PAI-1 deficiency attenuates the fibrogenic response to ureteral obstruction

BACKGROUND: Progressive renal disease is characterized by the induction of plasminogen activator inhibitor-1 (PAI-1), suggesting that impaired activity of the renal plasmin cascade may play a role in renal fibrosis. METHODS: To test this hypothesis, the severity of renal fibrosis caused by unilateral ureteral obstruction (UUO) was compared in PAI-1 wild-type (+/+) and PAI-1 deficient (-/-) mice. The extent of interstitial inflammation and fibrosis, renal plasminogen activator and plasmin activity, and renal expression of profibrotic genes was evaluated after 3, 7, and 14 days of UUO. RESULTS: Renal PAI-1 mRNA levels increased 8- to 16-fold in the +/+ mice after UUO surgery, and PAI-1 protein was detected in kidney homogenates. Interstitial fibrosis was significantly attenuated in -/- mice compared with +/+ mice at day 7 and day 14, based on the interstitial area stained with picrosirius red and total kidney collagen content. However, neither the mean renal plasminogen activator nor plasmin activities were increased in -/- mice compared with +/+ mice. The number of interstitial macrophages were significantly lower in the -/- mice three and seven days after UUO; interstitial myofibroblasts were significantly fewer at three days. At the same time points, this altered interstitial cellularity was associated with a significant reduction in renal mRNA levels for transforming growth factor-beta and procollagens alpha 1(I) and alpha 1(III). CONCLUSIONS: These studies establish an important fibrogenic role for PAI-1 in the renal fibrogenic response. The results demonstrate that one important fibrosis-promoting function of PAI-1 is its role in the recruitment of fibrosis-inducing cells, including myofibroblasts and macrophages.     

Asymptomatic fistula from a giant aneurysmatic left anterior descending artery to the right ventricular outflow tract

Coronary artery fistulas are unusual congenital or acquired coronary artery abnormalities in which blood is shunted into a cardiac chamber, great vessel or other structure, bypassing the myocardial capillary network (Jung et al. in Cardiovasc Ultrasound 5:10, 2007). We present a young adult patient with an asymptomatic fistula from a giant aneurysmatic left anterior descending artery to the right ventricular outflow tract, first diagnosed by echocardiography examination and further confirmed by 128-slice computed tomography coronary angiography.     

Dysphagia in Head and Neck Cancer Patients Treated with Chemoradiotherapy

Dysphagia is a very common complaint of head and neck cancer patients and can exist before, during, and after chemoradiotherapy. It leads to nutritional deficiency, weight loss, and prolonged unnatural feeding and also has a major potential risk for aspiration. This has a significant negative impact on the patient’s entire quality of life. Because treatment of dysphagia in this setting is rarely effective, prevention is paramount. Several strategies have been developed to reduce dysphagia. These include swallowing exercises, treatment modification techniques such as intensity-modulated radiotherapy, selective delineation of elective nodes, reducing xerostomia by parotid-sparing radiotherapy, and adding of radioprotectors. However, more research is needed to further decrease the incidence of dysphagia and improve quality of life.     

Reproducibility of Standing Posture for X-Ray Radiography: A Feasibility Study of the <Emphasis Type="Italic">BalancAid</Emphasis> with Healthy Young Subjects

Unreliable spinal X-ray radiography measurement due to standing postural variability can be minimized by using positional supports. In this study, we introduce a balancing device, named BalancAid, to position the patients in a reproducible position during spinal X-ray radiography. This study aimed to investigate the performance of healthy young subjects’ standing posture on the BalancAid compared to standing on the ground mimicking the standard X-rays posture in producing a reproducible posture for the spinal X-ray radiography. A study on the posture reproducibility measurement was performed by taking photographs of 20 healthy young subjects with good balance control standing on the BalancAid and the ground repeatedly within two consecutive days. We analyzed nine posterior–anterior (PA) and three lateral (LA) angles between lines through body marks placed in the positions of T3, T7, T12, L4 of the spine to confirm any translocations and movements between the first and second day measurements. No body marks repositioning was performed to avoid any error. Lin’s CCC test on all angles comparing both standing postures demonstrated that seven out of nine angles in PA view, and two out of three angles in LA view gave better reproducibility for standing on the BalancAid compared to standing on the ground. The PA angles concordance is on average better than that of the LA angles.     

Matching Capacity to Demand: A Regional Dashboard Reduces Ambulance Avoidance and Improves Accessibility of Receiving Hospitals

Objectives: Ambulance diversion is a dangerous repercussion of emergency department (ED) crowding and can reflect fragmentation and a lack of coordination in designating optimal patient offload sites for prehospital providers. The objective of this study was to evaluate whether proactive destination selection through the Regional Emergency Patient Access and Coordination (REPAC) program would enhance capacity and ED flow management. Methods: The REPAC system provides a dashboard that synthesizes real‐time capacity and acuity data for all three adult EDs in the city of Calgary, assigning a color code to reflect receiving status. It assigns destination for the next patient transported by emergency medical services (EMS) by categorizing ED sites as having either a favorable (green/yellow) status or unfavorable (orange/red) status. Three time windows were analyzed: a 6‐month window prior to REPAC implementation (pre), the first 6‐month window immediately following (post1), and the second 6‐month period following (post2). Primary outcomes of interest were the proportion of time spent in favorable versus unfavorable status and EMS avoidances for all adult ED sites in the region (percentage of total time with any center on EMS bypass). Information on total number of ED visits, percentage of patients arriving by EMS transports, admission rates, patient acuity (Canadian Triage and Acuity Score), age, and length of stay (LOS) for admitted and discharged patients was collected. The Kruskal‐Wallis test was employed for primary outcome analysis. Results: Implementation of the REPAC system resulted in an increase in the proportion of total time region hospitals reported favorable status (57.5% vs. 64.1%) pre versus post1, an effect that was accentuated at 1 year (post2, 78.7%; p < 0.001 for both comparisons). There was a concomitant decrease in EMS avoidances as a result of the REPAC system, 4.4% to 1.8% (pre vs. post1), also further improved at 1 year to 0.6% (p < 0.001 for both comparisons). Conclusions: Proactive EMS destination selection through a real‐time integrated electronic surveillance system enhances regional capacity and flow management while significantly reducing ambulance diversions. ACADEMIC EMERGENCY MEDICINE 2010; 17:1383–1389 © 2010 by the Society for Academic Emergency Medicine     

Questionnaire to Assess Relevance and Credibility of Modeling Studies for Informing Health Care Decision Making: An ISPOR-AMCP-NPC Good Practice Task Force Report

The evaluation of the cost and health implications of agreeing to cover a new health technology is best accomplished using a model that mathematically combines inputs from various sources, together with assumptions about how these fit together and what might happen in reality. This need to make assumptions, the complexity of the resulting framework, the technical knowledge required, as well as funding by interested parties have led many decision makers to distrust the results of models. To assist stakeholders reviewing a model’s report, questions pertaining to the credibility of a model were developed. Because credibility is insufficient, questions regarding relevance of the model results were also created. The questions are formulated such that they are readily answered and they are supplemented by helper questions that provide additional detail. Some responses indicate strongly that a model should not be used for decision making: these trigger a “fatal flaw” indicator. It is hoped that the use of this questionnaire, along with the three others in the series, will help disseminate what to look for in comparative effectiveness evidence, improve practices by researchers supplying these data, and ultimately facilitate their use by health care decision makers.     

Effect of ovarian endometriosis on ovulation in rabbits

To study the relationship between endometriosis and ovulatory dysfunction, we induced ovarian endometriosis in the rabbit model Adipose tissue was placed in the contralateral ovary as a control. Ovulation was induced with human chorionic gonadotropin, and ovulation points were counted before and after induction of endometriosis. Periovarian adhesions were graded, and ovaries were histologically examined. A significant decrease in the number of ovulation points was observed in ovaries with endometrial tissue (p = 0.001) but not in ovaries that contained adipose tissue (p = 0.095). Periovarian adhesions decreased the number of ovulation points (p less than 0.01) in ovaries that contained adipose or endometrial tissues. Multivariate analysis demonstrated that an increase in adhesion severity was correlated with a decrease in the number of ovulation points (p less than 0.05), but endometrial tissue was not (p = 0.45). We conclude that, in the rabbit model, minimal ovarian endometriosis impairs ovulation primarily through a mechanism related to periovarian adhesions.     

Impairment of neutrophil chemotactic and bactericidal function in children infected with human immunodeficiency virus type 1 and partial reversal after in vitro exposure to granulocyte-macrophage colony-stimulating factor

Because polymorphonuclear neutrophils are the most important component of host defense against bacteria, we assessed their function in 13 children with asymptomatic and 12 with symptomatic infection with human immunodeficiency virus type 1 (HIV-1), and compared their values with healthy adult control values. The functions assessed were (1) chemotaxis, (2) bacterial phagocytosis, (3) superoxide generation, and (4) bactericidal activity. Chemotaxis of polymorphonuclear neutrophils toward the chemoattractant N-formylmethionyl leucyl phenylalanine (FMLP) was significantly decreased in symptom-free infected children compared with control subjects (p less than 0.0001), but was increased in children with symptomatic infection (p less than 0.025). Bactericidal activity of the neutrophils against Staphylococcus aureus was defective in 8 of 12 children with asymptomatic infection (p = 0.016), and in 8 of 9 children with symptomatic infection (p less than 0.00001). Superoxide generation by polymorphonuclear neutrophils on stimulation with FMLP and phagocytosis of S. aureus were normal. Serum from patients with symptomatic HIV-1 infection was not as efficient in low concentrations as normal serum in the ability to opsonize S. aureus. The in vitro bactericidal defect was partially corrected by granulocyte-macrophage colony-stimulating factor (GM-CSF). The results suggest that both cellular (neutrophils) and humoral defects contribute to the increased incidence of bacterial infections in HIV-1-infected children, and that GM-CSF may improve the defective bactericidal activity of polymorphonuclear neutrophils in these patients.     

Superficially invasive carcinoma of the vagina following treatment for cervical cancer: A report of six cases

Six patients with superficially invasive squamous carcinoma of the vagina are described. All patients meet recently proposed criteria for the diagnosis of microinvasive vaginal carcinoma. The depth of invasion measured from the surface was less than 2.5 mm. There was no lymph-vascular space involvement. The invasive foci arose within a field of carcinoma in situ. Five of these six patients had previously been treated for invasive cervical cancer with pelvic radiation from 82 to 246 months before the diagnosis of vaginal carcinoma. All but one patient had the carcinoma confined to the upper one-third of the vagina. All patients were treated with a single vaginal radium application following vaginectomy. One of these six patients expired from recurrent vaginal cancer 35 months following diagnosis. During the same 17-year period, 17 other cases of Stage I epidermoid cancer of the vagina were treated which did not meet the above criteria for microinvasion. There were no statistically significant differences between these two groups with regard to age at diagnosis, history of cervical cancer, hysterectomy, or pelvic radiation or in survival. Additional experience with early vaginal carcinoma is needed before microinvasive carcinoma of the vagina should be accepted as a distinct clinical entity.