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Biomedical subjects

R D Lackman

Publications and source records attributed to R D Lackman.

At least 19 recordsLinked to original sources

Lymphoma masquerading as infection.

During surgical training, medical students and residents constantly are reminded to culture every suspected tumor and send tissue for pathologic evaluation for every suspected abscess. A diagnosis of cancer can be missed easily if this procedure is not followed, delaying the diagnosis and possibly adversely affecting the patient's prognosis. The confusion also may be compounded by a sterile abscess, positive culture results or a negative biopsy specimen. Therefore it is imperative to do a biopsy and a culture on any suspect lesion. An additional workup and possible biopsy may be warranted for a nonhealing wound that has been treated appropriately. The cases of three patients with lymphoma that were treated as infectious processes are presented. In all three instances, the appropriate treatment was delayed because of a delay in diagnosis.

Adult↗

The treatment of sacral giant-cell tumours by serial arterial embolisation.

Giant-cell tumours of the sacrum are difficult to treat. Surgery carries a high risk of morbidity, local recurrence and mortality. Radiation is effective in some patients, but has a risk of malignant change. We evaluated the effectiveness of serial arterial embolisation as an alternative to surgery. Five patients with giant-cell tumours of the sacrum which had been primarily treated by serial embolisation were retrospectively reviewed for changes in the size of the tumour. In four the symptoms resolved with full return of function and arrest in the growth of the tumour. They remained free from growth, recurrence, or metastases at follow-up (4 to 17 years). One patient died from metastatic disease within 18 months of the initial diagnosis.

Adult↗

Hip disarticulation using the lateral approach: a new technique.

A new approach to hip disarticulation is described. This technique uses a laterally based racquet incision. The advantage of this incision is that it uses a lateral approach to the hip, which is familiar to orthopaedic surgeons. This approach is combined with a circumferential incision to facilitate exposure of neurovascular structures. By basing the incision on the lateral approach to the hip, dissection of large blood vessels is minimized, which helps to decrease operative blood loss. Viability of the soft tissue flaps is excellent, with only two minor wound complications occurring. Phantom limb pain was minimal, and no patient required pain medication beyond the 3-month postoperative routine. The three patients who chose to use prostheses had no difficulty from the incisions. The clinical significance of this study is to enable orthopaedic surgeons to do hip disarticulation using the familiar anatomy of the lateral approach to the hip.

Blood Loss, Surgical↗

Concurrent administration of vinorelbine with human recombinant granulocyte-macrocyte stimulating factor.

Thirty-three patients with incurable neoplasms resistant to standard therapy received vinorelbine 10 mg/m(2)/day by continuous infusion with concurrent administration of rHGM-CSF 4 microg/m(2)/day. The duration of the vinorelbine infusion was individualized; the infusion was continued until early evidence of hematopoietic toxicity was noted. The concurrent administration of GM-CSF permitted a substantial increase in dose intensity of the anti-cancer agent without a corresponding increase in drug toxicity. There was no evidence that the anti-tumor effect of vinorelbine was compromised by the concurrent administration of GM-CSF.

Adult↗

Fluoroquinolone's effect on growth of human chondrocytes and chondrosarcomas. In vitro and in vivo correlation.

Clinical and in vitro studies have demonstrated that fluoroquinolones are toxic to chondrocytes; however, the exact mechanism of fluoroquinolone arthropathy is unknown. We investigated the toxicity of ciprofloxacin on normal cartilage and on cartilaginous tumors. Normal human cartilage, enchondroma, and chondrosarcoma explants were cultured either alone or with the addition of ciprofloxacin at 1, 10, or 20 mg/L of medium. Samples were collected up to twenty-one days after treatment and were processed for electron microscopy and conventional light microscopy. The specimens were characterized morphologically with use of conventional light microscopy, electron microscopy, and immunohistochemistry to identify extracellular matrix, cell proliferation, and apoptosis. Cultures of normal chondrocytes expressed type-II collagen. Electron microscopy revealed a large amount of glycogen in the cells; the presence of fat droplets, rough endoplasmic reticulum, and prominent Golgi apparatus; and a proteoglycan layer surrounding the cells. With prolonged ciprofloxacin treatment and with increased doses, there was an increase in dilated rough endoplasmic reticulum, the appearance of phagosomes, and disintegrated bundles of vimentin filaments. The treated chondrocytes showed a decrease in cell proliferation, but there was no induction of apoptosis or effect on the expression of extracellular matrix proteins. Ciprofloxacin-treated chondrosarcoma cultures and tissue samples showed changes in cartilage matrix composition. Ultrastructural analysis demonstrated clumped glycogen, dilation of endoplasmic reticulum, numerous abnormal lysosomes containing degeneration products, and a decreased proteoglycan deposit surrounding the tumor cells. Treated chondrosarcoma cells and tissue specimens did not proliferate, and apoptosis was induced. In contrast, the in vitro growth of other noncartilaginous malignant tumors like osteosarcoma and liposarcoma was unaffected by ciprofloxacin. Our results indicate that ciprofloxacin is toxic to chondrocytes. In vitro and in vivo treated chondrosarcomas are the most affected.

Anti-Infective Agents↗

Concurrent administration of vinorelbine with recombinant human granulocyte colony-stimulating factor: an effective method of increasing dose intensity.

Thirty-three patients with incurable neoplasms resistant to standard therapy received vinorelbine 8 mg/m2 to 10 mg/m2 per day by continuous infusion with concurrent administration of recombinant human granulocyte colony-stimulating factor 5 microm/m2 per day. The duration of the vinorelbine infusion was individualized; the infusion was continued until early evidence of hematopoietic toxicity was noted. The concurrent administration of recombinant human granulocyte colony-stimulating factor permitted a substantial increase in dose intensity of the anticancer agent without a corresponding increase in drug toxicity. There was no evidence that the antitumor effect of vinorelbine was compromised by the concurrent administration of recombinant human granulocyte colony-stimulating factor.

Adult↗

Therapy of desmoid tumors and fibromatosis using vinorelbine.

In patients with either desmoids or fibromatosis who do not tolerate vinblastine and methotrexate because of neurotoxicity, the combination of vinorelbine and methotrexate can be substituted in most. Patients with the same condition who had not been previously treated with a combination of vinblastine and methotrexate responded well to the combination of vinorelbine and methotrexate, with significantly less neurotoxicity and a similar objective and subjective response rate. Sixty percent of patients had either a substantial partial remission or a complete remission. In no patients did the disease progress while they were receiving this therapy. Symptomatic relief, primarily of pain, occurred in 80% of patients. While minimal neurotoxicity was seen in 16% of these patients, it did not interfere with the completion of therapy. The combination of vinorelbine and methotrexate appears to be active in the treatment of both desmoid tumors and fibromatosis and is associated with significantly less neurotoxicity then that seen with the combination of vinblastine and methotrexate. No long-term toxicity was seen in any patient in this series.

Adolescent↗

Limb salvage with osteoarticular allografts after resection of proximal tibia bone tumors.

A retrospective study was performed between 1980 and 1995 on 38 recipients of proximal tibial allografts after wide resection of benign and malignant tumors. Twenty-one (55%) patients experienced one or more complications. Of the 26 patients who received chemotherapy, 15 (58%) experienced one or more complications, whereas of the 12 patients who did not receive chemotherapy, six (50%) experienced one or more complications. In the chemotherapy group, there were 12 (46%) fractures, four (15%) infections, three (12%) nonunions, and four (15%) instabilities. In the nonchemotherapy group there were three (25%) infections, two (17%) fractures, one (8%) instability, and one (8%) nonunion. These complications were managed adequately with multiple subsequent surgical procedures. Three patients underwent amputations for deep wound infections. Twelve (32%) patients underwent removal of the allograft, and the limb was salvaged by reallografting or by total knee arthroplasty. The results of both groups were 66% (25 of 38 patients) satisfactory (good or excellent). The chemotherapy group had a significantly higher incidence of fractures. All other complication rates and functional outcomes were not significantly different between these groups.

Adult↗

Infusional chemotherapy combined with recombinant human granulocyte colony stimulating factor: advantages and limitations.

We have studied the simultaneous administration of granulocyte colony stimulating factor (G-CSF), given concomitantly with an infusion of either doxorubicin or ifosphamide--the former, both intraarterially (i.a.) and intravenously (i.v.), the latter, intravenously--to a group of patients with various malignancies. Such simultaneous administration enabled us to substantially increase the dosage intensity of both, thereby increasing the effectiveness of each drug. No untoward effects have been noted to date.

Antineoplastic Combined Chemotherapy Protocols↗

Purification and characterization of fully functional human osteoclast precursors.

The identification and purification of human osteoclast precursors is essential to further our understanding of the mechanisms that control human osteoclast differentiation. Osteoclastoma tissue potentially provides a rich source of human osteoclast precursors, and in previous studies we have demonstrated the existence of a population of mononuclear cells within this tissue that is reactive with osteoclast-selective vitronectin receptor monoclonal antibodies. In this study, mononuclear cells expressing the vitronectin receptor, as defined by their ability to react with a murine monoclonal antibody to the beta 3 chain of the vitronectin receptor (87MEM1), were isolated from collagenase digests of osteoclastoma tissue using a fluorescence activated cell sorter. Based on their fluorescence signal and size, approximately 2-3% of the viable cells (typically 2 x 10(5)) were obtained and prepared for further phenotyping. The isolated cells demonstrated a number of phenotypic characteristics of osteoclasts: positive tartrate-resistant acid phosphatase (TRAP) activity, reactivity with human osteoclast-selective antibodies, expression of calcitonin receptors, cathepsin K (a novel osteoclast-selective cysteine proteinase) mRNA, and osteopontin mRNA and protein. These phenotypic characteristics were also detected in mononuclear cells within cryostat sections of the native osteoclastoma tissue as well as in resorption lacunae of sections of human bone. In contrast, isolated peripheral blood monocytes were negative for TRAP activity and osteopontin expression and, unlike the osteoclastoma-derived cells, demonstrated strong nonspecific esterase activity. Significantly, when the osteoclastoma-derived 87MEM1 positive cells were cocultured on whale dentine for 1-3 weeks with stromal cells, extensive resorption of the dentine surface was observed. This is the first demonstration of the purification of human osteoclast precursors. These cells provide an homogeneous cell population for studying cellular events that occur during human osteoclast differentiation.

Antibodies, Monoclonal↗

Plantar fibromatosis: a review of primary and recurrent surgical treatment.

Plantar fibromatosis can be quite disabling to the patient, as well as a technical challenge to the surgeon. Patients who undergo previous local excisions and in whom aggressive recurrences develop are difficult to manage successfully. We present a consecutive series of five primary procedures on patients with painful plantar fibroma and seven revision operations on patients with recurrent plantar fibroma. The average follow-up was 47 months (range, 22-66 months) in the primary group and 40 months (range, 21-78 months) in the revision group. The overall results were satisfactory in four of the five primary operations, with only one recurrence. In the revision group, five of seven results were satisfactory with no recurrences. The major complication that led to unsatisfactory results was the development of a postoperative neuroma. In this article, we outline our present surgical techniques of wide primary excision and a staged revision procedure with delayed split-thickness skin graft closure. These techniques can be used successfully to manage this disabling, progressive disease.

Adult↗

Plantar fibromatosis: a benign aggressive neoplasm with a characteristic appearance on MR images.

PURPOSE: To define the magnetic resonance (MR) imaging characteristics of plantar fibromatosis. MATERIALS AND METHODS: Sixteen patients (19 feet) with proved plantar fibromatosis underwent preoperative MR imaging at 1.5 T. A control group of 19 people (24 feet) also underwent MR imaging. RESULTS: Twenty-seven lesions (mean size, 2.2 x 1.0 cm) were identified. All had infiltrative upper margins. Four (15%) of the 27 grew deep to the aponeurosis; 25 (92%) exhibited some signal intensity heterogeneity. All 27 of the lesions on T1-weighted conventional spin-echo (SE) images, seven (78%) of the nine on T2-weighted conventional SE images, and 17 (94%) of the 18 on T2-weighted fast SE images were isointense to minimally hyperintense (to the signal intensity of adjacent muscle). Five (83%) of the six lesions on short inversion time inversion-recovery images were hyperintense. Enhancement was variable on contrast material-enhanced images; nine (60%) of the 15 lesions on these images showed marked enhancement. CONCLUSION: Plantar fibromatosis is a benign but infiltrative neoplasm with a characteristic location and appearance on MR images.

Contrast Media↗

Massive distal femoral osteoarticular allografts after resection of bone tumors.

Records were reviewed for 96 patients who received distal femoral osteoarticular allografts to reconstruct femurs after wide resections of benign and malignant bone tumors. Thirteen of these were excluded from the study because of death or local recurrence. The mortality rate for all patients was 11%; for those with osteosarcomas it was 27%. The local recurrence rate was 3%. Eighty-three patients were subjected to further analysis. Their complications included fractures (14%), nonunions (12%), arthritis (10%), instability (7%), infections (6%), and resorption (6%). There was a significant difference in nonunion and infection rates between patients who received chemotherapy and those who did not. In the chemotherapy group, the infection rate was 13% versus 2% in the non-chemotherapy group. Nonunion rates were 23% versus 6% respectively. The differences in all other complication rates were not statistically significant. In patients not receiving chemotherapy (n = 53), final results were good or excellent in 70%, fair in 26%, and poor in 4%. In patients receiving chemotherapy (n = 30), final results were good or excellent in 53%, fair in 37%, and poor in 10%.

Adolescent↗

Intraarterial chemotherapy with limb-sparing resection of large soft-tissue sarcomas of the extremities.

Fifteen patients with large (average, 15-cm), high-grade soft-tissue sarcomas of the extremities received prolonged selective intraarterial infusions of chemotherapeutic agents in an attempt to permit limb-sparing resection of these tumors, which would otherwise have required amputation. There were seven malignant fibrous histiocytomas, four liposarcomas, two fibrosarcomas, one leiomyosarcoma, and one rhabdomyosarcoma; 73% were grade III. Seven patients underwent two catheterizations, for a total of 22 infusions, which averaged 11.3 days each. There were four catheterization-related complications, including catheter occlusion or dislodgement in one patient each and two cases of arterial thromboembolism in patients in whom anticoagulant dose was not adequate. Both of the latter patients required thrombectomy; one developed gangrene, which precluded limb-sparing surgery. Thirteen of the 15 patients underwent limb-sparing resections, and two underwent amputations. No wound complications occurred. With a median follow-up of 36 months (mean, 34 months), life-table analysis indicates overall and disease-free survivals of 72% and 59%, respectively, at 2 years and 64% and 59% at 3 years. In comparison to other reported therapies, this technique permits limb salvage in most patients without the high wound complication rate associated with preoperative radiation therapy, with equivalent local disease control and survival.

Adult↗