Risk factors for community-associated Staphylococcus aureus infections: results from parallel studies including methicillin-resistant and methicillin-sensitive S. aureus compared to uninfected controls.

Despite the increasing burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, the risk factors are not well understood. We conducted a hypothesis-generating study using three parallel case-control studies to identify risk factors for CA-MRSA and community-associated methicillin-susceptible S. aureus (CA-MSSA) infections. In the multivariate model, antimicrobial use in the 1-6 months prior to culture was associated with CA-MRSA infection compared to CA-MSSA [adjusted odds ratio (aOR) 1·7, P=0·07] cases. Antimicrobial use 1-6 months prior to culture (aOR 1·8, P=0·04), history of boils (aOR 1·6, P=0·03), and having a household member who was a smoker (aOR 1·3, P=0·05) were associated with CA-MRSA compared to uninfected community controls. The finding of an increased risk of CA-MRSA infection associated with prior antimicrobial use highlights the importance of careful antimicrobial stewardship.

Predictors of Clostridium difficile colitis infections in hospitals.

Hospital-level predictors of high rates of 'Clostridium difficile-associated disease' (CDAD) were evaluated in over 2300 hospitals across California, Arizona, and Minnesota. American Hospital Association data were used to determine hospital characteristics associated with high rates of CDAD. Significant correlations were found between hospital rates of CDAD, common infections and other identified pathogens. Hospitals in urban areas had higher average rates of CDAD; yet, irrespective of geographic location, hospital rates of CDAD were associated with other infections. In addition, hospitals with 'high CDAD' rates had slower turnover of beds and were more likely to offer transplant services. These results reveal large differences in rates of CDAD across regions. Hospitals with high rates of CDAD have high rates of other common infections, suggesting a need for broad infection control policies.

Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. III. Origins and frequency of occurrence of the terminals.

The cell bodies of the layer II/III pyramidal cells in rat visual cortex receive three morphologically distinct types of axon terminals. These axon terminals all form symmetric synapses and have been termed large, medium-sized, and dense axon terminals. The present study shows that each of these different kinds of axon terminals contains gamma-aminobutyric acid (GABA) which suggests that they are inhibitory. From an analysis of the profiles of 50 cell bodies it is calculated that the average layer II/III pyramidal cell has 65 axosomatic synapses, of which 43 are formed by medium-sized terminals, 10 by large terminals, and 12 by dense terminals. Comparison of these different kinds of axon terminals with labelled axon terminals of known origin suggests that the medium-sized terminals are derived from smooth multipolar cells with unmyelinated axons, and that at least some of the dense terminals originate from bipolar cells that contain vasoactive intestinal polypeptides. The source of the large axon terminals is not known, but it is suggested that they originate from multipolar non-pyramidal cells with myelinated axons. Since the initial axon segments of these same neurons receive GABAergic axon terminals from chandelier cells, at least four different types of neurons provide inhibition to the cell bodies and axons of layer II/III pyramidal cells. This serves as an illustration of the complexity of the neuronal circuits in which pyramidal cells are involved.

Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. II. Synaptic junctions.

Four different types of axon terminals form symmetric synapses with the cell bodies and initial axon segments of pyramidal cells in layer II/III of rat visual cortex. One type belongs to chandelier cells, and the other three kinds of terminals have origins that have not been established yet. These latter are referred to as large, medium-sized and dense terminals. The purpose of the present study was to examine the synaptic junctions formed by all four types of terminal. The synapses formed by the chandelier cell terminals are readily recognized in thin sections because of the characteristics features of both the terminals and the initial axon segments, which are the neuronal elements postsynaptic to them. In en face views of these axo-axonal synapses the junctions can be seen to have presynaptic dense projections that form a grid in which they are triagonally spaced, and have an average centre-to-centre spacing of 84 nm. As an ensemble the projections form the presynaptic grid, which usually has an oval or round outline, but may be notched on one side where projections are absent. The synaptic junctions of the large, medium-sized and dense terminals were examined by making reconstructions of the terminals from serial thin sections. It was found that at the interfaces between the axon terminals and the cell bodies of pyramidal cells, several separate synaptic junctions may be present, in addition to a number of puncta adhaerentia. Thus, there may be as many as five separate synaptic junctions and as few as one.(ABSTRACT TRUNCATED AT 250 WORDS)

Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. I. Morphometric analysis.

An examination of material prepared for conventional electron microscopy has indicated that there are at least four different types of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells in the rat visual cortex. One type of terminal synapses with the initial axon segment and it is derived from the chandelier cell. Because the location and features of these terminals allow them to be readily recognized, chandelier cell terminals were used to determine the extent of morphometric variability that can exist among terminals originating from one cell type. It was found that there is a wide range of mean synaptic vesicle size among chandelier terminals, so that calculated mean vesicle profile diameters for individual terminals can be between 32 and 39 nm. Similar ranges of mean synaptic vesicle sizes also exist among populations of the other three axon terminal types. These terminal types are referred to as 'large', 'medium-sized', and 'dense' terminals. The large terminals synapse with the cell bodies of layer II/III pyramids and their profiles often measure 1.5 X 0.8 microns. The large terminals contain rather loosely packed pleomorphic vesicles and they frequently synapse with a second neuronal element. The medium-sized terminals are smaller, being 1.0 X 0.6-0.8 microns in size, and their synaptic vesicles are usually more closely packed than those within the large terminals. The medium-sized terminals are the ones encountered most frequently on the cell bodies of pyramidal cells and they can also occur on the axon hillock and initial axon segment. The dense terminals are usually flattened against the cell body, and they contain rather rounded and closely packed synaptic vesicles, which often seem to be enmeshed in a rather dark cytoplasmic matrix. This matrix and the close packing of the vesicles makes these terminals appear to be more dense than the others. It is now necessary to determine the origins of the large, medium and dense terminals, and to ascertain if they all use GABA as their neurotransmitter.

Enigmatic bipolar cell of rat visual cortex.

Our earlier Golgi-electron microscopic study of bipolar cells in the rat visual cortex showed the axons of these neurons as forming asymmetric synapses (Peters and Kimerer; J. Neurocytol, 10:921-946, '81) in which the most common postsynaptic elements were dendritic spines. This result was unexpected, since Parnavelas (Parnavelas, Sullivan, Lieberman, and Webster: Cell Tissue Res. 183:499-517, '77) had earlier shown a bipolar cell from the same cortex to have an axon forming symmetric synapses with dendritic shafts. Here then was an enigma, strengthened by examination of neuronal components labelled by antibodies to two compounds in particular--namely, vasoactive intestinal polypeptide (VIP) and choline acetyltransferase (ChAT). Antibodies to these compounds preferentially label bipolar cells in the rat cerebral cortex, and the labelled axon terminals form symmetric synapses. Against this background the present study was performed, and it has been shown that the resolution to the enigma is that there are two different populations of bipolar cells in the rat visual cortex. Thus some Golgi-impregnated bipolar cells examined by electron microscopy after gold toning have been found to possess axons forming asymmetric synapses, and others have been found to have axons forming symmetric synapses. The axons of the bipolar cells forming asymmetric synapses most commonly synapse with dendritic spines (67%), although other terminals synapse with dendritic shafts (33%). In contrast, the bipolar cells with axons forming symmetric synapses preferentially synapse with dendritic shafts (100%). The population of bipolar cells that form symmetric synapses includes the ones that label with antibodies to vasoactive intestinal polypeptide (VIP), for the axons of VIP-labelled bipolar cells have been traced to labelled terminals forming symmetric synapses. However, examination of the population of VIP-labelled axon terminals shows that in addition to dendritic shafts, some of the labelled terminals synapse with the cell bodies of pyramidal and nonpyramidal cells. This includes bipolar cells, some of which receive large numbers of VIP-labelled axon terminals. It is also shown that some VIP-positive bipolar cells have myelinated axons. Analysis of tissue labelled with VIP antibody reveals that about 50% of the total population of bipolar cells in the rat visual cortex is VIP positive. These results are discussed in the light of information about labelling of bipolar cells with antibodies to gamma-aminobutyric acid (GABA) and to other peptides, and it is suggested that most VIP-positive bipolar cells also contain GABA.

Modification of therapy from insulin to chlorpropamide decreases HDL cholesterol in patients with non-insulin-dependent diabetes mellitus.

In 27 patients with non-insulin-dependent diabetes mellitus, we determined fasting serum glucose, hemoglobin A1, body weight, serum triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-chol), high-density lipoprotein cholesterol (HDL-chol), and very-low-density lipoprotein cholesterol during treatment with insulin and several months after changing treatment to chlorpropamide. In five patients, diabetic control deteriorated to the point where insulin was reinitiated. In the remaining 22 patients, despite a significant decrease in weight (122 +/- 5 vs. 114 +/- 5% ideal body wt; P less than .025) on chlorpropamide, HDL-chol fell from 49 +/- 4 to 40 +/- 4 mg/dl (P less than .01) when therapy was modified from insulin to the sulfonylurea. There was a concomitant increase in LDL-chol:HDL-chol from 3.6 +/- 0.3 to 4.4 +/- 0.5 (P less than .05). In the 5 patients in whom insulin was reinstituted, HDL-chol increased to its previous level on insulin (P less than .05). Changing antidiabetic medication from insulin to sulfonylureas may alter the lipoproteins in a manner that increases cardiovascular risk.

The effect of increased longevity, produced by dietary restriction, on the neuronal population of area 17 in rat cerebral cortex.

Area 17 of the brains of Sprague-Dawley derived rats, maintained on a limited ration of food to maintain their weights at the levels attained by two months of age, was compared with area 17 in control groups of rats fed ad lib. The oldest rats in the diet restricted group were sacrificed at 46 and 48 months of age, by which time their life spans had been extended about 12 months beyond the oldest age that rats fed ad lib achieve, for only few of the latter live as long as 33 months. In this study, the rats which were compared consisted of two groups of ad lib fed rats, one 3 and 6 months of age, and the other 33 months old, and two groups of diet restricted rats, one 26 months old and the other 46 to 48 month old rats (designated as 47 month old rats). Two indices were used to assess whether age affects the volume of area 17. One, the number of clusters of apical dendrites of layer V pyramidal cells per unit area of tangential sections, was the same in all groups, indicating that the lateral spread of area 17 did not alter with age. However, the other index, the thickness of area 17, did change with age, for area 17 was significantly thinner in the 47 month old diet restricted rats than in the other three groups. It was also found that the number of neuronal profiles in strips of sections passing through the entire depth of area 17 is decreased in the 47 month old rats, indicating that neurons had been lost from their cortices. This decrease in the number of neuronal profiles in the 47 month old rats was not due to nuclear shrinkage since the sizes of neuronal nuclei were not significantly different in the older ad lib and diet restricted rats. Determinations of neuronal packing densities in layers II/III, IV, V and VIa suggest that neurons are most frequently lost from the deeper cortical layers of the 47 month old rats, and in these layers large vacuolated spaces, the sizes of neuronal cell bodies, have been encountered. It is suggested that these spaces represent places from which neurons have been lost. It is concluded, therefore, that neurons are lost from area 17 in rats whose longevity is increased by diet restriction.

The neuronal composition of area 17 of rat visual cortex. III. Numerical considerations.

The neuronal population of area 17 of rat visual cortex has been examined by using tissue from brains fixed by perfusion. The tissue was osmicated and embedded in plastic so that the same neurons could be examined by both light and electron microscopy. In these preparations area 17 was 1.49 mm thick and by stereological procedures it was calculated that there are about 120,000 neurons beneath 1 mm2 of cortical surface. If one assumes area 17 in each hemisphere of the rat to occupy between 7.1 and 9.4 mm2 of cortical surface, then in each hemisphere the area contains between 850,000 and 1,128,000 neurons. Of these neurons 85% are pyramidal cells and 15% are nonpyramidal cells. About one-third of the nonpyramidal cells occur in layers I and VIb, both of which contain only this kind of neuron. The remaining two-thirds of the nonpyramidal cells are in layers II-VIa. Within these layers it has been possible to differentiate bipolar cells from other types of nonpyramidal cells and in each of these two nonpyramidal cell groups to recognize both small and large neurons. The greatest concentration of nonpyramidal cells occurs in layer II/III. To confirm the validity of the stereologically derived data direct counts were made of the medium and large pyramidal cells in layer V.