Stromal progenitor cell therapy corrects the wound-healing defect in the ischemic rabbit ear model of chronic wound repair

Chronic wounds create a formidable clinical problem resulting in considerable morbidity and healthcare expenditure. The etiology for wound healing impairment appears to be multifactorial; however, ischemia is a common factor in most types of chronic wounds. Ideal therapy for such wounds would be to correct deficiencies in growth factors and matrix components and provide cellular precursors required for timely wound closure. We hypothesized that stromal progenitor cell (SPC) therapy could correct the ischemic wound-healing defect through both direct and indirect mechanisms. To test this hypothesis, we used the ischemic rabbit ear model of chronic wound healing. We found that treatment of the wounds with SPCs was able to reverse the ischemic wound-healing impairment, with improved granulation tissue formation and reepithelialization compared with vehicle or bone marrow mononuclear cell controls. In vitro, SPCs were found to produce factors involved in angiogenesis and reepithelialization, and extracellular matrix components, providing evidence for both direct and indirect mechanisms for the observed correction of the healing impairment in these wounds. Treatment of ischemic wounds with SPCs can dramatically improve wound healing and provides a rationale for further studies focused on SPCs as a potential cellular therapy in impaired wound healing.     

End-of-life Models and Emergency Department Care

Many people die in emergency departments (EDs) across the United States from sudden illnesses or injuries, an exacerbation of a chronic disease, or a terminal illness. Frequently, patients and families come to the ED seeking lifesaving or life-prolonging treatment. In addition, the ED is a place of transition-patients usually are transferred to an inpatient unit, transferred to another hospital, or discharged home. Rarely are patients supposed to remain in the ED. Currently, there is an increasing amount of literature related to end-of-life care. However, these end-of-life care models are based on chronic disease trajectories and have difficulty accommodating sudden-death trajectories common in the ED. There is very little information about end-of-life care in the ED. This article explores ED culture and characteristics, and examines the applicability of current end-of-life care models.     

Patient experience with, and use of, an electronic monitoring system to assess vaccination responses

OBJECTIVE: To evaluate the user experience and acceptability of an electronic patient monitoring system. SETTING AND PARTICIPANTS: 822 Military and civilian personnel at a health clinic at a major US military headquarters used an Internet and telephone-based electronic monitoring system to report vaccination-site responses and symptoms after receiving the smallpox vaccination. Focus groups of vaccinees were conducted to help develop a survey about the experience that was distributed to 379 vaccinees (96% completion rate). RESULTS: Users of the electronic monitoring system reported that it was fast and easy to use and reported they would use a system like this again and recommend an electronic monitoring system to a friend or relative. Most users (84%) were comfortable with a physician tracking their vaccine reaction using their electronic reports, but only half (51%) were comfortable with eliminating the post-vaccination follow-up visit with their health-care provider based on their electronic reports. CONCLUSIONS: This electronic monitoring system was well received by vaccinees and allowed health-care providers to track the status of vaccinees. However, vaccinees were not comfortable replacing a physician visit with electronic monitoring, at least for the smallpox vaccination. A monitoring system like this may be useful in public health settings, such as mass vaccination or prophylaxis during a bioterrorism event, a pandemic influenza outbreak, or another public health emergency.     

Early Designs for the Occlusal Anatomy of Posterior Denture Teeth: Part III

Part III of this series of articles, like Part II, reviews the pioneering efforts in the 19th century to improve the quality of artificial teeth. The focus of this article, unlike that of Part II, is specifically modifications in the design of the occlusal anatomy of the 19th century denture teeth, along with the theories of mandibular movement that inspired those modifications. This article concludes the introductory phase of this project, which seeks to unravel the confusing history of the development of (posterior) denture teeth.     

Interaction of permanently charged chlorpromazine and dopamine analogs with the striatal D-1 dopaminergic receptor

Although a structural feature common to all dopaminergic agonists and antagonists is a side-chain basic amino group, it is unclear whether this moiety binds to the D-1 dopamine (DA) receptor in the charged or uncharged form. To obtain information on this point, we synthesized permanently charged dimethylsulfonium and quaternary ammonium analogs of chlorpromazine and DA and determined whether these compounds can bind to the D-1 receptor by measuring their abilities to inhibit the binding of SCH 23390, a D-1 receptor antagonist. Chlorpromazine and the dimethylsulfonium and trimethylammonium analogs of chlorpromazine were found to inhibit the binding of [3H]SCH 22390, which was maximally inhibited to the same extent by all three compounds. In addition, inhibition curves for the compounds fit a one-site binding model, indicating binding to a single class of sites. However, while the permanently charged chlorpromazine analogs were able to inhibit [3H]SCH-23390 binding, they were considerably less potent than chlorpromazine. DA and dimethyl DA were also able to inhibit [3H]SCH 23390 binding. However, the permanently charged dimethylsulfonium and trimethylammonium analogs of DA were ineffective in inhibiting [3H]SCH 23390 binding. In addition, the permanently uncharged methylsulfide analog did not inhibit binding. These studies show that permanently charged analogs of chlorpromazine can bind to the striatal D-1 receptor, which is consistent with an anionic recognition site on the D-1 receptor that interacts with antagonists in the cationic form. In addition, it appears that a nitrogen atom is not required for binding to the D-1 receptor, since the sulfonium analog of chlorpromazine bound to the receptor to the same extent as chlorpromazine. However, since the permanently charged or uncharged analogs of DA did not bind to the D-1 receptor, it is still unclear as to whether the charged form of a dopaminergic agonist can bind. The lower potency or ineffectiveness of the permanently charged analogs compared to the parent amines (chlorpromazine, DA, dimethyl DA) in binding to the D-1 receptor may reflect the inability of the permanently charged analogs to undergo hydrogen binding with the anionic site of the receptor.