Risk factors for septic arthritis in patients with joint disease. A prospective study

OBJECTIVE: To quantify potential risk factors for septic arthritis, in order to identify a basis for prevention. METHODS: The occurrence of potential risk factors for septic arthritis in patients with joint diseases attending a rheumatic disease clinic was prospectively monitored at 3-month intervals over a period of 3 years. Potential risk factors investigated were type of joint disease, comorbidity, medication, joint prosthesis, infections, and invasive procedures. The frequencies of risk factors in patients with and those without septic arthritis were compared using multiple logistic regression analysis. RESULTS: There were 37 patients with and 4,870 without septic arthritis. Risk factors for developing septic arthritis were age > or = 80 years (odds ratio [OR] = 3.5, 95% confidence interval [95% CI] 1.4-8.6), diabetes mellitus (OR = 3.3, 95% CI 1.1-10.1), rheumatoid arthritis (OR = 4.0, 95% CI 1.9-8.3), hip and/or knee prosthesis (OR = 15, 95% CI 4.1-54.3), joint surgery (OR = 5.1, 95% CI 2.2-11.9), and skin infection (OR = 27.2, 95% CI 7.6-97.1). CONCLUSION: These findings indicate that preventive measures against septic arthritis in patients with joint diseases should mainly be directed at those with joint prostheses and/or skin infection.     

A controlled trial of HA-1A in a canine model of gram-negative septic shock

OBJECTIVE: To investigate the therapeutic efficacy and microbiological and physiological effects of a human IgM monoclonal antibody (HA-1A) directed against the lipid A component of endotoxin in a canine model of sepsis that simulates the cardiovascular abnormalities of human septic shock. DESIGN: Blinded, placebo-controlled 28-day trial. INTERVENTIONS: Purpose-bred beagles were implanted with an intraperitoneal clot infected with Escherichia coli O111:B4. At clot placement, animals received HA-1A (10 mg.kg-1), control human IgM antibody (10 mg.kg-1), or control human serum albumin intravenously. All animals were given antibiotic and fluid therapy. MEASURES: Survival and microbiological and physiological events. RESULTS: Only two (15%) of 13 animals in the HA-1A group, compared with eight (57%) of 14 control animals (combined control human IgM antibody and control human serum albumin groups) (P = .05), survived 28 days. At 24 hours, the HA-1A group had lower mean arterial pressure (P = .04) and cardiac index (P = .004) and higher lactate levels (P = .05) compared with the combined-controls group. In addition, these parameters in the HA-1A group were significantly more predictive of death. The HA-1A and combined-controls groups had similar significant increases in the level of endotoxemia and bacteremia. Studies of toxic effects showed no harmful effects of control human IgM antibody in infected animals or HA-1A in non-infected animals. CONCLUSION: In a canine model of E coli sepsis, HA-1A did not alter levels of bacteremia or endotoxemia and actually decreased survival. If these data are relevant to human septic shock, HA-1A therapy should be limited until the conditions under which this monoclonal antibody has beneficial or deleterious effects are more completely defined.     

Mechanisms of inflammation and leukocyte activation

Loudness change is perceived over a far greater range than the discrimination range of single afferents-the "dynamic range problem" [1]. However, earlier neural count models have not fully considered how variability in the dynamic ranges, thresholds, spontaneous rates, and saturation rates of these afferents may affect overall dynamic range. In the present model, all four of these characteristics appear in a logistic rate-intensity function that fits well with sigmoidally firing cat neurons (a double logistic fits well with sloping-saturating units). These equations were averaged statistically over parameter distributions for each of three spontaneous rate groups. An average over these groups (weighted by relative group size) was used to compute discriminability for a patch of basilar membrane. The upper limit on dynamic range for a patch one critical band wide at 8 kHz was 89 dB SPL, less than implied by psychophysics [2]. A two-channel model extended the upper limit by only 3 dB, and splitting the population into four channels did not improve this limit. Seven channels, optimally combined, provided a dynamic range nearly equal to that of an ideal observer that treats each fiber as a separate channel. Moreover, the contribution of sloping-saturating units to discriminability was not as great as popularly expected. Changing the variances of fiber dynamic ranges did not strongly affect overall dynamic range in any of these computations. In sum, when the distributions of neural parameters are taken into account, local pooling can greatly mitigate the "dynamic range problem."     

Endothelial cell activation by leukocyte microparticles

The ability of polymorphonuclear leukocytes (PMNs) to modulate endothelial cell (EC) activation was investigated. Adding PMNs to cultured HUVECs resulted in a release of IL-6 (888 +/- 71 pg/ml, a 35-fold increase over release by the two cell types alone) and IL-8 (45.2 +/- 14.5 ng/ml, a 6.4-fold over PMN release alone and a 173-fold increase over EC release alone). In contrast, the release of TNF-alpha, IL-1beta, and platelet-derived growth factor was not affected by the EC-PMN coculture. Neutralizing mAbs to ICAM-1 or beta2 integrins or a physical segregation of PMNs and ECs did not reduce EC stimulation. In contrast, cell-free supernatants of PMNs recapitulated EC activation with an 18-fold up-regulation of EC IL-6 mRNA. The filtration of PMN supernatant or PMN pretreatment with metabolic antagonists or membrane cross-linking agents all suppressed EC activation. By flow cytometry, PMNs released in the supernatant, heterogeneous membrane-derived microparticles containing discrete proteins of 28 to 250 kDa as resolved by SDS-PAGE. PMN microparticle formation was enhanced by inflammatory stimuli, including formyl peptide and phorbol ester, and was time-dependent, reaching a plateau after a 1-h incubation from stimulation. Purified PMN microparticles induced EC IL-6 release in a reaction that was quantitatively indistinguishable from that observed with unfractionated PMN supernatant and unaffected by a neutralizing Ab to soluble IL-6R. These findings demonstrate that membrane microparticles released from stimulated PMNs are competent inflammatory mediators to produce EC activation and cytokine gene induction.     

Nail changes in patients infected with human immunodeficiency virus. A prospective controlled study

OBJECTIVES: To study the frequency of nail changes in a population of human immunodeficiency virus (HIV)-infected patients and to evaluate the specificity of these findings by comparison with HIV-negative control subjects. DESIGN: Prospective controlled study. Nail changes were recorded by a standardized clinical examination (curvature, nail plate, color, onychomycosis). In case of clinical diagnosis of onychomycosis, mycological culture was performed. SETTING: Primary care university hospital. PATIENTS: A total of 155 HIV-1-positive patients and 103 healthy HIV-negative control subjects of comparable age and sex ratio. INTERVENTION: None. MAIN OUTCOME MEASURE: Clinical examination findings. RESULTS: Nail symptoms were present in 67.7% of HIV-positive patients vs 34.0% of controls (P < .001). The following symptoms were significantly more frequent in the HIV group: clubbing (5.8%) (P < .05), transverse lines (7.1%) (P < .01), onychoschizia (7.1%) (P < .05), leukonychia (14.3%) (P < .001), and longitudinal melanonychia (14.8%) (P < .01). The main finding was onychomycosis in 30.3% of patients vs 12.6% of controls (P < .001). Trichophyton rubrum was present in 48% of onychomycoses and unusual Candida species were also recorded. Multiple fungi were frequently cultured in a single patient. The mean CD4+ cell count was lower in patients with onychomycosis and the frequency of onychomycosis increased in advanced stages of HIV disease. Acquired total leukonychia of the 20 nails was present in 4% of patients. CONCLUSION: Nail symptoms are much more frequent in patients with HIV than in healthy controls, and some of them could be linked to the level of immunosuppression.     

Prevention of hepatitis B in hemodialysis patients using hepatitis B immunoglobulin. A controlled study

In a controlled study, the protection effect of hepatitis B immune globulin (HBIG) was evaluated in patients hemodialyzed for less than one month in two collaborating units. Fifteen randomly selected patients received HBIG at five to eight week intervals throughout the study, and 13 other control patients received no immunoglobulin. During a follow-up period of 14 to 30 months, none of the HBIG-treated and 12 of the control patients developed evidence of exposure to virus B hepatitis, including 10 with HBs Ag antigenemia (p is less than 0.001): five of these remained persistently antigen positive. Evidence of non-B hepatitis was found in 8 HBIG-treated and in 3 non-treated patients. Only two HBIG-treated patients developed active antibodies against hepatitis B surface antigen. Thus, HBIG seems effective in preventing hepatitis B in hemodialysis patients, provided the interval between two injections is not greater than two months. However, prolonged administration of HBIG may impair passive-active immunization to hepatitis B virus.     

A study of corneal transplantation and human leukocyte antigen matching

OBJECTIVE: The effect of human leukocyte antigen (HLA) matching on immune rejection after keratoplasty was studied. METHODS: Immunoserologic HLA typing was performed on thirty-three eyes with corneal vascularization of 33 high-risk patients before keratoplasty, and HLA matching was made before the surgery. The donor corneas used for these cases were selected on the basis of obtaining a negative HLA cross-match test and matched ABO antigen compatibility of blood group before surgery. The mean follow-up was fifteen months. RESULTS: The findings suggested that there should be highly statistic significance (t = 7.36, P < 0.01) between the rate of rejection of well matched group and that of the poorly matched one. There was no correlation between the number of HLA antigen matched and the rejection rate (t = 0.917, P > 0.05). CONCLUSION: Lower incidence of corneal graft failure from allograft rejection occurs when well HLA matching is used for selecting donor in high-risk patients with corneal vascularization.     

Complement activation in septic shock due to gram-negative and gram-positive bacteria

Whole serum complement (CH50) and C3, C4, and C3PA plasma values were studied in 48 patients: 9 with nonseptic shock; 20 with sepsis; 14 with septic shock caused by gram-negative bacteria; 5 with septic shock caused by gram-positive bacteria. All were compared with a control group of 25 healthy individuals. Determinations were made upon admission and again 48 and 96 h later. No significant differences in complement values were found between the patients with nonseptic shock and the control group. In the patients with sepsis, decreased CH50 (p less than 0.001) and increased C3PA (p less than 0.02) values were observed, while C3 and C4 remained unaltered. In the patients with septic shock, markedly decreased levels of CH50, C3, and C4 were seen (p less than 0.001, and p less than 0.001, and p less than 0.001, respectively) without changes in C3PA levels. There were no differences between septic shock due to gram-negative and gram-positive bacteria, or between patients who died and those who survived. After 96 h, the altered values returned to the normal range. This underlines the transitory activation of the complement system through the classic pathway and suggests its possible role in the pathogenesis of septic shock in man.     

A controlled study of siblings of hyperactive children

A controlled study of siblings of hyperactive boys resulted in the following findings. The hyperactive child syndrome is more common among brothers of hyperactive children than among brothers of controls (26 per cent vs. 9 per cent). Both probands and their brothers presented with more symptoms of depression-anxiety than controls. The probands, but not their sibs, presented with more antisocial symptoms than controls. Although differences in intelligence and achievement scores were found between probands, their sibs, and controls, both intelligence level and academic achievement were within normal limits in all groups.     

Personality disorders in patients with eating disorders: a controlled study

A group of 24 eating-disordered female subjects (10 anorexia nervosa--AN--and 14 bulimia nervosa--BN--patients) were interviewed, using a semistructured interview for DSM-III-R Axis-II Personality Disorders (SCID-II). A group of 54 subjects without eating disorder acted as a control group. A high rate of personality disorder (PD) diagnoses occurred in eating disordered subjects (AN and BN patients), with a high prevalence of borderline, dependent, and self-defeating PD. Avoidant and obsessive-compulsive PD were more common in AN patients, whereas BN was associated with histrionic PD. Findings have implications for the assessment and diagnosis of eating-disordered patients and for treatment planning.     

Long-distance ESP: A controlled study.

Using a group of 22 transmitters (Ts) in Los Angeles, and 3 groups of receivers (Rs) in Los Angeles (N = 28), New York (N = 15), and Sussex, England (N = 14), a long-distance ESP study was conducted in which a series of 3 emotional episodes and 3 control episodes were shown Ts in Los Angeles. After each episode, Ts wrote their reactions, while at the same (local) time, Rs wrote their free associations. After writing these impressions, Rs were shown a pair of slides and chose the 1 slide which best matched their impressions. Results show that the 57 Rs scored significantly beyond chance expectations (p     

Complement activation in relation to capillary leakage in children with septic shock and purpura

To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.     

MMPI and race: A controlled study.

A 4-way, mixed-model, repeated-measures ANOVA; 13 1-way, balanced-cell ANOVA; and chi-square analyses of scales, items, high-points, number of scales with T?≥?70, and 4 high-scale categories were performed on MMPI results of 462 Black and White psychiatric patients matched for sex, age, residence, employment, years of education, marital status, socioeconomic status, and hospital status. Contrary to what has been reported previously, results indicate no differences beyond chance for any of the dependent variables. This finding is attributed to unique initial matching on crucial variables. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

N-acetyl-L-cysteine depresses cardiac performance in patients with septic shock

OBJECTIVE: To investigate the effects of adjunctive therapy with parenteral N-acetyl-L-cysteine in patients with newly diagnosed septic shock. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Multidisciplinary intensive care unit at a university teaching hospital. PATIENTS: Twenty patients (N-acetyl-L-cysteine group [n = 10], placebo group [n = 10]), 15 male and five female, of mean age 64 +/- 15 (SD) yrs and Acute Physiology and Chronic health Evaluation (APACHE) II score 33 +/- 6, with septic shock within 24 hrs of diagnosis. INTERVENTIONS: After a 2-hr stabilization period (time-zero minus 2 hrs to time-zero), patients received either N-acetyl-L-cysteine in 5% dextrose (150 mg/kg in 100 mL over 15 mins, followed by 50 mg/kg in 250 mL over 4 hrs, and then 100 mg/kg/24 hrs in 500 mL for 44 hrs; N-acetyl-L-cysteine group) or the equivalent volume of 5% dextrose (placebo group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport indices were measured at time-zero minus 2 hrs and time-zero, and at multiple time points thereafter until completion of the trial infusion (time-zero plus 48 hrs). A daily Organ Failure Score was recorded for 14 days. Treatment group demographics and hemodynamic variables did not differ significantly between the two groups at time-zero. Mean (SD), pooled mean arterial pressure (MAP), and cardiac index were 75 +/- 15 mm Hg and 3.9 +/- 1.2 L/min/m2, respectively. Over the next 48 hrs, in the N-acetyl-L-cysteine group, there was a progressive decrease, relative to both time-zero and the placebo group, in MAP, cardiac index, and left ventricular stroke work index (p < .01, repeated-measures analysis of variance). Percentage reductions in these values relative to the placebo group at 48 hrs were 23%, 18%, and 43%, respectively Oxygen transport indices, arterial blood gas analyses, Pao2/Fio2 ratio, and shunt did not differ over time between the groups. There was no difference in either daily Organ Failure Score over time (p > .01, repeated-measures analysis of variance) or hospital mortality rate (90% N-acetyl-L-cysteine group, 50% placebo group) (p > .1, logistic regression) between the two groups. CONCLUSION: Adjunctive therapy with N-acetyl-L-cysteine in newly diagnosed septic shock was associated with a depression in cardiovascular performance, as indicated by progressive reductions in cardiac index, left ventricular stroke work index, and MAP.     

Hydroperoxides in plasma are reduced by intensified insulin treatment. A randomized controlled study of IDDM patients with microalbuminuria

OBJECTIVE: An association between reactive oxygen species and diabetic micro- and macrovascular complications has been proposed. In the present study, we have examined the effect of an improved blood glucose control on plasma levels of hydroperoxides in patients with IDDM. RESEARCH DESIGN AND METHODS: Subjects included 30 young IDDM patients with microalbuminuria who were randomized to receive either continuous subcutaneous insulin infusion (CSII) by a portable insulin pump (n = 15) or conventional insulin treatment (CIT) (n = 15) for 24 months. Plasma levels of hydroperoxides were measured by the ferrous oxidation with Xylenol Orange, version 2 (FOX2) assay. This method measures total lipid hydroperoxides and, unlike other methods, does not suffer from extraction losses. RESULTS: The mean HbA1c level was lower in the CSII group at the end of the study than in the CIT group: (mean [95% CI]) 8.6 (8.1-9.1) vs. 9.6 (9.0-10.3)%, respectively (P < 0.002). The level of plasma hydroperoxides was very similar at the start of the study but was significantly lower in the CSII group compared with the CIT group at the end of the study: 2.9 (2.1-3.7) vs. 4.3 (3.2-5.4) mumol/l, respectively (P < 0.02). In the CSII group, hydroperoxides were reduced by 31% from baseline (P < 0.001), whereas there was no change in levels of hydroperoxides in the CIT group. Mean hydroperoxide levels correlated with mean HbA1c during the study (r = 0.39, P < 0.04). Hydroperoxide levels were associated with the levels of microalbuminuria (r = 0.45, P < 0.02). CONCLUSIONS: This study provides support for the hypothesis that hyperglycemia is an important factor in the generation of hydroperoxides, and, thus, reactive oxygen species, in the circulation of IDDM patients.     

The effects of intravenous antioxidants in patients with septic shock

Oxidative stress is implicated in septic shock. We investigated the effect of intravenous antioxidant therapy on antioxidant status, lipid peroxidation, hemodynamics and nitrite in patients with septic shock. Thirty patients randomly received either antioxidants (n-acetylcysteine 150 mg/kg for 30 min then 20 mg/kg/h plus bolus doses of 1 g ascorbic acid and 400 mg alpha-tocopherol) or 5% dextrose. Basal vitamin C was low and redox-reactive iron was elevated in all patients. In the 16 patients receiving antioxidants, vitamin C increased (p = .0002) but total antioxidant capacity was unaffected. Lipid peroxides were elevated in all patients but did not increase further in the patients receiving antioxidants. Plasma total nitrite also increased (p = .007) in the antioxidant group. Heart rate increased in patients receiving antioxidants at 60 min (p = .018) and 120 min (p = .004). Cardiac index also increased at 60 min (p = .007) and 120 min (p = .05). Systemic vascular resistance index decreased at 120 min in the antioxidant treated patients (p = .003). The effect of antioxidants on hemodynamic variables has not previously been reported. Antioxidant administration may be a useful adjunct to conventional approaches in the management of septic shock.     

铁矿烧结过程中的活化技术研究

添加活化剂是降低烧结能耗的有效措施。通过对烧结物理机制的探讨，得出了铁矿烧结活化技术开发中需要遵循的三条基本判据，即溶解度判据、偏析判据和扩散判据。经过分析得出扩散判据为其根本判据。还借助相图原理探讨了活化剂的筛选原则，并提出了逐级局部活化法。