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Biomedical subjects

D E Sweet

Publications and source records attributed to D E Sweet.

At least 19 recordsLinked to original sources
PubMed2000

Bone tumor dynamics: an orthopedic pathology perspective.

The diagnosis and classification of primary bone tumors remains as much a challenge today as it has for the last 80 plus years. Although pathology is invariably equated with the image of a diagnostic microscope, the vast majority of diagnoses are made grossly with the unaided eye, as are the tissue specimens selected for microscopic "confirmation." Radiologic studies, particularly plain radiographs, remain the gold standard in gross pathologic diagnosis of the skeleton. Today, confirmation and final classification continue as the pathologist's domain, but perhaps not for long, considering the evolving ancillary imaging techniques and progressive sophistication of magnetic resonance (MR) imaging. The bone tumor cases collected and compiled by Ernest Codman, M.D. during the second through fourth decades of this century formed the basis of the first tumor registry. The Codman Bone Sarcoma Registry demonstrated among other things the importance of radiographic/pathologic correlation, underscoring the reliability of a bone tumor's location, margin (host bone/tumor interface), periosteal reaction, and matrix patterns as an accurate guide to classification and likely future biologic behavior. "A General Theory of Bone Tumors," written by Lent C. Johnson nearly 50 years ago and published in the Bulletin of The New York Academy of Medicine (February 1953, second series, vol. 29, no. 2, pp. 164-171), provided a conceptual cellular approach to the understanding bone tumor dynamics reinforcing radiologic/pathologic correlation as a reliable diagnostic tool. At the time of Dr. Lent C. Johnson's death (1910-1998), he was literally working on an updated version of his original article, the latter of which is being reprinted as the core of this illustrated revision. Our continued experience with bone tumors over the past five decades has only served to validate, on a daily basis, the fundamental principles outlined in Johnson's original article. In like fashion, it is important to keep in mind that terminology and nomenclature has also evolved since 1953, despite a continued inability to achieve complete consensus.

Bone Neoplasms↗
PubMed1999

Safety and pharmacokinetics of abacavir (1592U89) following oral administration of escalating single doses in human immunodeficiency virus type 1-infected adults.

Abacavir (1592U89) is a nucleoside analog reverse transcriptase inhibitor that has been demonstrated to have selective activity against human immunodeficiency virus (HIV) in vitro and favorable safety profiles in mice and monkeys. A phase I study was conducted to evaluate the safety and pharmacokinetics of abacavir following oral administration of single escalating doses (100, 300, 600, 900, and 1,200 mg) to HIV-infected adults. In this double-blind, placebo-controlled study, subjects with baseline CD4+ cell counts ranging from < 50 to 713 cells per mm3 (median, 315 cells per mm3) were randomly assigned to receive abacavir (n = 12) or placebo (n = 6). The bioavailability of the caplet formulation relative to that of the oral solution was also assessed with the 300-mg dose. Abacavir was well tolerated by all subjects; mild to moderate asthenia, abdominal pain, headache, diarrhea, and dyspepsia were the most frequently reported adverse events, and these were not dose related. No significant clinical or laboratory abnormalities were observed throughout the study. All doses resulted in mean abacavir concentrations in plasma that exceeded the mean 50% inhibitory concentration (IC50) for clinical HIV isolates in vitro (0.07 microgram/ml) for almost 3 h. Abacavir was rapidly absorbed following oral administration, with the time to the peak concentration in plasma occurring at 1.0 to 1.7 h postdosing. Mean maximum concentrations in plasma (Cmax) and the area under the plasma concentration-time curve from time zero to infinity (AUC0-infinity) increased slightly more than proportionally from 100 to 600 mg (from 0.6 to 4.7 micrograms/ml for Cmax; from 1.0 to 15.7 micrograms.h/ml for AUC0-infinity) but increased proportionally from 600 to 1,200 mg (from 4.7 to 9.6 micrograms/ml for Cmax; from 15.7 to 32.8 micrograms.h/ml for AUC0-infinity. The elimination of abacavir from plasma was rapid, with an apparent elimination half-life of 0.9 to 1.7 h. Abacavir was well absorbed, with a relative bioavailability of the caplet formulation of 96% versus that of an oral solution (drug substance in water). In conclusion, this study showed that abacavir is safe and is well tolerated by HIV-infected subjects and demonstrated predictable pharmacokinetic characteristics when it was administered as single oral doses ranging from 100 to 1,200 mg.

Adult↗
PubMed1999

Liposclerosing myxofibrous tumor: a radiologic-pathologic-distinct fibro-osseous lesion of bone with a marked predilection for the intertrochanteric region of the femur.

PURPOSE: To describe the characteristic features of liposclerosing myxofibrous tumor (LSMFT) of bone. MATERIALS AND METHODS: The radiographs and clinical histories of 39 patients (21 male, 18 female; mean age, 42 years; age range, 15-69 years) with histologically verified LSMFT of bone were retrospectively studied. RESULTS: LSMFT had a predilection for the proximal femur; more than 90% (30 of 33) of the femoral lesions were in the intertrochanteric region. Radiographs showed an indolent growth pattern with a well-defined and often extensively sclerotic margin. The bone contour either was normal or showed mild expansile remodeling. Mineralization within the lesion was not uncommon. Scintigrams showed mild to moderate focal tracer accumulation. Findings at computed tomography reflected those at radiography, whereas magnetic resonance imaging findings were nonspecific. Four (10%) patients had evidence of malignant transformation. CONCLUSION: The radiologic appearance of LSMFT in the intertrochanteric region of the femur is characteristic. The substantial prevalence of malignant transformation associated with LSMFT underscores the need for close observation of this lesion.

Adolescent↗
PubMed1998

Focal myositis.

Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features.

Aged↗
PubMed1998

Osteoblastoma of the foot and ankle.

A total of 329 patients with osteoblastoma were retrospectively reviewed from the archives of the Armed Forces Institute of Pathology, of which 41 (12.5%) presented with tumors in the foot and ankle. This was the third most common site of disease after the spine and femur. Overall, the mean age was 22.5 years, which was the same for the foot and ankle subset of patients; however, there was a significant male predominance in foot and ankle patients compared with the whole group. The majority of patients were skeletally mature (85.4%). Clinically, most patients presented with pain (97.2%), although one-third of the total related a history of antecedent trauma. The interval between the onset of symptoms and biopsy was 84 days (range, 0-572 days). Radiographically, the majority of lesions were in the hindfoot (N = 18; 44%) of which 16 of 18 tumors (89%) were in the talus. Of these, one-half were subperiosteal and dorsally based and were associated with osseous tumor matrix and a soft tissue mass. Two osteoblastomas, both in the metatarsals, transitioned into sarcomas; the rest were histologically benign. For diagnostic purposes, it was essential to obtain clinical, radiographic, and histologic correlation.

Adolescent↗
PubMed1996

Tendon repair by laser welding: a histologic and biomechanical comparison and suture repair with CO2 and argon lasers.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine whether welding of tendinous tissue is possible with the application of thermal lasers. STUDY DESIGN MATERIALS AND METHODS: After sharp transection of a unilateral achilles tendon, 40 male outbred Spraque Dawley rats were divided equally between four treatment groups. Ten animals underwent repair using the modified Kessler suture technique. The remaining animals underwent application of laser after the tendon edges were reapproximated and held in place with a vascular clamp. CO2 and Nd:YAG lasers were applied using 25% human albumin as a solder. Fluorescein dye was added to albumin and used as solder for the Argon laser. Biomechanical and histologic testing were performed immediately and 14 days postoperatively. RESULTS: Argon and CO2 lasers successfully fused the tendon ends together. However, immediately postoperative, the resultant tissue weld was tenuous and conventional tensile strength testing was not possible. At 14 days postoperatively, all modes of tendon repair resulted in tensile failure at consistently lower levels of tension than those required for the normal uninjured tendons. The ultimate tensile strength for the suture-repaired, CO2 laser welded, and Argon laser welded tendons were 74%, 59%, and 64% of the strength of the control tendons respectively. No statistically significant difference was found in the tensile strength among the three repair groups. Histologic evaluation at 14 days revealed the greatest degree of inflammatory response in those tendons repaired with the Argon laser. Those tendons repaired with suture demonstrated the least amount of inflammatory change. CONCLUSION: Our study demonstrates that welding of a tendon is possible with the application of laser energy. However, we were unable to produce a weld sufficient to withstand significant tensile loads in the immediate postoperative period.

Achilles Tendon↗
PubMed1995

Aneurysmal bone cyst: concept, controversy, clinical presentation, and imaging.

The aneurysmal bone cyst is the result of a specific pathophysiologic change, which is probably the result of trauma or a tumor-induced anomalous vascular process. In approximately one third of cases, the preexisting lesion can be clearly identified. The most common of these is the giant cell tumor, which accounts for 19-39% of cases in which the preceding lesion is found. Other common precursor lesions include osteoblastoma, angioma, and chondroblastoma. Less common lesions include fibrous dysplasia, fibroxanthoma (nonossifying fibroma), chondromyxoid fibroma, solitary bone cyst, fibrous histiocytoma, eosinophilic granuloma, and even osteosarcoma. Interestingly, some of the controversy surrounding this lesion may be the result of a change in how the lesion was defined by Lichtenstein in 1953, when intramedullary lesions were added to the previously described juxtacortical (superficial) lesions. Members of the AFIP have suggested that many of the intramedullary lesions in which no previous lesion can be identified may represent giant cell tumors of bone. Their similarity to proved giant cell tumors in skeletally immature patients can be striking and seems more than coincidental. Appropriate treatment of an aneurysmal bone cyst requires the realization that it results from a specific pathophysiologic process, and identification of the preexisting lesion, if possible, is essential. Clearly an osteosarcoma with superimposed secondary aneurysmal bone cyst change must be treated as an osteosarcoma, and giant cell tumor with secondary features of aneurysmal bone cyst would be expected to be more likely to recur locally. The vast majority (approximately 80%) of patients presenting with aneurysmal bone cystlike findings are less than 20 years old. More than half of all such lesions occur in long bones, with approximately 12-30% of cases occurring in the spine. The pelvis accounts for about half of all flat bone lesions. Most patients present with pain and/or swelling, with symptoms usually present for less than 6 months. The imaging appearance of aneurysmal bone cyst reflects the underlying pathophysiologic change. Radiographs show an eccentric, lytic lesion with an expanded, remodeled "blown-out" or "ballooned" bony contour of the host bone, frequently with a delicate trabeculated appearance. Radiographs may rarely show flocculent densities within the lesion, which may mimic chondroid matrix. CT scanning will define the lesion and is especially valuable for those lesions located in areas in which the bony anatomy is complex, and which are not adequately evaluated by plain films. Fluid-fluid levels are common and may be seen on CT scans and MR images.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Cysts, Aneurysmal↗
PubMed1995

MIC2 detection in tumors of bone and adjacent soft tissues.

The diagnosis of Ewing's sarcoma has been based classically in large part on the exclusion of other similar small round-cell tumors by light microscopic and histochemical criteria. This study was undertaken to explore the use of a recently developed immunohistochemical stain directed against the glycoprotein p30/32MIC2 antigen (the gene product of MIC2), as a diagnostic tool and as a probe for the examination of potential interrelationships among the putative members of the family of peripheral primitive neuroectodermal tumors. Fifty-six small round-cell tumors of bone were selected for study from the files of the Armed Forces Institute of Pathology and Rhode Island Hospital; all tissues had been formalin fixed and paraffin embedded. Nine of 10 Ewing's sarcomas were MIC2 positive, as were 2 of 3 atypical Ewing's sarcomas (small round-cell tumors that diverged from the classic pattern of Ewing's sarcoma by exhibiting a greater degree of cytologic atypia and pleomorphism), and 7 of 8 Askin tumors of the thoracopulmonary region. Ten of 11 mesenchymal chondrosarcomas, 1 primitive neuroectodermal tumor of bone, 10 small cell osteosarcomas, 10 malignant lymphomas, and 3 sarcomas of bone (not additionally subclassified) were negative. The finding of MIC2 positivity in the majority of Ewing's sarcomas and Askin tumors provides additional support for earlier proposals (based on a shared cytogenetic abnormality, among other criteria) that these lesions be considered members of the same family, the peripheral primitive neuroectodermal tumors. The present study, drawing on archival and current case material (including decalcified and undecalcified specimens), indicates that neither the specimen age nor the application of any of a variety of decalcification solutions appears to adversely influence MIC2 staining of paraffin-embedded tissues. This suggests that this antibody has use in retrospective and prospective studies. The rare occurrence of false negative (in the case of Ewing's sarcoma) and positive results in tumors other than peripheral primitive neuroectodermal tumors (as in 1 of the mesenchymal chondrosarcomas) suggests that MIC2 staining should not be relied on as the sole criterion for identification or exclusion of Ewing's sarcomas and related tumors.

12E7 Antigen↗
PubMed1994

Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. A randomized, double-blind clinical trial. The Bristol-Myers Squibb AI454-010 Study Group.

OBJECTIVE: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. DESIGN: Randomized, double-blind, two-armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. SETTING: Outpatient clinics at 19 tertiary care medical centers. PATIENTS: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. INTERVENTION: Peroral didanosine tablets (600 mg/d adjusted for weight, "high dose") or zidovudine capsules (600 mg/d). MEASUREMENTS: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)--defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. RESULTS: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). CONCLUSIONS: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.

AIDS-Related Complex↗
PubMed1994

Oral and dermatologic manifestations of HIV infection.

Because an estimated 1 million persons in the United States are infected with HIV, all physicians, especially those in primary care, need to be able to recognize the protean manifestations of the disease and make a diagnosis as early as possible. In this article, Drs Jewell and Sweet review the mucocutaneous conditions that occur in patients with HIV infection and discuss diagnostic clues and treatment.

AIDS-Related Opportunistic Infections↗
PubMed1994

An activating Gs alpha mutation is present in fibrous dysplasia of bone in the McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is a sporadic disease characterized by polyostotic fibrous dysplasia, café-au-lait spots, and multiple endocrinopathies. The etiology of fibrous dysplasia is unknown. Activating mutations of codon 201 in the gene encoding the alpha-subunit of Gs, the G-protein that stimulates adenylyl cyclase, have been found in all affected MAS tissues that have been studied. Initial attempts to amplify DNA from decalcified paraffin-embedded bone specimens from MAS patients were unsuccessful. Therefore, we analyzed DNA from frozen surgical bone specimens from five MAS patients using polymerase chain reaction and allele-specific oligonucleotide hybridization. Most of the cells in four specimens of dysplastic bone contained a heterozygous mutation encoding substitution of Arg201 of Gs alpha with His, but the mutation was barely detectable in peripheral blood specimens from the patients. Only a small amount of mutant allele was detected in a specimen of normal cortical bone from the fifth patient, although this patient had a high proportion of mutation in other, affected tissues. The mosaic distribution of mutant alleles is consistent with an embryological somatic cell mutation of the Gs alpha gene in MAS. The presence of an activating mutation of Gs alpha in osteoblastic progenitor cells may cause them to exhibit increased proliferation and abnormal differentiation, thereby producing the lesions of fibrous dysplasia.

Adenylyl Cyclases↗
PubMed1994

Skeletal-extraskeletal angiomatosis. A clinicopathological study of fourteen patients and nosologic considerations.

We reviewed the consultation files of the ARmed Forces Institute of Pathology for 1951 through 1989 and identified fourteen patients who had had skeletal-extraskeletal angiomatosis. Skeletal-extraskeletal angiomatosis was defined as a benign vascular proliferation involving the medullary cavity of bone and at least one other type of tissue. The age of the patients at the time of initial biopsy ranged from nine months to sixty-nine years (average, twenty-two years; median, ten years). Ten of the patients were male and four were female. The presenting signs and symptoms were highly variable; they included pain (four patients), a mass noted at birth (three patients), a painless mass that developed after birth (two patients), both pain and a mass (one patient), a localized deformity of the thoracic spine (one patient), and anemia associated with chronic bleeding of the gastrointestinal tract (one patient); in this last patient, skeletal lesions subsequently were found and biopsied. Skeletal-extraskeletal angiomatosis was an incidental finding in the remaining two patients. Multiple bones were involved in thirteen of the fourteen patients. Histologically, three patterns of lesion could be identified: cavernous lymphangioma (six patients), cavernous hemangioma (six patients), and arteriovenous hemangioma (two patients). Five of the patients died (three of sepsis associated with persistent lesions of angiomatosis and two of unrelated causes); eight of the patients survived but had residual disease, and one survived and had no evidence of residual disease.

Adolescent↗
PubMed1994

Surface-based hemangiomas of bone. A review of 11 cases.

The surface-based hemangioma of bone is an uncommon cause of periosteal- or cortical-based lesions. The files of the Armed Forces Institute of Pathology were searched for lesions diagnosed as cortical hemangioma or periosteal hemangioma received between the years 1950 and 1990; 11 cases with follow-up results were identified. The 11 patients ranged in age from 11 to 31 years of age at the time of initial symptoms (average, 21 years; mean, 23 years). Sixty percent of the patients were male and 40% were female. Skeletal sites of involvement included the tibia (45%), the fibula (36%), the femur (9%), and the ulna (9%). Seventy percent of patients complained initially of pain (duration, two months to five years), whereas 30% reported pain and a mass at the time of initial diagnosis (duration, six months to two years). On plain film radiographs, eight lesions showed localized cortical thickening, two showed cortical erosion, and one had a permeative/destructive pattern. Bone scans showed solitary lesions with increased uptake in all 11 patients. The range of histologic types of cortical hemangioma included cavernous (six cases), arteriovenous (three cases), venous (one case), and pyogenic granuloma type (one case). Clinically, the majority of cases were diagnosed as osteoid osteomas; primary pathologic diagnoses included hemangioma (27%) and cortical sclerosis (18%). Persistent complaints were reported in three patients after intralesional biopsy; no recurrences were reported after en bloc excision.

Adolescent↗
PubMed1993

Synovial hemangioma: a report of 20 cases with differential diagnostic considerations.

True synovial-based hemangiomas are uncommon lesions and, as such, may enter the differential diagnosis of other lesions encountered more frequently in clinical practice, including pigmented villonodular synovitis and traumatic hemarthrosis. The consultation files of the Armed Forces Institute of Pathology were searched for benign vascular lesions diagnosed as synovial or bursal hemangiomas vascular lesions diagnosed as synovial or bursal hemangiomas submitted between the years 1960 and 1985; 20 cases of synovial hemangioma were identified. The patients ranged in age from 9 to 49 years at the time of presentation (average age, 25 years). Sixty-five percent of the patients were male; 35% were female. Presenting symptoms included pain and swelling (31%), pain alone (31%), and a painless mass (31%). Affected regions included the knee (60%), the elbow (30%), and the finger (10%). In 65% of cases the lesion was confined to the intra-articular synovium; in 30% of cases the hemangioma was located in a bursa adjacent to a joint. One case was located largely within the joint cavity but had an area of extension into the suprapatellar recess. The dominant histologic patterns included cavernous hemangioma (50%), lobular capillary hemangioma (25%), arteriovenous hemangioma (20%), and venous hemangioma (5%). One lesion (which had been incompletely excised) was removed in its entirety 3 months after the initial subtotal resection; otherwise, none of the patients studied developed recurrent disease. The clinical diagnosis of hemangioma was made in 22% of cases, while an initial pathologic diagnosis of hemangioma was reached in 67% of cases. Pathologic differential diagnostic considerations include nonspecific synovitis/bursitis, pigmented villonodular synovitis, nodular synovitis, and organizing hemorrhage. A relationship between synovial hemangioma and pigmented villonodular synovitis was not suggested by this analysis of our material.

Adolescent↗
PubMed1993

Small cell osteosarcoma of bone: an immunohistochemical study with differential diagnostic considerations.

Seventy-nine cases of small round cell tumors involving bone were studied in an attempt to learn whether the immunohistochemical features of the lesions might allow distinction of small cell osteosarcoma from other potential differential diagnostic considerations, including Ewing's sarcoma, atypical Ewing's sarcoma, primitive neuroectodermal tumor, mesenchymal chondrosarcoma, lymphoma, and the Askin tumor. The tissues studied were all formalin-fixed, decalcified, paraffin sections from patients between the ages of 16 and 48 years. With one exception (a small cell osteosarcoma), none of the lesions was cytokeratin positive. Moreover, none of the lesions was epithelial membrane antigen, desmin, factor VIII-related antigen, synaptophysin, or Leu-M1 positive. Accordingly, strong positivity for these antibodies in a majority of tumor cells should prompt inclusion of tumor types other than those listed above in the differential diagnosis. Vimentin positivity was seen in a majority of the tumors studied irrespective of histologic type. Scattered tumor cells (< 25%) showed positivity with antibodies to muscle-specific actin and smooth muscle actin in several of the different tumor types studied. No lesions other than lymphoma were leukocyte-common antigen (LCA) positive; all but two lymphomas were LCA positive, while all but one lymphoma were L26 positive. One (lymphoblastic) lymphoma was LCA and L26 negative. S-100, neuron-specific enolase, and Leu-7 did not prove to be specific for "neural-associated" tumors, but rather appeared in some small cell osteosarcomas, Ewing's sarcomas, atypical Ewing's sarcomas, primitive neuroectodermal tumors, mesenchymal chondrosarcomas, lymphomas, and Askin tumors. Antibody to cell surface antigen HBA71 was positive in three Ewing's sarcomas (two typical and one atypical) and negative in small cell osteosarcoma (three cases), mesenchymal chondrosarcoma (two cases), and lymphoma (one case). While some guidance may be derived from analysis of immunohistochemical staining patterns in a given lesion, the results reported in the present study do not suggest that routine immunohistochemistry alone will permit distinction of these small cell tumors of bone from one another. The value of immunohistochemical studies appears to lie particularly in the use of antibodies to LCA and S-100 protein to distinguish lymphoma and mesenchymal chondrosarcoma, and perhaps antibody to HBA71 to distinguish neural family lesions (such as Ewing's sarcoma), from other small cell tumors, such as small cell osteosarcoma.

Adolescent↗