BACKGROUND

Before licensure of varicella vaccine in 1995, varicella was a universal childhood disease in the United States, causing 4 million cases, 11,000 hospitalizations, and 100 deaths every year.

OBJECTIVE

To examine population-based disease surveillance data in 3 communities to document the impact of the varicella vaccination program.

METHODS

Active surveillance for varicella conducted among the populations of Antelope Valley, Calif; Travis County, Tex; and West Philadelphia, Pa; from January 1, 1995, to December 31, 2000. Reporting sites included child care centers, schools, universities, physicians, public health clinics, hospitals, emergency departments, and households.

METHODS

Trends in number and rate of varicella cases and hospitalizations; varicella vaccine coverage.

RESULTS

From 1995 through 1998, in each surveillance area, the number of verified varicella cases varied from year to year with marked springtime seasonality. In 1999, the number and rates of varicella cases and hospitalizations declined markedly. From 1995 through 2000, in Antelope Valley, Travis County, and West Philadelphia, varicella cases declined 71%, 84%, and 79%, respectively. Cases declined to the greatest extent among children aged 1 to 4 years, but cases declined in all age groups, including infants and adults. In the combined 3 surveillance areas, hospitalizations due to varicella declined from a range of 2.7 to 4.2 per 100,000 population in 1995 through 1998 to 0.6 and 1.5 per 100,000 population in 1999 and 2000, respectively (P =.15). By 2000, vaccine coverage among children aged 19 to 35 months was 82.1%, 73.6%, and 83.8% in Los Angeles County, Texas, and Philadelphia County, respectively.

CONCLUSIONS

Varicella disease has declined dramatically in surveillance areas with moderate vaccine coverage. Continued implementation of existing vaccine policies should lead to further reductions of varicella disease in these communities and throughout the United States.

We determined the Mr of neisserial lipooligosaccharides (LOS) by using discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis, minimal loading concentrations, and Salmonella isogenic rough mutant LOS as Mr standards. Salmonella LOS were resolved into three components. The migration distance of each component was linearly related to its theoretical Mr (r = 0.99). Neisserial LOS also contained multiple components whose calculated Mr ranged from 3,200 to 7,100. The relative abundance of components and their MrS varied greatly among strains. Meningococcal LOS were composed almost exclusively of two closely migrating components; gonococcal LOS were more heterogeneous. LOS from a gonococcus selected for resistance to a Pseudomonas pyocin contained only a single component that was different from and of intermediate Mr among the three components of the parent strain. A monoclonal antibody directed against the meningococcal L8 LOS epitope was used to determine whether heterogeneity of antigen expression reflected Mr heterogeneity. Single components of the L8 meningococcal LOS and of the LOS of 3 of 19 gonococcal strains bound the monoclonal antibody. Gonococcal LOS components that expressed the L8 epitope were of a similar Mr (4,800). Smaller components of these same LOS did not express the epitope.

The effect of cholesterol on the acyl chain order of three glycerophosphocholines with 14, 16, and 18 carbons per acyl chain, namely, di(14:0)PC, di(16:0)PC, and di(18:0)PC, above the gel to liquid-crystalline phase transition temperature was investigated by using 2H nuclear magnetic resonance spectroscopy. Average acyl chain lengths were calculated from the segmental order parameters (Smol) for the sn-1 and the sn-2 chains in the absence of cholesterol and at 3:1, 2:1, and 1:1 mole ratios of phospholipid-cholesterol. The three binary mixtures of cholesterol with phosphatidylcholines are in the liquid-ordered (lo) phase. For all the three phosphatidylcholine-cholesterol systems, the distance from the carbonyl groups to the terminal methyl groups is shorter than the length of the cholesterol molecule. A molecular model for the lo phase consistent with these observations has in a statistical sense a part of each cholesterol molecule in one monolayer extending into the other monolayer. This results in a packing arrangement akin to that in interdigitated systems. On the basis of the effect of cholesterol on phospholipid acyl chain orientational order, it is suggested that the liquid-disordered (ld) phase at low cholesterol concentrations corresponds to a packing mode in which the cholesterol molecule spans the entire transbilayer hydrophobic region. A molecular mechanism is proposed in which increasing the concentration of cholesterol has the effect of stretching the acyl chains of phospholipids by increasing the population of trans conformers up to a stage where the hydrophobic length is considerably longer than the cholesterol molecule. Beyond this concentration, the partially interdigitated phase forms.(ABSTRACT TRUNCATED AT 250 WORDS)

The intracellular distribution of the enzyme 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in resting and ionophore-activated human leukocytes has been determined using immuno-electronmicroscopic labeling of ultrathin frozen sections and subcellular fractionation techniques. 5-LO is a 78-kD protein that catalyzes the conversion of arachidonic acid to leukotrienes. FLAP is an 18-kD membrane bound protein that is essential for leukotriene synthesis in cells. In response to ionophore stimulation, 5-LO translocates from a soluble to a sedimentable fraction of cell homogenates. In activated leukocytes, both FLAP and 5-LO were localized in the lumen of the nuclear envelope. Neither protein could be detected in any other cell compartment or along the plasma membrane. In resting cells, the FLAP distribution was identical to that observed in activated cells. In addition, subcellular fractionation techniques showed>> 83% of immunoblot-detectable FLAP protein and approximately 64% of the FLAP ligand binding activity was found in the nuclear membrane fraction. A fractionation control demonstrated that a plasma membrane marker, detected by a monoclonal antibody PMN13F6, was not detectable in the nuclear membrane fraction. In contrast to FLAP, 5-LO in resting cells could not be visualized along the nuclear envelope. Except for weak labeling of the euchromatin region of the nucleus, 5-LO could not be readily detected in any other cellular compartment. These results demonstrate that the nuclear envelope is the intracellular site at which 5-LO and FLAP act to metabolize arachidonic acid, and that ionophore activation of neutrophils and monocytes results in the translocation of 5-LO from a nonsedimentable location to the nuclear envelope.

OBJECTIVE

We assessed whether multiple psychosocial factors are additive in their relationship to sexual risk behavior and self-reported HIV status (i.e., can be characterized as a syndemic) among young transgender women and the relationship of indicators of social marginalization to psychosocial factors.

METHODS

Participants (n = 151) were aged 15 to 24 years and lived in Chicago or Los Angeles. We collected data on psychosocial factors (low self-esteem, polysubstance use, victimization related to transgender identity, and intimate partner violence) and social marginalization indicators (history of commercial sex work, homelessness, and incarceration) through an interviewer-administered survey.

RESULTS

Syndemic factors were positively and additively related to sexual risk behavior and self-reported HIV infection. In addition, our syndemic index was significantly related to 2 indicators of social marginalization: a history of sex work and previous incarceration.

CONCLUSIONS

These findings provide evidence for a syndemic of co-occurring psychosocial and health problems in young transgender women, taking place in a context of social marginalization.

OBJECTIVE

To assess the incidence and possible causative factors of a newly recognized syndrome, the intraoperative floppy iris (IFIS).

METHODS

Clinical practices in Los Altos and San Rafael, California, USA.

METHODS

A retrospective chart review of consecutive cataract surgeries performed in a 2-surgeon practice over a 12-month period (706 eyes; 511 patients) was used to assess the percentage of cataract patients on systemic sympathetic alpha-1 antagonist medications as well as the percentage of patients who manifested the IFIS. A separate prospective study of 900 consecutive cases (741 patients) performed by another surgeon was used to determine the incidence of IFIS and the percentage of these patients who were taking alpha-1 antagonist medications.

RESULTS

Three percent (16/511) of the patients in the retrospective study, representing 3.0% (25/706) of the total eyes, were taking tamsulosin (Flomax) for benign prostatic hypertrophy. The overall prevalence of IFIS was 2.0% (10/511 patients). The syndrome was noted intraoperatively in 63.0% (10/16) of the tamsulosin patients but in none of the 11 patients on other systemic alpha-1 blockers. In the prospective study of 900 consecutive cataract surgeries, the prevalence of IFIS was 2.2% (16/741 patients). Ninety-four percent (15/16) of the IFIS patients were taking or had taken systemic tamsulosin. Twenty-six patients (36 eyes) in the 2 studies had IFIS associated with systemic tamsulosin. Sphincterotomies and mechanical pupil stretching were ineffective in maintaining adequate pupil dilation in this surgical population.

CONCLUSIONS

Intraoperative floppy iris syndrome occurred in approximately 2% of a cataract surgery population and appeared to be caused by tamsulosin, a systemic sympathetic alpha-1A antagonist medication that is the most frequently prescribed medication for benign prostatic hypertrophy.

BACKGROUND

Acute kidney injury (AKI) is a recognized complication of cardiac surgery; however, the variability in costs and outcomes reported are due, in part, to different criteria for diagnosing and classifying AKI. We determined costs, resource use and mortality rate of patients. We used the serum creatinine component of the RIFLE system to classify AKI.

METHODS

A retrospective cohort study was conducted from the electronic data repository at the University of Pittsburgh Medical Center of patients who underwent cardiac surgery and had an elevation >>or=0.5 mg/dl) of serum creatinine postoperatively. Data were compared to age- and APACHE III-matched controls. Cost, mortality and resource use of AKI patients were determined postoperatively for each of the three RIFLE classes on the basis of changes in serum creatinine.

RESULTS

Of the 3741 admissions, 258 (6.9%) had AKI and were classified as RIFLE-R 138 (3.7%), RIFLE-I 70 (1.9%) and RIFLE-F 50 (1.3%). Total and departmental level costs, length of stay (LOS) and requirement for renal replacement therapy (RRT) were higher in AKI patients compared to controls. Statistically significant differences in all costs, mortality rate and requirement for RRT were seen in the patients stratified into RIFLE-R, RIFLE-I and RIFLE-F. Even patients with the smallest change in serum creatinine, namely RIFLE-R, had a 2.2-fold greater mortality, a 1.6-fold increase in ICU LOS and 1.6-fold increase in total postoperative costs compared to controls.

CONCLUSIONS

Costs, LOS and mortality are higher in postoperative cardiac surgery patients who develop AKI using RIFLE criteria, and these values increase as AKI severity worsens.

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. This paper describes, on the basis of the currently available evidence, the consensus reached by a group of experts regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counselling should be provided emphasizing the importance of life style, especially weight reduction and exercise in overweight women, smoking and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotrophins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotrophins is associated with increased chances for multiple pregnancy and, therefore, intense monitoring of ovarian response is required. LOS alone is usually effective in <50% of women and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC, gonadotrophin paradigm) is reported to be highly effective with a cumulative singleton live birth rate of 72%. Recommended third-line treatment is in vitro fertilization. More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-, second- or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.

BACKGROUND

Clear communication is imperative if teams in any industry expect to make improvements. An estimated 85% of errors across industries result from communication failures.

OBJECTIVE

The purpose of this study was to evaluate and improve the effectiveness of communication during patient care rounds in the intensive care unit (ICU) using a daily goals form.

METHODS

We conducted a prospective cohort study in collaboration with the Volunteer Hospital Association (VHA), Institute for Healthcare Improvement (IHI), and Johns Hopkins Hospital's (JHH) 16-bed surgical oncology ICU. All patients admitted to the ICU were eligible. Main outcome variables were ICU length of stay (LOS) and percent of ICU residents and nurses who understood the goals of care for patients in the ICU. Baseline measurements were compared with measurements of understanding after implementation of a daily goals form.

RESULTS

At baseline, less than 10% of residents and nurses understood the goals of care for the day. After implementing the daily goals form, greater than 95% of nurses and residents understood the goals of care for the day. After implementation of the daily goals form, ICU LOS decreased from a mean of 2.2 days to 1.1 days.

CONCLUSIONS

Implementing the daily goals form resulted in a significant improvement in the percent of residents and nurses who understood the goals of care for the day and a reduction in ICU LOS. The use of the daily goals form has broad applicability in acute care medicine.

Large oncosomes (LO) are atypically large (1-10 µm diameter) cancer-derived extracellular vesicles (EVs), originating from the shedding of membrane blebs and associated with advanced disease. We report that 25% of the proteins, identified by a quantitative proteomics analysis, are differentially represented in large and nano-sized EVs from prostate cancer cells. Proteins enriched in large EVs included enzymes involved in glucose, glutamine and amino acid metabolism, all metabolic processes relevant to cancer. Glutamine metabolism was altered in cancer cells exposed to large EVs, an effect that was not observed upon treatment with exosomes. Large EVs exhibited discrete buoyant densities in iodixanol (OptiPrep(TM)) gradients. Fluorescent microscopy of large EVs revealed an appearance consistent with LO morphology, indicating that these structures can be categorized as LO. Among the proteins enriched in LO, cytokeratin 18 (CK18) was one of the most abundant (within the top 5th percentile) and was used to develop an assay to detect LO in the circulation and tissues of mice and patients with prostate cancer. These observations indicate that LO represent a discrete EV type that may play a distinct role in tumor progression and that may be a source of cancer-specific markers.

To learn how lipooligosaccharide (LOS) phase variations affect pathogenesis, we studied two male volunteers who were challenged intraurethrally with Neisseria gonorrhoeae that make a single LOS of 3,600 daltons and sequentially followed LOS expression by gonococci as urethritis developed. LOS variation occurred in vivo. Signs and symptoms of gonorrhea began with the appearance of variants making 4,700-dalton LOS that are immunochemically similar to glycosphingolipids of human hematopoietic cells (Mandrell, R.E., J.M. Griffiss, and B.A. Macher. 1989. J. Exp. Med. 168:107) and that have acceptors for sialic acid. A variant that appeared at the onset of leukorrhoea was shed by 34/36 men with naturally acquired gonorrhea at the time they sought medical attention; the other two shed the variant associated with dysuria. None shed the challenge variant. These data show that in vivo phase shifts to higher molecular mass LOS that mimic human cell membrane glycolipids are associated with the development of gonococcal leukorrhea.

OBJECTIVE

Since the 1970s incidence rates for esophageal and gastric cardia adenocarcinomas have risen substantially, particularly among white males in the United States. Reasons for the increase of these tumor types are not well understood. We sought to determine the role of smoking, alcohol use, and body size characteristics in the etiology of esophageal, gastric cardia, and distal gastric adenocarcinomas.

METHODS

A population-based case-control study that included Whites, African-Americans, Latinos and Asian-Americans diagnosed with incident esophageal (n = 222), gastric cardia (n = 277), and distal gastric adenocarcinomas (n = 443), and 1356 control subjects was conducted in Los Angeles County. Unconditional logistic regression was used to calculate odds ratios (ORs), as an estimate of the relative risk, and corresponding 95% confidence intervals (CIs) for the three tumor types of interest.

RESULTS

After adjustment for age, gender, race, birthplace, and education, current cigarette smoking was a significant risk factor for all tumor types; the association was strongest for esophageal adenocarcinomas (OR = 2.80, 95% CI = 1.8-4.3), intermediate for gastric cardia adenocarcinomas (OR = 2.12, 95% CI = 1.5-3.1), and weaker for distal gastric adenocarcinomas (OR= 1.50, 95% CI = 1.1-2.1). For esophageal adenocarcinomas only, cigarette smoking had a long-lasting deleterious effect, even 20 years after smoking cessation. Alcohol use was not associated with an increased risk of these tumor types. Risks of esophageal and gastric cardia adenocarcinomas also increased statistically significantly in a dose-dependent manner with increasing body mass index measured at ages 20 and 40 years and recently. The positive associations with smoking and body mass index were generally consistent when evaluated separately for Whites, non-Whites, males, and females.

CONCLUSIONS

Cigarette smoking and high body mass index are significant, independent risk factors for esophageal and gastric cardia adenocarcinomas. Studies designed to understand the mechanisms whereby smoking and high body mass influence these tumor types are needed.

OBJECTIVE

It is now established that unaccustomed eccentric exercise leads to muscle fiber damage and to delayed-onset muscle soreness (DOMS) in the days after exercise. However, a second bout of eccentric exercise, a week after the first, produces much less damage and soreness. The purpose of this study was to provide evidence from muscle mechanical properties of a proposed mechanism for this training effect in human hamstring muscles.

METHODS

The eccentric exercise involved 12 sets of 6 repetition "hamstring lowers," performed on specially designed equipment. Hamstring angle-torque curves were constructed for each of 10 subjects (8 male and 2 female) while they performed maximum voluntary knee extension and flexion movements on an isokinetic dynamometer. Testing sessions were performed over the week before eccentric exercise, immediately post exercise, and daily, up to 8 d post exercise. Subject soreness ratings and leg girth measurements were also made post exercise. Six subjects performed a second bout of eccentric exercise, 8 d after the first, and measurements were continued up to 10 d beyond that.

RESULTS

There was a significant shift in the optimum angle for torque generation (Lo), to longer muscle lengths immediately post exercise (7.7 degrees +/- 2.1 degrees, P < 0.01), indicating an increase in series compliance within some muscle fibers. Subsequent measurements showed increases in leg girth and some muscle soreness, suggesting muscle damage. The shift in Lo persisted, even after other injury parameters had returned to normal, consistent with a training effect. Subjects also showed fewer signs of muscle damage after the second exercise bout.

CONCLUSIONS

This is the first study to show a sustained shift in optimum angle of human muscle as a protective strategy against injury from eccentric exercise. Implications of this work for athletes, particularly those prone to hamstring strains are discussed.

We report physiological and anatomical characteristics of water transport across roots grown in soil of two cultivars of grapevine (Vitis vinifera) differing in response to water stress (Grenache, isohydric; Chardonnay, anisohydric). Both cultivars have similar root hydraulic conductances (Lo; normalized to root dry weight) that change diurnally. There is a positive correlation between Lo and transpiration. Under water stress, both cultivars have reduced minimum daily Lo (predawn) attributed to the development of apoplastic barriers. Water-stressed and well-watered Chardonnay had the same diurnal change in amplitude of Lo, while water-stressed Grenache showed a reduction in daily amplitude compared with well-watered plants. Hydraulic conductivity of root cortex cells (Lpcell) doubles in Chardonnay but remains unchanged in Grenache. Of the two most highly expressed plasma membrane intrinsic protein (PIP) aquaporins in roots (VvPIP1;1 and VvPIP2;2), only VvPIP2;2 functions as a water channel in Xenopus laevis oocytes. VvPIP1;1 interacts with VvPIP2;2 to induce 3-fold higher water permeability. These two aquaporins are colocated in the root from in situ hybridization and immunolocalization of VvPIP1 and VvPIP2 subfamily members. They occur in root tip, exodermis, root cortex (detected up to 30 mm), and stele. VvPIP2;2 mRNA does not change diurnally or with water stress, in contrast to VvPIP1;1, in which expression reflects the differences in Lo and Lpcell between cultivars in their responses to water stress and rewatering. VvPIP1;1 may regulate water transport across roots such that transpirational demand is matched by root water transport capacity. This occurs on a diurnal basis and in response to water stress that corresponds to the difference in drought tolerance between the cultivars.

BACKGROUND

Femoroacetabular impingement has been recently described as a common cause of hip pain and labral tears in young adults. We evaluated the early clinical results and quality of life after osteochondroplasty of the femoral head-neck junction for the treatment of femoroacetabular impingement.

METHODS

Thirty-seven hips in thirty-four patients with persistent hip pain and a mean age of 40.5 years underwent surgical dislocation of the hip and osteochondroplasty of the femoral head-neck junction for the treatment of camtype femoroacetabular impingement. All of the patients had had preoperative evidence of pathological changes in the labrum on imaging. The clinical course and the quality of life were assessed postoperatively.

RESULTS

The mean score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) increased from 61.2 points preoperatively to 81.4 points at a mean of 3.1 years postoperatively (p < 0.001), the mean University of California at Los Angeles (UCLA) activity score increased from 4.8 to 7.5 points (p < 0.001), the mean Short Form-12 (SF-12) physical component score increased from 37.3 to 45.6 points (p < 0.001), and the mean SF-12 mental component score increased from 46.4 to 51.2 points (p = 0.031). None of the hips underwent additional reconstructive surgery. There were no cases of osteonecrosis. Nine patients underwent screw removal from the greater trochanter because of persistent bursitis. Six of the thirty-four patients were dissatisfied with the outcome.

CONCLUSIONS

Cam-type femoroacetabular impingement is associated with insufficient concavity at the anterolateral head-neck junction and with pathological changes in the labrum. Osteochondroplasty of the femoral head-neck junction following surgical dislocation of the hip joint is safe and effective and can provide a significant improvement in the overall quality of life of most patients.

METHODS

Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

OBJECTIVE

To evaluate patient-reported reasons for discontinuing antimuscarinic prescription medications for overactive bladder (OAB).

METHODS

A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase-2 follow-up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow-up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre-coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo-Mendell-Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment.

RESULTS

In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo-Mendell-Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment.

CONCLUSIONS

Expectations about treatment efficacy and side-effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side-effects might enhance adherence.

The biological response to endotoxin mediated through the Toll-like receptor 4 (TLR4)-MD-2 receptor complex is directly related to lipid A structure or configuration. Endotoxin structure may also influence activation of the MyD88-dependent and -independent signaling pathways of TLR4. To address this possibility, human macrophage-like cell lines (THP-1, U937, and MM6) or murine macrophage RAW 264.7 cells were stimulated with picomolar concentrations of highly purified endotoxins. Harvested supernatants from previously stimulated cells were also used to stimulate RAW 264.7 or 23ScCr (TLR4-deficient) macrophages (i.e., indirect induction). Neisseria meningitidis lipooligosaccharide (LOS) was a potent direct inducer of the MyD88-dependent pathway molecules tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 3alpha (MIP-3alpha), and the MyD88-independent molecules beta interferon (IFN-beta), nitric oxide, and IFN-gamma-inducible protein 10 (IP-10). Escherichia coli 55:B5 and Vibrio cholerae lipopolysaccharides (LPSs) at the same pmole/ml lipid A concentrations induced comparable levels of TNF-alpha, IL-1beta, and MIP-3alpha, but significantly less IFN-beta, nitric oxide, and IP-10. In contrast, LPS from Salmonella enterica serovars Minnesota and Typhimurium induced amounts of IFN-beta, nitric oxide, and IP-10 similar to meningococcal LOS but much less TNF-alpha and MIP-3alpha in time course and dose-response experiments. No MyD88-dependent or -independent response to endotoxin was seen in TLR4-deficient cell lines (C3H/HeJ and 23ScCr) and response was restored in TLR4-MD-2-transfected human embryonic kidney 293 cells. Blocking the MyD88-dependent pathway by DNMyD88 resulted in significant reduction of TNF-alpha release but did not influence nitric oxide release. IFN-beta polyclonal antibody and IFN-alpha/beta receptor 1 antibody significantly reduced nitric oxide release. N. meningitidis endotoxin was a potent agonist of both the MyD88-dependent and -independent signaling pathways of the TLR4 receptor complex of human macrophages. E. coli 55:B5 and Vibrio cholerae LPS, at the same picomolar lipid A concentrations, selectively induced the MyD88-dependent pathway, while Salmonella LPS activated the MyD88-independent pathway.

OBJECTIVE

Reliable identification of stroke patients in the field by prehospital personnel could expedite delivery of acute stroke therapy. The Los Angeles Prehospital Stroke Screen (LAPSS) is a 1-page instrument designed to allow prehospital personnel to rapidly identify acute stroke patients in the field. We performed a prospective, in-the-field validation study of the LAPSS.

METHODS

Paramedics assigned to 3 University of California at Los Angeles-based advanced life support units were trained and certified in use of the LAPSS. Over 7 months, paramedics completed the LAPSS on noncomatose, nontrauma patients with complaints suggestive of neurological disease. LAPSS form stroke identification results were compared with emergency department and final hospital discharge diagnoses. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and likelihood ratios were calculated for LAPSS identification of ischemic stroke, currently symptomatic transient ischemic attack, and intracerebral hemorrhage.

RESULTS

Of a total of 1298 runs, 34% were for nontraumatic, noncomatose neurologically relevant complaints. Thirty-six of these patients (3% of all transports) had a final diagnosis of acute symptomatic cerebrovascular disease (21 ischemic strokes, 7 transient ischemic attacks, and 8 intracerebral hemorrhages). LAPSS forms were completed on 206 patients. Paramedic performance when completing the LAPSS demonstrated sensitivity of 91% (95% CI, 76% to 98%), specificity of 97% (95% CI, 93% to 99%), positive predictive value of 86% (95% CI, 70% to 95%), and negative predictive value of 98% (95% CI, 95% to 99%). With correction for the 4 documentation errors, positive predictive value increased to 97% (95% CI, 84% to 99%).

CONCLUSIONS

The LAPSS allows prehospital personnel to identify patients with acute cerebral ischemia and intracerebral hemorrhage with a high degree of sensitivity and specificity.

The majority of B lymphocytes in the adult mouse are generated in the bone marrow from hematopoietic stem cells (HSCs) that first appear in the aorta-gonado-mesonephros region of the fetus on embryonic day (E) 10.5-11. Comparatively less is known about B-cell development during embryogenesis. For example, which specific embryonic tissues participate in B lymphopoiesis and whether hematopoietic differentiation is skewed toward specific B-cell subsets in the embryo are unanswered questions, because the systemic circulation is initiated early during embryogenesis, resulting in an admixture of cells potentially originating from multiple sites. We demonstrate, using Ncx1(-/-) mice that lack systemic blood circulation, that the E9 yolk sac (YS) and the intra-embryonic para-aortic splanchnopleura (P-Sp) tissues independently give rise to AA4.1(+)CD19(+)B220(lo-neg) B progenitor cells that preferentially differentiate into innate type B-1 and marginal zone (MZ) B cells but not into B-2 cells upon transplantation. We have further demonstrated that these B-1 progenitor cells arise directly from YS and P-Sp hemogenic endothelium. These results document the initial wave of innate B lymphopoietic progenitor cells available for seeding the fetal liver at E11. The results of these studies expand our knowledge of hemogenic endothelial sites specifying distinct B-1 and MZ cell fates apart from B-2 cells and independent of an HSC origin during development.

This report deals with the reconstruction of the distribution of membrane thickness T from that of orthogonal length Lo, measured in random section planes. In such planes the membrane appears as a band and the linear distance from one of its boundaries perpendicular to the opposite one is the length of the orthogonal intercept. Using a membrane model, an integral equation relating the probability density functions of orthogonal intercept length f(lo) and membrane thickness g(tau) is derived. Relations between moments are derived and the analytic solution to the problem of reconstructing g(tau) from f(lo) is given. The parametric approach by which it assumed that g(tau) has some known analytic form with unknown parameters is considered, and the use of a suggested analytic form for describing the thickness distribution of the human glomerular basement membrane is discussed.

BACKGROUND

We sought to ascertain the extent to which advanced age influences the morbidity and mortality after rib fractures (fxs), to define the relationship between number of rib fractures and morbidity and mortality, and to evaluate the influence of analgesic technique on outcome.

METHODS

A retrospective cohort study involving all 277 patients>> or = 65 years old with rib fxs admitted to a Level I trauma center over 10 years was undertaken. The control group consisted of 187 randomly selected patients, 18 to 64 years old, with rib fxs admitted over the same time period. Outcomes included pulmonary complications, number of ventilator days, length of intensive care unit and hospital stay (LOS), disposition, and mortality. The specific analgesic technique used was also examined.

RESULTS

The two groups had similar mean number of rib fxs (3.6 elderly vs. 4.0 young), mean chest Abbreviated Injury Scores (3.0 vs. 3.0), and mean Injury Severity Score (20.7 vs. 21.4). However, mean number of ventilator days (4.3 vs. 3.1), intensive care unit days (6.1 vs. 4.0), and LOS (15.4 vs. 10.7 days) were longer for the elderly patients. Pneumonia occurred in 31% of elderly versus 17% of young (p < 0.01) and mortality was 22% for the elderly versus 10% for the young (p < 0.01). Mortality and pneumonia rates increased as the number of rib fxs increased with and odds ratio for death of 1.19 and for pneumonia of 1.16 per each additional rib fracture (p < 0.001). The use of epidural analgesia in the elderly (LOS >2 days) was associated with a 10% mortality versus 16% without the use of an epidural (p = 0.28). In the younger group (LOS >2 days), mortality with and without the use of an epidural was 0% and 5%, respectively.

CONCLUSIONS

Elderly patients who sustain blunt chest trauma with rib fxs have twice the mortality and thoracic morbidity of younger patients with similar injuries. For each additional rib fracture in the elderly, mortality increases by 19% and the risk of pneumonia by 27%. As the number of rib fractures increases, there is a significant increase in morbidity and mortality in both groups, but with different patterns for each group. Further prospective study is needed to determine the utility of epidural analgesia in this population.

Mycotic aneurysms are a fulminant infectious process frequently resulting in rupture and death if not properly treated. A review of the University of California, Los Angeles, medical records identified 10 patients with extrathoracic, extracranial mycotic aneurysms. In addition, a search of the English literature revealed 178 patients with 243 mycotic aneurysms. These patients were reviewed to identify the aneurysm location, etiology, bacteriology, and modality of treatment in order to determine the relationship between these factors and the outcome. The femoral artery was the most common site (38%), followed by the abdominal aorta (31%). Arterial trauma was the primary etiology in 42% of mycotic aneurysms. In 25% no clear source of infection could be identified. Staphylococcus aureus was cultured from 28% of mycotic aneurysms, and Salmonella from 15%. A trend toward the involvement of more gram-negative aerobes and anaerobes is noted. Aortic aneurysms were repaired with in situ Dacron in 61% of patients with a 32% mortality rate and 16% reinfection rate. Simple ligation of femoral artery mycotic aneurysms resulted in a 34% incidence of ischemia necessitating amputation. Methods of treatment of superior mesenteric, carotid, iliac, and peripheral arteries are also analyzed. On the basis of these data, specific surgical procedures are recommended for the treatment of mycotic aneurysms.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide. To investigate an association between antimicrobial use and MRSA, a case control study of 121 patients infected with MRSA compared with 123 patients infected with methicillin-susceptible S. aureus (MSSA) was carried out. Antimicrobial use was analysed by three different logistic regression models: all beta-lactam antibiotics, beta-lactam antibiotics grouped in classes and antimicrobial use in grammes. Patients infected with MRSA tended to have more co-morbidities, longer lengths of stay (LOS) and greater exposure to antibiotics than MSSA-infected patients. Multivariate analysis identified levofloxacin [odds ratio (OR) 8.01], macrolides (OR 4.06), previous hospitalization (OR 1.95), enteral feedings (OR 2.55), surgery (OR 2.24) and LOS before culture (OR 1.03) as independently associated with MRSA infection. All models were concordant with the exception of macrolides, which were not significant based on the number of grammes administered. There were no significant differences in the types of infection or the attributed mortality in either group. MRSA-infected patients had a significantly longer LOS before infection [18.8 +/- 18.2 compared with 8.4 +/- 6.9 (P < 0.001)] and a significantly longer post-diagnosis LOS [27.8 +/- 32.9 compared with 18.6 +/- 21 (P = 0.01)] than MSSA-infected patients.

Social determinants have been identified as a fundamental cause of health and disease in most industrialized countries. However, much less is known about which characteristics of communities may lead to disparities in health outcomes. Collective efficacy--the willingness of community members to look out for each other and intervene when trouble arises--is a social factor shown to be associated with outcomes related to obesity, including premature mortality and cardiovascular disease. The objective of this study is to determine whether neighborhood collective efficacy is associated with individual measures of body mass index (BMI) in adolescents. We use a multi-level, cross-sectional survey in Los Angeles County, involving 807 adolescents in 684 households in 65 neighborhoods in addition to a sample of 3000 adult respondents. The main outcomes measures are BMI, at risk of overweight, and overweight status. Using a two-level model, we find significant relationships between collective efficacy and all three outcomes, net of levels of neighborhood disadvantage. The associations between BMI and collective efficacy could potentially be explained by several factors, including a metabolic pathway, neighborhood differences in the physical and social environments, or a combination of these two. If group-level collective efficacy is indeed important in the regulation of individual-level net energy balance, it suggests that future interventions to control weight by addressing the social environment at the community level may be promising.