Outcome of definitive fractionated radiation followed by exenteration of the nasal cavity in dogs with sinonasal neoplasia: 16 cases.

Local control is a major challenge in treating canine nasal tumours. Surgical cytoreduction prior to radiation therapy has not been shown to offer a survival advantage. Only one study has previously evaluated the outcome when surgery is performed after radiation, which demonstrated an improved survival time compared with radiation alone. The purpose of this study was to investigate the outcome of surgery after definitive radiation on survival times in dogs with sinonasal tumours. Medical records were retrospectively reviewed for dogs with nasal tumours that received definitive radiation followed by surgery. Information obtained from medical record review included signalment, diagnosis, treatment and outcome. The median survival time was 457 days. No long-term side effects were observed. These findings suggest that exenteration of the nasal cavity following definitive radiation for treatment of dogs with nasal tumours is well-tolerated and provides a similar survival duration to previous reports of radiation alone.

Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs.

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well-defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause-specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.

Radiosensitivity and capacity for radiation-induced sublethal damage repair of canine transitional cell carcinoma (TCC) cell lines.

Understanding the inherent radiosensitivity and repair capacity of canine transitional cell carcinoma (TCC) can aid in optimizing radiation protocols to treat this disease. The objective of this study was to evaluate the parameters surviving fraction at 2 Gy (SF(2) ), α/ß ratio and capacity for sublethal damage repair (SLDR) in response to radiation. Dose-response and split-dose studies were performed using the clonogenic assay. The mean SF(2) for three established TCC cell lines was high at 0.61. All the three cell lines exhibited a low to moderate α/ß ratio, with the mean being 3.27. Two cell lines exhibited statistically increased survival at 4 and 24 h in the dose-response assay. Overall, our results indicate that the cell lines are moderately radioresistant, have a high repair capacity and behave similarly to a late-responding normal tissue. These findings indicate that the radiation protocols utilizing higher doses with less fractionation may be more effective for treating TCC.

Sequential low-dose rate half-body irradiation and chemotherapy for the treatment of canine multicentric lymphoma.

BACKGROUND: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels. HYPOTHESIS: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs. ANIMALS: Thirty-eight client-owned animals diagnosed with multicentric lymphoma. METHODS: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy. RESULTS: The median 1st remission was 410 days (95% confidence interval [CI] 241-803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334-1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.

Radiation therapy for canine appendicular osteosarcoma.

Radiation therapy (RT) for the management of canine appendicular osteosarcoma (OSA) can be described as either palliative- or curative intent. Palliative RT uses coarsely fractionated external beam RT or radiopharmaceuticals to provide relief of pain and lameness associated with OSA while resulting in minimal, if any, radiation-induced acute adverse effects. Limb amputation and chemotherapy are considered (together) the standard of care for curative-intent treatment of canine appendicular OSA. When limb amputation is not possible, RT can be used for limb sparing and is supplemented with chemotherapy for presumed micrometastatic disease. Fractionated tumour irradiation with curative intent appears to be ineffective and local disease control can more likely be achieved when stereotactic radiosurgery or intra-operative extracorporeal irradiation is combined with strict case selection and adjunctive chemotherapy. The availability of limb-sparing RT is limited by experience and availability of specialised equipment. When planned and administered appropriately, radiation-associated adverse effects are often mild and self-limiting.

Esomeprazole induces upper gastrointestinal tract transmucosal permeability increase.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most widely used drug classes in the US and are now frontline medications for gastro-oesophageal reflux disease (GERD) and dyspepsia. In a previous work, we observed that a transmucosal, upper gastrointestinal (GI) leak exists in Barrett's oesophagus (BO) patients. PPI medications are commonly used by Barrett's patients. AIM: To examine if the PPI, esomeprazole, affects the barrier function of the upper GI tract. METHODS: The sucrose permeability test (SPT) was used to assess the possible effect of the PPI, esomeprazole, on upper GI leak in 37 first-time-presenting GERD patients and 25 healthy controls. RESULTS: Esomeprazole induced a significant transmucosal leak in the upper GI tract of patients taking the drug for the first time. The leak occurred quickly, within days of first taking the drug. The leak was also reversed within days of stopping the medication. CONCLUSIONS: This is the first patient-based study showing that a PPI compromises upper GI barrier function. There are potential implications for transmucosal leak of other medications that a patient on a PPI may be taking, as well as possible leak of endogenous peptides/proteins. The clinical consequences of this phenomenon are currently unknown, but are potentially important.

Cisplatin: a review of toxicities and therapeutic applications.

Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The antineoplastic activity occurs from DNA cross-links and adducts, in addition to the generation of superoxide radicals. Nephrotoxicity is the most well-known and potentially most clinically significant toxicity. Unfortunately, the mechanism for cisplatin nephrotoxicity has not been completely elucidated; however, many theories have been developed. Other toxicities include gastrointestinal, myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the most accepted way to prevent cisplatin nephrotoxicity. Research has focused on pharmaceuticals and enzyme/molecular alterations as alternatives to long-term diuresis. No agents have currently been identified that can protect from all toxicities. Cisplatin has shown activity against osteosarcoma, transitional cell carcinoma, squamous cell carcinoma (SCC), melanoma, mesothelioma, carcinomatosis and germinal cell tumours in the dog. In the cat, cisplatin cannot be utilized because of fulminant pulmonary oedema that occurs at standard doses. Intralesional cisplatin has been utilized in horses for the treatment of SCC and sarcoids.

A toxicity study of low-dose rate half-body irradiation and chemotherapy in dogs with lymphoma.

Thirteen dogs with previously untreated multicentric lymphoma were enrolled in a prospective study investigating the effects of low-dose rate total body irradiation (TBI) and chemotherapy. Dogs received either 6 or 8 Gy TBI in half-body fractions, 2 weeks apart. Toxicity consisted of mild to moderate haematological and gastrointestinal (GI) signs. One dog died from treatment complications. Anorexia was noted independent of dose. Haematological toxicity was more common and more severe after 8 Gy treatment. GI toxicity was more likely postcaudal half-body irradiation with 8 Gy. Other than leukotrichia, late effects from radiation were not observed. Results indicated that haematological and nonhaematological toxicity was dose dependent. However, the protocol was well tolerated and treatment intensification using a 2-week inter-radiation interval was possible in all dogs treated with 6 Gy. Preliminary survival data for these dogs were very encouraging, providing a strong rationale to analyse the efficacy of low-dose rate irradiation (LDRI) in canine lymphoma.

Canine acute radiation dermatitis, a survey of current management practices in North America.

Acute radiation-induced dermatitis (ARID) is a common sequela of radiation therapy in dogs. There is no consensus regarding ARID management in human medicine and the standard of care in veterinary medicine has not been reported. The objective was to report the practice standards for ARID management in dogs in North America. The design used was a questionnaire survey. Fifty-eight private and university teaching veterinary hospitals were contacted, 54 participated. The topical and oral medications used to treat ARID, prevent or treat bacterial infection, control pain and the indications for and timing of treatment initiation were the outcome measures. A minority of facilities (4/54, 7.5%) use exactly the same protocol regarding all parameters. There was agreement (>75% of facilities) with respect to the general use of oral antibiotics (77.8%), the need for pain control (92.6%) and the use of tramadol for pain control (76%), although the details of their use varied widely. There is a divergence of opinions regarding all details of ARID management in dogs except the general use of oral antibiotics and pain control medications.

Non-homogeneous hyperechogenic echo pattern three days after frozen embryo transfer is associated with lower pregnancy rates.

OBJECTIVE: To evaluate the association of mid-luteal phase echo patterns and pregnancy rates (PRs) following frozen embryo transfer (ET). METHODS: Sonographic evaluation of endometrial echo patterns was performed three days after ET in the first frozen ET cycle of women < 40 years of age who used their own oocytes as well as all donor oocyte recipients. RESULTS: The distribution of echo patterns and clinical PRs were similar in women using their own eggs and women who used donor oocytes; therefore all data was combined. The clinical PR was 49.5% with a hyperechogenic echo pattern vs 38.8% with a non-hyperechogenic pattern, p = .007. CONCLUSION: A larger study of frozen ET and mid-luteal echo pattern now demonstrates conclusions similar to the data from fresh ET in hyperstimulated in vitro fertilization (IVF)-ET cycles in that failure to attain a hyperechogenic echo pattern three days after ET is associated with lower pregnancy rates.

T-cell-derived malignant lymphoma in the boxer breed.

The boxer breed of dog is at high risk for a variety of neoplasms including lymphoma. In this observational study, tissue sections from boxer dogs with lymphoma were immunostained for T and B lymphocyte distinction, and the results compared with similar studies carried out on lymphoma tissues from temporally selected cohorts of golden retriever and rottweiler dogs. The frequency of T-cell lymphomas was significantly (P < 0.001 for all comparisons) higher in the boxers than in the rottweilers or golden retrievers. We are unaware of other reports linking immunotype of canine lymphoma with breed; whether other brachycephalic breeds of dogs have a similar preponderance of T-cell lymphoma awaits further study.

Lack of the protein tyrosine phosphatase SHP-1 results in decreased numbers of glia within the motheaten (me/me) mouse brain.

Mice that are homozygous for the autosomal recessive motheaten allele (me/me) lack the protein tyrosine phosphatase SHP-1. Loss of SHP-1 leads to many hematopoietic abnormalities, as well as defects such as infertility and low body weight. However, little is known regarding the role SHP-1 plays in the development of the central nervous system (CNS). To define the role of SHP-1 in CNS development and differentiation, we examined the brains of me/me mice at various times after birth for neuronal and glial abnormalities. Although the brains of me/me mice are slightly smaller than age-matched wild-type littermates, both me/me and wild-type brains are similar in weight, possess an intact blood-brain barrier, and have largely normal neuronal architecture. Significantly, the current study reveals that me/me brain shows decreases in the number of glial fibriallary acidic protein (GFAP)+ astrocytes and F480+ microglia compared with wild-type mice. In addition, decreased immunostaining for the myelin-synthesizing enzyme CNPase was observed in me/me mice, confirming the loss of myelin in these animals, as reported (Massa et al. [2000] Glia 29:376-385). It is particularly significant that there is a decreased number of immunolabeled glia of all subtypes and that this deficit in glial number is not restricted to a particular class of glia. This suggests that SHP-1 is necessary for the normal differentiation and distribution of astrocytes, microglia, and oligendrocytes within the murine CNS.

Optimization of field-cycled PEDRI for in vivo imaging of free radicals.

A numerical model of the behaviour of the magnetization in a field-cycled dynamic nuclear polarization (DNP) experiment is presented, with the aim of optimizing pulse sequence parameters in field-cycled proton-electron double-resonance free radical imaging. The model is used to predict the observed enhancement of the NMR signal as a function of the magnetic field strength, EPR irradiation frequency and pulse sequence timing, as well as the properties of the sample including the NMR and EPR relaxation times. The model allowed optimization of parameters in the field-cycled DNP experiment, in particular the EPR irradiation frequency, to find the value which would give the largest difference between NMR signals recorded with and without EPR irradiation. Experiments to verify the model were carried out using aqueous solutions of TEMPOL, which exhibits three hyperfine lines in its EPR spectrum and triarylmethyl (TAM), which has a single, narrow line. It was found that the model predicted very well the variation in DNP enhancement with EPR irradiation power for both samples. The behaviour of the NMR signal with EPR irradiation frequency in studies using TEMPOL was also accurately modelled, with the optimum frequency lying between 60 and 80 MHz, depending on the EPR irradiation power. The optimum frequency obtained from the model also agreed with the experimental data obtained using the TAM free radical, but with this sample the theoretical curves tended to deviate from the experimental data at irradiation frequencies below 70 MHz.

Cumulative pregnancy rates after four embryo transfers of either fresh or frozen embryos.

PURPOSE: To evaluate in the modern era of in vitro fertilization (IVF) cumulative probability of pregnancy for the first four embryo transfers (ET) irrespective of whether the embryos were fresh or frozen. METHODS: Retrospective review over a 2 1/2 year period. Cumulative probability of pregnancy for four consecutive cycles of either fresh or frozen ETs divided into four age groups. RESULTS: The cumulative clinical and viable pregnancy rates after four ETs were 92% and 88%; 87% and 82%; 83% and 69%; and 68% and 52% for age groups <30, 30-34, 35-39, and 40-44. The cumulative rates decline with age. CONCLUSIONS: Pregnancy rates per transfer for the first four ETs regardless of age are similar even in IVF centers that emphasize frozen ETs.

Pregnancy rates (prs) according to embryo cell number at time of embryo transfer (ET).

PURPOSE: To evaluate pregnancy and implantation rates following fresh and frozen embryo transfer (ET) according to blastomere number. METHODS: A retrospective study from 1/1/97 to 9/30/98 including all cycles with ETs irrespective of age. RESULTS: 65% of fresh transfers had at least one 8-cell embryo vs only 39.6% for frozen ET. The clinical pregnancy and implantation rates were higher when one 8-cell embryo was transferred (64% and 24%) vs a 5-7 cell embryo (41% and 14.5%) for fresh transfers. There was less of a difference with frozen ETs (46% and 19% for 8-cell vs 38% and 17% for 5-7 cell). CONCLUSIONS: Since mostly only 8-cell embryos at day 3 reach the blastocyst stage, these data raise questions as to whether the quest to attain the highest pregnancy rate per transfer through blastocyst transfer, may be at the expense of overall pregnancy rate (fresh and frozen) from a given oocyte harvest.

Effect of fibroids on cumulative probability of pregnancy in women taking follicle maturing drugs without assisted reproductive technology.

PURPOSE: To determine if the presence of uterine fibroids adversely affect in vivo conception rates. METHODS: Pelvic ultrasound evaluation of the presence or absence of fibroids in consecutive infertility patients not treated with assisted reproductive technology in a two-year period. Conception outcome noted. Data analyzed according to the presence or absence of fibroids. RESULTS: No difference in cumulative probability of pregnancy after five months was seen in patients with or without the presence of fibroids. There were no confounding variables found that could have skewed the pregnancy rates in one direction or the other. CONCLUSION: In general the presence of fibroids do not adversely affect conception outcome for in vivo pregnancies. However, since the majority of the fibroids were small (< 6 cm) and were not submucosal and did not compress the endometrial cavity, larger studies are needed to address specific subtypes and circumstances on pregnancy outcome.

Transfer of refrozen twice-thawed embryos do not decrease the implantation rate.

PURPOSE: To assess the ability of twice frozen/thawed multi-cell embryos to implant in the human uterus. METHOD: Fourteen frozen embryo transfer (ET) cycles, in which at least one twice-frozen embryo was thawed for transfer, were matched to frozen ET cycles in which no twice-frozen embryos were thawed. The number of embryos thawed at the pronuclear stage and at the multi-cell stage were matched. RESULTS: Multi-cell embryos frozen once had a 76.3% survival rate after thaw and those frozen twice had a 74.0% survival rate. For frozen ET cycles that had no twice-frozen embryos, the viable pregnancy and implantation rates were 58.3% and 29.8%, respectively. The corresponding rates for cycles involving at least one twice-frozen embryo were 50.0% and 25.5%, respectively. CONCLUSION: The inclusion of twice-frozen embryos in the embryo pool did not reduce the implantation rate.

Baseline computed tomography changes and clinical outcome after thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke.

OBJECTIVE: Intravenous recombinant tissue plasminogen activator (rt-PA) is the only therapy of proven value for patients with acute ischemic stroke (AIS). Controversy exists with regard to the prognostic significance of early computed tomography (CT) changes in patients receiving rt-PA for AIS. The authors retrospectively reviewed all cases of AIS who received intravenous rt-PA for AIS in University of South Alabama hospitals between January 1996 and May 1999. A neuroradiologist, blinded to clinical outcomes, reviewed all baseline CT scans for the presence of the following signs: hyperdense middle cerebral artery (HMCA), loss of gray-white differentiation (LGWD), insular ribbon sign (IRS), parenchymal hypodensity (PH), and sulcal effacement (SE). Modified Rankin Scale (mRS) score was recorded 90 days after thrombolysis, and clinical outcome was dichotomized as favorable (0-1) or unfavorable (2-6). The authors performed both univariate and multivariate analyses to investigate the relationship between early CT signs, baseline clinical variables, and functional outcome as measured by the 90-day mRS scores. Any one early CT finding was detected in 23(64%) patients. The frequency of specific findings were as follows: SE in 13 patients (36%), LGWD in 12 patients (33%), PH in 9 patients (25%), HMCA in 4 patients (11%), and IRS in 3 patients (8%) patients. There was no statistically significant association between the occurrence of these imaging findings and subsequent functional outcome after thrombolysis. The data suggest that the presence of subtle acute CT changes in AIS patients is not predictive of clinical outcome following administration of rt-PA as per National Institute of Neurological Disorders and Stroke protocol.