Management of Respiratory Failure in Hemorrhagic Shock.

Hemorrhagic shock results in acute respiratory failure due to respiratory muscle fatigue and inadequate pulmonary blood flow. Because positive pressure ventilation can reduce venous return and cardiac output, clinicians should use the minimum possible mean airway pressure during assisted or mechanical ventilation, particularly during episodes of severe hypovolemia. Hypoperfusion also worsens dead space fraction. Therefore, clinicians should monitor capnography during mechanical ventilation and recognize that hypercapnia may be treated with fluid resuscitation rather than increasing minute ventilation.

Approach to the Patient with Cough.

Cough is a common presenting symptom for patients in a primary care setting. Chronic cough is defined as a cough lasting for more than 8 weeks. The most common causes of chronic cough are upper airway cough syndrome, asthma, and gastroesophageal reflux disease. Detailed history and physical examination are critical in identifying potential etiologies of cough. When there is no prevailing diagnosis, step-wise empiric trial of medication is a strategic and cost-effective approach. Certain features of chronic cough should provoke an expedited and invasive diagnostic strategy. Effectively treating patients with chronic cough has a high impact on quality of life.

Preponderance of free mediator in the yeast Saccharomyces cerevisiae.

Biochemical evidence suggesting that the predominant form of Mediator in the yeast Saccharomyces cerevisiae might be one in which the complex is associated with RNA polymerase II to form a holoenzyme has led to the proposition of a holoenzyme-based model for transcription initiation. We report that polymerase-free Mediator, isolated early on during a whole-cell extract fractionation protocol, is in fact the most abundant form of the Mediator complex. The existence of free Mediator would make possible independent recruitment of Mediator and RNA polymerase II to the pre-initiation complex. This is in agreement with reports from in vivo studies of time and spatial independence of Mediator and RNA polymerase II promoter interaction, with current models of pre-initiation complex structure in which promoter DNA upstream of the transcription start site is positioned between Mediator and polymerase, and with the proposed role of Mediator as the major component of the Scaffold complex involved in transcription reinitiation.

Structure of the yeast RNA polymerase II holoenzyme: Mediator conformation and polymerase interaction.

The holoenzyme formed by RNA polymerase II (RNAPII) and the Mediator complex is the target of transcriptional regulators in vivo. A three-dimensional structure of the yeast holoenzyme has been generated from electron microscopic images of single holoenzyme particles. Extensive changes in Mediator conformation required for interaction with RNAPII have been modeled by correlating the polymerase-bound and free Mediator structures. Determination of the precise orientation of the RNAPII in the holoenzyme indicates that Mediator contacts are centered on the RNAPII Rpb3/Rpb11 heterodimer, the eukaryotic homolog of the alpha(2) homodimer involved in transcription regulation in prokaryotes. Implications for the possible mechanism of transcription regulation by Mediator are discussed.