A particulate preparation was obtained by low speed centrifugation of guinea pig cerebral cortical homogenates prepared with a Krebs-Henseleit buffer. Light microscopic examination, using a reflected light differential interference contrast system, reveals the presence of intact neurons, axonal fragments, glial cells, and erythrocytes along with an abundance of small spherical entities (diameter about 1.1 micron) and snowman-shaped entities (diameter of larger sphere about 1.1 micron, diameter of attached smaller sphere about 0.6 micron). Many unattached smaller spherical entities are also present (diameter about 0.6 micron). Pressure filtration through 5- or 10-micron Millipore filters, followed by low speed centrifugation and resuspension, removes most of the larger entities to afford a suspension composed mainly of the small spherical and snowman-shaped entities. Electron microscopic examination reveals the presence of many synaptosomes with attached resealed postsynaptic entities. It is proposed that these correspond to the snowman-shaped entities to be termed synaptoneurosomes. Accumulations of cyclic AMP elicited by 2-chloroadenosine and histamine, and by combinations of 2-chloroadenosine, histamine, norepinephrine, and forskolin, are lower in filtered than in unfiltered preparations, whereas accumulations elicited by forskolin are unchanged. Levels of adenylate cyclase are reduced by filtration, whereas levels of phosphodiesterase are unchanged. Filtration reduces levels of markers for whole cells and endothelial cells, whereas neuronal markers such as acetylcholinesterase activity and norepinephrine uptake are increased. Levels of S-100 protein, a marker for glial cells, are not significantly decreased. There is no apparent change in the density of many receptors or ion channels. Levels of A1-adenosine and H1-histamine receptors are increased, whereas levels of so-called peripheral benzodiazepine-binding sites are decreased.

Reconstruction of the anterior cruciate ligament with use of a four-strand hamstring tendon autograft eliminated anterior tibial subluxation in 89% of patients who were examined at a minimum of two years postoperatively. The overall rate of failure was 11%. The functional knee scores were significantly increased at the time of follow-up, but these results did not correlate with the results of knee arthrometric testing.

At the 1948 Annual Meeting of the National Academy there was presented preliminary evidence indicating that each individual possesses what may be called a "metabolic personality"-that is, a distinctive pattern of metabolic traits.1 The existence of these distinctive patterns is established by analysis of body fluids and of physiological responses to chemical stimuli and is exemplified in figure 1. At the left is graphed, using polar co6rdinates, various metabolic traits of the "hypothetical average individual" whose every trait is the average of his fellows. At the right is graphed on the same scales the metabolic pattern of a typical real individual in which many traits vary widely from the average. This pattern is a relatively consistent one and is maintained for this individual at least over a period of several months.The hypothesis was set forth that the metabolic patterns of individuals are of great import in the lives of the individuals who possess them, not only with respect to susceptibility to disease, but also with respect to nutrition, sex, mental abilities and many other facets of their lives.Today we wish to present further and more specific evidence with respect to how these metabolic patterns are of moment in connection with the specific problem of alcoholism. This evidence is based primarily upon animal experimentation, the background of which is described elsewhere.2-4It should be noted at the outset that individual animals in an ordinary laboratory colony have distinctive metabolic traits just as do the members of a human population. In order to conserve space we will not present data to substantiate this statement. When such animals are placed in individual cages and are continuously given a choice between water and 10% alcohol (the positions of the two drinking bottles being switched daily), they exhibit individual patterns with respect to alcohol consumption. Some drink fairly heavily beginning perhaps the first day the alcohol is offered. At the other extreme, some continue to abstain for an indefinite period of time. Intermediate between these are those that drink very moderately for an indefinite period of time and those that drink very little at first but after a few weeks drink relatively heavily. Some individual animals exhibit a relatively steady consumption day after day; in others the consumnption fluctuates widely. (Figure 2) These individual patterns of alcohol consumption are genetically con-

Summary. The production of virulence factors was determined quantitatively for clinical isolates of methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains of Staphylococcus aureus from The London Hospital. The examined factors were: production of enterotoxins A, B, C and D, determined by ELISA; quantitation and differentiation of the membrane-damaging a, p, y and 6 haemolysins; and coagulase production determined by a chromogenic assay. Enterotoxin A was produced by MRSA but not by MSSA. All the strains produced haemolysins a, y and 6 at similar levels, but MRSA produced significantly more coagulase than MSSA. MRSA and MSSA were compared in a phagocytosis assay but there was no difference between the phagocytosis of MRSA and MSSA by human polymorphonuclear leucocytes. These findings indicate that MRSA from The London Hospital is at least as well equipped to cause disease as other isolates of S. aureus, and probably better equipped than most hospital isolates of MSSA.

We report herein that cartilage proteolytic activity increased in bovine and rabbit articular cartilage after treatment with a purified staphylococcal culture medium or intraarticular infection with Staphylococcus aureus. Staphylococcal culture medium increased the release of gelatinolytic, collagenolytic, and caseinolytic activity into the medium of isolated chondrocytes or cartilage organ culture. The proteolytic activities were determined in assays using radiolabeled substrate and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Staphylococcal culture medium was proteolytically inactive by both assay techniques. RNA synthesis of isolated chondrocytes was unaffected by staphylococcal culture medium, whereas overall protein synthesis was inhibited by 84%. An analysis of extracts of Staphylococcus aureus-infected rabbit knee cartilage by substrate gels showed increased gelatinolytic and caseinolytic activity compared with extracts of uninfected knee cartilage. Our data suggest that the rapid loss of proteoglycan and persistent degradation of cartilage in staphylococcal septic arthritis is due to the production and activation of chondrocyte proteases.Septic arthritis continues to be a serious problem in urban medical centers (I ,2) and is recognized as a complicating factor in rheumatoid arthritis and other chronic arthritic conditions (3). Although most joint infections are acquired hematogenously, direct infection can result from deep wounds, surgical procedures, and intraarticular joint injections (2). In nongonococcal septic arthritis, Staphylococcus aureus is the organism most frequently found by culture (64%); in 25% of the patients positive for S aureus, the bacteria are methicillin resistant (1). Sterile "postinfectious" arthritis provides the potential for residual joint damage (43).In an animal model of staphylococcal infectious arthritis, cartilage degradation was shown to continue, despite early antibiotic treatment (5). Infection of rabbit knees with S aureus was shown to cause a rapid loss of cartilage proteoglycan (PG) (a), with a loss of as much as 40% of the total PG from the cartilage matrix within the first 48 hours after infection (8). Loss of collagen becomes significant between the second and third weeks after infection (8). Antibiotic treatment begun within 24 hours of infection decreases collagen loss but fails to prevent loss of PG from the matrix (5).In vitro, S aureus or S aureus-conditioned culture medium induces cartilage degradation in viable cartilage explants (9). Cartilage degradation is marked by a loss of partially degraded PG, which is consistent with increased proteolytic activity. PG release from cartilage by S aureus or staphylococcal culture medium is significantly reduced by freeze-thawing cartilage (9). Killed bacteria have no effect on cartilage degradation. Staphylococcus-induced PG release is dependent on chondrocyte metabolism and can be blocked by inhibitors of RNA and protein synthesis, i.e., actinomycin D and cycloheximide, respectively