Why patients sign out against medical advice (AMA): factors motivating patients to sign out AMA

A retrospective review of the against medical advice (AMA) discharges revealed that the majority of the patients left AMA for personal reasons, i.e., sickness or death in the family; reconciliation with spouse, girl friend, or family members; financial problems; and legal issues such as a court date. Strategies to reduce AMA discharges and increase patient retention in treatment are suggested.     

A low concentration of nisoldipine reduces ischemic heart injury: enhanced reflow and recovery of contractile function without energy preservation during ischemia

Isolated working rat hearts which received no drug treatment had reduced ATP and creatine phosphate levels and increased lactate content during 20 min of ischemia. When subjected to 33 min of ischemia and 30 min of reperfusion, these hearts recovered low values of cardiac output (9.8 ml/min), heart rate, maximum developed pressure, pressure-rate product (72.9, 32.6, 27.5% of control, respectively), had low levels of tissue ATP, and reduced coronary flow upon reperfusion. Addition of nisoldipine (1 nM) 10 min before ischemia caused no decrease in cardiac output or heart rate, slightly decreased maximum developed pressure and pressure-rate product (93% of control), and did not reduce the degradation of ATP and creatine phosphate or the accumulation of lactate during 20 min of ischemia. When nisoldipine was included 10 min before ischemia, during ischemia (33 min) and reperfusion (30 min), however, the recovery of cardiac function and tissue ATP levels was significantly increased. This protective effect occurred when drug treated ischemic hearts were reperfused with control buffer, indicating residual effects. The beneficial effects of nisoldipine were not due to changes in afterload or preload (isolated perfused heart), collateral flow (zero flow model), energy preservation during ischemia (little contractile depression, ATP not enhanced during ischemia), or reduced lactate accumulation during ischemia. The beneficial effects were associated with increased coronary flow (31% higher than no drug) during reperfusion, indicating a reduction in the no-reflow phenomenon.     

Effects of progesterone on the pituitary responsiveness to, and priming effect of luteinizing hormone releasing hormone in female rats exposed to constant light

We have investigated the role of progesterone in the mating-induced release of luteinizing hormone (LH) and ovulation in female rats exposed to a 60-day period of constant light (LL). Plasma LH and progesterone concentrations were increased after mating; plasma estradiol concentrations, although not increased after mating, were increased compared with the concentrations in female rats on light-dark (LD) exposure during diestrus, proestrus evening and estrus. Progesterone induced ovulation in about half the number of female rats exposed to long-term LL, and in these animals, there was a significant increase in pituitary responsiveness to luteinizing hormone releasing hormone (LHRH) 5 h after progesterone injection. The magnitude of the priming effect of LHRH was markedly increased 2 h after progesterone treatment. Treatment with sodium pentobarbitone (SP) 15 min before an injection of progesterone, blocked the increase in pituitary responsiveness to LHRH 5 h later, but treatment with SP 4 h before progesterone injection did not block the increase in the magnitude of the priming effect of LHRH. These results suggest that progesterone acts both at the brain and pituitary to facilitate LH release, and that the increase in plasma progesterone produced by mating is at least partly responsible for the LH surge induced by mating in LL rats.     

Selection and gene flow on a diminishing cline of melanic peppered moths

Historical datasets documenting changes to gene frequency clines are extremely rare but provide a powerful means of assessing the strength and relative roles of natural selection and gene flow. In 19th century Britain, blackening of the environment by the coal-fired manufacturing industry gave rise to a steep cline in the frequency of the black (carbonaria) morph of the peppered moth (Biston betularia) across northwest England and north Wales. The carbonaria morph has declined across the region following 1960s legislation to improve air quality, but the cline had not been comprehensively described since the early 1970s. We have quantified changes to the cline as of 2002, equivalent to an interval of 30 generations, and find that a cline still exists but that it is much shallower and shifted eastward. Joint estimation of the dominant fitness cost of carbonaria and dispersal parameters consistent with the observed cline change indicate that selection against carbonaria is very strong across the landscape (s approximately 0.2), and that dispersal is much greater than previously assumed. The high dispersal estimate is further supported by the weak pattern of genetic isolation by distance at microsatellite loci, and it implies that in addition to adult dispersal, wind-dispersed first instar larvae also contribute to lifetime dispersal. The historical perspective afforded by this study of cline reversal provides new insight into the factors contributing to gene frequency change in this species, and it serves to illustrate that, even under conditions of high dispersal and strong reverse selection acting against it, complete erosion of an established cline requires many generations.     

Bisphosphonate treatment of osteoporosis

Bisphosphonates represent the agents of choice for most patients with osteoporosis. They are the best studied of all agents for the prevention of bone loss and reduction in fractures. They increase BMD, primarily at the lumbar spine, but also at the proximal femur. In patients who have established osteoporosis, bisphosphonates reduce the risk of vertebral fractures, and are the only agents in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. Bisphosphonates reduce the risk of fracture quickly. The risk of radiographic vertebral deformities is reduced after 1 year of treatment with risedronate [68]. The risk of clinical vertebral fractures is reduced after 1 year of treatment with alendronate [69] and just 6 months' treatment with risedronate [157]. The antifracture effect of risedronate has been shown to continue through 5 years of treatment [158]. Alendronate and risedronate are approved by the FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for prevention (risedronate) and treatment (alendronate and risedronate) of glucocorticoid-induced osteoporosis. Alendronate is also approved for treatment of osteoporosis in men. Other bisphosphonates (etidronate for oral use, pamidronate and zoledronate for intravenous infusion) are also available and can be used off label for patients who cannot tolerate approved agents. Although bisphosphonates combined with estrogen or raloxifene produce greater gains in bone mass compared with single-agent treatment, the use of two antiresorptive agents in combination cannot be recommended because the benefit on fracture risk has not been demonstrated and because of increased cost and side effects.