Results of plate fixation of type 5 olecranon fractures in 20 horses.

REASONS FOR PERFORMING STUDY: Previous olecranon fracture reports contain a small proportion of type 5 fractures, mostly treated with conservative therapy. OBJECTIVES: To evaluate the clinical details and outcome of type 5 olecranon fractures in a large group of horses treated by tension band plate fixation and to compare results with other treatment methods. METHODS: Medical records of 97 cases, including 32 (33%) classified as type 5, were reviewed. Subject details, history, radiographic findings, treatment and follow-up results (2-146 months post operatively) were recorded. RESULTS: Treatment included open reduction and internal fixation using a narrow or broad dynamic compression plate (n = 20), conservative therapy (n = 7) and euthanasia (n = 5). Long-term follow-up was available in 15 cases treated surgically, of which 2 were sound and in training, 11 sound and performing athletically and 2 unsound. Distal semilunar notch involvement, comminution or open status did not appear to affect prognosis. CONCLUSIONS: Internal plate fixation provides an excellent prognosis for an animal to be capable of athletic performance. POTENTIAL RELEVANCE: Describing tension band plate fixation and results offers a method of fracture repair that should improve treatment and prognosis for type 5 olecranon fractures.

The benefits of hospital-wide picture archiving and communication systems: a survey of clinical users of radiology services.

This paper describes one element of a broad evaluation of a hospital-wide picture archiving and communication system (PACS): an assessment of the views of users of the radiology service, their major causes of dissatisfaction with the service, the incidence of image unavailability, and the consequences of images being unavailable. The principal research design was a "before and after" comparison at Hammersmith Hospital, as the hospital site introducing PACS. Several other hospitals were included in this survey, for comparison. Questionnaires were distributed several times before PACS was operational at Hammersmith, and on one occasion after. The overall response rate was 54%. The main pre-PACS radiology-related problem areas were: the non-availability of images, the non-availability of written reports when clinically required, and the time devoted by junior staff to image searching. PACS greatly reduced the perceived problem of image non-availability. But Hammersmith's problems with the availability of radiological reports still remained when PACS was operational. The time junior doctors spent in image-searching was dramatically reduced by the introduction of PACS.

Examining the influence of picture archiving communication systems and other factors upon the length of stay for patients with total hip and total knee replacements.

OBJECTIVES: To examine the influence of a picture archiving and communication system (PACS) on the length of stay (LOS) for patients receiving total hip replacement (THR) or total knee replacement (TKR) procedures. METHODS: A before-and-after design was used. Data were collected on all THR and TKR procedures at Hammersmith Hospital from 1993-96. A regression approach was used to examine the influence of PACS on LOS. Factors such as patient age, sex, and physician were controlled for. RESULTS: Type of admission and discharge, month of procedure, complications, and number of procedures all significantly influenced LOS for patients undergoing THR. For patients receiving TKR, age, sex, admission, prosthetic complications, number of procedures, and PACS significantly influenced LOS. CONCLUSIONS: While this study shows an apparent reduction of 25% in the average LOS for TKR patients at the time PACS was introduced, this is unlikely to be a true PACS effect and no similar reduction in LOS was shown for THR patients.

Subchronic intravenous toxicity of the antineoplastic drug, amsacrine, in male Wistar rats.

Amsacrine, a DNA intercalator and topoisomerase II inhibitor, is efficacious as an antileukemogenic agent. This study was conducted to assess the subchronic toxicity of amsacrine in rats following a cyclic clinical dosing regimen and as a range-finding experiment for a subsequent carcinogenicity bioassay. Groups of 30 male Wistar rats were administered drug intravenously at doses of 0, 0.25, 1.0, and 3.0 mg/kg daily for 5 days followed by 23 days without treatment. This cycle of dosing and recovery was repeated six times to simulate human clinical usage of the drug. Assessments of hematology, clinical chemistry, and gross and microscopic pathology were conducted 3 and 21 days following completion of dosing in the first, third, and sixth cycles. There were no deaths during the study. Hair loss, diarrhea, tail injuries, chromodacryorrhea, and rhinorrhea were observed primarily in animals administered 3 mg/kg. Hair loss and diarrhea occurred during periods of dosing and generally resolved during the recovery phase of each cycle. Both of these signs became progressively more severe during the latter half of the study. Body weight loss and reduced food consumption also occurred in the 3 mg/kg group during each week of dosing. At study termination, mean body weight and food consumption of the 3 mg/kg group were significantly less than those of controls by approximately 20 and 50%, respectively. Marked, reversible leukopenia associated with reductions in both neutrophil and lymphocyte counts occurred in cycles one and three in animals administered 1 and 3 mg/kg, respectively. Reversible neutropenia was also observed in the 3 mg/kg group in cycle 6. Similar effects on platelet counts were seen in the 3 mg/kg group in all three cycles analyzed. Absolute and relative testes weights of the 3 mg/kg group were significantly less than the vehicle controls at all time points in the third and sixth cycles. Relative testes weights were also decreased in the 1 mg/kg group in cycle 6. Reversible decreases in absolute relative spleen weights occurred in all drug-treated groups in cycle 1 and for the 3 mg/kg group in cycle 3. Lymphoid depletion (spleen, thymus, lymph node), marked hypocellularity of bone marrow, segmental degeneration of seminiferous tubules, and intestinal epithelial cell degeneration were observed at 3 mg/kg. With the exception of testicular changes which remained evident at the end of cycle 6, pathologic lesions were reversible during the 23-day recovery period of each cycle. The results show that the subchronic toxicity of amsacrine is consistent with a cytotoxic mechanism and that target organs are generally tissues with the highest rates of cell turnover. The doses administered in this study induced a range of effects which were minimal at 0.25 mg/kg and dose-limiting at 3 mg/kg and therefore were considered appropriate for use in the subsequent carcinogenicity bioassay.

Chronic toxicity of the anticancer agent trimetrexate in rats.

Trimetrexate was administered to rats in an interrupted treatment regimen comparable to proposed human clinical treatment. Forty-five rats of each sex were dosed intravenously with trimetrexate at 0, 1, 10, or 30 mg/kg (0, 6, 60, or 180 mg/m2), once daily for 5 consecutive days, followed by a 23-day recovery period. This cycle of dosing and recovery was repeated for a total of six cycles. Hematology, urinalysis, clinical chemistry, and gross and microscopic pathology examinations were conducted for animals euthanatized 3 and 21 days after dosing cycles 1, 3, and 6. Additional rats in each group were maintained without dosing for an additional 56 days (77 days after the last trimetrexate dose) to assess the long-term reversibility of pathologic changes. Target organs were typical for an antifolate and included gastrointestinal tract, lymphoid tissues, and the hematopoietic and male reproductive systems. No toxicity was observed at 1 mg/kg. Treatment-related changes in hematology parameters following 10 and 30 mg/kg were fully reversible within 3 weeks of each dosing cycle. Except for testis and cecum, histopathological changes were also reversible within 21 days of dosing. Trimetrexate-induced testicular changes persisting during the course of multiple cycles of dosing were not reversible within 21 days, but required an additional 56 days for essentially complete recovery.

Cloning and nucleotide sequence of the Vibrio proteolyticus aminopeptidase gene.

The gene encoding the Vibrio proteolyticus aminopeptidase was cloned and sequenced and its amino acid sequence was deduced. The gene encodes a 54 kDa protein, larger than the previously reported size of 30 kDa for the purified aminopeptidase. Sequence alignments revealed a 43-45% homology with two other Vibrio sp. extracellular proteinases.

Toxicity of the anticancer folate antagonist trimetrexate in rats.

Trimetrexate is a nonclassical folate antagonist that is active against a number of experimental murine and human tumor cell lines. To assess its toxicity, rats were administered single or repeated (daily x5) doses by either the oral or the intravenous route. Oral doses were 0, 90, 180, 295, and 375 mg/kg (single dose) and 0, 32, 65, and 80 mg/kg (daily x5). Intravenous doses were 0, 6, 20, and 60 mg/kg (single dose) and 0, 10, 20, and 30 mg/kg (daily x5). In the oral studies, signs of toxicity first appeared 2 to 3 days after initiation of dosing. Clinical signs included hypoactivity, diarrhea, urine scald, rhinorrhea, emaciation, and death. Significant pathologic findings were degenerative enteropathy in small and large intestines, bone marrow hypocellularity, decreased WBCs (neutrophils, lymphocytes), generalized lymphoid depletion, and testicular tubular degeneration. Except for the testicular changes, these effects were most severe in animals dosed at 65 and 80 mg/kg in the oral x5 study (65-70% mortality). Repeated oral doses at 32 mg/kg and single oral doses through 375 mg/kg caused only mild to moderate effects and less than 5% mortality. In contrast, single intravenous doses at 60 mg/kg resulted in immediate death (20% mortality) due to apparent CNS toxicity. Intravenous doses below 60 mg/kg were essentially asymptomatic. Toxicity in the intravenous studies was limited to decreased WBCs, splenic and thymic lymphoid depletion (repeated dosing), and testicular tubular degeneration and/or atrophy. Except for the testicular lesions, most of the effects in the oral and intravenous studies were reversible within 4 weeks. The results show that the acute toxicity of trimetrexate in rats is somewhat dependent on its route of administration, although the spectrum of effects is qualitatively similar to that observed in other species and with other folate antagonists. The dose-limiting toxicity of trimetrexate in rats common to both routes of administration is myelosuppression.

Calcium valproate-induced uterine adenocarcinomas in Wistar rats.

Calcium valproate is an anticonvulsant agent with pharmacokinetic properties similar to sodium valproate and valproic acid. Potential carcinogenesis of calcium valproate was evaluated in B6C3F1 mice and Wistar rats given 125, 250 and 500 mg/kg in the diet for 104 weeks. Survival in treated rats increased in a dose-related pattern despite a tumorigenic response in females. Adenocarcinomas of the uterus and cervix were increased in treated rats when compared to controls. The incidence of uterine neoplasia was 8, 20, 14 and 32% in the control, 125, 250 and 500 mg/kg groups, respectively. Neoplasia in treated rats were detected against a higher than expected background of adenocarcinomas in concurrent controls, since 8% incidence in controls was substantially above the laboratory historical database value of 0.6%. Tumors varied from epithelial masses confined to the endometrium, to transmural, highly desmoplastic neoplasms that invaded the serosa lining and the peritoneal cavity. These tumors metastasized in treated rats but not in controls. The statistically significant (P less than 0.01) increase in uterine adenocarcinomas found in females given 500 mg/kg of calcium valproate contrasts the absence of this tumor type in a previous rat carcinogenicity bioassay with valproic acid. Subcutaneous fibrosarcomas were significantly increased in valproic acid-treated males, but no uterine tumors were reported in females. It is puzzling that a true carcinogenic potential would be expressed by markedly different target organs as obtained with the acid and calcium salt of this moiety.

Cataracts in dogs following subchronic administration of the phenylpiperazine antihypertensive agent PD 78787.

PD 78787, 3-[4-[4-(3-methylphenyl)-1-piperazinyl]butyl]-2,4-imidazolinedione, was an antihypertensive drug candidate with alpha 1 adrenoreceptor blockade identified as one of its pharmacologic activities. Beagle dogs were administered daily doses of 0, 1, 5, or 10 mg/kg for 41 weeks. During the study, periodic ophthalmic examinations were performed in addition to electrocardiography, blood pressure measurements, and hematological, clinical biochemical, and urinalysis assessments. At study termination, animals were euthanatized and the following procedures conducted; complete gross pathological examinations; histopathologic examination of lens; biochemical analysis of aqueous humor; and measurements of drug concentration in plasma, aqueous humor, and lens. Clinical signs observed included miosis, relaxed membrane nictitans, and somnolence. Ophthalmic examinations at Week 13 revealed unilateral posterior lenticular opacities at the dose of 10 mg/kg in two of four females. At Week 41, mature bilateral cataracts were observed in four of four females and three of four males administered the 10 mg/kg dose. The opacities appeared to develop from the posterior suture lines. No adverse effects on aqueous humor composition were observed. Significant concentrations of PD 78787 were found in lens and aqueous humor from all dose groups 24 hr following the last dose. These concentrations increased with increasing dose averaging 4 micrograms/ml in the lenses of dogs administered 10 mg/kg. Histopathologically, swelling, vacuolation, and dissolution of the lenticular fibers were observed at 10 mg/kg. All other study parameters were unaffected by drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Proliferative bone lesions in rats given anticancer compounds.

Proliferative endosteal lesions were observed in metaphysis and diaphysis of femur and sternebra of Wistar (CRL:[WI]BR) rats administered 3 chemically-distinct anticancer compounds with dissimilar mechanisms of action: trimetrexate glucuronate, an antifolate; pentostatin, an adenosine deaminase inhibitor; and CI-980, a mitotic inhibitor. Islands of woven bone, often circumscribed by conspicuous myelostromal proliferation, were seen on Days 8-28 in rats given trimetrexate glucuronate daily by gavage, and on Day 4 but not Day 29 in rats given a single intravenous dose of pentostatin. Intravenous administration of CI-980 for 1 or 5 days resulted in marrow necrosis, marked centripetal new bone formation, and myelostromal proliferation on Days 4 and 8, respectively. These lesions were not present at the termination of these latter studies (Days 29 and 35, respectively). In conclusion, anticancer compounds induced local bone marrow injury and the release of local inflammatory mediators which may have provided the stimulus for bone formation and myelostromal proliferation.

Preclinical toxicity of the new antineoplastic agent, ametantrone acetate, in mice and dogs.

Ametantrone acetate (anthracenedione diacetate, NSC 287513) is an experimental antineoplastic agent with activity against a comprehensive panel of solid transplantable tumors in mice and dogs were carried out to establish tolerable levels. In mice, LD10, LD50 and LD90 values were respectively, 26, 35 and 47 mg kg-1 28 days following single intravenous injection and 22, 67 and 206 mg kg-1 14 days after single intraperitoneal injection. Hemorrhage and necrosis of the small intestine occurred in intercurrent deaths. A 5-day, consecutive intraperitoneal dosing study yielded 28 day, LD10, LD50 and LD90 values of 18, 21 and 26 mg kg-1, respectively, in mice. Bone marrow hypoplasia, lymphoid depletion and focal cardiac changes were observed in animals which died during the 28-day postdose observation period. In dogs, single intravenous injections repeated twice at intervals of 3-8 weeks resulted in leukopenia and thrombocytopenia at a dose of 2.71 mg kg-1 and decreased myeloid: erythroid ratios at a dose of 0.68 mg kg-1. Five consecutive daily intravenous injections in dogs of 0.7 mg kg-1 induced significant clinical and laboratory signs of toxicity but 0.35 mg kg-1 day-1 was tolerated. In dogs, bone marrow, lymphoid tissue and gastro-intestinal tract in both sexes and gonads in the males were target organs for toxicity. Clinical signs and clinical laboratory abnormalities abated in surviving mice and dogs. The spectrum of tissue changes induced by ametantrone was qualitatively similar to that elicited with other intercalating agents.

Two B-cell subpopulations identified by flow cytometry.

Ig+ spleen cells were analysed by light scatter analysis on a flow cytometer and two distinct subpopulations were identified. The large Ig+ cells (10-11 micron in diameter) were found in spleen and bone marrow, whereas the small Ig+ cells (7-8 micron in diameter) were found in all lymphoid tissues. Of the total Ig+ splenic lymphocytes, 40-60% were large Ig+ cells and had surface IgM, Ia and Fc gamma receptors. The large Ig+ cells were highly enriched for responsiveness to the B-cell mitogens, anti-Ig, Nocardia water-soluble mitogen and LPS, whereas the small Ig+ splenic cells had little or no responsiveness to these mitogens.

Flow cytometric analysis of heterogeneity in blood group-related antigen expression in a human urinary bladder carcinoma cell line, 647V.

Previous immunohistological studies showed a relationship between expression of blood group-related antigens (BG-Ag) and invasive potential in human urinary bladder carcinoma, but the marked variability of antigen staining within many individual tumors has obscured the biological basis of this finding. We studied the expression of the A, H, and T (Thomsen-Friedenreich) BG-Ag by flow cytometry in a human bladder carcinoma cell line (647V) using fluoresceinated BG-Ag-specific lectins (Dolichos bifloris, Ulex europaeus, and Arachis hypogaea). Cell cycle compartments were quantitated by flow cytometry using propidium iodide staining. Expression of all three antigens was highly variable, but staining for each antigen produced a distinct profile. T antigen expression appeared independent of A or H antigen expression. Cell populations sorted by T antigen expression showed heritable antigenic differences persistent over many weeks in culture. However, much of the T antigen variability was nonheritable, since the stable staining profiles of the sorted cells were intermediate between the parental and the profiles obtained immediately after sorting. The nonheritable antigenic variation did not appear entirely explainable by cell size or cell cycle fluctuation. These results were confirmed by isolating 64 clones from the dim part of the T antigen staining profile, 19 of which had a persistently dim phenotype. The variability of BG-Ag expression by human bladder carcinoma cells in vitro may explain the staining patterns observed in the study of antigen expression in resected human bladder carcinomas.

Cardiotoxicity study of amsacrine in rats.

The cardiac functional and tissue changes produced by the antineoplastic agent, amsacrine, were evaluated in CD male rats. Amsacrine was administered intraperitoneally to groups of 12 male rats in single weekly doses of 12, 6, and 3 mg/m2 for 13 weeks. The drug elicited target organ toxicity in the bone marrow, lymphoid tissue, and gonads. There were blood biochemical alterations with transient elevations of total serum creatine phosphokinase, creatine phosphokinase-MB fraction, aspartate aminotransferase, and lactate dehydrogenase levels at 12 mg/m2, suggesting myocardial damage; however, there was no associated pathologic evidence of cardiotoxicity. This study indicates that amsacrine has negligible cardiotoxicity in rats when administered weekly for 13 weeks even at the lethal dose levels.

Characterization of functionally distinct subpopulations of rabbit T lymphocytes.

Two subpopulations of rabbit spleen and mesenteric lymph node T cells were identified by a monoclonal antibody, 8AC8. These subpopulations were separated on the flow cytometer and were analysed for their response to T cell mitogens and antigens, their responsiveness in mixed lymphocyte cultures, and their ability to function as cytotoxic effector cells. The 8AC8+ T cell subpopulation contained cells highly responsive to T cell mitogens, to antigen, and to allogeneic or autologous stimuli in a mixed lymphocyte reaction. In contrast, the 8AC8- T cell subpopulation was non-responsive to T cell mitogens, and responded, poorly to antigen, and to allogeneic and autologous stimuli in an MLR. Both the 8AC8+ and 8AC8- subpopulations exhibited xenogenic cytotoxic effector function. Thus, the 8AC8 MAb identified a subpopulation of mature differentiated rabbit T cells; these 8AC8+ cells share many of the characteristics of the human OKT4 helper/inducer T cell subpopulation.

Toxicology studies with a stable intravenous formulation of nitroglycerin.

The preclinical toxicologic profile of Nitrostat, a stable parenteral formulation of nitroglycerin, was determined in mice, rats, rabbits and dogs. Single-dose i.v. studies in rodents yielded LD50 values of 17.3 and 18.2 mg kg-1 in male and female mice, and 24.4 and 23.2 mg kg-1 in male and female rats, respectively. Subacute i.v. studies in rats at doses of 2.5, 5.0 and 10.0 mg per kg per day, and in dogs at doses 1.0 and 3.0 mg per kg per day for two weeks, elicited minimal reactions. In rats, suppression of body-weight gain and food consumption occurred among treated and vehicle-control animals. Mild tissue irritation at injection sites was noted in treated and vehicle-control groups. There were no clearly drug-related clinical or pathological findings in dogs. In rabbits, repeated intravenous administration of Nitrostat did not induce significant local venous irritation. The results of these studies indicated that the stabilized parenteral formulation of nitroglycerin did not elicit unusual toxic properties in intravenous infusion studies.

Functional studies of rabbit T lymphocytes.

Rabbit spleen and mesenteric lymph node cells were treated with a monoclonal anti-rabbit T-lymphocyte antibody (MAb) and complement and the effect of the treatment on various lymphocyte functions was determined. Lysis of spleen and mesenteric lymph node cells reactive with this MAb, 9AE10, essentially eliminated their proliferative responsiveness to allogeneic lymphocytes in the mixed lymphocyte reaction and to the T-cell mitogens, concanavalin A and phytohaemagglutinin; responsiveness to the B-cell mitogen, anti-immunoglobulin (Ig) was not decreased by lysis of 9AE10+ cells. In addition, the 9AE10+ cells were found to be necessary for the secondary in vitro antibody response to the T-dependent antigen sheep red blood cells (SRBC), as removal of 9AE10+ cells blocked the generation of plaque forming cells (PFC) in culture. The PFC's themselves were not sensitive to lysis by 9AE10 MAb and complement Thus, the 9AE10 MAb appears to recognize cells which have functions characteristic of T lymphocytes and this monoclonal antibody will be useful in further studies of the rabbit cellular immune system.

Image data-processing system for solar astronomy.

Image processing has become an invaluable tool in the analysis of solar astronomy and other scientific data. In particular, a number of powerful and intricate image-processing systems have been developed. One such system is the MSFC/S-056 Image Data Processing System (IDAPS), especially designed for the analysis of the Skylab/ATM S-056 X-Ray Telescope experiment data. This paper describes the IDAPS, discusses its unique interactive capabilities, and shows some recent results obtained using the IDAPS.