OBJECTIVE

To determine the impact of body mass index (BMI) on outcomes in critically ill patients.

METHODS

Retrospective analysis of a large multi-institutional ICU database.

METHODS

The influence of BMI classification (underweight, < 20 kg/m(2); normal [control subjects], 20 to 25 kg/m(2); overweight, 25 to 30 kg/m(2); obese, 30 to 40 kg/m(2); severe obesity,>> 40 kg/m(2)) on hospital survival, functional status at hospital discharge, and ICU/hospital length of stay (LOS) was analyzed via multivariate analysis, adjusting for age, gender, type of hospital admission, and severity score (ie, simplified acute physiologic score [SAPS] II and mortality prediction model [MPM] at time zero). Univariate analysis also was performed according to the quartile of the severity score. All comparisons were to the normal BMI group.

RESULTS

Of 63,646 patient datasets, 41,011 were complete for height, weight, and at least one of the two severity scores. We found increased mortality in underweight patients (odds ratio [OR] of death: SAPS group, 1.19; MPM group, 1.26) but not in overweight, obese, or severely obese patients. ICU and hospital LOS were increased in both the severely obese (OR of discharge: ICU, 0.81 and 0.84, respectively; hospital, 0.83 and 0.87, respectively) and underweight groups (OR of discharge: ICU, 0.96 and 0.94, respectively; hospital, 0.91 and 0.90, respectively). Only in the SAPS group did the obese group have increased ICU LOS (OR, 0.96) and hospital LOS (OR, 0.96). Functional status at discharge was impaired in underweight patients (OR of disability: ICU, 1.11; hospital, 1.19). Overweight patients had decreased discharge disability (OR of disability: SAPS, 0.93; MPM, 0.94), while the results in the obese group were discordant between the two severity score groups (SAPS, not significant; MPM, 0.91; p < 0.05 for all ORs).

CONCLUSIONS

Low BMI, but not high BMI, is associated with increased mortality and worsened hospital discharge functional status. LOS is increased in severely obese patients and, to a lesser extent, in underweight patients. Patients in the overweight and obese BMI groups may have improved mortality and discharge functional status.

Between October 1997 and June 2001, 140 English hospitals participating in the surveillance of surgical site infection (SSI) with the Nosocomial Infection National Surveillance Service (NINSS) reported 2832 SSIs following 67 410 surgical procedures in nine defined categories of surgery. Limb amputation had the highest incidence of SSI with 14.3 SSIs per 100 operations. For all categories of surgery, except knee prosthesis (P=0.128), there was a linear increase in the incidence of SSI when the American National Nosocomial Infections Surveillance risk index increased. Superficial incisional SSI was more common than deep incisional and organ/space SSI, and accounted for more than half of all SSIs for all categories of surgery. The postoperative length of stay (LOS) was longer for patients with SSI, and when adjusted for other factors influencing LOS, the extra LOS due to SSI ranged from 3.3 days for abdominal hysterectomy to 21.0 days for limb amputation, and was at least nine days for the other categories. The additional cost attributable to SSI ranged from pound959 for abdominal hysterectomy to pound6103 for limb amputation. Deep incisional and organ/space SSI combined incurred a greater extra LOS and cost than superficial incisional SSI for all categories of surgery, except limb amputation. The crude mortality rate was higher for patients with SSI for all categories of surgery but, after controlling for confounding, only patients with SSI following hip prosthesis had a mortality rate that was significantly higher than those without SSI [odds ratio (OR)=1.8, P=0.002]. However, the adjusted mortality rate for patients with deep incisional and organ/space SSI compared with those without SSI was significantly higher for vascular surgery (OR=6.8, P<0.001), hip prosthesis (OR=2.5, P=0.005) and large bowel surgery (OR=1.8, P=0.04). This study shows that the adverse impact of SSI differs greatly for different categories of surgery, and highlights the importance of measuring the impact for defined categories rather than for all SSIs and all surgical procedures.

OBJECTIVE

To determine whether altering the dietary content of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E(2) (PGE(2)) levels.

METHODS

Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection.

RESULTS

Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase-mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE(2) levels, and decreased vascular endothelial growth factor expression.

CONCLUSIONS

These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE(2) and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.

An E. coli mutant that lacks tRNA-guanine transglycosylase was isolated by random screening from a collection of Escherichia coli mutants obtained with N-methyl-N'-nitro-N-nitrosoguanidine. The defective gene, named tgt, was mapped at about 9 min on the E. coli chromosome, and the gene order was shown to be phoB-tgt-tsx. tgt was transferred to an E. coli strain with a defined genetic background by P1 transduction to investigate its function. The mutant thus obtained lacked queuosine (2-amino-5-[3S, 4R, 5S)-4,5-dihydroxycyclopent-1-en-3-ylaminomethyl]-7-(beta-D-ribofuranosyl)-pyrro lo-[2,3-D]-pyrimidin-4-one) in tRNA, indicating that the enzyme is actually involved in the biosynthesis of queuosine in tRNA. No clear biological defect was observed in the mutant, and, in fact, it grew slightly faster than the control isogenic strain. tRNATyr lacking queuosine, isolated from the mutant, showed no significant biological difference from normal queuosine-containing tRNA in amino acid acceptor activity or amino acid transfer in a cell-free protein synthesizing system directed by synthetic polynucleotide. The only phenotypic change observed in the mutant thus far is marked reduction of viability when the cells are kept under unsuitable conditions for growth, suggesting that the presence of queuosine in tRNA is important to E. coli for survival in the natural environment.

BACKGROUND

The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs.

METHODS

A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost.

RESULTS

Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost.

CONCLUSIONS

rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation.

BACKGROUND

NCT01898208.

Gonococcal lipooligosaccharides (LOSs) are a series of antigenically complex heteropolymers. To investigate whether all members of clonally selected populations of Neisseria gonorrhoeae express antigenically similar LOS, we studied gonococcal strains 4505 and 220 with monoclonal antibodies 6B4 and 3F11 which have specificity for different oligosaccharide epitopes on the same or comigrating LOS unit(s) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Fluorescent-antibody and immunoelectron microscopy studies indicated that all members of the clonally selected populations were not homogenous for the epitopes these antibodies recognized. Fluorescence-activated cell sorting studies of 3F11-coated strain 220 indicated that the density of epitope expression was a function of time of growth. The population could be separated into two broad groups corresponding to organisms staining strongly or weakly for the 3F11 epitope, and the epitope density decreased during the late-log and stationary phases of growth. Sequentially staining organisms on Formvar grids with 6B4 and 3F11, followed by staining with either 5- or 15-nm colloidal gold spheres conjugated to goat anti-mouse immunoglobulin M demonstrated the following populations of cells among organisms derived from a single clone: organisms which stained for both 6B4 and 3F11 epitopes and organisms which stained for either 6B4 epitopes alone or 3F11 epitopes alone. Immunofluorescence microscopy studies with rhodamine and fluorescein goat anti-mouse immunoglobulin M conjugates sequentially staining organisms on Formvar grids with 3F11 and 6B4 also demonstrated these three populations. Analysis of LOS preparations made over the last 5 years indicated no change in serotype antigen concentration or in sodium dodecyl sulfate-polyacrylamide gel electrophoresis migration pattern. These studies indicate that while clonally selected strains of Neisseria gonorrhoeae undergo phenotypic variation at the epitope level, the impact of this variation on the total LOS of the population has little overall effect on its antigenic or physicochemical properties.

The Mini-Mental State Evaluation (MMSE) was used in an epidemiological survey of a community of mixed ethnicity (Hispanic, white non-Hispanic) as part of the Los Angeles Epidemiologic Catchment Area Program. Results of the study showed that age, educational level, ethnicity, and language of the interview influenced the number of MMSE errors. Items on which the effects of ethnicity and language were most pronounced were identified, and suggestions on ways to minimize such sociocultural artifacts are provided in efforts to improve the epidemiological significance of the instrument, particularly as it concerns cross-cultural research.

BACKGROUND

Patients at the Philadelphia Veterans Affairs Medical Center frequently voice concern that air exposure during lung cancer surgery might cause tumor spread. Several African-American patients asserted that this belief was common in the African-American community.

OBJECTIVE

To assess the prevalence of the belief that air exposure during lung cancer surgery might cause tumor spread and gauge the influence of this belief on the willingness of African-American and white patients to have lung cancer surgery.

METHODS

Prospective questionnaire survey.

METHODS

Philadelphia Veterans Affairs Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Los Angeles Veterans Affairs Medical Center, Los Angeles, California; and Medical University of South Carolina, Charleston, South Carolina.

METHODS

626 consecutive patients in pulmonary and lung cancer clinics.

METHODS

None.

RESULTS

38% of patients (61% of whom were African American and 29% of whom were white) stated that they believe air exposure at surgery causes tumor spread. The most significant predictor of belief was African-American race (odds ratio, 3.5 [95% CI, 1.9 to 6.5]), even after controlling for other relevant variables in a multivariable analysis. Nineteen percent of African Americans stated that this belief was a reason for opposing surgery, and 14% would not accept their physicians' assertion that the belief is false. These rates were also statistically significantly higher among African-American than white patients.

CONCLUSIONS

Belief in accelerated tumor spread at surgery is prevalent among general pulmonary outpatients and lung cancer clinic patients facing lung surgery, particularly among African-American patients. Our findings may pertain to key racial disparities in lung cancer surgery and survival rates and suggest that culturally sensitive physician training or outreach programs directed at disparate beliefs and attitudes may help to address racial discrepancies in health care outcomes.

Rel and RelA, individually dispensable for lymphopoiesis, serve unique functions in activated B and T cells. Here their combined roles in lymphocyte development were examined in chimeric mice repopulated with c-rel(-/-) rela(-/-) fetal liver hemopoietic stem cells. Mice engrafted with double-mutant cells lacked mature IgM(lo)IgD(hi) B cells, and numbers of peripheral CD4(+) and CD8(+) T cells were markedly reduced. The absence of mature B cells was associated with impaired survival that coincided with reduced expression of bcl-2 and A1. bcl-2 transgene expression not only prevented apoptosis and increased peripheral B-cell numbers, but also induced further maturation to an IgM(lo)IgD(hi) phenotype. In contrast, the survival of double-mutant T cells was normal and the bcl-2 transgene could not rectify the peripheral T-cell deficit. These findings indicate that Rel and RelA serve essential, albeit redundant, functions during the later antigen-independent stages of B- and T-cell maturation, with these transcription factors promoting the survival of peripheral B cells in part by upregulating Bcl-2.

While the role of neurocognitive impairment in predicting functional outcome in chronic schizophrenia is now widely accepted, the results that have examined this relationship in the early phase of psychosis are surprisingly rather mixed. The predictive role of cognitive impairment early in the illness is of particular interest because interventions during this initial period may help to prevent the development of chronic disability. In a University of California, Los Angeles (UCLA) longitudinal study, we assessed schizophrenia patients with a recent first episode of psychosis using a neurocognitive battery at an initial clinically stabilized outpatient point and then followed them during continuous treatment over the next 9 months. Three orthogonal cognitive factors were derived through principal components analysis: working memory, attention and early perceptual processing, and verbal memory and processing speed. All patients were provided a combination of maintenance antipsychotic medication, case management, group skills training, and family education in a UCLA research clinic. A modified version of the Social Adjustment Scale was used to assess work outcome. Multiple regression analyses indicate that the combination of the 3 neurocognitive factors predicts 52% of the variance in return to work or school by 9 months after outpatient clinical stabilization. These data strongly support the critical role of neurocognitive factors in recovery of work functioning after an onset of schizophrenia. Cognitive remediation and other interventions targeting these early cognitive deficits are of major importance to attempts to prevent chronic disability.

Macrophage and dendritic cell (DC) progenitors (MDPs) and common DC progenitors (CDPs) are bone marrow (BM) progenitors with DC differentiation potential. However, both MDPs and CDPs give rise to large numbers of conventional DCs (cDCs) and few plasmacytoid DCs (pDCs), implying that more dedicated pDC progenitors remain to be identified. Here we have described DC progenitors with a prominent pDC differentiation potential. Although both MDPs and CDPs express the macrophage colony stimulating factor (M-CSF) receptor (M-CSFR), the progenitors were confined to a M-CSFR(-) fraction, identified as Lin(-)c-Kit(int/lo)Flt3(+)M-CSFR(-), and expressed high amounts of E2-2 (also known as Tcf4) an essential transcription factor for pDC development. Importantly, they appeared to be directly derived from either CDPs or lymphoid-primed multipotent progenitors (LMPPs). Collectively, our findings provide insight into DC differentiation pathways and may lead to progenitor-based therapeutic applications for infection and autoimmune disease.

The lipooligosaccharides (LOS) of nontypable Haemophilus influenzae are an antigenically heterogeneous group of macromolecules. Immunodiffusion and enzyme-linked immunosorbent assay inhibition studies with phenol-water-extracted LOS and absorbed antisera specific for the oligosaccharide portion of the LOS identified six LOS strain-specific antigens. To facilitate screening large numbers of strains to search for LOS antigenic heterogeneity, a system utilizing proteinase K whole cell digests in Western blots was developed. Seventy-two nontypable H. influenzae LOS extracts were analyzed in this Western blot assay. Thirty-seven of these extracts could be segregated into 10 antigenically distinct LOS groups based on immunologic recognition by one or more of the rabbit antisera. Thirty-five of the strains did not contain these LOS antigens. These results demonstrate that antigenic differences exist among the LOS of nontypable H. influenzae strains, and this heterogeneity has the potential to be used to establish an LOS-based serogrouping system.

BACKGROUND

The role of immuno-modulating diets (IMDs) in critically ill patients is controversial.

OBJECTIVE

The goal of this meta-analysis was to determine the impact of IMD's on hospital mortality, nosocomial infections and length of stay (LOS) in critically ill patients. Outcome was stratified according to type of IMD and patient setting.

METHODS

MEDLINE, Embase, Cochrane Register of Controlled Trials.

METHODS

RCT's that compared the outcome of critically ill patients randomized to an IMD or a control diet.

RESULTS

Twenty-four studies (with a total of 3013 patients) were included in the meta-analysis; 12 studies included ICU patients, 5 burn patients and 7 trauma patients. Four of the studies used formulas supplemented with arginine, two with arginine and glutamine, nine with arginine and fish oil (FO), two with arginine, glutamine and FO, six with glutamine alone and three studies used a formula supplemented with FO alone. Overall IMD's had no effect on mortality or LOS, but reduced the number of infections (OR 0.63; 95% CI 0.47-0.86, P = 0.004, I(2) = 49%). Mortality, infections and LOS were significantly lower only in the ICU patients receiving the FO IMD (OR 0.42, 95% CI 0.26-0.68; OR 0.45, 95% CI 0.25-0.79 and WMD -6.28 days, 95% CI -9.92 to -2.64, respectively).

CONCLUSIONS

An IMD supplemented with FO improved the outcome of medical ICU patients (with SIRS/sepsis/ARDS). IMDs supplemented with arginine with/without additional glutamine or FO do not appear to offer an advantage over standard enteral formulas in ICU, trauma and burn patients.

CD103(+) dendritic cells (DCs) are the major conventional DC population in the intestinal lamina propria (LP). Our previous report showed that a small number of cells in the LP could be classified into four subsets based on the difference in CD11c/CD11b expression patterns: CD11c(hi)CD11b(lo) DCs, CD11c(hi)CD11b(hi) DCs, CD11c(int)CD11b(int) macrophages, and CD11c(int)CD11b(hi) eosinophils. The CD11c(hi)CD11b(hi) DCs, which are CD103(+), specifically express TLR5 and induce the differentiation of naive B cells into IgA(+) plasma cells. These DCs also mediate the differentiation of Ag-specific Th17 and Th1 cells in response to flagellin. We found that small intestine CD103(+) DCs of the LP (LPDCs) could be divided into a small subset of CD8α(+) cells and a larger subset of CD8α(-) cells. Flow cytometry analysis revealed that CD103(+)CD8α(+) and CD103(+)CD8α(-) LPDCs were equivalent to CD11c(hi)CD11b(lo) and CD11c(hi)CD11b(hi) subsets, respectively. We analyzed a novel subset of CD8α(+) LPDCs to elucidate their immunological function. CD103(+)CD8α(+) LPDCs expressed TLR3, TLR7, and TLR9 and produced IL-6 and IL-12p40, but not TNF-α, IL-10, or IL-23, following TLR ligand stimulation. CD103(+)CD8α(+) LPDCs did not express the gene encoding retinoic acid-converting enzyme Raldh2 and were not involved in T cell-independent IgA synthesis or Foxp3(+) regulatory T cell induction. Furthermore, CD103(+)CD8α(+) LPDCs induced Ag-specific IgG in serum, a Th1 response, and CTL activity in vivo. Accordingly, CD103(+)CD8α(+) LPDCs exhibit a different function from CD103(+)CD8α(-) LPDCs in active immunity. This is the first analysis, to our knowledge, of CD8α(+) DCs in the LP of the small intestine.

BACKGROUND

Surgeon experience correlates with improved outcomes for complex operations. Endocrine operations are increasingly performed in the outpatient setting, where outcomes have not been systematically studied. We examined the effect of surgeon volume on clinical and economic outcomes for thyroid, parathyroid, and adrenal surgery across inpatient and outpatient settings.

METHODS

New York and Florida state discharge data (2002) were studied. Surgeons were grouped by annual endocrine operative volume: Group A, 1 to 3 operations; B, 4 to 8; C, 9 to 19; D, 20 to 50; E, 51 to 99; and F,>>or=100. Multiple regression analyses were applied to analyze complications, length of stay (LOS), and total charges (TC), while controlling for comorbidity, economic factors, and hospital-centric variables.

RESULTS

We identified 13,997 discharges, with 28% of operations performed on an outpatient basis (admission/discharge on same calendar day). For all cases, group A contributed disproportionately more complications (observed/expected [O/E] 1.65, P < .001) and Group F contributed disproportionately less (0.52; P < .001). High surgeon volume was associated with decreased LOS and reduced TC. Hospital volume had a negligible effect on outcomes.

CONCLUSIONS

Surgeon volume correlates inversely with complication rates, LOS, and TC, in endocrine surgery. The lowest complication rates are achieved by surgeons performing>>or=100 endocrine operations annually.

OBJECTIVE

The mechanical characteristics of the human free tendon and aponeurosis, in vivo, remains largely unknown. The present study evaluated the longitudinal displacement of the separate free Achilles tendon and distal (deep) aponeurosis of the medial gastrocnemius muscle during voluntary isometric contraction.

METHODS

Ultrasonography-obtained displacement of the free tendon and tendon-aponeurosis complex, electromyography of the gastrocnemius, soleus, and dorsiflexor muscles, and joint angular rotation were recorded during isometric plantarflexion (n = 5). Tendon cross-sectional area, moment arm and segment lengths (L(o)) were measured using magnetic resonance imaging. Tendon force was calculated from joint moments and tendon moment arm, and stress was obtained by dividing force by cross-sectional area. The difference between the free tendon and tendon-aponeurosis complex deformation yielded separate distal aponeurosis deformation. Longitudinal aponeurosis and tendon strain were obtained from the deformations normalized to segment lengths.

RESULTS

At a common tendon force of 2641 +/- 306 N, the respective deformation and Lo were 5.85 +/- 0.85 and 74 +/- 0.8 mm for the free tendon and 2.12 +/- 0.64 and 145 +/- 1.3 mm for the distal aponeurosis, P < 0.05. Longitudinal strain was 8.0 +/- 1.2% for the tendon and 1.4 +/- 0.4% for the aponeurosis, P < 0.01. Stiffness and stored energy was 759 +/- 132 N mm(-1) and 6.14 +/- 1.89 J, respectively, for the free tendon. Cross-sectional area of the Achilles tendon was 73 +/- 4 mm2, yielding a stress of 36.5 +/- 4.6 MPa and Young's modulus of 788 +/- 181 MPa.

CONCLUSIONS

The free Achilles tendon demonstrates greater strain compared with that of the distal (deep) aponeurosis during voluntary isometric contraction, which suggests that separate functional roles may exist during in vivo force transmission.

HIV-related stigma, discrimination, and homophobia impede community-based efforts to combat HIV disease among Latino and African American gay and bisexual men. This commentary highlights ways to address these social biases in communities of color in Los Angeles, California, from the perspectives of staff from HIV prevention programs. Information was collected from HIV prevention program staff participating in a 2-day symposium. The outcomes from the symposium offer strategies for developing and implementing HIV prevention services for Latino and African American gay and bisexual men, which include: (1) addressing social biases present in a community that can hinder, and even prohibit, utilization of effective HIV prevention programs; (2) recasting HIV prevention messages in a broader social or health context; (3) developing culturally appropriate HIV prevention messages; (4) exploring new modalities and venues for delivering HIV prevention messages that are appropriate for gay and bisexual men of color and the communities in which they live; and (5) broadening the target of HIV prevention services to include service providers, local institutions and agencies, and the community at-large. These strategies underscore the need to consider the social and contextual factors of a community when designing and implementing HIV prevention programs.

OBJECTIVE

Patients with cortical dysplasia (CD) are difficult to treat because the MRI abnormality may be undetectable. This study determined whether fluorodeoxyglucose (FDG)-PET/MRI coregistration enhanced the recognition of CD in epilepsy surgery patients.

METHODS

Patients from 2004-2007 in whom FDG-PET/MRI coregistration was a component of the presurgical evaluation were compared with patients from 2000-2003 without this technique. For the 2004-2007 cohort, neuroimaging and clinical variables were compared between patients with mild Palmini type I and severe Palmini type II CD.

RESULTS

Compared with the 2000-2003 cohort, from 2004-2007 more CD patients were detected, most had type I CD, and fewer cases required intracranial electrodes. From 2004-2007, 85% of type I CD cases had normal non-University of California, Los Angeles (UCLA) MRI scans. UCLA MRI identified CD in 78% of patients, and 37% of type I CD cases had normal UCLA scans. EEG and neuroimaging findings were concordant in 52% of type I CD patients, compared with 89% of type II CD patients. FDG-PET scans were positive in 71% of CD cases, and type I CD patients had less hypometabolism compared with type II CD patients. Postoperative seizure freedom occurred in 82% of patients, without differences between type I and type II CD cases.

CONCLUSIONS

Incorporating fluorodeoxyglucose-PET/MRI coregistration into the multimodality presurgical evaluation enhanced the noninvasive identification and successful surgical treatment of patients with cortical dysplasia (CD), especially for the 33% of patients with nonconcordant findings and those with normal MRI scans from mild type I CD.

The recent discovery of cat fleas (Ctenocephalides felis) infected with a typhuslike rickettsia (designated the ELB agent) raises the question of whether similar rickettsial infections exist in wild cat flea populations. We verified the presence of the ELB agent and Rickettsia typhi in urban and suburban areas of Los Angeles, Calif. Opossums trapped in close proximity to the residences of human murine typhus cases in Los Angeles county and other areas within the city of Los Angeles were tested for the presence of typhus group rickettsiae by the polymerase chain reaction (PCR). The presence of rickettsiae in the spleen tissues of three opossums (n = 9) and in 66 opossum fleas (n = 205) was determined by PCR and was verified by dot blot and Southern transfer hybridization. Further analysis of the amplified PCR products generated by a series of primer pairs derived from either the 17-kDa antigen gene or the citrate synthase gene revealed that both R. typhi and the ELB agent were present in the tested samples. Dual infection was not noted in the samples; however, the fleas were infected with either R. typhi or the ELB agent. The presence of the ELB agent in the cat flea population may have implications for public health. Whether this agent is responsible for the mild cases of human murine typhus in urban and suburban areas of Los Angeles or in other endemic foci remains to be determined.

Community-associated methicillin-resistant Staphylococcus aureus (MRSA) is the most common pathogen among patients with skin and soft tissue infections seeking treatment at a Los Angeles (USA) area emergency department. The proportion caused by MRSA increased from 29% in 2001 to 2002 to 64% in 2003 to 2004. No clinical or historical features reliably predict MRSA etiology.

High levels of viral replication occur in gut-associated lymphoid tissue (GALT) and other lymphoid tissues (LT) since the early phase of human/simian immunodeficiency virus (HIV/SIV) infection. Regulatory T cells (T(reg)), a subset of immunosuppressive T cells expressing CTLA-4 and the FoxP3 transcription factor, accumulate in LT during HIV/SIV infection. Here we show that FoxP3 and CTLA-4 mRNA are increased in leukocytes from the spleens, lymph nodes (LN), and mucosal sites of chronically SIV-infected macaques with high viremia (SIV(HI)) compared to animals with low viremia (SIV(LO)). FoxP3 and CTLA-4 correlated with SIV RNA levels in tissues; SIV virus levels in the spleen, inguinal LN, mesenteric LN, colon, and jejunum directly correlated with the plasma virus level. Importantly, CTLA-4 and FoxP3 mRNA were predominantly increased in the CD25(-) subpopulation of leukocytes from SIV(HI), further challenging the classical definition of T(reg) as CD4(+) CD25(+) T cells. Similar to CTLA-4 and FoxP3, expression of indoleamine 2,3-dioxygenase (IDO), an immunosuppressive enzyme induced by T(reg) in antigen-presenting cells, was increased in the spleens, mesenteric LN, colons, and jejuna from SIV(HI) compared to SIV(LO) and directly correlated to SIV RNA in the same tissues. Accordingly, plasma kynurenine/tryptophan, a marker for IDO enzymatic activity, was significantly higher in SIV(HI) compared to SIV(LO) and correlated with plasma viral levels. Increased T(reg) and IDO in LT of SIV-infected macaques may be the consequence of increased tissue inflammation and/or may favor virus replication during the chronic phase of SIV infection.

OBJECTIVE

To examine whether disclosure of HIV-positive status to sex partners at risk for HIV infection is associated with safer sex practices and to examine the prevalence and correlates of specific disclosure/sexual behavior patterns.

METHODS

Cross-sectional assessment of 206 HIV-positive men (41% homosexual, 35% bisexual, 24% heterosexual) sampled randomly at an outpatient HIV clinic in Los Angeles, who reported that their most recent sex partner was HIV-negative or of unknown serostatus. Unsafe sex was defined as unprotected anal or vaginal intercourse with that partner.

RESULTS

Twenty-five percent of the men engaged in unsafe sex, and 48% of the total sample withheld disclosure from the partner. The prevalence of safer sex was not significantly higher among disclosers than among nondisclosers (unadjusted odds ratio = 1.29; 95% confidence interval: 0.69-2.45), and disclosure was not significantly associated with safer sex in any of 25 demographic or partner subgroups examined in the study. In the full sample, 40% of the men disclosed and engaged in safer sex (informed protection), 35% withheld disclosure and engaged in safer sex (uninformed protection), 12% informed their partner and engaged in unsafe sexual behavior (informed exposure), and 13% withheld disclosure and engaged in unsafe sex (uninformed exposure). Risky behavior patterns were associated with using alcohol/drugs before sex, having an HIV-unknown partner, being less emotionally involved with one's partner, and testing seropositive in the previous 3 years.

CONCLUSIONS

Interventions for seropositive men that focus primarily on increasing disclosure of serostatus to sex partners may not reduce the prevalence of unsafe sex. Interventions are needed to address the social and psychologic processes that give rise to risky behavior patterns in HIV-infected men. Improved substance abuse counseling also may be needed.

The association of body size, lifestyle, and medical conditions with renal cell cancer risk was examined among 161,126 Hawaii-Los Angeles Multiethnic Cohort participants (1993-2002). After 8.3 years of follow-up, 347 renal cell cancer cases (220 men, 127 women) were identified. Renal cell cancer risk increased with increasing body mass index in men (multivariate relative risk (RR) = 1.06 per unit of body mass index, p = 0.001) and women (RR = 1.07, p < 0.0001). The relative risks associated with being obese compared with being lean were 1.76 (95% confidence interval (CI): 1.20, 2.58) for men and 2.27 (95% CI: 1.37, 3.74) for women. Hypertension was associated with renal cell cancer (RR-men = 1.42, 95% CI: 1.07, 1.87; RR-women = 1.58, 95% CI: 1.09, 2.28). Smoking was confirmed to be a risk factor for both sexes. Among women, diuretic use was associated with increased risk (RR = 1.63, 95% CI: 1.04, 2.57), whereas physical activity was associated with reduced risk (ptrend = 0.027). Alcohol consumption was inversely associated with risk for men (ptrend = 0.045). Compared with nondrinkers, men who drank>>or=1 drinks/day had a 31% lower risk (95% CI: 0.49, 0.96). Results show that body mass index, smoking, and hypertension are risk factors for renal cell cancer in both sexes.

CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8+ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8+ CTL in HIV-seropositive subjects. Purified CD8+ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIVIIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8+ CTL activity against gag, pol, and env proteins. CD8+ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR-CD38- CD8+ cells had little activity. Highly purified DR+CD38+ CD8+ cells had higher HIV-specific CTL activity than other CD8+ cells. DR+CD38- or DR-CD38+ CD8+ cells also mediated significant activity, but only about half as much on a per cell basis as DR+CD38+ CD8+ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag-specific CD8+ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 +/- 132/mm3) and AIDS patients (253 +/- 178/mm3) had markedly elevated levels of DR+CD38+ CD8+ cells compared with the levels in HIV-seronegative controls (7 +/- 3/mm3). However, the level of anti-HIV CTL activity was not correlated with the level of DR+CD38+ CD8+ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4+ cells numbers, suggesting that the loss of CD8+ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4+ cell immunodeficiency in HIV-infected subjects.