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1.
Transfusion ; 47(7): 1172-9, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17581151

ABSTRACT

BACKGROUND: The use of a donation sample archive has been in place within the Scottish National Blood Transfusion Service for almost 35 years but the advent of human immunodeficiency virus donor testing led to this archive being kept for an indefinite period. This article describes the uses made of our archive repository. STUDY DESIGN AND METHODS: Records of various potential transfusion transmission episodes were accessed and examined to assess the age of the archives investigated and the outcome of the investigations. Other uses of the archive repository were also investigated by reviewing the records of retrievals. The use of the archive to aid the interpretation of hepatitis C virus-indeterminate results was also conducted. Finally a global survey was performed to ascertain the temperature and length of storage used by various transfusion services. RESULTS: A 3-year archive would have allowed for the investigation of 45 percent of cases (including all hepatitis B virus cases), while a 10-year archive would have allowed for 90 percent of cases. Only 34 percent of cases were shown to be transfusion-transmitted. Of 16 donors with c22-indeterminate bands on recombinant immunoblot assay, 2 (12%) could have been classified as confirmed-positive on the basis of their archive samples. A considerable proportion (41%) of the most recent requests for retrieval from the archive have been associated with the need to perform new mandatory tests for tissue donations at issue. Samples older than 3 years accounted for 25 percent of all samples retrieved. The global survey showed a variety of conditions in terms of both length and temperature of storage. CONCLUSION: The use of a donation archive has been shown to be extremely useful in the investigation of potential transfusion-transmitted infections with most (66%) having no evidence of transfusion transmission. Although 90 percent of our cases could have been fully investigated with only a 10-year archive, perhaps the future retention period of hospital records should be considered when determining the length of storage of current donation archive samples.


Subject(s)
Blood Banking/methods , Blood Donors , Forms and Records Control/standards , International Cooperation , Blood Preservation , Blood Transfusion/standards , Data Collection , HIV/isolation & purification , HIV Infections/transmission , Humans , Records , Scotland , Time Factors , Transfusion Reaction
2.
Sex Abuse ; 12(2): 107-22, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10872240

ABSTRACT

Reliability, measured by Cronbach's coefficient alpha, and concurrent validity, measured by Pearson's r and polychoric correlation coefficients, were evaluated in this study. A sample of 371 sexual offenders referred to the Behavioral Medicine Institute of Atlanta for evaluation of sexual interests and behaviors by the courts were assessed using the Sexual Interest Cardsort Questionnaire (SI), a self-report measure of deviant and nondeviant sexual interest, as well as indicator variables obtained from classifications assigned by clinicians as a result of 2 hour-long, semistructured clinical interviews. Internal consistency of 75 items from the SI ranged from 0.71 to 0.96, across 15 categories of sexual interest and behavior. Additionally, the SI was shortened utilizing Cronbach's alphas to maintain a high level of internal consistency. The resulting questionnaire, the shortened SI (SIS), had 45 items and 15 categories. Cronbach's alpha ranged from 0.78 to 0.97. Utilizing Pearson's r and polychoric correlation coefficients, significant correlations were found for the 11 sexually deviant categories of the SI and indicator variables, and the 10 sexually deviant categories of the SIS and indicator variables. The SI and SIS showed a high level of reliability and concurrent validity. Clinical and research issues pertaining to the clinical assessment of male sexual offenders utilizing self-report and clinical interview data, both obtained as the result of comprehensive evaluations, are discussed.


Subject(s)
Paraphilic Disorders/diagnosis , Sexual Behavior , Surveys and Questionnaires , Adolescent , Adult , Aged , Humans , Male , Middle Aged , Psychometrics/statistics & numerical data , Reproducibility of Results , Sex Offenses
3.
J Med Chem ; 41(12): 1997-2009, 1998 Jun 04.
Article in English | MEDLINE | ID: mdl-9622541

ABSTRACT

New antipsychotic drugs are needed because current therapy is ineffective for many schizophrenics and because treatment is often accompanied by extrapyramidal symptoms and dyskinesias. This paper describes the design, synthesis, and evaluation of a series of related (aminomethyl)benzamides in assays predictive of antipsychotic activity in humans. These compounds had notable affinity for dopamine D2, serotonin 5-HT1A, and alpha1-adrenergic receptors. The arylpiperazine 1-[3-[[4-[2-(1-methylethoxy)phenyl]-1-piperazinyl]methyl]benzoyl]p ipe ridine (mazapertine, 6) was chosen because of its overall profile for evaluation in human clinical trials. The corresponding 4-arylpiperidine derivative 67 was also highly active indicating that the aniline nitrogen of 6 is not required for activity. Other particularly active structures include homopiperidine amide 14 and N-methylcyclohexylamide 31.


Subject(s)
Antipsychotic Agents , Piperazines , Piperidines , Receptors, Adrenergic, alpha-1/metabolism , Receptors, Dopamine D2/metabolism , Receptors, Serotonin/metabolism , Adrenergic Agents/chemical synthesis , Adrenergic Agents/chemistry , Adrenergic Agents/metabolism , Adrenergic Agents/pharmacology , Animals , Antipsychotic Agents/chemical synthesis , Antipsychotic Agents/chemistry , Antipsychotic Agents/metabolism , Antipsychotic Agents/pharmacology , Avoidance Learning/drug effects , Catalepsy/chemically induced , Cerebral Cortex/metabolism , Conditioning, Psychological/drug effects , Corpus Striatum/metabolism , Dopamine Agents/chemical synthesis , Dopamine Agents/chemistry , Dopamine Agents/metabolism , Dopamine Agents/pharmacology , Humans , Male , Piperazines/chemical synthesis , Piperazines/chemistry , Piperazines/metabolism , Piperazines/pharmacology , Piperidines/chemical synthesis , Piperidines/chemistry , Piperidines/metabolism , Piperidines/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Receptors, Serotonin, 5-HT1 , Serotonin Agents/chemical synthesis , Serotonin Agents/chemistry , Serotonin Agents/metabolism , Serotonin Agents/pharmacology , Structure-Activity Relationship
4.
J Med Chem ; 38(21): 4211-22, 1995 Oct 13.
Article in English | MEDLINE | ID: mdl-7473548

ABSTRACT

N1-(2-Alkoxyphenyl)piperazines additionally containing an N4-benzyl group bearing alcohol, amide, imide, or hydantoin functionalities were prepared and evaluated in the conditioned avoidance response (CAR) test predictive of clinical antipsychotic activity and in in vitro receptor-binding assays. Certain of the compounds display high affinity for the D2, 5-HT1A, and alpha 1-adrenergic receptors. Structures bearing acyclic amide, lactam, and imide functionalities display good biological activity, with a preference for the 1,3-disubstituted phenyl ring relative to the 1,4- and 1,2-congeners (7 vs 10 and 12). Every possible position of hydantoin attachment was investigated (e.g., substitution at N1, N3, and C5). The hydantoin involving attachment to N1 (24) was found to have good biological activity, whereas those hydantoins with attachment to N3 or C5 (22, 23, and 25) were inactive. Several of the smaller acetylated derivatives (30 and 33) have fair in vivo activity, which was lost in the case of the larger benzoyl analog 31. Uracil congener 34 had modest affinity for the D2 receptor (65 nM) as well as excellent in vivo activity. Benzylamino compounds display (viz. 27 and 35-38) moderate CAR activity but have surprising receptor affinity, often greater than those of comparable structures bearing a carbonyl (36 vs 7). Benzyl and benzhydryl alcohol compounds 40-48 are more active than amino structures 27 and 35-38 and also exhibit excellent in vivo activity in the CAR test with modest D2 and 5-HT1A receptor binding.


Subject(s)
Antipsychotic Agents/chemical synthesis , Piperazines/chemical synthesis , Piperidones/chemical synthesis , Animals , Antipsychotic Agents/metabolism , Antipsychotic Agents/pharmacology , Avoidance Learning/drug effects , Cell Membrane/metabolism , Cerebral Cortex/metabolism , Conditioning, Psychological/drug effects , Male , Molecular Structure , Piperazines/metabolism , Piperazines/pharmacology , Piperidones/metabolism , Piperidones/pharmacology , Rats , Rats, Wistar , Receptors, Adrenergic, alpha/metabolism , Receptors, Dopamine D2/metabolism , Receptors, Serotonin/metabolism , Structure-Activity Relationship
5.
J Med Chem ; 32(9): 2110-6, 1989 Sep.
Article in English | MEDLINE | ID: mdl-2769683

ABSTRACT

A series of monosaccharides containing a biguanide functionality was prepared and evaluated for hypoglycemic activity. Among the analogues prepared were those involving D-glucose substituted on the 6- or 1-position (19 and 24), D-galactose substituted on the 6-position (7), and D-arabinose (31). The target compounds were evaluated in a modified rat glucose-tolerance test (oral glucose load/oral drug, 100 mg/kg). Compounds 8 [6-biguanidino-1,2:3,5-bis-O-(1-methylethylidene)-6-deoxy-al pha-D- glucofuranose] and 23 [methyl 6-biguanidino-6-deoxy-2,3,4-O-tribenzyl-alpha-D-glucopyra nos ide] were the most active, exhibiting nearly equivalent hypoglycemic activity to that of phenformin (1) and metformin (2), as measured by the inhibition of the rise of blood glucose. Compound 31 was somewhat less active with 26% inhibition, as compared to 64% inhibition with 1 and 41% inhibition with 2.


Subject(s)
Biguanides/chemical synthesis , Hypoglycemic Agents/chemical synthesis , Monosaccharides/chemical synthesis , Administration, Oral , Animals , Biguanides/administration & dosage , Glucose Tolerance Test , Hypoglycemic Agents/administration & dosage , Male , Mass Spectrometry , Metformin/administration & dosage , Monosaccharides/administration & dosage , Phenformin/administration & dosage , Rats , Rats, Inbred Strains , Structure-Activity Relationship
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