Disseminated lymphangiosarcoma in a dog.
This case is unusual due to its extended clinical course. Clinical, histopathological, and immunohistochemical findings are presented.
Biomedical subjects
Publications and source records attributed to S M Taylor.
This case is unusual due to its extended clinical course. Clinical, histopathological, and immunohistochemical findings are presented.
A 10-month-old American cocker spaniel was evaluated for megaesophagus, aspiration pneumonia, but no appendicular muscle weakness. During hospitalization, weakness of the facial muscles developed, this resolved with anticholinesterase administration. Serum antibodies against acetylcholine receptors were documented, confirming the diagnosis of focal myasthenia gravis. Diagnosis, management, and medical treatment are discussed.
Double-phase parathyroid gland scintigraphy, using technetium Tc 99m sestamibi, correctly identified the existence and location of a parathyroid adenoma in a dog with primary hyperparathyroidism. The parathyroid adenoma was removed surgically 2 days after scintigraphy. An area of focal radionuclide uptake persisted in the region corresponding to the left external parathyroid gland in the delayed-phase image. Delayed-phase images from 3 healthy dogs and a dog with hypercalcemia of malignancy caused by lymphoma did not reveal an area of persistent radiotracer uptake. Double-phase parathyroid gland scintigraphy, using 99mTc-sestamibi, is a simple, rapid, noninvasive test, which can be used for detection and localization of parathyroid adenomas in hypercalcemic dogs. It also can help to differentiate these dogs from dogs with hypercalcemia of malignancy.
This study describes altered patterns of growth and upregulation of fibronectin expression of cultured canine airway smooth muscle cells grown in homologous serum, which provides a model of the vascular leakage occurring in asthma, compared to fetal bovine serum (FBS). Cells were incubated in increasing concentrations of serum (2.5-40%) for 72 hours. Both homologous serum and FBS caused cellular proliferation which reached a maximum increase at 2.5-5% serum concentration. Differences in the cellular responses to the two types of sera were noted at higher concentrations of sera. At a concentration of 40% FBS, airway smooth muscle cells increased in number by 307 +/- 16% (n = 5) compared to serum-free control cells, whereas in canine serum the increase in growth was significantly smaller, 239 +/- 25% (n = 7) (P < 0.05). Airway fibrocytes similarity treated increased in number by 256 +/- 43% (n = 3) in 40% FBS, but exhibited a reduction in cell number to 80 +/- 10% (n = 3) of controls in 40% homologous serum (P < 0.05). Smooth muscle cells demonstrated a dose-dependent increase in fibronectin expression when grown in homologous serum but not in FBS, suggesting phenotypic change occurred in these cells when exposed to homologous serum. These data suggest that the leakage of plasma in the asthmatic airway may trigger phenotypic change in both airway smooth muscle cells and airway fibrocytes leading to cellular proliferation and expression of extracellular matrix molecules. These in vitro changes are consistent with the histological findings in clinical asthma.
The management of vascular prosthetic graft infections confined to the groin continues to be controversial. To critically evaluate this problem, we reviewed the records of our vascular registry from December 1992 through February 1995 and found 17 incidences of groin sepsis involving a vascular prosthesis in 10 patients. These included a proximal prosthetic femoropopliteal bypass (n = 6), an aortobifemoral graft limb (n = 5), an ileofemoral bypass (n = 3), a prosthetic femoral patch (n = 2), and an aortofemoral/femorofemoral bypass (n = 1). The mean age of these patients was 65 years. Six patients were diabetic, four were on systemic steroids, and two were diabetic and on steroids. All infections were Szilagyi grade III including three in which the patients presented with local hemorrhage. Treatment consisted of irrigation, radical debridement with or without in situ graft replacement, and local rotational muscle flap coverage in nine cases, graft excision with extra-anatomic (obturator ileofemoral bypass) graft replacement in six cases, and excision alone in two cases. Of the 17 infections treated operatively and followed from 1 week to 18 months (median 5 months), eight (47%) showed no evidence of recurrence, six (35%) recurred, two (12%) caused early death, and one resulted in a thrombosed graft requiring extra-anatomic reconstruction. Of the nine infected grafted treated locally with muscle flaps, six showed recurrent infection from 3 weeks to 15 months and one thrombosed for a total local treatment failure rate of 78%. Only two grafts are free of infection at 4 and 5 months, respectively. Of the six incidences of infection treated with obturator bypass, four (66%) are free of infection and two resulted in patient death; both infections treated with excision alone were eradicated but resulted in a major lower extremity amputation. These data question the growing acceptance of debridement and local muscle flap coverage for the treatment of all prosthetic vascular graft infections confined to the groin, especially in patients who are diabetic or on systemic steroids.
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Clinicopathologic criteria were used to group 68 cats according to high, moderate, or low suspicion of having feline leukemia virus (FeLV)-related disease. Peripheral blood samples were tested for FeLV antigen by enzyme-linked immunosorbent assay (ELISA) and for FeLV DNA by polymerase chain reaction (PCR). There was no significant difference between ELISA and PCR results in the 68 cats. In the high-suspicion group, 46%(11/24) of cytopenic cats were test positive (ELISA and PCR) and 87% (13/15) with hemopoietic neoplasms were test-positive. Also within the high suspicion group, test-positive cats were 2.5 times more likely to die within the 1 year follow-up period than were test-negative (ELISA and PCR) cats. Among cats in the moderate-suspicion group, 15% (2/13) were test-positive, and none (0/16) of the cats in the low suspicion group was test positive. The relative risk of a positive test (ELISA and PCR) in the high suspicion group was 3.7 times that for the moderate-suspicion group and 22.8 times that for the low suspicion group. There was no significant difference in the relative risk of a positive test result between the moderate and low suspicion groups. The results indicate that FeLV detection by PCR can be adapted for diagnostic purposes using peripheral blood samples, however, results do not differ significantly from FeLV ELISA results. Also, a proportion of cats with a high suspicion of having FeLV-related cytopenia and hemopoietic tumors are negative for both circulating FeLV antigen and DNA. These cats may not have FeLV-related disease, or FeLV may exist in a disease-producing but nonreplicating form ultimately detectable by PCR in tissues other than peripheral blood.
Virtually no objective data exist regarding the natural history of arteriovenous (AV) dialysis access grafts placed in the lower extremity for routine hemodialysis. From March 1988 until October 1993, 45 consecutive lower extremity AV dialysis access grafts were placed in 39 patients (16 males; 23 females; mean age 58 years) at a large teaching community hospital. All 39 patients had long-standing end stage renal disease and had required chronic hemodialysis from 7 to 237 months mean, 72 months) prior to leg graft placement. Polytetrafluorethylene (n=39) or bovine (n=6) loop lower extremity dialysis grafts were placed after multiple upper extremity dialysis graft failures (mean, 2.7 previous grafts with 9.6 thrombectomies and/or access revisions per patient). There were no operative deaths; however, in follow-up (1-132 months; mean 20 months; median 18 months), 33 percent of the patients had died from systemic complications of their renal disease, and only 20 (44%) leg grafts are currently patent [correction of patient] . Graft complications, excluding graft thromboses, occurred in 20 grafts including graft infection (n=8; 18%), severe ipsilateral leg ischemia (n=7; 16%), graft aneurysmal degeneration requiring revision (n=3; 7%), fistula-induced congestive heart failure (n=2; 4%), and major lower extremity amputation (n=3; 7%). Primary patency by life-table analysis was 47 percent at 24 months. Fifteen (33%) grafts thrombosed at least once, and all but one were salvaged with thrombectomy. The need for lower extremity AV dialysis access appears to be a significant marker for late mortality in this group of chronically ill patients. They are associated with multiple complications and should probably be placed only if significant patient morbidity can be accepted and justified.
A panel of conformationally constrained, decapeptide agonists corresponding to the C-terminal "effector" region of human C5a (C5a65-74 or ISHKDMQLGR) was evaluated for the ability to increase vascular permeability. One constrained analog, acyl-YSFKPMPLaR, expressed between 2 and 10% of full C5a activity in increasing vascular permeability, as measured by the extravasation of Evans blue dye in guinea pig skin. This analog was at least 10-fold more potent than its unconstrained sister analog C5a65-74465, F67++ (YSFKDMQLGR), which was used as an internal standard in these assays. Neither acyl-YSFKPMPLaR nor YSFKDMQLGR changed the transvascular equillibrium of an electrolyte, 86Rb, at the peptide injection site. However, both peptides effected a significant increase in the extravasation of two macromolecules, 125I-labeled bovine serum albumin and 131I-labeled monoclonal antibody BL-3. The extravasation of Evans blue dye mediated by 0.03 to 0.1 nmol of acyl-YSFKPMPLaR was nearly abolished by 1 to 10 nmol of the antihistamine diphenhydramine. For YSFKDMQLGR, however, the sensitivity toward diphenhydramine was observed only at low concentrations of the peptide (1 nmol). When incubated in human and mouse sera, acyl-YSFKPMPLaR was shown to be stable toward the actions of serum carboxypeptidases. However, the unconstrained analog YSFKDMQLGR was rapidly converted to the des-Arg form under the same conditions. Taken together, these results support a growing body of evidence that unique topochemical features expressed in conformationally constrained agonist analogs of C5a contribute favorably to their ability to modulate vascular permeability and to their stability in serum.
OBJECTIVE: To compare maxillectomy patients with immediate versus delayed placement of an obturator prosthesis in terms of patient outcomes. DESIGN: Retrospective review. OUTCOME MEASURES: The outcomes of 23 maxillectomy patients seen between 1975 and 1993 at St. Joseph's Health Centre in London, Ontario, were analyzed. METHODS: For 17 patients, a prosthesis was placed immediately as part of the operative procedure, and for 6 patients, an occlusive dressing only was placed. RESULTS: In all parameters studied (length of stay, i.v. requirements, swallowing, clear fluid diet and ambulation), the prosthesis group progressed more quickly and had a more rapid return to normal function. CONCLUSION: This study demonstrates the benefits of immediate prostheses for maxillectomy patients and justifies their continued use.
The effect of hyperthyroidism on serum markers for increased bone metabolism and turnover was evaluated in 36 cats with elevated serum levels of thyroxine and alkaline phosphatase. Serum was analyzed for total and ionized calcium and phosphorous. Alkaline phosphatase isoenzymes were separated by agarose gel electrophoresis and osteocalcin was measured by radioimmunoassay. Values for hyperthyroid cats were compared with those for healthy cats. Alkaline phosphatase bone isoenzyme was markedly increased in all 36 hyperthyroid cats. Osteocalcin was increased in 44% of the cats. There was no correlation among the magnitude of increase in alkaline phosphatase bone isoenzyme, osteocalcin, and serum thyroxine concentrations. Increased serum phosphorus was found in 35% of the cats. Total calcium was within the reference range in all cats, while 50% of the cats had reduced levels of serum ionized calcium. We conclude that hyperthyroid cats do have altered bone metabolism, although it is usually clinically insignificant.
The cytotoxicity, and probably the selectivity, of folate antimetabolites depend upon the expression of the enzyme folylpoly-gamma-glutamate synthetase in tumor cells. Evidence for the existence of multiple forms of this enzyme and the need to define the control mechanisms determinant of expression levels in normal and neoplastic cells has focused attention on the gene(s) encoding these forms. The organization of the genomic locus for the human folylpoly-gamma-glutamate synthetase (FPGS) gene has been determined. The complete 2256 nucleotides of cDNA for the 5'-untranslated region, mitochondrial leader sequence, coding region, and 3'-untranslated region were distributed on 15 exons stretching over 11.2 kb of genomic DNA. All of the restriction fragments found in diploid human genomic DNA could be accounted for by fragments contained on the isolated genomic clones. Likewise, Southern analysis of the transfected human genomic DNA that complemented the FPGS- phenotype of a hamster cell line indicated that the same gene had been integrated in all of three independently derived transfectants. We conclude that the genomic locus that we now report appears to be the only gene encoding FPGS-related sequences in the human complement.
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A series of decapeptide analogues corresponding to the C-terminal region of the human C5a anaphylatoxin (C5a65-74) was synthesized with residue substitutions to restrict conformational flexibility in the C-terminal region (residues 71-74). These analogues behaved as full agonists of natural C5a in their ability to induce shape change (polarization) and the release of enzyme (beta-glucuronidase) from human neutrophils (PMNs). There was a significant pharmacological correlation between the polarization and enzyme-release assays, suggesting similarities in PMN responsiveness toward these constrained peptides. Good correlations were also observed between these two PMN responses and spasmogenic activity (smooth muscle contraction of human fetal artery). A structure-function analysis for PMN polarization and enzyme release led to the identification of the following preferred backbone conformations: a twisted, helix-like conformation for residues 65-69, an extended conformation for residues 70-71, and a beta-turn of type V for residues (71)72-74. The existence of a C-terminal, type V beta-turn is supported by the NOE (nuclear Overhauser effect) results of two peptides from this series. These conformational features are reminiscent of those that were shown to correlate with the expression of spasmogenic and platelet aggregatory activities in an earlier investigation (Sanderson, S.D.; et al. J. Med. Chem. 1994, 37, 3171). These results suggest that PMNs and the cells responsible for smooth muscle contraction possess C5a receptors that respond to similar topochemical features presented by the agonist peptide ligand.
Two groups of yearling suckled beef calves born between January and May of the preceding year and another two groups of lighter and slightly younger calves born between the previous March and July were grazed during their second year on four separate paddocks known to be contaminated with infective larvae of gastrointestinal nematodes. One of the heavier and one of the lighter groups were treated with a topical formulation of ivermectin three weeks and eight weeks after turnout. The treatment of the heavier group had only relatively minor parasitological effects and no effect on weight gains, whereas the treatment of the lighter cattle resulted in increased weight gains due to effective nematode control. The paper highlights that small differences in previous performances, age and exposure to parasites can have a substantial impact on the benefits accrued from anthelmintic treatment.
Folylpoly-gamma-glutamate synthetase (FPGS) is essential for the survival of proliferating mammalian cells and central to the action of all "classical" folate antimetabolites. We report the isolation of cDNAs corresponding to the 5' ends of FPGS mRNA from both human and hamster cells which include a start codon upstream of and in-frame with the AUG in the previously reported FPGS open reading frame. The predicted hamster and human amino-terminal extension peptides have features consistent with a mitochondrial targeting sequence. Ribonuclease protection and 5'-rapid amplification of cDNA ends assays indicated multiple transcriptional start sites consistent with the sequence of the promoter region of this gene, which was highly GC-rich and did not contain TATA or CCAAT elements. These start sites would generate two classes of transcripts, one including the upstream AUG and one in which only the downstream AUG would be available for translation initiation. Transfection of the full length human cDNA into cells lacking FPGS restored their ability to grow in the absence of glycine, a product of mitochondrial folate metabolism, as well as of thymidine and purines. Therefore, we propose that the mitochondrial and cytosolic forms of FPGS are derived from the same gene, arising from the use of the two different translation initiation codons, and that the translation products differ by the presence of a 42-residue amino-terminal mitochondrial leader peptide.
A comparison was made of the efficacy and parasitological sequelae over 2 years, of continuous and intermittent periods of anthelmintic suppression applied both early and in the middle of the first grazing season of calves. Five groups of 15 calves grazing separate paddocks within the same field were allotted to one of the following treatment regimes during their first year at grass: Group 1, untreated controls; Group 2, treated with ivermectin injections at 3, 8 and 13 weeks after turnout; Group 3, treated with ivermectin injections at 10, 15 and 20 weeks after turnout; Group 4, treated with a morantel slow release intraruminal bolus at turnout; Group 5, treated with a morantel slow release bolus at 10 weeks after turnout. Five animals from each group were slaughtered at the end of both grazing seasons. Two months after the end of the second season the remaining five calves were challenged with an experimental infection of 250,000 third-stage larvae (L3) of both Ostertagia ostertagi and Cooperia oncophora. All treatment regimes protected the respective calves from parasitic gastroenteritis. Over the 2 year observation period Groups 2 and 4 showed significantly better weight gain than other groups, and at the end of the first season, they were found to harbour significantly fewer O. ostertagi in the early fourth stage of development. During Year 1, Groups 2 and 3 excreted much lower percentages of Ostertagia spp. eggs than other groups. In Year 2, Group 2 excreted a higher percentage of Ostertagia spp. eggs although the total egg output was approximately half that of Group 1 during the same period. The results showed that the effects of anthelmintic suppression on egg output of different nematode species was affected by the activity of the anthelmintic used.