Robotic surgery does not affect upstaging of T1 renal masses

Partial nephrectomy is the mainstay of treatment for localized kidney cancer. A proportion of patients are upstaged post-operatively to locally advanced di     

Beyond C4d: Other Complement-Related Diagnostic Approaches to Antibody-Mediated Rejection

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor-independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody-mediated injury and T-cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.     

Intracellular trafficking of fluorescently tagged proteins associated with pathogenesis in Candida albicans.

Proteins that enter the secretory pathway play important roles in virulence and pathogenesis in Candida albicans, but our understanding of the trafficking of these proteins is in its early stages. In Saccharomyces cerevisiae, dominant negative alleles of YPT1 and SEC4 interrupt secretory traffic at pre- and post-Golgi steps, respectively. We therefore used a dominant negative genetic approach to examine the intracellular trafficking of several proteins associated with virulence or azole resistance. When the dominant negative ypt1(N121I) allele of C. albicans was overexpressed, yellow-fluorescent protein (YFP) tagged forms of two plasma membrane transporters (Cdrlp and Ftrlp) and the vacuolar membrane ABC transporter Mltlp accumulated in intracellular structures that appeared related to the ER, but localization of Cdc10p and Int1p was unaffected. When the dominant negative sec4(S28N) allele of C. albicans was overexpressed, Cdrlp and Ftrlp accumulated intracellularly, and localization of Mltlp, Cdc10p and Int1p was unaffected. These results imply that (i) Cdrlp and Ftrlp are transported to the plasma membrane by the general secretory pathway, (ii) Mlt1p enters the secretory pathway but is diverted to the vacuole at an early post-Golgi step, and (iii) like Cdc10p, Int1p does not enter the general secretory pathway.     

Combined prostacyclin and thromboxane synthetase inhibitor UK 38485 in flap survival

Thromboxane, a prostanoid derivative, is a central mediator of the progressive dermal ischemia seen in the distal dying flap. Prostacyclin; a vasoactive prostanoid derivative, has been found to enhance ischemic flap survival. This study examines the effects of prostacyclin and UK 38485 (specific thromboxane synthetase inhibitor), separately and combined, in axial flap survival in the pig. Each increased flap survival over control flaps; their combined use demonstrated an even greater flap survival (p less than 0.005).     

Proarrhythmia: a paradoxic response to antiarrhythmic agents

Antiarrhythmic drugs may effectively terminate and prevent symptomatic tachycardias, but they may also provoke life-threatening rhythm disturbances. The electrophysiologic mechanisms responsible for proarrhythmia can be extrapolated from the existing models of reentry and abnormal automaticity. Although all antiarrhythmic drugs may cause proarrhythmia with seemingly similar frequency, the profile of the disturbance with each class of agents appears somewhat distinct. All agents may cause an increased frequency of premature beats or new or worsened ventricular tachycardia, but the classic form of proarrhythmia due to type la agents is torsades de pointes. Recent information has provided clues to the underlying mechanism of drug-induced torsades de pointes and has provided a clinical picture of patients with this adverse effect. Types lb and lc agents only rarely precipitate torsades de pointes. The latter, however, may cause a rapid, sustained, monomorphic ventricular tachycardia in certain high-risk patients that can be resistant to resuscitation efforts. Amiodarone may cause a broad variety of arrhythmias that are complicated by their extended duration and difficulty in distinguishing proarrhythmia from simple inefficacy. Proarrhythmia is a relatively common, paradoxic side effect that necessitates the clinician to make careful risk-benefit decisions in choosing antiarrhythmic drug therapy.     

Effects of controllable vs. uncontrollable stress on circadian temperature rhythms

The effects of sustained stress on body temperature were investigated in rats implanted with mini-transmitters that permitted remote measurement of body temperature. Temperature was first monitored during control conditions. Following the control period, rats were either shaped to avoid/escape signalled around-the-clock intermittent footshock (controllable stress) or yoked to the controlling rats such that the controlling rat and the yoked rat received shock of the same duration, but only the controlling rat could terminate shock by pulling a ceiling chain. Under control conditions, rats demonstrated regular rhythms in body temperature which averaged 1 degree higher during the 12-h dark cycle than the light cycle. Stress disrupted the rhythm and markedly decreased the night-day difference in temperature, especially in the yoked rats in which almost no difference between light and dark cycle temperature was seen. The disruption was most marked for the first days of stress. A regular temperature rhythm was reestablished following about 5 days of stress although the stress condition continued. Leverpressing for food was also affected by the stress conditions with both stress groups leverpressing less than controls and the uncontrollable stress group pressing less than the controllable stress group. These data offer additional evidence of the increased pathophysiological effects of uncontrollable as compared to controllable stress.