Inhibition of Pseudomonas aeruginosa by Hyperbaric Oxygen II. Ultrastructural Changes

The ultrastructure of Pseudomonas aeruginosa cells treated with hyperbaric oxygen for 20 to 24 hr was examined by electron microscopy. A marked difference in the morphology of the nuclear area and cytoplasm of experimental cells was noted when compared to control cells grown under normobaric conditions. This difference was characterized by the absence of a definitive nuclear area and a reduced granularity of the cytoplasm.     

Gehirn,Nerven

Ohne Zusammenfassung     

Do family physicians and internists differ in knowledge,attitudes, and self-reported approaches for depression?

OBJECTIVES: The purpose of this investigation was to assess the relationship of primary care specialty training with self-assessed skill, knowledge, attitudes, and behavior toward depression recognition and management. METHOD: A baseline self-report questionnaire was administered to 184 internists and 138 family physicians participating in a multisite depression intervention study. RESULTS: There were no marked differences in knowledge of internists and family physicians regarding depression, in attitudes about the effectiveness of specific therapies, or in barriers to providing optimum treatment for depression. However, compared to internists, family physicians rated themselves as more skilled in the management of depression. When considering management of patients with moderate to severe depression, family physicians were more likely to report that they prescribed a selective serotonin-reuptake inhibitor (relative odds (RO) = 3.51, 95 percent Confidence interval (CI) [2.19, 5.60] and to personally counsel patients (RO = 1.97, 95 percent CI [1.16, 3.38]) more than half the patients, but were less likely to refer to a specialist in mental health (RO = 0.52, 95 percent CI [0.33, 0.82]) than were internists. Additional potentially influential characteristics did not wholly account for the reported differences in practice according to specialty. Physicians of both specialties expressed considerable uncertainty in their knowledge of psychotherapy and in their evaluation of the effectiveness of other strategies for the prevention of recurrence of depression. CONCLUSION: Strategies to improve mental health care should account for the orientation of primary care physicians to mental health issues.     

Outpatient consultation-liaison psychiatry: A valuable addition to the training of advanced psychiatry residents

With current health care reimbursement conditions and recent research denoting the important relationship between mental health status and poor functioning, especially in medically ill patients, one would think that consultation-liaison (C-L) psychiatry would have an increasingly viable role in the outpatient health care sector. However, only a small number of outpatient C-L clinics are reported and recently several of these have folded. These outpatient C-L clinics can follow different clinical models and have the potential, especially at the residency and fellowship training levels, for interesting and useful educational opportunities. This paper describes a recently founded outpatient C-L clinic—the Medical Illness Clinic—in a university medical center's department of Psychiatry. We highlight the structure of the clinic, the kinds of patients seen, and focus on the unique educational residency training opportunities this setting presents. The results of clinic rotation evaluations by residents are also presented. We conclude with recommendations for more exploration of this clinical model and evaluation of its utility in psychiatric residency education.     

Effects of dexamethasone on fetal hemoglobin synthesis in peripheral blood erythroid burst-forming units

Colonies derived from erythroid burst-forming units (BFU-E) synthesize fetal hemoglobin (HbF) in amounts that far exceed in vivo levels. There is some evidence that HbF synthesis is controlled at the level of a primitive erythroid precursor cell. Dexamethasone may potentiate the development of BFU-E. Since a means of augmenting HbF production in sickle cell anemia or severe β-thalassemia would be of great therapeutic value, we studied the effects of dexamethasone on HbF and γ-globin chain synthesis in BFU-E from patients with sickle cell anemia and controls. HbF was measured by radioimmunoassay of BFU-E lysate and γ-chain synthesis by the incorporation of ³H-leucine into globin, which was then purified by gel filtration and column chromatography. Dexamethasone (10^?9 M) produced an increase in the number of BFU-E in 16 of 19 subjects when compared with numbers of BFU-E cultured with only erythropoietin. The individual BFU-E were larger and contained more subcolonies. Dexamethasone did not increase HbF or γ-chain synthesis, and there was no relationship between increased proliferation of BFU-E and augmented HbF production. Thus, although dexamethasone augmented the development of erythroid bursts, there was no increment in HbF.     

In vitro and in vivo activities of a novel cephalosporin, BMS-247243, against methicillin-resistant and -susceptible staphylococci

The recent emergence of methicillin-resistant Staphylococcus aureus (MRSA) with decreased susceptibility to vancomycin has intensified the search for alternative therapies for the treatment of infections caused by this organism. One approach has been to identify a beta-lactam with improved affinity for PBP 2a, the target enzyme responsible for methicillin resistance in staphylococci. BMS-247243 is such a candidate, with MICs that inhibit 90% of isolates tested (MIC(90)s) of 4, 2, and 8 microg/ml for methicillin-resistant strains of S. aureus, S. epidermidis, and S. haemolyticus, respectively, as determined on plates with Mueller-Hinton agar and 2% NaCl. The BMS-247243 MICs for MRSA were minimally affected by the susceptibility testing conditions (inoculum size, prolonged incubation, addition of salt to the test medium) or by staphylococcal beta-lactamases. BMS-247243 MIC(90)s for methicillin-susceptible staphylococcal species ranged from < or = 0.25 to 1 microg/ml. The BMS-247243 MIC(90) for beta-lactamase-producing S. aureus strains was fourfold higher than that for beta-lactamase-nonproducing strains. BMS-247243 is hydrolyzed by staphylococcal beta-lactamases at 4.5 to 26.2% of the rates measured for cephaloridine. The affinity of BMS-247243 for PBP 2a was >100-fold better than that of methicillin or cefotaxime. BMS-247243 is bactericidal for MRSA, killing the bacteria twice as fast as vancomycin. These in vitro activities of BMS-247243 correlated with its in vivo efficacy against infections in animals, including the neutropenic murine thigh and rabbit endocarditis models involving MRSA strains. In conclusion, BMS-247243 has in vitro and in vivo activities against methicillin-resistant staphylococci and thus may prove to be useful in the treatment of infections caused by these multidrug-resistant organisms.     

Oral efficacy of a respiratory syncytial virus inhibitor in rodent models of infection

BMS-433771 is a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro. Mechanism of action studies have demonstrated that BMS-433771 halts virus entry through inhibition of F protein-mediated membrane fusion. BMS-433771 also exhibited in vivo efficacy following oral administration in a mouse model of RSV infection (C. Cianci, K. Y. Yu, K. Combrink, N. Sin, B. Pearce, A. Wang, R. Civiello, S. Voss, G. Luo, K. Kadow, E. Genovesi, B. Venables, H. Gulgeze, A. Trehan, J. James, L. Lamb, I. Medina, J. Roach, Z. Yang, L. Zadjura, R. Colonno, J. Clark, N. Meanwell, and M. Krystal, Antimicrob. Agents Chemother. 48:413-422, 2004). In this report, the in vivo efficacy of BMS-433771 against RSV was further examined in the BALB/c mouse and cotton rat host models of infection. By using the Long strain of RSV, prophylactic efficacy via oral dosing was observed in both animal models. A single oral dose, administered 1 h prior to intranasal RSV inoculation, was as effective against infection as a 4-day b.i.d. dosing regimen in which the first oral dose was given 1 h prior to virus inoculation. Results of dose titration experiments suggested that RSV infection was more sensitive to inhibition by BMS-433771 treatment in the BALB/c mouse host than in the cotton rat. This was reflected by the pharmacokinetic and pharmacodynamic analysis of the efficacy data, where the area under the concentration-time curve required to achieve 50% of the maximum response was approximately 7.5-fold less for mice than for cotton rats. Inhibition of RSV by BMS-433771 in the mouse is the result of F1-mediated inhibition, as shown by the fact that a virus selected for resistance to BMS-433771 in vitro and containing a single amino acid change in the F1 region was also refractory to treatment in the mouse host. BMS-433771 efficacy against RSV infection was also demonstrated for mice that were chemically immunosuppressed by cyclophosphamide treatment, indicating that compound inhibition of the virus did not require an active host immune response.     

Effects of a bacterial vaccine on the marginal zone of the spleen

The effect of systemic administration of a typhoid vaccine (T.A.B.) on the marginal zone of rat spleen has been investigated by light and electron microscopy. This bacterial preparation damages granulocytes in the circulating and marginated pools and the damaged cells are sequestered in the spleen, particularly in the marginal zone. The activities of the vaccine are attributed to its endotoxic properties. Terminations of arterial vessels in the marginal zone are also described.