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In this paper we address the ways in which surgeons, in collaboration with other members of the surgical team, create occasions for demonstration and instruction within the highly complex and demanding tasks of a surgical operation. Drawing on video recordings of surgical operations, augmented by field studies, we examine how particular phenomena and procedures are made accessible and intelligible to trainees and the ways in which brief episodes of insight and instruction enable complex procedures to be followed and understood. We consider the ways in which demonstration and instruction are achieved, whilst preserving the integrity of medical practice, and explore how trainees are provided with the opportunity to witness, and learn from, the contingent deployment of formal procedures in particular cases. We conclude by considering our observations in the light of recent discussions of practice and situated learning in healthcare training.

Serum from asymptomatic or symptomatic (with cardiovascular manifestations) chagasic patients depleted of the complement system displayed an antiproliferative effect on Trypanosoma cruzi epimastigotes, RA strain, when added to the growth medium. This effect was also observed when patient's serum was depleted of specific antibodies. The antiproliferative effect was both time and concentration dependent. It was confined to the non-dialyzable, high molecular weight, fraction of the serum. This effect was abrogated by allopurinol and catalase, and enhanced by N-ethylmaleimide. Xanthine oxidoreductase and xanthine oxidase activities were increased in the chagasic sera, while catalase activity remained unchanged. Parasites exposed to chagasic sera showed a decrease in Fe/superoxide dismutase activity as well as an increase in membrane lipoperoxidation. Our data provides evidence to support the idea that the antiproliferative activity observed in sera from chagasic patients may be due, at least partially, to a direct effect of hydrogen peroxide on the epimastigotes of T. cruzi. The increase of hydrogen peroxide to antiproliferative levels might result from an increase in xanthine oxidase activity in the serum of patients infected with the parasite.

Background: Hepatitis C virus (HCV) causes significant morbidity and mortality in injecting drug users (IDU) worldwide. HCV vaccine candidates have shown promise for reducing the infectivity of acute infection and averting chronic infection, yet the impact of varying levels of vaccine efficacy and vaccine delivery strategies on the HCV epidemic in IDU have not been explored., Methods: We utilized extensive data on injecting behavior collected in the UFO Study of young IDU in San Francisco to construct a stochastic individual-based model that reflects heterogeneous injecting risk behavior, historical HCV trends, and existing information on viral dynamics and vaccine characteristics., Results: Our modeled HCV rate closely paralleled observed HCV incidence in San Francisco, with estimated incidence of 59% per person year (ppy) early in the epidemic, and 27% ppy after risk reduction was introduced. Chronic HCV infection, the clinically relevant state of HCV infection that leads to liver disease and hepatocellular cancer, was estimated at 22% ppy (± 3%) early in the epidemic and 14% ppy (± 2%) after risk reduction was introduced. We considered several scenarios, and highlight that a vaccine with 50% to 80% efficacy targeted to high-risk or sero-negative IDU at a high vaccination rate could further reduce chronic HCV incidence in IDU to 2-7% ppy 30 years after its introduction., Conclusions: Our results underscore the importance of further efforts to develop both HCV vaccines and optimal systems of delivery to IDU populations.

Background: Early identification of acute coronary syndrome (ACS) in the emergency room is still a difficult task. The objective of this study is to estimate the reliability of heart-type fatty acid binding protein (H-FABP) in identifying ACS in the early stage of chest pain onset., Methods: In a prospective multicentre study in emergency room patients with suspected ACS lasting less than 3 h, heart heart-type fatty acid binding protein (H-FABP) was compared with conventional biomarkers. Protein levels >7 ng/ml were considered positive results., Results: A total of 419 patients were analyzed. Acute myocardial infarction was diagnosed in 148 patients (35%). H-FABP sensitivity was 60% (89 out of 148 patients), significantly higher than troponin T [19% (28 out of 148 patients); P<0,05]. Specificity of troponin T, however, [99% (270 out of 271 patients)] was better than H-FABP [88% (237 out of 271 patients)], though this was not statistically significant., Conclusion: H-FABP can be a useful early diagnostic biochemical marker, particularly within the first 6 h of symptoms, in patients attending the emergency department.

Hexachlorobenzene (HCB) is a widespread environmental pollutant. It has some properties that are typical for dioxin-like compounds that act mainly through the aryl hydrocarbon receptor (AhR) protein. Upon dioxin binding, the AhR translocates to the nucleus and modulates gene expression. At the same time, c-Src kinase frees from the AhR complex and thereby activates its own kinase activity, which acts as a trigger for the growth factor receptor signal transduction pathway. HCB is a weak agonist of the AhR, and the evidence that HCB toxicity is mediated via the AhR complex is limited and inconclusive. In the present study, female Wistar rats were administered HCB (1, 10 and 100mg/kg) for 30 days. Liver cytosolic AhR was translocated to the nucleus. The activity of liver microsomal c-Src increased at all assayed doses. HCB induced the association of the EGFR with c-Src and increased the phosphorylation of EGFR at tyrosine 845 (Tyr845), a known c-Src phosphorylation site. c-Src from WB-F344 cells treated with HCB exhibited increased protein levels and c-Src-pTyr416 phosphorylation than the control cells. Again HCB induced EGFR phosphorylation at Tyr845. Such an effect of HCB could not be detected when c-Src activity was blocked by PP2. All together, our data demonstrates that HCB may induce EGFR transactivation through an c-Src-dependent pathway.

The SWI/SNF complex is a chromatin-remodeling complex that uses the energy of ATP hydrolysis to modify chromatin structure in order to regulate gene expression. The SWI/SNF complex is evolutionarily conserved in all eukaryotes and is comprised of a catalytic subunit, either of BRG1 (also known as SMARCA4) or of BRM (also known as SMARCA2), and a variety of associated proteins that can modulate the recruitment of the complex and its activity. Key observations link the SWI/SNF complex with cancer. First, two of its subunits (SNF5 and BRG1) bear cancer-inactivating mutations and thus are bona fide tumor suppressors. The SNF5 gene is biallelically inactivated in malignant rhabdoid tumors (MRTs) whereas BRG1 is mutated in cancer cell lines of several types, such as those of the breast, prostate, lung, pancreas and colon. Second, mice heterozygous for mutations at Snf5 and Brg1 are cancer-prone, and, third, BRG1 binds or is related to important tumor-suppressor proteins. The present review focuses on the biological function and genetics of BRG1, particularly with respect to its role as a tumor suppressor.

In this article we examine how one of the most pervasive technological implementations in the healthcare domain--the alarm system--is used in anaesthesiology as part of patient monitoring. The utility and appropriateness of alarms in healthcare domains have been widely addressed in the literature. However, we argue that we still know little about the practical use of alarm systems in actual healthcare practice. Studies rarely examine in detail the everyday monitoring practices during normal operations in the absence of, or before, problems become critical and alarming. They have mainly considered how medical professionals manage the interpretation of and response to alarms. Rather than examining how the anaesthesiologist identifies and responds to alarms and critical problems, in this article we focus on how the anaesthesiologist is actively and prospectively engaged in implementing a situated and emergent organization of patient monitoring, using a wide range of different technological and material resources.

Purpose: To analyze the priority of morphological and functional defects in glaucoma., Methods: Nine-hundred seventy-three eyes of 973 subjects were examined with Heidelberg retinal tomograph (HRT II) and Octopus 311 perimeter (TOP strategy). These included 72 controls (C), 659 early and suspect open angle glaucoma (ESG) with perimetric mean defect (MD) lower than 6 dB, and 242 confirmed moderate and advanced glaucomas (AG) with perimetric MD>or=6 dB., Results: I. (Control group): Age was significantly correlated with mean sensitivity (MS) (r=0.50, p<0.00001) and nasal cup shape measure (r=0.33, p=0.005). II. (C and ESG groups): For 95.8% specificity, the best sensitivity was obtained with square root of loss variance (sLV) (ROC area=69.7%, sensitivity=33.7%) and maximum contour elevation (ROC area=69.6%, sensitivity=29.0%). Maximum contour elevation and sLV coincided in diagnosis in 12.4% of cases. An equation using 64 HRT II indices predicted MS with a standard error of estimate (SEE) of 1.87 dB (r=0.67, p<0.00001) and MD (SEE=1.88 dB, r=0.47, p<0.00001). III. (All cases): RB discriminant function value was the best HRT II index to estimate MS values (SEE=5.4 dB, r=0.52, p<0.0001), MD (SEE=5.2 dB, r=0.50, p<0.0001), sLV (SEE=1.9 dB, r=0.41, p<0.0001) and Number of Pathological Points (NPP; SEE=21.3 dB, r=0.49, p<0.0001). Sector correlation of the optic nerve and visual field was high (maximum r=0.66) in cases with superior visual field defects and low in the rest of cases. More than 95% of cases with established glaucoma had abnormal sLV, but <60% had abnormal optic disc indices., Discussion: Perimetry reveals age-related defects slightly more than HRT II. HRT II indices correlated better with MS than with MD, probably because none of them was age corrected. Good correlation between anatomical and functional data in C and ESG, and sensitivity results indicated small differences in early development between both methods. Perimetry identifies defects more clearly than structural measures in established glaucoma.

Context: Video has long been recognised as providing an important resource within medical education, particularly, perhaps, for training in primary health care. As a resource for research, and more specifically within qualitative social science studies of medical practice, video has proved less pervasive, despite its obvious advantages., Methods: In this paper, we sketch an approach to using video to inform the analysis of medical practice and the ways in which health care is accomplished through social interaction and collaboration. Drawing on our own research, we discuss two brief examples: the first involves the use of computing technology in primary health care and the second concerns informal instruction during surgery. The examples illustrate the multimodal character of medical work, how activities are accomplished through the interplay of talk, the visual and the use of material artefacts. They also illustrate the ways in which video provides access to the complex forms of social interaction and collaboration that underpin health care., Discussion: We reflect upon the research opportunities afforded by video and the ways in which video-based studies of interaction can contribute to the practice and practicalities of medicine.

This article discusses intravenous sedation, the authors' anesthesia of choice when performing most esthetic body contour refinement procedures. This technique is comfortable, safe, contemporary, and beneficial to the patient and medical crew. The preanesthesia evaluation is emphasized as a safety and high-quality action to any anesthesia procedure. Alternative anesthesia techniques are also discussed, including their possible advantages, disadvantages, indications, and counterindications.

Objective: Hair plays an important role in determining self-image, social perceptions, and psychosocial functioning. The objectives of this survey were to identify the impact of hair loss on the self-image of men in five European countries and their level of concern about hair loss with regard to image and personal attractiveness. Moreover, we evaluated participants' use of treatments for hair loss and whether treatment success was associated with psychological benefit., Research Design and Methods: A structured questionnaire of closed-ended questions was administered by telephone in major cities in Germany, France, Italy, Spain, and the United Kingdom. Random sampling was used, and eligible respondents were men from 18 to 45 years old., Results: Of the 1536 men responding to the telephone survey, 729 (47%) reported hair loss; these men are the subject of this report. Over 70% of these men reported hair to be an important feature of image, and 62% agreed that hair loss could affect self-esteem. The realization that they were losing hair was linked to concern about losing an important part of personal attractiveness (43% of men), fear of becoming bald (42%), concern about getting older (37%), negative effects on social life (22%), and feelings of depression (21%). Reduced self-confidence in personal attractiveness was also reported by 38% of men who were not in stable romantic relationships. Less than 10% of men were currently pursuing treatment for hair loss, and three out of four had never pursued treatment for hair loss, either at present or in the past. Those few men who pursued treatment and reported success (n = 73) also reported psychosocial benefits as a result: from 43% to 59% experienced improvements in parameters of self-esteem and perception of personal attractiveness. Reliance on self-reporting of hair loss and use of nonvalidated instruments to measure psychological outcomes are important study limitations., Conclusions: The results of this survey indicate a gap between the need for treatment of hair loss and initiation of such treatment among men in five European countries. Further research is needed into the factors affecting men's willingness to seek treatment for hair loss.

Host population thresholds for the invasion or persistence of infectious disease are core concepts of disease ecology and underlie disease control policies based on culling and vaccination. However, empirical evidence for these thresholds in wildlife populations has been sparse, although recent studies have begun to address this gap. Here, we review the theoretical bases and empirical evidence for disease thresholds in wildlife. We see that, by their nature, these thresholds are rarely abrupt and always difficult to measure, and important facets of wildlife ecology are neglected by current theories. Empirical studies seeking to identify disease thresholds in wildlife encounter recurring obstacles of small sample sizes and confounding factors. Disease control policies based solely on threshold targets are rarely warranted, but management to reduce abundance of susceptible hosts can be effective.

Hypoxia-inducible factor-1a (HIF-1a) is a key regulator of the angiogenic cascade. This study analyzed HIF-1a messenger RNA expression levels using real-time quantitative polymerase chain reaction (PCR) in paraffin-embedded surgical specimens from 54 stage IIB-III patients with non-small-cell lung cancer (NSCLC) treated with induction platinum/gemcitabine followed by surgery between September 1998 and December 2002. Radiographic response was observed in 61% of patients. Median survival was 37.8 months. Forty-five patients with complete resection attained a 52-month median survival, whereas 8 patients with incomplete resection had a 12-month median survival, and 1 unresectable patient had a survival of 14 months. No significant differences were observed in overall survival (OS) or event-free survival (EFS) according to HIF-1a expression levels. Patients were divided into quartiles according to HIF-1a gene expression levels. Median EFS for the 13 patients in the lowest quartile has not been reached yet, whereas median EFS for the 13 patients in the top quartile was 9 months (P = 0.192). Similarly, median OS for the 13 patients in the lowest quartile has not been reached yet, whereas median OS for the 13 patients in the top quartile was 52 months (P = 0.297). The cisplatin/gemcitabine combination is highly active in neoadjuvant treatment. Hypoxia-inducible factor-1a expression levels analyzed by real-time quantitative PCR in surgery specimens after platinum/gemcitabine therapy do not correlate with the outcome of patients with stage II/III NSCLC.

Purpose: To evaluate the diagnostic ability of a new perimetric procedure in glaucoma., Methods: Pulsar perimeter shows white circular sinusoidal grating patterns with decreasing amplitude, 5 degrees in diameter, 500 msec in duration in 66 locations. The stimuli scale combines spatial resolution and contrast. The stimuli were shown with centrifugal wave motion at 8 cyl/deg (K6W) or pulse at 30 Hz (T30W). Fifty-six normal eyes and 82 eyes with ocular hypertension and mild glaucoma were included. These 82 cases were classified into four levels of diagnostic certainty, from 0 (ocular hypertension) to 3 (mild glaucoma)., Results: Mean examination time was 3:49 min. Specificity was 96.4% (T30W) and 94.6% (K6W). Sensitivities for levels 0 and 3 were 34.5% to 100% (T30W) and 24.1 % to 75% (K6W). The receiver operating characteristic (ROC) curve areas for T30W at levels 1, 2, and 3 were 0.88, 0.94, and 0.99. The ROC areas for K6W were 0.83, 0.91, and 0.97. There was good correlation between both Pulsar perimetries (r=0.88), but it was lower with conventional perimetry (r=0.58 for T30W and r=0.59 for K6W)., Conclusions: The novel Pulsar T30W perimetry may be helpful for the study of mild glaucoma and ocular hypertension.

Lung cancer is the most common cancer, with dismal outcome. Treatment approaches, including cisplatin-based chemotherapy and surgery, are currently based on the clinical classification of the tumor, without genetic assessment for predicting differential chemosensitivity. BRCA1 plays a central role in DNA repair, and decreased BRCA1 mRNA expression in the human breast cancer HCC1937 cell line caused cisplatin hypersensitivity, but the relation between BRCA1 and survival in lung cancer patients has never been examined. We used real-time quantitative polymerase chain reaction to determine BRCA1 mRNA levels in 55 surgically resected tumors of non-small-cell lung cancer patients who had received neoadjuvant gemcitabine/cisplatin chemotherapy, and divided the gene expression values into quartiles. When results were correlated with outcome, two cut-offs were observed; patients with levels <0.61 had better outcome, and those >2.45 had poorer outcome. Median survival was not reached for the 15 patients in the bottom quartile, whereas for the 28 in the two middle quartiles, it was 37.8 months (95% CI, 10.6-65), and for the 12 patients in the top quartile, it was 12.7 months (95% CI, 0.28-28.8) (P=0.01). Moreover, when patients were stratified by pathologic stage, those in the bottom quartile had a decreased risk of death (HR=0.206; 95% CI, 0.05-0.83; P=0.026) compared with those in the top quartile, and those in the two middle quartiles also had a decreased risk of death (HR=0.294; 95% CI, 0.10-0.83; P=0.020) compared with those in the top quartile. BRCA1 expression is potentially an important tool for use in cancer management and should be assessed for predicting differential chemosensitivity and tailoring chemotherapy in lung cancer.

A photodestructible surfactant, sodium 4-hexylphenylazosulfonate (C6-PAS), has been introduced to AOT-stabilized water-in-heptane microemulsions. Proton NMR spectra show that C6-PAS undergoes UV-induced decomposition, to yield a mixture of 4-hexylphenol and hexylbenzene. The photostationary state was determined by 1H NMR, indicating that nearly 90% of the initial photosurfactant had been destroyed, yielding non-surface-active hexylbenzene as the main product. This phototriggered breakdown gives rise to changes in adsorption and aggregation properties of C6-PAS, representing a novel route to induce microemulsion destabilization. When a series of microemulsions containing different amounts of C6-PAS were exposed to UV light, part of the dispersed water phase-separated. Small-angle neutron scattering (SANS) was used to follow the resulting UV-induced shrinkage of the water nanodroplets: a maximum volume decrease was found to be in the order of 60-70%. Kinetic SANS studies were also carried out in order to follow the changes in aggregation as a function of UV irradiation time. Multicontrast SANS experiments gave further insight; for example, it was demonstrated that the shell thickness remained constant. This study represents the first example of light-induced microemulsion destabilization.

Mycobacterium tuberculosis represents a worldwide health risk and although macrophages are primarily infected, dendritic cells (DC) are important in inducing cellular immune responses against M. tuberculosis. Recent studies have demonstrated that M. tuberculosis targets the DC-specific C-type lectin DC-SIGN to inhibit the immuno-stimulatory function of DC through the interaction of the mycobacterial mannosylated lipoarabinomannan (ManLAM) to DC-SIGN, which prevents DC maturation and induces the immuno-suppressive cytokine IL-10. This may contribute to survival and persistence of M. tuberculosis. Here, we have identified the specific pathogen-derived carbohydrate structure on ManLAM that is recognized by DC-SIGN. We have synthesized the mannose-cap oligosaccharides man-ara, (man)2-ara and (man)3-ara, and demonstrate that these neoglycoconjugates are specifically bound by DC-SIGN. Moreover, we demonstrate that the human and murine DC-SIGN homologue L-SIGN and SIGNR1, respectively, also interact with mycobacteria through ManLAM. Both homologues have the highest affinity for the (man)3-ara structure, similar to DC-SIGN. This study provides information about the specific carbohydrate structures on pathogens that are recognized by DC-SIGN, and may provide strategies to develop vaccines against these pathogens. Moreover, the identification of SIGNR1 as a receptor for ManLAM will enable in vivo studies to investigate the role of DC-SIGN in M. tuberculosis pathogenesis.

One of the most significant developments in healthcare over the past 25 years has been the widespread deployment of information and communication technologies. These technologies have had a wide-ranging impact on the organisation of healthcare, on professional practice and on patients' experience of illness and its management. In this paper we discuss the ways in which Sociology of Health and illness has provided a forum for the analysis of these new technologies in healthcare. We review a range of relevant research published in the Journal; papers that address such issues as dehumanisation and emotional labour, professional practice and identity, and the social and institutional shaping of technology. Despite these important initiatives, we suggest that information and communication technologies in healthcare remain relatively under-explored within the Journal and, more generally, by the sociology of health and illness and point to developments in cognate areas which may have some bearing upon the analysis of technology in action.

The neuropeptide (N) glutamic acid (E) isoleucine (I) amide (NEI) injected into the ventral tegmental area (VTA) or intraventricularly (icv) induces excessive grooming behavior (EGB) and motor activity (MA). Here, we studied whether the cholinergic system is involved in the NEI-induced behavior. The present results demonstrate that atropine, a general muscarinic antagonist, injected icv previous to NEI, suppresses the behavior provoked by icv injections of the peptide, whereas the prior icv injection of dyhidro-beta-erythroidine, a general nicotinic antagonist, did not affect the EGB and MA induced by the peptide. From the experimental evidence, it is suggested that NEI may act specifically on a cholinergic afferent to dopaminergic cells. Also, the results appear to indicate that a neural target, different from the dopamine system, may be activated by the peptide to elicit behavioral changes, such as EGB.

Despite the widespread deployment of CCTV through most major cities and towns in great Britain, and the importance of surveillance to contemporary debates within the social sciences, there remains relatively little detailed research concerned with the practical use of these technologies in the workplace. In this paper, we examine how personnel in the operation rooms in London Underground use CCTV and related equipment to identify problems and events and to develop a co-ordinated response. In particular, we consider how personnel configure scenes to make sense of and interpret the conduct of the travelling public in organizationally relevant ways, and how they shape the ways in which both passengers and staff see and respond to each others' actions. In addressing how personnel constitute the sense and significance of CCTV images, we reflect on the development of information processing systems which are designed to automatically detect conduct and events.

In this study, we investigated: (a) the effect of melanocyte concentrating hormone (MCH) and neuropeptide glutamine (E)-isoleusine-(I) (NEI) on IP(3) production on an "in vitro" model using slices containing caudate putamen (CP) and accumbens nuclei (ACC); and (b) the interaction between these peptides and with alpha-melanocyte-stimulating-hormone (alpha-MSH) on the production of this second messenger. Only MCH at the highest dose studied (3.6 microM) increased the production of IP(3), whereas at the low concentration (0.6 microM) it did not affect IP(3) levels. NEI and alpha-MSH at both concentrations tested (0.6 and 3.6 microM), did not affect IP(3) production either. However, when NEI or alpha-MSH (at 3.6 microM) were added together with 3.6 microM MCH, the increase in the IP(3) content induced by this last peptide was blocked.

We have previously demonstrated that neuropeptide-EI, at high doses, stimulates the production of cAMP, in caudate putamen, through the activation of adenylate cyclase coupled to specific D1 receptors. The aim of the present work was to find evidences for a probable interaction between this neuropeptide and the dopamine D1 receptor in the mammalian central nervous system. The present data show that neuropeptide-EI, at high concentrations, affected both the maximum binding and the apparent affinity of [n-methyl-3H] (R)-(+)-8 chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hemimaleate to the dopamine D1 receptor in a concentration-dependent manner.

It is well established that melanocortic peptides, such as melanocyte-stimulating hormone (MSH) and adrenocorticotropin, induce grooming behavior. The MC3 and MC4 receptors are the MC receptors which are most abundantly expressed in the brain. gamma-MSH, a peptide with preference to the MC3 receptor, however, does not induce grooming. Recent studies have shown that MC4 receptor antagonists are very effective in inhibiting alpha-MSH induced grooming. These data have indicated that grooming behavior in rodents may be mediated by the MC4 receptor. In this study we investigated if the recently developed MC1 receptor selective agonist MS05 was able to induce grooming in comparison with alpha-MSH. The results show that MS05 is effective in inducing grooming after either intracerebroventricular or ventral tegmental area administration in rats. Central administration of either MS05 or alpha-MSH besides grooming also induced stretching, yawning, rearing and locomotion. The results indicate that the earlier hypothesis that the MC4 receptor is the main mediator of grooming behavior has to be modified. Moreover, as this behaviour does not pharmacologically correlate to the profile of any of the five cloned MC receptors, we suggest that alpha-MSH induced grooming may not primarily be mediated by any of these receptors., (Copyright 2000 Harcourt Publishers Ltd.)

Six different isogenic Deltacya Deltacrp derivatives of a strain of Salmonella choleraesuis var. kunzendorf-chi3246 virulent for pigs were constructed by transposon-mediated deletion mutagenesis. These strains were evaluated for virulence and ability to elicit a protective immune response in young weaned pigs after oral administration and were compared to a commercially available vaccine which lacks the 50-kb virulence plasmid (vpl(-)). These derivatives were Deltacya Deltacrp vpl(+), Deltacya Deltacrp vpl(-), Deltacya Delta(crp-cdt) vpl(+), Deltacya Delta(crp-cdt) vpl(-), Deltacya Deltacrp pmi-3834 vpl(+), and Deltacya Delta(crp-cdt) pmi-3834. In experiments to evaluate safety, no significant adverse effects of any of the vaccine constructs were observed, except that two of the strains which carried the virulence plasmid (vpl(+)) caused a small, short-term elevation in maximum temperature compared to pretreatment temperature values. Orally immunized animals, except for those vaccinated with the Deltacya Deltacrp pmi-3834 vpl(+) strain or SC-54, developed significant serum antibody responses 21 days postvaccination as measured by enzyme-linked immunosorbent assay. No cell-mediated immune responses to heat-killed S. choleraesuis were noted at the same time point as measured with heat-killed bacteria as antigen in a lymphocyte proliferation assay. In an oral challenge exposure model with a highly virulent heterologous strain of S. choleraesuis, the Deltacya Deltacrp strains with deletions in pmi were not protective. As measured by morbidity scores, the responses to challenge of the pigs vaccinated with the other four Deltacya Deltacrp derivatives were significantly better than those of the nonvaccinated, challenged group. With the exception of temperature elevation and slight differences in diarrhea scores postchallenge, none of these strains differed significantly from each other in the other clinical parameters analyzed. While the commercial vaccine was protective by most of the parameters measured, it was not fully protective against challenge with virulent S. choleraesuis as judged by diarrhea scores and temperature elevation. Collectively, these data demonstrate that Deltacya Deltacrp derivatives, with or without the virulence plasmid but not with deletions in the pmi gene, are candidates for vaccines for protection against salmonellosis in pigs.

The activity of novobiocin against Escherichia coli ATCC 25922 and three E. coli strains that were isolated from cases of bovine mastitis was determined in timekill studies in the presence of bovine lactoferrin. Lactoferrin alone did not affect the growth of any of the strains of E. coli. A combination of 1.0 mg/ml of lactoferrin and novobiocin at 1/16x minimum inhibitory concentration (MIC) was bactericidal for E. coli ATCC 25922. When the concentration was increased to 3.0 mg/ml of lactoferrin, novobiocin was bactericidal at 1/64x MIC. Among the mastitis strains tested, 6789 and 6806 were more susceptible to killing by novobiocin than was strain 6800. Strains 6789 and 6806 were killed when treated with novobiocin concentrations of 2, 1/2, and 1/4x MIC. When these strains were also treated with lactoferrin at 3.0 mg/ml, there was a bacteriostatic effect at novobiocin concentrations of 1/8 and 1/16x MIC for strains 6789 and 6800. Strain 6806 appeared to be more susceptible to the combination of lactoferrin and novobiocin as was evidenced by a bactericidal effect over the 24-h testing period. The combination treatment with cephapirin and lactoferrin showed that there was a synergistic bactericidal effect against all of the E. coli strains tested. These studies indicate that lactoferrin can potentiate the activity of antibiotics against Gram-negative bacteria.

It is known that alpha-MSH augments cAMP levels in rat brain slices containing accumbens and caudate-putamen nuclei. In this study we examined: a) the effect of other neuropeptides: MCH and NEI, on this cyclic nucleotide; b) if the effects of alpha-MSH on cAMP production can be modulated by addition of MCH or NEI to the incubation medium. Both MCH and NEI (3.6 microM) increased the production of cAMP, whereas at doses of 0.6 microM exerted no effects. When alpha-MSH 0.6 microM was added with NEI or MCH (0.6 microM), only MCH blocked the increase in the cAMP induced by alpha-MSH. Neither MCH nor NEI at the highest dose used (3.6 microM) had any additive effect on AMPc when added together with alpha-MSH. We conclude that, at a high concentration, (MCH/NEI)-like peptides can use the intracellular signal transduction linked to cyclic nucleotides in the CNS.

The protein sequences of different alleles of the rabbit immunoglobulin IGKC1 gene can differ at more than 40% of the amino acid positions. This exceptional degree of allelic divergence raises questions concerning the causal underlying mechanisms. We report the DNA sequence of the coding region of an allotype which is associated with the mitochondrial lineage A (Southwestern Spain). At the serological level, this b5wf allotype presents a patchwork of antigenic determinants which in domestic breeds are characteristic of the b4, b5, and b6 allotypes. The inferred protein sequence of the b5wf allotype was found to differ from that of the b4, b5, and b6 allotypes at 25, 10, and 15% of the amino acid positions, respectively. Sequence comparisons show that the b4-specific epitopes of the b5wf allotype are probably due to a shared ThrThrGlnThr motif at Kabat positions 153-156. Similarly, the shared b5-specific determinants should relate to the motifs 161ThrSerLys163 and/or 182LysSerAspGlu185. A monoclonal antibody binding epitope shared among the b5wf, b5, and b6 sequences appeared to be correlated with the presence of Asp190. Although there is evidence of interallelic genic exchange, sequence comparisons suggest that the apparent mosaic structure of the b5wf allotype is better explained by common ancestry and point mutation.

The in vitro activity of premafloxacin against 673 veterinary pathogens was evaluated. Premafloxacin was equivalent to ciprofloxacin, enrofloxacin, and danofloxacin in activity against the gram-negative bacilli but was much more active (MIC for 90% of the strains tested [MIC90], 0.015 to 0.25 microg/ml) than the comparison antimicrobial agents (MIC90, 0.13 to 16.0 microg/ml) against the staphylococci, streptococci, and anaerobes tested.

Atypical clinical and/or EEG presentation may complicate the diagnosis of juvenile myoclonic epilepsy (JME). To assess the sensitivity of a standard EEG recording, we retrospectively evaluated the EEG performed at their first referral in 56 consecutive JME patients first seen between 1986 and 1992 (26 M, 30 F, aged 12-53, mean 24.4, with onset of JME at age 10-33, mean 14.3). The diagnosis had been made in none of these patients prior to referral, and was often confirmed only during follow-up. A 20-minute standard EEG was recorded, including hyperventilation (HV) and intermittent light stimulation (ILS). This EEG was normal in 15 cases (27%), showing aspecific or misleading changes in 11 cases (20%) and typical changes in only 30 cases (54%). The baseline EEG was normal in 25 (45%), atypical in 11 (20%), and typical for JME in only 20 (35%). HV and ILS yielded 37 and 39 normal, 10 and 7 aspecific and 9 and 10 specific findings, respectively. A single standard EEG without activation may thus be inconclusive or misleading for the diagnosis of JME in more than 50% of newly referred patients.

The mouse model was used to determine the efficacy of the cytokine, tumor necrosis factor-alpha, and antibiotic in treatment of experimentally induced staphylococcal mastitis. Recombinant human tumor necrosis factor-alpha alone administered to the mammary glands of lactating mice recruited significantly more polymorphonuclear neutrophils into the gland by 4 h posttreatment than did the untreated control. One hundred times less recombinant mouse tumor necrosis factor-alpha than human tumor necrosis factor-alpha was required to enhance the killing of Staphylococcus aureus within the gland. Human tumor necrosis factor-alpha effectively enhanced the killing of the bacteria when it was administered 4 to 0 h prior to infection, but not 4 h after infection. When mice were first pretreated with tumor necrosis factor-alpha, infected, and then treated with antibiotics (ciprofloxacin and pirlimycin, but not cloxacillin), the combination of antibiotic and cytokine significantly reduced the number of bacteria within the gland compared with that for mice treated with antibiotic alone, cytokine alone, or placebo. Recombinant tumor necrosis factor-alpha may be an effective adjunct to antimicrobial therapy in treatment of staphylococcal mastitis in the bovine.

A bovine blood polymorphonuclear neutrophil system was used to determine the ability of cytokines, alone or in combination with various antibiotics, to enhance the intracellular killing of Staphylococcus aureus sequestered within these phagocytes. Pretreatment of blood polymorphonuclear neutrophils with human recombinant tumor necrosis factor-alpha, bovine macrophage supernatant tumor necrosis factor-alpha, or human recombinant interleukin-1 beta enhanced the killing of S. aureus by the phagocytes compared with that of untreated polymorphonuclear neutrophils. This enhancement was dose-dependent and required 30 min of contact between the cytokine and the blood polymorphonuclear neutrophils. However, mammary gland polymorphonuclear neutrophils, macrophages, and blood monocytes showed no enhanced killing activity following pretreatment with tumor necrosis factor. Pretreatment of polymorphonuclear neutrophils with tumor necrosis factor and subsequent exposure to various antibiotics after infection with S. aureus enhanced intracellular bacterial killing by certain antibiotics, including paldimycin, rifampin, and ciprofloxacin (antibiotics that normally kill intracellular S. aureus). However, no enhancement occurred with antibiotics that do not normally kill intracellular S. aureus. Cytokine therapy may be a useful adjunct to antibiotic therapy in the treatment of bovine staphylococcal infection and mastitis.

The intracellular location of certain strains of Staphylococcus aureus serves as a reservoir of bacteria which is thought to be important in therapy of recurrent infections in humans and in chronic staphylococcal mastitis in dairy cows. This overview summarizes data pertaining to the intracellular survival of Staphylococcus aureus within polymorphonuclear neutrophils (PMNs) both in vitro and in vivo in the face of antibiotic treatment. While compounds such as rifampin, clindamycin, erythromycin, and ciprofloxacin have been shown to be rapidly taken up by PMNs, the ability of antibiotics to concentrate within PMNs did not strictly correlate with their ability to kill intracellular Staphylococcus aureus. Rifampin and ciprofloxacin have been shown to be the most effective intraphagocytic killing agents, while clindamycin and erythromycin were inactive in these in vitro assays. In vivo, in therapy of Staphylococcus aureus arthritis and peritonitis in humans and in certain mouse models rifampin has generally been shown to be more effective than comparator antibiotics. In a staphylococcal subcutaneous abscess model, however, clindamycin was very effective in curing the Staphylococcus aureus abscesses in this system where PMNs were the primary inflammatory cells involved. The intracellular bacterial counts decreased as rapidly as the extracellular bacteria. Rifampin was also effective in the abscess model but ciprofloxacin was ineffective at the highest doses tested. The relevance of in vitro and in vivo models and the importance of PMNs as a reservoir of infection in staphylococcal diseases in humans and the dairy cow are discussed.

The prevalence of the herpes simplex virus infection was investigated in a chilean female population. During 1981 and 1985 a number of 1,003 women were analyzed through serological methods. A 29.1% of the group referred past history of oral herpes and 59.4% of these presented 1 to 2 recurrent episodes a year. The high prevalence of this infection in our population is shown when detecting that a 91.4% of the female population had antiherpes simplex antibodies and the titer of this antibodies were in direct correlation to the antecent of recurrent clinical herpes and to the frequency of these episodes.

A bovine polymorphonuclear leukocyte (PMN) monolayer system was used to determine the ability of different antibiotics to kill surviving intracellular Staphylococcus aureus. The following classes of antimicrobial agents were tested in this high-volume assay procedure: aminocyclitol, beta-lactam, coumarin, lincosaminide, macrolide, naphthalenic ansamycin, paulomycin, peptide, quinolone, and tetracycline. The activities of these compounds were compared with those of positive (rifampin), negative (cloxacillin), and non-antibiotic-treated controls. Only oxytetracycline, the ansamycins (rifampin, rifamycin SV, streptovaricin A, C, and D), paulomycin, and paldimycin caused a significant reduction in the viable count of intracellular S. aureus. Of these, however, the intracellular killing by the streptovaricins was directly related to the cytotoxicity (as determined by trypan blue exclusion) of these compounds for the PMNs. Although the paulomycins were cytotoxic for the PMNs, the cytotoxic and the intracellular killing activity of these new compounds could be distinguished. The relevance of these results to the therapeutic effectiveness of these antibiotics in the treatment of bovine staphylococcal mastitis is discussed.

Bovine mastitis due to Staphylococcus aureus may become chronic and refractory to antibiotic therapy because of the organism's ability to survive within the mammary gland macrophages and/or polymorphonuclear neutrophils (PMNs). Therefore, phagocytosis and killing of S. aureus by bovine udder macrophages, udder and blood neutrophils and blood monocytes were studied. Gland and blood PMNs were about equally effective at phagocytosing (2.5 log reduction in supernatant) and killing the bacteria (92% reduction of viable bacteria by two hours). Gland macrophages phagocytosed at a lower rate (1.5 log reduction) and were less effective at killing the bacteria (73% reduction by two hours). Blood monocytes phagocytosed and killed S. aureus at the lowest rate. An udder macrophage monolayer system was developed and used to evaluate the ability of antibiotics to kill surviving intracellular S. aureus. This assay was similar to our previously described system with blood PMNs. Several classes of antibiotics were investigated. These included naphthalenic ansamycin, lincosaminide, tetracycline, coumarin, peptide, paulomycin, quinolone, macrolide, cephalosporin, and penicillin-class antibiotics. The activity of these compounds was compared to positive (rifampicin), negative (cloxacillin), and nonantibiotic treated controls. Only naphthalenic ansamycin class antibiotics, paulomycin, paldimycin and ciprofloxacin caused significant reduction in viable intracellular bacteria in the macrophage system. These results were similar to those obtained in the blood PMN monolayer system. Because a low intraphagolysosomal pH could affect an antibiotic's ability to kill intracellular bacteria by affecting the drug itself or inhibiting bacterial growth, the effect of low pH on the minimum inhibitory concentration and the minimum lethal concentration of clindamycin and rifampicin against three strains of S. aureus was also tested. While the activity of clindamycin at pH 5.0 compared to pH 7.0 was not affected greatly, the activity of rifampicin was greatly enhanced at acidic pH. These results suggest that at least some of the excellent activity of rifampicin for intracellular S. aureus is due to potentiation of its activity in the intracellular acidic compartment of the phagolysosome.