Promoter independence as a feature of most skin papillomas in SENCAR mice.

In the present study, the fate of individual papillomas induced by initiation-promotion on the backs of SENCAR mice was monitored after discontinuation of limited promoter treatment. Groups of 40 SENCAR mice each were initiated by a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) at 2, 1, 0.5, or 0.25 micrograms/mouse. Animals were promoted with 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly during 10 weeks. At that time point, 10 papilloma bearing mice from each group were randomly selected to follow the growth of their existing tumors. Animals and their individual tumors were identified, charted, and photographed weekly. After an initial increase, the average number of papillomas/mouse remained constant after discontinuation of TPA in all the groups except the group receiving the highest DMBA dose (Group 1) and with highest tumor load. Twenty-one weeks after TPA was discontinued, only 10-20% of the papillomas had regressed and no statistically significant differences were found among the different DMBA dose groups. On the other hand, Group 1 showed the highest percentage of coalescing tumors which was apparently a function of tumor load. In addition, no differences were observed in the proportion of positive tumors with activating point mutations at codon 61 of the Ha-ras gene when comparing samples of papillomas from the highest DMBA initiation dose group (2 micrograms) versus the lowest DMBA initiation dose group (0.25 micrograms). Our present data suggest that papillomas induced with low doses of DMBA in SENCAR mice are no more TPA dependent than those induced by higher initiating doses. Furthermore, in SENCAR mice at the doses used in the present study (0.25-2 micrograms/mouse), the number of so-called "promoter dependent" papillomas represents only a small percentage of the total papillomas produced using the initiation-promotion protocol.

The Defence Medical Library Service and military medicine.

The Defence Medical Library Service (DMLS) supports the clinical practice and career development of military health professionals across the world. Clinical governance and the need for medical knowledge to be evidence-based means the DMLS has a central role to play in support of defence medicine. The DMLS is important for enabling health professionals to make sense of the evidence-based pyramid and the hierarchy of medical knowledge. The Royal Centre for Defence Medicine (RCDM) in Birmingham is recognised as an international centre of excellence. The information, knowledge and research requirements of the RCDM will provide opportunities for the DMLS to support and engage with the academic community.

The effect of baclofen on the cardiovascular system of the rat.

1 The cardiovascular responses to baclofen were investigated in anaesthetized rats. 2 Low doses of baclofen (less than 5 X 10(-8) mol), given intravenously, produced a transient fall in blood pressure and heart rate. Higher doses (greater than 5 X 10(-7) mol) produced a marked and prolonged increase in blood pressure accompanied by a rise in heart rate and cutaneous arterial dilatation. 3 The pressor and heart rate responses exhibited tachyphylaxis, and were abolished by hexamethonium, cervical cord section, reserpine-treatment and by a combination of alpha- and beta-adrenoceptor antagonists. 4 It is concluded that the increases in blood pressure and heart rate produced by high doses of baclofen are of central sympathetic origin.

The mechanism of enhancement of the neurogenic oedema response by baclofen.

The effect of baclofen on the neurogenic oedema response to electrical stimulation of the saphenous nerve in rats was investigated. Baclofen 2.5 x 10(-6) mol given intravenously enhanced the neurogenic oedema response and increased blood pressure. The enhancement was not specific to the neurogenic oedema response since plasma exudation responses to substance P, histamine and 5-hydroxytryptamine were also enhanced. No local interactions between baclofen and agents inducing plasma exudation were found which would account for this effect of baclofen. Since agents which abolished the pressor response to baclofen (alpha and beta-adrenoceptor antagonists, hexamethonium, reserpine) also abolished the enhancement of neurogenic oedema, it was concluded that baclofen enhanced the response by its action on the cardiovascular system.

Bitolterol mesylate: a beta-adrenergic agent. Chemistry, pharmacokinetics, pharmacodynamics, adverse effects and clinical efficacy in asthma.

Bitolterol, (3-4 diester colterol) is a new beta 2-adrenergic agonist. Since it in itself is biologically inactive, bitolterol is considered a pro-drug. When administered it is activated within the lung by esterase hydrolysis to the active compound colterol catecholamine N-t-butyl-arterenol). In preclinical and clinical studies to date, bitolterol has proved to be an effective bronchodilator for adult and pediatric patients with chronic stable asthma and for some with chronic obstructive pulmonary disease. Bitolterol has been compared with other beta 2 agents, including isoproterenol, metaproterenol and albuterol. There is no evidence for cardiotoxicity when bitolterol is used in combination with theophylline in human studies. It is effective for control of exercise-induced asthma.

Ultrasonic localization of anesthetic fluid in sub-Tenon's, peribulbar, and retrobulbar techniques.

PURPOSE: To determine the distribution of anesthetic fluid during 3 regional anesthetic techniques routinely used for phacoemulsification. METHODS: Patients having routine cataract extraction by phacoemulsification were studied after informed consent had been obtained. B-scan ultrasonography was performed on the eye before administration of the anesthetic agent. Kinetic echography was used to scan the eye during administration of the anesthesia to show the needle position and location of fluid in the orbit during the injection. Ten minutes after injection, another scan was performed to outline the pattern of fluid distribution. RESULTS: In all patients, the needle and the anesthetic fluid were seen on ultrasonography, with sub-Tenon's the most easily seen. In the sub-Tenon's group, fluid tracked behind the globe in the retrobulbar space, appearing as a dark outline during the injection. The fluid around the optic nerve developed a characteristic T sign. In the retrobulbar technique, the needle was less easily identifiable and fluid localized within the cone. The fluid distributed in the intraconal fat. Identification of the peribulbar needle and fluid was also more difficult; the fluid was, however, seen in the extraconal fat. After 10 minutes, fluid was seen within the cone. CONCLUSION: B-scan ultrasonography was a suitable method of identifying the needle position and the distribution of anesthetic fluid in regional ocular anesthesia. The sub-Tenon's technique appears to be the safest method of introducing anesthetic fluid into the retrobulbar space without the potential complications of sharp-needle techniques.

Prevalence of caseous lymphadenitis and usage of caseous lymphadenitis vaccines in sheep flocks.

OBJECTIVE: To estimate the prevalence of caseous lymphadenitis (CLA), determine the current usage of vaccines against CLA and to measure the effectiveness of these vaccines on sheep farms. DESIGN AND POPULATION: A survey was undertaken on 223 sheep flocks in New South Wales, Victoria and Western Australia. METHOD: The prevalence of CLA was measured by conventional inspection techniques at abattoirs in lines of sheep that could be traced back to a farm. Managers of the flocks were sent a questionnaire about their vaccine practices, management practices and knowledge of CLA. RESULTS: The average prevalence of CLA in adult sheep in these flocks was 26% and varied from 20% in Western Australia to 29% in New South Wales. About 43% of sheep producers used CLA vaccines; only 12% used them as recommended. Awareness of CLA was highest in Western Australia. More producers would use CLA vaccine if they knew the prevalence of CLA in their flock and producers obtained most information about CLA from vaccine resellers. CONCLUSIONS: Only 10 to 15% of producers are currently achieving effective CLA control through the use of recommended CLA vaccination programs. In Western Australian flocks more than 25% of effectively vaccinated ewes will be sent to abattoirs in the 2 to 3 years after this study. However, large decreases in the prevalence of CLA can be achieved by about 70% of producers by either making adjustments to their vaccination programs or buying a vaccine with a CLA component. Two or three key facts on effective CLA vaccination could be made available at the point of sale of vaccines and from abattoirs that reported the prevalence of CLA to farmers.

Isolation of Mycoplasma synoviae from infectious synovitis of chickens.

This report describes the first isolations of Mycoplasma synoviae from the synovial sheaths and joints of commercial chickens affected with synovitis in Australia. Over 4 years 3 separate outbreaks were investigated in which up to 20% of birds exhibited clinical signs of poor growth and "hot foot" syndrome (swollen inflamed footpads). Once an outbreak occurred, chronic infection of the farm usually ensued. Grossly the hocks and footpads were swollen by a purulent exudate and associated inflammatory changes with histological features of a severe acute synovitis. Seroconversion of the flocks occurred at the time of the development of lesions. M. synoviae specific antibodies were demonstrated by ELISA in the joint fluid of affected birds. It is concluded that the cases described are similar to avian infectious synovitis syndrome caused by M. synoviae previously described overseas.

Neonatal nurses' views on the barriers to parenting in the intensive care nursery--a pilot study.

A descriptive study, using a self-reporting questionnaire, was undertaken to identify neonatal nurses' views on barriers to parenting in the intensive care nursery. The objective of the study was to determine nurses' responses to the barriers to parenting identified in the nursing literature. Relevant literature was examined and the questionnaire developed. To determine reliability and validity, the questionnaire was examined by both medical and nursing experts and a pilot study was undertaken, with relevant changes made, as many answers reflect current unit policy rather than opinion. Questionnaires were distributed in an intensive care nursery in Brisbane, Australia; the nurses were asked to rate the extent of their agreement with the points identified in the literature on a seven-point scale, with 1 being the lowest score and 7 the highest. Of the 80 questionnaires distributed, 40 were returned. The results of the questionnaire indicated an understanding of the environmental and emotional barriers confronting parents. However, there was little acknowledgement of the nurse-initiated practices which also prevent parents fulfilling their parenting role. Evenly divided responses were received to several questions, indicating inconsistency in neonatal nurses' views on what constitute barriers to parenting. The results of the questionnaire are of value in extending neonatal nursing knowledge. They provide a snapshot of neonatal nurses' views on the barriers confronting parents as they attempt to fulfill their parenting role, and bring nurse-initiated barriers, such as policy and procedures, to the attention of neonatal intensive care nurses.

Neonatal nurses' views on the barriers to parenting in the intensive care nursery--a national study.

A descriptive research study was undertaken at a national level to identify neonatal nurses' views on the barriers to parenting in the intensive care nursery. The objective of the study was to determine nurses' responses to the barriers to parenting identified in the literature. Relevant literature was examined and a questionnaire developed and pilot tested. In all, 794 questionnaires were distributed with neonatal nursing newsletters and in intensive care nurseries throughout NSW, the ACT, South Australia, Western Australia, the Northern Territory and Queensland. The Neonatal Nurses Association of Victoria and Tasmania did not respond to the invitation for its members to participate, so no questionnaires were distributed in these states. Neonatal nurses were asked to indicate the extent of their agreement with the issues identified in the literature on a four-point scale, with 1 the lowest score and 4 the highest. Of the 794 questionnaires distributed 298 were returned, representing a 37.5 per cent response rate. The results of the questionnaire indicate nurses' understanding of the environmental and emotional barriers confronting parents; however, there was little acknowledgment of nurse-initiated practices which also prevent parents fulfilling their parenting role. Responses to several questions were evenly divided, indicating inconsistency in neonatal nurses' views on what constitute barriers to parenting. The results of the questionnaire provide a national snapshot of the views of neonatal nurses with respect to the barriers confronting parents as they attempt to fulfil their parenting role and bring nurse-initiated barriers, such as policies and procedures, to the attention of neonatal nurses.

Nurses' views on reporting medication incidents.

The purpose of this project was to identify nurses' beliefs about medication incident reporting. A new medication incident form was developed and trialled in six clinical units. Forty-three nurses from these areas were recruited to participate in the project, with a 20-point self-reporting questionnaire and focus group discussions being used to collect the data. Theme analysis of the data was undertaken with the results of the project indicating nurses report medication incidents that are life threatening to patients, but do not want identifying information collected about themselves. This situation represents nurses' fear of reprimand from those in authority and may also indicate an unwillingness to accept responsibility for errors in which they may be merely the final player in a complex series of events. The results of the project also highlight problems associated with self-reported medication incident monitoring and challenge its effectiveness in gathering data required by managers and staff development educators.

Pyrene actin: documentation of the validity of a sensitive assay for actin polymerization.

The fluorescence of pyrene-labelled actin is much higher after polymerization. We have characterized in detail the polymerization properties of pyrene actin and report that native and pyrene actin are identical using the following criteria: (1) the time course of polymerization; (2) the elongation rate constants; (3) the intrinsic viscosity; and (4) the critical concentration. Native and pyrene actin copolymerize. Fluorescence of polymerized pyrene actin is 7-10 times higher than monomer. The fluorescent signal is proportional to polymer weight concentration and is insensitive to filament length distribution. Bleaching can be minimized by appropriate filters to allow continuous monitoring of signal. Measurements do not influence polymerization kinetics. This establishes that pyrene actin fluorescence is a valid assay for actin polymerization that is more sensitive than any other current assay.

Comparison of the FemoStop device and manual pressure in reducing groin puncture site complications following coronary angioplasty and coronary stent placement.

This study compared two techniques, the FemoStop device (RADI Medical Systems, Uppsala, Sweden) and manual pressure, currently used by nurses to achieve haemostasis at the groin puncture site following removal of femoral arterial sheaths in patients following coronary angioplasty and coronary stent placement. Participants were randomly allocated the FemoStop device or manual pressure. Participants' groins were observed for evidence of complications including haemorrhage, haematoma formation and pseudoaneurysm following removal of the femoral arterial sheath and the following day. Of the 274 participants recruited into the study, 5.5% (n = 15) were unable to be included as a result of the absence of data on the Angioplasty Record of Care Form (n = 5) or excessive bleeding at the groin puncture site (n = 10). This left 259 eligible participants. Of these, 18.1% (n = 47) did not have their groin puncture site inspected by a post-procedural observer, thereby reducing the number of participants eligible to complete all stages of the study to 212. The results showed that the presence of a haematoma on removal of the femoral arterial sheath had a significant relationship with the type of treatment used, with those participants in the FemoStop device group showing a greater incidence of haematoma development at the time of sheath removal than those in the manual pressure group. No significant difference was detected in haematoma formation or bleeding between the two groups as a result of the risk factors identified in the literature, including participant anxiety, weight or anticoagulant therapy. There was not any significant difference between the two groups in reported pain during removal of the femoral arterial sheath; however, there was a significant distinction in the amount of time taken to achieve haemostasis. The results showed that haemostasis was achieved more quickly in those participants in the manual pressure group than those in the FemoStop group. The results of this research study indicate that although manual pressure achieved haemostasis more quickly than the FemoStop device, both methods are as effective in reducing groin complications in patients following removal of the femoral arterial sheath following coronary angioplasty and stent placement.

Bitolterol mesylate in exercise-induced asthma.

Exercise-induced asthma is a useful model for evaluating the activity and duration of action of pharmacologic agents of asthma. The main objective of this double-blind, crossover study was to determine the effect of the aerosolized beta-adrenergic agent, bitolterol mesylate, on exercise-induced asthma while its efficacy was being compared with isoproterenol and placebo. Twelve subjects with exercise-induced asthma performed cycloergometer exercise 45 minutes after three inhalations of bitolterol mesylate aerosol (1050 micrograms), or isoproterenol (255 micrograms), or placebo in random sequence. Bitolterol mesylate aerosol was very effective in protecting against exercise-induced asthma. The mean percent maximal decrease of FEV1 after exercise was 5.0% for bitolterol, 22.2% for isoproterenol, and 23.2% for placebo. Subjects experienced skeletal muscle tremor with both bitolterol mesylate (four subjects) and isoproterenol (three subjects), but not with placebo. No other side effects were noted.

Kinetic evidence for a monomer activation step in actin polymerization.

We measured the time course of skeletal muscle actin polymerization at different actin concentrations. In 0.1 M KCl with 1 mM Mg2+, log/log plots of the rate of the early, slow phase of polymerization vs. actin concentration were linear with slopes from 1.0 to 1.3. Computer-assisted calculations of similar curves from theoretical models with different sizes for the nucleus showed that no simple model gave a log/log plot with a slope less than 1.5. Addition of a first-order, monomer activation step before nucleation allowed models of any reasonable nucleus size to have a slope of 1. This is the first evidence that such a step is part of the kinetic pathway for actin polymerization. In 0.1 M KCl with 0.2 mM Ca2+, log/log plots of the rate of the slow phase vs. actin concentration were linear with slopes from 2.0 to 2.5. Monomer activation was not necessary to account for this slope. However, fits of kinetic curves calculated from theoretical models to experimental kinetic curves showed that filament fragmentation was important to achieve a good fit, confirming the finding of Wegner and Savko [Wegner, A., & Savko, P. (1982) Biochemistry 21, 1909-1913]. Our fit procedure also allowed us to estimate the size of the nucleus and the rate constants for activation, nucleation, and fragmentation. In 0.1 M KCl with 1 mM Mg2+, the nucleus was a dimer or trimer, and nucleation was fast. In 0.1 M KCl with 2.0 mM Ca2+, the nucleus was a trimer, and nucleation was slow.

Application of stable isotope methodology in the evaluation of sustained-release theophylline dosage forms.

We compared the kinetics of a single daily dosage form of theophylline (Theo-24) with the kinetics of a twice daily dosage form (Theo-Dur) while we controlled for intrasubject variation in theophylline clearance by use of stable isotope-labeled intravenous theophylline. The stable isotope methodology allowed correction for changes in patient clearance, which allowed more precise estimates of the bioavailability characteristics of these sustained-release theophylline products.

In vitro recoating of reovirus cores with baculovirus-expressed outer-capsid proteins mu1 and sigma3.

Reovirus outer-capsid proteins mu1, sigma3, and sigma1 are thought to be assembled onto nascent core-like particles within infected cells, leading to the production of progeny virions. Consistent with this model, we report the in vitro assembly of baculovirus-expressed mu1 and sigma3 onto purified cores that lack mu1, sigma3, and sigma1. The resulting particles (recoated cores, or r-cores) closely resembled native virions in protein composition (except for lacking cell attachment protein sigma1), buoyant density, and particle morphology by scanning cryoelectron microscopy. Transmission cryoelectron microscopy and image reconstruction of r-cores confirmed that they closely resembled virions in the structure of the outer capsid and revealed that assembly of mu1 and sigma3 onto cores had induced rearrangement of the pentameric lambda2 turrets into a conformation approximating that in virions. r-cores, like virions, underwent proteolytic conversion to particles resembling native ISVPs (infectious subvirion particles) in protein composition, particle morphology, and capacity to permeabilize membranes in vitro. r-cores were 250- to 500-fold more infectious than cores in murine L cells and, like virions but not ISVPs or cores, were inhibited from productively infecting these cells by the presence of either NH4Cl or E-64. The latter results suggest that r-cores and virions used similar routes of entry into L cells, including processing by lysosomal cysteine proteinases, even though the former particles lacked the sigma1 protein. To examine the utility of r-cores for genetic dissections of mu1 functions in reovirus entry, we generated r-cores containing a mutant form of mu1 that had been engineered to resist cleavage at the delta:phi junction during conversion to ISVP-like particles by chymotrypsin in vitro. Despite their deficit in delta:phi cleavage, these ISVP-like particles were fully competent to permeabilize membranes in vitro and to infect L cells in the presence of NH4Cl, providing new evidence that this cleavage is dispensable for productive infection.