Automated use of WHONET and SaTScan to detect outbreaks of Shigella spp. using antimicrobial resistance phenotypes.

Antimicrobial resistance is a priority emerging public health threat, and the ability to detect promptly outbreaks caused by resistant pathogens is critical for resistance containment and disease control efforts. We describe and evaluate the use of an electronic laboratory data system (WHONET) and a space-time permutation scan statistic for semi-automated disease outbreak detection. In collaboration with WHONET-Argentina, the national network for surveillance of antimicrobial resistance, we applied the system to the detection of local and regional outbreaks of Shigella spp. We searched for clusters on the basis of genus, species, and resistance phenotype and identified 19 statistical 'events' in a 12-month period. Of the six known outbreaks reported to the Ministry of Health, four had good or suggestive agreement with SaTScan-detected events. The most discriminating analyses were those involving resistance phenotypes. Electronic laboratory-based disease surveillance incorporating statistical cluster detection methods can enhance infectious disease outbreak detection and response.

Intercontinental spread of a new antibiotic resistance gene on an epidemic plasmid.

Bacteria of different genera isolated at nine medical centers in different parts of the United States and at one center in Venezuela during the first decade of gentamicin usage carried the gentamicin resistance gene 2"-aminoglycoside nucleotidyltransferase on the same transferable plasmid. Such widespread dissemination of a newly observed resistance gene on one plasmid suggests that a new resistance gene may emerge once on a single plasmid, which then carries it to other centers and other plasmids. The resistance gene might, therefore, be contained if detected early.

Cytokine expression by invariant natural killer T cells is tightly regulated throughout development and settings of type-2 inflammation.

Invariant natural killer T (iNKT) cells produce cytokines interleukin-4 (IL-4) and IL-13 during type-2 inflammatory responses. However, the nature in which iNKT cells acquire type-2 cytokine competency and the precise contribution of iNKT cell-derived IL-4 and IL-13 in vivo remains unclear. Using IL-13-reporter mice to fate-map cytokine-expressing cells in vivo, this study reveals that thymic iNKT cells express IL-13 early during development, and this IL-13-expressing intermediate gives rise to mature iNKT1, iNKT2, and iNKT17 subsets. IL-4 and IL-13 reporter mice also reveal that effector iNKT2 cells produce IL-4 but little IL-13 in settings of type-2 inflammation. The preferential production of IL-4 over IL-13 in iNKT2 cells results in part from their reduced GATA-3 expression. In summary, this work helps integrate current models of iNKT cell development, and further establishes non-coordinate production of IL-4 and IL-13 as the predominant pattern of type-2 cytokine expression among innate cells in vivo.

Detection and surveillance of antimicrobial resistance.

The clinical microbiology laboratory is strategically positioned to recognize changing patterns in bacterial resistance to antimicrobials. This requires the application of accurate testing methods and a methodological survey of drug-resistance patterns among clinically important bacteria. This information can be assembled into comprehensive international databases, using a common format to facilitate monitoring.

Glycoconjugate boundaries during early postnatal development of the neostriatal mosaic.

The dispositions of galactosyl-containing glycoconjugates were studied during postnatal development of the caudate putamen in mice. The binding of the lectin peanut agglutinin, which has an affinity for galactosyl B-1,3 N-acetylgalactosamine residues, was compared to acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity in the immature and adult neostriatum. The binding of peanut agglutinin conjugated to horseradish peroxidase, in sections that were processed for peroxidase histochemistry, was extremely pronounced in the neostriatum through the first postnatal week and constituted ringlike or polygonally shaped structures, which, overall, produced a variegated mosaic. These structures consist of outer rims of dense lectin-associated reaction product surrounding lightly labeled centers. Lectin delineations of the neostriatal mosaic are no longer visible in the second postnatal week. When adjacent sections were processed for lectin binding or acetylcholinesterase histochemistry, the dense lectin binding sites represented borders of acetylcholinesterase-rich and -poor zones. The distribution of dense patches of tyrosine hydroxylase immunoreactive fibers and terminals also coincides with the acetylcholinesterase-rich zones during the same times, and thus the glycoconjugate-delineated boundaries can also be directly compared with the distribution of nigrostriatal dopaminergic projections. The findings presented here represent the first demonstration of a probe that recognizes apparent borders of neostriatal compartments during a limited period of development. They are consistent with previous observations made on transient glycoconjugate "hidden boundaries" during development of other central nervous system structures, including the somatosensory cortical barrel field, and thalamic and brainstem nuclei (Cooper and Steindler, '86a,b; Steindler and Cooper, in press). In those studies, glia were shown to be the major source of glycoconjugate-associated patterns, and thus, glia and glycoconjugates that they synthesize during pattern formation events may be involved in the formation and stabilization of neurochemically distinct components of the neostriatal mosaic.

Listeroisis in immunosuppressed patients. A cluster of eight cases.

Bactermia due to listeria monocytogenes developed in eight patients who were receiving immunosuppresive medications during a 15 month period at one hospital. Seven survived. Meningitis was documented in only the four who received kidney transplants. Their neurologic signs were minimal, indicating a need to treat any immunosuppressed patient with Listeria bacteremia for meningitis. During this period the incidence of Listeria bactermia in immunosuppressed patients greatly exceeded that previously observed in this hospital or reported elsewhere, but the incidence of infection with other opportunistic agents was not increased. As with previously decreased listeria outbreaks in nonimmunosuppressed patients, no source or mechanism of spread could be identified. Thus, disease due to L. monocytogenes may occur focally among immunosuppressed populations, a pattern which also appears to be emerging for other opportunistic agents. A patient's exposure to different opportunistic agents may be as important as the kind of immunosuppressive therapy he recieves in determining which opportunistic infection he will acquire or even whether any infection will occur.

The epidemiology of bacterial resistance to quinolones.

The new fluoroquinolones have been in use for nearly 10 years in the treatment of community- and nosocomially-acquired infections. Resistant clones may be selected during therapy and disseminate if favourable epidemiological conditions prevail. Resistance to the fluoroquinolones is still rare in common pathogens with 97 to 100% of strains remaining susceptible. Resistance has been reported in methicillin-susceptible Staphylococcus aureus, Campylobacter jejuni/coli, Salmonella, Shigella and Escherichia coli. Among nosocomial pathogens, the incidence of fluoroquinolone resistance varies between bacterial species, countries and periods of study, and is dependent on local epidemiological factors and antibiotic policies. The highest incidence of resistance is observed in Serratia and Acinetobacter spp., and particularly in methicillin-resistant S. aureus. Surveillance programmes are needed to follow up trends in resistance to the fluoroquinolones and their possible association with clinical failures.

Neuron-glial interactions during the in vivo and in vitro development of the nigrostriatal circuit.

This paper examines a particular aspect of glial-neuronal interactions during central nervous system development: the possible influence of growing neurites on the expression of glial-associated extracellular matrix (ECM) molecules. In particular, using in vivo manipulations of the dopaminergic projections from the midbrain substantia nigra, as well as an in vitro model of the developing nigrostriatal circuit, we look at the reciprocal interactions between growing dopaminergic axons and astrocyte-derived ECM molecules in the striatum. Glial-derived glycoconjugates, including tenascin and a proteoglycan designated DSD-1, are developmentally expressed ECM molecules which have been shown to have different effects on immature neurons and their growing processes. Here we show that the glial expression of these ECM constituents in a target region (the caudate-putamen or neostriatum) may be affected by the presence or absence of an appropriate, maturing afferent projection (in this case, dopaminergic nigrostriatal axons). In general, our results reveal complex glial-neuronal interactions during the normal development of central nervous system circuits, and the ability to create in vivo and in vitro models which may be useful toward understanding these complex cellular and molecular interactions in degeneration and plasticity of the nigrostriatal circuit in diseases including Parkinson's.

Phycomycotic gangrenous cellulitis. A report of two cases and a review of the literature.

Progressive gangrenous cellulitis due to Rhizopus arrhizus following colostomy destroyed the entire abdominal wall of a young woman and caused her death. A similar infection in an 11-year-old kidney transplant recipient was diagnosed more promptly and treated successfully with extensive debridement and amphotericin B. Nine similar cases found in the literature were reviewed. All 11 patients appeared to have had prior tissue injury at the original site of infection, and seven had diabetes mellitus. The disease was initially misdiagnosed in most of the patients, progressed rapidly in eight, and was fatal in four. Phycomycotic gangrenous cellulitis should be included in the differential diagnosis of progressive necrotizing lesions of the skin, especially in diabetic patients, but it can be identified promptly only by histologic examination of the infected tissue. Urgent radical excision and amphotericin therapy are recommended.

WHONET: removing obstacles to the full use of information about antimicrobial resistance.

A rich store of detailed information about antimicrobial resistance is at each medical center in paper files inaccessible to analysis or in electronic files too diverse to support a common analytical software. WHONET puts that information on a personal computer at each center in a file code and format that is the same at all centers, so that one software can then fully analyze the files at any center or those merged from many centers. The software monitors the complex matrix of interrelationships between all the measurements of resistance to antimicrobials of tested isolates of each species and of control strains. Differences at a center over time or between centers reflect differences in test performance or in the prevalence of specific resistant strains, which may be tracked. The software helps workers who are knowledgeable about resistance, infection control and clinical use of antimicrobials at any center to control test quality and integrate the management of resistance there. Their ongoing monitoring and experience locally also builds the quality and interpretation of the files merged from many centers.

Diagnostic microbiology laboratory susceptibility test results discriminate distinctive antibiotic resistance plasmids.

The sizes of the zones of inhibition around routinely tested antibiotic disks classified gentamicin-resistant isolates of Klebsiella pneumoniae from one hospital into four major antibiotype classes. From each isolate of the prevalent class (A1), two plasmids could be transferred conjugally. One carried genes for resistance to tetracycline, sulfonamides, and chloramphenicol, and for the SHV beta lactamase. The other carried genes for two aminoglycoside-inactivating enzymes, APH (3')-I and AAC (3)-III, for the TEM 1 beta lactamase, and for resistance to sulfonamides. Transconjugants of either plasmid from any A1 isolate yielded the same DNA fragments after restriction endonuclease digestion, but the two plasmids had no fragments in common. Fragments or genes from either plasmid were variously combined or lacking in plasmids from variant isolates (A2, A3, and A4). Plasmids transferable from isolates of classes B and C shared no common DNA restriction fragments with each other or with either plasmid from Class A. Fragments and genes of the plasmids from C isolates, however, were identical with those of a plasmid endemic in a nearby hospital. Routine monitoring by diagnostic microbiology laboratories of distinctive antibiotypes and of the plasmids that produce them would aid infection control and antibiotic usage policy.

Therapeutic and epidemiologic recommendations to reduce the spread of type-I beta-lactamase resistance.

The objectives of this United States Consensus Panel meeting were to evaluate the effectiveness of current surveillance systems for the detection of bacterial resistance as well as to formulate recommendations that can assist hospitals in determining actions that should be taken when a resistance problem is detected. These recommendations may be particularly helpful in controlling the emergence and spread of type-I beta-lactamase resistance. Numerous case reports of antimicrobial resistance among Enterobacter species, Pseudomonas aeruginosa, and other Gram-negative nosocomial pathogens known to produce type-I beta-lactamases have appeared in the literature since the introduction of the newer "third-generation" cephalosporins. The widespread use of these newer antimicrobial agents, often selected as standard therapy for serious hospital-acquired infections, has been associated with a corresponding increase in resistance to them. The failure of hospitalwide surveillance methods to describe the scope of this problem, especially among the most critically ill patients, may have resulted in a false sense of security among some infectious disease specialists and clinicians prescribing these antimicrobials as empiric therapy. High-level resistance in individual hospital units may be masked in hospitalwide antibiograms. A variety of conclusions and recommendations were formulated based on the collective experiences of the Consensus Panel members. Microbiology laboratories must make it a high priority to identify markers that will assist in rapidly identifying resistant organisms. Cooperative efforts are needed among users of commercial and automated microbiology test instruments to standardize results and to improve quality control, thereby making the data more directly comparable between laboratories.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal glial and glycoconjugate dispositions in the somatosensory cortical barrel field of the early postnatal reeler mutant mouse.

During early postnatal development in reeler mutant mice, lectin binding delineates prospective abnormal barrels as they will appear in the adult mutant somatosensory cortex. Glial fibers also may be more condensed within fascicles in developing reeler barrels. These fibers also appear to be misaligned, coursing predominantly in the tangential plane within the abnormal reeler barrel sides as opposed to having a radial orientation as seen in normal mouse barrels. The thalamic barreloid complex, however, reveals a disposition of glycoconjugates that is completely normal in reeler. Thus, there are anomalies in glia and associated glycoconjugates during mainly cortical development in the reeler mutant mouse that might be related to the primary action of the abnormal gene.

Afferent-boundary interactions in the developing neostriatal mosaic.

The caudate-putamen (neostriatum) of the mammalian basal ganglia is composed of two neurochemically distinct compartments termed patch (island, striosome) and matrix that overall contribute to a mosaic organization. In the present study, the distribution of the developmentally regulated extracellular matrix molecule tenascin, as well as several other neural cell adhesion molecules, was examined in the neostriatal mosaic of the early postnatal mouse and compared with tyrosine hydroxylase distribution following partial destruction of the dopaminergic nigrostriatal projection. During normal neostriatal development, tenascin is most dense within the matrix compartment and highly concentrated in boundaries around patches. This pattern is apparent on embryonic day 18, and for the most part disappears by postnatal day 12. Tenascin immunoreactivity is altered in the neostriatum following lesions of the nigrostriatal pathway in the first postnatal week revealed by an overall reduced expression of this molecule and a marked reduction in tenascin staining of boundaries at the interface of tyrosine hydroxylase-rich patch and tyrosine hydroxylase-poor matrix compartments. When compared to tyrosine hydroxylase immunoreactivity, other cell adhesion molecules tested failed to show altered intensities and patterns of immunoreactivity within the neostriatum after similar lesions. Reduced levels of tenascin in the lesioned neostriatum, in register with altered levels of tyrosine hydroxylase immunostaining of dopaminergic inputs, suggests that axons may affect the expression of particular recognition molecules in their target structures. The fact that boundaries are malleable can be related to afferent-induced plastic events in the differentiation of cellular elements in the developing nigrostriatal system.

Urinary tract infections in an American rehabilitation hospital.

In order to gain a better understanding of urinary tract infection in a rehabilitation hospital, the hospital courses of 119 consecutively admitted patients were studied. Bacteriuria on admission and subsequent incidence of urinary tract infection occurred chiefly among those patients with diagnoses involving peripheral vascular disease and low level of function (Barthel Index) on admission assessment. Females and diabetics among that group were particularly at risk. It was concluded that by using admission screening for detection of bacteriuria and level of function, the members of the high risk group could be predicted, and early urology consultation for bladder training programmes could be focused on those patients who might derive the most benefit.

Hemangioblastoma of the radial nerve: case report.

A case of hemangioblastoma of the right radial nerve is presented. Hemangioblastomas are rare vascular neoplasms characteristically associated with the Von Hippel-Lindau syndrome, in which they are found in the retina, the posterior fossa, and, less often, the spinal cord. Thought of as primary central nervous system neoplasms, hemangioblastomas are rarely found adjacent to the spinal cord involving proximal nerve roots, which represent border zones between the central and peripheral nervous systems. We could find no other report of a pure hemangioblastoma situated this far distally in the peripheral nervous system. The histological findings, immunohistochemistry, and electron microscopic findings of this lesion are discussed. This case supports the hypothesis that hemangioblastoma is not derived from astrocytes, because of the location of this tumor in the peripheral nervous system and glial fibrillary acidic protein negativity.

Focal brain injury and upregulation of a developmentally regulated extracellular matrix protein.

Tenascin is an extracellular matrix glycoprotein expressed during both normal development and neoplastic growth in both neural and nonneural tissues. During development of the central nervous system (CNS), tenascin is synthesized by glial cells, in particular by immature astrocytes, and is concentrated in transient boundaries around emerging groups of functionally distinct neurons. In the mature CNS, only low levels of the glycoprotein can be detected. The present study demonstrates that following trauma to the adult human cerebral cortex, discrete populations of reactive astrocytes upregulate their expression of tenascin and dramatically increase their transcription of the tenascin gene. The enhanced expression of tenascin may be involved in CNS wound healing, and may also affect neurite growth within and around a brain lesion.

Plasmid diversity in Escherichia coli isolated from processed poultry and poultry processors.

Plasmids of bacteria selected from different bacterial populations because they shared a distinctive antimicrobial resistance phenotype have sometimes had identical restriction fragments. Such identical plasmids are thought to belong to small and thus epidemic clones because the plasmid content of unselected resistant isolates has seemed diverse. To survey this presumed diversity and its implications for the lineage of resistance plasmids we examined the transferability, sizes and EcoR1 restriction fragment sizes of plasmids in both Escherichia coli isolated randomly from poultry raised by 16 growers as they were being processed through two plants and in isolates from the urine of women processing poultry in those plants. Forty two (24%) of 175 resistant isolates from poultry of 16 growers and 9 (26%) of 34 resistant isolates from the poultry processors transferred resistance conjugatively to varied combinations of antimicrobials. No poultry isolate had both the same expressed and the same transferred combination as any processor's isolate. The DNA bands which could be discerned in electrophoresis gels of restricted or unrestricted plasmid extracts of isolates or their transconjugants from 156 of the poultry and 24 of the poultry processors appeared diverse. Pairs of related-appearing plasmids were seen in consecutive isolates of poultry from each of two growers and in one pair from different growers. One set of identical-appearing plasmids was seen in 3 consecutive isolates from poultry of one grower, others in 2 consecutive isolates from a second grower's poultry, in 2 non-consecutive isolates of a third grower's, and in single isolates from poultry of 2 different growers. None of the plasmids from any of the human isolates appeared related to those from any other human isolate or to those of any poultry isolate. These results indicate that resistance plasmids are highly diverse and that all but two of the exceptions to complete diversity in the isolates surveyed here could be ascribed to cross colonization within flocks of individual poultry growers. Also, while none of the plasmids in the poultry isolates appeared ancestral to any of plasmids in the poultry processors' isolates, their diversity indicates that those sampled plasmids would be only a very small fraction of the total number of different plasmids in bacteria colonizing poultry processed at that time or earlier.

Meningeal melanocytoma. An uncommon diagnostic pitfall in surgical neuropathology.

OBJECTIVE: To describe the neuropathologic findings in four cases of meningeal melanocytoma, a rare benign melanocytic tumor of the central nervous system. DESIGN: Retrospective analysis of surgical pathology and autopsy material. RESULTS: Grossly, all four tumors were well-circumscribed pigmented lesions, and three of four were attached to dura. Microscopically, the neoplasms were composed of spindle cells with epithelioid foci. Mitoses were not seen and only one case exhibited minimal necrosis. Immunohistochemistry and electron microscopy demonstrated the melanocytic nature of the lesions; all four cases showed S100 protein and neuron-specific enolase staining, and three cases exhibited melanoma-specific antigen staining. Immunostaining for epithelial markers and vimentin was uniformly negative. The single case in which electron microscopy was performed demonstrated premelanosomes. CONCLUSIONS: Meningeal melanocytoma is a benign pigmented neoplasm that can easily be confused with melanoma, especially on frozen section analysis. Practicing surgical pathologists should be aware of this entity.

Extragenital metastases to uterine leiomyomata. A case report.

Malignant extragenital neoplasms with metastases to the uterus are not common, and involvement of a uterine leiomyoma by an extragenital tumor is rare. A case of an infiltrating ductal carcinoma of the breast occurred, with widespread metastases that included a uterine myoma. This entity can be confused with a bizarre or symplastic leiomyoma.