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Biomedical subjects

A Scarborough

Publications and source records attributed to A Scarborough.

8 recordsLinked to original sources
PubMed1997

Paroxetine increases heart rate variability in panic disorder.

Panic patients have decreased heart rate variability, a risk factor for sudden cardiac death, and increased rates of cardiac death and stroke. Imipramine has been found to further reduce heart rate variability in panic. This study uses power spectral analysis to compare autonomic components of heart rate variability in 16 unmedicated control subjects and 17 panic patients before and after treatment with paroxetine at 20 mg/day for 4 weeks. Patients had higher predrug reclining and standing sympathetic activity than control subjects. After drug, patients' total sympathetic activity decreased. Predrug patients failed to increase sympathetic activity on orthostasis, lacking the normal baroreflex response found in control subjects. After drug, patients normalized this sympathetic component of the baroreflex response. Before drug, patients' parasympathetic reclining and standing activity did not differ from control subjects, and patients showed the normal orthostatic parasympathetic decrease. After drug, patients' total parasympathetic activity increased, whereas the baroreflex response was preserved. Nine medicated patients had more than a 50% reduction of panic attacks. In view of paroxetine's increase of heart rate variability, potential benefits of selective serotonin reuptake inhibitors in decreasing cardiac mortality in panic disorder are discussed.

Adult↗
PubMed1996

Cyclopent[a]anthraquinones as DNA intercalating agents with covalent bond formation potential: synthesis and biological activity.

A series of mitomycin C (MMC) analogues, namely cyclopentanthraquinone derivatives, were synthesized via Diels-Alder cyclization of naphthoquinone with 1-vinylcyclopent-1-enes. These new compounds are planar structures, like MMC, and bear an aziridine ring and a methyl carbamate side chain. After bioreduction, they are anticipated to be capable of intercalating into double-stranded DNA and bind covalently. Structure-activity relationships were studied. Of these compounds, 2,3-aziridino-4-[[(methylamino)carbonyl]methyl] cyclopent[alpha]anthracene-6,11-dione (4) was shown to have inhibitory activity against several leukemic and solid tumor cell lines. Mice (BDF1) bearing Lewis lung adenocarcinoma were treated with 4 and MMC (i.p., QD x 5). At a dose of 30.0 mg/kg, compound 4 was as effective as MMC (0.8 mg/kg). Compound 4 appears to be less toxic than MMC. DNA unwinding assay indicated that 4 is able to intercalate into DNA double strands and is also a topoisomerase II inhibitor.

Animals↗
PubMed1996

Drug combinations and effect parameters of zidovudine, stavudine, and nevirapine in standardized drug-sensitive and resistant HIV type 1 strains.

Reference strains of HIV-1 from the NIH AIDS Research and Reference Reagent Program, including wild-type IIIB, G762-3, and AZT resistant with RT 215T-->Y (G910-11/AZT); 67D-->N, 70K-->R, 215T-->F, 219K-->Q (G691-2/AZT); as well as nevirapine (NEV) resistant with 181Y-->C (N119/NEV); and 103K-->N, 181Y-->C (A17/NEV), were subjected to quantitative parametric efficacy analysis using AZT, stavudine (D4T), and nevirapine (NEV) singly or in combinations in MT4 or MT2 cells. The median-effect principle and combination index (CI) method of Chou-Talalay (see Ref. 26) have been used, which take into account both the potency (Dm value or EC50) and the shape of the dose-effect curve (m value). Under standardized assay conditions, G910-11 and G691-2 strains showed 600- and 7800-fold resistance to AZT, and N119 and A17 strains showed 3600- and 1000-fold resistance to NEV at the EC50 level, respectively. AZT-resistant strains exhibited slight cross-resistance to D4T. Computerized analysis indicates that IIIB gave sigmoidal dose-effect curves (m = 2.8, 3.4, and 3.1 for AZT, D4T, and NEV, respectively) whereas drug-resistant strains showed negative sigmoidicity toward the corresponding AZT or NEV, with m = 0.27-0.73. Therefore, the degrees of drug resistance are drastically different at classic EC50 and at therapeutically more relevant EC95 levels (ranging from severalfold to several log orders). Combinations of AZT+NEV and AZT+NEV+D4T showed synergism against IIIB, G762-3 (wild type) and A17/NEV, G910-11/AZT strains. D4T+NEV and AZT+D4T showed nearly additive or moderate antagonism. Synergism or additive effect leads to a favorable dose-reduction index (DRI). The present study on RT inhibitors provides quantitative assessment of the combinations of AZT, NEV, and D4T against HIV infections involving drug-sensitive and drug-resistant HIVs.

Antiviral Agents↗
PubMed1996

Training case managers in cognitive-behaviour therapy.

Four case managers with a nursing background took part in a 26 week in-service programme aimed at developing basic skills in cognitive-behaviour therapy. The programme occupied about 5 hours each week and included directly supervised therapy with at least 4 patients having serious mental illness. Patients' symptoms improved significantly after an average of less than 12 one hour therapy sessions. After the programme, case managers began treating patients autonomously, although all recognised the need for some continuing supervision and the necessity of referring unusually complex or challenging cases to clinical psychologists or others highly skilled in the area.

Adult↗
PubMed1994

Psychiatric specialty clinics: do they weed out comorbid depression and anxiety?

The concept of comorbidity of anxiety and depression was examined as it relates to specialty clinics, a growing trend as mental health care providers attempt to compete for patients and provide efficient and specialized treatments. Twenty-nine patients from an anxiety clinic were compared with 23 patients from a mood disorders clinic in a university-based outpatient setting. Axis I diagnoses obtained by structured clinical interview for DSM-III-R were generally consistent with each specialty clinic. Incidence of diagnosable comorbid anxiety and mood disorders was not significantly different for the two clinics and within the range cited (11-78%) in several other studies drawing from various patient populations. Similarly, in comparing self-reported symptoms on three rating scales using Student's tests, authors found elevated symptoms of both depression and anxiety in both clinic populations. The importance of addressing the needs of patients with co-occurring diagnoses and symptoms within a specialty clinic is discussed as it pertains to treatment and research.

Adult↗
PubMed1988

Biochemical studies on McLeod phenotype red cells and isolation of Kx antigen.

Red cells of the McLeod blood group phenotype have weak Kell antigens, lack Kx antigen and have acanthocytic morphology. We have immunoprecipitated Kell antigens from McLeod red cells and show that they are markers on the same 93 kDa membrane protein that carries Kell antigens on normal red cells. However, as determined by Western immunoblotting, McLeod red cells have a marked deficiency of this protein. We have also studied the near-neighbour relationship of McLeod and common Kell red-cell membrane proteins by cross-linking intrinsic sulphydryl groups by oxidation, catalysed with orthophenanthroline and copper, or by cross-linking amino groups with dimethyl-3,3'-dithiobispropionimidate. Results were analysed by diagonal mapping in two-dimensional gels. No abnormalities of membrane protein inter-relationship were detected in McLeod red cells. We have isolated Kx antigen from K0 red cells by immunoprecipitation with human alloimmune anti-Kx serum, isolation of immune complexes from detergent-solubilized cell membranes with protein A-Sepharose and analysis of the eluted immune complex by SDS-PAGE under reducing conditions. Kx antigen is a marker on a red-cell membrane protein of approximately 37 kDa. Ko (Knull) red cells have about twice the amount of Kx antigen as do red cells of common Kell type. McLeod red cells have no detectable Kx antigen by serological tests or by immunoprecipitation.

Antigens, Bacterial↗
PubMedDate not supplied

Parent-child agreement in prepubertal depression: findings with a modified assessment method.

OBJECTIVE: Lack of or low parent-child (P-C) agreement is a well-documented problem in child psychopathology assessment. This study proposed to improve this agreement by using a modified assessment approach. METHOD: Ninety-three depressed prepubertal children, aged 6 to 12 years, and their mothers underwent an assessment procedure that combined multiple assessment measures given separately to child and mother (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode [K-SADS-P], Children's Depression Inventory, and traditional psychiatric interviews), confrontation of either and/or both informants with intra- and interinformant discrepancies, and senior clinician's "best estimate" clinical judgment to solve discrepant ratings. Correlational statistics (r, kappa, and z) were used to compare child's with mother's ratings on 20 K-SADS-P depressive symptoms. RESULTS: The major hypothesis, that using our assessment procedure, P-C agreement would be significant and moderately high (r and kappa = .40 or higher), was confirmed. The second hypothesis on dissociation of P-C agreement on behavioral versus ideational symptoms was partially confirmed; the third hypothesis on adverse effects of maternal "depression" on P-C agreement was not confirmed. CONCLUSION: Our assessment method has potential clinical application in enhancing diagnostic reliability of childhood depression assessment.

Adult↗