Accuracy of formulae for calculating left ventricular volumes of the equine heart

Echocardiography may be an accurate method of measuring left ventricular (LV) volumes and mass of the horse's heart. If so, studies of the heart size and hypertrophy would be possible. This study evaluated geometric models of the external and internal LV shapes, to determine which could be applied to echocardiographic measurements. We preserved 30 horses' hearts and measured their dimensions and cross sectional areas. These measurements were entered into seven formulae representing different geometric models of the ventricle and its chamber. We derived a correction factor to estimate the long axis as a fixed proportion of the external diameter, so that volumes could be determined from an M-mode or a cross sectional echocardiogram. Statistical analysis of the regressions of known volumes against calculated volumes measured by water displacement, demonstrated that the ellipsoid formula using cross sectional areas was very accurate in representing the external shape of the left ventricle (slope = 1.01 r2 = 96.3) and its chamber (slope = 0.83, r2 = 94.3). Myocardial volume, measured by subtracting internal (chamber) volume from external volume, was also calculated accurately (slope = 1.01, r2 = 96.5). The ellipsoid formula using directly measured diameter was only slightly less accurate. LV mass could be calculated by applying the specific gravity of equine myocardium, 1.05, to the myocardial volume. Formulae recommended for evaluating are, with M-mode echocardiography: [equation: see text] and with 2D echocardiography [equation: see text] where De is the external diameter, Di is the internal diameter, Ae the external area and Ai the internal area.     

Compensation for decreased expression of B7 molecules on Leishmania infantum-infected canine macrophages results in restoration of parasite-specific T-cell proliferation and gamma interferon production

Infection of humans and dogs by Leishmania infantum may result in visceral leishmaniasis, which is characterized by impaired T-cell-mediated immune responses to parasite antigens. Dogs are natural hosts of Leishmania parasites and play an important role in the transmission of the parasites to humans. In an effort to characterize the immune response in dogs infected with this intracellular pathogen, we examined how infection with L. infantum affects canine macrophages and the consequences for T-cell activation in vitro. We showed that the proliferation of T-cell lines to cognate antigen decreases to background levels when infected autologous monocyte-derived macrophages are used as antigen-presenting cells (APC). The observed reduction of antigen-specific T-cell proliferation was shown to be dependent on the parasite load and to require cell-to-cell interaction of T cells with the infected APC. In addition, we observed a decreased expression of costimulatory B7 molecules on infected monocyte-derived macrophages. The expression of other surface molecules involved in T-cell activation, such as major histocompatibility complex class I and class II, on these cells did not change upon infection, whereas the expression of intracellular adhesion molecule 1 was marginally increased. Compensation for the decreased expression of B7 molecules by the addition of B7-transfected cells resulted in the restoration of cell proliferation and gamma interferon (IFN-gamma) production by a Leishmania-specific T-cell line. These results showed that for the activation of parasite-specific canine T cells producing IFN-gamma, which are most likely involved in protective immunity, sufficient expression of B7 molecules on infected macrophages is required. Provision of costimulatory molecules may be an approach for immunotherapy of leishmaniaisis as well as for vaccine development.     

Conservative surgical therapy for penile and urethral carcinoma

OBJECTIVES: Invasive penile and urethral tumors are traditionally treated with aggressive excision that requires involved organ and adjacent organ sacrifice. An alternative approach seeks to completely excise the tumor with adequate margins while preserving form and function of the organ. We present 6 patients who underwent such organ-sparing surgery. METHODS: Six selected cases (4 penile and 2 urethral) are presented with operative photographs and pertinent data. RESULTS: Three distal tumors of the penis were treated with excision limited to the glans with histopathologic findings of verrucous carcinoma, melanoma, and angiosarcoma. One patient with squamous cell carcinoma of the distal shaft refused partial penectomy and underwent a local wedge resection. A patient with locally advanced bulbourethral transitional cell carcinoma (TCC) refused cystourethrectomy and underwent an anterior urethrectomy and perineal urethrostomy. A 48-year-old woman with an adenocarcinoma contained in a very distal urethral diverticulum underwent simple diverticulectomy and excision of distal urethra. Postoperative voiding and sexual function were well preserved. Follow-up was 12 to 48 months. The patient with angiosarcoma died of lung metastases at 48 months with no local disease, and the patient with bulbourethral TCC developed pelvic disease at 12 months with no local recurrence and died of metastases at 25 months. CONCLUSIONS: Organ-sparing surgery is appropriate in selected patients on the basis of stage and location, high risk of distant failure, and patient disposition. Close follow-up is necessary. Comanagement with reconstructive and oncologic specialists optimizes results and outcomes.     

Significance of lymph node sampling in epithelial carcinoma of the ovary

Dendritic cells (DC) are a subset of leukocytes whose major function is antigen presentation. We investigated the phenotype and function of enriched (95-98.5%) rat DC. We show that both spleen and thymus DC express the natural killer cell receptor protein 1 (NKR-P1) as a disulfide linked homodimer of 60 kD. Freshly isolated DC express a low level of NKR-P1, which is strongly upregulated after overnight culture. Spleen, but not thymus DC, were able to kill the NK-sensitive YAC-1 cell line in vitro, and since this killing was Ca2+ dependent, a Fas ligand-Fas interaction was probably not involved. Besides their potent antigen-presenting function, DC can thus be cytotoxic for some tumor targets.     

Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic nonseminomatous germ cell tumor: multivariate analysis of individual patient data from six study groups

PURPOSE: To develop a statistical model that predicts the histology (necrosis, mature teratoma, or cancer) after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT). PATIENTS AND METHODS: An international data set was collected comprising individual patient data from six study groups. Logistic regression analysis was used to estimate the probability of necrosis and the ratio of cancer and mature teratoma. RESULTS: Of 556 patients, 250 (45%) had necrosis at resection, 236 (42%) had mature teratoma, and 70 (13%) had cancer. Predictors of necrosis were the absence of teratoma elements in the primary tumor, prechemotherapy normal alfa-fetoprotein (AFP), normal human chorionic gonadotropin (HCG), and elevated lactate dehydrogenase (LDH) levels, a small prechemotherapy or postchemotherapy mass, and a large shrinkage of the mass during chemotherapy. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > .20), which discriminated necrosis well from other histologies (area under the receiver operating characteristic (ROC) curve, .84), but which discriminated cancer only reasonably from mature teratoma (area, .66). Internal and external validation confirmed these findings. CONCLUSION: The validated models estimate with high accuracy the histology at resection, especially necrosis, based on well-known and readily available predictors. The predicted probabilities may help to choose between immediate resection of a residual mass or follow-up, taking into account the expected benefits and risks of resection, feasibility of frequent follow-up, the financial costs, and the patient's individual preferences.     

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

This review highlights recent research on the properties and functions of the enzyme transketolase, which requires thiamin diphosphate and a divalent metal ion for its activity. The transketolase-catalysed reaction is part of the pentose phosphate pathway, where transketolase appears to control the non-oxidative branch of this pathway, although the overall flux of labelled substrates remains controversial. Yeast transketolase is one of several thiamin diphosphate dependent enzymes whose three-dimensional structures have been determined. Together with mutational analysis these structural data have led to detailed understanding of thiamin diphosphate catalysed reactions. In the homodimer transketolase the two catalytic sites, where dihydroxyethyl groups are transferred from ketose donors to aldose acceptors, are formed at the interface between the two subunits, where the thiazole and pyrimidine rings of thiamin diphosphate are bound. Transketolase is ubiquitous and more than 30 full-length sequences are known. The encoded protein sequences contain two motifs of high homology; one common to all thiamin diphosphate-dependent enzymes and the other a unique transketolase motif. All characterised transketolases have similar kinetic and physical properties, but the mammalian enzymes are more selective in substrate utilisation than the nonmammalian representatives. Since products of the transketolase-catalysed reaction serve as precursors for a number of synthetic compounds this enzyme has been exploited for industrial applications. Putative mutant forms of transketolase, once believed to predispose to disease, have not stood up to scrutiny. However, a modification of transketolase is a marker for Alzheimer's disease, and transketolase activity in erythrocytes is a measure of thiamin nutrition. The cornea contains a particularly high transketolase concentration, consistent with the proposal that pentose phosphate pathway activity has a role in the removal of light-generated radicals.     

Histamine release from rat mast cells induced by the metabolic activation of drugs of abuse into free radicals

Techniques such as positron-emission tomography, single-photon-emission computed tomography, functional magnetic-resonance imaging and magnetoencephalography permit the observation of biological processes in the brain in a noninvasive manner. They have yielded new insights into the biological interrelations of sensory, motor and cognitive functions, as well as into brain diseases. Combined use of these techniques may provide more information than just the sum of its constituents, and this may narrow the gap between the biological data provided by these techniques and the mental models described by clinicians, mathematicians, psychologists and philosophers.     

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.