Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy for symptomatic choledocholithiasis after recent myocardial infarction

In the general population, endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy is preferable to surgery as therapy for gallstone pancreatitis and acute cholangitis. It is particularly attractive to perform therapeutic. ERCP for symptomatic choledocholithiasis after recent myocardial infarction because of the increased risk of the alternative therapy of cholecystectomy and choledochal exploration. However, after myocardial infarction, patients might theoretically be particularly susceptible to the cardiopulmonary risks of ERCP. The safety of therapeutic ERCP after myocardial infarction is unknown, with only one previously reported case. In a review of 11,367 patients with acute myocardial infarction at four hospitals, four patients (0.04%) underwent therapeutic ERCP after recent myocardial infarction, for indications of recent biliary pancreatitis in three of the patients and recent cholangitis in all four. Cholangitis occurred before, simultaneous with, or after myocardial infarction in the four cases. Initially, the cholangitis was managed medically in three patients. The fourth patient underwent cholecystostomy with local anesthesia. ERCP was performed at 15, 25, 30, or 56 days after myocardial infarction. Endoscopic cholangiography revealed multiple choledocholithiasis in all cases. The calculi were successfully extracted by endoscopic papillotomy and by sweeping the choledochus with a balloon-tipped catheter or basket in all cases. During ERCP, the vital signs remained stable; no cardiac arrhythmias or cardiovascular complications occurred. However, one patient developed mild pancreatitis after ERCP, which rapidly resolved with medical therapy. The four patients rapidly improved after ERCP, with normalization of serum levels of routine biochemical parameters of liver function. These four cases and the one prior case report demonstrate that therapeutic ERCP is not absolutely contraindicated after myocardial infarction and suggest that therapeutic ERCP is preferable to surgery for symptomatic choledocholithiasis after myocardial infarction because of the increased mortality of surgery after myocardial infarction.     

The origin of the Australasian marsupial fauna and the phylogenetic affinities of the enigmatic monito del monte and marsupial mole

Alternative hypotheses in higher-level marsupial systematics have different implications for marsupial origins, character evolution, and biogeography. Resolving the position of the South American monito del monte (Order Microbiotheria) is of particular importance in that alternate hypotheses posit sister-group relationships between microbiotheres and taxa with disparate temporal and geographic distributions: pediomyids; didelphids; dasyuromorphians; diprotodontians; all other australidelphians; and all other marsupials. Among Australasian marsupials, the placement of bandicoots is critical; competing views associate bandicoots with particular Australasian taxa (diprotodontians, dasyuromorphians) or outside of a clade that includes all other Australasian forms and microbiotheres. Affinities of the marsupial mole are also unclear. The mole is placed in its own order (Notoryctemorphia) and sister-group relationships have been postulated between it and each of the other Australasian orders. We investigated relationships among marsupial orders by using a data set that included mitochondrial and nuclear genes. Phylogenetic analyses provide support for the association of microbiotheres with Australasian marsupials and an association of the marsupial mole with dasyuromorphs. Statistical tests reject the association of diprotodontians and bandicoots together as well as the monophyly of Australasian marsupials. The origin of the paraphyletic Australasian marsupial fauna may be accounted for by (i) multiple entries of australidelphians into Australia or (ii) bidirectional dispersal of australidelphians between Antarctica and Australia.     

Developing a CQI program in a family medicine department

BACKGROUND: Efforts to implement continuous quality improvement (CQI) principles in ambulatory or primary care settings still lag behind efforts in the hospital setting. Many physicians view the concept of CQI with unconcealed skepticism; the process of ambulatory care is very different from that of hospital-based care; and the data necessary to guide CQI efforts are often either missing or inaccurate in the outpatient setting. Since fall 1995, the Department of Family Medicine (DFM) at the University of Michigan (Ann Arbor), including approximately 35 faculty members at seven family practice sites, has been engaged in CQI projects. PLANNING AND IMPLEMENTATION: The CQI committee had a six-month deadline to lay out a plan for educating all faculty and staff in the importance of the CQI approach to problems; design methods for all faculty and staff to buy in to the concepts; and develop a plan to address basic clinical CQI activities, administrative systems change and work environment improvement, and larger ad hoc projects in clinical care, educational programs, and research programs. IMPLEMENTATION: CQI activities were incorporated into the routine monthly business agendas at each clinical site, each of which had a functioning local committee and had begun development of at least one CQI project. PROJECTING INTO THE FUTURE AND CONCLUSIONS: Cost cutting has further moved CQI from the sideline to center stage in the DFM's activities. An effective CQI program can be a major asset in the current competitive health care market, but designing and implementing an outpatient CQI program is a difficult and complex process. Three major problems--the ongoing resistance to change, the slow pace of adding CQI projects to already overburdened work schedules, and the need to conduct the program with ever-decreasing resources available-persist.     

The compound 14-keto-stypodiol diacetate from the algae Stypopodium flabelliforme inhibits microtubules and cell proliferation in DU-145 human prostatic cells

We investigated the effects of the drug 14-keto-stypodiol diacetate (SDA) extracted from the seaweed product Stypopodium flabelliforme, in inhibiting the cell growth and tumor invasive behavior of DU-145 human prostate cells. In addition, the molecular action of the drug on microtubule assembly was analyzed. The effects of this diterpenoid drug in cell proliferation of DU-145 tumor cells in culture revealed that SDA at concentrations of 5 microM decreased cell growth by 14%, while at 45 microM a 61% decrease was found, as compared with control cells incubated with the solvent but in the absence of the drug. To study their effects on the cell cycle, DU-145 cells were incubated with increasing concentrations of SDA and the distribution of cell-cycle stages was analyzed by flow cytometry. Interestingly, the data showed that 14-keto-stypodiol diacetate dramatically increased the proportion of cells in the G2/M phases, and decreased the number of cells at the S phase of mitosis, as compared with appropriate controls. Studies on their action on the in vitro assembly of microtubules using purified brain tubulin, showed that SDA delayed the lag period associated to nucleation events during assembly, and decreased significantly the extent of polymerization. The studies suggest that this novel derivative from a marine natural product induces mitotic arrest of tumor cells, an effect that could be associated to alterations in the normal microtubule assembly process. On the other hand, a salient feature of this compound is that it affected protease secretion and the in vitro invasive capacity, both properties of cells from metastases. The secretion of plasminogen activator (u-PA) and the capacity of DU-145 cells to migrate through a Matrigel-coated membrane were significantly inhibited in the presence of micromolar concentrations of SDA. These results provide new keys to analyze the functional relationships between protease secretion, invasive behavior of tumor cells and the microtubule network.