Exposure to human blood inactivates swine endothelial ecto-5'-nucleotidase.

Ecto-5'-nucleotidase (E5'N) is an extracellular enzyme forming anti-inflammatory and immunosuppressive adenosine. We evaluated whether confrontation of pig heart and endothelial cells with human blood changes the activity of E5'N. Pig hearts were perfused ex vivo with fresh human blood for 4 h. Pig aortic endothelial cells (PAEC) were incubated in vitro with human plasma for 3 h. Ex vivo perfusion of pig heart with fresh human blood resulted in a decrease in E5'N activity to 62% and 61% of initial in wild-type and transgenic pig hearts, respectively. PAEC activity of E5'N decreased to 71% and 50% of initial after 3 h exposure to heat-inactivated and active complement human plasma, respectively, while it remained constant in controls. Pig heart activity of E5'N decreased following exposure to human blood, which may affect adenosine production and exacerbate hyperacute and vascular rejection.

Valve interstitial cells induce donor-specific T-cell anergy.

OBJECTIVES: Valve allografts produce an immune response, which can influence their performance. The exact role of the interaction between recipient T cells and the different cellular components of the donor valve in stimulating an immune response is not known. Therefore the T-cell response to valve endothelial and interstitial cells was investigated in vitro. METHODS: Valve endothelial and interstitial cells were characterized for cell-surface molecules before and after interferon gamma treatment by means of a panel of specific monoclonal antibodies and flow cytometry. The proliferative response of highly purified T lymphocytes was used to assess the immunogenicity of cultured valve endothelial and interstitial cells. This was further investigated by using a 2-step tolerance-induction protocol. RESULTS: Valve endothelial and interstitial cells express similar levels of human leukocyte antigens and adhesion and costimulatory molecules, which are either induced or upregulated after interferon gamma treatment. T-cell responses to endothelial cells were detected after interferon gamma treatment, but responses to interferon gamma-treated interstitial cells were not detected. This lack of response resulted in the induction of T-cell anergy, which was reversed by the presence of the costimulatory molecule B7-1. CONCLUSIONS: Although valve endothelial and interstitial cells express a similar range of cell-surface molecules, it is only the endothelial cells that are immunogenic. In addition, we have shown that these 2 cell types interact in a donor-specific manner to orchestrate the immune response and therefore may have clinical relevance in the allogeneic response of the heart valve recipients.

A 36-year history of fatal road rage in Marion County, Oregon: 1963-1998.

This paper documents the 36-year history, with five examples, of fatal road rage in Marion County, Oregon. Relevant details (all that were available) from each case are presented. Alcohol intoxication was present in four of our five cases. We include two deaths by gunshot at close range, two deaths as a result of a motor vehicle traffic accident, and one natural death. All subjects were males. Three were Caucasian and two were Hispanic. The three subjects in Cases 1, 2 and 3 were complete strangers to the occupants of the other involved vehicles. The subjects in Cases 4 and 5 (along with the occupants of their own vehicles) were acquaintances of the occupants of the involved vehicle. There appears to be no previous forensic, medical or psychiatric literature on road rage as such. We present an initial psychiatric evaluation of the perpetrators of this type of fatal assault. There are no specific statutes in Oregon, at the state or county levels, regarding road rage. However, the city of Gresham, Oregon, recently enacted an ordinance regarding road rage. We stress the need for further study of this phenomenon, especially through the use of the psychological-psychiatric autopsy.

Human T cell responses to human and porcine endothelial cells are highly sensitive to cyclosporin A and FK506 in vitro.

BACKGROUND: Human T cells proliferate in response to both human umbilical vein endothelial cells (HUVEC) and porcine aortic endothelial cells (PAEC) via the second signals LFA-3/CD2 and B7-2 (CD86), respectively. Previous studies have shown that stimulation of T cells via CD28 or phorbol myristate acetate (PMA) activation is highly resistant to inhibition by cyclosporine A (CsA) and tacrolimus (FK506), as is the response of T cells to phytohemmaglutinin in the presence of endothelial cells. We have investigated the inhibitory effects of CsA and FK506 on the direct response of human CD4+ T cells to HUVEC and PAEC and the effect of adding B7-1 transfectants. METHODS: T cell proliferation, interleukin-2 release bioassays and a multiple cytokine bioassay employing the TF-1 cell line were used as indicators of T cell responses to HUVEC and PAEC either in the presence or absence of CsA and FK506. In some experiments, B7-1 transfectants were also added. RESULTS: Proliferative responses and interleukin-2 release were highly sensitive to CsA, the ID50 being significantly less for HUVEC (6.5 ng/ml) than PAEC (15 ng/ml). The ID50 of CsA for the mixed lymphocyte response (MLR) was similar to PAEC (18.6 ng/ml), all these values being significantly less than the T cell activation by phytohemmaglutinin (PHA) (227 ng/ml). Addition of B7-1 transfectants significantly increased interleukin-2 production by T cells/HUVEC and resistance to CsA was greatly increased to an ID50 of > 1000 ng/ml. In contrast, addition of B7-1 transfectants to T cells/PAEC had no effect either on T cell proliferation, IL-2 production, or CsA resistance. Similar results were obtained with FK506. Using the TF-1 cell line, it was determined that cytokines other than IL-2 are released during CD4+ T cell/EC interactions, with similar sensitivity to CsA and FK506. CONCLUSIONS: It is concluded that both allogeneic and xenogeneic T cell/endothelial responses should be inhibited by therapeutic levels of CsA in vivo, assuming the absence of trans-stimulation by B7 molecules.

Native low density lipoprotein-induced calcium transients trigger VCAM-1 and E-selectin expression in cultured human vascular endothelial cells.

Low density lipoprotein (LDL) interactions with the endothelium are thought to play a major role in the development of atherosclerosis. The mechanism(s) involved are not fully understood, although several lines of evidence support the idea that oxidation of LDL increases its atherogenicity. In this study we report for the first time that native LDL (n-LDL) binding to the LDL receptor (100-700 mug/ml) triggers a rise in intracellular calcium which acts as a second messenger to induce vascular cell adhesion molecule-1 (VCAM-1) expression in human coronary artery (HCAEC) and pig aortic endothelial cells (PAEC) and VCAM-1 and E-selectin expression in human aortic (HAEC) endothelial cells. Preincubation of HCAEC with a monoclonal antibody (IgGC7) to the classical LDL receptor or pretreatment with pertussis toxin blocked the n-LDL-induced calcium transients. Preincubation of each of the endothelial cell lines with the calcium chelator 1,-2-bis(o-aminophenoxy)ethane-N,N,N', N'-tetraacetic acetomethyl ester (BAPTA/AM) prevented the expression of VCAM-1 and E-selectin. The increase in VCAM-1 by n-LDL results in increased monocyte binding to HCAEC which can be attenuated by inhibiting the intracellular calcium rise or by blocking the VCAM-1 binding sites. These studies in human and pig endothelial cells link calcium signaling conferred by n-LDL to mechanisms controlling the expression of endothelial cell adhesion molecules involved in atherogenesis.

Homicide or suicide: the killing of suicidal persons by law enforcement officers.

This paper presents 15 deaths of suicidal persons in Oregon and Florida who, by their behavior, sufficiently provoked law enforcement officers into killing them. Four deaths were certified as suicide, one as undetermined and ten as homicide. All of the deaths are individually described in detail and their case characteristics are presented in a table. The method of study is a descriptive analysis of the case characteristics, including 21 variables which are determined to be relevant to the classification of death. The variables were grouped into six categories: (a) personal information; (b) criminal behavior during the fatal incident; (c) dangerous behavior during the fatal incident; (d) toxicological data; (e) mental illness information; and (f) certification data. From the analysis, reasons for the opinions on manner of death classification are presented. All incidents were perceived as life-threatening to law officers, family members, or hostages. All victims were male except one, and all were Caucasian except two. All victims resisted arrest and verbally threatened homicide during the fatal incident. Two-thirds of the victims took hostages. All victims possessed an apparent handgun or other weapon (knife, iron bar). All victims posed their weapon and threatened others during the incident, 60% of victims actually used the weapon with apparent intent to inflict damage to others. 40% of victims were intoxicated with alcohol but other drug-involvement was uncommon. Seven of 15 had previous suicide attempts, 40% had medically documented psychiatric diagnoses and 60% had reasonable historical evidence of psychiatric diagnoses, most commonly depression or substance abuse. One of the co-authors presents the case for some of the deaths to be certified as suicides, whereas two present the case for all to be certified as homicide. A brief discussion of psychiatric issues is also presented concerning individuals who use others to commit suicide and who may engage in dangerous and/or criminal behavior to do so. A major conclusion is that there is lack of a unified opinion on death certification procedures for individuals who have provoked law enforcement officers to kill them. For such cases, it is recommended that professional organizations of medical examiners/coroners develop guidelines to promote consistency in death certification practices including manner of death classification and selection of death certificate wording so that "police-assisted suicide" may be appropriately reported and studied.

MHC class II expression on human heart microvascular endothelial cells: exquisite sensitivity to interferon-gamma and natural killer cells.

BACKGROUND: Immunocytochemical analysis of human organs in situ reveals differential expression of MHC class II antigens by microvascular endothelial cells (MVEC) and endothelial cells (EC) from large vessels. In view of the role of EC as initiators of allograft rejection, it is of interest to understand the regulation of MHC class II regulation by human MVEC. We have previously isolated, cultured, and characterized MVEC from the human heart, showing that although these cells were initially MHC class II positive, the antigens were lost after about 14 days in culture. These results suggest that basal expression in vivo is maintained by circulating factors. METHODS: Here we have compared the sensitivity of human heart MVEC, human umbilical vein endothelial cells (HUVEC), and adult large vessel EC (aorta, coronary artery, and pulmonary artery) to interferon (IFN)-gamma and natural killer (NK) cell-mediated induction of MHC class II antigens. MVEC and HUVEC were cultured with 1, 5, 10, 50, 100, and 500 U/ml of IFN-gamma for 4 days, the cells were washed, and flow cytometry was used to examine HLA-DR expression at days 1, 2, 4, 7, 10, 14, and 21. EC were also cultured with purified NK cells in the presence and absence of neutralizing antibodies to IFN-gamma, and MHC class II expression was analyzed. RESULTS: As little as 5 U/ml of IFN-gamma produced 98% positive cells in heart MVEC compared with 100-500 U/ml needed for the same effect in HUVEC or other large vessel EC (coronary, aorta, pulmonary). Class II expression was maintained longer by MVEC (for 17 days) compared with HUVEC (for 10 days). NK cells and supernatant from MVEC/NK cultures induced MHC class II antigens on MVEC and HUVEC in a dose-dependent fashion; the MVEC showed an enhanced sensitivity compared with the HUVEC. The NK effects were inhibited by neutralizing antibodies to IFN-gamma. The allostimulatory ability of MHC class II-positive EC was shown to be proportional to the amount of MHC class II on the cell surface. CONCLUSIONS: The results suggest that basal expression of MHC class II on human MVEC is maintained by circulating IFN-gamma and NK cells. This conclusion has implications for therapeutic interventions.

Effect of human cytokines (IFN-gamma, TNF-alpha, IL-1 beta, IL-4) on porcine endothelial cells: induction of MHC and adhesion molecules and functional significance of these changes.

Previous studies using cultured human endothelial cells have demonstrated the role of inflammatory cytokines [interferon-gamma (IFN-gamma), tumour necrosis factor-gamma (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-4] in the regulation of major histocompatibility complex (MHC) and adhesion molecule expression. These cytokines are therefore implicated in the amplification of allograft, and more recently xenograft, rejection. In view of the likely event of grafted porcine tissues being exposed to human cytokines, we have investigated the effect of IFN-gamma, TNF-alpha, IL-1 beta, IL-4 and recombinant porcine IFN-gamma (rpoIFN-gamma) on cultured porcine aortic endothelial cells (PAEC) with respect to induction/up-regulation of porcine MHC and adhesion molecules and B7 receptors. Expression was detected using monoclonal antibodies (mAb) against porcine ligands and human CTLA-4-immunoglobulin; binding was analysed by flow microfluorimetry. TNF-alpha but not the other human cytokines unregulated swine leucocyte antigens (SLA) class I, class II and B7 receptor expression and induced vascular cell adhesion molecule (VCAM) and E-selectin expression. Porcine IFN-gamma also up-regulated SLA class I and class II, the ligand for CTLA-4-immunoglobulin and VCAM expression; the magnitude and kinetics of this response differed to that produced by recombinant human TNF-alpha (rhTNF-alpha). The ability of untreated, rpoIFN-gamma- and rhTNF-alpha-treated PAEC to stimulate CD4+ T cell was compared. CD4+ T-cell proliferation and IL-2 production were significantly enhanced by rhTNF-alpha and rpoIFN-gamma, rpoIFN-gamma being more effective than rhTNF-alpha. Use of blocking antibodies and CTLA-4-immunoglobulin demonstrated that the enhanced proliferative response, but not apparently IL-2 production, was dependent on cytokine-mediated up-regulation of SLA class II and B7 receptors. In conclusion, human TNF-alpha acts as a proinflammatory cytokine on PAEC and is likely to enhance the cellular response to xenogeneic organs in vivo.

Direct recognition of SLA- and HLA-like class II antigens on porcine endothelium by human T cells results in T cell activation and release of interleukin-2.

To investigate whether human T cells can directly recognize pig xenoantigens, highly purified human CD4+ and CD8+ T cells were incubated with pig aortic endothelial cells (PAEC). The response was measured by [3H]thymidine uptake and release of bioactive interleukin-2. A detailed examination of MHC expression by cultured PAEC and tissue sections of porcine aorta and heart showed porcine endothelial cells (EC) to be constitutively positive for SLA class II and antigens that crossreact with HLA class II molecules. Low level expression of B7 receptors was detected by binding of both human and mouse CTLA-4-Ig to untreated PAEC, which was enhanced significantly by treatment with recombinant porcine interferon-gamma. Human T cells, purified by positive selection and residual DR+ cells removed by lymphocytolysis, were shown to be functionally free of monocytes. Untreated PAEC elicited strong proliferation by human CD4+ T cells: CD8+ T cells also proliferated, but more weakly. This response was inhibited by CTLA-4-Ig. Blocking studies were performed with mAbs that bind to PAEC and not human EC (MSA3, TH16B), an mAb that binds to human and porcine EC (DA6.231), and L243, which binds to human and not porcine EC. The proliferative response of CD4+ T cells to PAEC was inhibited significantly by mAbs against swine and human determinants. In contrast, the response of CD4+ T cells to human EC was inhibited only by mAbs against human determinants. Experiments that directly compared the CD4+ and CD8+ T cell responses to PAEC and the human EC line EAhy.926, both with and without prior treatment with species-specific interferon gamma, demonstrated greater proliferation and 5-10 times more interleukin-2 in response to pig EC than to human EC.

Human anti-mouse xenorecognition. Provision of noncognate interactions reveals plasticity of T cell repertoire.

DAP.3 transfectants expressing native H-2E molecules with or without human LFA-3 and ICAM-1 (intercellular adhesion molecule-1) failed to induce proliferation by human peripheral blood T cells. Introduction of sequence from the DR beta 2 domain into the H-2E molecule led to the induction of detectable proliferation, which was substantially augmented by co-expression of human LFA-3 and ICAM-1 to levels comparable to those induced by DAP.3 cells co-expressing wild-type DR alloantigens with human LFA-3/ICAM-1. In marked contrast, cells expressing native H-2A molecules together with human accessory molecules provoked strong primary proliferative responses. The results of Ab inhibition experiments confirmed that this was caused by direct xenorecognition. In limiting dilution assays the frequency of anti-H-2A, IL-2-secreting, CD4+ human T cells was only fivefold lower than that measured against a DR alloantigen expressed on the same background. No measurable frequency was recorded against H-2E-expressing cells. Evidence to suggest that this difference was a result of isotype-specific differences in the interaction with CD4 was provided using transfectants expressing DR alloantigens with either the H-2E or H-2A beta 2 domain. DR molecules with the H-2A beta 2 domain stimulated a substantially stronger response than those with the H-2E beta 2 domain. These results challenge the view that xenogeneic T cell responses between evolutionarily distant species are weak; further emphasize the influence of the interaction between the T cell co-receptor molecule CD4, with its MHC class II molecular ligand on the strength of primary xenoresponses; and suggest that MHC class II isotypes may differ substantially in their interaction with CD4.

The descriptive epidemiology of unnatural deaths in Oregon's state institutions: a 25-year (1963-1987) study. IV. The reduction of unnatural death rates during 1988-1992 in three facilities as a result of planned changes.

This paper documents the most recent five-year (1988-1992) analysis of unnatural deaths in Oregon's state mental and correctional institutions. The current findings are compared with those of the preceding five years (1983-1987) within the context of the long term trend in unnatural death rates for the previous 25 years. The unnatural death rates for the institutional clients are also compared with those for the noninstitutionalized citizens of Marion County, Oregon. There are two major findings in these 1988-1992 data: (a) There have been highly significant reductions in unnatural death rates in Oregon State Hospital and in the Forensic Psychiatric Program, which the authors believe are largely due to the implementation of planned changes to reduce the previously very high suicide rates in these two facilities; and (b) There was a dramatic reduction (to zero) of unnatural deaths at the Fairview Training Center. The authors also believe that this was attainable mostly because of large-scale improvements made at that facility, by the Department of Human Resources and the Oregon Legislature, just before and during the present study time frame. Changes in these three facilities which led to the improvement in unnatural death rates of clients are discussed.

Comparison of two methods for determining the toxicokinetics of fluazifop-butyl after intravenous dosing in rats.

1. We have described and compared the use of two blood sampling techniques to measure the kinetics of fluazifop-butyl, a selective herbicide. Following intravenous administration of radiolabelled compound, blood samples were collected from female rats either by tail vein puncture or from chronically implanted catheters inserted in tethered rats. Urine samples were also collected from tethered animals. 2. Both techniques indicate that fluazifop-butyl is rapidly eliminated from blood into urine (t(1/2)3-4.5 h) and the overall blood concentration profiles were comparable between the two methods. However, by using cannulated rats, kinetic data were obtained from individual animals, providing evidence of inter-animal variation and allowing compartmental and statistical analysis. 3. The tethered rat technique is relatively simple and reliable. Compared to tail vein bleeding, results obtained from cannulated animals are more informative, providing comprehensive data from a small number of rats. It is therefore the preferred method for our kinetic based research studies using compounds known to exhibit multicompartmental elimination kinetics.

Biological monitoring for pesticide exposure--the role of human volunteer studies.

Predictions of human pesticide metabolism which are needed for the interpretation of biological monitoring data are frequently made from animal studies. Consequently, assumptions have to be made about the relationship between absorbed dose and metabolite excretion. The results from two human volunteer studies highlight the problems associated with extrapolating from animal studies in this way. The pyrethroid insecticide cypermethrin shows markedly different metabolite patterns when administered orally or dermally in man. Following dermal dosing the ratio of trans/cis cyclopropane acids is approximately 1:1, compared to 2:1 after oral administration. The ratio of total cyclopropane acids to phenoxybenzoic acids also differs depending on the route (dermal 1:4, oral 1:0.8). A knowledge of human metabolism by these two routes enables a much more meaningful interpretation of biological monitoring measurements. The herbicide molinate forms a mercapturate conjugate as a major urinary metabolite in the rat (35%). In volunteers at low dose levels this metabolite is present at insignificant levels (< 1%) and 4-hydroxymolinate is a much more abundant metabolite (39%). This shows that extrapolation between species can be very misleading. It is concluded that the benefits of using human volunteers for metabolism studies at low doses far outweigh the minimal risks involved. As a basis for biological monitoring such studies can lead to a greatly improved risk assessment for pesticides in use.

Further validation of an in vitro method to reduce the need for in vivo studies for measuring the absorption of chemicals through rat skin.

Current requirements for the registration of agrochemicals, particularly in the U.S.A., often require the provision of dermal absorption data. In this process the rat is often used and complex in vivo studies, using large numbers of animals, are performed. We have compared the data obtained from in vivo and in vitro dermal absorption studies using eight pesticides with a range of physicochemical properties. Measurements were made of the 14C-labeled pesticides which could be washed from the skin, were associated with (on/in) skin, or absorbed through the skin following dermal applications in vivo and in vitro at various time points over a 24-hr exposure period. Good agreement was found between the amounts washed from and associated with the skin in vivo and in vitro. Over the time period 4-24 hr after application the in vitro experiments predicted the in vivo absorption within a factor of 2-3. These results show that, with a range of pesticide molecules, the in vitro method accurately predicted in vivo absorption supporting the utilization of the in vitro method for risk assessment from exposure to pesticides and other chemicals.

Pharmacokinetics of fluazifop-butyl in human volunteers. II: Dermal dosing.

1. The absorption of the herbicide fluazifop-butyl (f-b), has been determined from plasma and urine measurements in groups of six male volunteers following dermal administration of 2.5, 25 and 250 micrograms cm-2 from standardized formulations containing 0.05, 0.5 and 5.0% (w/v) fluazifop-butyl to a skin area of 800 cm2. 2. Urinary excretion rate of the principal metabolite fluazifop, following dosing with the 5% formulation, was described by a two-compartment pharmacokinetic model; the average elimination half-lives of initial and terminal phases were 18 h and approximately 70 h, respectively. For the other dose levels the elimination half-life was estimated to be 17 h; urine concentrations at later time points were too low to characterize a second compartment. 3. The estimated total fluazifop-butyl absorbed was 8.0, 3.4 and 1.6% of the applied dose for the 0.05, 0.5 and 5.0% formulations, respectively. 4. Up to 50% of the applied fluazifop-butyl was readily removed by skin washing and the majority of the remainder was transferred to clothing during the 24 h following application. 5. When six volunteers were given a daily dermal dose of the 0.5% formulation for five consecutive days, the plasma and urinary excretion kinetics of fluazifop could be accurately predicted by simple mathematical extrapolation of the kinetic data from the single exposure study at the equivalent daily dose. 6. It is concluded that fluazifop-butyl is only slowly and poorly absorbed through human skin and has a low potential to accumulate in man.

The descriptive epidemiology of unnatural deaths in Oregon's state institutions: a 25-year (1963-1987) study. II. Analysis of the incidence rate and its many variations.

We have analyzed suicide data of the Forensic Psychiatric Program of the Oregon State Hospital in terms of the various ways of expressing occurrence rates that are found in the literature. All of these rates are ultimately based upon either (a) the average daily population, computed from occupancy rates of institutional beds, or (b) a measure of the total number of individuals at risk (that is, all who were in the study population during the time frame of the study). We discuss reasons for the use of these different rates. We have also calculated the risk of suicide for each of two factors: (a) the primary psychiatric diagnosis and (b) the type of legal commitment under which these patients were admitted to the Forensic Psychiatric Program. We discovered that virtually the entire risk of suicide in this program was borne by patients whose primary diagnosis was that of chronic schizophrenia and who were committed there because of diminished criminal responsibility for a crime of which they were found guilty in a court of law.

The descriptive epidemiology of unnatural deaths in Oregon's state institutions: a 25-year (1963-1987) study. III. A 25-year overview of unnatural deaths in the mental and correctional facilities.

I document 25 consecutive years (1963-1987) of unnatural deaths within the State of Oregon's mental and correctional institutions in Marion County. This study includes 93 unnatural deaths in the Oregon State Hospital, 18 in the Forensic Psychiatric Program, 52 in the Fairview Training Center, and 45 in the Corrections Department facilities. These institutional unnatural deaths are compared with the 2,618 unnatural deaths that occurred during this same period in Marion County (exclusive of these state facilities). Death rates are shown in five 5-year blocks of time to illustrate death trends. Accidents and suicides were the predominant types of unnatural death in the Oregon State Hospital; suicides predominated in the Forensic Psychiatric Program and the corrections facilities; and accidents predominated in the Fairview Training Center. Extremely high total unnatural death rates were found in the Oregon State Hospital (approximately 520/100,000 or 8.46 times that found in Marion County) and the Forensic Psychiatric Program (approximately 561/100,000 or 9.13 times that found in Marion County). The overall accident death rate for the Fairview Training Center was approximately 119/100,000 or 2.84 times that found in Marion County. The overall total unnatural death rate for the corrections facilities was approximately 75/100,000 or 1.23 times that found in Marion County. I compare these data with those of other investigators in the United States, Canada, and western Europe. The total unnatural death rate appears to represent a valid criterion of violent death within a community.

A 28-year (1963-90) study of homicide in Marion County, Oregon.

We describe 240 consecutive homicidal deaths that occurred in Marion County, Oregon, over a 28-year period (1963-90). An epidemiological assessment of the homicides yielded the following information: More than 91% of these deaths were primary homicides. In primary homicide, 63% of the victims and 88% of the offenders were male. In secondary homicide, 76% of the victims and all of the offenders were male. A high percentage of victims (83%) and offenders (84%) in primary homicide were Caucasian, as were 100% of victims and offenders in secondary homicide. About 12% of victims and 10% of offenders in primary homicide were Hispanic. Fifty-nine percent of primary homicides were intrasexual, as compared to 87% of secondary homicides. An intraracial pattern was found in 90% of primary homicides and in 100% of secondary homicides. The most frequent means of death in both primary and secondary homicides were firearms, physical beating, and stabbing. Strangers committed 80% of secondary homicides. This was in marked contrast to the victim-offender relationship found in primary homicides, where strangers were responsible for approximately 16% of the total, acquaintances for approximately 36%, and family members for approximately 48%. The overall clearance rate (i.e., the identification and charging of a suspect for the death) was 88%.

Oral pharmacokinetics of fluazifop-butyl in human volunteers.

1. Fluazifop-butyl, the active ingredient of FUSILADE, a selective herbicide, was administered orally to three male volunteers at a dose level of 0.07 mg kg-1 body weight. Over a period of 6 d between 80 and 93% of the dose was excreted in urine as the metabolite fluazifop, the majority within the first 24 h. Peak plasma concentrations of fluazifop occurred 1-2.5 h after administration. 2. The elimination of fluazifop from plasma and urine can be described by a one-compartment pharmacokinetic model and the elimination half-life was estimated from blood and urine data to be within the range 9-37 h. Fluazifop was found to bind to serum proteins. 3. The study indicates that the amount of fluazifop-butyl absorbed in exposed persons can be assessed by measuring fluazifop concentrations in urine.