Self-expanding intestinal expansion sleeves (IES) for short gut syndrome.

PURPOSE: Many disease processes (necrotizing enterocolitis, caustic esophageal injury, malrotation with volvulus), can result in short-gut syndrome (SGS), where remnant intestinal segments may dilate axially, but rarely elongate longitudinally. Here we mechanically characterize a novel model of a self-expanding mesh prototype intestinal expanding sleeve (IES) for use in SGS. METHODS: Gut lengthening was achieved using a proprietary cylindrical layered polyethylene terephthalate IES device with helicoid trusses with isometric ends. The IES is pre-contracted by diametric expansion, deployed into the gut and anchored with bioabsorbable sutures. IES expansion to its equilibrium dimension maintained longitudinal gut tension, which may permit remodeling, increased absorptive surface area while preserving vascular and nervous supplies. We performed mechanical testing to obtain the effective force-displacement characterization achieved on these prototypes and evaluated minimal numbers of sutures needed for its anchoring. Furthermore, we deployed these devices in small and large intestines of New Zealand White rabbits, measured IES length-tension relationships and measured post-implant gut expansion ex vivo. Histology of the gut before and after implantation was also evaluated. RESULTS: Longitudinal tension using IES did not result in suture failure. Maximum IES suture mechanical loading was tested using 4-6 sutures; we found similar failure loads of 2.95 ± 0.64, 4 ± 1.9 and 3.16 ± 0.24 Newtons for 4, 6 and 8 sutures, respectively (n = 3, n.s). Pre-contracted IES tubes were deployed at 67 ± 4% of initial length (i.l.); in the large bowel these expanded significantly to 81.5 ± 3.7% of i.l. (p = 0.014, n = 4). In the small bowel, pre-contracted IES were 61 ± 3.8% of i.l.; these expanded significantly to 82.7 ± 7.4% of i.l. (p = 0.0009, n = 6). This resulted in an immediate 24 ± 7.8% and 36.2 ± 11% increase in gut length when deployed in large and small bowels, respectively, with maintained longitudinal tension. Maintained IES induced tension produced gut wall thinning; gut histopathological evaluation is currently under evaluation. CONCLUSION: IES is a versatile platform for gaining length in SGS, which may be simply deployed via feeding tubes. Our results need further validation for biocompatibility and mechanical characterization to optimize use in gut expansion.

Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels.

BACKGROUND: Cavalier King Charles Spaniels (CKCS) have a high prevalence of inherited macrothrombocytopenia. The purpose of this study was to determine if a mutation in beta1-tubulin correlated with presumptive inherited macrothrombocytopenia. HYPOTHESIS: A mutation in beta1-tubulin results in synthesis of an altered beta1-tubulin monomer. alpha-beta tubulin dimers within microtubule protofilaments are unstable, resulting in altered megakaryocyte proplatelet formation. ANIMALS: Blood samples were obtained from CKCS and non-CKCS dogs. METHODS: DNA was used in polymerase chain reaction (PCR) assays to evaluate beta1-tubulin. Platelet numbers and mean platelet volume (MPV) were evaluated for a correlation with the presence or absence of a mutation identified in beta1-tubulin. Platelets obtained from homozygous, heterozygous, and clear CKCS were further evaluated using electron microscopy and immunofluorescence. RESULTS: A mutation in the gene encoding beta1-tubulin correlated with macrothrombocytopenia in CKCS. Electron microscopy and immunofluorescence studies suggest that platelet microtubules are present but most likely are unstable and decreased in number. CONCLUSIONS AND CLINICAL IMPORTANCE: The macrothrombocytopenia of CKCS correlated with a mutation in beta1-tubulin. alpha-beta tubulin dimers within protofilaments most likely are unstable, leading to altered proplatelet formation by megakaryocytes. This information will aid in distinguishing inherited from acquired thrombocytopenia. It also provides insight into the mechanism of platelet production by megakaryocytes, and also may prove useful in understanding heart-related changes in macrothrombocytopenic CKCS with concurrent mitral valve regurgitation.

Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) exhibit an adverse cardiovascular risk profile, characteristic of the metabolic cardiovascular syndrome (MCS). The aim of this study was to determine the prevalence of coronary artery (CAC) and aortic (AC) calcification among middle-aged PCOS cases and controls and to explore the relationship among calcification, MCS, and other cardiovascular risk factors assessed 9 yr earlier. This was a prospective study of 61 PCOS cases and 85 similarly aged controls screened in 1993-1994 for risk factors and reevaluated in 2001-2002. The main outcome measures were CAC and AC, measured by electron beam tomography. Women with PCOS had a higher prevalence of CAC (45.9% vs. 30.6%) and AC (68.9% vs. 55.3%) than controls. After adjustment for age and body mass index, PCOS was a significant predictor of CAC (odds ratio = 2.31; P = 0.049). PCOS subjects were also 4.4 times more likely to meet the criteria for MCS than controls. High-density lipoprotein cholesterol and insulin appeared to mediate the PCOS influence on CAC. Interestingly, total testosterone was an independent risk factor for AC in all subjects after controlling for PCOS, age, and body mass index (P = 0.034). We conclude that women with PCOS are at increased risk of MCS and demonstrate increased CAC and AC compared with controls. Components of MCS mediate the association between PCOS and CAC, independently of obesity.

The relationship between C-reactive protein and carotid intima-media wall thickness in middle-aged women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with premature carotid atherosclerosis. C-Reactive protein (CRP) has been implicated as a vascular disease risk factor. The objective of this study was to determine whether elevated CRP is associated with increased carotid intima-media wall thickness (IMT) in PCOS women. Forty-seven PCOS patients and 59 similarly aged controls were screened for cardiovascular risk factors and concurrently underwent carotid ultrasonography (1996-1999). The main outcome measure was carotid IMT. CRP was significantly higher in PCOS patients than in controls (3.4 vs. 2.1 mg/dl; P = 0.002). In regression modeling, PCOS associated with IMT independently of CRP and age (P = 0.019). Body mass index reduced the association of PCOS and CRP with IMT and was also associated with IMT (P = 0.029). The CRP-IMT relationship was attenuated when either insulin or visceral fat was included in the PCOS-age-CRP model (P = 0.197 and P = 0.550, respectively). PCOS remained associated with IMT independent of insulin (P = 0.033) or visceral fat (P = 0.040). CRP does not appreciably mediate the effect of PCOS on IMT. Obesity partially explained the influence of PCOS and CRP on IMT. The effect of body mass index on the PCOS-IMT relationship was not completely determined by hyperinsulinemia or visceral fat, and might be mediated by other aspects of PCOS-related adiposity.

There are at least three genetically distinct small piroplasms from dogs.

The 18S nuclear subunit ribosomal RNA (18S rRNA) gene of small piroplasms isolated from dogs from Okinawa (Japan), Oklahoma, North Carolina, Indiana, Missouri, and Alabama, was isolated and sequenced. Phylogenetic analysis of these sequences and comparisons with sequences from other Babesia, Cytauxzoon, and Theileria species revealed that all canine small babesial isolates, with the exception of isolates from California and Spain, were placed in a group containing the Babesia spp. sensu stricto. Within the Babesia spp. sensu stricto, there was support for separating the small canine piroplasms from the large canine piroplasm, Babesia canis. The isolate from California was in a distinct phylogenetic clade, closely related to babesial isolates from wildlife and humans from the Western US. The canine isolate from Spain was closely related to Babesia microti. These results suggest that there are multiple small piroplasm species in dogs. The isolates from the Midwestern and Eastern US and the one from Japan probably represent a single species with wide geographic distribution.

Collaborative care for obstetric patients at low and high risk: an evolving model.

OBJECTIVE: In this article we describe a program that evolved from collaborative care given to a low-risk population into collaborative care that included patients at high risk. STUDY DESIGN: The study population comprised women attending a prenatal program in an urban, underserved neighborhood. Clinic records were reviewed for number of patient enrollments and total patient visits, as well as providers utilized. Episodic audit over a 3-year period of 180 of 869 patients initiating prenatal care was done. Data from vital statistics for 1992 and 1993 were evaluated for adequacy of prenatal care and yearly births for the census tract served. Analysis was descriptive. RESULTS: Almost all of the patient population served was found to be at psychosocial high risk. Approximately 10% had significant obstetric or medical complications. Infections, especially sexually transmitted diseases, were common. Fewer than 1% of the patients were referred to another provider for treatment. The program demonstrated an increase in patient volume, improved retention of patients for complete prenatal care and delivery, a reduction in patients receiving no or inadequate care, and a reduction in yearly births. CONCLUSION: The collaborative practice model may be extended to high-risk populations.

The pony as an animal model for vascular implants.

This study evaluated the pony as a potentially suitable model for vascular implant research. Healthy, conditioned ponies were randomly assigned to one of three groups: group I, carotid artery autografts (n = 6); group II, e-PTFE carotid interpositional grafts (n = 5); and group III, e-PTFE carotid interpositional grafts plus aspirin (10 mg/kg) and dipyridamole (3.5 mg/kg) drug administration. It was found that autografts remained patent longest (mean = 396.2 days; grafts were still patent at time of writing) followed by group III grafts (157.5 days), with group II grafts remaining patent for the shortest duration (61.1 days), (p less than 0.01). Patency was determined using two-dimensional real-time ultrasonography with Doppler velocimetry and/or arteriography. It was demonstrated that the pony's response to antithrombotic drugs was consistent and comparable to that in other animal models, both with respect to platelet function and affect on patency rate. The combination of the ease of surgical manipulation, drug administration, and platelet function testing, the comparable size of the pony and its heart and blood vessels to that of an adult human, the long life span of ponies, and the patency results of this study have demonstrated that the pony is a valuable animal model for vascular research.

Identification of an intrinsic platelet function defect in Spitz dogs.

A recently identified intrinsic platelet function defect in 2 Spitz dogs is described. Both affected dogs had a history of chronic intermittent bleeding primarily from the nasal, oral, and gastrointestinal mucosa. Platelet aggregation in response to adenosine diphosphate (ADP), collagen, and platelet activating factor (PAF) was absent; however, platelet shape change did occur. Platelets aggregated in response to gamma thrombin, although a delayed onset and a reduced velocity of aggregation were present. Platelet 14C-serotonin release was diminished in response to collagen and PAF. Glycoprotein IIIa was detected on the surface of platelets by flow cytometry. Platelets were morphologically normal under light and electron microscopy. Two male Spitz dogs, related to one of the affected dogs, did not have a bleeding diathesis. Collagen-induced platelet aggregation, however, was diminished in these 2 dogs. This platelet defect most closely resembles the defect described in Basset hounds.

Platelet function, antithrombin-III activity, and fibrinogen concentration in heartworm-infected and heartworm-negative dogs treated with thiacetarsamide.

Platelet aggregation and release, platelet number, mean platelet volume, antithrombin-III activity, and fibrinogen concentration were evaluated in heartworm-negative and heartworm-infected dogs at baseline and on days 3, 10, and 21 after treatment with thiacetarsamide. Platelet reactivity was enhanced in a group of dogs naturally infected with Dirofilaria immitis, compared with 2 groups of heartworm-negative dogs, but platelet reactivity was not further enhanced after treatment with thiacetarsamide. A significant decrease in antithrombin-III activity was detected 21 days after treatment. The platelets from a group of laboratory Beagles implanted with 50 adult D immitis displayed enhanced reactivity 6 months after implantation, but by 18 months, platelet reactivity had returned to near, or less than, baseline. Platelet reactivity was enhanced after thiacetarsamide treatment in this group. Thiacetarsamide-associated changes were not observed in platelet number or size; antithrombin-III activity decreased, but the change was not significant. Fibrinogen concentration was increased significantly (P less than 0.05) on day 10. Enhanced adenosine diphosphate (ADP)-induced platelet aggregation was observed on days 3, 10, and 21 after treatment in heartworm-negative dogs. This change was not observed in 6 control Beagles not treated with thiacetarsamide. Although antithrombin-III activity was decreased on day 3 and fibrinogen concentration was increased on day 10, paralleling changes observed in the heartworm-infected dogs, the changes were not statistically significant. In this study, thiacetarsamide was procagulatory in heartworm-negative dogs and may be an important contributing factor to the thromboembolism observed with adulticidal therapy.

Molecular and genetic basis for thrombasthenic thrombopathia in otterhounds.

OBJECTIVES: To determine the molecular and genetic basis for thrombasthenic thrombopathia in Otterhounds and establish whether the defect would be best classified as type-I Glanzmann's thrombasthenia. ANIMALS: 57 dogs, including 13 affected Otterhounds, 23 carrier Otterhounds, 17 unaffected Otterhounds, and 4 clinically normal unrelated dogs of other breeds. PROCEDURE: Functional (platelet aggregation, clot retraction, buccal mucosa bleeding time) and biochemical (electrophoresis, flow cytometry, fibrinogen content) analyses were conducted. In addition, first-strand cDNA synthesis from platelet total RNA was performed. Exons of the genes encoding for glycoproteins (GP) IIb and IIIa were amplified in overlapping fashion. The resulting products were excised from agarose gels and sequenced. The sequences obtained were compared with known cDNA sequences for canine GPIIb and GPIIIa. RESULTS: A single nucleotide change at position G1193 (1100) was detected in exon 12 of the gene encoding for platelet GPIIb in 2 affected Otterhounds. Carrier Otterhounds were heterozygous at this position, and 2 unaffected Otterhounds were unchanged. This nucleotide change would result in substitution of histidine for aspartic acid at position 398 (367) within the third calcium-binding domain of GPIIb. CONCLUSIONS AND CLINICAL RELEVANCE: These studies suggest that thrombasthenic thrombopathia of Otterhounds is homologous phenotypically and has a similar molecular basis to type-I Glanzmann's thrombasthenia in humans.

Evaluation of ploidy of mature canine megakaryocytes, using Feulgen staining and microspectrophotometry.

OBJECTIVE: To evaluate megakaryocyte size and ploidy, using Feulgen staining and microspectrophotometry, in adult dogs with normal platelet count. ANIMALS: Group A contained 8 and group B contained 11 adult dogs. PROCEDURE: Megakaryocytes were evaluated by light microscopy and staged according to maturation status. Stage-III megakaryocytes were measured and mapped for future relocation. Bone marrow aspirates were destained and restained, using the Feulgen method. Previously identified stage-III megakaryocytes were measured for DNA content, using microspectrophotometry. RESULTS: Megakaryocyte size correlated with ploidy values, and mean sizes within ploidy groups were significantly (P < 0.05) different from each other for both groups. The model ploidy value of stage-III megakaryocytes, which represented 18% of the total megakaryocyte population of the combined groups, was 32N. This is in contrast to results of flow cytometric studies, which indicated that the modal ploidy value for all canine megakaryocytes was 16N. CONCLUSIONS: Reasons for the disparate results between microspectrophotometric techniques and flow cytometry include maturation stage of the megakaryocyte population evaluated and percentage of megakaryocytes within that maturation stage. Flow cytometric methods, which evaluate all megakaryocytes detectable by antibody, may include cells still capable of DNA synthesis, resulting in a shift in the observed modal ploidy value. Recognition of the difference between canine and human megakaryocyte ploidy distribution is important, particularly in studies in which the dog is used as an animal model for human megakaryocytopoiesis.

Nucleotide sequence of the canine alphaIIb gene from platelet-derived cDNA.

OBJECTIVE: To determine the nucleotide sequence of the alphaIIb gene from canine platelet-derived cDNA. ANIMALS: 3 adult dogs. PROCEDURE: First-strand cDNA was prepared from total RNA isolated from canine platelets. The cDNA was amplified, using specific primers in polymerase chain reaction (PCR), and the nucleotide sequence was obtained from purified PCR products. RESULTS: Except for the nucleotide at position 694, results of all sequencing reactions of alphaIIb were identical for canine platelet-derived cDNA. Canine alphaIIb had 3 fewer codons than alphaIIb of humans. The nucleotide and deduced amino acid sequences of full-length canine alphaIIb shared > or = 83% similarity with the sequences established for humans. Segments of canine alphaIIb nucleotide and deduced amino acid sequences were > or = 78% similar to alphaIIb associated with 7 functional domains (extracellular, transmembrane, cytoplasmic, and 4 calcium-binding domains) in humans, with the highest degree of similarity correlating with the sequences of the 4 calcium-binding domains. Amino acid residues associated with development of alloantibodies in humans (Met837, Val837, Ile843, Ser843) are not encoded by canine alphaIIb. CONCLUSIONS AND CLINICAL RELEVANCE: The nucleotide variation at position 694 of canine alphaIIb may represent a polymorphism. The species differences in the alphaIIb sequence may contribute to variations in receptor-li gand interactions. The high degree of alphaIIb sequence conservation of the 4 calcium-binding domains implies functional importance. Some disorders associated with alphaIIbbeta3 in dogs are clinically analogous to diseases in humans, and results indicate that dogs are an appropriate model for the evaluation of gene therapy and other treatments of platelet-associated disorders.

Platelet, antithrombin, and fibrinolytic activities in taurine-deficient and taurine-replete cats.

Cats with cardiomyopathy, especially dilated cardiomyopathy associated with taurine deficiency, often develop systemic thrombi. To investigate the relation of taurine deficiency to formation and persistence of thrombi, cats were made taurine-deficient by consumption of a casein-based taurine-deficient diet, then were evaluated for anticoagulant and profibrinolytic activities and platelet function. The cats served as their own controls in the taurine-replete state; then, values were compared for the taurine-deficient state. Plasma (P < 0.01), blood (P < 0.05), and platelet (P < 0.05) taurine concentrations were decreased markedly after cats consumed the taurine-deficient diet for 6 weeks, compared with baseline concentrations before diet. Compared with the taurine-replete state, taurine deficiency induced significantly (P < 0.05) increased mean antithrombin III activity, no significant change in plasminogen and fibrinolytic activities, and similar clot retraction/lysis test results. Decreased (P < 0.01) adenosine diphosphate (ADP)-induced platelet aggregation and [14C]serotonin release, and slightly increased (P < 0.05) collagen-induced platelet [14C]serotonin release, but unchanged collagen-induced platelet aggregation were observed in taurine-deficient cats, compared with taurine-replete cats. Changes in antithrombin III activity most likely reflected hepatocellular acute-phase reaction, which indicates that taurine deficiency may induce a stress-responsive state. Results of platelet function testing indicate that taurine may modulate platelet responsiveness to physiologic agonists, but not in consistent manner. That platelets from the taurine-deficient cats had decreased responsiveness to ADP, but increased responsiveness to collagen is surprising, because irreversible aggregation is mediated by release of granule-associated ADP after sufficient initial stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of antithrombin-III activity as a coindicator of disseminated intravascular coagulation in cats with induced feline infectious peritonitis virus infection.

Six adult specific-pathogen-free cats were inoculated intraperitoneally with a cell culture-adapted strain of feline infectious peritonitis virus. Plasma samples were evaluated for antithrombin-III (AT-III) activities at post-inoculation days (PID) 0, 4, and 11 and at termination on PID 16 (1 cat) or 21 (5 cats). Other hemostatic values evaluated were activated partial thromboplastin times, prothrombin times, thrombin times, fibrinogen, platelet counts, and fibrin/fibrinogen degradation products. Antithrombin-III activity remained within normal or above normal range (89 to 246%) in all cats, with the exception of one cat on PID 4 (AT-III, 70%). Mean baseline AT-III activity for 6 cats at PID 0 was 123%. Mean AT-III activity on PID 4, 11, and 16 or 21 was 98, 162, and 130%, respectively. On PID 4 and 16 or 21, results of coagulation screening tests indicated that all cats had disseminated intravascular coagulation. Histologically, cats also had severe fibrinonecrotizing thrombovasculitis.

Enhanced platelet reactivity in heartworm-infected dogs.

Platelet number, mean platelet volume, and platelet function were evaluated in 34 clinically normal dogs and 28 heartworm-infected (HWI) dogs. Mean platelet numbers for dogs of the HWI group was not significantly lower than those for dogs of the control group (214,000 vs 254,000 cells/microliter); however, 6 (21%) HWI dogs had platelet numbers less than 150,000/microliter, compared with only 2 (6%) heartworm-negative dogs. The mean platelet volume was not significantly different (7.8 vs 7.7 fl) between the 2 groups of dogs. Mean platelet aggregation responses to intermediate and low concentrations of collagen (3.0 and 1.5 micrograms) and to high, intermediate, and low concentrations of ADP (25, 10, and 5 microM) were greater in dogs of the HWI group. Mean platelet 14C-serotonin release was also greater in HWI dogs in response to high concentration of ADP (25 microM) and to intermediate concentration of collagen (3.0 micrograms).

Effects of treatment with aspirin or aspirin/dipyridamole combination in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.

Effects of treatment with ticlopidine in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

Ticlopidine hydrochloride was evaluated for its effectiveness in inhibiting platelet aggregation and serotonin release in 5 laboratory Beagles before and after heartworm implantation with 7 adult Dirofilaria immitis, and after embolization with 7 dead heartworms to mimic what happens after heartworm adulticide treatment. Five other laboratory Beagles, similarly implanted and embolized with heartworms, were used as nonmedicated controls. During the heartworm-negative stage, the dosage of ticlopidine that inhibited adenosine diphosphate (ADP)-induced platelet aggregation in 5 dogs by at least 50% after 5 days of treatment was 62 mg/kg of body weight once a day. In the same dogs implanted with 7 adult heartworms 21 days previously, mean (+/- SD) ticlopidine dosage required to obtain similar results was 71 (+/- 13) mg/kg given once daily. During the 21 days after dead heartworms were implanted in heartworm-infected dogs, mean ticlopidine dosage was 108 (+/- 35) mg/kg (range, 62 to 150 mg/kg). Ticlopidine treatment was associated with increased platelet numbers in all 5 dogs during the heartworm-negative stage and in 4 of 5 dogs during the heartworm implantation and heartworm embolization stages. Mean platelet volume tended to decrease as platelet numbers increased. At necropsy, gross and histologic pulmonary lesions were less severe in ticlopidine-treated dogs than in nonmedicated control dogs.

Platelet function and antithrombin, plasminogen, and fibrinolytic activities in cats with heart disease.

Platelet function, antithrombin and plasminogen activities, and fibrinolytic capabilities in 11 cats with acquired heart disease were compared with results in 4 healthy cats. Of 11 cats with heart disease, 9 had hyperthyroidism with secondary cardiac dysfunction. One cat with hyperthyroidism had renal disease and heart failure, and of 2 cats with idiopathic hypertrophic cardiomyopathy, 1 also had renal disease. At the time of testing, 3 cats had thromboembolic events associated with the disease. Compared with healthy cats, cats with acquired heart disease had increased activity of antithrombin III, a protein that behaves as an acute-phase reactant. Plasminogen activity was decreased, although not significantly, in cats with acquired heart disease, compared with results in healthy cats. In cats with left ventricular dysfunction, clot retraction was decreased (marginal significance, P = 0.058) and might be attributed, in some cases, to the medications received by the cats. Dilute whole blood clots from all cats failed to lyse in vitro. This observation, at present, lacks adequate explanation. Platelets from cats with acquired heart disease, compared with platelets from healthy cats, had decreased responsiveness (aggregation and [14C]serotonin release) to adenosine diphosphate and increased responsiveness to collagen. Hyperthyroid cats were receiving various drugs (propranolol, atenolol, or diltiazem) to empirically treat clinical signs of disease attributable to cardiac dysfunction. Although numbers of cats in each group were small, definite trends were observed in the results of tests. Platelets from cats receiving atenolol had decreased responsiveness to adenosine diphosphate and unaltered responsiveness to collagen, compared with platelets from healthy cats, and may have decreased risk of thrombus formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of thrombospondin as a high molecular mass protein released from activated equine platelets.

OBJECTIVE: To establish the existence of platelet-derived proteins in equine plasma, with the future goal of developing an assay for the detection of in vivo platelet activation. ANIMALS: 5 mature healthy horses. PROCEDURE: Platelet-rich plasma and platelet-poor plasma were prepared from anticoagulated blood. Platelets were separated from plasma proteins by gel filtration, then activated with 0.5 microM platelet-activating factor. Protease inhibitors were added, and the released platelet proteins were harvested. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed on the released platelet proteins and platelet-poor plasma, and the resultant silver-stained bands were compared. Immunoblot analysis was performed on released platelet proteins, using an antibody to human thrombospondin; human platelet-derived proteins served as the positive control for the antibody. RESULTS: Released platelet proteins in the presence of beta-mercaptoethanol (reduced samples) contained several proteins that were not observed in plasma including (mean +/- SEM) 194 +/- 2, 159 +/- 2, 151 +/- 2, 104 +/- 2, and 95 +/- 1 kd. Immunoblots of released platelet proteins had a prominent 180 +/- 2-kd protein in reduced samples that was recognized by an antibody to human thrombospondin, and with prolonged color development, 2 additional less prominent proteins (166 +/- 1 and 155 +/- 1 kd) were observed. CONCLUSIONS: Several proteins are released from activated equine platelets that are not detectable in normal equine plasma. Thrombospondin is one of the high molecular mass proteins released by activated equine platelets. CLINICAL RELEVANCE: An assay can be developed for detection of thrombospondin in equine plasma and may be useful for detection of in vivo platelet activation in horses.

Child abduction: aged-based analyses of offender, victim, and offense characteristics in 550 cases of alleged child disappearance.

Crimes against children, particularly cases involving abduction and/or homicide, continue to be problematic as both a social phenomenon and judicial responsibility. Such cases routinely receive immense community and media attention and rapidly overwhelm investigative resources. Research in the area of childhood victimization, however, has only recently gained national prominence. While numerous studies on child abuse and neglect have been conducted, research on child abduction and homicide remains scant. Previous studies examining child abduction suffer from limited geographical scope or fail to base predictive analyses on victim characteristics. The current study reports the results of a nationally representative sample (47 states, the District of Columbia, and Puerto Rico) of 550 cases of alleged child abduction obtained from Federal Bureau of Investigation files for the period 1985 through 1995. Study results demonstrate that both offender and offense characteristics vary significantly according to victim age, gender, and race. Such differences appear critical to crime reconstruction, criminal profiling, and investigative resolution. Additionally, these data suggest that current child abduction prevention programs may emphasize inaccurate offender traits.