Mechanism of the effect of coronary artery stenosis on coronary flow in the dog

The hemodynamic mechanism of the effect of coronary artery stenosis on coronary flow was studied in the circumflex artery of 10 open-chest dogs by simultaneously measuring coronary flow, aortic pressure, and coronary artery pressure distal to an adjustable constrictor; while the distal coronary bed was intermittently maximally vasodilated by intracoronary injections of angiographic contrast media (Hypaque-M, 75 per cent). For each stenosis, the pressure gradient across the stenosis varied directly with the flow through the stenosis (r = 0.99), the slope of the regression indicating the severity of the stenosis. An important observation was that this regression line did not intercept the flow axis at zero flow, but at a positive flow, meaning that for a given regression line slope the pressure gradient was much less than expected. At rest, distal bed resistance decreased as progressive stenosis lowered the distal bed pressure, maintaining flow at control level until the distal bed pressure dropped below 60 mm. Hg. However, at maximum hyperemia, distal bed resistance was at a fixed minimum value such that flow was directly proportional to distal bed pressure. Hence, progressive stenosis decreased the ratio of hyperemic to resting flow by: (1) causing the vasodilatory reserve to be used to maintain resting flow, decreasing that available for hyperemia, and (2) dropping the distal bed pressure relatively more for smaller increases in flow. This study provides a hemodynamic explanation for the known fact that progressive stenosis initially limits the maximum hyperemic flow, and only after this flow is decreased almost to resting level, does resting flow fall.     

Do Live Discharge Rates Increase as Hospices Approach Their Medicare Aggregate Payment Caps?

Context

The rate of live discharge from hospice and the proportion of hospices exceeding their aggregate caps have both increased for the last 15 years, becoming a source of federal scrutiny. The cap restricts aggregate payments hospices receive from Medicare during a 12-month period. The risk of repayment and the manner in which the cap is calculated may incentivize hospices coming close to their cap ceilings to discharge existing patients before the end of the cap year.

Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study

OBJECTIVES: The causes of death among HIV-positive patients may have changed since the introduction of highly active antiretroviral therapy (HAART). We investigated these changes, patients who died without an AIDS diagnosis and factors relating to pre-AIDS deaths. METHODS: Analyses of 1826 deaths among EuroSIDA patients, an observational study of 8556 patients. Incidence rates of pre-AIDS deaths were compared to overall rates. Factors relating to pre-AIDS deaths were identified using Cox regression. RESULTS: Death rates declined from 15.6 to 2.7 per 100 person-years of follow-up (PYFU) between 1994 and 2001. Pre-AIDS incidence declined from 2.4 to 1.1 per 100 PYFU. The ratio of overall to pre-AIDS deaths peaked in 1996 at 8.4 and dropped to < 3 after 1998. The adjusted odds of dying following one AIDS defining event (ADE) increased yearly (odds ratio, 1.53; P < 0.001), conversely the odds of dying following three or more ADE decreased yearly (odds ratio, 0.79; P < 0.001). The proportion of deaths that followed an HIV-related disease decreased by 23% annually; in contrast there was a 32% yearly increase in the proportion of deaths due to known causes other than HIV-related or suicides. Injecting drug users (IDU) were significantly more likely to die before an ADE than homosexuals (relative hazard, 2.97; P < 0.0001) and patients from northern/eastern Europe (relative hazard, 2.01; P < 0.0001) were more likely to die pre-AIDS than southern patients. CONCLUSIONS: The proportion of pre-AIDS deaths increased from 1994 to 2001; however, the incidence of pre-AIDS deaths and deaths overall declined. IDU and subjects from northern/eastern Europe had an increased risk of pre-AIDS death. HIV-positive patients live longer therefore it is essential to continue to monitor all causes of mortality to identify changes.     

Occlusion of the Modified Blalock–Taussig Shunt: Unique Methods of Treatment and Review of Catheter‐based Intervention

Objective. To report unique methods of treatment and review catheter‐based intervention for occluded modified Blalock–Taussig shunts (BTS). Methods. Case reports and articles involving children undergoing catheter‐based treatment for occluded modified BTS were reviewed. Results. Literature review detailed 38 patients in whom occluded modified BTS were treated with 39 catheter‐based interventions. Thrombolytics alone were delivered by catheter in 13 cases. Balloon angioplasty was performed in 23 cases, 5 with stent implantation. Both thrombolytic delivery and angioplasty were performed in 3 cases, 2 with stent implantation. Intervention was initially successful at re‐establishing modified BTS patency in 35/39 (90%) of cases. Patency could not be established in 2 patients who then proceeded to the operating for surgical shunt revision. Two deaths occurred during the procedures. Three cases at Emory University demonstrate uncommon or unique instances of catheter‐based intervention: (1) declotting of a shunt in a patient supported by extracorporeal membrane oxygenation (ECMO); (2) declotting of a shunt via a right axillary arterial approach; and (3) declotting of a shunt using a carotid arterial (ECMO) cannula for percutaneous access. Conclusions. The use of catheter‐based techniques for the treatment of BTS occlusion is highly successful, and potentially avoids high‐risk re‐operative intervention. ECMO can provide for a stable patient during the procedure. Hopefully, with improved technology and innovative procedures, more children in the future with BTS occlusion can be served by successful percutaneous intervention.     

Myocardial micronecrosis produced by microsphere embolization. Role of an alpha-adrenergic tonic influence on the coronary microcirculation

Microspheres approximately 25 or 50 micrometers in diameter were systemically embolized from the left ventricular cavity. The number of microspheres given was empirically chosen to minimize the possibility of more than one microsphere lodging in an arteriole (3 mg/kg), yet was sufficient to allow for adequate histological assessment. The dogs were sacrificed after 24 hours, and focal areas of myocytolytic necrosis were noted in the myocardium. Groups of dogs were given pretreatment with drugs 10 minutes before embolization. Dogs pretreated with phentolamine (n = 8) and prazosin (n = 2) did not reveal any areas of myocardial necrosis after embolization with 25-micrometers microspheres. Cardiac lesions were also prevented in four of five dogs pretreated with verapamil. In contrast, cardiac lesions were not prevented by pretreatment with yohimbine (n = 2), dipyridamole (n = 3), propranolol (n = 2), or atropine (n = 2). Drug pretreatment with phentolamine or verapamil was not able to prevent cardiac lesions after embolization with 50-micrometers microspheres. Furthermore, despite a greater number of microspheres physically present in the subendocardial layer, the necrotic lesions were more frequent in the mid-wall and epicardial layers. Lesions produced by 25- or 50-micrometers emboli were also significantly smaller in the endocardium. Systemic embolization with microspheres excluding the coronary circulation did not produce cardiac lesions. We conclude that mechanical interruption of the coronary circulation with a 25-micrometers microsphere may be a necessary but not sufficient condition to produce cardiac necrosis. An alpha 1-adrenergic mechanism is also involved in the production of these lesions.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository

The National Institutes of Health have placed significant emphasis on sharing of research data to support secondary research. Investigators have been encouraged to publish their clinical and imaging data as part of fulfilling their grant obligations. Realizing it was not sufficient to merely ask investigators to publish their collection of imaging and clinical data, the National Cancer Institute (NCI) created the open source National Biomedical Image Archive software package as a mechanism for centralized hosting of cancer related imaging. NCI has contracted with Washington University in Saint Louis to create The Cancer Imaging Archive (TCIA)—an open-source, open-access information resource to support research, development, and educational initiatives utilizing advanced medical imaging of cancer. In its first year of operation, TCIA accumulated 23 collections (3.3 million images). Operating and maintaining a high-availability image archive is a complex challenge involving varied archive-specific resources and driven by the needs of both image submitters and image consumers. Quality archives of any type (traditional library, PubMed, refereed journals) require management and customer service. This paper describes the management tasks and user support model for TCIA.     

Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial

Recent studies indicate that mindfulness meditation training interventions reduce stress and improve stress-related health outcomes, but the neural pathways for these effects are unknown. The present research evaluates whether mindfulness meditation training alters resting state functional connectivity (rsFC) of the amygdala, a region known to coordinate stress processing and physiological stress responses. We show in an initial discovery study that higher perceived stress over the past month is associated with greater bilateral amygdala-subgenual anterior cingulate cortex (sgACC) rsFC in a sample of community adults (n = 130). A follow-up, single-blind randomized controlled trial shows that a 3-day intensive mindfulness meditation training intervention (relative to a well-matched 3-day relaxation training intervention without a mindfulness component) reduced right amygdala-sgACC rsFC in a sample of stressed unemployed community adults (n = 35). Although stress may increase amygdala-sgACC rsFC, brief training in mindfulness meditation could reverse these effects. This work provides an initial indication that mindfulness meditation training promotes functional neuroplastic changes, suggesting an amygdala-sgACC pathway for stress reduction effects.     

Chemoprevention of colorectal cancer with nonsteroidal anti‐inflammatory drugs

Colorectal carcinoma is one of the commonest solid organ tumors in the world and its prevalence appears to be increasing in Asia. Recently, there has been much interest in various chemotherapeutic agents for the management of this condition, in particular nonsteroidal anti‐inflammatory drugs (NSAIDs). There is a large amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase (COX)‐2 selective inhibitors such as rofecoxib and celecoxib, have a role in the setting of primary and secondary prevention, and adjuvant therapy of both sporadic colorectal carcinoma and familial adenomatous polyposis. This review examines some of this data, as well as the potential problems and limitations of using these agents, particularly in light of the recent withdrawal of rofecoxib.