Search PubMed⌕ Search

Biomedical subjects

S J Withrow

Publications and source records attributed to S J Withrow.

At least 19 recordsLinked to original sources
PubMed2000

Identification of matrix metalloproteinases in canine neoplastic tissue.

OBJECTIVE: To identify matrix metalloproteinases (MMP) 2 and 9 in canine tumor tissue and to compare the amount of activity to that in unaffected stromal tissue. ANIMALS: 30 dogs with spontaneously developing, high-grade osteosarcoma. PROCEDURE: Tumor and nearby stromal tissue (muscle) were obtained at the time of surgery. Specimens were homogenized, and supernatants were assayed, using gelatin zymography. Human derived standards were run concurrently. Densitometry was done to obtain a semiquantitative arbitrary unit value for each specimen. The amount of activity in tumor tissue was compared with the amount in stromal tissue. RESULTS: Gelatinolytic bands were observed from the analysis of all tumor tissues and in most stromal tissues. These bands migrated in the same molecular weight area as the human MMP 2 and 9 standards. Gelatinolytic activity could be quenched by the addition of 50 mM EDTA and 1 microg of synthetic tissue inhibitor of metalloproteinase (TIMP) 2 per 100 ml. There was significantly more gelatinolytic activity in tumor tissue than in stromal tissue. CONCLUSIONS AND CLINICAL RELEVANCE: MMP 2 and 9 are detectable in canine neoplastic tissue. Matrix metalloproteinases activity in tumor tissue is higher than in unaffected stromal tissue, indicating that canine MMP may be involved in the pathogenesis of tumor growth and metastasis.

Animals↗
PubMed1999

Effects of a controlled-release cisplatin delivery system used after resection of mammary carcinoma in mice.

OBJECTIVE: To evaluate efficacy of a controlled-release cisplatin delivery system, used after marginal resection of mammary carcinoma (ie, resection of grossly evident tumor) in mice, to prevent tumor regrowth and metastasis. ANIMALS: 42 female C3H-HeJ mice. PROCEDURE: Mice were inoculated with mammary carcinoma cells. Between 2 and 6 days later, tumors were marginally resected and mice were assigned to 1 of 3 groups: no treatment (control; n = 14), cisplatin administered intraperitoneally (i.p. cisplatin; 14), and cisplatin delivered by use of an open-cell polylactic acid system placed within the tumor bed (slow-release cisplatin; 14). Tumor regrowth was measured daily. Mice were euthanatized 14 days after surgery, and complete necropsies were performed. RESULTS: Tumor regrowth was not detected in the slow-release cisplatin group; however, tumor regrowth was detected in 7 of 14 mice in the i.p. cisplatin group and 14 of 14 mice in the control group. Median (+/-SD) number of days to tumor regrowth was 13.5+/-0.64 and 7.79+/-0.87 in the i.p. cisplatin and control groups, respectively. Mice in the i.p. cisplatin group had significantly delayed tumor regrowth, compared with control mice. Metastases to lungs were detected in 8 of 14 control mice but were not detected in mice in either cisplatin treatment group. CONCLUSIONS AND CLINICAL RELEVANCE: The open-cell polylactic acid with cisplatin delivery system was successful in delaying local tumor regrowth and metastasis in mice with marginally resected mammary carcinoma. Use of a controlled-release cisplatin delivery system may be an effective adjunct treatment following excision of mammary carcinoma in humans and other animals.

Animals↗
PubMed1998

Prognostic importance of alkaline phosphatase activity in serum from dogs with appendicular osteosarcoma: 75 cases (1990-1996).

OBJECTIVE: To determine whether alkaline phosphatase activity in dogs with appendicular osteosarcoma can be used as a prognostic indicator. DESIGN: Retrospective study. ANIMALS: 75 dogs with appendicular osteosarcoma. PROCEDURE: Serum total alkaline phosphatase (TALP) and bone-specific alkaline phosphatase (BALP) activities were determined from archival serum samples obtained at various times during treatment of appendicular osteosarcoma and follow-up evaluations. Associations among activities of TALP and BALP and survival and disease-free intervals, percentage of bone length involved with tumor, histologic subtype, and method of surgical treatment were evaluated. RESULTS: High activities of TALP and BALP before surgery were significantly associated with shorter survival and disease-free intervals in dogs undergoing surgery (amputation or limb-sparing procedure) and adjuvant chemotherapy. Activity of BALP significantly decreased in 29 dogs for which postoperative samples were available. Failure of BALP activity to decrease after surgery was correlated with shorter survival and disease-free intervals. CLINICAL IMPLICATIONS: Activities of TALP and BALP in serum are important prognostic factors for appendicular osteosarcoma in dogs. Prognostic factors may help clinicians initiate more aggressive treatment for dogs that are at higher risk of death or relapse.

Alkaline Phosphatase↗
PubMed1998

The evolution of veterinary surgical oncology.

Tremendous change and progress have occurred in the field of oncology over the last several decades. Progression in diagnostic techniques, patient support, adjuvant therapies and surgeon training has allowed the field of surgical oncology to make continued improvements in the human cancer field. Although a relatively young field, veterinary surgical oncology has followed in the progressive footsteps of our human counterparts. This article describes the evolution of this rapidly expanding field of veterinary medicine.

Animals↗
PubMed1998

Preoperative patient planning and margin evaluation.

Preoperative assessment of the cancer patient can be broken down into: (1) What is it? (2) Where is it? and (3) What is the status of the patient? Evaluation of local disease begins with obtaining and interpreting cytologic or histologic (biopsy) samples. Tumor staging involves the assessment of tumor invasion into local tissues, draining lymph nodes, and distant sites, especially the pulmonary parenchyma. Staging is performed with the aid of imaging techniques and special procedures such as lymph node and bone marrow aspiration. Because many veterinary cancer patients are geriatric, examination of physiologic patient status through laboratory and other diagnostic avenues is vital to the appropriate selection and success of therapy. After these questions are answered, appropriate treatment options and an ultimate treatment plan can be formulated. This article describes logical and practical approaches for diagnosis, staging, patient assessment, and treatment planning of the animal presented with tumor disease. With appropriate preoperative assessment, we can offer our patients and clients the best care possible.

Animals↗
PubMed1998

Surgery for skeletal sarcomas.

Skeletal neoplasms in pet animals are uncommon, but can represent a diagnostic and treatment challenge for the veterinary clinician. Osteosarcoma represents the most common histology of primary bone tumor and although the prognosis after treatment is still gaurded, major strides have been made in the treatment of this disease. Treatment success, however, requires a multidisciplinary approach. Additional histologic types cannot be ignored from the diagnosis of cases presenting as bone neoplasms, and many of these can have excellent long-term prognoses if treated appropriately. This article discusses the presentation, diagnosis, and treatment of skeletal neoplasms in general with a specific emphasis on osteosarcoma.

Animals↗
PubMed1998

Principles of treatment for soft tissue sarcoma.

Soft tissue sarcomas (STS) are mesenchymal tumors arising from connective tissue elements and are grouped together based on a common biologic behavior. The most common histologic types include malignant peripheral nerve sheath tumors (schwannoma and neurofibrosarcoma) "hemangiopericytoma," fibrosarcoma, and malignant fibrous histiocytoma. These tumors are relatively slow growing yet locally invasive with a high rate of recurrence following conservative management. Appropriate preoperative planning and aggressive surgical resection often result in long-term remission or cure. Identification and evaluation of resection margins are paramount in appropriate case management. The addition of radiotherapy after surgical resection can aid in remission for incompletely resected masses. Systemic chemotherapy for STS should be considered for high-grade tumors with a moderate metastatic potential. Potential prognostic factors include grade, resection margins, size, location, histologic type, and previous treatment, with grade and margins being the most important. Tumor types classified as STS that differ slightly in their presentation or treatment, including synovial cell sarcoma, rhabdomyosarcoma, liposarcoma, and vaccine-associated STS in cats, are discussed. Soft tissue sarcomas can be a frustrating disease to treat, but adherence to solid surgical oncology principles can greatly increase the odds of good disease control.

Animals↗
PubMed1998

Preparation and in vitro characterization of gentamycin-impregnated biodegradable beads suitable for treatment of osteomyelitis.

A new method for preparing poly(L-lactide) (PLA) biodegradable beads impregnated with an ionic aminoglycoside, gentamycin, is described. The process employs hydrophobic ion pairing to solubilize gentamycin in a solvent compatible with PLA, followed by precipitation with a compressed antisolvent (supercritical carbon dioxide). The resulting precipitate is a homogeneous dispersion of the ion-paired drug in PLA microspheres. The microspheres are approximately 1 microm in diameter and can be compressed into beads (3-6 mm in diameter) strung on surgical sutures for implantation. The bead strings exhibit no significant change in release kinetics upon sterilization with a hydrogen peroxide plasma (Ster-Rad). The kinetics of gentamycin release from the PLA beads are consistent with a matrix-controlled diffusion mechanism. While nonbiodegradable poly(methyl methacrylate) (PMMA) beads initially release gentamycin in a similar manner, the drug release from PMMA ceases after 8 or 9 weeks, while the PLA beads continue to release drug for over 4 months. Moreover, only 10% of the gentamycin is released from the PMMA beads, while PLA beads release more than 60% of their load, if serum is present in the release medium. The PLA system displays improved release kinetics relative to PMMA, is biodegradable, is unaltered by gas sterilization, can be used for a range of antibiotics, and can be manipulated without disintegration. These are all desirable properties for an implantable drug delivery system for the prevention or treatment of osteomyelitis.

Absorption↗
PubMed1998

Abdominal tumors.

Explore the source record for details and available documents.

Abdominal Neoplasms↗
PubMed1998

Osteosarcoma.

Explore the source record for details and available documents.

Amputation, Surgical↗
PubMed1998

Apparent interaction of dimethyl sulfoxide with cisplatin released from polymer delivery devices injected subcutaneously in dogs.

Local tissue toxicity, systemic toxicity and platinum pharmacokinetics were evaluated in 6 normal healthy beagle dogs injected subcutaneously with two formulations of a polylactide biodegradable polymer (Atrigel) system containing cisplatin. Dogs were injected 4 times at 30 day intervals at platinum dosages of 70, 105 and 157.5 mg/m2 (dose escalation). Once pharmacokinetics were established, 29 dogs with spontaneous stage IIb appendicular osteosarcoma were treated with 4 injections of the same polymer system containing cisplatin at 70 mg/m2 (20 dogs) and 100 mg/m2 (9 dogs) to establish efficacy against micrometastatic disease. Local tissue toxicity was variable. Systemic toxicity, as judged by clinicopathologic evaluation was not noted at any dose level or injection number. Interim (6 month) survival analysis revealed a median disease-free interval of 180 days. Consistent platinum release characteristics were found, however, the lack of toxicity and decreased disease-free-interval raised concerns over the biologic activity of the cisplatin. Prior to completion of the study, it was discovered that dimethyl sulfoxide, the solvent used in the co-polymer system, may be responsible for biologic inactivation of cisplatin. This was subsequently demonstrated in tissue culture assays. The clinical trial was suspended and dogs were treated with traditional chemotherapy.

Animals↗
PubMed1997

Evaluation of prognostic factors for dogs with primary lung tumors: 67 cases (1985-1992).

OBJECTIVE: To determine associations between clinical and histologic factors in dogs with primary lung tumors and outcome and to develop a histologic grading method for primary lung tumors. DESIGN: Retrospective study. ANIMALS: 67 dogs undergoing thoracotomy and lobectomy for primary lung tumors. PROCEDURE: Medical records and histologic sections were reviewed to evaluate factors of prognostic importance. Association of these factors with disease-free interval (DFI) and survival time was evaluated, using the Cox proportional hazards model. Median DFI and survival time were determined, using the Kaplan-Meier product-limit method. RESULTS: Clinical and histologic factors significantly associated with prognosis were histologic score, detection of clinical signs, and metastasis to regional lymph nodes. On the basis of histologic score, a histologic grading method was developed. Dogs with well-differentiated tumors had significantly longer survival time and DFI (median DFI, 493 days) than dogs with moderately (median DFI, 191 days) or poorly (median DFI, 0 days) differentiated tumors. Dogs with clinical signs or metastasis to regional lymph nodes had shorter survival times and DFI than dogs in which lung masses were discovered as an incidental finding. CLINICAL IMPLICATIONS: Dogs with well-differentiated, nonmetastasized, primary lung tumors that do not have clinical signs associated with the tumor have a favorable prognosis. Dogs with more advanced disease or aggressive tumors histologically may require treatment, such as chemotherapy in combination with surgery. The grading method proposed here for primary lung tumors may be useful in other dogs with primary lung tumors.

Animals↗
PubMed1997

Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996).

OBJECTIVE: To determine results of surgery for treatment of soft-tissue sarcomas in dogs and to identify prognostic variables that can be used to predict outcome. DESIGN: Retrospective case series. ANIMALS: Dogs with soft-tissue sarcomas that had surgical treatment only. PROCEDURE: Records were examined for clinically relevant data. Histologic samples were reviewed. Follow-up information was obtained by physical examination or telephone conversations with referring veterinarians or owners. RESULTS: 75 dogs with soft-tissue sarcomas of the trunk and extremities were identified. Median age was 10.6 years. Malignant peripheral nerve sheath tumors were of a significantly lower grade than other tumors. Tumors recurred locally in 11 of 75 (15%) dogs. Evaluation for lack of tumor cells at surgical margins was prognostic for local recurrence. Metastatic disease developed in 13 of 75 (17%) dogs. Tumor mitotic rate was prognostic for development of metastasis. Twenty-five of 75 (33%) dogs died of tumor-related causes. Percentage of tumor necrosis and tumor mitotic rate were prognostic for survival time. Median survival time was 1,416 days. CLINICAL IMPLICATIONS: On the basis of a low local recurrence rate and high median survival time, wide excision of tumor margins or radical surgery appeared to be an effective means for managing soft-tissue sarcomas of the trunk and extremities. Analysis of histologic characteristics for prognosis supported use of preoperative biopsy. Surgical margins should be evaluated, and early use of aggressive surgery is indicated in the management of soft-tissue sarcomas in dogs.

Animals↗
PubMed1996

Pancreatic beta cell tumor in ferrets: 20 cases (1986-1994).

OBJECTIVE: To characterize survival times, disease-free intervals, and prognostic variables in ferrets with pancreatic beta cell neoplasia. DESIGN: Retrospective study. ANIMALS: 20 ferrets with histologically confirmed pancreatic beta cell tumors. PROCEDURE: Medical records of ferrets with pancreatic beta cell tumors were reviewed. Variables such as age, sex, duration of clinical signs, existence of other neoplasia, single versus multiple masses in the pancreas, benign or malignant histologic features, and the type of treatment used at redevelopment of clinical signs were examined to determine their relationship to survival times and disease-free intervals. RESULTS: Duration of clinical signs prior to diagnosis and initial surgery was inversely correlated with survival time and disease-free interval. Overall median survival time for all ferrets with pancreatic beta cell tumors was 483 days. Median disease-free interval for ferrets that had abdominal surgery for pancreatic beta cell tumor removal was 240 days. Distant tumor metastasis was not found in this group of ferrets, but local tumor recurrence was common. In 4 ferrets that had a second celiotomy, removal of recurrent pancreatic tumors did not prolong survival but did result in a second disease-free interval. CLINICAL IMPLICATIONS: Pancreatic beta cell tumors should be considered in ferrets over 2 years of age that have clinical signs of seizures, episodic lethargy, ptyalism, ataxia, and hind limb weakness. In the study reported here, complete surgical excision of the tumor resulted in temporary resolution of clinical signs in ferrets; however, redevelopment of clinical signs at a later time was common.

Animals↗