Vasorelaxation responses to insulin in laminar vessel rings from healthy, lean horses.

Hyperinsulinemia causes laminitis experimentally and is a risk factor for naturally occurring laminitis. The aim of this study was to investigate the effects of insulin on laminar vascular relaxation and to induce insulin-associated vascular dysfunction in vitro. Relaxation responses of isolated laminar arterial and venous rings to acetylcholine and insulin were evaluated. To alter vascular function in response to insulin, all vessel rings were incubated with insulin or vehicle, submaximally contracted, administered insulin again and relaxation responses recorded. Laminar arteries were also incubated with the mitogen-activated protein kinase (MAPK) inhibitor, PD-98059. Relaxation in response to acetylcholine was not different between arteries and veins, but veins relaxed less in response to insulin than arteries. In arteries incubated with insulin, the subsequent relaxation response to insulin was blunted. Veins had minimal relaxation to insulin regardless of incubation. Arteries incubated with PD-98059 relaxed more in response to insulin than arteries not exposed to PD-98059, indicating that MAPK plays a role in maintenance of basal tone in laminar arteries. A differing response of laminar veins and arteries to insulin-induced relaxation may be important in understanding the link between hyperinsulinemia and laminitis. In vitro induction of vascular dysfunction in response to insulin in laminar arteries may be useful for testing therapeutic interventions and for understanding the pathophysiology of laminitis.

Increased expression of MAIL, a cytokine-associated nuclear protein, in the prodromal stage of black walnut-induced laminitis.

REASONS FOR PERFORMING STUDY: The mediators and signalling cascades important in the initiation of laminitis remain unclear. We therefore wanted to explore the genes and overall signalling mechanisms that play an important role in the developmental stage of laminitis. OBJECTIVE: To use a broad genomic screening technique to identify novel genes that are differentially regulated in the equine lamellae during the developmental period of laminitis. METHODS: Differential mRNA display (DRD) was performed to discover regulated genes, and real-time quantitative polymerase chain reaction (RT-qPCR) was then used to evaluate lamellar mRNA levels of a regulated gene (MAIL) and mediators related to that gene (IL-1beta and IL-6) in control horses (n = 5) and horses administered black walnut extract (BWE; n = 5). RESULTS: Using DRD, MAIL was identified as a regulated gene. RT-qPCR indicated a 4-fold increase in expression of the MAIL mRNA in BWE lamellae compared to controls. A 30-fold increase in IL-1beta, and a 160-fold difference in IL-6 mRNA expression was present in BWE lamellae. Differences in MAIL, IL-1beta and IL-6 mRNA expression were statistically significant between groups (P < 0.05). CONCLUSIONS AND POTENTIAL RELEVANCE: The data strongly support a role for inflammatory cytokines in the developmental stages of laminitis, possibly inducing the vascular and metabolic alterations reported to occur in the affected digit. These results potentially support the use of anti-inflammatory drugs in horses at risk of laminitis, and warrant further investigation of the link between systemic disease processes associated with laminitis and the reported digital inflammation.

Contact-tip Nd:YAG laser applications: squamous nasal papillomatosis.

Concurrent use of nasal endoscopes and the contact-tip Nd:YAG laser provides the necessary visualization and control for treating a widespread condition such as nasal papillomatosis. This laser should decrease the likelihood of spread to other sites within the patient's upper respiratory tract or to attending health care personnel.

Perilymphatic fistulas.

The oft-quoted dictum that clinical suspicion rather than any specific test leads to the diagnosis is confirmed by our study. Further work is needed to define the vestibular findings more precisely and to work out relationships between CSF and perilymph pressures. Temporal bone study will be necessary to document the double membrane break theory. Future study may include analysis of suspected fistula fluid to determine if it represents a mixture of perilymph and endolymph. From our study, fistulae may occur from minimal or no trauma. The presentation is usually subtle. Because no diagnostic test is available to assure correct diagnosis, one must maintain a high index of suspension. Diagnosis usually cannot be made until the ear is surgically explored. The low morbidity of an exploratory tympanotomy, coupled with the high positive to negative ratio of exploration and the high degree of successful results, leads the authors to encourage exploration. Indeed, the overall concensus is that many active fistulae remain undiagnosed because of the lack of suspension and the reluctance to explore an ear without a concrete preoperative diagnosis. The duration of the fistulae and the recurrent nature of the problem poses another diagnostic dilemma. The first positive exploratory tympanotomy for perilymphatic fistula often leaves the surgeon with a dichotomy of emotion from pride of a correct diagnosis to fear that perhaps his observations of the minute clear fluid seepage was an error. Reversal of patient symptoms quickly erases such fears and presumptive diagnosis of perilymphatic fistula becomes easier to make. Eventually, one begins to worry, "How many have I missed."