastic sarcoma, and histiocytic sarcoma. The following diagnostic techniques were employed: light microscopy, scanning electron microscopy, and immunohistochemistry. The mechanism of carcinogenicity appeared to be that of foreign-body induced tumorigenesis.

Reconstruction of the nose damaged by cocaine.

Nasal snorting of cocaine crystals causes destruction of the septal and nasal mucosa, which eventually provides exposure of the septal cartilage and nasal bones. This exposure eventually leads to septal chrondritis and nasal bone osteomyelitis. As this process continues, the severe loss of cartilage and bone allows gradual to total collapse of the nose. Correction of this deformity is best achieved by supplying new lining; this is possible by turning nasolabial flaps into the nasal vestibule to replace the lost and released lining. Once this has been accomplished, costal cartilage grafts can be inserted along the bridge and alae to maintain the structural integrity of the reconstruction.

Designs for correction and camouflage of bilateral clefts of the lip and palate.

The bilateral cleft anomaly is difficult to correct and camouflage because of the double lack of many important landmarks and the shortness of skin in the midvertical plane. A possible solution in patients who have some columella or in those of races not needing a long columella is the strap flap advancement of the nostril sills and alar bases. In all other cases, the forked flap is the method of choice for adequate correction and camouflage of the bilateral cleft lip-nose deformity.

Cleft lip and palate treated by presurgical orthopedics, gingivoperiosteoplasty, and lip adhesion (POPLA) compared with previous lip adhesion method: a preliminary study of serial dental casts.

Comparing the treatment protocols for cleft lip and palate requires a study of facial growth and development. Serial orthodontic study models aid in delineating the effects of surgery on maxillary mandibular relationships. In 1978, a new protocol, POPLA (presurgical orthopedics followed by periosteoplasty and lip adhesion), was developed and put into practice. This article compares the results obtained using POPLA (group I) with those using the previous method (lip adhesion alone) (group II) for cases of unilateral and bilateral clefts. Complete orthodontic study models were available for 124 patients, 63 in group I and 61 in group II. Specific timing sequences and surgical details are discussed. Dental cast analyses evaluated alveolar gap, arch width, anteroposterior distance, incisor crossbite (single tooth and multiple tooth), and buccal crossbite (single and multiple tooth) at birth and at 3, 6, and 9 years of age. X-ray studies evaluated the bony bridge. Additional comments are made regarding the incidents and effects of pharyngeal flaps and bone grafts on maxillary-mandibular relationships. Results included less buccal crossbite in the POPLA group, with a wider transverse distance of the upper dental arch. There was a greater frequency of anterior crossbite in the POPLA group, and the anteroposterior distance was shorter at 6 years of age but less so by age 9. This may be because of the different orthodontic care received by the patients in the two groups. In conclusion, the POPLA approach achieves the main goal of moving the palate into a normal position and stabilizing the arch with a bony bridge that attracts teeth. It avoids the difficult anterior fistulae and presents a more symmetrical platform upon which the lip can be united and the nose can be corrected early.

Lymphocyte subpopulations in healthy 1-3-day-old infants.

The primary objective of this study was to establish reference ranges for the major (B, T, and natural killer; NK) and clinically relevant minor lymphocyte subsets in the peripheral blood of healthy 1-3-day-old infants and then to compare the results with those obtained in a group of healthy adults analyzed simultaneously. Forty-three infants aged 1-3 days and 38 healthy adults were recruited to the study to establish the median, 10th, and 90th percentiles of the proportions and absolute numbers of relevant lymphocyte subsets. The samples obtained from the healthy adults served as a flow cytometry process control in addition to providing a group comparator. The peripheral blood of the newborns (vs. adults) contained elevated proportions of total T cells (83% vs. 77%) and T helper cells (63% vs. 46%), with decreased proportions of T suppressor/cytotoxic cells (23% vs. 28%) and NK cells (4% vs. 10.5%). The newborns had a higher proportion (P < 0.0001) of immature B lymphocytes compared with those of adults (CD10+CD19+, 1.5% vs. 0% and CD20+CD5+, 13% vs. 6%), and the proportion of activated T cells was significantly lower (P < 0.0001; CD3+CD25+, 7.0% vs. 15%;CD3+HLA-DR+, 2.0% vs. 6% and CD8 and CD57, 0.0% vs. 8.0%). In contrast, the proportions of neonatal CD8 cells expressing CD28 (90.2% vs. 67.7%) and CD38 (96.6% vs. 70.9%) were significantly higher (P < 0.0001). The reference ranges for 1-3-day-old healthy newborns generated in this study provides a valuable tool for the assessment of immune abnormalities in very young infants.

Primary unilateral cleft nose correction: a 10-year follow-up.

Primary nasal correction at the time of rotation-advancement of the lip has been rendered practical by developing a symmetrical nasal platform by presurgical orthodontics and a gingivoperiosteoplasty. The nasal correction involves unilateral columella lengthening, alar cartilage positioning, and alar base cinching to present a nose within normal limits. This is accomplished before the age of recall, and by avoiding retention of the nasal deformity through childhood, it by-passes the ridicule that invariably accompanies it.

Purpuric phototherapy-induced eruption in transfused neonates: relation to transient porphyrinemia.

OBJECTIVE: Blue light phototherapy is commonly administered to neonates as treatment of indirect hyperbilirubinemia, often in conjunction with blood transfusions to treat hemolytic anemia. We observed a distinctive cutaneous complication of phototherapy in six neonates with hyperbilirubinemia. METHODOLOGY: We studied the clinical and histologic characteristics of the eruption, as well as the porphyrin levels in affected neonates. Five of the patients had erythroblastosis fetalis; the other had profound anemia from twin-twin transfusion. All of the neonates developed purpuric patches at sites of maximal exposure to the phototherapy lights, with dramatic sparing at shielded sites within 24 hours after initiation of the phototherapy. On discontinuation of phototherapy, all eruptions cleared within 1 week. Examination of skin biopsy sections showed purpura without significant inflammation or keratinocyte necrosis. Plasma porphyrins (copro- and proto-) were elevated in the two patients in which they were assessed. CONCLUSIONS: The distribution of the eruption in areas exposed to light and presence of circulating porphyrins suggest that porphyrinemia may underlie the light-induced purpuric eruption. Additional studies will be required to determine definitively the mechanisms of both the purpuric phototherapy-induced eruption and the development of increased blood porphyrin levels in these transfused neonates.

Flight and size constraints: hovering performance of large hummingbirds under maximal loading.

As the smallest birds, hummingbirds are the only birds capable of prolonged hovering. This suggests that hovering locomotion scales unfavourably with size. Is the hovering performance of larger hummingbird species more constrained by size than that of smaller ones? Maximal load-lifting capacities of the two largest species of hummingbirds found in the United States, the blue-throated (Lampornis clemenciae, 8.4 g) and magnificent (Eugenes fulgens, 7.4 g) hummingbird, as well as the two other local small species, the black-chinned (Archilochus alexandri, 3.0 g) and rufus (Selasphorus rufus, 3.3 g) hummingbird, were determined under conditions of short-burst performance. The power reserves of hummingbirds are substantial relative to normal hovering performance. The two large species lifted maximal loads close to twice their body mass for a very brief duration of over 0.4 s. The small species lifted maximal loads approximately equal to their own mass with a longer duration of over 0.6 s. For the two large species under maximal loading, estimates of burst muscle mass-specific mechanical power output assuming perfect elastic energy storage averaged 309 W kg-1, compared with 75 W kg-1 during free hovering without loading. For the two small species, these values were 228 W kg-1 and 88 W kg-1, respectively. The differences in aerodynamic force production and power output between the large and small size classes occur despite their similar wing stroke velocity. This indicates that, during burst performance in these hummingbirds, the larger ones had a higher load-lifting capacity and generated more muscle power. In spite of the twofold difference in body mass, both large and small hummingbirds have evolved to become potent aerial competitors in order to exploit their common food resource, nectar. Both size classes have evolved to cope with the multi-dimensional effects of size constraining their aerodynamics, muscle mechanics, metabolism and ecology.