Breakdown and assembly of polyribosomes in synchronized Chinese hamster cells.

Polyribosomes were absent in metaphase Chinese hamster cells and were reassembled after mitosis. This assembly correlated temporally with formation of nuclear membrane and decondensation of chromatin, accounted for a threefold increased rate of protein synthesis, and occurred independently of de novo RNA synthesis, that is, it utilized preexisting messenger RNA.

Written Versus Simulation-Based Evaluation Methods to Assess Competency and Confidence in the Use of Electronic Medical Records.

BACKGROUND: This study compares data on the use of written versus patient simulator methods to evaluate the competence and confidence of RNs after electronic medical record training. METHOD: A randomized controlled trial compared evaluations of the competence and confidence of newly hired nurses using a written patient admission and discharge versus a high-fidelity simulation manikin. Trained observers evaluated nurses' competence, and the nurses rated their own levels of confidence in their performance. RESULTS: No differences were found in confidence or competence. CONCLUSION: Evaluating nurse training on electronic medical records via simulation is as good as evaluating them using the traditional written method. J Contin Educ Nurs. 2018;49(6):262-268.

Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker.

The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.

A comparison between portable ultrasound (MIDUS) and nocturnal RigiScan when confirming the diagnosis of vascular organic erectile disorder.

In recent years, the use of RigiScan and ultrasound to assess erectile dysfunction has fallen from favour. However, in a small minority of specialist cases, where a vascular, neurogenic or psychogenic aetiology requires confirmation, there remains a need for further investigation. To establish if in a preliminary assessment the use of nocturnal RigiScan or male impotence diagnostic ultrasound system (MIDUS) represents best practice as a diagnostic investigation in patients with a history suggestive of vascular organic erectile disorder. Men attending both urological and psychosexual therapy clinics with erectile dysfunction were assessed using a generic assessment schedule. Patients with a history suggestive of vascular erectile disorder were offered the opportunity of dual investigation of their condition. After screening using a provocative RigiScan using visual stimuli that gleaned inconclusive results, patients were offered the chance to enter a study with both nocturnal RigiScan and MIDUS investigation. These were confined for the purposes of this study to RigiScan events, peak systolic flow velocity (PSV) and end-diastolic flow velocity (EDV) from ultrasound examination where an abnormal EDV is defined as in excess of 4.5 cm/s and a normal PSV is variously defined as being greater than 35 cm/s. In all, 38/43 (88%, 95% CI: 76-95%) of men had a nocturnal event exceeding 3 min on the RigiScan investigation. This compares with 17/43 (40%, 95% CI: 26-54%) of men with a normal EDV blood flow of less than 4.5 cm/s (P<0.017) and 32/43 (74%, CI: 60-85%) of men with a normal PSV flow greater than 35 cm/s (NS). Rigiscan and ultrasonography of the cavernosal vessels are of equal usefulness in suspected arterial penile disease although where veno-occlusive disease is suspected, ultrasonography is more specific.

Dose-dense and less dose-intense Total Therapy 5 for gene expression profiling-defined high-risk multiple myeloma.

Multiple myeloma (MM) is a heterogeneous disease with high-risk patients progressing rapidly despite treatment. Various definitions of high-risk MM are used and we reported that gene expression profile (GEP)-defined high risk was a major predictor of relapse. In spite of our best efforts, the majority of GEP70 high-risk patients relapse and we have noted higher relapse rates during drug-free intervals. This prompted us to explore the concept of less intense drug dosing with shorter intervals between courses with the aim of preventing inter-course relapse. Here we report the outcome of the Total Therapy 5 trial, where this concept was tested. This regimen effectively reduced early mortality and relapse but failed to improve progression-free survival and overall survival due to relapse early during maintenance.

Genetic association between sensitivity to warfarin and expression of CYP2C9*3.

Cytochrome P4502C9 (CYP2C9) is largely responsible for terminating the anticoagulant effect of racemic warfarin via hydroxylation of the pharmacologically more potent S-enantiomer to inactive metabolites. Mutations in the CYP2C9 gene result in the expression of three allelic variants, CYP2C9*1, CYP2C9*2 and CYP2C9*3. Both CYP2C9*2 and CYP2C9*3 exhibit altered catalytic properties in vitro relative to the wild-type enzyme. In the present study, a patient was genotyped who had proven unusually sensitive to warfarin therapy and could tolerate no more than 0.5 mg of the racemic drug/day. PCR-amplification of exons 3 and 7 of the CYP2C9 gene, followed by restriction digest or sequence analysis, showed that this individual was homozygous for CYP2C9*3. In addition, patient plasma warfarin enantiomer ratios and urinary 7-hydroxywarfarin enantiomer ratios were determined by chiral-phase high performance liquid chromotography in order to investigate whether either parameter might be of diagnostic value in place of a genotypic test. Control patients receiving 4-8 mg warfarin/day exhibited plasma S:R ratios of 0.50 +/- 0.25:1, whereas the patient on very low-dose warfarin exhibited an S:R ratio of 3.9:1. In contrast, the urinary 7-hydroxywarfarin S:R ratio of 4:1 showed the same stereoselectivity as that reported for control patients. Therefore, expression of CYP2C9*3 is associated with diminished clearance of S-warfarin and a dangerously exacerbated therapeutic response to normal doses of the racemic drug. Analysis of the plasma S:R warfarin ratio may serve as a useful alternative test to genotyping for this genetic defect.

Antipicornavirus activity of substituted phenoxybenzenes and phenoxypyridines.

Phenoxybenzenes and phenoxypyridines were prepared and tested for the effect of substituents on antipicornavirus activity. The most active compound, 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (8), demonstrated broad-spectrum antipicornavirus activity. Compound 8 and several analogues each given orally prior to and during infection protected mice against an otherwise lethal challenge with coxsackievirus A21.

Changes in lens membrane major intrinsic polypeptide during cataractogenesis in aged Hannover Wistar rats.

Cataracts previously have been shown to occur spontaneously in aged Hannover Wistar rats. The morphology and time course of opacification of these cataracts are very similar to those appearing in the human lens, where it has been previously shown that the major intrinsic polypeptide (MIP26K) of the fiber cell membrane undergoes covalent modification during cataractogenesis. To ascertain possible biochemical similarities between the two cataract systems, antisera were made against synthetic peptides corresponding to the sequence of MIP26K to probe Western blots of lens proteins from transparent versus opaque lenses from normal aged rats. The results of this analysis showed that these antisera can detect the presence of covalent changes occurring in the MIP26K molecule during the development of cortical opacities in the normal aged rat.

Intramyocardial pH as an index of myocardial metabolism during cardiac surgery.

At present, a practical method for continuous monitoring of the state of tissue metabolism in the individual patient's heart during cardiac operations is not available. We have explored the use of miniature electrode measurements of myocardial interstitial pH to provide this monitoring capability, making comparisons with intracellular pH in left ventricular biopsy specimens and with tissue PCO2 measured by mass spectrometry. The electrode system consisted of a hydrogen ion-sensitive glass miniature electrode, housed in the beveled end of a 21 gauge (0.8 mm diameter) hypodermic needle, and a 2 mm diameter reference electrode, with an internal silver-silver chloride electrode coupled to tissue through a saline bridge (150 mM/L sodium chloride) saturated with silver chloride. Accuracy in blood at 37 degrees C was compared with conventional instrumentation (Radiometer BMS-3 MK-2 Blood Micro System) over a pH range of 7.4 to 6.4 with linear regression analysis (n = 26) revealing a high correlation (r = 0.997) and a mean difference in paired observations of only 0.01 +/- 0.004 (mean +/- SEM) pH units. In two groups of dogs on cardiopulmonary bypass, the pH needle and reference electrodes were inserted into the anterior wall of the left ventricle. Ischemic arrest of the heart at 37 degrees C was used to vary myocardial pH. In Group 1 (n = 8), intracellular pH was estimated from left ventricular biopsy specimens (400 mg each) taken over a microelectrode pH range of 7.37 to 6.37, snap frozen, and homogenized. In Group II (n = 6), tissue PCO2 in the anterior wall of the left ventricle was determined by mass spectrometry (sampling catheter 1.3 mm diameter). Miniaturized electrode (interstitial) pH exceeded biopsy (intracellular) pH under control conditions by 0.28 +/- 0.025 pH units (p less than 0.001), but below an electrode pH of 6.8 the results of the two techniques did not differ significantly. The tissue PCO2 rose from 69 +/- 2 mm Hg to a final plateau of 419 +/- 25 mm Hg, which was similar to the predicted value of 427 +/- 28 mm Hg calculated from the pH change (7.37 +/- 0.01 to 6.01 +/- 0.07), providing a further independent check on the pH electrode technique. These data indicate that our intramyocardial pH measurements do reflect intracellular metabolism during elective arrest of the heart and may have potential for clinical use.

Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis.

Multidose administration of cardioplegic solution during cardiac operation is intended to maintain both electromechanical arrest of the heart and myocardial hypothermia as well as to remove accumulated metabolites of anaerobic glycolysis. This study was conducted to assess the effect of multidose infusion of three different types of cardioplegic solution on tissue acidosis during global myocardial ischemia. Three groups of five dogs each were placed on cardiopulmonary bypass and the aorta was cross-clamped for 3 hours. The hearts were maintained at a constant temperature (20 degrees C) and cardioplegic solution was infused at an initial dose of 500 ml and five supplementary doses of 250 ml administered every 30 minutes. Group 1 received a crystalloid solution weakly buffered with sodium bicarbonate, Group 2 received a blood-based solution, and Group 3 received a crystalloid solution strongly buffered with histidine (Bretschneider's solution). The buffering capacities of the solutions used in Groups 2 and 3 were 40 and 60 times, respectively, that of the solution used in Group 1. The average myocardial tissue pH at the end of 3 hours of ischemia was 6.54 +/- 0.07 in Group 1, 7.23 +/- 0.05 in Group 2, and 7.19 +/- 0.06 in Group 3 (Group 1 significantly lower than Groups 2 and 3). Multidose infusion of a cardioplegic solution with low buffering capacity was unable to prevent the progressive development of tissue acidosis during 3 hours of ischemia. However, the multidose infusion of either blood-based or crystalloid solutions with high buffering capacity completely prevented any further reduction of tissue pH after the first 30 minutes of ischemia.

Failure of the urinalysis and quantitative urine culture in diagnosing symptomatic urinary tract infections in patients with long-term urinary catheters.

Since urine culture and urinalysis are both of uncertain reliability in diagnosing symptomatic urinary tract infections in patients with chronic urinary catheters, we performed sequential quantitative cultures and urinalyses on 177 urine specimens from 14 patients with long-term urinary catheters during a 12-month period. We found high concentrations of greater than or equal to 2 species of aerobic bacteria or fungi in most specimens examined. Pyuria was common even during asymptomatic periods; hematuria was less common. During symptomatic urinary tract infections, neither urinalyses nor quantitative urine cultures exhibited changes specific for such infections. Thus neither urinalysis nor urine culture appears to be a reliable test for symptomatic urinary tract infections in patients with chronic urinary catheters.

Hypothermia in conjunction with hyperbaric oxygenation in the treatment of massive air embolism during cardiopulmonary bypass.

Massive gas embolism during cardiopulmonary bypass is a rare but ever-present danger. Following this catastrophic event, the immediate institution of core cooling on bypass may be advantageous. The remarkable complete recovery of our patient is attributed to this technique, which was used in conjunction with standard therapy.

Intramyocardial pH during elective arrest of the heart: relative effects of hypothermia versus potassium cardioplegia on anaerobic metabolism.

Using an intramyocardial pH needle probe (21 gauge) to monitor myocardial metabolism during ischemia, we determined the effect of potassium cardioplegia at both moderate and deep hypothermia. Five groups of 5 dogs each were placed on cardiopulmonary bypass and the pH probe was inserted approximately 10 mm into the left ventricular free wall. Cardiac ischemia was achieved by cross-clamping the ascending aorta at 37 degrees C (Group 1), 27 degrees C (Group 2), or 17 degrees C (Group 3). In the remaining two groups, aortic cross-clamping was followed by the infusion of 600 to 800 ml of potassium cardioplegic solution adjusted to cardiac temperatures of 27 degrees C (Group 4) or 17 degrees C (Group 5). In each group, myocardial temperature was maintained constant, electrical and mechanical activity observed, and pH recorded until a plateau was reached or for 3 hours. Our results show a progressive and significant decrease in the metabolic rate with reduction in temperature over the 37 degrees to 17 degrees C range. By abolishing contractile activity, potassium cardioplegia markedly reduces the rate of hydrogen ion accumulation at 27 degrees C, but at 17 degrees C the additive effect of cardioplegia is much less pronounced. These observations support the principle of reducing contractile activity to a minimum during elective arrest of the heart but indicate that potassium cardioplegia does little to further reduce the rate of anaerobic metabolism, as shown by the measurement of intramyocardial pH, under conditions of deep hypothermia.

Does vibration offer any advantage over visual stimulation studies (VSS) in the assessment of erectile capacity?

The purpose of this work was to determine whether vibration stimulation or erotic videotape material can provide an acceptable diagnostic yield for patients with erectile dysfunction (ED) without the patient needing to endure more explicit erotic films, which may be distasteful to some patients, or intracavernous injections, to which there may be a high inhibitory response. Ninety-five subjects were randomly exposed to either vibration or videotape alone and erectile response monitored by the RigiScan. Where no clinical response was recorded by the RigiScan or by self-report by the patient, both stimuli were presented to the subject. Forty-nine subjects received vibration first and 46 received videotape first. Use of clinically based standardised measures revealed neither group achieving above threshold responses to the first stimulation and there were no differences between the two groups. Eight subjects (8%) between both groups exceeded the tip threshold during combination stimulation. Single stimulation with vibration or erotic videotape with provocative RigiScan monitoring is unhelpful in the assessment of ED in any of the diagnostic subgroups of ED. In comparison to previous provocative studies, combination of stimuli sets, whilst increasing penile response (circumferential change and rigidity) did not lead to significant evidence of clinically relevant responses using current RigiScan measures or patient self-report of change. Further studies are necessary to determine the most useful set of stimuli for provocation studies with the RigiScan.

Outpatient transesophageal echocardiography with intravenous propofol anesthesia in children and adolescents.

Outpatient transesophageal echocardiography (TEE) was performed in 10 children and adolescents (aged 3 to 19.5 years, mean 13.5 years; weight 12 to 91 kg, mean 49 kg), including two with Down's syndrome and one with autism, for diagnostic evaluation of issues unresolved by transthoracic echo examination (TTE). Issues for TEE: evaluation for atrial septal defect (two patients); anatomy of left ventricular outflow tract obstruction (one patient); aortic valve anatomy before valvuloplasty for insufficiency (one patient); evaluation for cause of cyanosis after Fontan operation (one patient); determination of source of high-velocity intracardiac turbulence after atrioventricular septal defect repair (one patient); rule out cardiac embolic source in patient with stroke (one patient); evaluate prosthetic valve function and rule out thrombus (one patient); determination of anatomic relationship of mitral valve to a ventricular septal defect before surgery for complex cyanotic heart disease (one patient); and evaluation for aortic dissection in Marfan's syndrome (one patient). Intravenous propofol anesthesia administered without endotracheal intubation by an anesthesiologist allowed successful outpatient TEE in nine patients; midazolam-conscious sedation was used in one. Outpatient TEE resolved diagnostic issues in all patients without complication, thereby avoiding cardiac catheterization in six patients and supplementing catheterization for preoperative planning in four patients. TEE can be performed safely and effectively with propofol anesthesia in the outpatient setting in carefully selected children and adolescents to provide vital diagnostic information. However, given the invasive nature of the procedure and the use of anesthesia, outpatient pediatric TEE should be used judiciously.

A survey of medical school teachers to identify basic biomedical concepts medical students should understand.

Insights from the cognitive sciences indicate a continuing need for physicians to understand conceptual knowledge from the basic sciences, despite recent concerns regarding the increasing amount of information in medicine and the growing emphasis on performance skills. A 1987 survey of selected basic science and clinical teachers in North American medical schools was undertaken to identify basic biomedical concepts that are important in the practice of medicine and to specify how difficult these are for students to learn, apply, or both. Responses from faculty (nominated by their deans to answer the survey) from 82% of the medical schools indicated considerable agreement between the basic science teachers and clinical teachers on the relative importance of a set of biomedical concepts, and showed relatively minor levels of disagreement on how difficult these concepts are. The judgments of these teachers could prove extremely useful in (1) determining concepts that--because of their importance--should receive special attention in curriculum efforts, and (2) determining concepts that--because of their difficulty--need "special handling."

Validity of simple approach to scoring and standard setting for standardized-patient cases in an examination of clinical competence.

The results are disappointing, providing little support for the validity of the case-passing decisions based on this simple approach to scoring and standard setting. The case-passing decisions predicted what the case author intended for about only 73% or 74% of the students on average and, with agreement expected by chance removed, predicted what the case author intended for about only 25% of the students. Even with the use of the optimal pass/fail cutoffs and the dropping of students with ambiguous borderline global ratings, the case-passing decisions failed to agree with the case authors' global ratings for 15% to 30% of the students. The findings might be dismissed as simply due to low reliabilities of passing decisions and global ratings based on a single case. Although this concern would apply to intercase reliabilities, which would be subject to case specificity, the appropriate reliabilities here would seem to be intracase (i.e., intrarater), which should be fairly high (if they could be computed). Nevertheless, it seems reasonable to expect much better agreement between results of case scoring and of standard setting developed by the case author and the case author's global ratings of performance on that case, given that the case author might recall the checklist, assign a weight to each item, and so forth. Also, case-passing decisions would possibly agree more with global ratings of live or videotaped performances than with ratings of written summaries of performance; however, that question remains a challenge for further research. In conclusion, the study provides only weak evidence, at best, for the validity of the scoring and standard setting commonly used with SP assessment. The results do not undermine claims about the realism of the SP approach, however, nor do they call into question the standardization afforded by this method of assessing clinical competence. The results do raise serious concerns about this simple approach to scoring and standard setting for SP-based assessments and suggest that we should focus more on the observation and evaluation of actual student performance on SP cases in the development of valid scoring and standard setting.

Assessment of pediatric patients for general anesthesia: the child with an upper respiratory infection and the ex-premature infant.

There are two types of patients that commonly lead surgeons and anesthesiologists into discussions relating to the possible cancellation or postponement of a minor pediatric surgical procedure; the child with a recent upper respiratory infection, and the patient who was born prematurely. Current opinion of the risks of anesthesia in such patients and the factors that influence perioperative course are reviewed, and a plan of management is suggested.

Do steroids reduce morbidity of tonsillectomy? Meta-analysis of randomized trials.

OBJECTIVES/HYPOTHESIS: The study aims to reconcile conflicting published reports regarding the clinical efficacy of a single intraoperative dose of dexamethasone in reducing post-tonsillectomy morbidity. STUDY DESIGN: Systematic overview (meta-analysis). METHODS: To critically evaluate the existing evidence, we performed a formal meta-analysis of eight double-blinded, randomized, placebo-controlled studies of dexamethasone in pediatric patients undergoing tonsillectomy or adenotonsillectomy. Reduction in postoperative emesis and pain, as well as early return to soft or solid diet, were studied as distinct end points. RESULTS: Children being given a single intraoperative dose of dexamethasone (dosing, 0.15-1.0 mg/kg; maximum dose, 8-25 mg) were two times less likely to vomit in the first 24 hours than children being given placebo (relative risk [RR] = 0.55; 95% confidence interval [CI], 0.41-0.74; P < .0001). Routine use in four children would be expected to result in one less patient having post-tonsillectomy emesis (risk difference [RD] = -0.24; 95% CI, -0.38 to -0.10; P = .0006). In addition, children being given dexamethasone were more likely to advance to a soft or solid diet on post-tonsillectomy day 1 (RR = 1.69; 95% CI, 1.02-2.79; P = .04) than those being given placebo. Because of missing data and varied outcome measures, pain could not be meaningfully analyzed as a distinct end point. CONCLUSION: Given the frequency of tonsillectomy, relative safety and low cost of dexamethasone, and the reduction in postoperative morbidity, we recommend routine use of a single intravenous dose during pediatric tonsillectomy.