High frequency of myelomonocytic tumors in aging E mu L-myc transgenic mice.

Transgenic mice that contain constructs of the L-myc gene under the transcriptional control of the immunoglobulin heavy chain enhancer (E mu) develop thymic hyperplasia and are predisposed to T cell lymphomas. Here we describe a second form of malignancy that occurs in aging E mu L-myc transgenic mice. The mean latency period for the development of this malignancy is longer compared with the E mu L-myc T cell lymphomas but the overall incidence is increased threefold. The histopathological morphology is that of a highly malignant mesenchymal neoplasm that closely resembles human fibrous histiocytoma. The tumor cells were classified as myelomonocytic on the basis of several lineage-specific markers and the lack of rearrangements of the immunoglobulin heavy chain and the T cell receptor beta loci. Cultured tumor cells produce macrophage colony-stimulating factor (M-CSF) protein and express the M-CSF receptor, suggesting the involvement of an autocrine loop in this malignancy. Similar to the E mu L-myc T cell lymphomas, these tumors show high-level transgene expression but no detectable levels of endogenous c-myc mRNA, directly implicating the deregulated expression of L-myc in the generation of this malignancy. E mu L-myc myelomonocytic tumors show consistent trisomy of chromosome 16, implicating this as a secondary event in the development of this tumor. In the light of recent findings that L-myc is expressed in human myeloid leukemias and in several human myeloid tumor cell lines, the results described here might implicate L-myc in the development of naturally occurring myeloid neoplasias.

Cardiovascular evidence for an intermediate or higher metabolic rate in an ornithischian dinosaur.

Computerized tomography scans of a ferruginous concretion within the chest region of an ornithischian dinosaur reveal structures that are suggestive of a four-chambered heart and a single systemic aorta. The apparently derived condition of the cardiovascular system in turn suggests the existence of intermediate-to-high metabolic rates among dinosaurs.

Indirect recognition of donor HLA-DR peptides in organ allograft rejection.

To determine whether indirect allorecognition is involved in heart allograft rejection T cells obtained from peripheral blood and graft biopsy tissues were expanded in the presence of IL-2 and tested in limiting dilution analysis (LDA) for reactivity to synthetic peptides corresponding to the hypervariable regions of the mismatched HLA-DR antigen(s) of the donor. Serial studies of 32 patients showed that T cell reactivity to donor allopeptides was strongly associated with episodes of acute rejection. The frequency of allopeptide reactive T cells was 10-50-fold higher in the graft than in the periphery indicating that T cells activated via the indirect allorecognition pathway participate actively in acute allograft rejection. In recipients carrying a graft differing by two HLA-DR alleles the response appeared to target only one of the mismatched antigens of the donor. Indirect allorecognition was restricted by a single HLA-DR antigen of the host and directed against one immunodominant peptide of donor HLA-DR protein. However, intermolecular spreading was demonstrated in patients with multiple rejection episodes by showing that they develop allopeptide reactivity against the second HLA-DR antigen. These data imply that early treatment to suppress T cell responses through the indirect pathway of allorecognition, such as tolerance induction to the dominant donor determinant, may be required to prevent amplification and perpetuation of the rejection process.

Hyperthermia increases accumulation of technetium-99m-labeled liposomes in feline sarcomas.

The effect of hyperthermia on the accumulation of technetium-99m-labeled liposomes was studied in feline sarcomas. Each cat received two separate injections of liposomes. The first was used to quantify the amount of technetium-99m-labeled liposomes within the tumor under normothermic conditions. The second injection was made at the beginning of a 60-min hyperthermia procedure. Planar scintigraphy was used to measure the activity of technetium-99m-labeled liposomes within the tumor at predetermined times up to 18 h after injection. Regions of interest were drawn for the tumor, lungs, liver, kidney, and aorta. Counts in the regions of interest were decay corrected. Counts/pixel in the tumor under normothermic and hyperthermic conditions were normalized to aorta counts/pixel. A total of 16 cats were eligible for the study. In two of the 16 cats, incomplete count data precluded analysis. In the remaining 14 cats, hyperthermia resulted in a significant increase in liposome accumulation in the tumor (P = 0.001). Tumor volume ranged from 1.2 to 236.2 cm3, and thermal dose ranged from 2.0 to 243.3 CEM43CT90 (equivalent time that the 10th percentile temperature was equal to 43 degrees C). There was not a relationship between either tumor volume or hyperthermia dose on the magnitude of increased liposome accumulation, suggesting that this method has application across a range of tumor volumes and degrees of heatibility.

New strategies for early diagnosis of heart allograft rejection.

BACKGROUND: Allograft rejection is mediated by T cells that recognize allogeneic major histocompatibility complex (MHC) molecules via the direct and indirect pathway. The direct pathway involves T cells that react against MHC/peptide complexes expressed on the surface of donor antigen-presenting cells (APCs). In contrast, T cells involved in the indirect pathway recognize peptides derived from processing and presentation of allogeneic MHC molecules by self (recipient) APCs. To explore the relative contribution of these two pathways to rejection, we have evaluated the response of peripheral blood T cells from 50 heart transplant recipients against donor APCs (direct recognition) and against self APCs pulsed with synthetic peptides corresponding to the hypervariable region of the mismatched HLA-DR antigens of the donor (indirect recognition). METHODS: T cell reactivity against donor APCs was quantitated by measuring the expression of CD69 on allostimulated CD3+ LDA1+ cells. Reactivity to synthetic allopeptides was determined in limited dilution assays. RESULTS: Serial studies of the kinetics of direct and indirect recognition showed that both pathways contribute to early acute rejection episodes. Primary rejection was accompanied invariably by indirect recognition of a dominant allopeptide. Intermolecular spreading of T cell epitopes was observed during recurrent rejections. Enhanced recognition of donor alloantigens via the direct pathway was found predominantly during early rejection episodes. A single form of allorecognition was shown to occur in some rejection episodes. CONCLUSIONS: Monitoring of the direct and indirect pathway of allorecognition provides a reliable method for prediction and differential diagnosis of acute rejection of heart allografts.

Improvement of rejection-induced diastolic abnormalities in rat cardiac allografts with inducible nitric oxide synthase inhibition.

OBJECTIVE: Inhibition of inducible nitric oxide synthase (nitric oxide II) activity has been proposed as a method to attenuate capillary leak and edema during rejection of heterotopically transplanted rat hearts. Myocardial edema has previously been implicated in diastolic dysfunction during allograft rejection. Accordingly, we tested the hypothesis that inducible nitric oxide synthase inhibition with aminoguanidine would alleviate left ventricular stiffening and myocardial edema formation in 4-day heterotopic rat heart allografts. METHODS: Passive left ventricular filling was studied in American Cancer Institute Lewis rats receiving heterotopic heart transplants receiving either aminoguanidine, a selective nitric oxide synthase inhibitor (n = 6); dexamethasone (1 mg. kg(-1). d(-1) administered subcutaneously) for 4 days after transplantation (n = 6); or intravenous saline solution (n = 6). American Cancer Institute-to-American Cancer Institute isografts (n = 6) were used as controls. RESULTS: Serum nitrite/nitrate levels in the aminoguanidine group (18 +/- 3 mmol/L) and dexamethasone group (22 +/- 4 mmol/L) were reduced versus the intravenous saline group (144 +/- 36 mmol/L [SEM]) to levels seen in controls (25 +/- 9 mmol/L). Left ventricular volume at 15 mm Hg for the aminoguanidine group was increased versus that for the intravenous saline solution group, similar to that for controls, and reduced versus dexamethasone-treated animals. Myocardial water content for the aminoguanidine-treated animals (78.3% +/- 0.4%) was similar to those of intravenous saline-treated animals (78.0% +/- 0. 3%) but greater than those of controls (77.1% +/- 0.2%) and dexamethasone-treated animals (76.7% +/- 0.3%). CONCLUSIONS: Nitric oxide II inhibition with aminoguanidine minimizes the reduction in left ventricular filling that is seen with allograft rejection through a mechanism that is not associated with attenuation of myocardial edema.

Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in human immunodeficiency virus-infected subjects.

We conducted a single-center, double-blind, placebo-controlled phase I study in HIV-positive subjects to ascertain the safety, tolerance, bioavailability, pharmacokinetics, and maximum tolerated dose of HPMPC (cidofovir). Five subjects were randomized to receive drug and two to receive placebo at each of three dosage tier (1, 3, and 10 mg/kg) with a 2-week washout period doses. Subjects at 1 and 3 mg/kg received single doses of HPMPC by subcutaneous (s.c.) intravenous (i.v.), and oral (p.o.) routes, while subjects at 10 mg/kg received only i.v. and p.o. doses. For subjects already taking zidovudine, zidovudine AUC values are determined before and then with HPMPC administration for each route. The AUC values of HPMPC were dose-proportional. Subcutaneous bioavailability was essentially equivalent to that of the intravenous route, but the development of transient local fibrosis ad the volumes needed for subcutaneous dosing precluded higher subcutaneous dosing than 3 mg/kg. Oral bioavailability was poor, estimated to be less than 5%. Drug elimination was predominantly renal. Nephrotoxicity in one subject was the only serious adverse event observed. This subject had a significant lag period prior to oral absorption and also had the highest AUC values for both HPMPC and zidovudine. We found no consistent effect on zidovudine AUC concomitant HPMPC.

Additive value of immunologic monitoring to histologic grading of heart allograft biopsy specimens: implications for therapy.

BACKGROUND: Currently the sole method available for diagnosis of heart allograft rejection is endomyocardial biopsy. Although this procedure offers important criteria for treatment, it cannot always discriminate between mild episodes of rejection which might be self-limiting and forms which may progress. In an effort to monitor rejection, we have implemented a cellular monitoring strategy aimed at identifying episodes of rejection in biopsy specimens which may evolve into higher grades of rejection. The lymphocyte growth assay is based on the capacity of interleukin-2 receptor-positive T cells to expand in the presence of interleukin-2 and antigen provided by the biopsy fragment. In this study we investigated whether a positive lymphocyte growth assay correlated with and was predictive of subsequent histologic allograft rejection and the development of anti-human leukocyte antigen antibodies. METHODS: Lymphocyte growth assay was performed on 437 biopsy specimens from 76 patients. Patients with mild allograft rejection defined as grade 2 rejection were randomized to treatment according to the results of the lymphocyte growth assay. Anti-human leukocyte antigen antibodies was also measured monthly. Cells grown from the biopsy specimens were tested against the donor cells and allopeptides derived from the donor human leukocyte antigen-DR. RESULTS: A highly significant correlation was observed between the histologic grade of rejection and growth of graft infiltrating cells (p < 0.0001). Lymphocyte growth occurred in 10% of grade 0 versus 60% of grade 3A biopsy specimens. Only 4% of histologically negative cases with negative lymphocyte growth assay progressed to rejection in the next month. In the randomized study in which treatment was based on the lymphocyte growth assay results, progressive rejection occurred in three of four cases with positive lymphocyte growth assay versus only 1 of 11 with a negative lymphocyte growth assay (p < 0.001). A highly significant correlation was found between a positive lymphocyte growth assay and subsequent development of antihuman leukocyte antigen antibodies (p < 0.0006). This finding indicates that cellular rejection evidenced by lymphocyte growth assay ultimately results in humoral antihuman leukocyte antigen antibody mediated rejection. Limiting dilution analysis showed that although the direct recognition pathway prevails in early rejection, cells participating in the indirect pathway also proliferate vigorously in the graft during rejection. CONCLUSIONS: Monitoring of rejection with lymphocyte growth assay is a simple method which provides prognostic information on the outcome of cardiac allografts. Lymphocyte growth assay correlates with histologic rejection and is predictive of future histologic rejection episodes. Lymphocyte growth assay also predicts subsequent development of antihuman leukocyte antigen antibodies and thus may provide a useful method for ascertaining the onset of chronic rejection.

Diastolic properties, myocardial water content, and histologic condition of the rat left ventricle: effect of varied osmolarity of a coronary perfusate.

BACKGROUND: Although myocardial edema is known to impair diastolic filling of the left ventricle, the interrelation of edema, histologic condition, and function has not been quantitated sufficiently for extrapolation to studies of multifactorial influences on diastolic properties. METHODS: Accordingly, ACI rat hearts arrested at 4 degrees C underwent coronary artery perfusion with a cardioplegia solution that was either unaltered (288 mOsm/L, P288 group, n = 6), diluted (144 mOsm/L, P144 group, n = 6), or concentrated (380 mOsm/L, P380 group, n = 6). Postmortem left ventricular pressure-volume curves and myocardial water content were measured. Myocardial samples were fixed in varying dilutions of glutaraldehyde. After dehydration and paraffin embedding, edema was graded subjectively (0 to 5), and myocardial interstitial spaces were determined by use of a semiquantitative method. RESULTS: Mean normalized left ventricular filling volume at 20 mm Hg filling pressure in the P144 group, 189 +/- 16 microliters (SEM), was reduced versus both the P288 (278 +/- 26 microliters) and the P380 (332 +/- 18 microliters) groups (p < 0.05, ANOVA). Mean myocardial water content in the P144 group, 80.7% +/- 1%, was increased versus the P380 (76.7% +/- 0.4%, p < 0.05) but not versus the P288 group (78.4% +/- 0.8%). In hearts preserved with 2.5% glutaraldehyde, mean edema grade and interstitial space in the P144 group (4.0 +/- 0.3) were increased versus the P380 (1.8 +/- 0.3, p < 0.05) but not the P288 group (2.7 +/- 0.5). Derived linear regressions relate water content to filling volume and histologic condition. CONCLUSIONS: Coronary perfusate osmolarity is thus associated with predictable changes in myocardial water content, left ventricular filling volume, and edema. These correlations allow definition of new hypotheses for the study of cardiac allograft rejection in patients and experimental animals.

Effect of improved myocardial protection on edema and diastolic properties of the rat left ventricle during acute allograft rejection.

BACKGROUND: Studies of myocardial edema and diastolic dysfunction in rat heart transplantation have been flawed by ischemic injury. This study uses improved methods to prevent ischemic contracture. METHODS: Hearts of 30 ACI rats were transplanted into the abdomen of Lewis rats by use of cold University of Wisconsin solution for improved preservation. Left ventricular diastolic properties were expressed as volume at standardized pressure intervals. RESULTS: On posttransplantation day 3, mean left ventricular volume at 15 mm Hg in allografts (290 +/- 9 microl, SEM) was not significantly different vs isografts (299 +/- 32 microl), allografts on day 0 (337 +/- 28 ml) or day 1 (324 +/- 20 microl), or native hearts (334 +/- 19 microl). However, volume was reduced to 173 +/- 17 microl on day 4 and to 70 +/- 23 microl on day 5 (p < 0.05). Similar findings were obtained for volume at 5 and 10 mm Hg. Allograft myocardial water content on day 3, 76.3% +/- 5%, similar to allografts on day 0 and 1 and to isografts on day 3, increased to 77.6% +/- 8% on day 4 (NS) and 79.4% +/- 6% on day 5 (p < 0.05 vs day 0). Histologically, rejection in allografts was mild on day 3, moderate on day 4, and severe on day 5. CONCLUSIONS: Reduced left ventricular filling volume during rejection is only partially explained by edema. Abnormalities of diastolic properties previously attributed to the unloaded state of nonworking heart models may actually reflect inadequate peritransplantation myocardial protection.

Histologic analysis of transmyocardial channels: comparison of CO2 and holmium:YAG lasers.

BACKGROUND: Transmyocardial laser revascularization using different lasers is being tested in the treatment of refractory angina. We conducted comparative analysis of the acute and chronic myocardial effects of these different lasers. METHODS: Transmyocardial channels were made in normal dog hearts with either a holmium:yttrium-aluminum garnet or a CO2 laser. Channels were examined histologically 6 to 24 hours, 2 to 3 weeks, and 6 weeks after creation. RESULTS: Regardless of the laser source, the channels were occluded by thrombus within 6 to 24 hours. Subsequently, organization and neovascularization of the channel region occurred. Thermoacoustic damage was initially greater with the holmium:yttrium-aluminum garnet laser, but the channel appearances were indistinguishable from those made with the CO2 laser by 6 weeks. CONCLUSIONS: Histologically, the myocardial effects of the CO2 and holmium:yttrium-aluminum garnet lasers are similar and differ predominantly in the amount of acute thermoacoustic injury. Channels are rapidly occluded by thrombus and are replaced by neovascularized collagen. This suggests that the physiologic effects of these two lasers may be similar and that mechanisms other than blood flow through chronic patent channels should be considered as contributing to the clinical benefits observed with this procedure.

Histologic appearance of transmyocardial laser channels after 4 1/2 weeks.

Preliminary results of clinical studies suggest that transmyocardial laser revascularization is an effective treatment for patients with chronic angina that cannot be treated by other means. The mechanism of this effect remains controversial. We present autopsy results from a patient obtained 4 1/2 weeks after operation that show that the channels do not maintain patency. Further work is needed to determine the frequency of channel patency and its relation to clinical benefit.

Physiology, histology, and 2-week morphology of acute transmyocardial channels made with a CO2 laser.

BACKGROUND: Transmyocardial revascularization with a CO2 laser appears to improve symptoms in patients with refractory angina. However, it remains controversial as to whether blood flow through the channels is the mechanism of benefit, especially in the acute setting. METHODS AND RESULTS: Three protocols were used to test whether blood flows through transmyocardial CO2 laser revascularization channels. First, channels were made in excised, cross-perfused dog hearts (n = 5) using a CO2 laser (The Heart Laser; PLC Systems Inc, Milford, MA; 40 J/pulse) followed by ligation of the proximal left anterior descending coronary artery. Colored microspheres injected into the left ventricular chamber failed to detect any significant transmyocardial blood flow. In the second protocol (n = 4), laser channels were created in the left anterior descending artery territory, the left anterior descending artery was ligated, and the hearts were excised after 24 hours. Triphenyltetrazolium chloride staining revealed that no viable myocardium was detected around the laser channels in the ischemic myocardium. Finally, channels examined 2 weeks after creation in normal (n = 6) or ischemic (n = 4) myocardium did not maintain their original caliber but were invaded by granulation tissue, which included a large amount of smaller vascular spaces and vessels of various sizes. CONCLUSIONS: Transmyocardial laser revascularization channels made with this CO2 laser did not provide acute myocardial perfusion or preserve myocardial viability in the face of acute ischemia. Channel morphology changes dramatically within the first 2 weeks. To the degree that these findings pertain to human myocardium, the results suggest that transmyocardial blood flow may not be the mechanism of benefit of this procedure, particularly in the acute setting.

Does blood flow through holmium:YAG transmyocardial laser channels?

BACKGROUND: Early reports indicate that transmyocardial laser revascularization improves symptoms in patients with refractory angina. However, there is little experimental evidence of whether blood flow through channels is the mechanism of action. METHODS: Endocardial channels were made in the distribution of the left anterior descending coronary artery in canine hearts (n = 5) using a holmium:yttrium-aluminum garnet laser. Hearts were excised acutely while perfused in a retrograde fashion from a second dog so that the aortic valve always remained closed. The proximal left anterior descending coronary artery was ligated. To measure direct transmyocardial blood flow, colored microspheres were injected into the left ventricular chamber. RESULTS: The number of spheres per gram of tissue in the channel region was significantly higher than in the control region (low load, 302.5 +/- 169.0 versus 41.8 +/- 59.4; high load, 208.4 +/- 138.3 versus 5.8 +/- 11.7; both, p < 0.05). However, the estimated regional blood flow through the channels was extremely low (<0.01 mL/g/min. In the chronic setting (n = 4) (2-week survival), no flow as detected through the channels, and the endocardial entry points were closed. CONCLUSIONS: Transmyocardial blood flow does not appear to occur through channels made with the holmium:yttrium-aluminum garnet laser. It remains to be determined whether this is the case with other types of lasers.

Evidence of vascular growth associated with laser treatment of normal canine myocardium.

BACKGROUND: Transmyocardial laser revascularization is a new therapy for patients with refractory angina. Although clinical studies suggest that transmyocardial laser revascularization decreases angina and may improve regional blood flow, the underlying mechanisms are not elucidated. We hypothesized that one mechanism may relate to stimulation of vascular growth in laser-treated regions. METHODS: Transmyocardial laser revascularization channels were made with holmium:yttrium-aluminum garnet or carbon dioxide lasers in eight normal canine hearts; animals were sacrificed 2 to 3 weeks later and examined for vascular density and for evidence of smooth muscle proliferation. RESULTS: The original channels were infiltrated by granulation tissue with associated vascularity. Vascular growth was stimulated immediately surrounding the channel remnant as evidenced by an increase in the number of vessels (approximately twice that of the control region) and an increase in the number of vascular cells staining positive for markers of cellular proliferation. CONCLUSIONS: Transmyocardial laser revascularization leads to local vascular growth as early as 2 weeks after treatment. It remains to be determined whether this mechanism contributes to increased regional blood flow or to clinical benefits associated with this novel form of therapy.

Coronary perfusate composition influences diastolic properties, myocardial water content, and histologic characteristics of the rat left ventricle.

BACKGROUND: Recent studies found that edema, histology, and left ventricular diastolic compliance exhibit quantitative relationships in rats. Edema due to low osmolarity coronary perfusates increases myocardial water content and histologic edema score and decreases left ventricular filling. The present study examined effects of perfusate osmolarity and chemical composition on rat hearts. METHODS: Arrested American Cancer Institute (ACI) rat hearts (4 degrees C) were perfused with different cardioplegia solutions, including Plegisol (289 mOsm/L), dilute Plegisol (172 mOsm/L), Stanford solution (409 mOsm/L), and University of Wisconsin solution (315 mOsm/L). Controls had blood perfusion (310 mOsm/L). Postmortem left ventricular pressure-volume curves and myocardial water content were measured. After glutaraldehyde or formalin fixation, dehydration, and paraffin embedding, edema was graded subjectively. RESULTS: Myocardial water content reflected perfusate osmolarity, being lowest in Stanford and University of Wisconsin solutions (p<0.05 versus other groups) and highest in dilute Plegisol (p<0.05). Left ventricular filling volumes were smallest in dilute Plegisol and Plegisol (p<0.05). Osmolarity was not a major determinant of myocardial edema grade, which was highest with University of Wisconsin solution and dilute Plegisol (p<0.05 versus other groups). CONCLUSIONS: Perfusate osmolarity determined myocardial water content and left ventricular filling volume. However, perfusate chemical composition influenced the histologic appearance of edema. Pathologic grading of edema can be influenced by factors other than osmolarity alone.

Iodinated nanoparticles for indirect computed tomography lymphography of the craniocervical and thoracic lymph nodes in normal dogs.

RATIONALE AND OBJECTIVES: We evaluated the imaging characteristics of an interstitially or intraperitoneally delivered iodinated particulate contrast agent for computed tomography (CT) lymphography of the craniocervical and thoracic lymph nodes. METHODS: We injected 2-4 ml of 15% wt/vol iodinated nanoparticle suspension subcutaneously, submucosally, or intraperitoneally in eight normal dogs. CT and plain radiographic images were obtained prior to contrast administration and 4 hr, 24 hr, and 7 days after injection. Correlation was made to detailed postmortem assessment. RESULTS: CT images showed enhancement of regional nodes draining injection sites. Mean attenuation of opacified nodes was 313 +/- 297 (mean +/- standard deviation), 536 +/- 453, and 492 +/- 372 Hounsfield units at 4 hr, 24 hr, and 7 days postinjection, respectively. Lymph node opacification on CT images correlated well with node location found at postmortem. CONCLUSION: Craniocervical and thoracic lymph nodes can be effectively opacified from interstitial or intraperitoneal delivery of this iodinated nanoparticulate contrast agent.

Fine needle aspiration biopsy of intramammary neurilemoma.

A case of benign neurilemoma (schwannoma) arising in the breast is presented, including the fine needle aspiration (FNA) biopsy findings. The aspirate yielded a cellular smear composed of clusters of spindle-shaped cells showing minimal atypia. The absence of mitotic figures and breast epithelium suggested a benign neoplasm. The final diagnosis was established on the excised mass by histopathologic study and the use of special stains. The utility and pitfalls of FNA biopsy in diagnosing this rare entity are discussed.

Fine needle aspiration biopsy diagnosis of mucoepidermoid carcinoma. Statistical analysis.

Fine needle aspiration (FNA) biopsy is an increasingly popular method for the evaluation of salivary gland tumors. Of the common salivary gland tumors, mucoepidermoid carcinoma is probably the most difficult to diagnose accurately by this means. A series of 96 FNA biopsy specimens of salivary gland masses, including 34 mucoepidermoid carcinomas, 51 other benign and malignant neoplasms, 7 nonneoplastic lesions and 4 normal salivary glands, were analyzed in order to identify the most useful criteria for diagnosing mucoepidermoid carcinoma. Thirteen cytologic criteria were evaluated in the FNA specimens, and a stepwise logistic regression analysis was performed. The three cytologic features selected as most predictive of mucoepidermoid carcinoma were intermediate cells, squamous cells and overlapping epithelial groups. Using these three features together, the sensitivity and specificity of accurately diagnosing mucoepidermoid carcinoma were 97% and 100%, respectively.

Exercise-induced pulmonary haemorrhage in the horses: results of a detailed clinical, post mortem and imaging study. VII. Ventilation/perfusion scintigraphy in horses with EIPH.

Detailed post mortem examination of the lungs of horses with exercise-induced pulmonary haemorrhage (EIPH) has demonstrated significant small airway disease and intense bronchial arterial proliferation in the dorsocaudal lungfields. The purpose of this study was to investigate ventilation and perfusion distribution in the lungs of a similar group of horses to compare changes in the live animal with the previously reported post mortem findings. Thoracic radiography and ventilation/perfusion (V/Q) scintigraphy were performed on five racing Thoroughbreds with recent histories of EIPH. Parametric images of V/Q ratios for left and right lungfields were also generated from the scan images. In all horses, ventilation and perfusion deficits were demonstrated in the dorsocaudal areas of the lung corresponding closely to the observed radiographic lesions. In particular, the perfusion images and V/Q ratio displays indicated that, in affected areas of lung, pulmonary arterial perfusion was the more seriously impaired. This finding appears to confirm the post mortem evidence of reduced pulmonary arterial perfusion and bronchial arterial dominance in these areas. Ventilation deficits in the same areas also confirmed the likelihood of partial airway obstruction consistent with the small airway disease noted in previous post mortem observations. These results suggest that the vascular and airway lesions demonstrated in detailed post mortems of horses with EIPH are also functionally important in affected horses, even at rest. As a consequence of the apparent persistent, insidious and progressive nature of the lesions associated with EIPH there are serious long term implications for management of the condition.