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Human conflict generally has substantial negative impacts on wildlife and conservation. The recent civil war (1995-2006) in the Democratic Republic of Congo (DRC) resulted in a significant loss of wildlife, including elephants, due to institutional collapse, lawlessness and unbridled exploitation of natural resources such as minerals, wood, ivory and bushmeat. We used data from distance sampling surveys conducted before and after the war in a protected forest, the Okapi Faunal Reserve, to document changes in elephant abundance and distribution. We employed Generalized Additive Models to relate changes in elephant distribution to human and environmental factors. Populations declined by nearly fifty percent coinciding with a major increase in elephant poaching as indicated by reports of ivory trade during the war. Our results suggest that humans influenced elephant distribution far more than habitat, both before and after the war, but post-war models explained more of the variation. Elephant abundance declined more, closer to the park boundary and to areas of intense human activity. After the war, elephant densities were relatively higher in the centre of the park where they were better protected, suggesting that this area may have acted as a refuge. In other sites in Eastern DRC, where no protection was provided, elephants were even more decimated. Post-war dynamics, such as weakened institutions, human movements and availability of weapons, continue to affect elephants. Survival of remaining populations and recovery will be determined by these persistent factors and by new threats associated with growing human populations and exploitation of natural resources. Prioritizing wildlife protection, curbing illegal trade in ivory and bushmeat, and strengthening national institutions and organizations in charge of conservation will be crucial to counter these threats.

A cholestatic liver chemistry profile (elevations in alkaline phosphatase and bilirubin) is commonly encountered in patients with hepatic venous outflow obstruction due to right heart failure. Liver biopsies from these patients demonstrate varying degrees of sinusoidal dilatation, red blood cell extravasation and sinusoidal congestion. Recently, a bile ductular reaction mimicking biliary tract disease has been identified in ∼ 50% of patients with venous outflow obstruction possibly explaining the cholestatic profile encountered in these patients. In this study, we evaluated the liver biopsies from 22 patients with heart failure. Marked sinusoidal dilatation involving zones 2 and 3 was observed in 15 patients. Similar to a previous study, 7 of 22 patients had histologic evidence of a mild ductular reaction. Cytokeratin 7 immunohistochemistry revealed a mild ductular reaction in an additional two cases. Strikingly, CK7 was aberrantly expressed in perivenular hepatocytes in 20 of 22 cases. Perivenular CK7 immunoreactivity was focal in most cases; however, in five cases it was quite extensive and extended into zone 2. There was no significant association between marked sinusoidal dilatation and extensive perivenular CK7 positivity. Extensive perivenular CK7 positivity was significantly associated with both elevated bilirubin, as well as the presence of fibrosis. However, a ductular reaction was not associated with a cholestatic liver chemistry profile.

Predicting the statistics of realistic wave-chaotic scattering systems requires, in addition to random matrix theory, introduction of system-specific information. This paper investigates experimentally one aspect of system-specific behavior, namely, the effects of short ray trajectories in wave-chaotic systems open to outside scattering channels. In particular, we consider ray trajectories of limited length that enter a scattering region through a channel (port) and subsequently exit through a channel (port). We show that a suitably averaged value of the impedance can be computed from these trajectories and that this can improve the ability to describe the statistical properties of the scattering systems. We illustrate and test these points through experiments on a realistic two-port microwave scattering billiard.

The distinction of hepatocellular carcinoma (HCC) from metastatic tumor in the liver often presents a diagnostic challenge that carries significant impact on prognostication and therapy. The number of diagnostically useful immunohistochemical markers of hepatocytes is limited to hepatocyte paraffin antigen (HepPar-1), polyclonal carcinoembryonic antigen, and CD10, with alpha-fetoprotein and glypican-3 labeling HCCs. Arginase-1 (Arg-1) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of arginine to ornithine and urea. We used immunohistochemistry to compare the sensitivity of Arg-1 to that of HepPar-1 in 151 HCCs. We found that the overall sensitivities of Arg-1 and HepPar-1 are 96.0% and 84.1%, respectively. The sensitivities of Arg-1 in well, moderately, and poorly differentiated HCCs are 100%, 96.2%, and 85.7%, respectively, whereas, in comparison, HepPar-1 demonstrated sensitivities of 100%, 83.0%, and 46.4% for well, moderately, and poorly differentiated tumors, respectively. There were no HCCs in our study that were reactive for HepPar-1 but nonreactive for Arg-1. We also examined Arg-1 expression in nonhepatocellular tumors, including many that are potential mimics of HCC (renal cell carcinomas, neuroendocrine tumors, melanomas, gastric adenocarcinomas, and adrenocortical carcinomas) and found that only 2 non-HCC tumors were reactive for Arg-1. Arg-1 represents a sensitive and specific marker of benign and malignant hepatocytes that may ultimately prove to be a useful diagnostic tool in routine surgical pathology practice.

Prediction of the statistics of scattering in typical wave-chaotic systems requires combining system-specific information with universal aspects of chaotic scattering as described by random matrix theory. This Rapid Communication shows that the average impedance matrix, which characterizes such system-specific properties, can be semiclassically calculated in terms of ray trajectories between ports. Theoretical predictions are compared with experimental results for a microwave billiard, demonstrating that the theory successfully uncovered universal statistics of wave-chaotic scattering systems.

Purpose: Vaccination rates for pneumococcal polysaccharide vaccine (PPV) and influenza vaccine are relatively low in disadvantaged urban populations. This study was designed to assess which physician and practice characteristics might explain differences in rates across physicians., Methods: PPV and influenza vaccination rates were determined for 2,021 patients aged 65 years and older receiving care from 30 physicians in 17 practices surveyed about their office systems for providing adult immunizations. Hierarchical linear modeling (HLM) analyses were used to examine the relationships among vaccination rates, patient-level characteristics, and physician variables., Results: Overall, the weighted PPV vaccination rate was 60.0% and varied widely across physicians (range, 11%-98%). At the patient level in HLM, patient race (P=.01) and age (P = .02), but not neighborhood income, were associated with PPV status. By linking physician survey data with PPV rates, we found the best pair of physician variables to be "reported time spent with patients for a well visit" (P = .01) and "use of enhanced immunization documentation" (P=.10). The overall influenza vaccination rate was 51.9% (range, 22%-96%). Patient race (P=.003) and age (P = .002) were associated with influenza vaccination. The pair of physician variables with the strongest association with influenza vaccination was "use of standing orders" (P <.001) and "average observed physician examination room time," regardless of visit type (P=.02)., Conclusions: Vaccination rates vary widely in urban settings and are associated with practice characteristics such as time spent with patients and, for influenza vaccine, use of standing orders.

Objective: To assess which characteristics of primary care practices serving low- to middle-income white and minority patients relate to pneumococcal polysaccharide vaccine (PPV) and influenza vaccination rates., Methods: In an intentional sample of 18 primary care practices, PPV and influenza vaccination rates were determined for a sample of 2289 patients >or=65 years old using medical record review. Office managers and lead nurses were surveyed about their office systems for providing adult immunizations, beliefs about PPV and influenza vaccines, and their own vaccination status. Hierarchical linear modeling (HLM) analyses were used to account for the clustered nature of the data., Results: Sampled patients were most frequently female (61%) and white (83%), and averaged 76 years of age. Weighted vaccination rates were 61.1% for PPV and 52.5% for influenza; rates varied by practice. Using HLM, with patient age and race entered as level 1 variables and office factors entered as level 2 variables, time allotted for an annual well visit was associated with a higher likelihood of influenza vaccination (odds ratio [OR] = 1.04; 95% confidence interval [CI] = 1.02, 1.07; P = .003). Nurse influenza vaccination status was associated with a higher likelihood of PPV vaccination (OR = 3.81; 95% CI = 1.49, 9.78; P = .009)., Conclusions: In addition to race and age, visit length and the nurses' vaccination status were associated with adult vaccination rates. Quality improvement initiatives for adult vaccination might include strengthening social influence of providers and/or ensuring that adequate time is scheduled for preventive care.

In many situations, the statistical properties of wave systems with chaotic classical limits are well described by random matrix theory. However, applications of random matrix theory to scattering problems require introduction of system-specific information into the statistical model, such as the introduction of the average scattering matrix in the Poisson kernel. Here, it is shown that the average impedance matrix, which also characterizes the system-specific properties, can be expressed in terms of classical trajectories that travel between ports and thus can be calculated semiclassically. Theoretical results are compared with numerical solutions for a model wave chaotic system.

Osteochondral defects are common in younger, active patients. Multiple strategies have been used to treat these lesions, including microfracture and osteochondral plug transfer. We describe a patient experiencing chronic knee pain and a full-thickness cartilage defect on the lateral femoral condyle. After failing conservative management and microfracture surgery, the patient underwent osteochondral autograft plug transfer, with backfilling of the donor sites using synthetic bone graft substitute. Initial recovery was uncomplicated until the patient experienced pain following a twist of the knee. Magnetic resonance imaging for the subsequent knee injury revealed poor healing at the donor sites. The donor sites were debrided, and specimens revealed a foreign body giant cell reaction. Donor-site morbidity is of primary concern during osteochondral plug transfer; however, insufficient data exist to support the use of synthetic bone graft material. Our results indicate that off-label use of synthetic bone graft substitute during a primary procedure requires further investigation.

Intra-articular hyaluronic acid viscosupplementation is gaining popularity as a treatment option in the nonoperative management of patients with osteoarthritis. Recent clinical studies have demonstrated that the anti-inflammatory, anabolic, and chondroprotective actions of hyaluronic acid reduce pain and improve patient function. With evidence mounting in support of the efficacy of this treatment modality for patients with osteoarthritis, its potential use in additional patient populations and for other pathologies affecting the knee is being investigated. The current article reviews the use of intra-articular hyaluronic acid viscosupplementation in the management of knee osteoarthritis and presents the potential for expanding its indications for other joints and alternative patient subpopulations. Additionally, future directions for the use of hyaluronic acid and areas of active research are discussed.

The marine cyanobacterium Trichodesmium is ubiquitous in tropical and subtropical seas and is an important contributor to global N and C cycling. We sought to characterize metabolic uptake patterns in individual Trichodesmium IMS-101 cells by quantitatively imaging (13)C and (15)N uptake with high-resolution secondary ion mass spectrometry (NanoSIMS). Trichodesmium fix both CO(2) and N(2) concurrently during the day and are, thus, faced with a balancing act: the O(2) evolved during photosynthesis inhibits nitrogenase, the key enzyme in N(2) fixation. After performing correlated transmission electron microscopy (TEM) and NanoSIMS analysis on trichome thin-sections, we observed transient inclusion of (15)N and (13)C into discrete subcellular bodies identified as cyanophycin granules. We speculate that Trichodesmium uses these dynamic storage bodies to uncouple CO(2) and N(2) fixation from overall growth dynamics. We also directly quantified both CO(2) and N(2) fixation at the single cell level using NanoSIMS imaging of whole cells in multiple trichomes. Our results indicate maximal CO(2) fixation rates in the morning, compared with maximal N(2) fixation rates in the afternoon, bolstering the argument that segregation of CO(2) and N(2) fixation in Trichodesmium is regulated in part by temporal factors. Spatial separation of N(2) and CO(2) fixation may also have a role in metabolic segregation in Trichodesmium. Our approach in combining stable isotope labeling with NanoSIMS and TEM imaging can be extended to other physiologically relevant elements and processes in other important microbial systems.

Multiple ligament knee injuries are serious and rare injures that have not been studied using advanced gait analysis techniques. The purpose of this study was to perform clinical follow-up and gait analysis on patients with multiple knee ligament reconstruction. Twenty-four patients who underwent a multi-ligament knee reconstruction by a single surgeon volunteered to participate in this study. We performed complete clinical exam including instrumented ACL exam (KT-1000), and radiological exam including weight-bearing and PCL stress radiographs (TELOS) at minimum 2 years post index surgery. In addition, we performed complete three-dimensional gait analysis on 18 patients. We used a 10-camera, high speed (120 Hz) motion analysis system in conjunction with a multi-axis strain-gage force plate which calculated knee joint kinetics and kinematics while subjects performed flat-ground walking and stair-descent tasks. Kinematic and kinetic variables were compared between reconstructed and contralateral knees and unmatched, healthy control knees. All knee joint moments were normalized to subjects' weight. Clinical: Average knee joint flexion/extension 123.6 +/- 15.5/1.7 +/- 3.5, respectively. Average KT-1000 side-to-side difference was 1.2 +/- 2.0 mm, TELOS side-to-side difference on stress radiographs was 4.0 +/- 3.1 mm. Median IKDC score was 67 (range 13-94). Fifty-three percent of patients exhibited radiographic evidence of osteoarthritis (OA) on the operative side; one patient on the contralateral knee. During gait analysis, patients exhibited significantly reduced total knee joint range of motion, and external knee flexion moment in the reconstructed knee compared to the contralateral knee and healthy control knees. The magnitude of these differences was greater while descending a step. Finally, patients who had radiographic evidence of knee joint OA had significantly lower magnitude external knee flexion moment compared to those who did not have OA at the time of follow-up. Greater than 2 years after reconstruction, patients with multi-ligament knee injuries are able to return to daily activities. Gait analysis data suggests that patients may be experiencing higher magnitude changes in sagittal plane kinematics and kinetics during demanding functional tasks (stair decent). Changes in walking gait biomechanics may help explain why this group is experiencing unilateral knee joint degeneration.

The ensemble averaged power scattered in and out of lossless chaotic cavities decays as a power law in time for large times. In the case of a pulse with a finite duration, the power scattered from a single realization of a cavity closely tracks the power-law ensemble decay initially, but eventually transitions to an exponential decay. In this paper, we explore the nature of this transition in the case of coupling to a single port. We find that for a given pulse shape, the properties of the transition are universal if time is properly normalized. We define the crossover time to be the time at which the deviations from the mean of the reflected power in individual realizations become comparable to the mean reflected power. We demonstrate numerically that, for randomly chosen cavity realizations and given pulse shapes, the probability distribution function of reflected power depends only on time, normalized to this crossover time.

Femoral and tibial tunnel widening following ACL reconstruction using hamstring autograft has been described. Greater tunnel widening has been reported with suspensory fixation systems. We hypothesized that greater tunnel widening will be observed in patients whose hamstring autograft was fixated using a cortical, suspensory system, compared to double cross-pin fixation on the femur. We performed clinical and radiographic evaluation on 46 patients at minimum 2 years after primary ACL reconstruction. We measured subjective and objective outcomes including KT-1000 and AP, lateral radiographs. A musculoskeletal radiologist, independent of the surgical team, measured tunnel width, while correcting for magnification, at the widest point and at 1 cm away from tibial and femoral tunnel apertures. Patients in the suspensory graft fixation group exhibited significantly greater absolute change and greater percent change in femoral tunnel diameter compared to patients with double cross-pin fixation (P

Perfluorobutyrate (PFBA) has been detected in precipitation, surface waters, water treatment effluent, and in public and private wells in Minnesota at up to low microg/l concentrations. We evaluated the pharmacokinetics of PFBA in rats, mice, monkeys, and humans to provide a rational basis for dose selection in toxicological studies and to aid in human-health-risk assessment. Studies included (1) rats--iv and oral; (2) mice--oral; (3) monkeys--iv; and (4) humans--occupationally exposed volunteers. PFBA was determined in serum (all species), liver (rats and mice), urine (rats, mice, and monkeys), and feces (rats and mice). In addition, we characterized serum PFBA concentrations in 177 individuals with potential exposure to PFBA through drinking water. Mean terminal serum PFBA elimination half-lives for males (M) and females (F), respectively, in h were (1) for rats given 30 mg/kg, 9.22 and 1.76 (oral), and 6.38 and 1.03 (iv); (2) for mice given oral doses of 10, 30, or 100 mg/kg ammonium PFBA, 13.34 and 2.87 at 10 mg/kg, 16.25 and 3.08 at 30 mg/kg; and 5.22 and 2.79 at 100 mg/kg; (3) for monkeys given 10 mg/kg iv, 40.32 and 41.04; and (4) for humans, 72.16 and 87.00 (74.63 combined). Volume of distribution estimates indicated primarily extracellular distribution. Among individuals with plausible exposure via drinking water, 96% of serum PFBA concentrations were < 2 ng/ml (maximum 6 ng/ml). These findings demonstrate that PFBA is eliminated efficiently from serum with a low potential for accumulation from repeated exposure.

Background & Aims: Recent studies have claimed long neoplasia-free survival rates with endoscopic mucosal resection of high-grade dysplasia (HGD) in Barrett's esophagus (BE). However, reports have contended that approximately 40% of patients who have esophagectomy for HGD have occult invasive cancer. The aim of this study was to use explicit criteria to determine the true prevalence of invasive adenocarcinoma in reports of patients who had esophagectomy for HGD in BE., Methods: Studies reporting rates of esophageal cancer in patients who underwent esophagectomy for HGD in BE were gathered using MEDLINE and PUBMED. We defined invasive esophageal adenocarcinoma (IEAC) as tumor with submucosal invasion or beyond. Intramucosal carcinoma (IMC) was not considered IEAC., Results: Twenty-three articles were selected for analysis. Most investigators reported rates of invasive cancer in the esophagectomy specimen, and the pooled average was 39.9% among the 441 patients who underwent an esophagectomy for HGD. Reported rates varied from 0% to 73%. A total of 267 patients had American Joint Committee on Cancer stage 0 postoperatively, 132 patients had stage I, 23 patients had stage IIa, 10 patients had stage IIb, and 9 patients had stage III. Fourteen studies provided differentiation between intramucosal and submucosal invasion. Among 213 patients, only 12.7% had IEAC, whereas 87.3% had HGD or IMC. The IEAC rate of 11% among patients with visible lesions is greater than the rate of 3% among patients with no visible lesion., Conclusions: By using strict pathologic definitions of invasive disease, the present study indicates the true prevalence of IEAC in BE and HGD may have been overestimated significantly. Separating IMC from IEAC is clinically relevant because endoscopic techniques potentially may treat IMC.

Background: A new generation of flexible all-inside meniscal repair devices is available, but clinical studies with these devices are lacking., Hypothesis: The RapidLoc has an intermediate-term meniscal healing rate that is equivalent to literature reports of inside-out suture technique in patients undergoing concurrent anterior cruciate ligament reconstruction., Study Design: Case series; Level of evidence, 4., Methods: Retrospective analysis was performed for 75 meniscal tears in 66 consecutive patients undergoing anterior cruciate ligament reconstruction who underwent meniscal repair with the RapidLoc. Patients with at least 2 years' follow-up were evaluated for symptoms suggestive of a meniscal tear and were assessed with the International Knee Documentation Committee form and the Knee Disorders Subjective History visual analog scale. Subjects were asked to return for a clinical examination to include evaluation for an effusion and joint line tenderness as well as McMurray test and KT-1000 arthrometry readings. Patients with symptoms consistent with meniscal repair failure underwent magnetic resonance arthrography and repeat arthroscopy., Results: Twenty patients with 21 meniscal tears were excluded, resulting in 54 meniscal tears in 46 patients. At a mean follow-up of 34.8 months, the clinical success rate for meniscal repair was 90.7% (49/54), with 5 failures requiring meniscectomy. Univariate analysis revealed predictive variables for failure: bucket-handle configuration, multiplanar tears, tear length greater than 2 cm, and chronicity longer than 3 months. Non-predictive variables included compartment, zone, ligament graft choice, gender, age, follow-up, and visual analog scale score. Analysis of healed patients revealed a negative correlation between chronicity of tear and International Knee Documentation Committee score., Conclusions: The RapidLoc has an acceptable intermediate-term clinical healing rate in patients undergoing concurrent anterior cruciate ligament reconstruction. Predictive variables for failure should be considered during operative decision making.

Our aim was to determine whether p53 and Rab11a immunoreactivity enhance diagnostic assessment of esophageal dysplasia. Histologic sections from 68 cases of Barrett esophagus obtained as part of a 12-institution study were stained with antibodies to p53 and Rab11a, randomized, and coded. The mucosal surface layer and deeper glands were scored blindly on a semiquantitative scale. The correlations between p53 and Rab11a scoring with the consensus diagnosis of dysplasia were analyzed. The histologic scale was as follows: no dysplasia, indefinite, low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma, and invasive carcinoma. Rab11a staining was most prominent in epithelia negative for dysplasia but with regenerative features. There was an inverse relationship between Rab11a staining and findings of surface dysplasia (P < .02, chi(2)). However, statistical significance largely reflected loss of Rab11a immunoreactivity in intramucosal and invasive carcinoma, which was not a diagnostic dilemma. There was a strong positive correlation of p53 immunoreactivity with an increasing degree of epithelial dysplasia and carcinoma (P < .03, chi(2)). Rab11a immunoreactivity did not enhance the diagnostic assessment of dysplasia in Barrett esophagus. The previously reported positive correlation of p53 immunoreactivity with the presence of dysplasia in Barrett esophagus was confirmed.

Even with the rapid advancement in technology and medical imaging, there is still no substitute for the history and physical examination that can be obtained from a patient. With a well-performed history and physical, the majority of pathology can be determined prior to any expensive imaging or surgical procedures. The knee is one of the most commonly injured joints, and its function is critical to basic ambulation and participation in sports, work, and activities of daily living. This article reviews the key concepts to a complete evaluation of the knee and highlights aspects of the physical examination and radiographic imaging that best aid in diagnosing knee pathology.

Effect of continuous passive motion (CPM) protocols on outcomes after total knee arthroplasty. In this prospective randomized controlled study, 147 patients were assigned to 1 of 3 treatment groups: CPM from 0 degrees to 40 degrees and increased by 10 degrees per day, CPM from 90 degrees to 50 degrees (early flexion) and gradually progressed into full extension over a 3-day period, and a no-CPM group. The CPM was administered twice a day for 3 hours over a 5-day period. All patients participated in the same postoperative physiotherapy program. Patients were assessed preoperatively, day 5, 3 months, and 1 year postoperatively. The early flexion group had significantly more range of flexion than both the standard and control groups at day 5. There was no significant difference between the groups for any other variable tested at any time frame. Key words: total knee arthroplasty, CPM, rehabilitation, outcomes.

All-inside meniscal repair has become a popular technique. The number of meniscal repairs done in the United States has increased dramatically since the introduction of the Meniscal Arrow (Linvatec Corp, Largo, FL). Although these devices are easy to use, there have been several compliations reported with their use. Newer devices (Mitek RapidLoc and Smith and Nephew Fas-T-Fix) allow tensioning of the construct after insertion. There are also problems and pitfalls with their use, but improvements continue to be made in all-inside meniscal repair devices.

Joint replacement is the most effective healthcare measure in improving patient quality-of-life outcomes. More than 46000 hip and knee replacements were performed in Australia between July 2000 and July 2001. The need for joint replacements will increase as the population ages. More than 90% of hip and/or knee replacements survive for 10-15 years. Prosthesis selection needs to be tailored to each patient, although rationalisation of types of prosthesis used is required.

The Ituri Forest, Democratic Republic of Congo (formerly Zaire) is an example of a closed canopy forest showing extreme depletion in (13)C. delta(13)C values for plants from the canopy top, from gaps in the canopy, and from the subcanopy average -29.0+/-1.7 per thousand, -30.4+/-0.9 per thousand, and -34.0+/-1.5 per thousand, respectively. The delta(13)C of forest mammals show these differences, with the subcanopy browsers (okapi, dwarf antelope) having delta(13)C values for tooth enamel much more negative than subcanopy frugivores who derive their food from the canopy top, and from folivores and omnivores living in gap or clearing areas. Nitrogen isotopes in plants from this ecosystem have an average delta(15)N value of 5.4+/-1.8 per thousand and do not show significant differences at the 95% confidence interval between plants from the canopy top, from gaps in the canopy, and from the subcanopy. The delta(18)O(SMOW) values of surface waters in the study area are between -2.0 and -2.7. The delta(18)O(PDB) for tooth enamel ranged from -3 to +7 per thousand.

Knockout mutations were constructed in the arcA gene of a virulent type b strain of Haemophilus influenzae, and the behavior of the resulting mutants was investigated in a number of conditions that mimicked distinct steps in the natural infection pathway. In arcA mutants, synthesis of capsule and lipooligosaccharide (LOS) and growth in synthetic media were unaltered compared to synthesis of capsule and LOS and growth in synthetic media in the wild-type H. influenzae type b parent strain. However, the virulence of the arcA mutants for BALB/c mice was significantly reduced. Upon exposure to human blood or serum, the arcA mutants showed markedly reduced survival compared with the survival of its wild-type parent. Serum resistance could be fully restored by complementation in cis with the H. influenzae arcA gene but not by complementation in cis with the homologous gene from Escherichia coli. The proteomes of wild-type and mutant bacteria were markedly different, especially under anaerobic conditions, underscoring the global regulatory role of ArcAB in H. influenzae. Evaluation of antibody titers and classical complement activities in various serum samples pointed to complement-mediated bactericidal activity as the factor that distinguishes between the arcA mutant and wild-type phenotypes. Comparative analysis of the membrane fractions of the arcA mutants and the wild-type strain revealed several ArcA-regulated proteins, some of which may be implicated in the serum hypersensitivity phenotype.

Osteotomy is an alternative treatment for unicompartmental osteoarthritis of the knee. In genu varum, a high valgus closing wedge osteotomy is preferred, with overcorrection by 5 degrees. Complications and poor outcomes can be overcome by incomplete osteotomy with careful preoperative planning, precise use of cutting jigs, compression fixation, and early mobilization and weight bearing. Patella baja is related to postoperative immobilization, and unicompartmental arthroplasties are more difficult to revise because of bone loss. Supracondylar femoral osteotomy is preferred for genu valgum using a lateral opening wedge with a toothed plate, allowing easy access to the lateral compartment of the knee. Osteotomy, far from being obsolete, has an increasing role in joint resurfacing procedures., (Copyright 2002, Elsevier Science (USA).)

Objective: To characterize effects of intranasal inoculation of virulent Brucella melitensis strain 16M in mice., Animals: Female Balb/c mice, 6 to 8 weeks old., Procedure: Studies were designed to elucidate gross morphologic lesions, bacterial burden in target organs, and histologic changes in tissues following experimental intranasal inoculation of mice with B melitensis 16M, which could be used to characterize a model for testing vaccine efficacy., Results: Measurable splenomegaly was evident at 3 and 7 weeks after inoculation. A demonstrable increase in splenic colony-forming units (CFU) from infected mice increased over time with increasing dose when comparing inocula of 10(3), 10(4), and 10(5) CFU. Recovery of brucellae from the lungs was possible early in infection with 10(1), 10(3), and 10(5) CFU, but only the group inoculated with 10(5) CFU consistently yielded quantifiable bacteria. At a dose of 10 CFU, few organisms were located in the spleen. Bacteria were recovered up to 140 days after inoculation in mice given 10(3) CFU. At an inoculum of 10(5) CFU, bacterial counts were highest early in infection. Histologic examination of tissues revealed an increase in white pulp and marginal zone in the spleen and lymphohistiocytic hepatitis., Conclusion and Clinical Relevance: Changes in the spleen and liver increased with increases in dose and with increased time following intranasal inoculation with B melitensis 16M. Surprisingly, histologic changes were not observed in the lungs of inoculated mice.

We used site-directed mutagenesis to construct 55 single-site variants of rhPTH, a recombinantly-expressed form of human parathyroid hormone (1-34) containing three amino acid changes compared to the natural sequence (ML8, ML18 and FY34). We identified several mutations, at residues Lys(13), Glu(19), Val(21), Glu(22), Lys(27) and Asp(30), that increase biological activity by up to 2. 5-fold, as measured by stimulation of adenylate cyclase activity in rat UMR-106 cells. We constructed a series of 15 variants in which two to eight substitutions at these positions were combined, and found that the mutations behaved additively, leading to peptides with significantly enhanced potency. The most active combination variant, with six substitutions (KS13, ES19, VQ21, ES22, KQ27 and DN30), is 15 times more active than the parent molecule. However, the extent to which such combinations increase the activity of the peptide depends critically on the identity of the residues at positions 8 and 18. We constructed two of the combination variants in a variety of sequence backgrounds containing different combinations of leucine, methionine and norleucine at positions 8 and 18. Enhancements in potency were significantly reduced when Met or Nle was present at either of these positions, both in UMR-106 cells and human SaOS-2 cells. A corresponding non-additivity was observed in direct measurements of receptor binding affinity on UMR-106 cells. These results suggest that interactions, either direct or indirect, between certain PTH side chains prevent these mutations from behaving in an additive manner.

Casemix funding has markedly increased surgeons' awareness of the economies of the activities they undertake. Surgery has become a major focus at all large public hospitals, because of its high earning potential, and this pressure to maximise funding could influence surgical practice. Casemix funding's emphasis on length of hospital stay has encouraged forward planning for earlier discharge after surgical procedures. Patients are now assessed in pre-admission clinics, educated about their condition and their hospital stay, and a plan formulated for their discharge and rehabilitation. Funding for major surgical procedures of long duration in patients with complex conditions should reflect the higher level of resource utilisation. Tertiary referral centres, because of their commitment to training and research and their more severely ill patient population, are less cost-effective and require funding to ensure their viability. The improved information that casemix generates should be used to evaluate outcomes and improve patient care; efficiency must not take precedence over quality of care and compassion.

This article describes two prospective, randomized, double-blind clinical trials designed to investigate this. Trial 1 compared a conventional local anaesthetic agent (100 mg bupivacaine) injected intra-articularly (i.a.) with a control (normal saline) and 1 mg of i.a. morphine. No significant difference was noted in the first 4 hours between the groups with respect to visual analogue pain (VAS) scores. However, at 6 and 24 hours, the group of patients who received 1 mg i.a. morphine recorded lower pain scores and required less supplementary analgesia. Trial 2 assessed the dose response relationship for i.a. morphine comparing 5 mg intravenous (i.v.) morphine (control) with 1 mg and 5 mg i.a. morphine. At early time points (1, 2, and 4 hours) similar VAS pain scores were recorded for both 5 mg i.v. morphine and 5 mg i.a. morphine, both significantly lower than the group receiving 1 mg i.a. morphine. At 6 and 24 hours, 5 mg of i.a. morphine produced significantly lower pain scores, less analgesic requirement, and less sleep disturbance on the first postoperative night than the other groups. It can be concluded from these two studies that 5 mg i.a. was the most effective analgesic following knee arthroscopy.

Alanine scanning mutagenesis of human granulocyte colony-stimulating factor (G-CSF) was used to identify residues critical for the cell-proliferative activity of the protein. Fifty-eight residues, most of them on the protein surface, were independently mutated to alanine. Most of the variants retained full biological activity; however, 15 mutants were significantly impaired in their ability to stimulate bone marrow cell proliferation in vitro. Four of these variants contain mutations at buried residues and two have substitutions at side chains involved in intramolecular hydrogen bonds. The remaining nine down mutations identify two regions on the surface of the molecule important for biological activity. Consistent with these observations, measurements of binding to NFS-60 cells indicate that the residues most important for receptor binding are Lys40 and Phe144 in site 1 and Glu19 in site 2. In addition to these residues, Val48 and Leu49 in site 1 and Leu15, Asp112, and Leu124 in site 2 are also important for biological activity. These results suggest the presence of two binding sites on the cytokine surface required for dimerization of the G-CSF receptor.

This study investigated the in vitro and in vivo excitotoxic properties of a novel conformationally constrained analogue of L-glutamate, L-trans-2,3-pyrrolidine dicarboxylate (L-trans-2,3-PDC). When tested for excitotoxic activity in rat cortical cultures, L-trans-2,3-PDC mimicked the action of NMDA in both acute (30 min) and chronic (24 h) exposure paradigms. This neurotoxicity was attenuated by co-addition of MK-801 (10 microM). Microinjections of L-trans-2,3-PDC into the dorsal hippocampus of male rats also induced a selective pattern of pathology indicative of an NMDA receptor excitotoxin. In contrast to the equipotency observed in vitro, 100 nmol of L-trans-2,3-PDC were needed to produce cellular damage comparable to that induced by 25 nmol of NMDA. Consistent with an action at NMDA receptors, L-trans-2,3-PDC-induced damage could be significantly reduced by co-administration of MK-801 (3 mg/kg i.p.), but not by NBQX (25 nmol). In radioligand binding assays L-trans-2,3-PDC inhibited the binding of 3H-L-glutamate to NMDA receptors (IC50 1 microM), although it also exhibited some cross reactivity with KA and AMPA receptors. L-trans-2,3-PDC was also identified as a competitive inhibitor (Ki = 33 microM) of 3H-D-aspartate uptake into rat forebrain synaptosomes. In contrast to the action of a transported substrate, such as L-glutamate, L-trans-2,3-PDC did not exchange with 3H-D-aspartate that had been previously loaded into the synaptosomes.

Twenty-six patients with major fractures of the talus were studied to assess the long-term outcome. The patients were admitted to a university teaching hospital and major trauma center from 1983 to 1991. The study excluded isolated fractures of the talar dome and posterior tubercle. Fifteen patients were treated using internal fixation and 11 patients were treated using nonsurgical methods. Avascular necrosis was detected in only four of the 26 patients. Subtalar osteoarthritis was a significant problem in 61%. Seven of these patients have come to secondary fusion procedures, with another three contemplating fusion procedures at the time of review. Only one patient developed significant avascular necrosis requiring a fusion procedure. Only three of 26 patients had not returned to work at a mean 6 years after their injury. Eleven of the 26 (42%) had not returned to their premorbid activity level. The majority of these patients (25/26) had sustained multiple injuries, which compromised the functional recovery from the talar injury. Early accurate diagnosis and anatomical reduction gave the best results. The low incidence of avascular necrosis in this study has been attributed to early anatomical stabilization of the fracture. We believe an early CT scan can more accurately assess the severity of the talar fracture and offers the best information for an appropriate treatment plan.

Objective: To evaluate the safety and efficacy of a preoperative autologous blood donation (PABD) program with liberal patient exclusion criteria., Design: Prospective patient accrual from September 1990 to May 1992., Setting: A PABD program in a public tertiary care hospital linked with a specialist orthopaedic practice in a private hospital., Patients: One hundred and twenty patients consecutively scheduled for orthopaedic surgery were referred for PABD. There were 77 women (median age, 63 years) and 43 men (median age, 62 years). One-third of patients were 70 or more years old. Coexistent medical disease, mainly cardiovascular, was present in 46% of patients and 3% were excluded because of coexisting morbidity. Total hip or total knee replacement was performed in a private hospital with intraoperative or postoperative blood salvage in 37% of the patients., Outcome Measures: Adverse effects of PABD, autologous blood collected and used and homologous blood transfused., Results: One hundred and sixteen patients donated 267 units of autologous blood. In 70 patients undergoing total hip replacement, 78% donated three and 20% donated two units, with 95% of autologous blood being used. In 38 patients undergoing total knee replacement, 42% donated two units and 55% donated one unit, with 87% of autologous blood being transfused. Seventy-eight per cent of all patients only received autologous blood. In the remaining patients, homologous blood use was confined to two units or less in 80%. Hypotensive episodes associated with phlebotomy occurred in 3% of patients, and 13% of patients had preoperative haemoglobin levels ranging from 85-100 g/L without adverse clinical effects., Conclusion: A hospital-based PABD program with less strict patient exclusion criteria does not prejudice the clinical status of the donors. Its linkage to private hospitals can significantly reduce the use of homologous blood in selected elective surgery.

Abstract- The classical view of rust phylogeny is that rusts found on ferns and conifers are primitive, while rusts that parasitize angiosperms are advanced. This belief was based on the theory that primitive hosts harbor primitive parasites; that is, it assumed coevolution (co-speciation) of hosts and parasites. A cladistic analysis of 30 genera and 28 characters representative of the major patterns of rust fungi diversity is presented. The results of this analysis suggest that tropical short-cycle rusts on angiosperms form the cladistically basal group of rusts, while the rusts on conifers and ferns (Melampsoraceae sensu lato) form a nested terminal clade. These results suggest that rusts and their hosts have not undergone a long period of parallel cladogenesis (co-speciation); host transfer has probably been at least as frequent as co-speciation. The cladograms indicate evolutionary trends of spore stages and life history: urediniospores evidently preceded the evolution of aeciospores and pycniospores within Uredinales, and heteroecism is a derived condition which evolved at least several times. This study stresses the importance of making use of independent cladistic analyses of both host and parasite in order to test assumptions of coevolution and host transfer., (© 1988 The Willi Hennig Society.)

Recent studies indicate that early mobilization of surgically repaired collateral ligaments leads to a more rapid gain in tensile strength compared to immobilized ligaments. Other advantages of early mobilization include prevention of muscle atrophy, joint stiffness, and articular cartilage fibrillation. Because of these observations, a professional Australian Rules footballer with a complete rupture of the right medial collateral ligament of his knee joint, was commenced, after surgical repair, on an early controlled mobilization program using a limited motion cast (LMC) and isokinetic exercise. Rehabilitation was commenced after 2 weeks of immobilization in a LMC, and progressed through four stages, all coupled with isokinetic exercise. Weeks 2-6, exercise in LMC through 20-60 degrees ; weeks 7-8, exercise out of LMC through 15- 1 OOO; weeks 8-9, exercise through a full range of movement, 0-130'; weeks 10- 12, exercise through a full range plus inner range 0-30' repetitions. The footballer returned to full competition approximately 12 weeks postsurgery with no medial collateral laxity and almost normal Cybex IP parameters. J Orthop Sports Phys Ther 1986;7(4):154-158.

The pharmacological response to vitamin K has been determined by measuring prothrombin complex activity (P.C.A.) in male New Zealand White rabbits anticoagulated (P.C.A. less than 20%) with the long acting 4-hydroxycoumarin brodifacoum, at a dose (10 mg/kg) which produces maximum antagonism of vitamin K1. Thus, according to current concepts, this animal model may be used to assess vitamin K requirements in the absence of a functional vitamin K-epoxide reductase. After intravenous administration of vitamin K1 (1 mg/kg) P.C.A. reached a maximum (64 +/- 19%) at 3 hr and then declined at a rate which corresponds to complete inhibition of clotting factor synthesis. Vitamin K2 (1 mg/kg) stimulated clotting factor synthesis for 2 hr, while cis-vitamin K1, vitamin K3, vitamin K1 2,3-epoxide and oral administration of vitamin K1 were ineffective. Plasma concentrations of vitamin K1 fell steeply during the 12 hr following administration of a pharmacological dose, and then declined with a terminal half-life of 18.9 +/- 9.0 hr. Comparison of the pharmacodynamic and pharmacokinetic data indicated that plasma concentrations in the range 0.4-1.0 microgram/ml are required for clotting factor synthesis in the limiting situation of maximum antagonism of vitamin K by coumarin anticoagulants. These findings explain why frequent and repeated administration of vitamin K1 may be necessary during coumarin poisoning.

The research into acquisition of urinary-tract infection over the last few decades has established three ways in which organisms may gain access to the urinary tract of the catheterized patients: Firstly, during the process of passing the catheter into the bladder should complete asepsis not be observed; secondly by travelling along the urethra in the small, fluid-filled cavity between catheter and mucosa; Thirdly following contamination of the drainage system, along the inside of the catheter directly into the bladder. The relative importance of each route is not clear and is still the subject of much controversy but it would seem that all these routes have a part to play in allowing infection to develop. The risk of catheterized patients acquiring urinary-tract infection is so great that where possible catheterization should be avoided. The most important preventive measure which may be taken is to limit the duration of indwelling catheterization. In addition, a considerable amount of research has attempted to distinguish other factors which might affect the rate at which urinary-tract infection in the catheterized patient becomes established so that high-risk patients may be identified. The evidence indicates that the risk increases with duration of catheterization, age, length of hospital stay, immunosuppressant treatment, that it is greater in female than male patients and that a patient with a serious or fatal underlying disease is also more likely to develop bacteriuria. Finally, properties of the urine and the host defence mechanisms may affect the susceptibility of the individual to urinary-tract infection. Identification of the routes of infection and patients at risk is only part of the problem. The next stage is to formulate criteria for the care of catheterized patients which reduce the risk of infection to the absolute minimum and will hopefully go some way towards diminishing the unsatisfactory high levels of urinary-tract infection that are currently associated with indwelling catheterization.

The Northern Cheyenne Indians of eastern Montana recognized at least 138 species of plants. The collection, preparation, utilization and names of these plants are described, and their role in Cheyenne culture for food, technology, medicine and religion are discussed. Cheyenne plant medicines, though combined with ritualistic healing practices, included the use of many herbal teas which they drank for internal problems, and powders and poultices which they applied externally; many of these were combined to form medicinal mixtures. Certain plants, believed to possess benevolent powers, were employed in various religious ceremonies. Though Cheyennes once cultivated crop plants, their more recent nomadic existence encouraged the use of wild food plants, especially fruits and roots which they sun-dried and stored for winter use.

A long-term study of patients treated by primary closed Küntscher nailing of fractures of the femoral shaft was carried out. Minimal reaming allowed nails of only 9.5-11 mm diameter to be used. One hundred and sixteen patients with 120 fractures treated in this way from 1959 to 1978 attended for clinical examination. Primary bony union was achieved in 98 per cent and the infection rate was less than 1 per cent. Full, unsupported weight bearing was possible at an average of 15.6 weeks. Symptoms and residual deformity were minimal. These results support the use of this technique in adults with most types of fracture of the femoral shaft.

The pharmacokinetics and pharmacodynamics of the 4-hydroxycoumarin anticoagulants, brodifacoum, difenacoum, and warfarin have been studied in the rabbit. Sensitive (50 ng ml-1) and specific high performance liquid chromatography assays have been developed for the determination of plasma concentrations of warfarin, brodifacoum and difenacoum. After administration of a single intravenous dose (20 mumol kg-1), plasma concentrations of warfarin underwent mono-exponential decay, with a terminal half-life of 5.6 +/- 0.7 h (mean +/- s.e. mean), whereas plasma concentrations of brodifacoum and difenacoum underwent bi-exponential decay with terminal half-lives of 60.8 +/- 1.9 h and 83.1 +/- 10.3 h respectively. The plasma half-life of brodifacoum in a single patient poisoned with the compound was 487 h. The pharmacological response to the anticoagulants was measured as changes in prothrombin complex activity, from which the rate of clotting factor synthesis was determined. Clotting factor synthesis recovered in a monophasic fashion after a single intravenous dose of warfarin, compared with a more complex biphasic, pattern of recovery of clotting factor synthesis after administration of either brodifacoum or difenacoum. The slope (m) of the intensity of effect-log (amount of drug in the body) curve was derived for each anticoagulant. There was no significant difference in the value of m after single intravenous doses of racemic, R-, and S-warfarin, difenacoum and brodifacoum, which is consistent with the hypothesis that all the 4-hydroxycoumarin anticoagulants produce their anticoagulant effect by acting at the same receptor site, vitamin K epoxide reductase. Determination of the minimum plasma concentration of each anticoagulant that corresponded with the complete inhibition of clotting factor synthesis indicated that racemic warfarin, R-warfarin and brodifacoum have similar potencies in the rabbit and are less potent than S-warfarin and difenacoum.