Hard superconducting nitrides

Detailed study of the equation of state, elasticity, and hardness of selected superconducting transition-metal nitrides reveals interesting correlations among their physical properties. Both the bulk modulus and Vickers hardness are found to decrease with increasing zero-pressure volume in NbN, HfN, and ZrN. The computed elastic constants from first principles satisfy c11 > c12 > c44 for NbN, but c11 > c44 > c12 for HfN and ZrN, which are in good agreement with the neutron scattering data. The cubic delta-NbN superconducting phase possesses a bulk modulus of 348 GPa, comparable to that of cubic boron nitride, and a Vickers hardness of 20 GPa, which is close to sapphire. Theoretical calculations for NbN show that all elastic moduli increase monotonically with increasing pressure. These results suggest technological applications of such materials in extreme environments.     

Differences in airway cytokine profile in severe asthma compared to moderate asthma

BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.     

Decreased sensitivity to alpha-adrenergic stimulation in hypothyroid patients

Nine hypothyroid patients had blood pressure and pulse rate responses to the alpha-adrenergic agonist phenylephrine measured before [T4 index, 45.045 +/- 9.009 nmol/L (mean +/- SEM); TSH, 57.1 +/- 23.6 mU/L] and after 4 +/- 0.5 months of thyroid replacement therapy (T4 index, 141.570 +/- 29.601 nmol/L; TSH, 2.6 +/- 1.0 mU/L). Hypothyroid patients had a smaller blood pressure increment and heart rate decrement at both 66.7 and 100 micrograms/min infusion rates of phenylephrine. Furthermore, the slope of the dose-response curves for systolic (2.06 +/- 0.22 vs. 1.32 +/- 0.19; P less than 0.01) and diastolic (1.04 +/- 0.18 vs. 0.62 +/- 0.08; P less than 0.01) blood pressures were significantly greater after thyroid replacement therapy. Pulse rate changes remained proportional to blood pressure changes in hypothyroid patients, so there was no change in baroreflex sensitivity. Plasma norepinephrine levels were higher before than after thyroid replacement (2.41 +/- 0.28 vs. 1.82 +/- 0.29 nmol/L, respectively; P less than 0.01). Thus, hypothyroid patients have diminished pressor sensitivity to an alpha-adrenergic agonist and increased plasma levels of the alpha-adrenergic neutrotransmitter norepinephrine.     

Treatment and prophylaxis of ventricular arrhythmias in acute myocardial infarction

Remarkable advances have been made in the management of cardiac disease in the last 20 years, but antiarrhythmic drug strategy in the acute phase of myocardial infarction remains less than satisfactory. Primary ventricular fibrillation (VF), once considered predictable on the basis of detection of “warning arrhythmias,” cannot be anticipated. Management must be either expectant or prophylactic. Restriction of drug use to selected patients and the apparent lack of effect of VF on late prognosis argue for the former approach, yet safe and effective prevention of VF is an attractive therapeutic goal. High-dose intravenous lidocaine probably offers efficacy but the risk-benefit ratio of this regimen is still debated. Adoption of a prophylactic regimen mandates drug administration to a large number of patients who either are not at risk of developing VF (noninfarct patients) or who are destined not to develop VF (70 to 95% of infarct patients). Ventricular arrhythmias other than VF are common in acute infarction and, for emotional rather than scientific reasons, often are aggressively treated. Little evidence exists to support this management. Few ventricular arrhythmias at this time in infarction have either immediate importance or prognostic significance. Reevaluation of antiarrhythmic drug use and arrhythmia treatment in acute myocardial infarction is long overdue. However, there is a paucity of controlled data upon which to base new strategies, and clinical research in this field is hampered by ethical considerations, by rigidly held but unscientifically based beliefs and by a lack of fundamental knowledge of arrhythmia mechanisms and their significance.     

Quality of emergency room triage of medical inpatients to an acute care clinic or chronic health care facilities

OBJECTIVE: To evaluate the accuracy of emergency room triage by general internists assigning medical patients to four different health care settings. DESIGN: Prospective trial. SETTING: Medical emergency room of a university hospital providing primary and referral care. PATIENTS: 974 consecutive patients admitted for acute medical care, excluding patients admitted to intensive care units. INTERVENTION AND MEASUREMENTS: After primary evaluation patients were assigned to one of four groups: A) acutely ill requiring acute care in a general medical ward (n = 598); B) acutely ill requiring acute care limited to two to three days (n = 201); C) chronically ill with realistic chances for rehabilitation (n = 77); and D) chronically ill requiring definite referral to skilled nursing home care (n = 98). Nine months later, outcome and placement after index hospitalization were evaluated in surviving patients. MAIN RESULTS: 159 (16%) patients died; three (1%) were lost to follow-up. Evolution confirmed the appropriateness of the initial triage of 90% of the remaining 812 patients (83%). Allocations were correct in 96%, 95%, and 91% of cases in groups A, B, and C, respectively. In group D, only 44% were definitely transferred to nursing homes; 56% were rehabilitated and returned to their previous social settings or entered homes for the aged. CONCLUSIONS: Clinical judgment of general internists in an emergency room adequately identifies patients requiring acute care of regular or short duration and chronically ill patients with realistic prospects for rehabilitation. But the need for nursing home placement is overestimated. To avoid patient misplacement the authors propose direct access to a specialized geriatric assessment facility.     

Parallel analysis of genetic selections using whole genome oligonucleotide arrays

Thousands of genes have recently been sequenced in organisms ranging from Escherichia coli to human. For the majority of these genes, however, available sequence does not define a biological role. Efficient functional characterization of these genes requires strategies for scaling genetic analyses to the whole genome level. Plasmid-based library selections are an established approach to the functional analysis of uncharacterized genes and can help elucidate biological function by identifying, for example, physical interactors for a gene and genetic enhancers and suppressors of mutant phenotypes. The application of these selections to every gene in a eukaryotic genome, however, is generally limited by the need to manipulate and sequence hundreds of DNA plasmids. We present an alternative approach in which identification of nucleic acids is accomplished by direct hybridization to high-density oligonucleotide arrays. Based on the complete sequence of Saccharomyces cerevisiae, high-density arrays containing oligonucleotides complementary to every gene in the yeast genome have been designed and synthesized. Two-hybrid protein–protein interaction screens were carried out for S. cerevisiae genes implicated in mRNA splicing and microtubule assembly. Hybridization of labeled DNA derived from positive clones is sufficient to characterize the results of a screen in a single experiment, allowing rapid determination of both established and previously unknown biological interactions. These results demonstrate the use of oligonucleotide arrays for the analysis of two-hybrid screens. This approach should be generally applicable to the analysis of a range of genetic selections.     

Relation of silent myocardial ischemia after coronary artery bypass grafting to angiographic completeness of revascularization and long-term prognosis

The prevalence and characteristics of silent myocardial ischemia as detected by 24-hour ambulatory electrocardiography ST-segment depression were prospectively assessed in 94 patients examined early (1 to 3 months) and 184 patients examined late (12 months) after coronary artery bypass grafting (CABG), and followed for a mean of 48 +/- 11 (range 4 to 62) months. The relation of ambulatory electrocardiographic silent ischemia to evidence of completeness of revascularization as defined by cardiac angiography performed 1 and 12 months after CABG, and to prognosis by follow-up of adverse clinical events was analyzed. Silent ischemia was detected early in 20% (19 of 94) and late in 27% (50 of 184) of patients, and showed a mean frequency of episodes ranging from 6 to 10 episodes/24 hours with a mean duration ranging from 15 to 23 minutes. The circadian distribution of episodes disclosed a significant peak of ischemic activity during the period of 6 A.M. to noon and a secondary peak between 6 P.M. and midnight (p less than 0.01 and p less than 0.001, respectively). Silent ischemia was not found by univariate analysis to be associated with graft or anastomotic site occlusions, low graft flow rates, grafted arteries with significant distal residual stenoses or ungrafted stenotic native coronary arteries. Kaplan-Meier analysis of time to cardiac event showed that silent ischemia was not predictive of an adverse clinical event in the early years after CABG. Cox regression analysis of 30 covariates only disclosed age (relative risk 1.06 [95% confidence interval, 1.01 to 2.94]) as having an effect on time to adverse clinical event.(ABSTRACT TRUNCATED AT 250 WORDS)     

Results of colectomy for severe slow transit constipation

PURPOSE: This study assesses the outcome of a standardized operation performed by two surgeons for severe idiopathic slow transit constipation that was resistant to laxative treatment. METHODS: Fifty-nine consecutive patients, 4 men and 55 women, with a mean age of 42.3 years, underwent colectomy with ileorectal anastomosis. Slow colonic transit was demonstrated in each case. Fifty-two patients were available for follow-up, with median time to follow-up being 42 (range, 3–81) months. RESULTS: Median bowel frequency was 4 per 24 hours. Sixty-nine percent had four or less bowel movements daily. Ten percent used antidiarrheal medication regularly. One patient had a stoma for recurrent severe constipation. Mean continence score was 1.8 (on a scale of 0–20); six patients were incontinent, and four of these six had normal preoperative anal manometry. Fourteen patients (27 percent) had difficulty with rectal evacuation. Preoperative defecating proctography was a poor predictor of postoperative evacuation difficulties. Twenty-seven patients (52 percent) had persisting abdominal pain, but there was a significant improvement in the degree of pain (P <0.00001). Forty-seven patients (90 percent) were satisfied with the outcome of the operation (and would elect to have it done again). Dissatisfied patients had recurrent constipation or diarrhea and incontinence. CONCLUSION: Colectomy with ileorectal anastomosis produces a satisfactory functional outcome in the majority of patients undergoing surgery for severe constipation with proven slow colonic transit.Supported by the Division of Surgery and the Colorectal Research Fund.Read at the meeting of the Royal Australasian College of Surgeons, Perth, Australia, May 1995.     

Merozoite surface protein 3 and protection against malaria in Aotus nancymai monkeys

A blood-stage vaccine based on Plasmodium falciparum merozoite surface protein 3 (MSP3) was tested for efficacy in a primate model. Aotus nancymai monkeys were vaccinated with yeast-expressed MSP3 before a lethal challenge with Plasmodium falciparum parasites. Five of 7 control monkeys had acute infections and required treatment to control parasitemia. Only 1 of 7 monkeys vaccinated with MSP3 required this treatment. The efficacy of the MSP3 vaccination appeared to be comparable to that of MSP1(42), a leading asexual vaccine candidate, in response to which 2 monkeys experienced acute infections. In the MSP3-vaccinated group, protection correlated with prechallenge titers of antibody to MSP3. In the MSP1 and control groups, protection correlated with antibody to MSP3 raised by challenge infection.