A laser driven pulsed X-ray backscatter technique for enhanced penetrative imaging.

X-ray backscatter imaging can be used for a wide range of imaging applications, in particular for industrial inspection and portal security. Currently, the application of this imaging technique to the detection of landmines is limited due to the surrounding sand or soil strongly attenuating the 10s to 100s of keV X-rays required for backscatter imaging. Here, we introduce a new approach involving a 140 MeV short-pulse (< 100 fs) electron beam generated by laser wakefield acceleration to probe the sample, which produces Bremsstrahlung X-rays within the sample enabling greater depths to be imaged. A variety of detector and scintillator configurations are examined, with the best time response seen from an absorptive coated BaF2 scintillator with a bandpass filter to remove the slow scintillation emission components. An X-ray backscatter image of an array of different density and atomic number items is demonstrated. The use of a compact laser wakefield accelerator to generate the electron source, combined with the rapid development of more compact, efficient and higher repetition rate high power laser systems will make this system feasible for applications in the field. Content includes material subject to Dstl (c) Crown copyright (2014). Licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@ nationalarchives.gsi.gov.uk.

The Teamwork Study: enhancing the role of non-GP staff in chronic disease management in general practice.

There is evidence for a team-based approach in the management of chronic disease in primary health care. However, the standard of care is variable, probably reflecting the limited organisational capacity of health services to provide the necessary structured and organised care for this group of patients. This study aimed to evaluate the impact of a structured intervention involving non-GP staff in GP practices on the quality of care for patients with diabetes or cardiovascular disease. A cluster randomised trial was undertaken across 60 GP practices. The intervention was implemented in 30 practices with staff and patients interviewed at baseline and at 12-15 months follow up. The change in team roles was evaluated using a questionnaire completed by practice staff. The quality of care was evaluated using the Patient Assessment of Chronic Illness Care questionnaire. We found that although the team roles of staff improved in the intervention practices and there were significant differences between practices, there was no significant difference between those in the intervention and control groups in patient-assessed quality of care after adjusting for baseline-level score and covariates at the 12-month follow up. Practice team roles were not significantly associated with change in Patient Assessment of Chronic Illness Care scores. Patients with multiple conditions were more likely to assess their quality of care to be better. Thus, although previous research has shown a cross-sectional association between team work and quality of care, we were unable to replicate these findings in the present study. These results may be indicative of insufficient time for organisational change to result in improved patient-assessed quality of care, or because non-GP staff roles were not sufficiently focussed on the aspects of care assessed. The findings provide important information for researchers when designing similar studies.

Tissue microarray (TMA) use in post mortem neuropathology.

BACKGROUND: Tissue microarrays (TMAs), where each block (and thus section) contains multiple tissue cores from multiple blocks potentially allow more efficient use of tissue, reagents and time in neuropathology. NEW METHOD: The relationship between data from TMA cores and whole sections was investigated using 'virtual' TMA cores. This involved quantitative assessments of microglial pathology in white matter lesions and motor neuron disease, alongside qualitative TDP-43 inclusion status in motor neuron disease cases. Following this, a protocol was developed for TMA construction. RESULTS: For microglial pathology we found good concordance between virtual cores and whole sections for volume density using one 1.75 mm core (equivalent to a 2 mm core after accounting for peripheral tissue loss). More sophisticated microglial cell size and measures required two cores. Qualitative results of pTDP-43 pathology showed use of one 1.75 mm core gave a 100 % sensitivity and specificity within grey matter, and 88.3 % sensitivity and 100 % specificity within white matter. A method of producing the TMAs was suitable for immunohistochemistry both manually and by autostainer, with the minimal core loss from the microscope slide. COMPARISON WITH EXISTING METHODS: TMAs have been used infrequently in post mortem neuropathology research. However, we believe TMAs give comparable tissue assessment results and can be constructed, sectioned and stained with relative ease. CONCLUSIONS: We found TMAs could be used to assess both quantitative (microglial pathology) and qualitative pathology (TDP-43 proteinopathy) with greatly reduced quantities of tissue, time and reagents. These could be used for further work to improve data acquisition efficiency.

Permeability of edible coatings.

The permeabilities of water vapour, O2 and CO2 were determined for 18 coating formulations. Water vapour transmission rate ranged from 98.8 g/m(2).day (6% beeswax) to 758.0 g/m(2).day (1.5% carboxymethyl cellulose with glycerol). O2 permeability at 14 ± 1°C and 55 ± 5% RH ranged from 1.50 to 7.95 cm(3)cm cm(-2)s(-1)Pa(-1), with CO2 permeability 2 to 6 times as high. Permeability to noncondensable gases (O2 and CO2) was higher for hydrophobic (peanut oil followed by beeswax) coatings as compared to hydrophilic (whey protein concentrate and carboxymethyl cellulose).

Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis.

BACKGROUND: Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. METHODS: A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. KEY RESULTS: Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). CONCLUSIONS & INFERENCES: Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.

Voyaging into the third dimension: A perspective on virtual methods and their application to studies of juvenile sex estimation and the ontogeny of sexual dimorphism.

In contrast to the well-established and highly accurate morphological methods available for sexing adult skeletons, juvenile sex estimation is widely recognised as a difficult task that faces a series of challenges. The acquisition of 3D data, and construction of 3D models from volume or surface scans, has become increasingly common in forensic sciences, and these data offer considerable opportunity for the development and refinement of methods in sex estimation. The suitability and potential of virtual methods for juvenile sex estimation are evaluated with the aims of identifying (1) the benefits and challenges associated with virtual data and quantitative analysis of 3D models, and (2) pathways that may lead to practical improvements for sexing juveniles. The issues associated with sex estimation in juveniles are discussed and approached in the context of a framework that unifies classification results for a given trait, which provide information on its capacity to discriminate between the sexes, with the underlying patterns of dimorphism over ontogeny. Virtual collections of 3D models are suggested as integral to this framework because they enable the magnitude and mode of sexual dimorphism to be comprehensively quantified for a chosen trait or set of traits. Those data can be used to inform decisions about how to apply a method for sex estimation to maximize its success. Virtual collections, through extending the scope of analyses and impacting the way in which questions on sexual dimorphism in juveniles may be answered, are undoubtedly set to play a central role in future research.

IL-2Ralpha-Directed monoclonal antibodies provide effective therapy in a murine model of adult T-cell leukemia by a mechanism other than blockade of IL-2/IL-2Ralpha interaction.

Adult T-cell leukemia (ATL) develops in a small proportion of human T-cell lymphotrophic virus-I infected individuals. The leukemia consists of an overabundance of activated T cells, which are characterized by the expression of CD25, or IL-2Ralpha, on their cell surface. Presently, there is not an accepted curative therapy for ATL. We developed an in vivo model of ATL in non-obese diabetic/severe combined immunodeficient (NOD/ SCID) mice by introducing cells from an ATL patient (MET-1) into the mice. The leukemic cells proliferated in these mice that lack functional T, B, and natural killer (NK) cells. The MET-1 leukemic cells could be monitored by measurements of both serum soluble Tac (IL-2Ralpha) and soluble human beta2-microglobulin (beta2mu) by ELISA. The disease progressed to death in the mice after approximately 4-6 weeks. The mice developed grossly enlarged spleens and a leukemia involving ATL cells that retained the phenotype and the T-cell receptor rearrangement and human T-cell lymphotrophic virus-I integration pattern of the patient's ATL leukemia cells. This model is of value for testing the efficacy of novel therapeutic agents for ATL. The administration of humanized anti-Tac (HAT), murine anti-Tac (MAT), and 7G7/B6, all of which target IL-2Ralpha, significantly delayed the progression of the leukemia and prolonged the survival of the tumor-bearing mice. In particular, HAT induced complete remissions in 4 of 19 mice and partial remissions in the remainder. It appears that the antibodies act by a mechanism that had not been anticipated. The prevailing view is that antibodies to the IL-2Ralpha receptor have their effective action by blocking the interaction of IL-2 with its growth factor receptor, thereby inducing cytokine deprivation apoptosis. However, although both HAT and MAT block the binding of IL-2 to IL-2Ralpha of the high affinity receptor, the 7G7/B6 monoclonal antibody binds to a different epitope on the IL-2Ralpha receptor, one that is not involved in IL-2 binding. This suggested that the antibodies provide an effective therapy by a mechanism other than induction of cytokine deprivation. In accord with this view, the MET-1 cells obtained from the spleens of leukemic mice did not produce IL-2, nor did they express IL-2 mRNA as assessed by reverse transcription-PCR. Another possible conventional mechanism of action involves complement-mediated killing. However, although MAT and 7G7/B6 fix rabbit complement, HAT does not do so. Furthermore, in the presence of NOD/SCID mouse serum, there was no complement-mediated lysis of MET-1 cells. In addition, the antibodies did not manifest antibody-dependent cellular cytotoxicity with NOD/SCID splenocytes that virtually lack NK cells as the effector cells as assessed in an in vitro chromium-release assay. However, in contrast to the efficacy of intact HAT, the F(ab')2 version of this antibody was not effective in prolonging the survival of mice injected with MET-1 ATL cells. In conclusion, in our murine model of ATL, monoclonal antibodies, HAT, MAT, and 7G7/B6, appear to delay progression of the leukemia by a mechanism of action that is different from the accepted mechanism of IL-2 deprivation leading to cell death. We consider two alternatives: the first, antibody-dependent cellular cytotoxicity mediated by FcRI- or FcRIII-expressing cells other than NK cells, such as monocytes or polymorphonuclear leukocytes. The second alternative we consider involves direct induction of apoptosis by the anti-IL-2R antibodies in vivo. It has been shown that the IL-2R is a critical element in the peripheral self-tolerance T-cell suicide mechanism involved in the phenomenon of activation-induced cell death.

A new family of bizarre durophagous carnivorous marsupials from Miocene deposits in the Riversleigh World Heritage Area, northwestern Queensland.

A new specimen of the bizarrely specialised Malleodectes mirabilis from middle Miocene deposits in the Riversleigh World Heritage Area provides the first and only information about the molar dentition of this strange group of extinct marsupials. Apart from striking autapomorphies such as the enormous P3, other dental features such as stylar cusp D being larger than B suggest it belongs in the Order Dasyuromorphia. Phylogenetic analysis of 62 craniodental characters places Malleodectes within Dasyuromorphia albeit with weak support and without indication of specific relationships to any of the three established families (Dasyuridae, Myrmecobiidae and Thylacinidae). Accordingly we have allocated Malleodectes to the new family, Malleodectidae. Some features suggest potential links to previously named dasyuromorphians from Riversleigh (e.g., Ganbulanyi) but these are too poorly known to test this possibility. Although the original interpretation of a steeply declining molar row in Malleodectes can be rejected, it continues to seem likely that malleodectids specialised on snails but probably also consumed a wider range of prey items including small vertebrates. Whatever their actual diet, malleodectids appear to have filled a niche in Australia's rainforests that has not been occupied by any other mammal group anywhere in the world from the Miocene onwards.

Experiment and simulation of novel liquid crystal plasma mirrors for high contrast, intense laser pulses.

We describe the first demonstration of plasma mirrors made using freely suspended, ultra-thin films formed dynamically and in-situ. We also present novel particle-in-cell simulations that for the first time incorporate multiphoton ionization and dielectric models that are necessary for describing plasma mirrors. Dielectric plasma mirrors are a crucial component for high intensity laser applications such as ion acceleration and solid target high harmonic generation because they greatly improve pulse contrast. We use the liquid crystal 8CB and introduce an innovative dynamic film formation device that can tune the film thickness so that it acts as its own antireflection coating. Films can be formed at a prolonged, high repetition rate without the need for subsequent realignment. High intensity reflectance above 75% and low-field reflectance below 0.2% are demonstrated, as well as initial ion acceleration experimental results that demonstrate increased ion energy and yield on shots cleaned with these plasma mirrors.

NASH resolution is associated with improvements in HDL and triglyceride levels but not improvement in LDL or non-HDL-C levels.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is associated with dyslipidemia and cardiovascular disease (CVD). AIM: To determine the relationship between resolution of NASH and dyslipidemia. METHODS: Individuals in the Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial with paired liver biopsies and fasting lipid levels were included (N = 222). In the PIVENS trial individuals were randomised to pioglitazone 30 mg, vitamin E 800 IU or placebo for 96 weeks. Change in lipid levels at 96 weeks was compared between those with and without NASH resolution. RESULTS: Dyslipidemia at baseline was frequent, with low high-density lipoprotein (HDL) (<40 mg/dL in men or <50 mg/dL in women) in 63%, hypertriglyceridaemia (≥150 mg/dL) in 46%, hypercholesterolaemia (≥200 mg/dL) in 47% and triglycerides (TG)/HDL >5.0 in 25%. Low-density lipoprotein (LD) ≥160 mg/dL was found in 16% and elevated non-HDL cholesterol (non-HDL-C) (≥130 mg/dL) in 73%. HDL increased with NASH resolution but decreased in those without resolution (2.9 mg/dL vs. -2.5 mg/dL, P < 0.001). NASH resolution was associated with significant decreases in TG and TG/HDL ratio compared to those without resolution (TG: -21.1 vs. -2.3 mg/dL, P = 0.03 and TG/HDL: -0.7 vs. 0.1, P = 0.003). Non-HDL-C, LDL and cholesterol decreased over 96 weeks in both groups, but there was no significant difference between groups. Treatment group did not impact lipids. CONCLUSIONS: NASH resolution is associated with improvements in TG and HDL but not in other cardiovascular disease risk factors including LDL and non-HDL-C levels. Individuals with resolution of NASH may still be at increased risk of cardiovascular disease. ClinicalTrials.gov identifier: NCT00063622.

Experimental regeneration in canine muscular dystrophy--1. Immunocytochemical evaluation of dystrophin and beta-spectrin expression.

The expression of dystrophin and beta-spectrin was examined from 1 to 56 days in regenerating muscle fibres in normal and dystrophic dogs, following necrosis induced by the venom of Notechis scutatis. Normal and dystrophic dog muscle regenerated at an equal rate and new myotubes were present in both at the periphery of necrotic fibres by 3 days. In normal dogs dystrophin was detected in the sarcoplasm of the regenerating fibres by 3 days and was localized to the plasma membrane by 4 days. The localization of dystrophin is independent of beta-spectrin and was detected before beta-spectrin, which was not observed until 5-6 days. Normal peripheral labelling of both was restored by 14 days in normal dogs. Normal beta-spectrin labelling of regenerating dystrophic fibres was also restored by 14 days and is not dependent on the presence of dystrophin in dystrophic dogs. A proportion of regenerating fibres in normal and dystrophic dogs showed weak immunolabelling of beta-spectrin prior to 14 days. This is a feature of immature muscle fibres. Antibodies to different domains of dystrophin bound to the periphery and sarcoplasm of regenerating fibres in dystrophic dogs, particularly during the first 7 days of regeneration, but the fluorescence was less intense than in normal dogs. Weak labelling with antibodies corresponding to the C-terminus of the rod domain of dystrophin persisted on dystrophic regenerating fibres up to 21 days. This may relate to developmental isoforms of dystrophin.

Expression of laminin subunits in congenital muscular dystrophy.

The expression of laminin subunits M, A, B1 and B2 was studied immunocytochemically in 25 cases of classical congenital muscular dystrophy (CMD), 11 hypotonic infants, 20 cases of a variety of inherited and acquired neuromuscular disorders, and 11 controls. Merosin, as indicated by labelling for the M chain, was deficient in 12 (48%) of the cases of classical CMD. Seven cases had no detectable labelling for the M chain whereas five showed traces, including three cousins from the same family. This suggests that very low expression may relate to a possible difference in the molecular defect, compared with cases completely devoid of the M chain. The A chain was abundant in regenerating fibres and in immature fibres expressing fetal myosin. In all merosin-deficient cases the A chain was over-expressed but this was not due to immaturity. A secondary reduction in sarcolemmal expression of the B1 chain occurred in five merosin-deficient cases, whilst expression in vascular tissue was normal. B1 was also reduced in one merosin-positive case of CMD, suggesting that other subunits may be involved in other forms of CMD. No differences in the expression of the B2 chain were observed in any of the cases studied. No abnormality in laminin subunits was found in controls or other neuromuscular disorders.

Experimental regeneration in canine muscular dystrophy--2. Expression of myosin heavy chain isoforms.

The sequential expression of neonatal, fast and slow myosin heavy chain isoforms was examined during the regeneration of normal and dystrophic dog muscle from 1 to 56 days, following necrosis induced by the venom of Notechis scutatis, to assess the regenerative potential of dystrophic muscle. Regeneration was equally rapid in normal and dystrophic dogs but morphological and immunocytochemical abnormalities were more apparent in the dystrophic fibres. New myotubes were formed by 3 days, and by 4 days all myosin isoforms were expressed. Neonatal myosin persisted in normal dogs after morphological restoration of the muscle and after dystrophin and beta-spectrin expression had returned to normal. Neonatal myosin was considerably reduced by 21 days in normal dogs, but persisted beyond 28 days in dystrophic dogs, suggesting a delay in maturation. At 42 and 56 days, dystrophic dogs showed a population of small fibres expressing neonatal myosin, which may represent a second cycle of degeneration and regeneration. The reciprocal pattern of fast and slow myosin was not fully restored in normal or dystrophic regenerating muscle, and co-expression persisted. Thus, dystrophic muscle retains its potential to regenerate, but maturation is slower than normal. The persistent co-expression of isoforms has implications for the long-term function of fibres formed after myoblast therapy, but the results imply that a stable state can be achieved if dystrophin expression is restored by gene or myoblast transfer therapy.

Variable clinical phenotype in merosin-deficient congenital muscular dystrophy associated with differential immunolabelling of two fragments of the laminin alpha 2 chain.

Approximately half the cases of classical congenital muscular dystrophy (CMD) have a pronounced deficiency or absence of the laminin alpha 2 chain of laminin-2 (merosin). This is caused by mutations in the LAMA2 gene that codes for laminin alpha 2, and all informative cases so far studied show linkage to the appropriate region on chromosome 6q. Most CMD patients with a deficiency of laminin alpha 2 have a severe phenotype that involves skeletal muscle, and the central and peripheral nervous system. We have identified four cases that have minimal reduction of laminin alpha 2 using a commercial antibody that only recognises a C-terminal 80 kDa fragment, but show a pronounced reduction using an antibody to the 300 kDa fragment. Haplotype analysis is compatible with linkage to the LAMA2 locus in three informative families, whilst the fourth family was not informative. Two of the affected children are ambulant and have a mild phenotype. The third case is unusual in having severe muscle weakness but does not show the white matter changes on magnetic resonance imaging of the brain that is usually seen in merosin-deficient cases of CMD; the fourth case has a severe phenotype, typical of merosin-deficient patients but shows good immunolabelling of the 80 kDa fragment of laminin alpha 2, corresponding to the C-terminal region. Our data show that there is a broad spectrum of phenotype and protein expression associated with a primary deficiency in laminin alpha 2, and that a wider range of clinical cases need to be screened for a deficiency of merosin. It is also important to study the expression of laminin alpha 2 with more than one antibody.

Xenoantibody directed against molecular components of the HLA system. Quantitation of antibody to serologically defined HLA complexes on the cell surface.

A quantitative absorption-blocking assay was used to measure the levels of antibody in immune rabbit sera that react with the serologically defined HLA molecular complex on the cell surface. Quantitation was determined by comparing the number of xenoantibody-treated cells with the number of untreated control cells needed to absorb a defined amount of cytolytic alloantibody. Complement-dependent cytolytic titers were used to standardize the total antibody content reactive with cell surface antigens of xenoantisera used to treat absorbing cells. The ability of xenoantibody to "block" or inhibit the reaction of alloantibody with the absorbing cell was observed to be the result of concomitant removal of both xeno- and alloantigenic determinants from the cell surface. Immunofluorescence data with xenoantibody suggested that removal was accomplished by temperature-dependent selective redistribution and endocytosis of the serologically defined HLA molecule complex. By using these procedures, xenoantisera have been characterized that contain different amounts of antibody to the two-component HLA complex relative to their total cytolytic antibody content. Variation ranges from a xenoantiserum with little or no blocking capacity to several highly effective serologically defined HLA blocking xenoantisera.

Blocking induction of human cytotoxic T lymphocytes with anti-Ia xenoantiserum.

A xenoantiserum to human Ia antigens has been described that is capable of blocking not only stimulation in the mixed lymphocyte reaction (MLR) but also the induction of cytotoxic T lymphocytes (CTLs). Data from immunofluorescence as well as complement-dependent cytolytic assays indicate that the anti-Ia xenoantiserum is directed against B cell surface antigens. Inhibition of complement-dependent cytolysis with column fractions of B cell antigens and autoradiography of immune precipitates electrophoresed on sodium dodecyl sulfate (SDS)-polyacrylamide gels have established that the antigen detected by the xenoantiserum has characteristics of the human two-polypeptide Ia molecular complex. Allogeneic stimulator cells pretreated with anti-Ia at very low doses were unable to stimulate in the MLR and failed to induce CTLs. Neither anti-beta 2-microglobulin nor a non-HLA-associated antilymphocyte serum in similar dose ranges inhibited MLR or cell-mediated lympholysis (CML) assays. Absorption of anti-Ia xenoantiserum with B lymphoblasts, but not T lymphoblasts, removed inhibitory activity for both MLR and CML. Untreated third-party stimulator cells cocultivated with anti-Ia-pretreated stimulator cells provided stimulation in the MLR that apparently allowed partial recovery of CML against targets from the same donor as the anti-Ia-treated stimulator cells. Elimination of the helper effect, normally provided by MLR stimulation, may be one mechanism by which anti-Ia xenoantiserum prevents induction of CTLs.

Complement potentiation of phagocyte-mediated ADCC of HSV-infected corneal cells.

The authors have shown previously that rabbit alveolar macrophages, peritoneal exudate macrophages, and polymorphonuclear leukocytes are highly effective mediators of antibody-dependent cellular cytotoxicity (ADCC) against herpes simplex virus (HSV)-infected rabbit stromal keratocytes. Using a completely homologous system of nonimmune rabbit phagocytes, anti-HSV serum, complement, and HSV-infected stromal keratocyte targets, the authors have found significant potentiation of ADCC by complement. Lymphocyte-mediated ADCC, on the other hand, was not potentiated by complement. Using a 1:100 dilution of complement (noncytolytic in antibody-mediated lysis) and a 1:10 dilution of antiserum obtained from rabbits undergoing stromal keratitis, ADCC mediated by the three phagocytic cell types was augmented by approximately 22%. For example, using alveolar macrophages as effector cells, the addition of complement increased the level of ADCC From 40% to 60%, a 20% increase. Percent ADCC was augmented less by complement at higher antiserum dilutions. However, the percent of the total ADCC attributable to complement potentiation increased at these higher antiserum dilutions. In some cases, ADCC was not detectable at these high antiserum dilutions without the added complement. The potentiating effect was observed at complement dilutions as high as 1:400. Further dilution or heat-inactivation resulted in ADCC values comparable to those obtained without complement. Target cells exposed to complement alone were not killed by phagocytes.

Cefazolin levels after intravitreal injection. Effects of inflammation and surgery.

Cefazolin (2.25 mg) was injected into the vitreous cavity of phakic, aphakic, and aphakic/vitrectomized rabbits; inflamed eyes were compared to controls. Vitreous levels of cefazolin were determined at selected times from 2 to 48 hr, and the half-life was calculated. The effect of inflammation was to increase the half-life or to reduce the rate of elimination of cefazolin from the vitreous cavity. The drug was cleared substantially faster from aphakic/vitrectomized eyes than from phakic or aphakic eyes. Vitreous levels of cefazolin were above the MIC for most common gram-positive organisms causing endophthalmitis in all study groups at 24 hr, but in only the phakic inflamed eyes and in the aphakic eyes with intact vitreous at 48 hr.

Spontaneous sterilization in experimental Staphylococcus epidermidis endophthalmitis.

We created a standardized model of endophthalmitis in the aphakic rabbit eye using a laboratory strain of Staphylococcus epidermidis of known characteristics (ATCC 155). Eyes were injected with the following number of organisms: 170, 3760, 8750, 170,000 and 460,000. Serial quantitative cultures, clinical grading of infection and histopathologic studies were performed on days 1, 2, 3, 7 and 14. Bacteria appeared to multiply rapidly during the first 24 hr with peak recovery at 8 to 24 hr. Fewer bacteria were cultured on the third day after injection, and positive cultures were rare after the third day. Inflammatory scores were initially higher with each increased number of injected bacteria and tended to increase for the first 3 to 5 days.