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Biomedical subjects

E U Conrad

Publications and source records attributed to E U Conrad.

At least 37 records · Page 2Linked to original sources

Pediatric soft-tissue sarcomas.

Pediatric soft-tissue sarcomas represent a relatively common problem in pediatric oncology. The evaluation of these lesions has contributed significantly to the understanding of the molecular basis of sarcomas, and the adjuvant treatment of these tumors has resulted in improved local control and significant improvements in long-term survival. The essence of successful treatment involves preoperative imaging, followed by needle biopsy, preoperative neoadjuvant chemotherapy, and well-documented surgical resection. Indications for radiation therapy and the adequacy of surgical margins remain areas of further investigation. The identification and treatment of well-defined histologic and molecular subtypes will allow further improvements in treatment decisions and clinical results.

Child↗

An unusual round cell tumor of the tibia with granular cells.

We present the clinical, radiographic and histopathologic findings of an unusual tumor that originated in the diaphysis of the tibia in a 10-year-old boy. Clinical symptoms had been present for approximately 2 years and radiographic abnormalities for > or = 8 months before biopsy and subsequent resection of the neoplasm. The child is doing well 4 1/2 years later. Microscopically, the tumor was not typical of any bone tumor with which we are familiar. It was a round-cell tumor with extensive fibrosis, prominent cytoplasmic granularity, and isolated immunoreactivity for vimentin, epithelial membrane antigen, and antichymotrypsin. Ultrastructural examination uncovered the presence of both well-formed desmosomes and cell-associated basement membrane material in addition to abundant phagolysosomes. Classification of this tumor is a challenge; the differential diagnosis includes atypical adamantinoma, atypical Ewing's sarcoma, and small-cell osteosarcoma. We favor the former interpretation, although we raise the possibility that it may be a unique lesion.

Bone Neoplasms↗

Transmission of the hepatitis-C virus by tissue transplantation.

The hepatitis-C virus has been the most prevalent cause of chronic hepatitis in both blood and organ recipients. The introduction of a second-generation immunoassay for antibodies to the hepatitis-C virus (HCV 2.0) provided the opportunity to determine if the hepatitis-C virus can be transmitted through tissue transplantation. Banked sera from tissue donors that had previously been found to be non-reactive to the first-generation hepatitis-C virus antibody assay (HCV 1.0) and non-reactive for antibodies to hepatitis-B core antigen were retested with HCV 2.0. The sera from two donors were reactive; the transplant records of recipients of tissues from these donors were reviewed, and the surgeons or hospitals were contacted. The tissue recipients were tested with HCV 2.0, and positive sera were tested for hepatitis-C virus RNA by polymerase chain reaction. Viral nucleic acids isolated from viremic donors and recipients were analyzed for identity by sequencing of the hepatitis-C virus envelope gene (E2) hypervariable region. There were twenty-one grafts, which had been treated with gamma radiation, from one donor; thirteen had been transplanted to twelve recipients. Serum samples from six of the recipients were tested; one was reactive. This patient had other risk factors for infection with the hepatitis-C virus, and sequence analysis demonstrated non-identity between the donor and recipient hepatitis-C virus isolates. Nine of twelve grafts from a second donor had been transplanted in nine recipients. Serum samples from five patients were tested with HCV 2.0; four were reactive. In three of the four patients, the sera were determined to be positive for the hepatitis-C virus by polymerase chain reaction. E2 sequence analyses of hepatitis-C virus RNA isolates from two of these recipients demonstrated sequence identity with the donor isolate. The results of the present report demonstrate that the hepatitis-C virus can be transmitted by bone, ligament, and tendon allografts. They also support the need for testing of all tissue donors for antibodies to the hepatitis-C virus before the tissue is released for transplantation. The results also suggest that seventeen kilo-gray of gamma radiation may inactivate the hepatitis-C virus in tissue.

Adolescent↗

Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11.

Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant condition characterized by growth of multiple benign cartilage-capped tumors. EXT greatly increases the relative risk to develop chondrosarcoma, although most chondrosarcomas are sporadic. This observation suggests that, like the genes responsible for retinoblastoma and other dominantly inherited cancer susceptibility disorders, the genes that cause EXT may have tumor-suppressor function and may play a role in the pathogenesis of the related sporadic tumors. To investigate this hypothesis, we evaluated chondrosarcomas for loss of constitutional heterozygosity (LOH) at polymorphic loci linked to three recently identified genomic regions containing genes involved in EXT. LOH for markers linked to EXT1 on chromosome 8 was detected in a chondrosarcoma that arose in a man with EXT. Four of 17 sporadic tumors showed LOH for markers linked to EXT1, and 7 showed LOH for markers linked to EXT2 on chromosome 11. In all, LOH was observed for markers linked to EXT1 or EXT2 in 44% of the 18 tumors, whereas heterozygosity was retained for markers on 19p linked to EXT3. These findings support the hypothesis that genes on 8q and the pericentromeric region of 11 have tumor-suppressor function and play a role in the development of chondrosarcomas.

Alleles↗

Carcinogenicity and metallic implants.

The literature related to the carcinogenetic potential of metallic implants was reviewed. There were 20 cases described in which tumors were identified in proximity to metallic implants. These cases occurred over a 34-year period. Investigators have identified a 70% increased incidence of lymphomas and hematopoietic tumors over that in the general population in patients who had received total hip arthroplasties. Carcinogenicity theories include the potential direct toxicity of materials, the effects of surface properties, the electromotive potential created by dissimilar metals in contact, the immunologic response to implants, and finally, the sustained presence of low-grade infection. Corrosion is a well-documented phenomenon and occurs with any type of metal. The rate of formation of corrosion products and their toxicity varies with the implant composition. Toxic effects of metals, such as malignant potential and other adverse effects, have been demonstrated in animal models. The published information on this controversial and very poignant issue of metallic carcinogenesis is useful for all orthopedic surgeons.

Animals↗

MR appearance of skeletal neoplasms following cryotherapy.

Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations.

Adult↗

The natural history of hereditary multiple exostoses.

We established a database of hereditary multiple exostoses for the state of Washington, on the basis of a retrospective review of the medical records and a clinical evaluation of family members, to determine the prevalence, clinical range of expression, and rate of malignant degeneration. The database comprised forty-six kindreds with 113 affected members; all kindreds had at least one member living in the state of Washington. The over-all prevalence was at least one in 50,000. Approximately 10 per cent of the subjects had no family history of multiple exostoses. With the use of twenty-three pedigrees that demonstrated an adequate multigenerational history for determination of penetrance of the gene, we identified one unaffected individual among twenty-six obligate heterozygotes, a rate of penetrance of 96 per cent. There was no evidence for a substantial reduction of penetrance in female subjects. The median age at the time of the diagnosis in the 113 affected individuals was three years (range, birth to twelve years). In a cohort of eighty-four subjects for whom we had complete information, the clinical range of expression was wide: thirty-three (39 per cent) had an obvious deformity of the forearm, eight (10 per cent) had an inequality in the lengths of the limbs, seven (8 per cent) had an angular deformity of the knee, and two (2 per cent) had a deformity of the ankle. The average number of operations for the patients for whom the operative history was known was two.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms↗

Effect of sterilization and storage treatments on screw pullout strength in human allograft bone.

Many conflicting studies have been performed evaluating the effects of sterilization and storage treatments on the mechanical properties of allograft bone. In the current study, four right and left matched, sterile, deep-frozen, tibial pairs from human donors with an average age of 32 years were tested. One tibia from each pair served as a matched control for the opposite side. Each tibia was cut into four equal segments. One segment of each tibia underwent no treatment; the other three underwent one of the following treatments: irradiation, freeze drying, or ethylene oxide (ETO). Screw pullout tests were performed using four 3.5-mm cortical screws per segment. Sixteen screw pullout tests were performed for each allograft treatment. The freeze-dried specimens required significantly less force for screw pullout. The screw pullout force for the irradiated specimens and the ETO specimens did not significantly differ from their controls. These results indicate that freeze drying affected screw pullout strength. This method of processing should be questioned for structural allografts in which screw fixation is mandatory. The use of irradiation or ETO for sterilization may not have an adverse effect on screw pullout strength.

Biomechanical Phenomena↗

Measurement and prediction of the short-term response of soft tissue sarcomas to chemotherapy.

BACKGROUND: Preoperative chemotherapy has been advocated for the treatment of soft tissue sarcomas, yet there is little information about how these tumors respond pathologically to therapy or whether tumor response can be predicted from a pretreatment biopsy. METHODS: Biopsy was done of 25 intermediate- or high-grade soft tissue sarcomas before they were treated with three cycles of doxorubicin and cisplatin and resected. The authors compared the pathologic features of the treated tumors with clinical and radiologic evidence of response to identify the pathologic features that best reflected chemotherapeutic effect. They analyzed the pretreatment biopsy specimens by light microscopic study and flow cytometry to identify parameters that predict short-term response to chemotherapy. RESULTS: In the treated tumors, the clearest indicator of early chemotherapeutic effect was the percentage of the resected mass composed of viable neoplasm. Eleven of 25 resection specimens contained less than 15% viable neoplasm (patients with pathologic response); 9 of these had 5% or less. Flow cytometric estimates of the proliferative rate in the initial biopsy specimen predicted early chemotherapeutic effect; 7 of 10 tumors with S-phase fractions (SPF) greater than 6% responded pathologically, whereas only 3 of 12 tumors with lower SPF responded (P = 0.041). Initial tumor grade, cell type, percent tumor necrosis, mitotic rate, cellularity, and ploidy did not predict chemotherapy response. CONCLUSION: These results indicate that soft tissue sarcomas often respond dramatically to chemotherapy, that the amount of residual viable sarcoma is an indicator of short-term effect, and that flow cytometric estimates of cell proliferation predict early response to chemotherapy.

Adolescent↗

Genetic heterogeneity in families with hereditary multiple exostoses.

We have carried out a linkage analysis on 11 families segregating gene(s) for hereditary multiple exostoses (EXT). Four highly informative, short tandem-repeat (STR) markers that have been physically mapped to an interval surrounding the Langer-Giedion chromosomal region (8q24.11-q24.13) were used in a multipoint linkage analysis. Significant evidence for linkage of EXT with genetic heterogeneity was found. A model of heterogeneity with linkage of the disease gene to the STR markers in 70% of the families (with a 95% confidence interval of 26%-96%) produced a maximum LOD score of 8.11, with the most likely position of EXT between D8S85 and D8S199. Thus there are at least two genes that are capable of causing hereditary multiple exostoses, one in the Langer-Giedion region and one at another, unlinked location.

Cell Line↗

Intradural recurrence with chondrosarcoma of the spine. A case report and review of the literature.

Known for its resistance to chemotherapy and radiation therapy, chondrosarcoma remains largely a surgically managed tumor predisposed to local recurrence and late distant metastasis. A 42-year-old man with known thoracic chondrosarcoma developed progressive low back pain, lower extremity weakness, and urinary incontinence. Magnetic resonance imaging and computed tomographic myelography demonstrated multiple filling defects throughout the lumbosacral region. Surgical excision of these lesions disclosed intradural, extramedullary drop metastases of the chondrosarcoma. The spread of neoplasms within the dural space is uncommon, accounting for less than 5% of spinal metastases, and has not previously been reported for chondrosarcoma.

Adult↗

The effects of freeze-drying and rehydration on cancellous bone.

Processing technique significantly affects the strength and stiffness of bone for use as a structural alloimplant in reconstructive surgery. The effects of the rehydration of freeze-dried human cancellous bone were studied using 14-mm-diameter cancellous dowels taken from matched cadaveric sites. Three different methods of rehydration were evaluated and compared with unrehydrated freeze-dried and frozen grafts. All samples were biomechanically tested in anatomically matched pair groups to determine compressive strength and stiffness. The strength of each tested graft was expressed as a percentage of its matched pair control. Freeze-dried grafts rehydrated for 24 hours compared with frozen grafts showed no significant difference in mean compressive strength (92.6% +/- 13.3% of control). Analysis of in vacuo versus ex vacuo rehydration at one hour showed a 38% greater mean compressive strength and a 42% greater mean stiffness for the ex vacuo group. Unrehydrated grafts appeared to be both stronger and stiffer than their rehydrated counterparts. These results suggest that the rehydration of freeze-dried grafts may adversely affect graft strength and stiffness. Rehydration under a negative pressure may proceed more rapidly than the process at atmospheric pressures. These findings limit the acceptability of freeze-dried grafts as structural implants.

Adolescent↗

Comparison of STIR and spin-echo MR imaging at 1.5 T in 45 suspected extremity tumors: lesion conspicuity and extent.

Short inversion time inversion recovery (STIR) imaging and a double-echo spin-echo (SE) sequence at 1.5 T in 45 sequential patients with suspected extremity tumors were compared to assess the number of lesions detected, subjective conspicuity of lesions, approximate volume of abnormality detected in each lesion, and identification of peritumoral brightening in tissues adjacent to each lesion. STIR sequences enabled detection of all 45 lesions; 44 were detected with the SE sequence. Tumor appeared most conspicuous on STIR images in 35 patients (78%) and was most conspicuous on SE images in 10 patients (22%). Peritumoral brightening, which indicated either peritumoral edema or microscopic tumor infiltration, was detected in 20 patients but was detected only with STIR sequences in nine patients. It is concluded that, although STIR and SE sequences are comparable for lesion detection in the extremities, most lesions appear more conspicuous with STIR. STIR may enable detection of a greater volume of abnormality than SE sequences and may therefore have important implications for local staging and surgical and radiation therapy planning.

Adolescent↗

Pitfalls in diagnosis: pediatric musculoskeletal tumors.

In general, the 5-year survival for patients with most types of sarcomas has doubled since the 1970s; improved chemotherapy, surgery, radiographic, and pathologic techniques all have contributed to this accomplishment. The 5-year survival for patients with osteosarcoma, like most sarcomas, is approximately 60% when the disease is treated with appropriate chemotherapy, surgery or radiation therapy. The details of treatment are complex and many controversies remain. The initial workup, biopsy, chemotherapy, and surgery should be delivered by a center with experience in the treatment of sarcomas.

Bone Neoplasms↗