Persistent and aggressive interactions with the police: potential mental health implications.

AIMS: Little is known about the potential health impact of police encounters despite a ubiquitous police presence in many disadvantaged urban environments. In this paper, we assess whether persistent or aggressive interactions with the police are associated with poor mental health outcomes in a sample of primarily low-income communities of colour in Chicago. METHODS: Between March 2015 and September 2016, we surveyed 1543 adults in ten diverse Chicago communities using a multistage probability design. The survey had over 350 questions on health and social factors, including police exposure and mental health status. We use sex-stratified logistic regression to examine associations between persistent police exposure (defined as a high number of lifetime police stops) or aggressive police exposure (defined as threat or use of police force during the respondent's most recent police stop) and the presence of post-traumatic stress disorder (PTSD) or depressive symptoms. RESULTS: Men reporting a high number of lifetime police stops have three times greater odds of current PTSD symptoms compared with men who did not report high lifetime police stops (OR 3.1, 95% CI 1.3-7.6), after adjusting for respondent age, race/ethnicity, education, history of homelessness, prior diagnosis of PTSD and neighbourhood violent crime rate. Women reporting a high number of lifetime police stops have two times greater odds of current PTSD symptoms, although the results are not statistically significant after adjustment (OR 2.0, 95% CI 0.9-4.2). Neither persistent nor aggressive police exposure is significantly associated with current depressive symptoms in our sample. CONCLUSIONS: Our findings support existing preliminary evidence of an association between high lifetime police stops and PTSD symptoms. If future research can confirm as causal, these results have considerable public health implications given the frequent interaction between police and residents in disadvantaged communities in large urban areas.

Age-associated differences in immunoglobulin G1 (IgG1) and IgG2 subclass antibodies to pneumococcal polysaccharides following vaccination.

Immunoglobulin G (IgG) subclass antibody responses to pneumococcal vaccines were determined for human subjects in four age groups. The ratios of IgG1/IgG2 antibody concentrations declined with advancing age for all five of the serotypes tested. Protein-conjugate vaccines elicited enhanced IgG antibody responses over plain polysaccharide vaccines in infants but not in adult groups.

Reliability of information on physical activity and other chronic disease risk factors among US women aged 40 years or older.

Data on chronic disease risk behaviors and related variables, including barriers to and attitudes toward physical activity, are lacking for women of some racial/ethnic groups. A test-retest study was conducted from July 1996 through June 1997 among US women (n = 199) aged 40 years or more who were white, black, American Indian/Alaska Native, or Hispanic. The sample was selected and interviews were conducted using a modified version of the methods of the Behavioral Risk Factor Surveillance System. For behavioral risk factors such as physical inactivity, smoking, and low fruit and vegetable consumption, group prevalences were generally similar between interviews 1 and 2. However, kappa values for selected physical activity variables ranged from 0.26 to 0.51 and tended to be lower for black women. Discordance was low for variables on cigarette smoking and exposure to environmental tobacco smoke (kappa = 0.64-0.92). Discordance was high (kappa = 0.33) for low consumption of fruits and vegetables. Additional variables for barriers to and access to exercise ranged widely across racial/ethnic groups and in terms of measures of agreement. These methods illustrate an efficient way to sample and assess the reliability of data collected from women of racial/ethnic minority groups.

Amino acid motifs required for isolated beta cytoplasmic domains to regulate 'in trans' beta1 integrin conformation and function in cell attachment.

The role of beta cytoplasmic domains in regulating beta1 integrin conformation and function in cell attachment is not fully understood. In this study, we tested the ability of transiently expressed beta cytoplasmic domains connected to an extracellular reporter domain to regulate 'in trans' the conformation of endogenous beta1 integrins, and compared these effects on cell attachment. We found that chimeric receptors containing either the beta1, beta3 or beta5 cytoplasmic domains inhibited the expression of the conformationally dependent 9EG7 and 12G10 epitopes on endogenous beta1 integrins. In contrast, chimeric receptors containing the beta4 or alpha5 cytoplasmic domain, or a control receptor lacking a cytoplasmic domain, had no effect. This inhibition occurred in a dose-dependent manner that required high levels of expression of the chimeric receptor. These results suggest that beta1 integrin conformation can be regulated by conserved cytosolic interactions involving beta cytoplasmic domains. This is further supported by our findings that mutations within amino acid motifs conserved among these beta cytoplasmic domains, specifically the NXXY, NPXY and TST-like motifs, reduced the ability of these chimeric receptors to regulate beta1 integrin conformation. Interestingly, the chimeric receptors inhibited cell attachment in a similar dose-dependent manner and required intact NXXY, NPXY, and TST-like motifs. The beta1 chimera also inhibited the binding of soluble fibronectin to endogenous beta1 integrins. Thus, the concomitant inhibition in the expression of conformation-dependent integrin epitopes, cell attachment and ligand binding by the chimeras, suggests that the expression of the 9EG7 and 12G10 epitopes correlates with integrin function. However, Mn2+, which is an extracellular activator of integrin function, increased 9EG7 expression to basal levels in the presence of the beta1 chimera, but did not rescue cell attachment to the same extent. Thus, although the beta1 integrin conformation recognized by mAb 9EG7 may be required for cell attachment, it is not sufficient, suggesting that the beta chimeras may be inhibiting both ligand binding and post-ligand binding events required for cell attachment. In addition, the inhibitory effects of the chimeric receptors on cell attachment were not reversed by the addition of the pharmacological agents that inhibit intracellular signals previously shown to inhibit integrin function. This finding, together with the requirement for high levels of the chimeric receptors and the fact that mutations in the same conserved motifs in heterodimeric beta1 integrins have been reported to regulate beta1 integrin conformation and function in cell attachment, suggest that beta cytoplasmic domains regulate these processes by interacting with cytosolic factors and that the regulatory effect of the chimeras may be due to their ability to titrate proteins from endogenous integrins.

Endothelial cells assemble two distinct alpha6beta4-containing vimentin-associated structures: roles for ligand binding and the beta4 cytoplasmic tail.

The alpha6beta4 laminin binding integrin functions in the assembly of type I hemidesmosomes, which are specialized cell-matrix adhesion sites found in stratified epithelial cells. Although endothelial cells do not express all the components of type I hemidesmosomes, endothelial cells can express the alpha6beta4 integrin. Because endothelial cells lose expression of alpha6beta4 in culture, we expressed recombinant alpha6beta4 in the dermal microvascular endothelial cell line, HMEC-1, to test whether endothelial cells can assemble adhesion structures containing alpha6beta4. Using immunofluorescence microscopy, we found that recombinant alpha6beta4 concentrates specifically in a novel fibrillar structure on the basal surface of endothelial cells in the absence of an exogenous laminin substrate. This localization is regulated by an intracellular mechanism, because the beta4 cytoplasmic domain is sufficient to direct a reporter domain (IL-2R) to the fibrillar structures independently of recombinant alpha6beta4. In addition, this IL-2R-beta4 chimera is sufficient to recruit the intermediate filament-associated protein HD1/plectin to these fibrillar structures and this also occurs in the absence of recombinant alpha6beta4. The fibrillar localization pattern, as well as the recruitment of HD1/plectin, requires the first and second fibronectin type III repeats and the connecting segment of the beta4 tail. In addition, when endothelial cells are provided a laminin 5-rich matrix, recombinant alpha6beta4 redistributes from the fibrillar structure to type I hemidesmosome-like structures. The beta4 cytoplasmic domain can also direct a reporter domain to these type I hemidesmosome-like structures; however, this process is dependent upon the expression of recombinant alpha6beta4 Biochemical analysis indicates that both the fibrillar and the type I hemidesmosome-like structures are associated with the vimentin intermediate filament cytoskeleton. Thus, the results illustrate that endothelial cells have the essential components necessary to assemble at least two distinct alpha6beta4-containing and vimentin-associated structures on their basal surface and that the alpha6beta4 cytoplasmic tail and the availability of specific alph6beta4 ligands regulate receptor localization to these structures.

Integrin cytoplasmic domains as connectors to the cell's signal transduction apparatus.

Integrins mediate the bidirectional transfer of signals across the plasma membrane. Integrin cytoplasmic domains provide one pathway linking integrin engagement with the cell's signal transduction apparatus. Recent structure-function studies have defined regions of beta cytoplasmic domains required for integrin function and have identified distinct roles for individual alpha cytoplasmic domains in regulating cell behavior. Newly identified proteins that bind to integrin alpha and beta cytoplasmic domains have provided new insights and new questions into the mechanisms involved in integrin signaling.

Chlorhexidine gluconate (CHG) activity against clinical isolates of vancomycin-resistant Enterococcus faecium (VREF) and the effects of moisturizing agents on CHG residue accumulation on the skin.

The effectiveness of skin decontamination by chlorhexidine gluconate (CHG) in the presence of commonly-used skin moisturizing lotions was evaluated using vancomycin-resistant Enterococcus faecium (VREF) as a representative nosocomial pathogen. Anti-bacterial efficacy was determined in vitro using pigskin preparations inoculated with five VREF clinical isolates to evaluate Calgon Vestal 2 and 4% (by weight) CHG solutions in comparison with Hibiclens Antiseptic Antimicrobial Cleaner (4% CHG solution). Control inocula were determined for each experiment from recovery of VREF harvested directly from the surface of each control piece of skin. These CHG formulations were evaluated in the presence and absence of Calgon Vestal 'Lotion Soft Skin Conditioner' (LSSC) to determine potential interactions of CHG with LSSC, and also with ¿Vaseline Intensive Care' lotion as a CHG-deactivating agent. The 2% Calgon Vestal CHG alone reduced VREF 10(2)-10(3)-fold, as well as 10(3)-10(4)-fold when LSSC was present, and was as efficacious as either 4% CHG solution when these were tested in the presence of LSSC. Four percent Calgon Vestal CHG produced reductions of 10(3)-10(5)-fold with or without LSSC present. Conversely, ¿Hibiclens' showed similar reductions in the presence of LSSC to that for the Calgon Vestal 4% CHG, but only a 10(1)-10(3)-fold reduction without LSSC. ¿Vaseline Intensive Care' lotion completely inactivated the VREF-killing effects for all of the CHG formulations tested, while LSSC and ¿Vaseline Intensive Care' lotion both showed minimal activity alone against these VREF isolates. These results indicate that the Calgon Vestal 2% CHG solution is as effective against VREF, even in the presence of LSSC, as either the 4% Calgon Vestal or Hibiclens 4% CHG formulations; the use of this lower concentration of CHG may be associated with less irritation, particularly with concomitant use of LSSC.

Fibronectin attenuates increased endothelial monolayer permeability after RGD peptide, anti-alpha 5 beta 1, or TNF-alpha exposure.

Endothelial permeability can be altered by tumor necrosis factor-alpha (TNF-alpha), a cytokine released in association with inflammation-induced tissue injury. In the subendothelial matrix, fibronectin (Fn) influences endothelial cell adhesion by the interaction of integrins with RGD and non-RGD attachment sites in Fn. We compared the effect of TNF-alpha, RGD-containing peptides (GRGDSP), or antibody to alpha 5 beta 1-integrins on the protein permeability of bovine lung endothelial monolayers as assessed by transendothelial 125I-labeled albumin clearance. We also examined the influence of purified human plasma fibronectin (hFn) on this permeability response. TNF-alpha, RGD peptides, and antibodies to alpha 5 beta 1-integrins elicited a dose- and time-dependent increase in protein permeability as well as a reorganization and/or disruption of the endogenous Fn matrix. A control RGE peptide (GRGESP) as well as immunoglobulin G purified from nonimmune rabbit serum did not increase endothelial protein permeability or disrupt the endogenous fibrillar Fn pattern in the matrix. Likewise, a LDV peptide derived from the alternatively spliced type III connecting segment (IIICS) within bovine Fn (bFn) was unable to increase permeability of the bovine endothelial monolayer. Co-incubation of purified soluble hFn (300 or 600 micrograms/ml) with either TNF-alpha, the RGD peptide, or the antibody to alpha 5 beta 1-integrins prevented the increase in endothelial permeability. This protective effect was also observed when the purified hFn (600 micrograms/ml) was added after the TNF-alpha-induced increase in endothelial permeability had taken place. Immunofluorescent analysis confirmed the incorporation of the hFn into the subendothelial matrix and its co-localization with the endogenous bFn. The similar alteration of the subendothelial matrix after exposure to RGD peptides, anti-alpha 5 beta 1-antibodies, or TNF-alpha, coupled with the ability for hFn to attenuate the permeability increase typically elicited by all three agents, suggests that disruption of cell-matrix interactions may be the mechanism by which TNF-alpha alters endothelial permeability.

Determining transition probabilities: confusion and suggestions.

Confusion regarding proper use of the terms rate and risk persists in the literature. This has implications for the proper modeling of prognosis and transition between health states in decision analysis and related techniques. The issue is complicated by the plethora of terms related to rate and risk. Although the suggestion to use the terms force and probability as substitutes for rate and risk has some appeal, the change in terminology by itself is unlikely to solve all the confusion or misuse of terms. This paper clarifies the proper definitions and estimations of rates and risks and suggests critical factors for the decision analyst to remember when using, modeling, or interpreting transition rates and risks.

When do alcoholics first discuss drinking problems?

Data from a sample of 338 alcoholics who were identified from medical record reviews and diagnosed as alcohol dependent according to DSM-III criteria by means of a structured psychiatric interview were analyzed to determine when in the course of alcohol disorder development first discussion with a health professional about their drinking problems had occurred. The data support an image of alcoholics as experiencing many drinking problems before seeking professional help and, particularly, before attending AA. These data point to early identification as a possible fruitful strategy to alleviate some of the social costs of drinking problems.

Intraoperative autologous blood salvage with cardiac surgery: an analysis of five years' experience in more than 3,000 patients.

STUDY OBJECTIVE: To analyze intraoperative autologous salvage of shed mediastinal blood and subsequent transfusion in cardiac surgery. DESIGN: Retrospective statistical analysis. SETTING: University hospital. PATIENTS: Three thousand twenty two patients undergoing cardiac surgery from 1984 to 1988. INTERVENTIONS: A review of anesthesia and transfusion records of all patients who underwent intraoperative salvage of shed blood and autologous transfusion using the Sorenson Receptal Auto Transfusion System (ATS) with saline wash prior to reinfusion in cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The salvaged blood volume ranged from 36 to 2,795 ml, with a mean of 321 +/- 222 ml (SD). Eighteen percent of patients did not receive any homologous blood products during their hospitalization. Patients who received only salvaged autologous transfusion were younger, had higher preoperative hemoglobin and hematocrit values, had a larger body surface area, and had shorter surgeries compared with patients who received only homologous blood or both autologous and homologous blood. More blood products were given to patients who received salvaged autologous blood compared with those who did not. Patients who underwent normovolemic hemodilution prior to extracorporeal circulation with subsequent reinfusion received significantly fewer blood products. Ten preoperative and four intraoperative variables significantly influenced the salvaged volume. Previous cardiac surgery was the most significant preoperative variable, and repair of ventricular septal defect produced by myocardial ischemia was the most significant intraoperative variable. CONCLUSION: Considering the average salvaged volume and its current autologous transfusion-related expense, autologous blood salvage is potentially an economic benefit. Perioperative blood conservation requires a considerable commitment from surgeons, anesthesiologists, perfusionists, and intensive care physicians to be effective.

Overexpression of sigma receptors in nonneural human tumors.

Previous data indicated that opioid receptors occur in both neural and nonneural human tumors. However, it has recently been shown that some of the putative opioid binding may be attributable to sigma sites. In this study the occurrence of sigma and opioid receptors in nonneural human tumors was assessed. The neoplasms included renal and colon carcinomas and a sarcoma. [3H]1,3-di-o-tolylguanidine was used to assay sigma receptors by homologous competition binding assays, which when analyzed provided dissociation constant and receptor density values. Opioid binding was measured with [3H]-(-)-ethylketocyclazocine, a ligand which interacts with mu, delta, and kappa subtypes. Fresh surgical specimens were obtained from 9 human neoplasms, selected for their large size, and compared with nonmalignant tissues. All 9 tumors contained sigma sites, and dissociation constant values were within the range of 27-83 nM. Occasionally, two-site fit the data better than one-site binding, suggesting the presence of multiple sigma sites. Opioid binding was not detected. Intratumoral variability was evaluated by sampling several locations on the periphery of the mass and one in the center. Each of the samples was bisected, with a portion reserved for histological examination to correlate morphological features with receptor data. Changes in sigma binding were not associated with the extent of fibrosis, viability, or necrosis. Receptor density values displayed moderate intra- and intertumoral variation (coefficients of variation, 8-39 and 27-49%, respectively). More important, sigma binding in tumors was found to be greater than or equal to 2-fold higher than that of control nonmalignant tissue.

In vitro reappraisal of the pulmonary artery catheter balloon volume-pressure relationship: comparison of four different catheters.

The most serious risk of the use of the flow-directed pulmonary artery (PA) catheter is PA rupture due to high balloon inflation pressure of the catheter. Previously reported measurements of PA catheter intra-balloon pressure and volume during balloon inflation were performed mostly in a static fashion, that is, measurements were performed after a certain volume of air had been injected into the balloon. In this study, simultaneous measurements of pressure and volume, in addition to a static study, were performed in vitro using four PA catheters (Abbott Opticath, Arrow Hands-Off, Baxter Edwards and Spectramed). The peak intra-balloon pressure was recorded immediately before loss of resistance was felt in the inflating syringe. Contrary to previously reported studies, the peak intra-balloon pressure was not the pressure exerted on the pulmonary artery wall unless the tip of the catheter was already in the peripheral pulmonary artery. The loss of resistance volume which was constant for each catheter could be used reliably as an indicator of instantaneous balloon inflation. The slower the rate of injection, the lower were the peak pressure and the injection volume at the peak pressure. The Abbott, Edwards and Spectramed catheters had similar characteristics of inflation volume and intra-balloon pressure. The Arrow catheter had higher balloon opening and plateau pressures, and a smaller balloon volume compared with the other three catheters.

Measurement of blood cyanide with a microdiffusion method and an ion-specific electrode.

The use of a cyanide ion-specific electrode in combination with the Conway microdiffusion method was modified for the measurement of cyanide concentration in human red blood cells and plasma. With our modified method, the optimal pH of cyanide isolation from red blood cells and plasma was investigated. Cyanide recovery from red blood cells increased with decreasing pH. The maximal recovery of 96.9 +/- 2.6% was obtained at a pH of less than 1. Cyanide recovery from plasma, however, peaked at a pH between 7 and 8, and further changes in pH reduced the recovery rate. The maximal recovery rate from plasma was 74.1 +/- 1.5%. In previous studies, cyanide isolations from both plasma and red blood cells were carried out at a pH of less than 1. This study shows that cyanide isolation from plasma should be performed at a pH between 7 and 8.

The effects of monitoring and feedback on compliance.

A two-group randomized experimental design was employed to assess the effects of monitoring and feedback on the compliance of 93 psychiatric outpatients treated with lithium. Compliance in both groups was measured using self-report, lithium level, appointment-keeping, and medication refill frequency. The experimental group was also monitored using a unique electronic device that records the time and day pills are removed. At the midpoint of the study, the experimental group received feedback about serum lithium levels and patterns of removing medications from the monitoring device while the control group received feedback about serum lithium levels only. The study demonstrated no sustained effect of the monitoring and feedback interventions on compliance.

Relation of silent myocardial ischemia after coronary artery bypass grafting to angiographic completeness of revascularization and long-term prognosis.

The prevalence and characteristics of silent myocardial ischemia as detected by 24-hour ambulatory electrocardiography ST-segment depression were prospectively assessed in 94 patients examined early (1 to 3 months) and 184 patients examined late (12 months) after coronary artery bypass grafting (CABG), and followed for a mean of 48 +/- 11 (range 4 to 62) months. The relation of ambulatory electrocardiographic silent ischemia to evidence of completeness of revascularization as defined by cardiac angiography performed 1 and 12 months after CABG, and to prognosis by follow-up of adverse clinical events was analyzed. Silent ischemia was detected early in 20% (19 of 94) and late in 27% (50 of 184) of patients, and showed a mean frequency of episodes ranging from 6 to 10 episodes/24 hours with a mean duration ranging from 15 to 23 minutes. The circadian distribution of episodes disclosed a significant peak of ischemic activity during the period of 6 A.M. to noon and a secondary peak between 6 P.M. and midnight (p less than 0.01 and p less than 0.001, respectively). Silent ischemia was not found by univariate analysis to be associated with graft or anastomotic site occlusions, low graft flow rates, grafted arteries with significant distal residual stenoses or ungrafted stenotic native coronary arteries. Kaplan-Meier analysis of time to cardiac event showed that silent ischemia was not predictive of an adverse clinical event in the early years after CABG. Cox regression analysis of 30 covariates only disclosed age (relative risk 1.06 [95% confidence interval, 1.01 to 2.94]) as having an effect on time to adverse clinical event.(ABSTRACT TRUNCATED AT 250 WORDS)

Natural history of potentially lethal ventricular arrhythmias in patients treated with long-term antiarrhythmic drug therapy.

To examine the natural history of long-term anti-arrhythmic therapy in patients with benign and potentially lethal ventricular premature complexes (VPCs), 28 patients with initial efficacy with moricizine (greater than 75% suppression of baseline mean VPCs/hr and greater than 90% suppression of repetitive VPCs) were prospectively followed for 1 to 56 (mean +/- standard deviation 25 +/- 17) months. Patients were examined during baseline placebo, anti-arrhythmic drug therapy and intermittent pulsed-placebo reexamination periods. The mean VPCs of all patients at baseline entry were 233 +/- 47 VPCs/hr, and after moricizine therapy 14 +/- 4 VPCs/hr. Follow-up demonstrated that antiarrhythmic efficacy decreased to 75% at 12 months and to 62% at 24 months. Loss of antiarrhythmic drug efficacy most commonly occurred as a "transient" event (10 patients [36%]), and efficacy was spontaneously reestablished without a change in antiarrhythmic therapy. In contrast, increased dose titration of moricizine was necessary to reestablish antiarrhythmic suppression efficacy in 4 patients (14%), and 4 patients (14%) lost antiarrhythmic drug responsiveness during follow-up. Spontaneous decrease in baseline VPCs resulted in discontinuation of antiarrhythmic therapy in 3 patients, and increase in baseline VPCs was associated with a loss of antiarrhythmic response in 2 patients. Late proarrhythmic effects (2 patients, 7%), delayed side effects necessitating drug withdrawal (6 patients, 21%) and medical events (4 patients, 14%) occurred during 56 months of follow-up. Individual serum moricizine levels remained in the therapeutic range throughout the study and did not correlate with changes in antiarrhythmic efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Graphical aid for determining power of clinical trials involving two groups.

Physicians need to evaluate clinical research critically, and determining the power of a study is an essential component of research evaluation. This report presents a graphical aid that permits rapid power determination for clinical trials with two groups. Power curves were developed for dichotomous outcomes by setting two tail alpha at 0.05 and varying the sample size, the control group response rate, and the clinically important difference between control and experimental groups as defined by the user. Use of the graphical aid was demonstrated to a group of 18 medical students, residents, fellows, and faculty in a 15 minute session. Evaluation of the trainees' application of the aid showed a small average bias of -0.0003 and an average variance of 0.006. Ninety percent of power estimates were within 0.05 of the true value determined by formula. This graphical aid is recommended as a rapid and accurate method for determining power in the critical appraisal of clinical research.

Therapy of ovarian carcinoma: the relationship of dose level and treatment intensity to survival.

Following primary maximal cytoreduction, 71 previously untreated patients with advanced epithelial ovarian carcinoma received at least six courses of combination chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide. The cumulative dose (CD) through three (CD3) and six (CD6) courses was calculated for each drug and for all drugs combined. The dose intensity (DI) through three (DI3) and six (DI6) courses was calculated for each drug by dividing CD3 and CD6 by the interval (in weeks) between surgery and the third and sixth course. The interval from surgery to the third or sixth course had no effect on survival. Similarly, there was no significant difference in survival between patients with high and low CD3 or CD6 for any drug or for all drugs combined. Patients with high DI6 for cisplatin, doxorubicin, and all drugs combined survived significantly longer than those with low DI6. The survival difference for patients with high and low DI6 for cyclophosphamide approached, but did not attain, statistical significance at the 0.05 level. The intensity with which combination chemotherapy is administered may have an impact upon survival in patients with ovarian carcinoma.