bluuebunny/crossref_metadata_2025 huggingface dataset:
Paclitaxel in Breast Cancer
Authors: Patt Debra , Gauthier Michelle , Giordano Sharon
Published: December 2005

Paclitaxel, a chemotherapeutic drug isolated from the Pacific yew, was approved for the treatment of metastatic breast cancer in 1994 and remains one of the most important agents in the treatment of patients with this disease. It is currently approved for the adjuvant treatment of node-positive breast cancer, administered sequentially after a standard doxorubicin-containing regimen, and for metastatic disease after failure of combination chemotherapy or relapse within 6 months of adjuvant chemotherapy. In this article, data on the pharmacology, clinical efficacy and safety of paclitaxel for the treatment of breast cancer will be reviewed.
Bisphosphonates as Adjuvant Therapy for Breast Cancer
Authors: Burkinshaw Roger , Coleman Robert
Published: December 2005

Great strides have been made over the last 20 years in the treatment of breast cancer and despite an increasing incidence, the number of deaths has fallen sharply since the late 1980s. The advent of new therapies, including taxanes and aromatase inhibitors, and exciting results announced recently using trastuzumab in the adjuvant treatment of HER2-positive patients should decrease this even further. However, although most patients present with disease that appears to be localized to the breast, a significant proportion of women will eventually develop metastatic breast cancer. Therefore, the detection and treatment of micrometastatic disease represents perhaps the most important remaining challenge in breast cancer management, and is the focus of extensive ongoing research. Bone is the most frequent site of distant relapse, accounting for approximately 40% of all first recurrences. In addition to the well recognized release of bone cell-activating factors from the tumor, it is now appreciated that the release of bone-derived growth factors and cytokines from resorbing bone can attract cancer cells to the bone surface and facilitate their growth and proliferation. Bisphosphonates are potent inhibitors of bone osteolysis and the inhibition of bone resorption could therefore have an effect on the development and progression of metastatic bone disease. They could represent an adjuvant therapeutic strategy of potential importance. Clinical trial results with the early bisphosphonate, clodronate, have proved inconclusive. A large, randomized, controlled trial has recently completed accrual and should provide the definitive answer to the question of the role of clodronate in this setting. More potent second- and third-generation bisphosphonates have also shown enhanced antitumor effects in preclinical evaluation and further studies are required to determine whether this antitumor potential of bisphosphonates translates to the clinical setting. Adjuvant bisphosphonates are, therefore, currently only recommended in the research setting and clinical trials evaluating the adjuvant use of these newer compounds are currently recruiting or being established. This article will review in more detail the rationale for the adjuvant use of bisphosphonates, the results of early trials, the progress of the later trials and the potential future role of bisphosphonates in the adjuvant treatment of breast cancer. In addition, it is increasingly acknowledged that many cancer treatments have detrimental effects on bone and can increase the risk of fracture. The increasing use of aromatase inhibitors, in particular, will become a major cause of treatment-induced bone loss. This bone loss can be prevented with bisphosphonate treatment and this will also be discussed.
Update on the Treatment of Recurrent Ovarian Cancer
Authors: Eltabbakh Gamal H , Goodrich Scott
Published: December 2005

Ovarian cancer is the leading cause of death for all gynecologic malignancies in developed countries, largely owing to the late stage of diagnosis. Despite response to initial surgery and chemotherapy, more than 65% of patients will have recurrent or persistent diseases. Approximately 50% of patients with recurrent ovarian cancer are asymptomatic. Recurrences are often diagnosed using a combination of tests, including cancer antigen 125, computed tomography, magnetic resonance imaging and positron emission tomography scan. The most significant prognostic factor among women with recurrent ovarian cancer is the length of time from initial diagnosis to recurrence. Treatment of recurrent ovarian cancer involves chemotherapy, with or without surgery. In selected patients, secondary cytoreductive surgery might significantly improve survival. Radiotherapy may have a role in the treatment of a small group of patients with localized symptomatic masses. New treatment modalities for women with recurrent ovarian cancer are needed, as none of the available treatments are curative.
Evolving Role of Serum Biomarkers in the Management of Ovarian Cancer
Authors: Gadducci Angiolo , Cosio Stefania , Zanca Giulia , Genazzani Andrea Riccardo
Published: December 2005

The availability of an ideal serum tumor marker would be of great clinical benefit for both the diagnosis and management of patients with epithelial ovarian cancer. Serum cancer antigen 125 assay significantly increases the diagnostic reliability of ultrasound in discriminating a malignant from a benign ovarian mass, especially in postmenopausal women, and it is the only well validated tumor marker for monitoring disease course. Several other tumor-associated antigens have been assessed, including glycoprotein antigens other than cancer antigen 125, soluble cytokeratin fragments, kallikreins, cytokines and cytokine receptors, vascular endothelial growth factor, D-dimer, and lisophosphatidic acid. This article assesses the potential diagnostic and prognostic role of these novel biomarkers, both alone and in combination with cancer antigen 125. The future for serum tumor marker research is represented by the emerging technology of proteomics, which may allow scientific advances comparable to those achieved with the introduction of monoclonal antibody technology.
Managing Anemia in HIV-Positive Women
Authors: O'Connell Casey , Levine Alexandra M
Published: December 2005

Anemia is a clinically significant complication of infection with HIV, especially in patients who develop clinical AIDS. Several large studies have demonstrated that HIV-infected women, particularly African–American women, are disproportionately affected by anemia. These studies also reveal an association between anemia and statistically significant decreases in survival. In this review, the impact of anemia, the demographic characteristics of affected patients and the known risk factors for development of anemia in HIV-infected women are discussed. In addition, the diverse etiologies of anemia in the setting of HIV infection are reviewed, as are current treatment recommendations.
Non-Oral Reversible Contraceptive Methods
Authors: Simon Melissa , Shulman Lee P
Published: December 2005

There are many contraceptives in the world market today. Knowledge of the vast spectrum of contraceptive methods is essential to the everyday practice of healthcare personnel. Such knowledge translates to improved care and access for women so they can obtain and utilize the appropriate contraception for their individual needs. This is a review of non-oral and nonsurgical contraceptive methods.
Alendronate plus Cholecalciferol for the Treatment of Osteoporosis
Authors: Heaney Robert P
Published: December 2005

Osteoporosis is a common medical condition in older individuals, responsible for approximately 1.5 million fragility fractures in the USA each year. Alendronate sodium with cholecalciferol (vitamin D3) is a newly developed combination formulation for the treatment of osteoporosis in women and for increasing bone mass in men with osteoporosis. It complements the existing once-weekly dosage formulation of alendronate sodium alone, providing, in addition to alendronate, a 2800 international unit (IU) dose of cholecalciferol (vitamin D3), equivalent to 400 IU daily. Its efficacy in reducing fracture risk is expected to be at least as good as that of once-weekly alendronate given for the same indications.
Tegaserod in the Treatment of Irritable Bowel Syndrome with Constipation
Authors: Saad Richard , Chey William D
Published: December 2005

Tegaserod, a novel serotonin receptor agonist, has gained acceptance and widespread use for the treatment of women with irritable bowel syndrome and constipation. Development of this therapy evolved from the emerging role of serotonin in gastrointestinal motor, secretory and sensory functions. The efficacy and safety of tegaserod has been well established in women suffering from irritable bowel syndrome with constipation. Large, randomized, double-blind, placebo-controlled trials involving more than 3500 predominantly female patients with irritable bowel syndrome and constipation have demonstrated the superiority of tegaserod over placebo in improving global and individual symptoms. The most common side effects of tegaserod in clinical trials were diarrhea and headache. Recent data suggest that retreatment with tegaserod after a drug holiday is efficacious, opening the door to the possibility of intermittent therapy for patients with irritable bowel syndrome and constipation. Areas in need of further investigation include the role of tegaserod in the treatment of pain and bloating in irritable bowel syndrome, whether tegaserod has a role in male patients, the long-term efficacy of tegaserod, whether tolerance develops in a subset of patients with extended therapy and whether tegaserod is beneficial for the treatment of other functional gastrointestinal disorders.
Paroxetine Use in the Treatment of Premenstrual Dysphoric Disorder
Authors: Misri Shaila , Kendrick Kristin
Published: December 2005

Premenstrual dysphoric disorder, which affects 3–8% of women of reproductive age, is characterized by a combination of symptoms that may include depressed mood, irritability, anxiety and/or physical symptoms. These symptoms occur during the luteal phase of the menstrual cycle, with remission generally occurring within 3 days after the onset of menses. Presently, treatment guidelines for premenstrual dysphoric disorder focus on lifestyle management and psychopharmacologic interventions, with selective serotonin reuptake inhibitors being considered the first line of medication intervention. The US Food and Drug Administration and Health Canada recently approved paroxetine for the treatment of premenstrual dysphoric disorder. This article reviews the properties of this medication and its use in the treatment of premenstrual dysphoric disorder.
Are we ‘WISE’r? Findings from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation Study
Authors: Ahmed Bina , Merz C Noel Bairey , Sopko George
Published: December 2005

Recognition of cardiovascular disease as the leading healthcare threat to women continues to shape the prioritization of efforts to more effectively diagnose and treat heart disease in women. At its inception almost 8 years ago, the National Heart, Lung and Blood Institute in the USA sponsored the Women's Ischemia Syndrome Evaluation (WISE) study, aiming to optimize symptom evaluation and diagnostic testing for ischemic heart disease in women and to explore pathophysiologic mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenosis. The WISE study has investigated the spectrum of anginal symptoms, diagnostic strategies for micro- and macrovascular coronary disease, and the role of psychosocial variables and reproductive hormones in ischemic heart-disease presentation. One of the pivotal WISE findings sheds light on chest pain in the absence of significant obstructive epicardial luminal coronary stenosis, otherwise known as Cardiac Syndrome X. In the WISE study, using coronary vasomotor testing during angiography, investigators observed prevalent abnormalities in coronary flow reserve, suggestive of microvascular coronary dysfunction in relation to adverse morbidity and mortality among these women. Findings such as these from the WISE study have significantly added to the current management approach to heart disease in women.
Glucocorticoid-Induced Osteoporosis
Authors: Kennedy Courtney C , Papaioannou Alexandra , Adachi Jonathan D
Published: December 2005

Glucocorticoids are widely used to treat several diseases; however, one of their major consequences is a deleterious effect on bone that may lead to glucocorticoid-induced osteoporosis. Fractures may begin to occur within 3 months of commencing oral glucocorticoid therapy, and may even occur in patients receiving low doses. The good news is that with effective management, bone loss and fractures can be prevented or greatly reduced in patients receiving glucocorticoids. Despite clear practice guidelines, glucocorticoid-induced osteoporosis often goes undiagnosed and untreated in many patients. In this article, a current overview of glucocorticoid-induced osteoporosis is provided, including how to recognize, prevent and treat osteoporosis in pre- and postmenopausal women receiving glucocorticoid therapy.
Adjuvant Systemic Therapy for Elderly Women with Breast Cancer
Authors: Henry N Lynn , Diehl Kathleen M , Hayes Daniel F
Published: December 2005

Although breast cancer is increasing in incidence, mortality from the disease is decreasing due to better treatment options. As the population ages, more women are being diagnosed with breast cancer at increasingly older ages. Tumors in elderly women tend to be more indolent than those in younger women, and physicians are sometimes reluctant to treat this cohort of patients simply because of their age. It is important for both primary care physicians and oncologists to be aware of breast cancer characteristics and treatments in the elderly in order to better serve this segment of the population. This review will discuss the benefits of both adjuvant chemotherapy and hormonal therapy in women with early stage breast cancer, with specific emphasis on the special attributes of elderly patients that should be considered when devising treatment plans.
Aromatase Inhibitors in the Adjuvant Treatment of Postmenopausal Women with Early Stage Breast Cancer
Authors: Ligibel Jennifer A , Winer Eric P
Published: December 2005

This article summarizes the current data regarding the use of the aromatase inhibitors as adjuvant hormonal therapy for postmenopausal women with early stage breast cancer. The article focuses on the five major trials examining the use of these drugs and their toxicity in the adjuvant setting. The data currently available suggest that the aromatase inhibitors are efficacious, either as upfront therapy or after a course of tamoxifen. Ongoing trials will compare these approaches and guide the use of these agents in the years to come.
Taxane Therapy for Early Stage Breast Cancer
Authors: Nabholtz Jean-Marc , Gligorov Joseph
Published: December 2005

Breast cancer is the most frequent cancer of women in developed countries. Systemic adjuvant chemotherapy has dramatically improved the outcome of patients treated for early stage invasive breast cancer. Among novel chemotherapeutic agents, the taxanes have emerged as the most powerful compounds since anthracycline regimens. Two taxanes are available (paclitaxel and docetaxel) and they share some characteristics, while having a number of significant differences, both in terms of preclinical and pharmacokinetic profiles and, most importantly, clinical consequences. In clinical practice, the taxanes are now standard therapy in metastatic breast cancer. Their role as monochemotherapy or in combination with anthracyclines in advanced breast cancer has suggested their potential therapeutic impact in the treatment of patients with early breast cancer. Available results in the adjuvant and neoadjuvant setting demonstrate that taxanes, used in combination with other chemotherapeutic agents or trastuzumab, or in sequential therapy, possess the capability to induce significant improvements, in particular in terms of survival, confirming the positive impact of taxanes on the natural history of breast cancer.
Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses
Authors: Sellon Debra C. , Monroe Veronica L. , Roberts Malcolm C. , Papich Mark G.
Published: December 2005

Objective—To determine an infusion rate of butorphanol
tartrate in horses that would maintain therapeutic
plasma drug concentrations while minimizing
development of adverse behavioral and gastrointestinal
tract effects.

Animals—10 healthy adult horses.

Procedure—Plasma butorphanol concentrations
were determined by use of high-performance liquid
chromatography following administration of butorphanol
by single IV injection (0.1 to 0.13 mg/kg of
body weight) or continuous IV infusion (loading dose,
17.8 µg/kg; infusion dosage, 23.7 µg/kg/h for 24
hours). Pharmacokinetic variables were calculated,
and changes in physical examination data, gastrointestinal
tract transit time, and behavior were determined
over time.

Results—A single IV injection of butorphanol was
associated with adverse behavioral and gastrointestinal
tract effects including ataxia, decreased borborygmi,
and decreased defecation. Elimination half-life of
butorphanol was brief (44.37 minutes). Adverse gastrointestinal
tract effects were less apparent during
continuous 24-hour infusion of butorphanol at a
dosage that resulted in a mean plasma concentration
of 29 ng/ml, compared with effects after a single IV
injection. No adverse behavioral effects were
observed during or after continuous infusion.

Conclusions and Clinical Relevance—Continuous
IV infusion of butorphanol for 24 hours maintained
plasma butorphanol concentrations within a range
associated with analgesia. Adverse behavioral and
gastrointestinal tract effects were minimized during
infusion, compared with a single injection of butorphanol.
Continuous infusion of butorphanol may be a
useful treatment to induce analgesia in horses. (Am J
Vet Res 2001;62:183–189)
Evaluation of effectiveness of a vaccination program against an infectious disease at the population level
Authors: Carpenter Tim E.
Published: December 2005

Objective—To evaluate the application of a vaccine in a population of animals.

Sample Population—Field-trial data from the literature.

Procedure—A spreadsheet simulation model was constructed to estimate the impact of a vaccination program, assuming various population sizes, transmission rates, and vaccine efficacies.

Results—Total effectiveness (proportion of affected animals [ie, cases] avoided) increased with the vaccinated proportion of the population. However, with a highly efficacious vaccine, this relationship discontinued after a sufficient vaccination proportion was reached, reflecting herd immunity. Evaluation of a case study indicated that what may be considered a poor vaccine on the basis of its low efficacy may protect a substantial portion of the population if the vaccine is administered to a sufficient number of susceptible animals. Further investigation of a case study of horses indicated that evaluating a vaccine based solely on its efficacy could greatly underestimate its value.

Conclusions and Clinical Relevance—When evaluating a vaccine applied to a population, in addition to the vaccine efficacy, the vaccination rate, cost of the vaccine, potential disease transmission rate, and number and cost of cases avoided must also be considered. Efficacy may underestimate vaccine value in terms of the reduction of indirect cases typically avoided when vaccination is applied in a population. (Am J Vet Res2001;62:202–205)
Quantitative assessment of mast cells and expression of IgE protein and mRNA for IgE and interleukin 4 in the gastrointestinal tract of healthy dogs and dogs with inflammatory bowel disease
Authors: Locher Christine , Tipold Andrea , Welle Monika , Busato André , Zurbriggen Andreas , Griot-Wenk Monika E.
Published: December 2005

Objective—To characterize the mucosal IgE network in dogs affected with inflammatory bowel disease (IBD) and compare it with that for healthy dogs.

Animals—9 healthy dogs and 20 dogs with IBD.

Procedure—In situ hybridization of mRNA specific for IgE and interleukin 4 (IL-4) and immunohistochemical analysis for IgE protein and 2 markers of mast cells (ie, tryptase and chymase) were performed on tissue sections obtained from the gastrointestinal (GI) tract and lymph nodes of dogs.

Results—Dogs with IBD had significantly more cells positive for IgE protein and more mast cells in the GI mucosa than healthy dogs. Despite this significant increase in number of cells positive for IgE, cells positive for IgE mRNA were rarely detected in the GI mucosa; most cells positive for IgE mRNA were found in mesenteric lymph nodes. Signal pattern of IL-4 mRNA was similar to that of IgE mRNA.

Conclusions and Clinical Relevance—The increased numbers of cells positive for IgE and mast cells in dogs with IBD suggest hypersensitivity such as hypersensitivity to bacterial or dietary-derived antigens in the intestinal lumen. Future studies need to elucidate whether this represents a cause of inflammation or is a result of the inflammatory process of IBD. (Am J Vet Res2001;62:211–216)
Effect of commercially available nasal strips on airway resistance in exercising horses
Authors: Holcombe Susan J. , Berney Cathy , Cornelisse Cornelis J. , Derksen Frederik J. , Robinson N. Edward
Published: December 2005

Objective—To determine the effect of a commercially
available nasal strip on airway mechanics in exercising
horses.

Animals—6 horses (5 Standardbreds and 1
Thoroughbred).

Procedure—Horses exercised on a treadmill at
speeds corresponding to 100 and 120% of maximal
heart rate with and without application of a commercially
available nasal strip. Concurrently, tracheal pressures,
airflow, and heart rate were measured. Peak
inspiratory and expiratory tracheal pressures, airflow,
respiratory frequency, and tidal volume were recorded.
Inspiratory and expiratory airway resistances
were calculated by dividing peak pressures by peak
flows. Endoscopic examination of the narrowest point
of the nasal cavity (ie, nasal valve) was performed in
1 resting horse before, during, and after application of
a nasal strip.

Results—During exercise on a treadmill, peak tracheal
inspiratory pressure and inspiratory airway
resistance were significantly less when nasal strips
were applied to horses exercising at speeds corresponding
to 100 and 120% of maximal heart rate.
Application of the nasal strip pulled the dorsal conchal
fold laterally, expanding the dorsal meatus.

Conclusions and Clinical Relevance—The commercially
available nasal strip tented the skin over the
nasal valve and dilated that section of the nasal passage,
resulting in decreased airway resistance during
inspiration. The nasal strip probably decreases the
amount of work required for respiratory muscles in
horses during intense exercise and may reduce the
energy required for breathing in these horses.
(Am J Vet Res 2002;63:1101–1105)
Effect of transforming growth factor-β1, insulin-like growth factor-I, and hepatocyte growth factor on proteoglycan production and regulation in canine melanoma cell lines
Authors: Serra Montserrat , Pastor Josep , Domenzain Clelia , Bassols Anna
Published: December 2005

Objective—To identify extracellular proteoglycans
produced by canine melanoma cell lines and analyze
the effect of transforming growth factor-β1 (TGF-β1),
insulin-like growth factor-I (IGF-I), and hepatocyte
growth factor (HGF) on these proteoglycans.

Sample Population—3 canine melanoma cell lines
(ie, CML-1, CML-6M, and CML-10c2).

Procedure—Extracellular proteoglycans were analyzed
by use of metabolic labeling and western
immunoblot analysis. The effect of TGF-β1 on cell proliferation
was determined by incorporation of 5-
bromo-2'-deoxyuridine.

Results—The CML-1 and CML-6M melanoma cell
lines produced 2 main extracellular proteoglycans.
One of them was identified as versican, a proteoglycan
found in undifferentiated human melanoma cell
lines. The CML-10c2 cells produced a small amount of
extracellular proteoglycans. Addition of TGF-β1 (1.25 to
6.25 ng/ml) increased the release of sulfated proteoglycans
into the medium. The TGF-β1 had mainly a
posttranslational effect, because it increased the molecular
mass of the sulfated bands. Addition of IGF-I
(50 ng/ml) slightly increased production of proteoglycans
in the CML-6M cell line, whereas HGF (50 ng/ml)
did not have any effect on proteoglycan production.

Conclusions and Clinical Relevance—The proteoglycan
content and response to TGF-β1 treatment for
CML-1 and CML-6M canine melanoma cell lines are
similar to that for undifferentiated human melanoma
cell lines. In contrast, CML-10c2 cells produced a low
amount of proteoglycans with high molecular weight.
Because these extracellular proteoglycans are
involved in the control of cell adhesion, proliferation,
and migration, they may play an important role in the
progression of melanomas in dogs. (Am J Vet Res
2002;63:1151–1158)
Cerebrospinal fluid glutamine, tryptophan, and tryptophan metabolite concentrations in dogs with portosystemic shunts
Authors: Holt David E. , Washabau Robert J. , Djali Sina , Dayrell-Hart Betsy , Drobatz Kenneth J. , Heyes Melvyn P. , Robinson Michael B.
Published: December 2005

Objective—To determine whether glutamine (GLN), tryptophan (TRP), and tryptophan metabolite concentrations are higher in cerebralspinal fluid (CSF) dogs with naturally occurring portosystemic shunts (PSS), compared with control dogs.

Animals—11 dogs with confirmed PSS and 12 control dogs fed low- and high-protein diets.

Procedure—Cerebrospinal fluid and blood samples were collected from all dogs. Serum and CSF concentrations of GLN, alanine, serine, TRP, 5-hydroxyindoleacetic acid (5-HIAA), and quinolinic acid (QUIN) were measured.

Results—Cerebrospinal fluid concentrations of GLN, TRP, and 5-HIAA were significantly higher in PSS dogs, compared with control dogs fed high- or lowprotein diets. Cerebrospinal fluid QUIN concentration was significantly higher in PSS dogs, compared with control dogs fed the low-protein diet. Serum QUIN concentration was significantly lower in PSS dogs, compared with control dogs fed either high- or lowprotein diets.

Conclusions and Clinical Relevance—An increase in CNS GLN concentration is associated with high CSF concentrations of TRP and TRP metabolites in dogs with PSS. High CSF 5-HIAA concentrations indicate an increased flux of TRP through the CNS serotonin metabolic pathway, whereas high CSF QUIN concentrations indicate an increased metabolism of TRP through the indolamine-2,3-dioxygenase pathway. The high CSF QUIN concentrations in the face of low serum QUIN concentrations in dogs with PSS indicates that QUIN production from TRP is occurring in the CNS. High concentrations of QUIN and other TRP metabolites in the CNS may contribute to neurologic abnormalities found in dogs with PSS and hepatic encephalopathy. (Am J Vet Res2002;63:1167–1171)
Liver glutathione concentrations in dogs and cats with naturally occurring liver disease
Authors: Center Sharon A. , Warner Karen L. , Erb Hollis N.
Published: December 2005

Objective—To determine total glutathione (GSH) and
glutathione disulfide (GSSG) concentrations in liver
tissues from dogs and cats with spontaneous liver
disease.

Sample Population—Liver biopsy specimens from
63 dogs and 20 cats with liver disease and 12 healthy
dogs and 15 healthy cats.

Procedure—GSH was measured by use of an enzymatic
method; GSSG was measured after 2-vinylpyridine
extraction of reduced GSH. Concentrations were
expressed by use of wet liver weight and concentration
of tissue protein and DNA.

Results—Disorders included necroinflammatory liver
diseases (24 dogs, 10 cats), extrahepatic bile duct
obstruction (8 dogs, 3 cats), vacuolar hepatopathy (16
dogs), hepatic lipidosis (4 cats), portosystemic vascular
anomalies (15 dogs), and hepatic lymphosarcoma
(3 cats). Significantly higher liver GSH and protein
concentrations and a lower tissue DNA concentration
and ratio of reduced GSH-to-GSSG were found in
healthy cats, compared with healthy dogs. Of 63 dogs
and 20 cats with liver disease, 22 and 14 had low liver
concentrations of GSH (µmol) per gram of tissue; 10
and 10 had low liver concentrations of GSH (nmol) per
milligram of tissue protein; and 26 and 18 had low
liver concentrations of GSH (nmol) per microgram of
tissue DNA, respectively. Low liver tissue concentrations
of GSH were found in cats with necroinflammatory
liver disease and hepatic lipidosis. Low liver concentrations
of GSH per microgram of tissue DNA
were found in dogs with necroinflammatory liver disease
and cats with necroinflammatory liver disease,
extrahepatic bile duct occlusion, and hepatic lipidosis.

Conclusions and Clinical Relevance—Low GSH values
are common in necroinflammatory liver disorders,
extrahepatic bile duct occlusion, and feline
hepatic lipidosis. Cats may have higher risk than dogs
for low liver GSH concentrations. (Am J Vet Res
2002;63:1187–1197)
Evaluation of bacteriologic culture of pooled fecal samples for detection of Mycobacterium paratuberculosis
Authors: Wells Scott J. , Whitlock Robert H. , Lindeman Cynthia J. , Fyock Terry
Published: December 2005

Objective—To compare sensitivity of several methods
of bacteriologic culture of pooled bovine fecal
samples for detection of Mycobacterium paratuberculosis
and evaluate homogeneity in number of
M paratuberculosisin pooled fecal samples.

Sample Population—Feces from 10 dairy cows that
shed M paratuberculosis at various concentrations
and 1 dairy cow known to be free of infection with
M paratuberculosis.

Procedure—5 fecal pooling methods, 2 culture methods,
and 2 pool sizes were evaluated. Each pooled
sample contained 1 infected sample and 4 or 9 uninfected
samples.

Results—Sensitivity of detection of M paratuberculosis was
greater with smaller pool size (5 vs 10 samples/
pool). Detection sensitivity was also associated
with concentration of bacteria in the infected sample.
Results indicated that, compared with concurrent
bacterial culture of individual infected samples, 37 to
44% of pooled samples with low bacterial concentrations
yielded positive culture results and 94% of
pooled samples with high bacterial concentrations
yielded positive results.

Conclusions and Clinical Relevance—Bacteriologic
culture of pooled fecal samples may provide a valid
and cost-effective method of detecting M paratuberculosis
infection in cattle herds. (Am J Vet Res
2002;63:1207–1211)
Use of noninvasive dental dolorimetry to evaluate analgesic effects of intravenous and intrathecal administration of morphine in anesthetized dogs
Authors: Brown Dorothy C. , Bernier Noemie , Shofer Frances , Steinberg Sheldon A. , Perkowski Sandra Z.
Published: December 2005

Objective—To determine whether changes in amplitude of the reflex-evoked muscle action potential (REMP) elicited by noninvasive dental dolorimetry (electrical stimulation of the tooth pulp) in anesthetized dogs may be used to objectively evaluate the effectiveness of IV and intrathecal (IT) administration of morphine.

Animals—6 male Beagles that were 2 to 6 years old.

Procedure—Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin via the IV and IT routes of administration; however, only results for morphine and saline treatments were reported here. Dogs were anesthetized and prepared for noninvasive dental dolorimetry. After IV or IT administration, electrical stimulation was applied to a tooth, and REMPs of the digastricus muscle were recorded at 5-minute intervals for 60 minutes. To determine differences in REMP amplitude between treatments, a linear regression line was fitted for each dog-treatment combination.

Results—The IV administration of morphine significantly inhibited REMP amplitude, compared with IV administration of saline solution. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution.

Conclusions and Clinical Relevance—Noninvasive dental dolorimetry in anesthetized dogs has promise as a technique for use in evaluating the analgesic potential of drugs administered IV and IT through evaluation of their effect on REMP amplitude recorded for the digastricus muscle. (Am J Vet Res2002;63: 1349–1353)
Differentiation of Haemobartonella canis and Mycoplasma haemofelis on the basis of comparative analysis of gene sequences
Authors: Birkenheuer Adam J. , Breitschwerdt Edward B. , Alleman A. Rick , Pitulle Christian
Published: December 2005

Objective—To determine whetherHaemobartonella canisandMycoplasma haemofelis(formerly known asH felis[large form]) can be differentiated by use of comparative analysis of gene sequences.

Sample Population—Blood samples obtained from 3 dogs infected withH canisand 2 cats infected withM haemofelis.

Procedure—The partial 16S rDNA and ribonuclease P RNA (RNase P) genes were amplified, cloned, and sequenced in blood samples obtained fromH canis-infected dogs andM haemofelis-infected cats. The DNA sequences were subjected to comparative analysis.

Results—The 16S rDNA sequences ofH canisandM haemofeliswere nearly identical (homology of 99.3 to 99.7%). In contrast, RNase P gene sequences had a lower degree of sequence homology between the 2 organisms (94.3 to 95.5%).

Conclusions and Clinical Relevance—Haemobartonella canisandM haemofelisare not identical organisms. Molecular differentiation ofH canisandM haemofelisis more clearly evident by use of comparative analysis of RNase P gene sequences than by comparative analysis of 16S rDNA gene sequences. (Am J Vet Res2002;63:1385–1388)
In vitro evaluation of an intraluminal solution to attenuate effects of ischemia and reperfusion in the small intestine of horses
Authors: Hoogmoed Linda M. Van , Nieto Jorge E. , Snyder Jack R. , Harmon Faye A.
Published: December 2005

Objective—To evaluate the efficacy of intraluminal administration of a customized solution during low-flow ischemia and reperfusion in the jejunum of horses.

Sample Population—Segments of jejunum obtained from 13 healthy adult horses.

Procedure—In isolated segments of jejunum maintained in an extracorporeal circuit, arterial flow was reduced to 20% of baseline for 40 minutes (ischemia) followed by 60 minutes of reperfusion. In 2 groups, a customized solution (concentrations, 12.5 and 25%, respectively) was placed in the lumen prior to lowflow ischemia and maintained during reperfusion. The control group received intraluminal lactated Ringer's solution for the same duration. Various metabolic, hemodynamic, histologic, and permeability variables were recorded.

Results—The 12.5% solution resulted in less histomorphologic injury and reduced mucosal permeability to albumin, compared with the 25% solution and the lactated Ringer's solution. Morphologic injury and permeability were reduced in tissues that received the 25% solution, compared with the control group, but this difference was not significant.

Conclusions and Clinical Relevance—Use of a 12.5% customized solution appeared to minimize injury in the isolated extracoporeal jejunal loop, which provides some indication that it might be useful in clinical situations. (Am J Vet Res2002;63:1389–1394)
Effect of caprine arthritis-encephalitis virus infection on expression of interleukin-16 in goats
Authors: Sharmila C. , Williams John W. , Reddy P. Gopal
Published: December 2005

Objective—To determine the effect of caprine arthritis- encephalitis virus (CAEV) infection on expression of interleukin-16 (IL-16).

Animals—-6 goats experimentally infected with CAEV and 6 age-matched healthy uninfected control goats.

Procedure—-Peripheral blood mononuclear cells (PBMCs) and synovial membrane cells from infected and control goats cultured with or without phytohemagglutinin were analyzed for IL-16 mRNA by use of a reverse transcriptase-polymerase chain reaction assay with goat-specific primers, after cloning and sequencing of a 384-bp fragment of the goat IL-16 gene. Synovial fluid, serum, and culture supernatants of PBMCs and synovial cells of control and CAEVinfected goats were analyzed for IL-16 by use of an ELISA.

Results—-The 384-bp product was 86% homologous to the corresponding human IL-16 nucleotide sequence. Higher expression of IL-16 mRNA in PBMCs (unstimulated or stimulated with phytohemagglutinin) was detected in samples from CAEVinfected goats, compared with control goats, but the difference was not significant. Synovial membrane cells infected in vitro had higher expression than uninfected control cells. Higher IL-16 concentration was detected in synovial fluid, serum, and culture supernatants of PBMCs of infected goats than in samples from control goats.

Conclusions and Clinical Relevance—Infection with CAEV increases expression of IL-16, a proinflammatory and chemotactic cytokine. This cytokine appears to be constitutively expressed at low concentrations in normal uninfected PBMCs and synovial membrane cells. Increased production of IL-16 in CAEV infection may partly be responsible for increased lymphoid cell infiltrations observed in arthritic joints and other tissues of CAEV-infected goats. (Am J Vet Res2002;63:1418–1422)
Effects of stimulus with proinflammatory mediators on nitric oxide production and matrix metalloproteinase activity in explants of cranial cruciate ligaments obtained from dogs
Authors: Riitano Marco C. , Pfister Hedi , Engelhardt Petra , Neumann Ulf , Reist Martin , Zurbriggen Andreas , Stoffel Michael , Peel John , Jungi Thomas , Schawalder Peter , Spreng David E.
Published: December 2005

Objective—To evaluate the origin and degree of activity of nitric oxide (NO) and matrix metalloproteinase (MMP) in explants of cranial cruciate ligaments (CCLs) obtained from dogs and cultured with and without inflammatory activators.

Sample Population—Tissue specimens obtained from 7 healthy adult Beagles that were (mean ± SD) 4.5 ± 0.5 years old and weighed 12.5 ± 0.8 kg.

Procedure—The CCLs were harvested immediately after dogs were euthanatized, and specimens were submitted for explant culture. Cultures were stimulated by incubation with a combination of interluekin-1, tumor necrosis factor-α, and lipopolysaccharide, or they were not stimulated. Culture supernatants were examined for production of NO nitrite-nitrate metabolites (NOts) and activity of MMP. Cultured specimens were evaluated by use of immunohistochemical analysis to detect activity of inducible NO synthase (iNOS).

Results—All ligament explants produced measurable amounts of NOts. Stimulated cultures produced significantly more NOts after incubation for 24 and 48 hours, compared with nonstimulated cultures. Production of MMP in supernatants after incubation for 48 hours was significantly higher in stimulated cultures than in nonstimulated cultures. Cells with positive staining for iNOS were detected on all slides. Positively stained cells were predominantly chondroid metaplastic. There was a significant difference in intensity of cell staining between stimulated and nonstimulated cultures.

Conclusion and Clinical Relevance—Explant cultures of intact CCLs obtained from dogs produce iNOS-induced NO. Stimulation of chondroid metaplastic cells in CCL of dogs by use of inflammatory activators can increase production of iNOS, NOts, and MMP. (Am J Vet Res2002;63:1423–1428)
Inheritance of pancreatic acinar atrophy in German Shepherd Dogs
Authors: Moeller E. Michael , Steiner Jörg M. , Clark Leigh Anne , Murphy Keith E. , Famula Thomas R. , Williams David A. , Stankovics Mary E. , Vose Amy S.
Published: December 2005

Objective—To assess the heritability of pancreatic acinar atrophy (PAA) in German Shepherd Dogs (GSDs) in the United States.

Animals—135 GSDs belonging to 2 multigenerational pedigrees.

Procedure—Two multigenerational pedigrees of GSDs with family members with PAA were identified. The clinical history of each GSD enrolled in the study was recorded, and serum samples for canine trypsinlike immunoreactivity (cTLI) analysis were collected from 102 dogs. Dogs with a serum cTLI concentration ≤ 2.0 µg/L were considered to have exocrine pancreatic insufficiency (EPI) and were assumed to have PAA.

Results—Pedigree I consisted of 59 dogs and pedigree II of 76 dogs. Serum cTLI concentrations were measured in 48 dogs from pedigree I and 54 dogs from pedigree II. A total of 19 dogs (14.1%) were determined to have EPI, 9 in pedigree I (15.3%) and 10 in pedigree II (13.6%). Of the 19 dogs with EPI, 8 were male and 11 were female.

Conclusion and Clinical Relevance—Evaluation of data by complex segregation analysis is strongly suggestive of an autosomal recessive mode of inheritance for EPI in GSDs in the United States. (Am J Vet Res2002;63:1429–1434)
Use of a high-molecular-weight carboxymethylcellulose in a tissue protective solution for prevention of postoperative abdominal adhesions in ponies
Authors: Murphy David J. , Peck Lynn S. , Detrisac Carol J. , Widenhouse Christopher W. , Goldberg Eugene P.
Published: December 2005

Objective—To evaluate efficacy and safety of IP administration of high-molecular-weight carboxymethylcellulose (HMW CMC) for the prevention of postoperative intra-abdominal adhesions in ponies.

Animals—10 ponies.

Procedure—A 1% solution of HMW CMC was instilled intra-abdominally prior to surgery in 5 ponies, whereas 5 control ponies did not receive HMW CMC. Postoperative adhesions were induced by use of a bowel-abrasion method comprising laparotomy, typhlotomy, and abrasion of jejunal serosa at multiple sites with placement of 3 sutures at each site. Day of surgery was day 0. After surgery, ponies were monitored, and hematologic, serum biochemical, and peritoneal fluid analyses were performed on days 1, 2, 3, 5, 7, and 10. On day 10, ponies were euthanatized. Intra-abdominal adhesions were recorded, and tissue samples were collected for histologic examination.

Results—A significantly greater number of adhesions, number of multiple adhesions, and mean incidence of adhesions were identified in control ponies, compared with CMC-treated ponies. Mean peritoneal fluid WBC count on day 7 and serum fibrinogen concentrations on days 5 and 7 were significantly higher in control ponies, compared with CMC-treated ponies. Results of serum biochemical analyses did not differ significantly between the 2 groups.

Conclusions and Clinical Relevance—Intra-abdominal use of 1% HMW CMC during surgery was effective for preventing postoperative adhesions in ponies. Use of HMW CMC did not have detrimental effects on wound healing, intra-abdominal defenses, or patient health. A 1% solution of HMW CMC may be used routinely during abdominal surgery of horses for prevention of postoperative adhesions. (Am J Vet Res2002;63:1448–1454)
Influence of long-term treatment with tetracycline and niacinamide on antibody production in dogs with discoid lupus erythematosus
Authors: Mueller Ralf S. , Fieseler Kathryn V. , Bettenay Sonya V. , Rosychuk Rodney A.W.
Published: December 2005

Objective—To evaluate the effect of long-term treatment with tetracycline and niacinamide on antibody production in dogs by measuring postvaccinal serum concentrations of antibodies against canine parvovirus and canine distemper virus.

Animals—10 dogs receiving long-term treatment with tetracycline and niacinamide (treatment group) and 10 healthy dogs (control group).

Procedure—The treatment group included 9 dogs with discoid lupus erythematosus and 1 dog with pemphigus foliaceus on long-term treatment (> 12 months) with tetracycline and niacinamide. The control group included 10 healthy dogs with no clinical signs of disease and no administered medications for the past 3 months. Blood samples were obtained from all dogs by jugular venipuncture. Serum antibody titers against canine parvovirus and canine distemper virus antigens were measured, using hemaglutination inhibition and serum neutralization, respectively, and compared between groups.

Results—A significant difference in antibody titers between treatment- and control-group dogs was not found. All dogs had protective antibody titers against canine distemper virus, and 8 of 10 dogs from each group had protective titers against canine parvovirus infection.

Conclusion and Clinical Relevance—These results provide evidence that long-term treatment with tetracycline and niacinamide does not interfere with routine vaccinations and thus does not seem to influence antibody production in dogs. (Am J Vet Res2002; 63:491–494)
Finasteride-induced prostatic involution by apoptosis in dogs with benign prostatic hypertrophy
Authors: Sirinarumitr Kaitkanoke , Sirinarumitr Theerapol , Johnston Shirley D. , Sarkar Dipak K. , Kustritz Margaret V. Root
Published: December 2005

Objective—To determine the effect of finasteride on programmed cell death (apoptosis) of prostatic cells during prostatic involution in dogs with benign prostatic hypertrophy (BPH).

Animals—9 dogs with BPH.

Procedure—Dogs were randomly assigned to treatment or control groups. Treatment dogs (n = 5) were administered finasteride (0.1 to 0.5 mg/kg, PO, q 24 h) for 16 weeks, whereas the 4 control dogs were administered an inert compound. Prostatic cells from the prostatic fluid portion of the ejaculate of treatment and control dogs were obtained before and 1, 2, 3, 4, 8, and 16 weeks after initiation of treatment. Cells were concentrated by use of centrifugation. Prostatic cells were examined for indications of apoptosis by use of a terminal deoxyribonucleotidyl transferase- mediated deoxyuracil triphosphate nick-end labeling technique. After receiving the inert compound for 16 weeks, the 4 control dogs were administered finasteride for 16 weeks, and evaluations were repeated.

Results—Percentage of apoptotic prostatic cells in ejaculated prostatic fluid of treatment dogs increased significantly (from 9% before treatment to 33, 31, 26, and 27% after 1, 2, 3, and 8 weeks of treatment, respectively). There was no significant change in percentage of apoptotic prostatic cells in the ejaculated prostatic fluid of control dogs.

Conclusions and Clinical Relevance—Finasterideinduced prostatic involution appears to be via apoptosis in dogs with BPH. Finasteride treatment of dogs with BPH causes prostatic involution by apoptosis rather than necrosis. (Am J Vet Res2002;63:495–498)
Cardiovascular changes associated with intravenous administration of fumonisin B1 in horses
Authors: Smith Geoffrey W. , Constable Peter D. , Foreman Jonathan H. , Eppley Robert M. , Waggoner Amy L. , Tumbleson Mike E. , Haschek Wanda M.
Published: December 2005

Objective—To determine whether cardiovascular dysfunction is evident in horses with leukoencephalomalacia experimentally induced by administration of fumonisin B1.

Animals—11 healthy horses of various breeds (body weight, 252 to 367 kg).

Procedure—Horses were randomly assigned to 3 groups and administered fumonisin B1daily. Horses received IV injections of 0 (control horses; n = 4), 0.01 (3), or 0.20 mg (4) of fumonisin B1/kg for 7 to 28 days. Horses were examined daily for evidence of neurologic disease. When neurologic signs consistent with leukoencephalomalacia were evident, horses were anesthetized, and catheters were inserted for evaluation of the cardiovascular system. After recovery from anesthesia, hemodynamic measurements were obtained.

Results—Fumonisin-treated horses with clinical signs of neurologic disease had evidence of cardiovascular dysfunction manifested as decreases in heart rate, cardiac output, right ventricular contractility (assessed by measuring the maximal rate of change of right ventricular pressure), coccygeal artery pulse pressure, and pH and base excess in venous blood as well as increases in systemic vascular resistance, compared with values for control horses. Fumonisin-treated horses with and without clinical signs of neurologic disease also had higher serum and right ventricular sphinganine and sphingosine concentrations than control horses.

Conclusions and Clinical Relevance—An association was detected among fumonisin-induced neurologic disease, increased serum and myocardial sphinganine and sphingosine concentrations, and decreased cardiovascular function in horses. Fumonisin-induced decreases in cardiovascular function may contribute to the pathophysiologic development of leukoencephalomalacia in horses. (Am J Vet Res2002;63:538–545).