Bernadette Dunham

Gap junctional channels in adult mammalian sinus nodal cells. Immunolocalization and electrophysiology.

The subcellular mechanism of cell-to-cell communication in the natural pacemaker region of the mammalian heart was studied using electrophysiological and immunofluorescence techniques in isolated pairs of rabbit sinus nodal cells. By measuring whole-cell currents using a double patch-clamp approach, it was demonstrated that communication in the sinus node is mediated through gap junctional channels similar to those in other types of adult cardiac cell pairs. Macroscopic sinus nodal junctional resistance had a mean value of 387.9 +/- 97.1 M omega (mean +/- SEM, n = 10) and was greatly increased by superfusion with alkanols. Single-channel junctional conductance could be resolved in three cell pairs. Given their high membrane resistance (1.16 +/- 0.32 G omega, n = 12), the electrical coupling provided by as few as three gap junctional channels between nodal cells will allow for pacemaker synchronization. Further evidence for the presence of the channels was obtained from immunofluorescent double-labeling of desmin and the gap junction protein (connexin43) in sinus nodal tissue as well as in cultured sinus nodal cells. Using antisera against residues 243-257 of the connexin43 protein, a specific staining at the site of cell-to-cell apposition was demonstrated. These data provide direct evidence in favor of electronic coupling as the means for achieving pacemaker synchronization in the rabbit sinus node.

Therapeutic benefits of 5-hydroxytryptamine inhibition following pulmonary embolism.

The smooth muscle-constricting, platelet amine, serotonin (5-hydroxytryptamine; 5-HT) is theorized to play an important role in the cardiopulmonary dysfunction that accompanies embolization. The present study was designed to examine this hypothesis. Autologous clot, 0.75 g/kg, was injected IV into 14 dogs. After 30 minutes, one half of the animals were randomly assigned to the treatment group and received a bolus infusion of 0.15 mg/kg ketanserin, a quinazoline derivative known to be a selective 5-HT receptor antagonist. Five minutes after embolization there were increases in mean pulmonary arterial pressure (MPAP) from 12 mm to 48 mmHg (p < 0.001); pulmonary vascular resistance (PVR) from 2.2 mm to 12.2 mmHg · min/L (p < 0.001); physiologic shunt (QS/QT) from 12% to 44% (p < 0.01); and physiologic dead space (VD/ VT), calculated from end tidal and arterial PCO2, from 8% to 39% (p < 0.001). Within 15 minutes platelet counts decreased from 186,000/mm3 to 134,800/mm3 (p < 0.05); 5-HT contained in circulating platelets fell from 1.71 μg/ to 1.44 μg/ 109 platelets (p < 0.05). Five minutes after ketanserin, MPAP declined to 27 mmHg and was lower than the control value of 41 mmHg (p < 0.05); PVR decreased to 6.2 mmHg · min/L, lower than 12 mmHg-min/L in controls (p < 0.01); QS/QT fell to 26% in contrast to 47% in controls (p < 0.05); and VD/ VT declined moderately to 32% (p < 0.05), although this value was not different from 38% in control animals. Cardiopulmonary function continued to improve in treated animals until termination of the experiment at four hours when pulmonary angiograms and perfusion scans demonstrated vascular recruitment compared with untreated embolized control dogs. These data demonstrate that the cardiopulmonary consequences of experimental embolization are primarily determined by the vasoconstrictive and bronchoconstrictive actions of 5-HT.

Histocytology of lymphoid tumors in the dog, cat and cow.

In a retrospective study of lymphomas in animals, tumors in 72 dogs, 81 cats and 90 cows were classified on the basis of cell size (small, medium and large), nuclear cleavage (follicular center cells), and histologic architecture (nodular or diffuse). Each subtype was classified by age of animal at death, number of metastases, breed, and sex. As in man, nodular cleaved tumors are rare in animals, the cow having the most varied tumor types. There was one cleaved-cell tumor in 72 lymphomas in dogs, 23 of 81 in cats, and 33 of 90 in cows. There were six nodular tumors of 72 in dogs, two of 81 in cats, and eight of 90 in cows. Fifteen of 16 nodular lymphomas had noncleaved cells and twelve had small or predominantly small cells. Cats with nodular lymphomas were older at death than cats with diffuse lymphomas. Nodularity was not associated with greater age at death in dogs and cows. Animals with cleaved-cell lymphomas were older at death than those with noncleaved tumors; this difference was highly significant in cows. The number of metastases was greater with nodular tumors in all three species, and was equal in cleaved and noncleaved tumors. The biological behaviour of lymphoid tumors in animals is similar to those in man when the same criteria of classification are used.

Maintenance of cardiodynamics with aspirin during abdominal aortic aneurysmectomy (AAA).

The importance of prostacyclin (PGI2) and thromboxane (Tx) mediation of depressed cardiac performance during abdominal aortic aneurysm operative surgery was studied by contrasting the effects of 650 mg aspirin administered 12 hours before operation to that of a placebo. In 11 patients who received a placebo, the stable metabolite of PGI2, 6-keto-PGF1a rose from 0.050 ± 0.032ηg/ml to 0.419 ± 0.257 ηg/ml (p < 0.01) 30 minutes after the skin incision. The stable metabolite of TxA2, TxB2 did not increase until the aorta was clamped when TxB2 rose from 0.089 ± 0.054 ηg/ml to 0.193 ± 0.138 ηg/ml (p < 0.05); this was prior to blood transfusion. During aortic clamping cardiac output decreased 27% (p < 0.001). In vitro testing of patient plasma showed: 1) depressed developed tension (Tpd) of a rat papillary muscle by 16% (p < 0.05); 2) reduction of Ca++-ATPase and Mg++-ATPase activity in a rat myocardial subfraction of sarcoplasmic reticulum (p < 0.05); 3) reduction of Ca++-ATPase in a rat myocardial subfraction of myofibrils (p < 0.01). Aspirin administered to 11 patients produced no measurable change in blood loss or fluid requirements. Aspirin lowered preoperative 6-keto-PGF](, and TxB2 levels (p < 0.01) and prevented an increase of either agent during operation. The low Tx levels were associated with a stable cardiac output during aortic clamping. Further, plasma obtained from aspirin-treated patients did not depress papillary muscle contractility nor decrease ATPase activity of either myocardial subfraction. The observation that TxB2 when added to a papillary muscle or myocardial subfractions, did not decrease Tpd or ATPase suggests that TxB2 plays an indirect role in altering cardiac muscle activity. The results indicate that Txs modulate cardiac depression, which can be prevented with 650 mg aspirin before operation

Review of Institute of Medicine and National Research Council Recommendations for One Health Initiative

Human health is inextricably linked to the health of animals and the viability of ecosystems; this is a concept commonly known as One Health. Over the last 2 decades, the Institute of Medicine (IOM) and the National Research Council (NRC) have published consensus reports and workshop summaries addressing a variety of threats to animal, human, and ecosystem health. We reviewed a selection of these publications and identified recommendations from NRC and IOM/NRC consensus reports and from opinions expressed in workshop summaries that are relevant to implementation of the One Health paradigm shift. We grouped these recommendations and opinions into thematic categories to determine if sufficient attention has been given to various aspects of One Health. We conclude that although One Health themes have been included throughout numerous IOM and NRC publications, identified gaps remain that may warrant targeted studies related to the One Health approach.

Renal Dysplasia with Multiple Urogenital and Large Intestinal Anomalies in a Calf

Due to the benign appearance histologically and the tumor’s conflicting malignant behavior, the term multilobular osteosarcoma has clinical and diagnostic significance and should be used exclusively for this canine neopla~ia.~ Metastasis of multilobular osteosarcoma has been reported in one other dog, in which the tumor arose in the occipital bone and metastasized to the lungs.3 We report a primary mandibular site with thoracic metastasis. The mandible is an uncommon site of origin, although invasion of the orbital space by these tumors from other sites has been reported.2 Presumptive diagnosis may be made radiographically, the characteristic feature being a faint stippled appearance within a solitary nodular maw4 Definitive diagnosis is by histologic evaluation; the unique multilobular arrangement of osseous, cartilaginous, or osteocartilaginous tissues surrounded by mesenchymal stroma of variable densities is characteristic of this Histologic features of the reported case demonstrate a previously unreported structural arrangement, in that lobular aggregates were separated by thick collagenous septa into large nodules which often differed in cellular composition from neighboring nodules. Malignant transformation may not be evident histologically, as this case illustrates. While the pulmonary masses demonstrated malignant features histologically, the recurring cranial mass retained its benign morphologic characteristics. The histogenetic origin of multilobular osteosarcoma is unknown, but these tumors may arise from periosteal elements of the membranous bones of the skull. However, reported sites of tumor origin are in bones of the chondro-

Making One Health a Reality—Crossing Bureaucratic Boundaries

A One Health approach requires that nontraditional partners with differing mandates collaborate and communicate effectively. Barriers to such redefined relationships range from personality and institutional cultural and value differences to impediments that require changes in agency-specific policies. This article reviews interagency One Health collaborations, nationally and internationally. It presents a series of case studies that describe situations in which barriers were overcome, thus culminating in successful One Health outcomes. The case studies illustrate challenges, tipping points, and externally enabling factors that help institutionalize cross-bureaucratic working relationships. Likewise, the cases demonstrate the added value of taking a One Health approach to solving (or preventing) public health problems.

Making One Health a reality: crossing bureaucratic boundaries: Chapter 18 in One Health

A One Health approach requires that nontraditional partners with differing mandates collaborate and communicate effectively. Barriers to such redefined relationships range from personality and institutional cultural and value differences to impediments that require changes in agency-specific policies. This article reviews interagency One Health collaborations, nationally and internationally. It presents a series of case studies that describe situations in which barriers were overcome, thus culminating in successful One Health outcomes. The case studies illustrate challenges, tipping points, and externally enabling factors that help institutionalize cross-bureaucratic working relationships. Likewise, the cases demonstrate the added value of taking a One Health approach to solving (or preventing) public health problems.