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Biomedical subjects

R Crosby

Publications and source records attributed to R Crosby.

17 recordsLinked to original sources
PubMed1995

Ten-year follow-up of anorexia nervosa: clinical course and outcome.

The clinical course and outcome of anorexia nervosa are presented in a 10-year follow-up study of 76 severely ill females with anorexia nervosa who met specific diagnostic criteria and had participated in a well-documented hospital treatment study. Information was obtained on 100% of the subjects. A comprehensive assessment was made in 93% of the living subjects in specific categories of weight, eating and weight control behaviours, menstrual function, anorexic attitudes, and psychological, sexual, social and vocational adjustment. Five subjects had died, which gives a crude mortality rate of 6.6%. Standardized mortality rates demonstrated an almost 13-fold increase in mortality in the anorexia nervosa subjects. Only eighteen (23.7%) were fully recovered. Sixty-four per cent developed binge-eating at some time during their illness, 57% at least weekly. Twenty-nine (41%) were still bulimic at follow-up. The high frequency and chronicity of the bulimic symptoms plus the high rate of weight relapse (42% during the first year after hospital treatment) suggest that intensive intervention is needed to help anorexics restore and maintain their weight within a normal range and to decrease abnormal eating and weight control behaviours.

Adolescent↗
PubMed1994

Peptide inhibitors of src SH3-SH2-phosphoprotein interactions.

Activated pp60c-src has been implicated in a number of human malignancies including colon carcinoma and breast adenocarcinoma. Association of the src SH2 domain with tyrosine-phosphorylated proteins plays a role in src-mediated signal transduction. Inhibitors of src SH2 domain-phosphoprotein interactions are, thus, of great interest in defining the role(s) of src in signal transduction pathways. To facilitate such studies, an enzyme-linked immunosorbent assay (ELISA) was developed to detect inhibitors of src SH2-phosphoprotein interactions. This assay measures inhibition of binding of a fusion construct (glutathione S-transferase src SH3-SH2) with autophosphorylated epidermal growth factor receptor tyrosine kinase domain. Activities of phosphopeptide segments derived from potential src SH2 cognate phosphoprotein partners were determined, with the focal adhesion kinase-derived segment VSETDDY*AEIIDE yielding the highest inhibitory activity. Structure activity studies starting from acetyl (Ac)-Y*EEIE have identified Ac-Y*Y*Y*IE as the most active compound screened in the ELISA. This compound is at least 20-fold more active than the parent peptide Ac-Y*EEIE. A high resolution (2 A) crystal structure of human src SH2 complexed with Ac-Y*EEIE was obtained and provided a useful framework for understanding the structure-activity relationships. Additionally, Ac-Y*EEIE was able to block interactions between src and its cellular phosphoprotein partners in vanadate-treated cell lysates from MDA-MB-468 breast carcinoma cells. However, it is unable to abrogate proliferation of MDA-MB-468 cells in culture, presumably because of poor cell penetration and/or lability of the phosphate group on tyrosine.

Amino Acid Sequence↗
PubMed1994

Violence in patients with narcissistic personality pathology: observations of a clinical series.

This paper presents clinical observations on a group of nine patients whose action consisted of either the commission of violent acts or of seriously threatening behaviors suggestive of precursors to violence. A cluster of common features was observed to be present to some degree in all patients: (1) significant narcissistic personality pathology, (2) recent narcissistic injury, (3) inability to acknowledge or express affect related to this injury, (4) some history of impulsiveness when stressed, and (5) the availability of a weapon. Discussion is presented that the clinician's ability to predict the potential for violence may be enhanced by special attention to these features.

Adult↗
PubMed1992

Treatment of crack cocaine use with carbamazepine.

Crack is a rock crystalline alkaloid form of cocaine which can be smoked. At the University of Minnesota, we have developed an experimental pharmacologic treatment for cocaine abusers. Of 26 patients treated to date, 16 have been crack cocaine users. During the hundred days preceding treatment, the 16 crack subjects used cocaine by all routes an average of 71 days each. Improvement was based on a self-reported decrease in cocaine frequency of use. Using carbamazepine, seven highly successful and six partially successful patients reduced their use to 0.7 days and 26 days per 100 days, respectively. These results, though hopeful, must be viewed with caution and considered preliminary and tentative.

Adult↗
PubMed1985

Precise localization of the autonomic nerves from the pelvic plexus to the corpora cavernosa: a detailed anatomical study of the adult male pelvis.

The anatomical location of the branches of the pelvic plexus that innervate the corpora cavernosa has been identified previously in stillborn male neonates and fetuses. Based upon these observations, the techniques of radical retropubic prostatectomy and cystectomy have been modified to avoid injury to the autonomic innervation of the corpora cavernosa. However, the exact anatomical relationships of these nerves to the prostate, urethra and other pelvic structures in adults are unclear, since the initial anatomical studies of the pelvic plexus were performed in stillborn neonates in whom the accompanying vessels and fascia had been removed. Because these nerves are microscopic in size and can only be identified by their association with other pelvic structures, it was believed that a more refined understanding of the anatomy was necessary. In an effort to identify precisely the relationship of the cavernous branches of the pelvic plexus to the lateral pelvic fascia and the branches of the prostatovesicular arteries and veins, the following study was performed. Shortly after death a 60-year-old man was perfused completely with Bouin's fixative solution. The entire bladder, prostate, urethra, penis, corpora cavernosa, rectum, and pelvic sidewall fascia and musculature were removed en bloc. The specimen was serially sectioned transversely at 10 mu thickness, and every tenth section was stained with hematoxylin and eosin. An anatomical reconstruction in 3 dimensions was performed and illustrated. Thus, the specific location of the nerves that innervate the corpora cavernosa and their important relationships to the urethra, prostatic capsule, Denonvilliers' fascia and pelvic floor vasculature have been identified.

Autonomic Nervous System↗
PubMed1980

Modular approach to CPR training.

Basic and advanced cardiopulmonary resuscitation training is worthwhile yet time consuming. Anesthesiologists should be among the most qualified leaders in CPR teaching programs. Using a modular self-teaching presentation for basic and advanced cardiac life support courses, minimal instructor time is required to accomplish proficiency in both didactic and mannequin performance for participants. This method can be adapted to various educational levels and time constraints without compromising quality of teaching.

Anesthesiology↗
PubMed1978

Antimalarial activities of various 4-quinolonemethanols with special attention to WR-142,490 (mefloquine).

Pilot appraisals of the activities of a selected group of 4-quinolinemethanols against acute Plasmodium falciparum infections in owl monkeys indicated that compounds of this class are equally active against infections with chloroquine-resistant and chloroquine-susceptible strains and that this efficacy is not compromised by concomitant resistance to pyrimethamine, and in addition, identified three derivatives with outstanding activity (WR-226,253; WR-142,490; and WR-184,806). WR-142,490, the second 4-quinolinemethanol evaluated in the above model, was five times as active as chloroquine against infections with the chloroquine-susceptible, pyrimethamine-resistant strain and had a much larger therapeutic index. Expanded evaluations designed to support projected studies in human volunteers provided full confirmation of the pilot appraisals and in addition showed: (i) that the activity of WR-142,490 was a function of the total dose delivered, single doses being as effective as three or seven fractional doses administered over as many days; (ii) that intravenous administration of this agent was feasible and effective; and (iii) that the compound was at least as active against infections with P. vivax as against infections with P. falciparum. Companion studies in rhesus monkeys infected with P. cynomolgi showed that WR-142,490 lacked prophylactic or radical curative activity, but that it was as effective as chloroquine as a companion to primaquine in a combination curative drug regimen. The results of human volunteer and field trials agree well with comparable segments of these experimental evaluations.

Administration, Oral↗
PubMed1978

Antimalarial activities of various 9-phenanthrenemethanols with special attention to WR-122,455 and WR-171,669.

Pilot appraisals of the activities of 16 specially selected 9-phenanthrenemethanols against acute infections with Plasmodium falciparum in owl monkeys showed that all were more active than the reference compound, WR-33,063. WR-122,455, the most active derivative, and WR-171,669, ranked sixth, were selected for study in human volunteers. To assist this undertaking, appraisals of both compounds in owl monkeys infected with various strains of P. falciparum were expanded. These assessments showed: (i) that WR-122,455 was four times as active as chloroquine against infections with chloroquine-sensitive strains and that WR-171,669 equalled chloroquine in activity; (ii) that these compounds were fully active against infections with strains resistant to chloroquine, pyrimethamine, or quinine, or to all three standard drugs; (iii) that the activity of WR-122,455 was a function of total dose, single doses being as effective as the same amounts delivered in three or seven daily fractions; and (iv) that a single dose of WR-122,455 conferred extended, although only partial, protection against challenges with trophozoites. Complementary experiments in rhesus monkeys inoculated with sporozoites of P. cynomolgi showed that the activity of WR-122,455 was limited to blood schizonts and did not extend to early or late tissue schizonts. These evaluations were compatible with the results of preliminary studies of the activities of WR-122,455 and WR-171,669 in human volunteers.

Animals↗
PubMed1978

Antimalarial activities of various 4-pyridinemethanols with special attention to WR-172,435 and WR-180,409.

Pilot appraisals of the activities of 10 specially selected 2,6-substituted-4-pyridinemethanols against acute Plasmodium falciparum infections in owl monkeys identified three derivatives that were two to three times as active as chloroquine against infections with a 4-aminoquinoline-susceptible strain and, at the same doses, were equally effective against infections with a strain fully resistant to treatment with maximally tolerated doses of chloroquine, quinine, and pyrimethamine. Two of these derivatives, WR-172,435 and WR-180,409, deemed worthy of evaluation in human volunteers, were studied in greater depth in owl monkeys infected with either the multidrug-resistant Smith strain of P. falciparum or the pyrimethamine-resistant Palo Alto strain of P. vivax. These studies showed (i) that at the same total oral dose, 3-day and 7-day treatment schedules were equally effective and slightly superior to a single-dose schedule; (ii) that WR-172,435 was slightly more active than WR-180,409 in each treatment regimen; (iii) that intravenous delivery of WR-180,409 phosphate was feasible and effective; (iv) that both compounds effected control of parasitemia more rapidly than any standard or newly discovered antimalarial drug; and (v) that WR-172,435 and WR-180,409 had therapeutic indexes at least four to eight times those exhibited by chloroquine in infections with 4-aminoquinoline-susceptible strains, indexes retained by these pyridinemethanols against infections with various drug-resistant strains.

Animals↗
PubMed1978

Antimalarial activities of WR-194,965, an alpha-amino-o-cresol derivative.

Pilot appraisals of the activities of WR-194,965 and WR-204,165, two closely related o-cresol derivatives (both Mannich bases), in owl monkeys infected with the multidrug-resistant Vietnam Smith strain of Plasmodium falciparum showed that these compounds had similar levels of efficacy. Total course doses effecting 90% cures (CD(90)s) were 27 and 37 mg/kg of body weight for the respective compounds, values almost identical to the CD(90) of mefloquine (a highly promising 4-quinolinemethanol) against infections with the same strain, and the CD(90)s of chloroquine against infections with 4-aminoquinoline-susceptible strains. Expanded studies of the activities of WR-194,965 against infections with the Smith strain of P. falciparum and Vietnam Palo Alto strain of P. vivax, designed to guide projected evaluations in human volunteers, showed: (i) that the activity of this compound was a function of total dose administered, with single doses as effective as the same amount delivered in three or seven successive daily fractions; (ii) that all regimens effected rapid clearance of parasitemia; and (iii) that based on CD(90)s, this agent was twice as active against infections with the Palo Alto strain of P. vivax as against the Smith strain of P. falciparum. These findings, together with results of preclinical pharmacological studies pursued elsewhere, provided support for studies in human volunteers now underway.

Animals↗
PubMed1978

Antimalarial activities of the 4-quinolinemethanols WR-184,806 and WR-226,253.

WR-184,806 and WR-226,253, two 4-quinolinemethanols structurally similar to WR-142,490 (mefloquine), have been studied in depth in owl monkeys infected with various drug-resistant and drug-susceptible strains of Plasmodium falciparum and P. vivax in an effort to provide support and guidance for projected evaluations in human volunteers. The results of these studies, confirmatory of preliminary appraisals, showed that WR-184,806 was approximately one-third as active as WR-142,490 against infections with a multidrug-resistant strain of P. falciparum, whereas WR-226,253 was twice as active. Additionally, the current studies showed: (i) that both WR-184,806 and WR-226,253 were significantly more active against infections with blood schizonts of P. vivax than against those of P. falciparum; (ii) that their activities against established infections with either Plasmodium species were functions of the total doses delivered, single doses being as effective as three or seven fractional doses given on successive days; (iii) that WR-184,806 could be administered intravenously as the phosphate salt and was curative via this route in single doses; and (iv) that based on comparative curative doses, WR-184,806 was slightly more active and WR-226,253 was seven times more active against infections with a multidrug-resistant strain of P. falciparum than was chloroquine against infections with a 4-aminoquinoline-susceptible strain.

Administration, Oral↗
PubMed1977

Activities of various 4-aminoquinolines against infections with chloroquine-resistant strains of Plasmodium falciparum.

The studies reported here stemmed from a personal report by Geiman on the capacity of the 4-aminoquinoline amodiaquin to inhibit in vitro maturation of ring stages of the chloroquine-resistant Monterey strain of Plasmodium falciparum. This observation, confirmed in owl monkeys infected with this strain, led to a comparison of the activities of chloroquine, amodiaquin, amopyroquin, and dichlorquinazine (12,278 RP) against infections with various chloroquine-susceptible and chloroquine-resistant strains. The results showed that: (i) these 4-aminoquinolines were essentially equally active against infections with chloroquine-susceptible strains and (ii) the activities of amodiaquin, amopyroquin, and dichlorquinazine were reduced significantly in the face of chloroquine resistance, but (iii) well-tolerated doses of these compounds would cure infections with strains that fully resisted treatment with maximally tolerated doses of chloroquine. Two other 4-aminoquinolines, SN-8137 and SN-9584, which also exhibited activity against chloroquine-resistant parasites in vitro, displayed curative activity in monkeys infected with a chloroquine-resistant strain. These observations show that there is cross-resistance among the 4-aminoquinolines, confirming earlier findings, but indicate that the dimensions of this phenomenon are sufficiently limited so that some derivatives are therapeutically effective against infections refractory to maximally tolerated doses of chloroquine.

Aminoquinolines↗
PubMed1977

Quantitative aspects of pyrimethamine-sulfonamide synergism.

The experiments described in this report have dealt with the dimensions of therapeutic potentiation achieved when combinations of pyrimethamine and sulfadiazine were administered to rhesus monkeys infected with a drug-susceptible strain of Plasmodium cynomolgi or its pyrimethamine-resistant variant and to owl monkeys infected with strains of P. falciparum and P. vivax of varying degrees of resistance to this pyrimidine. These evaluations showed: 1) that when delivered in combination, the activities of both pyrimethamine and sulfadiazine against infections with any of the above strains were enhanced significantly; 2) that in infections with the Ro and Ro/PM strains of P. cynomolgi and the Vietnam Palo Alto strain of P. vivax, concomitant delivery of the two agents resulted in a 32-fold increase in the activity of pyrimethamine and a 50- to 100-fold increase in the activity of sulfadizine; 3) that as a result of this synergism, infections with the pyrimethamine resistant Ro/PM and Palo Alto strains could be cured with a fraction of the maximum tolerated dose of this drug; 4) that in marked contrast to the above result, infections with the Malayan Camp and Vietnam Smith strains of P. falciparum could not be cured regularly by combination regimens which included the maximally tolerated dose of pyrimethamine. This poor response has been attributed to the high levels of pyrimethamine-resistance possessed by these strains. It is believed that the comparatively small but not insignificant incidences of treatment failures associated with delivery of pyrimethamine-sulfonamide combinations to both patients and human volunteers infected with multidrug-resistant strains of P. falciparum rest on a similar basis.

Animals↗
PubMedDate not supplied

The measurement of craving in cocaine patients using the Minnesota Cocaine Craving Scale.

Drug craving is an irresistible urge that compels drug-seeking behavior, and which often accounts for relapse among treated cocaine users. A cocaine craving scale that has proven reliable and practical in clinical treatment research with cocaine-using subjects is presented. It assesses intensity, frequency, and duration of this entirely subjective phenomenon. Data from 234 scales completed by 35 patients in treatment showed that craving for cocaine was of variable intensity, experienced relatively few times per day (zero to two), and of short duration (less than 20 minutes). Internal consistency among the three scales was robust, shown by a standardized item alpha of .826. The use of this scale should allow for each component of craving to be studied separately.

Adult↗