The problem of poor retention of cardiopulmonary resuscitation skills may lie with the instructor, not the learner or the curriculum.

Many studies (several even before American Heart Association recommended in 1973 that lay public be trained in cardiopulmonary resuscitation (CPR] have documented that retention of CPR skills is poor, unaffected by modifications in curriculum or whether the students are lay or professional. We chose to investigate what actually occurs during a CPR course, and gained the following insights: despite clearly defined curricula, we found that instructors did not teach in a standardized way. Practice time was limited and errors in performance were not corrected. Instructors consistently rated the students' overall performance as acceptable; at the same time, using the same checklist, we consistently rated performance as unacceptable. The checklist is an inaccurate tool for evaluating CPR performance. Despite the poor performance that we documented, students and instructors were satisfied with the courses and believed that the level of performance was high. As a result of these studies, we discovered that the problem of poor retention of CPR skills may lie not with the learner or the curriculum, but with the instructor. But, since lives are being saved with bystander CPR, does this documented poor retention matter? Perhaps the solution is not only to improve instructor training to make certain that students receive adequate practice time and accurate skill evaluation, but also to modify the criteria for correct performance when testing for retention. These criteria should be based on the minimum CPR skills that are required to sustain life for the critical 4-8 min before defibrillation and other advanced cardiac life support are delivered.

Sequential Cdk1 and Plk1 phosphorylation of protein tyrosine phosphatase 1B promotes mitotic cell death.

Mitotic cell death following prolonged arrest is an important death mechanism that is not completely understood. This study shows that Protein Tyrosine Phosphatase 1B (PTP1B) undergoes phosphorylation during mitotic arrest induced by microtubule-targeting agents (MTAs) in chronic myeloid leukaemia cells. Inhibition of cyclin-dependent kinase 1 (Cdk1) or polo-like kinase 1 (Plk1) during mitosis prevents PTP1B phosphorylation, implicating these kinases in PTP1B phosphorylation. In support of this, Cdk1 and Plk1 co-immunoprecipitate with endogenous PTP1B from mitotic cells. In addition, active recombinant Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B. Furthermore, overexpression of wild-type PTP1B induced mitotic cell death, which is potentiated by MTAs. Moreover, mutation of serine 286 abrogates the cell death induced by PTP1B, whereas mutation of serine 393 does not, highlighting the importance of serine 286 phosphorylation in the execution of mitotic cell death. Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity. Collectively, these data reveal that PTP1B activity promotes mitotic cell death and is regulated by the co-operative action of Cdk1 and Plk1 during mitotic arrest.

Aetiology and pathogenesis of hormonal and metabolic disorders in HIV infection.

Many hormonal and metabolic disturbances are documented in HIV infection, the most important of which is the wasting syndrome associated with progressive HIV infection. We are only now beginning to understand the pathogenesis of these disturbances. In rare cases, infiltration of endocrine tissue by secondary infectious or malignant processes is the underlying cause of hormonal insufficiency. In most instances, however, hypofunction is secondary to the well-known effects of severe illness. Similarly, hyperfunction of the adrenal axis along with many of the derangements in substrate metabolism are also likely to be secondary to severe illness, perhaps through activation of cytokines and other molecules. Specific disturbances in asymptomatic patients are more difficult to document and may represent unique and as yet unexplained manifestations of HIV disease. Hypermetabolism and depletion of lean body mass are most profound in the acutely ill patient with active secondary infection. At this stage, the HIV-infected patient is in a catabolic state and adaptive mechanisms which normally decrease energy expenditure and preserve lean body mass are either overridden or not operative. Strategies to reverse the catabolic state and diminish wasting are only now being developed.

Effect of sodium intake on insulin sensitivity.

To examine the effects of sodium intake on insulin sensitivity, we performed euglycemic insulin clamp studies (40 mU.m-2.min-1) in eight healthy normotensive nondiabetic white males (age = 36 +/- 5 yr; wt = 66 +/- 3 kg) after 5 days on high (200 meq/day)- and low (10 meq/day)-sodium diets administered in random order. High sodium intake was associated with significantly greater urinary sodium excretion (160 +/- 7 vs. 8 +/- 2 meq/day; P < 0.0001), suppression of plasma aldosterone (7 +/- 3 vs. 38 +/- 6 ng/dl; P < 0.001) and renin (1.5 +/- 0.2 vs. 6.0 +/- 0.9 ng.ml-1.h-1; P < 0.005) levels, but no change in blood pressure (116 +/- 3/63 +/- 2 vs. 114 +/- 3/64 +/- 2 mmHg; P = not significant). The rate of glucose infusion during the clamp was significantly reduced during the high- vs. low-sodium diet (279 +/- 19 vs. 334 +/- 24 mg.m-2.min-1; P < 0.01). This impairment in insulin sensitivity was not related to changes in serum potassium, epinephrine, norepinephrine, cortisol, or growth hormone but was highly correlated with an increment in circulating free fatty acid levels during high sodium intake (r = 0.82, P < 0.05). These data suggest that 1) high sodium intake may exacerbate insulin resistance by increasing circulating free fatty acids, and 2) differences in sodium intake may influence measures of insulin sensitivity in other disease states.

Bone mass and vitamin D deficiency in adults with advanced cystic fibrosis lung disease.

Osteoporosis and fractures are increasingly recognized in children and adults with cystic fibrosis. To investigate the prevalence and pathogenesis of osteoporosis and low bone mass in adults with advanced pulmonary disease due to cystic fibrosis, we examined the relationships between bone mineral density (BMD), anthropomorphic variables, pulmonary status, glucocorticoid therapy, and vitamin D concentrations. BMD of the lumbar spine, hip, and proximal radius was measured by dual energy X-ray absorptiometry in 30 white adults (16 women), age 30 +/- 2 yr (mean +/- SEM). Compared with a normal control population, the patients had significantly reduced BMD at the lumbar spine (17 +/- 3%), total hip and femoral neck (24 +/- 3% and 20 +/- 4%, respectively). The radius was significantly less demineralized (4 +/- 2%; p <= 0.003) than the other sites. Moreover, only 21% of patients with cystic fibrosis had normal BMD (T score > -1.0) at the lumbar spine, 23% at the hip sites, and 39% at the radius. Age, weight, and body mass index (BMI) were most strongly correlated with bone mass, whereas glucocorticoid therapy and pulmonary function were not predictive. Despite oral vitamin D (400 to 800 IU daily), the mean serum 25-hydroxyvitamin D (25-OHD) concentration was at the low end of the normal range (16 +/- 2 ng/ml; normal 10 to 52 ng/ml); 8 of 20 patients (40%) had frankly low (<= 10 ng/ml) levels. BMD was significantly lower in patients with low 25-OHD concentrations at the lumbar spine (0.774 +/- 0.02 versus 0.913 +/- 0.04 g/cm2; p = 0.01) and total hip (0.648 +/- 0.04 versus 0.811 +/- 0.04 g/cm2; p = 0.01). Vertebral fractures were present in 19% of subjects and 41% had a confirmed history of previous fracture. In summary, osteoporosis, low bone mass, and fractures are common in adults with advanced cystic fibrosis lung disease. Despite oral supplements, vitamin D deficiency is also common and is associated with more severe demineralization at the lumbar spine and hip. We conclude that the widespread practice of oral supplementation with 400 to 800 units of vitamin D is ineffective in maintaining normal vitamin D stores in many patients with cystic fibrosis. To ensure adequacy of vitamin D stores, measurement of serum 25-OHD should be included in the routine management of patients with cystic fibrosis.

Can better basic and advanced cardiac life support improve outcome from cardiac arrest?

The effect of basic and advanced cardiac life support (BLS and ACLS) on long-term survival is dependent upon both the response time and the quality of intervention. Retention research using the results of classroom testing as indirect indicators has shown that performance of BLS and ACLS skills is poor. This suggests that BLS and ACLS courses do not teach the knowledge and skills well, the information is too difficult to retain, testing procedures are faulty, and/or the performance standards are unrealistic. To maximize the likelihood of successful resuscitation from cardiac arrest, we propose the following: (a) simplify the BLS procedures; (b) simplify the BLS and ACLS curricula; (c) simplify teaching strategies; (d) simplify testing based on what steps are required to sustain life; (e) define objective criteria for knowledge acquisition and skill performance; (f) base refresher training on diagnosed deficiencies and evaluate innovative ways to improve retention; (g) develop a resuscitation record to provide accurate documentation of patient status, dysrhythmias, therapy, and responses to therapy; (h) develop a process evaluation tool to evaluate individual and group performances during actual resuscitation; and (i) form an international consortium of BLS and ACLS investigators.