Fatal septicemia caused by the zoonotic bacterium Streptococcus iniae during an outbreak in Caribbean reef fish.

An outbreak of Streptococcus iniae occurred in the early months of 2008 among wild reef fish in the waters of the Federation of St Kitts and Nevis, lasting almost 2 months. Moribund and dead fish were collected for gross, histological, bacteriological, and molecular analysis. Necropsy findings included diffuse fibrinous pericarditis, pale friable livers, and serosal petechiation. Cytological and histological analysis revealed granulocytic and granulomatous inflammation with abundant coccoid bacterial organisms forming long chains. Necrosis, inflammation, and vasculitis were most severe in the pericardium, meninges, liver, kidneys, and gills. Bacterial isolates revealed ß-hemolytic, Gram-positive coccoid bacteria identified as S. iniae by amplification and 16S ribosomal RNA gene sequencing. Results from biochemical and antimicrobial susceptibility analysis, together with repetitive element palindromic polymerase chain reaction fingerprinting, suggest that a single strain was responsible for the outbreak. The inciting cause for this S. iniae-associated cluster of mortalities is unknown.

Trichomonosis in free-ranging Eurasian collared doves (Streptopelia decaocto) and African collared dove hybrids (Streptopelia risoria) in the Caribbean and description of ITS-1 region genotypes.

We report the first documented occurrence of an outbreak of trichomonosis in a free-ranging small flock of Eurasian collared doves (Streptopelia decaocto) and African collared dove hybrids (Streptopelia risoria) in the Caribbean. In total, 18 birds were examined, including six African collared dove x Eurasian collared dove hybrids and 12 Eurasian collared doves. The affected age class consisted of adults. Sex distribution was equal. With a flock population size of 200 birds, mortality rate for the outbreak was estimated at 15-20%. Living birds were weak, showing evidence of mucus-stained beaks and open-mouth breathing. Caseous ulcerative yellow lesions were restricted to the upper gastrointestinal tract, with the exception of one bird, which had lesions in the upper gastrointestinal tract and in the liver. Ninety-four percent (17/18) of the affected birds had multiple extensive lesions. Lesions located on the roof of the oral cavity extended in 33% (6/18) into the orbit and in 11% (2/18) into the braincase. Using wet-mount microscopy, we were able to confirm Trichomonas gallinae in 22% (4/18) of the sampled animals. Fifteen samples submitted for PCR analysis tested positive. Sequence analysis of the internal transcribed spacer 1 (ITS-1) region of the ribosomal RNA (rRNA) revealed two distinct genotypes of Trichomonas. One sequence had 100% identity to the prototype T. gallinae isolate, whereas the other sequences had 98-100% identity to recently described Trichomonas-like parabasalid. On the basis of gross and histologic findings, along with the sequence results from the columbids in this report, it is likely that this Trichomonas-like parabasalid is pathogenic.

Prognostic markers for myeloid neoplasms: a comparative review of the literature and goals for future investigation.

Myeloid neoplasms include cancers associated with both rapid (acute myeloid leukemias) and gradual (myelodysplastic syndromes and myeloproliferative neoplasms) disease progression. Percentage of blast cells in marrow is used to separate acute (rapid) from chronic (gradual) and is the most consistently applied prognostic marker in veterinary medicine. However, since there is marked variation in tumor progression within groups, there is a need for more complex schemes to stratify animals into specific risk groups. In people with acute myeloid leukemia (AML), pretreatment karyotyping and molecular genetic analysis have greater utility as prognostic markers than morphologic and immunologic phenotypes. Karyotyping is not available as a prognostic marker for AML in dogs and cats, but progress in molecular genetics has created optimism about the eventual ability of veterinarians to discern conditions potentially responsive to medical intervention. In people with myelodysplastic syndromes (MDS), detailed prognostic scoring systems have been devised that use various combinations of blast cell percentage, hematocrit, platelet counts, unilineal versus multilineal cytopenias and dysplasia, karyotype, gender, age, immunophenotype, transfusion dependence, and colony-forming assays. Predictors of outcome for animals with MDS have been limited to blast cell percentage, anemia versus multilineal cytopenias, and morphologic phenotype. Prognostic markers for myeloproliferative neoplasms (eg, polycythemia vera, essential thrombocythemia) include clinical and hematological factors and in people also include cytogenetics and molecular genetics. Validation of prognostic markers for myeloid neoplasms in animals has been thwarted by the lack of a large case series that requires cooperation across institutions and veterinary specialties. Future progress requires overcoming these barriers.

Abnormal neuronal metabolism and storage in mucopolysaccharidosis type VI (Maroteaux-Lamy) disease.

Mucopolysaccharidosis (MPS) type VI, also known as Maroteaux-Lamy disease, is an inherited disorder of glycosaminoglycan catabolism caused by deficient activity of the lysosomal hydrolase, N-acetylgalactosamine 4-sulphatase (4S). A variety of prominent visceral and skeletal defects are characteristic, but primary neurological involvement has generally been considered absent. We report here that the feline model of MPS VI exhibits abnormal lysosomal storage in occasional neurones and glia distributed throughout the cerebral cortex. Abnormal lysosomal inclusions were pleiomorphic with some resembling zebra bodies and dense core inclusions typical of other MPS diseases or the membranous storage bodies characteristic of the gangliosidoses. Pyramidal neurones were shown to contain abnormal amounts of GM2 and GM3 gangliosides by immunocytochemical staining and unesterified cholesterol by histochemical (filipin) staining. Further, Golgi staining of pyramidal neurones revealed that some possessed ectopic axon hillock neurites and meganeurites similar to those described in Tay-Sachs and other neuronal storage diseases with ganglioside storage. Some animals evaluated in this study also received allogeneic bone marrow transplants, but no significant differences in neuronal storage were noted between treated and untreated individuals. These studies demonstrate that deficiency of 4S activity can lead to metabolic abnormalities in the neurones of central nervous system in cats, and that these changes may not be readily amenable to correction by bone marrow transplantation. Given the close pathological and biochemical similarities between feline and human MPS VI, it is conceivable that children with this disease have similar neuronal involvement.

Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease.

A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.

Critical role for glycosphingolipids in Niemann-Pick disease type C.

Niemann-Pick type C (NPC) disease is a cholesterol lipidosis caused by mutations in NPC1 and NPC2 gene loci. Most human cases are caused by defects in NPC1, as are the spontaneously occurring NPC diseases in mice and cats. NPC1 protein possesses a sterol-sensing domain and has been localized to vesicles that are believed to facilitate the recycling of unesterified cholesterol from late endosomes/lysosomes to the ER and Golgi. In addition to accumulating cholesterol, NPC1-deficient cells also accumulate gangliosides and other glycosphingolipids (GSLs), and neuropathological abnormalities in NPC disease closely resemble those seen in primary gangliosidoses. These findings led us to hypothesize that NPC1 may also function in GSL homeostasis. To evaluate this possibility, we treated murine and feline NPC models with N-butyldeoxynojirimycin (NB-DNJ), an inhibitor of glucosylceramide synthase, a pivotal enzyme in the early GSL synthetic pathway. Treated animals showed delayed onset of neurological dysfunction, increased average life span (in mice), and reduced ganglioside accumulation and accompanying neuropathological changes. These results are consistent with our hypothesis and with GSLs being centrally involved in the pathogenesis of NPC disease, and they suggest that drugs inhibiting GSL synthesis could have a similar ameliorating effect on the human disorder.

Mucopolysaccharidosis VII in a cat.

Mucopolysaccharidosis VII was diagnosed in a domestic shorthair cat from California. The cat was small and had multiple abnormalities, including a small body disproportionate to the size of the skull, angular deformities of the ribs, abnormally short forelimbs, luxating patellas, generalized epiphyseal dysplasia involving the vertebrae and long bones, cuboidal vertebrae, pectus excavatum, subluxation of both hips, osteosclerosis of the tentorium cerebelli and left petrous temporal bone, tracheal hypoplasia, and corneal clouding. Beta-glucuronidase activity was markedly decreased in peripheral blood leukocytes. The cat died at 21 months of age, and a complete necropsy was performed. Tissues were examined by light and transmission electron microscopy. Large clear, round vacuoles representing distended lysosomes were present in many epithelial and connective tissue cells, including fibrocytes, chondrocytes, smooth muscle cells, hepatocytes, astrocytes, and macrophages.

Inhibition of canine and feline alcohol dehydrogenase activity by fomepizole.

OBJECTIVE: To determine and compare substrate specificity and kinetic rate constants of feline and canine alcohol dehydrogenase (ADH) with ethanol (EtOH) and ethylene glycol (EG) as substrates in vitro, with and without fomepizole. SAMPLE POPULATION: Livers from 3 dogs and 3 cats. PROCEDURE: Canine and feline ADH activity, in cytosolic fractions of homogenized liver, was determined by use of various concentrations of nicotinamide adenine dinucleotide (NAD), EtOH, or EG as substrates. Initial reaction velocities were calculated, and kinetic inhibition rate constants (Ki) for fomepizole were determined. RESULTS: Substrate specificity of canine and feline ADH for EtOH or EG was not significantly different. A 2-fold difference was detected in the maximal velocity of canine, compared with feline, ADH, using either substrate. Fomepizole Ki in feline hepatic homogenates was significantly greater than Ki in canine hepatic homogenates when either EtOH or EG was used as substrate (10- and 30-fold, respectively). A 6-fold increase in the concentration of fomepizole was required to achieve ADH inhibition, with feline homogenates equivalent to those of canine homogenates. CONCLUSIONS AND CLINICAL RELEVANCE: Feline ADH has lower enzymatic capacity for turnover or is less concentrated in liver than canine ADH with regard to EtOH and EG catalysis. Canine ADH was more effectively inhibited by fomepizole than feline ADH. Results suggest that higher dosages of fomepizole may be more effective to treat cats with EG intoxication than dosages reported to treat dogs.

Complementation studies in human and feline Niemann-Pick type C disease.

Complementation studies were performed to determine if the gene responsible for the major form of human Niemann-Pick type C disease (NPC) and a feline model of NPC are orthologous. Cell fusions between human NPC and feline NPC fibroblasts were conducted to assess whether the multinucleated heterokaryons that were formed showed a reversal of the NPC phenotype. Cultured fibroblasts from NPC-affected humans and NPC-affected cats were hybridized and then analyzed for complementation by challenging the cells with low-density lipoprotein (LDL) and subsequently staining with the fluorescent antibiotic filipin to visualize any abnormal accumulation of unesterified cholesterol. All of the multinucleated cells formed from these fusions retained the NPC staining phenotype, indicating an absence of complementation and suggesting that the underlying defect in the major form of human NPC and this feline model of NPC involve orthologous genes.

Regional seroprevalence of Cryptosporidium parvum-specific IgG of cats in the United States.

The objective of this study was to determine the regional prevalence of Cryptosporidium parvum-specific IgG in the sera of cats in the United States. The continental United States was partitioned into eight regional areas. Serum samples from 75 cats from each region were assayed for C. parvum-specific IgG using an indirect enzyme-linked immunosorbent assay (ELISA). Age, sex, breed, and indoor/outdoor status were examined as possible risk factors for developing a positive C. parvum-specific IgG antibody titer. The presence of gastro-intestinal signs and Toxoplasma gondii-specific IgG in the serum were also evaluated for association with C. parvum seropositivity. Of the 600 samples assayed, 50 (8.3%) were positive for C. parvum-specific IgG. Regional seroprevalence ranged from 1.3% in the mid-Atlantic states to 14.7% in the south-eastern states. The oldest group of cats (>10 years) had the highest seroprevalence (15.3%). The prevalence of C. parvum-specific IgG was higher among male (10.1%) than among female cats (6.9%), although, the difference was not statistically significant (p = 0.17). Seropositivity was not associated with pure-bred status. C. parvum-specific IgG antibodies was detected most frequently in T. gondii-specific IgG seropositive cats, outdoor cats, and cats with gastro-intestinal signs. These results suggest that cats in the United States are commonly exposed to C. parvum.

Mechanisms of echinocytosis induced by Crotalus atrox venom.

Transient echinocytosis has been reported in association with snake envenomation in humans and dogs. An in vitro model of echinocytosis induced by venom of crotalus atrox (western diamondback rattlesnake) was established to characterize erythrocyte morphologic changes and to investigate potential mechanisms of echinocytic transformation. Erythrocyte morphologic changes produced after the addition of venom to canine, feline, equine, and human blood were characterized by dose-dependent echinocytosis. Type III echinocytosis were consistently induced in vitro at a dose comparable to in vivo envenomation; higher venom doses produced spheroechinocytic and spherocytic transformations. The changes could not be induced in vitro in the presence of ethylenediaminetraacetic acid but were observed in heparinized and citrated blood samples, suggesting the participation of calcium or a metalloprotein in echinocytic change. These findings suggest that phospholipase A2 (PLA2), a calcium-dependent enzyme in snake venom, may be responsible for echinocytic transformation via the production of lysolecithin, a known echinocytic agent. Purified PLA2 from C. atrox venom induced dose-dependent echinocytic change in vitro in canine blood. Other potential mechanisms of echinocytic change evaluated in canine blood included erythrocyte cation loss and erythrocyte ATP depletion. In canine blood mixed with venom, erythrocyte sodium and potassium concentrations were consistently less than those of controls, likely as a result of membrane alteration produced by the actions of PLA2. There was no difference in blood ATP concentrations from dogs with snakebite when compared with normal controls; however, the power of this comparison was low. Echinocytosis induced by rattlesnake venom is related to the degree of venom exposure and may correlate clinically with the amount of venom absorbed. Echinocytic transformation in vitro is induced by PLA2 present in venom.

Enzyme-linked immunosorbent assay for the detection of Cryptosporidium parvum IgG in the serum of cats.

The objective was to develop an enzyme-linked immunosorbent assay (ELISA) for the detection of Cryptosporidium parvum IgG in the serum of cats. The ELISA was an indirect ELISA using soluble C. parvum oocyst antigens and a peroxidase-labeled anti-feline IgG secondary antibody. Sera from cats with Toxocara felis, Giardia spp., Aelurostrongylus abstrusus, Isospora felis, Isospora rivolta, Toxoplasma gondii, or Taenia spp. infections were assayed in specificity studies. Following optimization, the ELISA and fecal examination for oocysts were performed on samples from 170 client-owned or humane society source cats and 1 cat inoculated orally with C. parvum oocysts. Cryptosporidium parvum oocysts were detected in feces (4/170; 2.4%), and C. parvum IgG was detected in serum (26/170; 15.3%) from naturally exposed cats. The seroprevalence data suggest that some cats in the geographical area studied were exposed to C. parvum, but persistent oocyst shedding was less common. The ELISA is not useful for predicting oocyst shedding in individual cats.

GABAergic neuroaxonal dystrophy and other cytopathological alterations in feline Niemann-Pick disease type C.

Feline Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal storage disease which shares many of the clinical, biochemical and pathological features of the corresponding human disorder. Cytopathological alterations in distinct neuronal cell populations were investigated in this animal model to gain a better understanding of the pathogenesis of brain dysfunction. Golgi and immunocytochemical methods were employed to characterize the cell architectural changes occurring in neuronal somata, dendrites and axons at different stages of disease progression. Cortical pyramidal neurons in laminae II, III, and V exhibited various degrees of meganeurite and/or swollen axon hillock formation with or without ectopic dendritogenesis. Enlarged axon hillock regions with neuritic processes and spines were recognized early in the progression of feline NPC but were less prevalent in mid to late stages of the disease. Glutamic acid decarboxylase (GAD) immunocytochemistry demonstrated immunoreactive spheroids in numerous GABAergic axons in neocortex, subcortical areas, and cerebellum. Parvalbumin-immunoreactive axonal spheroid distribution in brain closely mirrored results from the GAD studies, whereas calbindin D-28k-immunoreactive spheroids were conspicuously absent in most cortical and subcortical areas examined. Purkinje cell axonal spheroid formation progressed in a distal to proximal direction, with eventual involvement of recurrent axon collaterals. Purkinje cell death and a concomitant decrease in the numbers of spheroids in the cerebellum were observed late in the disease course. Clinical neurological signs in feline NPC occur in parallel with neuronal structural alterations and suggest that GABAergic neuroaxonal dystrophy is a contributor to brain dysfunction in this disease.

Urine glycosaminoglycan concentrations in mucopolysaccharidosis VI-affected cats following bone marrow transplantation or leukocyte infusion.

Urinary glycosaminoglycan (GAG) concentrations were determined in nineteen normal cats (eleven kittens and eight adult cats), eighteen mucopolysaccharidosis VI (MPS VI)-affected untreated cats (ten kittens and eight adult cats), thirteen cats MPS VI-affected cats following bone marrow transplants (BMT), and two MPS VI-affected cats following intravenous infusion of leukocytes from normal cats. Mucopolysaccharidosis VI-affected cats treated with BMT had a precipitous decrease in urinary GAG by day 7 post-BMT, then a transient increase just prior to engraftment, followed by a sustained decrease to within, or near, the range of urinary GAG concentration established for normal cats. The pre-engraftment changes in urinary GAG excretion were reproduced by leukocyte infusion. After infusion of comparable members of normal peripheral blood leukocytes, a significant decrease in urinary GAG concentrations, specifically dermatan sulfate (DS), was seen with a nadir at day 5 post-infusion, followed by a return by day 9 to pre-infusion values. Post-engraftment, a continued low urinary GAG concentration with a specific decrease in DS can be utilized to document successful autologous engraftment in MPS VI-affected cats.

Malignant histiocytosis in a domestic cat: cytomorphologic and immunohistochemical features.

Malignant histiocytosis (MH) was diagnosed in a 13-year-old neutered male Domestic Shorthair cat on the basis of light microscopic and immunohistochemical findings. Thoracic fluid analysis showed a modified transudate which contained a very few atypical discrete cells. Cytologic and histologic evaluation of mediastinal and splenic masses revealed a pleomorphic population of large, discrete, round cells 10 to 30 micrometers in diameter with marked cellular atypia. Nuclei were oval to reniform, often with prominent, bizarre nucleoli. Multinucleated cells and mitotic figures were commonly seen. Erythro- and leucocytophagia were noted. Immunohistochemistry indicated a scattered positive staining pattern with the histiocytic antigenic marker Mac387 and a minor population of cells showing positive reactivity for lysozyme. This report describes the characterization of MH in a cat and emphasizes that MH should be considered as a differential diagnosis in proliferative disorders of discrete-cells in this species.

Safety and efficacy of 4-methylpyrazole for treatment of suspected or confirmed ethylene glycol intoxication in dogs: 107 cases (1983-1995).

OBJECTIVE: To evaluate safety and efficacy of 4-methylpyrazole (4-MP) treatment in dogs and to determine clinical signs and outcome of, and clinicopathologic abnormalities in, dogs treated in early or late stages of ethylene glycol (EG) intoxication. DESIGN: Retrospective study. ANIMALS: 107 dogs. PROCEDURE: For dogs treated with 4-MP, 1 of 2 dosage regimens was usually used: 20 mg/kg of body weight, IV, initially, 15 mg/kg 17 hours later, and 5 mg/kg 25 and 36 hours after the initial dose, or 20 mg/kg, IV, initially, 15 mg/kg 12 and 24 hours later, and 5 mg/kg 36 hours after the initial dose. RESULTS: Neither adverse clinical signs nor clinicopathologic abnormalities were associated with the administration of 4-MP except in 1 dog, which developed tachypnea, gagging, excess salivation, and trembling after the second dose of 4-MP was given. Ethylene glycol intoxication was confirmed in 37 dogs. Of these, 21 were azotemic or became azotemic within 18 hours after admission, and only 1 of the 21 survived. All 16 dogs that did not become azotemic survived. Median time from EG ingestion to treatment with 4-MP was 5 hours (range, 2 to 8.5 hours) for dogs that were not azotemic at admission and 14.5 hours (range, 8.5 to 38 hours) for dogs that were azotemic at admission. CLINICAL IMPLICATIONS: 4-MP was a safe and effective treatment for EG intoxication when it was given before sufficient quantities of EG had been metabolized to induce renal failure. Dogs treated within 8 hours of EG ingestion had a good prognosis.

Metabolic abnormalities in feline Niemann-Pick type C heterozygotes.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal storage disorder in which cholesterol lipidosis results from defective intracellular transport of unesterified cholesterol. The primary molecular defect of NPC is unknown; regulatory mechanisms of cholesterol metabolism are impaired, resulting in retarded esterification of exogenous cholesterol with accumulation of unesterified cholesterol in lysosomes and secondary storage of glycolipids and sphingomyelin. In obligate heterozygotes from a feline NPC model, cultured skin fibroblasts challenged with exogenously derived cholesterol exhibited intermediate rates of cholesterol esterification and accumulation of unesterified cholesterol. Liver lipid analyses of obligate heterozygote cats demonstrated intermediate cholesterol and sphingomyelin concentrations. Vacuolated skin fibroblasts were found in 2 of 3 heterozygote cats, and occasional cortical neurons exhibited intracellular inclusions immunoreactive for GM2-ganglioside. Ultrastructural studies provided evidence of storage in liver and brain. We believe these morphological and biochemical findings are the first example of manifestations of CNS abnormalities in a genetic carrier for a neuronal storage disease.

Comparison of the effects of diltiazem and aspirin on platelet aggregation in cats.

Platelet aggregation in response to collagen (1 or 3 micrograms/ml), arachidonic acid (10(-2) M), and adenosine diphosphate (ADP, 2 microM) was compared in healthy cats treated with diltiazem (approximately 2 mg/kg body weight, q 8 hrs for 10 doses), aspirin (approximately 21 mg/kg body weight [1 baby aspirin], q 72 hrs for three doses), or a combination of diltiazem and aspirin. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood resulted in an impedance change (i.e., aggregation) with time in samples from the nontreated cats and the cats treated with diltiazem, but the addition had no effect in blood from cats treated with aspirin alone or with a combination of diltiazem and aspirin. Platelet aggregation in response to either concentration of collagen or to ADP was not altered by any treatment. Secretion of adenosine triphosphate (ATP) from the platelets was measured when the aggregating agent was 3 micrograms/ml collagen; secretion was not affected by any treatment.

Bone marrow cytological findings in 4 dogs and a cat with hemophagocytic syndrome.

Hemophagocytic syndrome or hemophagic histiocytosis was diagnosed in 4 dogs and 1 cat by evaluation of bone marrow aspirate smears. One of the dogs had a suspected infection with canine parvovirus and a confirmed infection with Salmonella spp, 2 dogs had presumptive diagnoses of myeloproliferative and lymphoproliferative disease, respectively, and 1 dog died without a diagnosis. The cat had hepatic lipidosis and lesions compatible with feline calicivirus infection. All animals had cytopenias involving 2 or more cell lines, and fragmented erythrocytes in the blood, along with mild to moderate increases in the number of macrophages in the bone marrow. Numerous marrow macrophages contained phagocytized hematopoietic cells. Other cytological features of the bone marrow were variable in each patient, but the degree of response in the blood was inadequate, even in those with bone marrow hyperplasia. The phagocytosis of hematopoietic elements did not appear to be caused by a primary immune disorder, but rather by the inappropriate activation of normal macrophages secondary to infectious, neoplastic, or metabolic diseases. These findings suggest that hemophagocytic syndrome may be an important factor in the development of cytopenias; the data also support the cytological evaluation of bone marrow aspirates as an aid in the diagnosis of hemophagocytic syndrome.

Bone changes in mucopolysaccharidosis VI in cats and the effects of bone marrow transplantation: mechanical testing of long bones.

Mucopolysaccharidosis VI (MPS VI) is a genetic lysosomal storage disease in which a defect in aryl sulfatase B leads to accumulation of the glycosaminoglycan dermatan sulfate and abnormalities in the development of cartilage and bone. A feline model of this disease was used to evaluate the efficacy of bone marrow transplant (BMT) therapy. Long bones from MPS VI cats (N = 6) and MPS VI + BMT cats (N = 7) were compared with control cats (N = 11) and control + BMT cats (N = 5) in mechanical tests. Dissected femurs and tibias were subjected to three-point bending and a subgroup of tibias were tested with the mechanical response tissue analyzer (MRTA) in which vibration is used to measure tissue impedance. Cats with MPS VI had markedly decreased stiffness and strength in both bone (p < 0.01). There was no significant difference in the MPS VI + BMT group. In the tibias, there was also decreased stiffness and strength in the control + BMT group as compared to controls (p < 0.05). However, when cross-sectional area was used to normalize for bone size there was good correlation with strength in both femurs (r = 0.907, p < 0.01) and tibias (r = 0.915, p < 0.1), and there were no significant differences between groups in the modulus of elasticity. In the tibias, in which stiffness was measured by MRTA, there was significant correlation with three-point bending stiffness. These results indicate that, in cats with MPS VI, the decreases in stiffness and strength of long bones can be largely accounted for by the decrease in bone size (osteopenia) that is present.