bluuebunny/crossref_metadata_2025 huggingface dataset:
Rotordynamic characteristics of a rotor with labyrinth gas seals. Part 2: a non-linear model
Authors: Huang Diangui , Li Xuesong
Published: May 2004

This paper focuses mainly on a model of the aerodynamic force of rotors subjected to an unsteady flowfield in labyrinth gas seals. An unsteady three-dimensional Navier-Stokes solver is used to simulate the flowfield in labyrinth gas seals. The basic time marching algorithm used to solve the fully three-dimensional unsteady governing equations is known as a hybrid finite analytic difference scheme. The ɛ- k model is chosen to model the turbulent components in the governing equations owing to its widely acknowledged reputation. The three-dimensional unsteady flowfield in labyrinth gas seals and the aerodynamic force acting on the rotor under various conditions are predicted, and then the rotordynamic coefficients of the rotor are estimated. It is shown that the relationship between the force excited by the flow and the displacement and velocity is not simply linear. A non-linear model of aerodynamic force for labyrinth seals is developed. The study shows that the direct stiffness increases rapidly with increase in the non-dimensionalized amplitude in the x direction, Āx the cross-coupled stiffness increases in a very moderate manner with increase in Āx, the direct damping decreases dramatically with increase in the non-dimensionalized maximum velocity in the x di1rection, V V xmax and the cross-coupled damping decreases at a small rate with increase in V V xmax. Furthermore, the direct stiffness and damping coefficients are also functions of displacement and velocity.
Rotordynamic characteristics of a rotor with labyrinth gas seals. Part 3: coupled fluid-solid vibration
Authors: Huang Diangui , Li Xuesong
Published: May 2004

This paper focuses on the fluid-solid interaction between a vibrating rotor and the unsteady flowfield around it in labyrinth gas seals. The object under consideration is a zero damping Jeffcott rotor subjected to an unsteady fluid field in labyrinth gas seals. An unsteady time-accurate three-dimensional Navier-Stokes solver is used to simulate the flowfield in the labyrinth gas seals, and the unsteady aerodynamic force vector acting on the vibrating rotor is obtained. A fourth-order explicit Adams scheme is used to simulate the dynamic response of the rotor. The coupled fluid-solid vibration of the rotor is studied under various inlet tangential velocities. The research shows that the current method is more accurate in predicting the stability of such shafts than the conventional method.
Enantioselective CO2 Fixation Catalyzed by Optically Active Cobalt Complexes
Authors: Tanaka Hirotaka , Kitaichi Yasunori , Sato Mitsuo , Ikeno Taketo , Yamada Tohru
Published: May 2004

In the presence of a catalytic amount of optically active cobalt complexes and amine bases, a racemic epoxide, such as N,N-diphenylaminomethyloxirane, reacted with gaseous carbon dioxide to afford the optically active cyclic carbonate along with the optically active starting epoxide.
Microbial Metabolism of Di-n-butyl Phthalate by Bacterium Bacillus Natto
Authors: Begum Aleya , Katsumata Hideyuki , Kaneco Satoshi , Suzuki Tohru , Ohta Kiyohisa
Published: May 2004

Microbial metabolism behavior of di-n-butyl phthalate (DBP) in aqueous solution by bacterium Bacillus natto was quantitatively characterized by HPLC. Under the optimal conditions, the degradation percentage of DBP was 72% after 24 h of cultivation. Concerning the metabolites of DBP degradation, dipropyl phthalate, monobutyl phthalate, and phthalic acid were identified by GC/MS.
p53 Expression and Environmental Tobacco Smoke Exposure in Feline Oral Squamous Cell Carcinoma
Authors: Snyder L. A. , Bertone E. R. , Jakowski R. M. , Dooner M. S. , Jennings-Ritchie J. , Moore A. S.
Published: May 2004

The purpose of this study was to determine the prevalence of p53 overexpression in feline oral squamous cell carcinomas (SCC) and to determine, if any, the association between p53 overexpression and lifestyle factors and environmental exposures, including exposure to environmental tobacco smoke (ETS). Questionnaires concerning exposure to ETS and other environmental factors were sent to owners of cats presenting to the Harrington Oncology Program with a diagnosis of oral SCC between 1991 and 2000. Additionally, 23 formalin-fixed biopsy samples from these cats, with information regarding ETS, were evaluated immunohistochemically for p53 expression using the CM-1 clone and the avidin-biotin-horseradish peroxidase method. Of the 23 samples evaluated, 15 (65%) showed positive nuclear staining for the CM-1 clone. Tumor biopsy samples from cats exposed to any ETS were 4.5 times more likely to overexpress p53 than were tumors from unexposed cats (P = 0.19). Among cats with any ETS exposure, those with 5 years or longer of exposure were 7.0 times more likely to overexpress p53 (P = 0.38). Longhaired cats (P = 0.18) and female cats (P = 0.35) were also more likely to show p53 expression in their tumors. These results provide additional support for a relationship between oral SCC development and exposure to household ETS and may implicate p53 as a potential site for carcinogen-related mutation in this tumor.
Summer Pheasant's Eye (Adonis aestivalis) Poisoning in Three Horses
Authors: Woods L. W. , Filigenzi M. S. , Booth M. C. , Rodger L. D. , Arnold J. S. , Puschner B.
Published: May 2004

Three horses died as a result of eating grass hay containing summer pheasant's eye ( Adonis aestivalis L.), a plant containing cardenolides similar to oleander and foxglove. A 9-year-old thoroughbred gelding, a 20-year-old appaloosa gelding, and a 5-year-old quarter horse gelding initially presented with signs of colic 24–48 hours after first exposure to the hay. Gastrointestinal gaseous distension was the primary finding on clinical examination of all three horses. Two horses became moribund and were euthanatized 1 day after first showing clinical signs, and the third horse was euthanatized after 4 days of medical therapy. Endocardial hemorrhage and gaseous distension of the gastrointestinal tract were the only necropsy findings in the first two horses. On microscopic examination, both horses had scattered foci of mild, acute myocardial necrosis and neutrophilic inflammation associated with endocardial and epicardial hemorrhage. The third horse that survived for 4 days had multifocal to coalescing, irregular foci of acute, subacute, and chronic myocardial degeneration and necrosis. A. aestivalis (pheasant's eye, summer adonis) was identified in the hay. Strophanthidin, the aglycone of several cardenolides present in Adonis spp., was detected by liquid chromatography-mass spectrometry-mass spectrometry in gastrointestinal contents from all three horses. Although Adonis spp. contain cardiac glycosides, cardiac lesions have not previously been described in livestock associated with consumption of adonis, and this is the first report of adonis toxicosis in North America.
A von Willebrand's Factor Genomic Nucleotide Variant and Polymerase Chain Reaction Diagnostic Test Associated with Inheritable Type-2 von Willebrand's Disease in a Line of German Shorthaired Pointer Dogs
Authors: Kramer J. W. , Venta P. J. , Klein S. R. , Cao Y. , Schall W. D. , Yuzbasiyan-Gurkan V.
Published: May 2004

Heritable, type-2 von Willebrand's disease (vWD) was studied in a line of German Shorthaired Pointers (GSPs) in which some members had a nucleotide variant in exon 28 of the von Willebrand factor ( VWF) gene. A polymerase chain reaction (PCR) diagnostic test for the nucleotide variant was developed to establish the disorder's mode of inheritance and to eliminate it from the line. Thirty-six of the 49 GSPs in the line, 14 unrelated GSP controls, and 71 unrelated dogs of various breeds were tested for the presence of the variant nucleotide. All the dogs with a vWF antigen deficiency (<70% of normal) were either homozygous or heterozygous for the nucleotide variant. The variant was not located in any tested dog in the line or outside of the line with a vWF antigen value greater than 68%. Of the GSPs in the line tested, two were homozygous for the variant, 15 were heterozygous, and 19 were variant free. The collective evidence of this and other studies is consistent with the variant nucleotide being the cause of the type-2 vWD in this line of GSPs and German Wirehaired Pointers. The PCR diagnostic test for the variant nucleotide was successfully used to select and produce progeny that were variant free and vWD free. This test should be effective in the subsequent elimination of this same variant from other lines of dogs.
Hepatic Alveolar Echinococcosis in Cynomolgus Monkeys (Macaca fascicularis)
Authors: Bacciarini L. N. , Gottstein B. , Pagan O. , Rehmann P. , Gröne A.
Published: May 2004

Alveolar echinococcosis was diagnosed in 12 cynomolgus monkeys ( Macaca fascicularis) at postmortem examination within a period of 6 years. Besides consistent involvement of the liver, parasitic lesions were also present in mesenteric lymph nodes, pancreas, lung, and kidney. In the liver, various patterns of host's responses to parasitic tissue could be distinguished. Infiltration of macrophages, often multinucleated, around usually intact metacestodes was the main feature of one pattern. A second pattern was characterized by the presence of abundant, normally degenerate granulocytes in addition to macrophages surrounding collapsed laminated structures. Finally and as a third pattern, some cysts were surrounded by marked collagen deposition, which was usually not a significant feature of the other foci. Parasitic cysts with protoscolices were observed in foci with the first and third pattern but not in the second one. The simultaneous occurrence of all three patterns was observed in most animals. Type AA amyloid was identified either in the space of Dissé, macro-phages or blood vessel walls in nine animals using immunohistochemistry. Identity of parasitic structures such as metacestodes of Echinococcus multilocularis was confirmed immunohistochemically. All animals that could be tested serologically (7/12) had detectable antibodies against the E. multilocularis-specific Em2 antigen. Liver lesions of six animals were additionally analyzed by polymerase chain reaction, yielding the amplification of a specific E. multilocularis DNA fragment in each case.
Interleukin-1β and Tumor Necrosis Factor-α Produce Distinct, Time-dependent Patterns of Acute Arthritis in the Rat Knee
Authors: Bolon B. , Campagnuolo G. , Zhu L. , Duryea D. , Zack D. , Feige U.
Published: May 2004

Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) synergistically induce and sustain arthritis. Two competing hypotheses of arthritis induction are 1) that TNF preferentially mediates inflammation, whereas IL-1 impels bone destruction, or 2) that either cytokine controls the entire process. In this study, these propositions were tested in two experiments by instilling IL-1β or TNF-α into one knee of Lewis rats ( n = 6/group) to incite arthritis, after which semiquantitative scores for inflammation, bone resorption, osteoclasts, and cartilage integrity were acquired. In the induction study, IL-1β or TNF-α (3, 10, or 30 μg) was given once to incite arthritis. After 2 days, IL-1β induced significant, dose-dependent increases in inflammation (mild to marked), bone resorption (minimal to moderate), and osteoclasts (minimal to moderate). In contrast, TNF-α induced minimal to mild inflammation but had little impact on resorption or osteoclasts. Both IL-1 and TNF (≥10 μg) yielded mild cartilage degeneration. Most lesion scores in TNF-treated rats were significantly lower than those in animals given the same dose of IL-1β. In the persistence study, rats were injected once with IL-1 or TNF (10 μg) and maintained for 2, 3, or 7 days. IL-1β significantly enhanced inflammation (all 3 days), bone resorption (days 2 and 3), osteoclasts (days 2 and 3), and cartilage matrix loss (days 2 and 3), whereas TNF-α augmented inflammation (days 2 and 3) and cartilage degeneration (day 2) but not bone resorption or osteoclasts. Thus, both IL-1β and TNF-α can launch inflammation, but IL-1β drives skeletal destruction.
Histopathologic Findings and Classification of Feline Renal Transplants
Authors: De Cock H. E. V. , Kyles A. E. , Griffey S. M. , Bernsteen L. , Gregory C. R.
Published: May 2004

Seventy-seven feline transplant kidney specimens, obtained from 1 to 3,183 days (9 years) after transplantation, were reevaluated histologically and classified on the basis of the Banff '97 guidelines for human renal transplant kidneys. Overall, this classification system appeared useful in detecting rejection reactions and confirmed the finding in humans that biopsies can diagnose subclinical rejection and therefore are an important diagnostic tool for the follow up of renal transplants. However, on the basis of serum creatinine values, the severity of the acute or active and chronic lesions was not accurately reflected by this scoring system. This is thought to be due to the significant differences in histologic rejection patterns, especially in acute or active rejection, in cats when compared with humans. Tubulitis, lymphocytic glomerulitis, and vasculitis, which are the main pillars of the Banff '97 acute or active rejection scoring system, are either rare or not found in cats. The presence of significant necrotizing glomerulitis and vasculitis in feline renal transplants might imply that the rejection is complicated by acute antibody-mediated rejection. Alternatively, cyclosporine toxicity also should be considered because some of these kidneys show other signs of cyclosporine toxicity. Finally, the significance of subcapsular and interlobular phlebitis, rarely described in human rejection reactions but a distinct entity in cats, is unknown. From this study, it is clear that there are significant differences in the histology of acute or active rejection between humans and cats and that a better understanding of the histologic appearance of renal allografts will be especially beneficial for treatment and prognostic purposes.
Pathologic, Immunohistochemical, and Electron Microscopic Findings in Naturally Occurring Virulent Systemic Feline Calicivirus Infection in Cats
Authors: Pesavento P. A. , Maclachlan N. J. , Dillard-Telm L. , Grant C. K. , Hurley K. F.
Published: May 2004

Infection with feline calicivirus (FCV) is a common cause of upper respiratory and oral disease in cats. FCV infection is rarely fatal, however, virulent, systemic strains of FCV (VS-FCV) that cause alopecia, cutaneous ulcers, subcutaneous edema, and high mortality in affected cats have recently been described. Seven cats with natural VS-FCV infection all had subcutaneous edema and ulceration of the oral cavity, with variable ulceration of the pinnae, pawpads, nares, and skin. Other lesions that were present in some affected cats included bronchointerstitial pneumonia, and pancreatic, hepatic, and splenic necrosis. Viral antigen was present within endothelial and epithelial cells in affected tissues as determined by immunohistochemical staining with a monoclonal antibody to FCV. Mature intranuclear and intracytoplasmic virions in necrotic epithelial cells were identified by transmission electron microscopy. VS-FCV infection causes epithelial cell cytolysis and systemic vascular compromise in susceptible cats, leading to cutaneous ulceration, severe edema, and high mortality.
Multipotential Osteosarcoma with Various Mesenchymal Differentiations in a Young Dog
Authors: Hoenerhoff M. J. , Kiupel M. , Rosenstein D. , Pool R. R.
Published: May 2004

Apparently synchronous, aggressive, mixed mesenchymal tumors in the right tibia, right femur, left femur, and rib cage produced multiple microscopic metastases in the lungs and macroscopic metastases in the liver, kidney, and spleen in a 1.5-year-old, neutered male, mixed-breed dog. No primary soft tissue tumor mass was present. Microscopically, the neoplasm exhibited osteosarcomatous, chondrosarcomatous, liposarcomatous, leiomyosarcomatous, fibrosarcomatous, angiosarcomatous, and leukocytic differentiation and was diagnosed as a multipotential osteosarcoma with various mesenchymal differentiation. Immunohistochemically, the neoplasm was cytoplasmically immunoreactive for vimentin, osteonectin, osteocalcin, CD 18, CD 31, desmin, and muscle-specific actin. Oil Red O staining was positive within liposarcomatous areas. Skeletal metastases from a primary bone tumor are exceedingly rare in human and veterinary medicine. However, the history, clinical signs, location, microscopic and immunohistochemical features were similar to those described in aggressive, poorly differentiated osteosarcomas of children. In addition, the wide range of mesenchymal tissue differentiation of this neoplasm was unusual, and to the authors' knowledge, an osteosarcoma with this degree of multiple differentiation has not been previously reported in the dog.
Immunohistochemical Expression of Estrogen Receptor β in Normal and Tumoral Canine Mammary Glands
Authors: Martín De Las Mulas J. , Ordás J. , Millán M. Y. , Chacón F. , De Lara M. , Espinosa De Los Monteros A. , Reymundo C. , Jover A.
Published: May 2004

To date, two isoforms of estrogen receptors (ER) have been identified, cloned, and characterized from several species, estrogen receptor-α (ERα) and estrogen receptor-β (ERβ). Although the presence of ERα has been demonstrated in normal and tumoral canine mammary tissues, the issue of ERβ expression has not been addressed in the dog. In this study, we have analyzed the expression of ERβ in formalin-fixed, paraffin-embedded tissue samples of nonaltered mammary gland, 30 malignant (six complex carcinoma, 12 simple carcinoma, three carcinosarcoma, and nine carcinoma or sarcoma in benign tumor), and five benign (one fibroadenoma, one complex papilloma, one complex adenoma, and two benign mixed tumors) mammary tumors of the dog by using a polyclonal ERβ antibody and the avidin-biotin-peroxidase complex immunohistochemical technique. Our results show that high numbers of normal ductal and acinar epithelium and approximately one third of canine mammary tumors express ERβ. This expression was higher in benign than in malignant tumors. Furthermore, expression was higher in complex and mixed histologic subtypes of malignant tumors when compared with simple subtypes.
Multifocal Rhabdomyosarcomas Within the Tongue and Oral Cavity of a Dog
Authors: Brockus C. W. , Myers R. K.
Published: May 2004

A 10-year-old terrier crossbreed presented with a change in bark intonation of 3–4 month's duration and pronounced panting. Four variably sized masses were observed within the oral cavity. The largest mass was located within the parenchyma at the caudal region of the tongue. Others were located on the left arytenoid, within the soft palate, and in the oropharynx above the soft palate. Histopathologic specimens consisted of large round to polygonal cells occasionally containing multiple nuclei and rare faint cytoplasmic cross striations. Staining was weakly positive with periodic acid-Schiff. Immunocytochemistry was strongly diffusely positive for muscle-specific actin, myoglobin, and desmin and scattered positive for S-100 and vimentin. Phosphotungstic acid-hematoxylin staining enhanced cytoplasmic cross striations. The cytoplasm of all neoplastic cells was filled with mitochondria on electron microscopy. The final diagnosis was multifocal/metastatic rhabdomyosarcoma.
Expression of Myogenic Regulating Factors, Myogenin and MyoD, in Two Canine Botryoid Rhabdomyosarcomas
Authors: Kobayashi M. , Sakai H. , Hirata A. , Yonemaru K. , Yanai T. , Watanabe K. , Yamazoe K. , Kudo T. , Masegi T.
Published: May 2004

Myogenin and MyoD regulate the development of skeletal muscle, and their expressions are specific to the stages of myogenesis. Therefore, these myogenic regulatory proteins could be considered as sensitive and specific markers for rhabdomyosarcoma. In this report we investigated the immunohistochemical reactivities of myogenin and MyoD in two canine bladder botryoid rhabdomyosarcomas that were different in the degree of differentiation. MyoD was stained in the Ki-67 antigen-positive undifferentiated mesenchymal cells, which had proliferative activity similar to myoblasts differentiated from mesoblasts. In contrast, multinucleated neoplastic cells were positive for myogenin and α-sarcomeric actin but not for Ki-67 antigen, similar to the myotubes differentiated from myoblastic cells. The expressions of myogenin and MyoD were closely correlated to the histologic features of myogenic neoplastic cells.
The Roles of Smad2 and Smad3 in the Development of Chemically Induced Skin Tumors in Mice
Authors: Tannehill-Gregg S. H. , Kusewitt D. F. , Rosol T. J. , Weinstein M.
Published: May 2004

Transforming growth factor-β (TGF-β) plays a complex role in skin carcinogenesis, acting as a suppressor early in tumor development but later as a promoter. Smad proteins are important intracellular mediators of TGF-β signaling. To determine the effect of disrupting Smad genes and TGF-β signaling on chemically induced skin carcinogenesis in mice, transgenic mice heterozygous for Smad2 or Smad3 deletions and wild-type controls were treated with topical dimethylbenzanthracene for 7 months. Tumor multiplicity, type, and degree of differentiation were assessed by histopathology and immunohistochemistry. Smad3± mice developed significantly fewer tumors than the wild-type group ( P < 0.05). This indicated a possible oncogenic function for Smad3 in skin carcinogenesis. Smad2± mice formed less-differentiated tumors than their wild-type counterparts, supporting a tumor suppressor role for Smad2. There was a significant difference ( P < 0.05) in tumor type between Smad2± and Smad3± groups, suggesting that Smad2 and Smad3 may regulate different targets.
Cerebral Ganglioneuroblastoma in a Golden Retriever Dog
Authors: Kuwamura M. , Kotera T. , Yamate J. , Kotani T. , Aoki M. , Hori A.
Published: May 2004

An 8-month-old Golden Retriever dog was euthanatized because of a large cerebral mass extending from the right frontal lobe to the thalamus that was composed of both mature and immature neuronal cells. The better differentiated cells had abundant eosinophilic cytoplasm with prominent Nissl substance and were generally positive for neurofilament and variably positive for synaptophysin. The generally smaller and less-differentiated cells were infrequently positive for proliferating cell nuclear antigen and were negative for any neuronal and glial markers. No apparent glial differentiation of the immature tumor cells was detected. Based on morphologic and immunohistochemical features, the diagnosis of cerebral ganglioneuroblastoma was made. This neoplasm is very rare in all species, especially in the central nervous system, and has never been reported previously in this site in a dog.
Nodular Thyroid Hyperplasia in a Cynomolgus Monkey
Authors: Kouchi M. , Okimoto K.
Published: May 2004

Nodular thyroid hyperplasia was found in a 4-year-old male cynomolgus monkey ( Macaca fascicularis). The monkey was clinically normal; however, necropsy revealed multiple variably sized nodules in both lobes of the thyroid gland. In contrast to the fairly uniform diameter of the lumen of follicles in the surrounding gland, the diameter of the follicular lumen within the hyperplastic nodules was highly variable and ranged from nonexistent to cystlike. Occasionally, in the larger follicles there were papillary infoldings of epithelium. The hyperplastic nodules were partially encapsulated by a fibrous capsule and showed little compression of the surrounding tissue. The follicular cells and colloid comprising the hyperplastic nodule were immunohistochemically positively stained with the antibody for thyroglobulin. Ultrastructurally, the cells forming follicles had numerous microvilli along the luminal surface, and lysosomal bodies and dilated rough endoplasmic reticulum in the cytoplasm. All these morphologic findings are consistent with nodular thyroid hyperplasia, which is rare in nonhuman primates.
Malignant Astrocytoma with Binucleated Granular Cells in a Sprague-Dawley Rat
Authors: Pruimboom-Brees I. M. , Brees D. J. J. E. , Shen A. C. , Ibebunjo C.
Published: May 2004

A 2-year-old Sprague-Dawley rat with hindlimb paralysis was diagnosed with a cerebral malignant astrocytoma. The distinctive feature of this astrocytoma was the presence of scattered binucleated cells that contained hypereosinophilic, 1–2 μm in diameter, cytoplasmic granules. The neoplastic astrocytes stained positively for vimentin (VIM), lysozyme, and phosphotungstic acid hematoxylin (PTAH). Within the binucleated cells, granules stained with PTAH and periodic acid-Schiff (PAS) before and after diastase digestion. Ultrastructurally, neoplastic astrocytes were characterized by cytoplasmic aggregates of electron-dense intermediate filaments consistent with VIM and desmin. The cytoplasm of binucleated cells contained numerous phagolysosomes enlarged by myelin figures and glycoprotein or glycolipid. Intermediate filaments were not present. This is the first description, in the rat, of a neoplasm with features resembling the human granular cell astrocytoma. Our findings suggest that an astrocytic origin should be considered for the binucleated cells in this neoplasm.
Overexpression of the erbB-2 Proto-oncogene in Canine Osteosarcoma Cell Lines and Tumors
Authors: Flint A. F. , U'Ren L. , Legare M. E. , Withrow S. J. , Dernell W. , Hanneman W. H.
Published: May 2004

The status of the erbB-2 (human epidermal growth factor receptor 2/neu) proto-oncogene in canine osteosarcoma (OSA) has not been reported previously. In this study we used real-time reverse transcriptase polymerase chain reaction to evaluate erbB-2 expression in seven canine OSA cell lines and 10 canine OSA tissue samples. We determined erbB-2 to be significantly overexpressed in 86% (six of seven) of the cell lines and 40% (4 of 10) of the OSA tissues samples. Given the importance of erbB-2 in human breast cancer, the finding of erbB-2 overexpression in canine OSA may be important in further understanding the pathogenesis and possible therapies of OSA.
Immunohistochemical Expression of p27 and p21 in Canine Cutaneous Mast Cell Tumors and Histiocytomas
Authors: Wu H. , Hayashi T. , Inoue M.
Published: May 2004

The objective of this study was to evaluate by immunohistochemical means the nuclear expression of p27 and p21 proteins in cutaneous mast cell tumors and histiocytomas of dogs. In mast cell tumors, nine of the 13 grade I tumors, 13 of the 19 grade II tumors, and 10 of the 15 grade III tumors showed no detectable or mild p27 immunoreactivity. In contrast, one of the 13 grade I tumors, 12 of the 19 grade II tumors, and 11 of the 15 grade III tumors showed moderate or marked p21 immunoreactivity. Nineteen of the 28 histiocytomas showed no detectable or mild p27 immunoreactivity, and 24 cases showed moderate or marked p21 immunoreactivity. These findings indicate that a loss or absence of p27 expression is an early pathogenic event in mast cell and histiocyte tumorigenesis and that p21 expression may be a marker of mast cell tumor progression and histiocytoma cell proliferation.
Acute Bacterial Cystitis Does not Cause Deoxyribonucleic Acid Damage Detectable by the Alkaline Comet Assay in Urothelial Cells of Dogs
Authors: Alves A. , De Miranda Cabral Gontijo A. M. , Salvadori D. M. F. , Rocha N. S.
Published: May 2004

Considering the high incidence of dogs with acute bacterial cystitis (BC) and the relationship among inflammation, genotoxicity, and carcinogenesis, we conducted a case-control study comparing the frequency of deoxyribonucleic acid (DNA) lesions assessed by the comet assay between disease-free animals (13 males and 13 females) and cytology-confirmed cases of acute BC (12 males and 12 females), which was mainly caused by Staphylococcus sp. (40%) and Escherichia coli (35%). The results show no increase in DNA damage in cells obtained by bladder washings and no influence of age, sex, and breed due to acute BC. In conclusion, DNA damage was seemingly not associated with the infection by specific bacteria.
Dementia with Lewy Bodies: Review and Pharmacotherapeutic Implications
Authors: Rojas‐Fernandez Carlos H. , MacKnight Chris
Published: May 2004

Alzheimer's disease accounts for 50–60% of dementia cases in older people. Dementia with Lewy bodies is now recognized as the second most common type of dementia. It is different from Alzheimer's disease and has important pharmacotherapeutic implications. Key features include early‐onset, persistent, well‐formed, visual hallucinations and motor features of parkinsonism. Pharmacologic management of neurobehavioral symptoms is complicated by an exaggerated response to neuroleptics, which causes excessive morbidity and mortality. Patients with dementia with Lewy bodies may be particularly responsive to cholinesterase inhibitors. When neurobehavioral symptoms are severe enough to require pharmacologic intervention, it is recommended that agents such as trazodone or cholinesterase inhibitors be considered first‐line therapy. If these fail, neuroleptics may be prescribed with caution.
Treatment of ACE Inhibitor‐Induced Cough
Authors: Luque Carla A. , Ortiz Mariola Vazquez
Published: May 2004

Angiotensin‐converting enzyme (ACE) inhibitors are widely administered to treat numerous medical conditions. Although they are generally well tolerated, they are associated with a dry cough that can lead to discontinuation of treatment. Data concerning the frequency, onset, and clinical effects vary among the agents. When discontinuing the ACE inhibitor is not an ideal option, pharmacologic treatment of the cough may be considered, such as cromolyn, baclofen, theophylline, sulindac, and local anesthetics.
Atypical Antipsychotics in Older Adults
Authors: Chan Yiu‐Chung , Pariser Stephen F. , Neufeld Gayle
Published: May 2004

Psychotic symptoms are common in older adults and reflect a variety of psychiatric and medical conditions. Antipsychotic drugs form the core of the treatment of these symptoms; however, treatment of the elderly is complicated by a high frequency of comorbid medical illnesses, risk of side effects, and age‐related changes in pharmacodynamics and pharmacokinetics. The superior safety and efficacy of atypical antipsychotics makes them first‐line agents for managing psychotic patients with schizophrenia. Their uses now extend to other conditions such as schizoaffective disorders, delusional disorder, and mood disorders with psychotic features. Although the drugs have been studied extensively in young subjects, well‐designed, double‐blind, placebo‐controlled studies are relatively lacking in the elderly. Our knowledge of their safety, efficacy and dosage in older adults is based on a few studies with small samples or extrapolated from studies of younger patients. Several psychiatric and medical conditions that are associated with psychotic symptoms in older people are reviewed, as well as how these patients may benefit from treatment with these agents.
Management of and Counseling for Psychotropic Drug‐Induced Sexual Dysfunction
Authors: Gutierrez Mary A. , Stimmel Glen L.
Published: May 2004

Clinicians are increasingly faced with the need to identify, treat, and counsel patients regarding psychotropic drug‐induced sexual dysfunction. Antipsychotic and antidepressant drugs have both rational mechanisms to explain their effects on sexual function and established literature documenting these effects. The agents have potential for causing decreased libido, delayed ejaculation, and anorgasmia. Management and counseling can be highly effective for patients taking these agents.
The Effect of Amiodarone on the Ventricular Fibrillation Threshold
Authors: Chen Bonnie P. , White C. Michael , Fan Chengde , Kluger Jeffrey , Chow Moses S. S.
Published: May 2004

We evaluated the antifibrillatory effect of two different doses of amiodarone after cardiac arrest with a cardiopulmonary resuscitation (CPR) model in 19 pigs. Ventricular fibrillation was induced by pacing the right ventricle using a primary drive train at a cycle length of 270 msec for 8 beats. The minimum current strength necessary to induce sustained ventricular fibrillation was defined as the ventricular fibrillation threshold (VFT) measured in mA. Three VFT determinations were made at baseline, followed by 9 minutes of continuous CPR with two determinations of VFT, and three after stabilization. The pigs were placed into one of three groups: amiodarone 2 or 5 mg/kg, or placebo. The average poststabilization VFT in each group was compared with the average baseline VFT. Pigs receiving amiodarone 2 mg/kg had significantly higher VFT after stabilization than at baseline (22.88 ± 12.76 to 27.10 ± 10.18 mA, p=0.048), as did those receiving 5 mg/kg (17.03 ± 7.01 to 28.08 ± 11.58 mA, p=0.002). The ΔVFT was significantly greater with amiodarone 5 mg/kg than with vehicle (placebo), but not with 2 mg/kg. There were no changes in VFT in any group during CPR versus baseline. When active treatments were combined, the trend was toward better survival in the amiodarone groups (13/13) compared with the placebo group (4/6, p=0.076).
Can We Justify Ipratropium Therapy as Initial Management of Acute Exacerbations of COPD?
Authors: Demirkan Kutay , Kuhl David , Headley A. Stacey , Self Timothy
Published: May 2004

Although inhaled ipratropium is commonly accepted as the drug of choice for long‐term management of chronic bronchitis and emphysema, little evidence is available to promote its administration in conjunction with a β2‐agonist as part of initial management of exacerbations of chronic obstructive pulmonary disease (COPD) in the acute care setting. Reasons for its widespread acceptance for acutely ill patients may include its status as a first‐line agent for long‐term therapy, its relative safety, and attempts to provide optimal patient care. Since inhaled ipratropium is beneficial as immediate therapy for asthma in the emergency department, some practitioners attempted to extrapolate these findings to treatment of COPD. Review of available studies reveals wide variability in methodologies and results. Although some studies reported improvement in pulmonary function tests, no clinically significant differences in patient outcomes, including shorter hospitalization, were evident. In patients who fail traditional therapies, inhaled ipratropium is reasonable. Double‐blind, randomized, placebo‐controlled trials in patients receiving emergency department care and in hospitalized patients that reveal shorter length of stay or other improved outcomes, are necessary to establish routine addition of inhaled ipratropium to β2‐agonists in the initial management of acute COPD.
Phenytoin and Fosphenytoin: A Model of Cost and Clinical Outcomes
Authors: Armstrong Edward P. , Sauer Karen Ann , Downey Madeline J.
Published: May 2004

We developed a pharmacoeconomic model to compare costs and clinical outcomes of administering phenytoin and fosphenytoin alone and in combination in hospitalized patients. Effectiveness data were obtained by distributing a questionnaire to 33 registered nurses at three acute care hospitals who worked in critical care, neurology services, or emergency department. The questionnaire addressed methods of phenytoin and fosphenytoin administration, frequency of adverse reactions, methods of treating adverse reactions, and demographic information. The model estimated that if 50% of phenytoin loading doses were substituted with fosphenytoin, a reduction in adverse events resulted in an estimated increase of $36/patient cost to the hospital. If phenytoin maintenance dosages were substituted with fosphenytoin, the model predicted essentially no change in cost to the hospital. It appears that fosphenytoin reduces adverse events at a reasonable increase in total hospital costs.
Low‐Dose Diclofenac, Naproxen, and Ibuprofen Cohort Study
Authors: Péez‐Gutthann Susanne , García‐Rodríguez Luis Alberto , Duque‐Oliart Alberto , Varas‐Lorenzo Cristina
Published: May 2004

The risk of a newly diagnosed episode of upper gastrointestinal bleeding, acute liver and renal failure, agranulocytosis, aplastic anemia, severe skin disorders, and anaphylaxis was examined within 30 days after the first prescription for a low dose of diclofenac, naproxen, or ibuprofen in a cohort in the United Kingdom. We identified 22,146 persons using diclofenac (≤ 75 mg), 46,919 using naproxen (≤ 750 mg), and 54,830 using ibuprofen (≤ 1200 mg). Age, gender, and comorbidity were similar in the three cohorts. Overall 64 potential cases were identified, and 20 were confirmed by medical record review. Incidence rates (95% CI) of upper gastrointestinal bleeding/10,000 people using diclofenac, naproxen, and ibuprofen were 1.8 (0.5‐4.6), 2.3 (1.2–4.2), and 0.4 (0.04–1.3), respectively. There were three cases of hepatic injury, one with naproxen and two with ibuprofen. Although low, the incidence of gastrointestinal toxicity remains the main serious adverse event for all study drugs.
Pharmaceutical Care of Patients with Congestive Heart Failure: Interventions and Outcomes
Authors: Varma Sumanthra , McElnay James C. , Hughes Carmel M. , Passmore A. Peter , Varma Mahandra
Published: May 2004

We evaluated a structured pharmaceutical care program for elderly patients (> 65 yrs) with congestive heart failure (CHF) based on objective measures of disease control, quality of life, and use of health care facilities in a randomized, controlled, longitudinal, prospective clinical trial. The 42 patients in group A received education from a pharmacist on the disease and its treatment, and lifestyle changes that could help control symptoms. Patients also were encouraged to monitor their symptoms and comply with prescribed drug therapy. If necessary, dosage regimens were simplified in liaison with hospital physicians. The 41 control patients (group B) received standard care. The following outcome measures were assessed in all patients at baseline (before the start of the trial) and at 3, 6, 9, and 12 months: 2‐minute walk test, blood pressure, body weight, pulse, forced vital capacity, quality of life [disease‐specific (Minnesota Living with Heart Failure questionnaire) and generic (SF‐36)], knowledge of symptoms and drugs, compliance with therapy, and use of health care facilities (hospital admissions, visits to emergency room, emergency calls). Patients in group A showed improved compliance with drug therapy, which in turn improved their exercise capacity compared with those in group B; education on management of symptoms, lifestyle changes, and dietary recommendations were also of benefit. Group A patients significantly improved knowledge of their drug therapy over the 12‐month study and had fewer hospital admissions compared with group B patients. They also had improved outcomes compared with group B, despite the small samples. An extension of this trial to other sites with pooling of results would provide additional evidence of the value of this structured program in elderly patients with CHF.
Potentiation of Warfarin by Dong Quai
Authors: Page Robert Lee , Lawrence Julie D.
Published: May 2004

Dong quai is a Chinese herbal supplement touted for treatment of menstrual cramping, irregular menses, and menopausal symptoms. Phytochemical analyses found it to consist of natural coumarin derivatives, as well as constituents possessing antithrombotic, antiarrhythmic, phototoxic, and carcinogenic effects. A 46‐year‐old African‐American woman with atrial fibrillation stabilized on warfarin experienced a greater than 2‐fold elevation in prothrombin time and international normalized ratio after taking dong quai concurrently for 4 weeks. No identifiable cause was ascertained for the increase except dong quai. The patient's coagulation values returned to acceptable levels 1 month after discontinuing the herb. One animal study suggests a pharmacodynamic interaction between the product and warfarin, but the true mechanism remains unknown. Practitioners should be aware of the possibility of such an interaction and should inform patients of potential hazards of taking the two together.
Lamotrigine‐Induced Blepharospasm
Authors: Verma Amit , Miller Patricia , Carwile Sandra T. , Husain Aatif M. , Radtke Rodney A.
Published: May 2004

Movement disorders such as tremor and ataxia occur commonly during therapy with antiepileptic drugs (AEDs). Dystonias, however, are rare. Blepharospasm, although reported with neuroleptic agents, has never been reported with AEDs. Our patient developed blepharospasm during therapy with lamotrigine.
Acute Myocardial Infarction Associated with Anabolic Steroids in a Young HIV‐Infected Patient
Authors: Varriale Philip , Mirzai‐Tehrane Majid , Sedighi Abdollah
Published: May 2004

The use and abuse of anabolic‐androgenic steroids have increased over the past decade and pose a medical and public health problem. In addition to their use by athletes to increase muscle mass and improve performance, people with wasting and malignant diseases are finding that the agents improve both their physical appearance and strength. Unfortunately, anabolic steroids are associated with a number of adverse effects, not the least of which is acute myocardial infarction, which occurred in a 39‐year‐old man with human immunodeficiency virus infection. It is important for clinicians to be aware of the association and to counsel patients carefully about this and other untoward effects that may occur with the agents.
Generalized Tetanus in a Patient with a Diabetic Foot Infection
Authors: Panning Chad A. , Bayat Maryam
Published: May 2004

Tetanus is a preventable disease that continues to affect people in the United States due to poor immunization practices in our health care system. A 57‐year‐old man with type 2 diabetes mellitus, hypertension, and end‐stage renal disease with many hospital admissions came to the hospital emergency department because of a blackened great toe. He denied pain in the toe or knowledge of foot injury. The patient also complained of temporomandibular tenderness accompanied by inability to open his mouth completely. The man's problems progressed to generalized tetanus and required a long hospitalization. Clostridium tetani can flourish in the anaerobic environment of a diabetic foot infection. Practitioners should be aware of tetanus as a rare but potentially serious complication of diabetic foot infections.
Sudden Hearing Loss Associated with Tacrolimus in a Kidney‐Pancreas Allograft Recipient
Authors: Min David I. , Ku Yi‐Min , Rayhill Stephen , Corwin Claudia , Wu You‐Min , Hunsicker Lawrence G.
Published: May 2004

A 38‐year‐old woman with type 1 diabetes underwent kidney‐pancreas transplantation. Her postoperative course was complicated due to recurrent acute graft rejections and pancreatitis. After initial immunosuppression with microemulsion cyclosporine, mycophenolate mofetil, and prednisone with muromonab‐CD3 induction, cyclosporine was switched to tacrolimus on day 44. The initial dosage was 5 mg twice/day, but it was gradually increased to 10 mg twice/day, aiming at 15–20 ng/ml. On day 17 of tacrolimus therapy the woman developed sudden hearing loss with tinnitus. The serum tacrolimus level was 28.3 ng/ml (therapeutic range 10–20 ng/ml) on day 20 of tacrolimus therapy, and peaked at 34.9 ng/ml on day 28. Two audiograms performed on days 28 and 29 confirmed bilateral hearing loss of 80% for speech perception, characterized as mild to moderate sensorineural hearing loss with speech reception threshold of 35 dB (normal < 20 dB) in both ears. The tacrolimus dosage was gradually reduced to 6 mg twice/day by day 36, with drug level 9.7 ng/ml, after which her hearing gradually recovered.
Serotonin Syndrome in a Child Associated with Erythromycin and Sertraline
Authors: Lee Douglas O. , Lee Cara D.
Published: May 2004

Serotonin syndrome is an uncommon, serious adverse reaction that is usually associated with the interaction of two or more serotonergic agents. A 12‐year‐old boy receiving sertraline developed the syndrome after erythromycin was added to his regimen. The proposed mechanism involves erythromycin inactivation of cytochrome P450 3A4 inhibition of sertraline metabolism, accumulation of the drug, and precipitation of the syndrome. It is important for clinicians to consider both pharmacokinetic and pharmacodynamic interactions to minimize the risk of the reaction.
Prolonged Opioid Antagonism with Naloxone in Chronic Renal Failure
Authors: Hanes Scott D. , Franklin Michael , Kuhl David A. , Headley A. Stacey
Published: May 2004

Respiratory depression secondary to morphine intoxication occurred in an elderly patient with chronic renal failure (CRF). It was reversed with a continuous infusion of naloxone. Approximately 11 hours after the infusion was discontinued, the patient relapsed into respiratory depression consistent with opioid intoxication. He was rechallenged with a naloxone infusion with resolution of the opioid effects. This case suggests prolonged antagonism of opioid effects inconsistent with naloxone's reported pharmacologic effects. Serum naloxone concentrations measured after the end of the infusion suggest that the drug's pharmacokinetics were significantly altered. Further research is necessary to characterize pharmacokinetic changes that occur in CRF. In the absence of this information, similar patients should be closely monitored for relapse of respiratory depression after naloxone is discontinued.
Potential Interaction Between Azithromycin and Warfarin
Authors: Foster David R. , Milan Nikki L.
Published: May 2004

Azithromycin is considered unlikely to interact with warfarin. Unlike other macrolide antibiotics, it is not hepatically metabolized and did not produce an interaction with warfarin in a single‐dose study. A 71‐year‐old woman with a prosthetic heart valve, stabilized with warfarin, had international normalized ratios (INRs) maintained between 2.5 and 3.5. Six days after she received a prescription for a 5‐day course of azithromycin, her INR was 15.16. Phytonadione 10 mg was administered subcutaneously, and warfarin was held for 3 days until her INR fell to 2.10. She then was restabilized with warfarin. Until more information is known about the safety of warfarin and azithromycin, caution is advised when the agents are given together. Close monitoring of INR is recommended, and warfarin dosage adjustment may be necessary.
Distant and Delayed Mitomycin C Extravasation
Authors: Patel Jalpa S. , Krusa Michele
Published: May 2004

Mitomycin C is a vesicant chemotherapeutic agent used to treat solid tumors. Its ability to cause delayed and remote tissue injury after intravenous administration is reported in the literature. Two cases of delayed and distant mitomycin C extravasation injury occurred in our institution. In both patients, no evidence of acute extravasation was visible during or immediately after administration. Within 48 hours, one patient reported erythema, burning, and pain in the hand contralateral to the administration site. The second patient developed three distinct ulcerated lesions on her forearm within 6 weeks of receiving the agent. The lesions, located at sites of venipunctures, occurred 12–15 cm proximal to the site of mitomycin infusion. Because the drug has the potential to cause such unusual and unanticipated tissue injuries, health care professionals and patients should be aware of this hazard.
Delayed‐Onset Ticlopidine‐Induced Cholestatic Jaundice
Authors: Kubin Christine J. , Sherman Olga , Hussain Khozema B. , Feinman Lawrence
Published: May 2004

An 86‐year‐old man experienced a rash approximately 2 weeks after starting ticlopidine therapy, necessitating discontinuation of the drug. About 1 month later, despite discontinuation, he developed jaundice and liver test abnormalities. These resolved gradually over the next few months. Based on case reports and the drug's pharmacokinetic profile, a high index of suspicion for ticlopidine‐induced jaundice is prudent in patients with recent exposure to the agent who have evidence of liver damage.