No abstract

Plasma membrane neurotransmitter transporters determine in part the concentration, time course, and diffusion of extracellular transmitter. Much has been learned about how substrate translocation through the transporter occurs; however, the precise way in which transporter structure maps onto transporter function has not yet been fully elucidated. Here, biochemical and electrophysiological approaches were used to test the hypothesis that intracellular domains of the rat brain GABA transporter (GAT1) contribute to the transport process. Injection of a peptide corresponding to the presumed fourth intracellular loop of the transporter (IL4) into oocytes expressing GAT1 greatly reduced both forward and reverse transport and reduced the transport rate in a dose-dependent manner. Coinjection of the IL4 peptide with a peptide corresponding to the N-terminal cytoplasmic tail of GAT1 reversed the IL4-mediated inhibition; this reversal, and direct binding between these two domains, was prevented by mutagenesis of charged residues in either the IL4 or N-terminal domains. Furthermore, syntaxin 1A, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein that inhibits GAT1 transport rates via interactions with the N-terminal tail of GAT1 was unable to regulate the GAT1 IL4 mutant. Together, these data suggest a model in which the GAT1 IL4 domain serves as a barrier for transport, and this barrier can be regulated through intra-molecular and inter-molecular interactions.

The clinical presentation of methicillin-resistant Staphylococcus aureus (MRSA) infection ranges from asymptomatic colonization to cutaneous and invasive involvement. This review discusses the cutaneous presentations of community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA) that one may encounter in the hospital or outpatient setting. Cutaneous CA-MRSA and HA-MRSA are often clinically indistinguishable, although they have different epidemiologic profiles and virulence factors. Bacterial culture is necessary for diagnosis and guides treatment, as infection with CA-MRSA and HA-MRSA require distinct clinical management. Guidelines for surgical interventions and antibiotic treatment of CA-MRSA and HA-MRSA will be discussed. Strategies for MRSA decolonization and prevention of further spread will also be reviewed.

The prevalence of dermatologic disease and its effect on quality of life has not been well studied in patients with advanced illness. We sought to describe skin findings in inpatient palliative care patients and determine how often they are addressed by the primary or palliative care teams. We collected patient demographic and clinical data from the medical record, performed total body skin examinations, and determined how often significant cutaneous findings were documented in the chart. We also characterized skin findings as uncomfortable and treatable. Twenty palliative care patients participated in the study over a 2-month period. Common findings included skin breakdown (20/54; 37%), skin infections (14/54; 26%), inflammatory dermatoses (9/54; 17%), and skin conditions related to systemic disease (7/54; 13%) or treatment of systemic disease (4/54; 7%). Most of these conditions were not documented by primary or palliative care clinicians. Eighty percent of the patients had uncomfortable, but treatable skin conditions of which 62% (13/21) were undocumented or incorrectly documented. These limited data suggest the need for palliative care clinicians to conduct more complete skin examinations, and to improve their knowledge of common skin abnormalities in patients with serious illness. A larger scale investigation of skin disease and its effect on quality of life in the palliative care population is warranted.

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient's case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. A 66-year-old man presented to the Emergency Department (ED) with rash and malaise in early April. He was in his usual state of good health until the morning of presentation, when he awoke feeling lethargic. Over the course of the day, his hands and feet grew cold and numb, his nose became dark red, and he developed a diffuse, net-like red rash over his legs, hands, buttocks, and trunk. He had multiple maroon bowel movements. His wife noted that he became ''incoherent'' and brought him to the ED.This apparently previously healthy man presented with an acute episode of fatigue and altered mental status accompanied by a prominent cutaneous eruption. The differential diagnosis will ultimately be guided by the morphology of the rash. At this stage, infectious diseases, drug or toxin exposure, and allergic processes including anaphylaxis must all be considered in this patient with rash and acute illness. The maroon bowel movements likely represent a gastrointestinal bleed that may be part of a unifying diagnosis-a hematologic disorder, a vasculitis, or liver disease.In the ED, the patient was reportedly febrile (exact temperature not recorded) with a blood pressure of 96/54 mmHg. He had pulse oximetry of 88% on room air and a diffuse purpuric rash. The patient was noted to have a leukocytosis, thrombocytopenia, coagulopathy, and an elevation of his creatinine and cardiac enzymes. He was given fluids, fresh frozen plasma, and broad-spectrum antibiotics, and transferred directly to the intensive care unit of a tertiary medical center for further management.Upon arrival to the intensive care unit, he complained of fatigue, progression of his nonpruritic, nonpainful rash, and worsening numbness and tingling of his extremities. He denied headache, nuchal rigidity, photophobia, vision or hearing changes, chest pain, cough, abdominal pain, myalgias, or arthralgias. While being interviewed, he had dark brown emesis and a bloody bowel movement.The patient's past medical history included bacterial pericarditis as a teenager and remote hepatitis of unclear etiology. He rarely saw a physician, took no medications, and had no known medication allergies.