ABSTRACT
BACKGROUND: Stalking is often viewed as a precursor to violence, but determining which stalkers might attack is a difficult task. This study overcomes shortfalls in previous investigations by adopting a pseudo-prospective design and examining potential risk factors for different types of stalker. METHOD: Demographic, behavioural and diagnostic information was collected from stalkers referred to a community forensic mental health service (n=211). Potential risk factors for stalking violence were identified using odds ratios and chi2 tests, and entered into logistic regression models. Model utility was assessed using receiver operating characteristic curves. RESULTS: Amongst Rejected ex-intimate stalkers, violence was best predicted by previous violence, making threats and being employed (area under the curve=0.75), while for stalkers with other motives and relationships to the victim, being aged less than 30 years, substance use at the time of stalking and prior violence best predicted stalking violence (area under the curve=0.80). CONCLUSIONS: Stalkers at increased risk of violence can be accurately identified by examining motivational and relationship type in conjunction with specific relevant risk factors. Previous violence is a particularly important risk factor, as are threats amongst ex-intimate stalkers. Approach behaviours and psychosis were shown to be less useful in predicting violence.
Subject(s)
Stalking/psychology , Violence/psychology , Adolescent , Adult , Age Factors , Aged , Community Mental Health Services , Comorbidity , Cross-Sectional Studies , Delusions/epidemiology , Delusions/psychology , Female , Humans , Interview, Psychological , Male , Mental Disorders/epidemiology , Mental Disorders/psychology , Middle Aged , Motivation , Odds Ratio , Personality Assessment , Prospective Studies , Psychotic Disorders/epidemiology , Psychotic Disorders/psychology , Recurrence , Referral and Consultation/statistics & numerical data , Rejection, Psychology , Risk Factors , Stalking/epidemiology , Substance-Related Disorders/epidemiology , Substance-Related Disorders/psychology , Violence/statistics & numerical data , Young AdultABSTRACT
(E)-4-[4-(Methylthio)phenyl]-1-(2-piperidinyl)-3-buten-2-one hydrochloride (44, RMI 14 133A) was found to inhibit ADP-induced aggregation of blood platelets. It was selected from a large series of (2-piperidinyl)- and (2-pyrrolidinyl)ethanones synthesized by a modified Schopf reaction from enolate magnesium salts of beta-keto acids and 2,3,4,5-tetrahydropyridine trimer or 3,4-dihydro-2H-pyrrole trimer, respectively. Evaluation of the compounds was carried out in vitro on human blood platelets. Structure-activity relationships are discussed. 44 also inhibited platelet aggregation ex vivo in guinea pigs. Subacute toxicity evaluation in dogs and guinea pigs showed it to have an unfavorable therapeutic ratio. 1-[4'-Chloro(1,1'-biphenyl)-4-yl-a1-2-(2-piperdinyl)ethanone hydrochloride (18, RMI 12436A) was found to lower serum cholesterol levles in rats with concurrent accumulation of (3beta)-cholesta-5,7-dien-3-ol, suggesting inhibition of 7-dehydrocholesterol delta7-reductase.
Subject(s)
Piperidines/pharmacology , Platelet Aggregation/drug effects , Pyrrolidines/pharmacology , Adenosine Diphosphate/pharmacology , Animals , Blood Platelets/drug effects , Cholestadienols/blood , Cholesterol/blood , Depression, Chemical , Dogs , Ethanol/analogs & derivatives , Ethanol/chemical synthesis , Ethanol/pharmacology , Guinea Pigs , Humans , In Vitro Techniques , Male , Piperidines/chemical synthesis , Platelet Factor 3/metabolism , Pyrrolidines/chemical synthesis , Rats , Structure-Activity RelationshipABSTRACT
N-[1-(p-Phenoxyphenyl)ethyl]hexahydro-2H-azepin-2-imine hydrochloride (10) and N-[1-(2-dibenzothienyl)-ethyl]hexahydro-2H-azepin-2-imine hydrochloride (22) were found to inhibit in vitro aggregation of human blood platelets induced by ADP with minimal release of procoagulant platelet factor 3. The compounds were selected from a series of substituted alpha-methylbenzyl and tricyclic arylalkyl lactamimides that were free of hypoglycemic and diuretic effects. Compounds 10 and 22, as well as N-[1-(1-naphthyl)ethyl]hexahydro-2H-azepin-2-imine hydrochloride (I) and N-(2,2-diphenylpentyl)hexahydro-2H-azepin-2-imine hydrochloride (II), were evaluated for effects on ADP-induced platelet aggregation after repeated oral administration to guinea pigs. Compound II (RMI 12,366A) showed in vivo activity in this system 2 h after the last of four daily doses of 100 mg/kg po.
Subject(s)
Lactams/pharmacology , Platelet Aggregation/drug effects , Adenosine Diphosphate/pharmacology , Benzyl Compounds/chemical synthesis , Benzyl Compounds/pharmacology , Depression, Chemical , Humans , Imides/chemical synthesis , Imides/pharmacology , Lactams/chemical synthesis , Platelet Factor 3/metabolismABSTRACT
Since no practical animal model is available for the evaluation of compounds in vivo, we have developed an in vitro model for determining the effect of compounds on the rate of sickling of erythrocytes in whole blood taken from patients with sickle cell anaemia. RMI 6792 (a phenethanol-diamine derivative), procaine, and L-glutamine were tested in this in vitro system. RMI 6792 was tested at various concentrations in whole blood. The data indicate that RMI 6792 decreased the rate of sickling at and above 60 microgram/ml. Procaine slightly decreased sickling rate at 100 microgram/ml. L-glutamine at 555 had no inhibitory effect. RMI 6792 and procaine had no effect on the oxygen dissociation curve. RMI 6792 affected the calcium flux of the erythrocytes and the calcium concentration in the erythrocytes.
Subject(s)
Aniline Compounds/pharmacology , Antisickling Agents/pharmacology , Erythrocyte Membrane/drug effects , Erythrocytes/drug effects , Ethanolamines/pharmacology , Glutamine/pharmacology , Procaine/pharmacology , 2-Hydroxyphenethylamine/analogs & derivatives , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/physiopathology , Calcium/blood , Erythrocytes/analysis , Humans , Methods , Oxygen/bloodABSTRACT
Tilorone hydrochloride was tested in vitro for inhibition of platelet aggregation in the ADP, collagen, and epinephrine-induced platelet aggregation systems. Tilorone did not significantly inhibit the first phase of platelet aggregation induced by ADP, but was a very potent inhibitor of the second phase of platelet aggregation (release reaction) as illustrated by the epinephrine-induced system. When the compound was given to rats by stomach tube at 100 mg/kg for 2 doses, 24 h apart and blood taken 24 h after the second dose, an inhibition of collagen-induced platelet aggregation was found. This result is interpreted as inhibiting the release reaction and second phase platelet aggregation.
Subject(s)
Fluorenes/pharmacology , Platelet Aggregation/drug effects , Tilorone/pharmacology , Adenosine Diphosphate/pharmacology , Animals , Collagen/pharmacology , Depression, Chemical , Drug Interactions , Epinephrine/pharmacology , Humans , Male , RatsSubject(s)
Collagen , Platelet Adhesiveness , Aspirin/blood , Aspirin/pharmacology , Chlorpromazine/pharmacology , Dialysis , Dose-Response Relationship, Drug , Edetic Acid/pharmacology , Glutaral/pharmacology , Humans , In Vitro Techniques , Platelet Aggregation/drug effects , Time Factors , Uremia/bloodSubject(s)
Blood Coagulation/drug effects , Castration , Ethinyl Estradiol/pharmacology , Hysterectomy , Animals , Antithrombins/blood , Blood Coagulation Factors/metabolism , Body Weight/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Fibrinogen/analysis , Fibrinolysis/drug effects , Organ Size , Rats , Thromboplastin/metabolism , Uterus/anatomy & histology , Uterus/drug effects , Uterus/pathologySubject(s)
Amidines/chemical synthesis , Anti-Inflammatory Agents/chemical synthesis , Diuretics/chemical synthesis , Hypoglycemic Agents/chemical synthesis , Lactams/chemical synthesis , Platelet Adhesiveness/drug effects , Abscess/drug therapy , Amidines/pharmacology , Amidines/therapeutic use , Anaphylaxis/prevention & control , Animals , Anti-Inflammatory Agents/therapeutic use , Blood Glucose/analysis , Chlorides/urine , Diuretics/pharmacology , Dogs , Guinea Pigs , Histamine H1 Antagonists/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Lactams/pharmacology , Lactams/therapeutic use , Potassium/urine , Rats , Sodium/urineSubject(s)
Amines/pharmacology , Blood Platelets/drug effects , Adenosine Diphosphate/antagonists & inhibitors , Adenosine Diphosphate/pharmacology , Administration, Oral , Amines/administration & dosage , Animals , Blood Coagulation/drug effects , Chemical Phenomena , Chemistry , Drug Interactions , Guinea Pigs , Humans , Platelet Adhesiveness/drug effects , Structure-Activity Relationship , Time FactorsSubject(s)
Blood Platelets , Collagen , Staining and Labeling , Histological Techniques , Humans , Methods , Microscopy, Interference , Platelet AdhesivenessSubject(s)
Amides/chemical synthesis , Imides/chemical synthesis , Platelet Adhesiveness/drug effects , Adenosine Diphosphate/pharmacology , Azepines/chemical synthesis , Azepines/pharmacology , Collagen/pharmacology , Depression, Chemical , Humans , Imides/pharmacology , Lactams/chemical synthesis , Lactams/pharmacology , Naphthalenes/chemical synthesis , Naphthalenes/pharmacology , Optical Rotation , Stereoisomerism , Structure-Activity Relationship , Thromboplastin/analysisSubject(s)
Blood Coagulation/drug effects , Fluorenes/pharmacology , Piperidines/pharmacology , Platelet Adhesiveness/drug effects , Adenosine Diphosphate/antagonists & inhibitors , Adenosine Diphosphate/pharmacology , Animals , Blood Coagulation Tests , Collagen/antagonists & inhibitors , Dicumarol/antagonists & inhibitors , Epinephrine/antagonists & inhibitors , Ethanol/blood , Ethanol/pharmacology , Fluorenes/blood , Guinea Pigs , Male , Phenylbutazone/pharmacology , Piperidines/blood , Rats , Serotonin Antagonists , Thrombin/antagonists & inhibitorsABSTRACT
Free fatty acids (FFA), the uranyl ion, and the basic dye Rhodamine B form colored complexes, which are extractable into toluene or benzene. Fatty acids of different chain lengths above C(10) and different degrees of unsaturation gave constant molar yield. Complexes in toluene alone are unstable, especially in the light, but a small amount of aqueous uranyl acetate stabilizes them sufficiently for determination. At constant uranyl and Rhodamine B concentrations, a plot of optical density vs. FFA concentration yields two straight lines of different slope, i.e., a biphasic standard curve. Phospholipids interfere, and must be removed with zeolite during FFA extraction. Recovery of FFA added to rat plasma was very similar to that with titration. Assay of rat and dog plasma samples under fasting and fed conditions gave good agreement with the titration method. Values of human plasma samples tended to be higher by the colorimetric procedure; a few samples gave significant disagreement. The method compares well with previous methods in sensitivity and accuracy, and offers advantages in speed, simplicity, and possibly specificity.