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Biomedical subjects

Timothy M Fan

Publications and source records attributed to Timothy M Fan.

8 recordsLinked to original sources

Inflammatory polyps and aural neoplasia.

Although aural neoplasia is a relatively uncommon entity in companion animals, it remains a group of heterogeneous conditions that can have a significant negative impact on quality and duration of life of dogs and cats. Chronic ear disease that responds poorly or partially to empiric therapy should raise the suspicion that an underlying condition, such as neoplasia, may be the perpetrator of inflammation. Early diagnosis followed by appropriate therapy improves the likelihood of disease control and prolonged survival.

Animals↗

Lymphoma updates.

Canine and feline lymphoma is a common hematopoietic malignancy that generally responds well to systemic chemotherapy. In dogs, several recent investigations have underscored the beneficial effects of adjunctive radiation therapy for the treatment of multicentric lymphoma. With the emergence of effective immunotherapeutic agents against non-Hodgkin's lymphoma in people, some of these specific targeted immunotherapeutics may soon be a viable option for treating lymphoid malignancies in dogs. Although the effective and durable treatment of feline lymphoma remains disappointing, the identification of environmental etiologic factors may help to shape future recommendations for disease prevention. It is only reasonable to assume that as our fundamental understanding of lymphoid malignancies grows, better diagnostic tools, predictive markers, and therapeutic options will also emerge.

Animals↗

T-cell lymphoma of the tympanic bulla in a feline leukemia virus-negative cat.

This report constitutes the first description of a T-cell lymphoma of the tympanic bulla in a cat. This feline leukemia virus (FeLV)-negative cat originally presented with signs referable to middle ear disease; it deteriorated rapidly after definitive diagnosis. Lymphoma of the middle ear is extremely rare in all species.

Animals↗

Bisphosphonates and cancer.

Bisphosphonates form a family of drugs characterized pharmacologically by their ability to inhibit bone resorption and pharmacokinetically by similar intestinal absorption, skeletal distribution, and renal elimination. Two groups of bisphosphonates exist chemically, non-amino-bisphosphates and amino-bisphosphonates. The amino-bisphosphonates have greater antiresorptive capabilities and represent a newer generation of bisphosphonates. The primary mechanism of action of bisphosphonates is inhibition of osteoclastic activity. Non-amino-bisphosphonates are incorporated into the energy pathways of the osteoclast, resulting in disrupted cellular energy metabolism leading to apoptosis. Amino-bisphosphonates exert their effect on osteoclasts via their inhibition of the mevalonate pathways, resulting in disruption of intracellular signaling and induction of apoptosis. Bisphosphonates also inhibit cancer cell proliferation, induce apoptosis in in vitro cultures, inhibit angiogenesis, inhibit matrix metalloproteinase, have effects on cytokine and growth factors, and are immunomodulatory. Clinical applications in oncology could include therapy for hypercalcemia of malignancy, inhibition of bone metastasis, and therapy for bone pain. Although bisphosphonates are regarded as metabolically inert in the body, adverse effects do occur and include esophagitis, gastritis, suppression of bone repair, and allergic reactions. Little is published on the effects of bisphosphonates in dogs with cancer. Further research into the role of bisphosphonates in veterinary oncology is needed to identify clinical efficacy and safety of these potentially beneficial drugs.

Animals↗

Evaluation of intravenous pamidronate administration in 33 cancer-bearing dogs with primary or secondary bone involvement.

The purpose of this study was to evaluate the clinical safety of pamidronate when administered at a mean dosage of 1.0 mg/kg IV q28d in 33 tumor-bearing dogs. Biochemical tests of renal function were evaluated before each successive pamidronate treatment. Of 33 dogs treated with pamidronate, 1 dog had clinically relevant increases in serum creatinine and blood urea nitrogen concentrations. The biologic activity of IV pamidronate was assessed prospectively in 10 dogs with appendicular osteosarcoma and was assessed on reductions in urine N-telopeptide excretion (P = .042) and enhanced bone mineral density of the primary tumor measured with dual-energy x-ray absorptiometry (P = .024). Additionally, in these 10 dogs, pamidronate's therapeutic activity was supported by subjective improvement in pain control in 4 of the 10 dogs treated. IV pamidronate appears clinically safe in tumor-bearing dogs and may possess modest biologic activity for managing neoplastic complications associated with pathologic bone resorption.

Absorptiometry, Photon↗

Bone metabolic effects of single-dose zoledronate in healthy dogs.

Zoledronate, an aminobisphosphonate with potent antiresorptive activity in bone, has the potential for treatment of malignant osteolysis and hypercalcemia in dogs. The purpose of this study was to evaluate the bone metabolic effects of a single dose of zoledronate in healthy dogs. Four skeletally mature, male, intact dogs received a 15-minute i.v. infusion of zoledronate at a dosage of 0.25 mg/kg. Urine N-telopeptide of type I collagen (NTx) excretion decreased significantly from baseline by 76, 63, 77, and 73% on days 7, 14, 21, and 28, respectively (P < .0125). Serum bone-specific alkaline phosphatase (bALP) decreased significantly from baseline by 36 and 42% on days 21 and 28, respectively (P < .0125). No changes were detected in indices of calcium homeostasis (ionized calcium, intact PTH, or urine calcium excretion). Single-dose i.v. zoledronate at 0.25 mg/kg appears to inhibit homeostatic osteolytic activity in healthy, skeletally mature dogs. Prospective studies should assess repeated-dose safety and activity in healthy and diseased animals of various age groups.

Alkaline Phosphatase↗

Urine N-telopeptide excretion in dogs with appendicular osteosarcoma.

Canine appendicular osteosarcoma (OSA) is a commonly diagnosed cancer that is capable of inducing pathologic bone remodeling. Investigating surrogate indices of bone metabolism may contribute to the diagnostic and therapeutic management of bone malignancies in companion animals. This study evaluated the excretion of N-terminal telopeptide (NTx), a marker of bone resorption that is detected in urine. Sixty-three dogs with appendicular OSA were compared with 29 age-matched healthy dogs. Dogs with appendicular OSA had significantly higher baseline urine NTx excretion than healthy controls (P < .0001). In 17 dogs with OSA treated with either amputation or standardized palliative therapies, significant reductions in urine NTx excretion were observed, suggesting that excessive bone resorption in dogs with OSA may be linked with focal skeletal osteolysis or its consequences. To identify any relationship between indicators of pathologic bone turnover, baseline urine NTx excretion was correlated with serum bone alkaline phosphatase (bALP) or radiographic tumor lengths at diagnosis. No significant correlations were identified between baseline urine NTx excretion and either bALP or tumor length. The findings from this study suggest that high urinary NTx excretion may support the diagnosis of focal skeletal osteolysis in dogs, and reductions in urine NTx excretion after treatment may reflect elimination or minimization of pathologic bone resorption.

Alkaline Phosphatase↗

Hematological toxicity and therapeutic efficacy of lomustine in 20 tumor-bearing cats: critical assessment of a practical dosing regimen.

Twenty cats with spontaneously arising tumors received oral lomustine at a dose range of 32 to 59 mg/m2 every 21 days. Due to biohazard concerns associated with lomustine capsule reformulation, a standardized 10-mg capsule dosage was used for all cats regardless of body weight. Severe hematological toxicity was infrequent, with the incidence of either grade III or IV neutropenia and thrombocytopenia being 4.1% and 1.0%, respectively. Cats receiving higher cumulative doses of lomustine trended toward a greater likelihood for progressive neutropenia (P=0.07). Two cats with lymphoma, two cats with fibrosarcoma, and one cat with multiple myeloma achieved a measurable partial response to lomustine therapy. Cats treated with higher dosages of lomustine trended toward statistically significant higher response rates (P=0.07).

Administration, Oral↗