The Multicenter AIDS Cohort Study was designed to elucidate the natural history of the infection causing acquired immunodeficiency syndrome (AIDS), identify risk factors for occurrence and clinical expression of the infection, and establish a repository of biologic specimens for future study. A variety of recruitment techniques, including special assurance of confidentiality, were used to enroll participants. Nearly 5,000 homosexual men volunteered for semiannual interview, physical examination, and laboratory testing in four metropolitan areas. A significant majority of these men in each center (69-83%) reported having 50 or more lifetime sexual partners, and over 80% had engaged in receptive anal intercourse with at least some of their partners in the previous two years. By the time of the participants' initial evaluation (April 1984-April 1985), infection with the human immunodeficiency virus (HIV) had occurred in higher proportions of men in Los Angeles (51%) and Chicago (43%) than in Baltimore/Washington, DC (31%) and Pittsburgh (21%), presumably as a result of the higher number of partners and proportion with whom these men had engaged in high-risk practices (e.g., receptive anal intercourse). Follow-up evaluations are underway in this comprehensive longitudinal investigation of HIV infection.

Leukotrienes (LTs) and prostaglandins (PGs) amplify acute inflammation, whereas lipoxins (LXs) have unique anti-inflammatory actions. Temporal analyses of these eicosanoids in clinical and experimental exudates showed early coordinate appearance of LT and PG with polymorphonuclear neutrophil (PMN) recruitment. This was followed by LX biosynthesis, which was concurrent with spontaneous resolution. Human peripheral blood PMNs exposed to PGE2 (as in exudates) switched eicosanoid biosynthesis from predominantly LTB4 and 5-lipoxygenase (5-LO)-initiated pathways to LXA4, a 15-LO product that "stopped" PMN infiltration. These results indicate that first-phase eicosanoids promote a shift to anti-inflammatory lipids: functionally distinct lipid-mediator profiles switch during acute exudate formation to "reprogram" the exudate PMNs to promote resolution.

The single gene reassortant virus that derives its PB2 gene from the avian influenza A/Mallard/NY/78 virus and remaining genes from the human influenza A/Los Angeles/2/87 virus exhibits a host range restriction (hr) phenotype characterized by efficient replication in avian tissue and failure to produce plaques in mammalian Madin-Darby canine kidney cells. The hr phenotype is associated with restriction of viral replication in the respiratory tract of squirrel monkeys and humans. To identify the genetic basis of the hr phenotype, we isolated four phenotypic hr mutant viruses that acquired the ability to replicate efficiently in mammalian tissue. Segregational analysis indicated that the loss of the hr phenotype was due to a mutation in the PB2 gene itself. The nucleotide sequences of the PB2 gene of each of the four hr mutants revealed that a single amino acid substitution at position 627 (Glu->>Lys) was responsible for the restoration of the ability of the PB2 single gene reassortant to replicate in Madin-Darby canine kidney cells. Interestingly, the amino acid at position 627 in every avian influenza A virus PB2 protein analyzed to date is glutamic acid, and in every human influenza A virus PB2 protein, it is lysine. Thus, the amino acid at residue 627 of PB2 is an important determinant of host range of influenza A viruses.

The development of an adequate assessment instrument is a necessary prerequisite for social psychological research on loneliness. Two studies provide methodological refinement in the measurement of loneliness. Study 1 presents a revised version of the self-report UCLA (University of California, Los Angeles) Loneliness Scale, designed to counter the possible effects of response bias in the original scale, and reports concurrent validity evidence for the revised measure. Study 2 demonstrates that although loneliness is correlated with measures of negative affect, social risk taking, and affiliative tendencies, it is nonetheless a distinct psychological experience.

The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 micro m), fine (< 2.5 microm), and ultrafine (< 0.1 microm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria.

OBJECTIVE

Health-related quality of life (HRQOL) is an increasingly important endpoint in prostate cancer care. However, pivotal issues that are not fully assessed in existing HRQOL instruments include irritative urinary symptoms, hormonal symptoms, and multi-item scores quantifying bother between urinary, sexual, bowel, and hormonal domains. We sought to develop a novel instrument to facilitate more comprehensive assessment of prostate cancer-related HRQOL.

METHODS

Instrument development was based on advice from an expert panel and prostate cancer patients, which led to expanding the 20-item University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) to the 50-item Expanded Prostate Index Composite (EPIC). Summary and subscale scores were derived by content and factor analyses. Reliability and validity were assessed by test-retest correlation, Cronbach's alpha coefficient, interscale correlation, and EPIC correlation with other validated instruments.

RESULTS

Test-retest reliability and internal consistency were high for EPIC urinary, bowel, sexual, and hormonal domain summary scores (each r>>/=0.80 and Cronbach's alpha>>/=0.82) and for most domain-specific subscales. Correlations between function and bother subscales within domains were high (r >0.60). Correlations between different primary domains were consistently lower, indicating that these domains assess distinct HRQOL components. EPIC domains had weak to modest correlations with the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12), indicating rationale for their concurrent use. Moderate agreement was observed between EPIC domains relevant to the Functional Assessment of Cancer Therapy Prostate module (FACT-P) and the American Urological Association Symptom Index (AUA-SI), providing criterion validity without excessive overlap.

CONCLUSIONS

EPIC is a robust prostate cancer HRQOL instrument that complements prior instruments by measuring a broad spectrum of urinary, bowel, sexual, and hormonal symptoms, thereby providing a unique tool for comprehensive assessment of HRQOL issues important in contemporary prostate cancer management.

Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody responses through mechanisms that remain poorly defined. A unique memory B cell subpopulation (CD20(hi)/CD27(lo)/CD21(lo)) in human tonsillar tissues was recently defined by the expression of the inhibitory receptor Fc-receptor-like-4 (FCRL4). In this study, we describe a similar B cell subpopulation in the blood of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV-viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched on B cells with a tissuelike memory phenotype (CD20(hi)/CD27(-)/CD21(lo)) when compared with B cells with a classical memory (CD27(+)) or naive (CD27(-)/CD21(hi)) B cell phenotype. Tissuelike memory B cells expressed patterns of homing and inhibitory receptors similar to those described for antigen-specific T cell exhaustion. The tissuelike memory B cells proliferated poorly in response to B cell stimuli, which is consistent with high-level expression of multiple inhibitory receptors. Immunoglobulin diversities and replication histories were lower in tissuelike, compared with classical, memory B cells, which is consistent with premature exhaustion. Strikingly, HIV-specific responses were enriched in these exhausted tissuelike memory B cells, whereas total immunoglobulin and influenza-specific responses were enriched in classical memory B cells. These data suggest that HIV-associated premature exhaustion of B cells may contribute to poor antibody responses against HIV in infected individuals.

BACKGROUND

B-cell epitopes are the sites of molecules that are recognized by antibodies of the immune system. Knowledge of B-cell epitopes may be used in the design of vaccines and diagnostics tests. It is therefore of interest to develop improved methods for predicting B-cell epitopes. In this paper, we describe an improved method for predicting linear B-cell epitopes.

RESULTS

In order to do this, three data sets of linear B-cell epitope annotated proteins were constructed. A data set was collected from the literature, another data set was extracted from the AntiJen database and a data sets of epitopes in the proteins of HIV was collected from the Los Alamos HIV database. An unbiased validation of the methods was made by testing on data sets on which they were neither trained nor optimized on. We have measured the performance in a non-parametric way by constructing ROC-curves.

CONCLUSIONS

The best single method for predicting linear B-cell epitopes is the hidden Markov model. Combining the hidden Markov model with one of the best propensity scale methods, we obtained the BepiPred method. When tested on the validation data set this method performs significantly better than any of the other methods tested. The server and data sets are publicly available at http://www.cbs.dtu.dk/services/BepiPred.

BACKGROUND

Peroral endoscopic myotomy (POEM) was developed by our group to provide a less invasive permanent treatment for esophageal achalasia.

METHODS

POEM was performed in 17 consecutive patients with achalasia (10 men, 7 women; mean age 41.4 years). A long submucosal tunnel was created (mean length 12.4 cm), followed by endoscopic myotomy of circular muscle bundles of a mean total length of 8.1 cm (6.1 cm in distal esophagus and 2.0 cm in cardia). Smooth passage of an endoscope through the gastroesophageal junction was confirmed at the end of the procedure.

RESULTS

In all cases POEM significantly reduced the dysphagia symptom score (from mean 10 to 1.3; P = 0.0003) and the resting lower esophageal sphincter (LES) pressure (from mean 52.4 mmHg to 19.9 mmHg; P = 0.0001). No serious complications related to POEM were encountered. During follow-up (mean 5 months), additional treatment or medication was necessary in only one patient (case 17) who developed reflux esophagitis (Los Angeles classification B); this was well controlled with regular intake of protein pump inhibitors (PPIs).

CONCLUSIONS

The short-term outcome of POEM for achalasia was excellent; further studies on long-term efficacy and on comparison of POEM with other interventional therapies are awaited.

Microglia are crucial for immune responses in the brain. Although their origin from the yolk sac has been recognized for some time, their precise precursors and the transcription program that is used are not known. We found that mouse microglia were derived from primitive c-kit(+) erythromyeloid precursors that were detected in the yolk sac as early as 8 d post conception. These precursors developed into CD45(+) c-kit(lo) CX(3)CR1(-) immature (A1) cells and matured into CD45(+) c-kit(-) CX(3)CR1(+) (A2) cells, as evidenced by the downregulation of CD31 and concomitant upregulation of F4/80 and macrophage colony stimulating factor receptor (MCSF-R). Proliferating A2 cells became microglia and invaded the developing brain using specific matrix metalloproteinases. Notably, microgliogenesis was not only dependent on the transcription factor Pu.1 (also known as Sfpi), but also required Irf8, which was vital for the development of the A2 population, whereas Myb, Id2, Batf3 and Klf4 were not required. Our data provide cellular and molecular insights into the origin and development of microglia.

Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease. Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes. Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state. This new understanding also prompts reconsideration of the function of circulating monocytes. Classical Ly6c(hi) monocytes patrol the extravascular space in resting organs, and Ly6c(lo) nonclassical monocytes patrol the vasculature. Inflammation triggers monocytes to differentiate into macrophages, but whether resident and newly recruited macrophages possess similar functions during inflammation is unclear. Here, we define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation.

OBJECTIVE

We measured the extent to which a set of psychosocial health problems have an additive effect on increasing HIV risk among men who have sex with men (MSM).

METHODS

We conducted a cross-sectional household probability telephone sample of MSM in Chicago, Los Angeles, New York, and San Francisco.

RESULTS

Psychosocial health problems are highly intercorrelated among urban MSM. Greater numbers of health problems are significantly and positively associated with high-risk sexual behavior and HIV infection.

CONCLUSIONS

AIDS prevention among MSM has overwhelmingly focused on sexual risk alone. Other health problems among MSM not only are important in their own right, but also may interact to increase HIV risk. HIV prevention might become more effective by addressing the broader health concerns of MSM while also focusing on sexual risks.

In an unblinded trial of intravenous streptokinase (SK) in early acute myocardial infarction, 11 806 patients in one hundred and seventy-six coronary care units were enrolled over 17 months. Patients admitted within 12 h after the onset of symptoms and with no contraindications to SK were randomised to receive SK in addition to usual treatment and complete data were obtained in 11 712. At 21 days overall hospital mortality was 10.7% in SK recipients versus 13% in controls, an 18% reduction (p = 0.0002, relative risk 0.81). The extent of the beneficial effect appears to be a function of time from onset of pain to SK infusion (relative risks 0.74, 0.80, 0.87, and 1.19 for the 0-3, 3-6, 6-9, and 9-12 h subgroups). SK seems to be a safe drug for routine administration in acute myocardial infarction.

Much of the visual cortex is organized into visual field maps: nearby neurons have receptive fields at nearby locations in the image. Mammalian species generally have multiple visual field maps with each species having similar, but not identical, maps. The introduction of functional magnetic resonance imaging made it possible to identify visual field maps in human cortex, including several near (1) medial occipital (V1,V2,V3), (2) lateral occipital (LO-1,LO-2, hMT+), (3) ventral occipital (hV4, VO-1, VO-2), (4) dorsal occipital (V3A, V3B), and (5) posterior parietal cortex (IPS-0 to IPS-4). Evidence is accumulating for additional maps, including some in the frontal lobe. Cortical maps are arranged into clusters in which several maps have parallel eccentricity representations, while the angular representations within a cluster alternate in visual field sign. Visual field maps have been linked to functional and perceptual properties of the visual system at various spatial scales, ranging from the level of individual maps to map clusters to dorsal-ventral streams. We survey recent measurements of human visual field maps, describe hypotheses about the function and relationships between maps, and consider methods to improve map measurements and characterize the response properties of neurons comprising these maps.

OBJECTIVE

Phenotypic and functional features of myeloid suppressor cells (MSC), which are known to serve as critical regulators of antitumor T-cell responses in tumor-bearing mice, are still poorly defined in human cancers. Here, we analyzed myeloid subsets with suppressive activity present in peripheral blood of metastatic melanoma patients and evaluated their modulation by a granulocyte-macrophage colony-stimulating factor (GM-CSF)--based antitumor vaccine.

METHODS

Stage IV metastatic melanoma patients (n = 16) vaccinated with autologous tumor-derived heat shock protein peptide complex gp96 (HSPPC-96) and low-dose GM-CSF provided pre- and post-treatment whole blood specimens. Peripheral-blood mononuclear cells (PBMCs) were analyzed by flow cytometry, separated into cellular subsets, and used for in vitro proliferation assays. PBMCs from stage-matched metastatic melanoma patients (n = 12) treated with non-GM-CSF-based vaccines (ie, HSPPC-96 alone or interferon alfa/melanoma-derived peptides) or sex- and age-matched healthy donors (n = 16) were also analyzed for comparison.

RESULTS

The lack of or low HLA-DR expression was found to identify a CD14+ cell subset highly suppressive of lymphocyte functions. CD14+HLA-DR-/lo cells were significantly expanded in all metastatic melanoma patients, whereas they were undetectable in healthy donors. Suppressive activity was mediated by transforming growth factor beta (TGF-beta), whereas no involvement of the arginase and inducible nitric oxide synthase pathways could be detected. CD14+HLA-DR-/lo cells, as well as spontaneous ex vivo release and plasma levels of TGF-beta, were augmented after administration of the HSPPC-96/GM-CSF vaccine. No enhancement of the CD14+-mediated suppressive activity was found in patients receiving non-GM-CSF-based vaccines.

CONCLUSIONS

CD14+HLA-DR-/lo cells exerting TGF-beta-mediated immune suppression represent a new subset of MSC potentially expandable by the administration of GM-CSF-based vaccines in metastatic melanoma patients.

Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MOs), Gr-1(lo) MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin(+) niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169(+) MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin(+) niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly.

Clonogenic multipotent mouse hematopoietic stem cells (HSCs) and progenitor cells are contained within the c-kit(+) (K) lineage(-/lo) (L) Sca-1(+) (S) population of hematopoietic cells; long-term (LT) and short-term (ST) HSCs are Thy-1.1(lo). c-kit is a member of the receptor tyrosine kinase family, a class of receptors that are important in the proliferation and differentiation of hematopoietic cells. To establish whether the Flk-2/Flt3 receptor tyrosine kinase was expressed on the most primitive LT-HSCs, we sorted highly purified multipotent stem and progenitor cells on the basis of Flk-2 surface expression and used them in competitive reconstitution assays. Low numbers of Flk-2(-) HSCs gave rise to long-term multilineage reconstitution in the majority of recipients, whereas the transfer of Flk-2(+) multipotent cells resulted in mostly short-term multilineage reconstitution. The KLS subset of adult mouse bone marrow was analyzed for Flk-2 and Thy-1.1 expression. Three phenotypically and functionally distinct populations were isolated: Thy(lo) Flk-2(-) (LT-HSCs), Thy(lo) Flk-2(+) (ST-HSCs), and Thy(-) Flk-2(+) multipotent progenitors. The loss of Thy-1.1 and gain of Flk-2 expression marks the loss of self-renewal in HSC maturation. The addition of Flk-2 antibody to the lineage mix allows direct isolation of LT-HSC from adult bone marrow as c-kit(+) lin(-) Sca-1(+) Flk-2(-) from many strains of mice. Fetal liver HSCs are contained within Flk-2(-) and Flk-2(+) KTLS cells.

Autoimmune diseases often result from an imbalance between regulatory T (Treg) cells and interleukin-17 (IL-17)-producing T helper (TH17) cells; the origin of the latter cells remains largely unknown. Foxp3 is indispensable for the suppressive function of Treg cells, but the stability of Foxp3 has been under debate. Here we show that TH17 cells originating from Foxp3(+) T cells have a key role in the pathogenesis of autoimmune arthritis. Under arthritic conditions, CD25(lo)Foxp3(+)CD4(+) T cells lose Foxp3 expression (herein called exFoxp3 cells) and undergo transdifferentiation into TH17 cells. Fate mapping analysis showed that IL-17-expressing exFoxp3 T (exFoxp3 TH17) cells accumulated in inflamed joints. The conversion of Foxp3(+)CD4(+) T cells to TH17 cells was mediated by synovial fibroblast-derived IL-6. These exFoxp3 TH17 cells were more potent osteoclastogenic T cells than were naive CD4(+) T cell-derived TH17 cells. Notably, exFoxp3 TH17 cells were characterized by the expression of Sox4, chemokine (C-C motif) receptor 6 (CCR6), chemokine (C-C motif) ligand 20 (CCL20), IL-23 receptor (IL-23R) and receptor activator of NF-κB ligand (RANKL, also called TNFSF11). Adoptive transfer of autoreactive, antigen-experienced CD25(lo)Foxp3(+)CD4(+) T cells into mice followed by secondary immunization with collagen accelerated the onset and increased the severity of arthritis and was associated with the loss of Foxp3 expression in the majority of transferred T cells. We observed IL-17(+)Foxp3(+) T cells in the synovium of subjects with active rheumatoid arthritis (RA), which suggests that plastic Foxp3(+) T cells contribute to the pathogenesis of RA. These findings establish the pathological importance of Foxp3 instability in the generation of pathogenic TH17 cells in autoimmunity.

The Thy-1.1loSca-1hiLin-/lo population, representing 0.05% of C57BL/Ka-Thy-1.1 bone marrow, is highly enriched for hematopoietic stem cells and includes all multipotent progenitors in this mouse strain; however, the functional reconstituting activity of this fraction is heterogeneous. Only around 25% of clonal reconstitutions by cells from this population are long term; remaining clones yield transient multilineage reconstitutions. By fractionating based on lineage marker expression, the Thy-1.1loSca-1hiLin-/lo population has been resolved into three subpopulations: Lin-Mac-1-CD4-; Lin-Mac-1loCD4-; and Mac-1loCD4lo. Of these, only the Lin-Mac-1-CD4- population is highly enriched for long-term reconstituting hematopoietic stem cells. A comparison of transient and long-term multipotent progenitors indicates that long-term progenitors have less CFU-S activity, are equally radioprotective, and are less frequently in cell cycle. The ability to predict the longevity of reconstitution based on lineage marker expression indicates that reconstitution potential is deterministic, not stochastic.

Aberrant activation of Notch receptors has been shown to cause mammary tumors in mice. We therefore used in situ hybridization to analyze expression of Notch ligands and receptors in human breast cancer. High levels of JAG1 and NOTCH1 were noted in a subset of tumors with poor prognosis pathologic features (P < 0.05). We therefore used tissue microarrays to analyze the expression of these genes in a collection of breast cancers from patients representing a wide spectrum of clinical stages, and from whom associated follow-up survival data was available (n = 184). Patients with tumors expressing high levels of JAG1 or NOTCH1 had a significantly poorer overall survival compared with patients expressing low levels of these genes [5-year survival rate of 42% versus 65% and median survival of 50 versus 83 months, respectively, for JAG1(Hi vs. Lo) (P = 0.01); 49% versus 64% and 53 versus 91 months, respectively, for NOTCH1(Hi vs. Lo) (P = 0.02)]. Moreover, a synergistic effect of high-level JAG1 and high-level NOTCH1 coexpression on overall survival was observed (5-year survival rate of 32% and median survival of 40 months; P = 0.003). These data (a) identify novel prognostic markers for breast cancer, (b) suggest a mechanism whereby Notch is activated in aggressive breast tumors, and (c) may identify a signaling pathway activated in poor prognosis breast cancer which can be therapeutically targeted.

BACKGROUND

Intensive care unit (ICU) physician staffing varies widely, and its association with patient outcomes remains unclear.

OBJECTIVE

To evaluate the association between ICU physician staffing and patient outcomes.

METHODS

We searched MEDLINE (January 1, 1965, through September 30, 2001) for the following medical subject heading (MeSH) terms: intensive care units, ICU, health resources/utilization, hospitalization, medical staff, hospital organization and administration, personnel staffing and scheduling, length of stay, and LOS. We also used the following text words: staffing, intensivist, critical, care, and specialist. To identify observational studies, we added the MeSH terms case-control study and retrospective study. Although we searched for non-English-language citations, we reviewed only English-language articles. We also searched EMBASE, HealthStar (Health Services, Technology, Administration, and Research), and HSRPROJ (Health Services Research Projects in Progress) via Internet Grateful Med and The Cochrane Library and hand searched abstract proceedings from intensive care national scientific meetings (January 1, 1994, through December 31, 2001).

METHODS

We selected randomized and observational controlled trials of critically ill adults or children. Studies examined ICU attending physician staffing strategies and the outcomes of hospital and ICU mortality and length of stay (LOS). Studies were selected and critiqued by 2 reviewers. We reviewed 2590 abstracts and identified 26 relevant observational studies (of which 1 included 2 comparisons), resulting in 27 comparisons of alternative staffing strategies. Twenty studies focused on a single ICU.

RESULTS

We grouped ICU physician staffing into low-intensity (no intensivist or elective intensivist consultation) or high-intensity (mandatory intensivist consultation or closed ICU [all care directed by intensivist]) groups. High-intensity staffing was associated with lower hospital mortality in 16 of 17 studies (94%) and with a pooled estimate of the relative risk for hospital mortality of 0.71 (95% confidence interval [CI], 0.62-0.82). High-intensity staffing was associated with a lower ICU mortality in 14 of 15 studies (93%) and with a pooled estimate of the relative risk for ICU mortality of 0.61 (95% CI, 0.50-0.75). High-intensity staffing reduced hospital LOS in 10 of 13 studies and reduced ICU LOS in 14 of 18 studies without case-mix adjustment. High-intensity staffing was associated with reduced hospital LOS in 2 of 4 studies and ICU LOS in both studies that adjusted for case mix. No study found increased LOS with high-intensity staffing after case-mix adjustment.

CONCLUSIONS

High-intensity vs low-intensity ICU physician staffing is associated with reduced hospital and ICU mortality and hospital and ICU LOS.

OBJECTIVE

Experience with pancreatic resection for the last 10 years has resulted in new trends in patient characteristics and, for pancreaticoduodenectomy (PD), a decrease in the length of stay (LOS). This decrease is due in part to the implementation of case management and clinical pathways.

METHODS

Retrospective case series of patients undergoing pancreatic resection.

METHODS

A university-affiliated, tertiary care referral center.

METHODS

The study comprised 733 consecutive patients undergoing pancreatic resection for benign or malignant disease at the Massachusetts General Hospital in Boston from April 1990 to March 2000.

METHODS

Of the 733 pancreatic resections, 489 were PD; 190, distal pancreatectomy; 40, total pancreatectomy; and 14, middle-segment pancreatectomy.

METHODS

Length of stay; occurrence of delayed gastric emptying, pancreatic fistula, reoperation, readmission, or other complications; mortality; and comparison of patients in 3 periods according to the implementation of case management (July 1995) and clinical pathways (September 1998).

RESULTS

For PD, patients in group 1 (April 1990 to June 1995) were significantly younger (mean +/- SD, 57 +/- 15 years) than those in group 2 (July 1995 to August 1998; mean +/- SD, 62 +/- 13 years) and group 3 (September 1998 to October 2000; mean +/- SD, 65 +/- 13 years)(P <.01). Over time, the proportion of PD for cystic tumors increased from 9.9% to 20% (P =.01), and the proportion of PD for chronic pancreatitis decreased from 23% to 10% (P <.01). Use of pylorus-preserving PD decreased from 45% to 0% (P <.001). Delayed gastric emptying decreased from 17% to 6.1% (P <.01). Pancreatic fistula, reoperation, and mortality were unchanged. Length of stay for PD decreased from 16.1 +/- 0.6 to 9.5 +/- 0.4 days (mean +/- SE) (P <.001). Multivariate analysis showed that period, case volume, pylorus-preserving PD, and presence of complications are all independent predictors of LOS (P <.05 for all). For distal pancreatectomy, patients in groups 2 and 3 were older than those in group 1 (mean +/- SD, 57 +/-14 vs 52 +/- 17 years) (P <.05). Resections for cystic tumors increased from 26% to 52% (P <.05), and resections for chronic pancreatitis decreased from 32% to 14% (P =.06). Median LOS decreased from 9 days to 6. For total pancreatectomy, resections for cystic tumors increased from 18% to 43%. Median LOS decreased from 14.5 days to 11. For all resections, case volume increased from 4 resections per month in 1990 to 5.8 in 1995 and 12 in 2000 (r = 0.83; P <.001).

CONCLUSIONS

Older patients are increasingly being selected for pancreatic resection. This reflects an increasing frequency of operations performed for cystic tumors and fewer for chronic pancreatitis. With the exception of delayed gastric emptying, complications and mortality have remained the same or decreased slightly during the past 10 years. However, there has been a significant decrease in LOS; this is the result of implementation of case management and clinical pathways, increasing case volume, decreasing incidence of delayed gastric emptying, and decreasing use of pylorus-preserving PD.

BACKGROUND

Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction.

RESULTS

In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths.

CONCLUSIONS

The early effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.

The invariant properties of human cortical neurons cannot be studied directly by fMRI due to its limited spatial resolution. Here, we circumvented this limitation by using fMR adaptation, namely, reduction of the fMR signal due to repeated presentation of identical images. Object-selective regions (lateral occipital complex [LOC]) showed a monotonic signal decrease as repetition frequency increased. The invariant properties of fMR adaptation were studied by presenting the same object in different viewing conditions. LOC exhibited stronger fMR adaptation to changes in size and position (more invariance) compared to illumination and viewpoint. The effect revealed two putative subdivisions within LOC: caudal-dorsal (LO), which exhibited substantial recovery from adaptation under all transformations, and posterior fusiform (PF/LOa), which displayed stronger adaptation. This study demonstrates the utility of fMR adaptation for revealing functional characteristics of neurons in fMRI studies.