Induction of Fos immunoreactivity in the brain by exposure to the elevated plus-maze

The log-rank test is commonly used to assess therapeutic effect in prospective, randomised clinical trials. This test is sensitive to differences in survival between treatment groups at a specific endpoint, but cannot determine whether such a difference is due to an enhanced cure rate or an enhanced survival time among uncured patients. To investigate the clinical impact of such limitations, an algorithm was constructed to simulate clinical, randomised, adjuvant therapy trials in patients with a cured fraction of 0.27 and a median survival time for uncured patients of 3.4 years. Hypothetical therapies were introduced to increase rate of cure, increase median survival time, or achieve a combination of these effects. For 500 simulated patients recruited over a 5 year period and then followed for three additional years, a 50% enhancement of median survival time (to 5.1 years) led to a survival increase detectable at the P = 0.05 level in 780 of 1000 trials, whereas a 50% enhancement of cured fraction (to 40.5%) led to a detectable increase at the same level in only 449 of 1000 trials. These findings suggest that, in clinical trials of adjuvant therapy for stage 2 breast cancer, the log rank test may be more sensitive to increases in tumour-related survival time than to increases in cured fraction.     

Variables affecting results of sodium chloride tolerance test for identification of rapidly growing mycobacteria

The sodium chloride tolerance test is often used in the identification of rapidly growing mycobacteria, particularly for distinguishing between Mycobacterium abscessus and Mycobacterium chelonae. This test, however, is frequently unreliable for the identification of some species. In this study we examined the following variables: medium manufacturer, inoculum concentration, and atmosphere and temperature of incubation. Results show that reliability is improved if the test and control slants are inoculated with an organism suspension spectrophotometrically equal to a 1 McFarland standard. Slants should be incubated at 35 degrees C in ambient air and checked weekly for 4 weeks. Growth on control slants should be critically evaluated to determine the adequacy of the inoculum; colonies should number greater than 50. Salt-containing media should be examined carefully to detect pinpoint or tiny colonies, and colonies should number greater than 50 for a positive reaction. Concurrent use of a citrate slant may be helpful for distinguishing between M. abscessus and M. chelonae. Molecular methodologies are probably the most reliable means for the identification of rapidly growing mycobacteria and should be used, if possible, when unequivocal species identification is of particular importance.     

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB), a neural member of the EGF family of differentiation factors, is implicated in neurite formation

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB) was identified by combining binding assays with immunological screens in the chicken nervous system as a novel member of the EGF family of differentiation factors. cDNA cloning indicates that CALEB is a multidomain protein that consists of an NH2-terminal glycosylation region, a leucine-proline-rich segment, an acidic box, a single EGF-like domain, a transmembrane, and a short cytoplasmic stretch. In the developing nervous system, CALEB is associated with glial and neuronal surfaces. CALEB is composed of a 140/130-kD doublet, an 80-kD band, and a chondroitinsulfate-containing 200-kD component. The latter two components are expressed in the embryonic nervous system and are downregulated in the adult nervous system. CALEB binds to the extracellular matrix glycoproteins tenascin-C and -R. In vitro antibody perturbation experiments reveal a participation of CALEB in neurite formation in a permissive environment.     

Professional integrity in clinical research

In response to public concern over abuses in human medical experimentation, the dominant approach to the ethics of clinical research during the past 30 years has been regulation, particularly via institutional review board review and approval of scientific protocols and written consent forms. However, the effectiveness of regulatory mechanisms in ensuring the ethical conduct of clinical research is limited. Little attention has been devoted to the nature and role of professional integrity of physician investigators, a conscientious framework for guiding investigators in the socially important but morally complex activity of clinical research. Professional integrity is vital in forging an ethically sound relationship between investigators and patient volunteers, a relationship that differs in important ways from the patient-physician relationship in standard clinical practice. We examine critically 2 models of the moral identity of physician investigators, the investigator as clinician and the investigator as scientist; in neither of these 2 models can the physician investigator eliminate completely the moral conflicts posed by clinical research. The professional integrity of physician investigators depends on a coherent moral identity that is proper to the enterprise of clinical research. The roles of clinician and scientist must be integrated to manage conscientiously the ethical complexity, ambiguity, and tensions between the potentially competing loyalties of science and care of volunteer patients.     

Formation of droplets on Si surfaces bombarded by In from a capillary type liquid metal ion source

Droplet formation on Si surfaces bombarded by 10 keV beams from a liquid metal indium ion source has been observed. It has been verified that excess indium is transported in the ion beam, probably in the form of charged droplets. SIMS, SEM and RBS techniques have been used to study the distribution of droplets at the surface. At the specified ion source operating conditions, equilibrium droplet coverage is of the order of 25%. Individual droplets have an average diameter of 0.35 ωm and an average height of 2.2 nm. At a bombardment current density of 0.1 mA cm^?2, equilibrium coverage is reached in about 1 s.     

The neurotrophic analogue of ACTH(4-9) reduces the perineuronal microglial reaction after rat facial nerve crush

Rats bled to a severe condition of volume-controlled hemorrhagic shock were randomly assigned to one of the following treatments: (1) saline, 1 ml/kg i.v.; (2) saline, 0.2 ml/kg per min i.v. for 10 min; (3) ACTH-(1-24), 160 micrograms/kg i.v.; 4) methylprednisolone, 40 mg/kg i.v.; (5) methylprednisolone, 80 mg/kg i.v.; (6) aprotinin, 10,000 KIU/kg i.v.; (7) norepinephrine, 5 micrograms/kg per min i.v. for 10 min; (8) norepinephrine, 10 micrograms/kg per min i.v. for 10 min. All rats treated with saline or with either of the two doses of methylprednisolone, and half of the rats treated with aprotinin, died within the subsequent 2 h. On the other hand, rats treated with norepinephrine, at either dose, or with ACTH-(1-24) were all still alive 2 h later, a similar improvement in cardiovascular and respiratory parameters being obtained with the two treatments. The effect of ACTH on mean arterial pressure was however more sustained throughout the observation period. These results further support the potential usefulness of ACTH-(1-24) as first-aid treatment in cases of severe blood losses.     

Results of bypasses to the anterior tibial artery through the interosseous membrane

Two month-old Wistar male albino rats were exposed during a 30-day period to a daily oral intake ad libitum of either 200 microg/mL Cd (as CdCl2), 0.1 microg/mL Se (as Na-selenite), or the same dosages of Cd + Se in drinking water. The daily intake from the water was calculated to be 15 mg Cd/kg and 7 microg Se/kg. Cadmium (Cd) accumulates in the heart (p < 0.005) and, in rats, decreases both body mass growth (p < 0.005) and heart mass (p < 0.02). Selenium (Se) significantly decreases the negative effect of Cd on body mass growth. In the hearts of Cd-treated rats, cadmium caused the decrease (p < 0.05) of selenium-dependent glutathione peroxidase (GSH-Px, EC 1.11.1.9) activity. At the same time, the activities of total superoxide dismutase (total SOD, EC 1.15.1.1), manganese-containing superoxide dismutase (Mn SOD), and copper-zinc-containing superoxide dismutase (CuZn SOD) were increased (p < 0.005). The activities of total SOD, CuZn SOD (p < 0.005), GSH-Px (p < 0.02), and glutathione-S-transferase (GST, p < 0.005) were increased in the hearts of Se-treated rats. However, by concomitant administration of Cd and Se, these changes were diminished (total SOD, GST) or were completely eliminated (Mn SOD, GSH-Px). These results indicate that Se only partly diminishes the effects of Cd cardiotoxicity.