Collaboration in care - Paper 3.
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Biomedical subjects
Publications and source records attributed to K Brown.
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We analyzed a random sample of general medicine clinic patients to determine the natural history of newly treated hypertensive (NH) patients: discontinuation patterns, critical intervention periods, and hypertension's (HBP) utility as an indicator condition. The NH patients exhibited a 48% dropout rate in the first year and better continuation adherence than new nonhypertensive (NNH) patients. Patients with HBP and other chronic diseases had better continuation adherence than those with HBP alone, although no predictive patterns emerged. New patients displayed rapid early discontinuation, with further linear decline by four months for NNH and by eight months for NH patients. All patients showed similar subsequent falloff: linear annual decline at 13% to 36%. We conclude that discontinuation rates are unacceptably high, that interventions must be continued throughout treatment, and that HBP has limited utility as an indicator chronic disease.
1. An indenopyridine (YG19-256) and a benzothiazepin (thiazesim) were investigated in rats for possible effects on shock-induced defensive fighting, shock reactivity and locomotor activity. 2. YG19-256 significantly reduced aggression at the higher dose levels employed. Thiazesim produced no significant decrease in aggression at the dose levels used. 3. Neither compound produced any consistent effect on shock reactivity or locomotor activity.
When space-filling models of the peroxy radical precursor of PGG were compared with models of 2(S)-(3-chloro-4-cyclohexylphenyl) propionic acid and other acidic cyclooxygenase inhibitors several common structural features were revealed. This led us to propose a template for designing non-steroidal anti-inflammatory drugs (NSAID's) based on the conformation of the peroxy radical immediately prior to its cyclisation to PGG. The template can be equated with a complementary cyclooxygenase receptor site.
When space-filling models of the peroxy radical precursor of PGG were compared with models of 2(S)-(3-chloro-4-cyclohexylphenyl)propionic acid and other acidic cyclooxygenase inhibitors several common structural features were revealed. This led us to propose a template for synthesising non-steroidal anti-inflammatory drugs (NSAIS's) based on the geometry of the peroxy radical immediately prior to its cyclisation to PGG.
An academic general medicine clinic (GMC) was studied to determine current patterns, shortcomings, and potential solutions. Retrospective medical record review of 349 randomly selected GMC patients from 1975 permitted profile generation. Only 11.5% of the patients had first visits in the study year. Almost 75% of the study group used the university hospital as their major source of care. Over two years only 58% continued in active care, while 5% died, 8% needed no further follow-up, and 29% were lost from care. The prevalence of hypertensive cardiovascular disease was disproportionately high. Patients exhibited chronic disease exclusively in 91% of return visits. The authors conclude that the GMC offers insufficient variety of patient presentations for optimal postgraduate medical education and inadequate accessibility for comprehensive medical care. Potential improvements include expanding the patient base, extending availability, and employing nonphysician clinicians.
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The pheA structural gene of the phenylalanine operon of Escherichia coli is preceded by a transcribed leader region of about 170 nucleotide pairs. In vitro transcription of plasmids and restriction fragments containing the phe promoter and leader region yields a major RNA transcript about 140 nucleotides in length. This transcript, pheA leader RNA, has the following features: (i) a potential ribosome binding site and AUG translation start codon about 20 nucleotides from its 5' end; (ii) 14 additional in phase amino acid codons and a UGA stop codon after the AUG; 7 of these 14 are Phe codons; (iii) a 3'-OH terminus about 140 nucleotides from the 5' end (transcription termination occurs in an A.T-rich region which is subsequent to a G.C-rich region; just beyond the site of transcription termination there is a sequence corresponding to a ribosome binding site and the AUG translation start codon of the pheA structural gene); (iv) a sequence which would permit extensive intrastrand stable hydrogen bonding. In addition to G.C-rich stem structures, highly analogous to those proposed for the leader RNAs of the tryptophan operons of E. coli and Salmonella typhimurium [Lee, F. & Yanofsky, C. (1977) Proc. Natl. Acad. Sci. USA 74, 4365-4369], there is also extensive base-pairing possible between the phe codon region and a more distal region of the leader transcript. The roles of synthesis of the Phe-rich leader peptide and secondary structure of the leader transcript in the regulation of transcription termination at the attenuator of the phe operon are discussed.
We have looked at the effect of in vivo cortisone acetate treatment on effector cells for antibody-dependent cell-mediated cytotoxicity in mice and rats, using both chicken erythrocytes and the mouse lymphoma cell line AKR.A as target cells, since the AKR.A cell line is susceptible to antibody-dependent cell-mediated cytotoxicity killing only by the lymphoid effector cell, whereas a wide variety of effector cells will lyse chicken erythrocytes in the presence of antibody. The lymphoid K cell, detectable in rat spleen and blood, was unaffected by steroid treatment sufficient to cause lymphopenia, whereas splenic anti-chicken erythrocyte cytotoxicity of whole spleen and of phagocyte-free spleen was depressed in mice and rats. The greatest suppression was seen with nonphagocytic mouse spleen, and may have been in part attributable to steroid-induced redistribution of the effector cell(s), since the cytotoxic capacity of nonphagocytic bone marrow cells was increased by 70% at a time when the activity in spleen was 25% of normal.
Captive L. rosalia were observed to exchange food routinely in family groups, a process varying from donation to theft. Donation involved the use of 'invitational' signals which operated most efficiently in parent-infant sharing and in donating live prey. Food moved, by sharing and theft, toward: (a) males prior to the female's first conception; (b) females during late pregnancy; (c) carriers of infants; (d) weanlings; (e) juveniles when infants died; (f) third animals in trios, regardless of their age and relatedness to the pair. Successful reproduction, a complex behavior involving all group members in cooperative infant care and provisioning, is probably enhanced by captive L. rosalia's food-sharing habits.
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EcoRI endonuclease digestion of the deoxyribonucleic acid of a phi80 transducing phage carrying the entire tryptophan (trp) operon of Salmonella typhimurium (phi80 S.t.trpE-A) yielded a 4.3 X 10(6)-dalton fragment containing intact trpE, trpD, and trpC and a 3.35 X 10(6)-dalton fragment containing intact trpA. The trpA fragment inserted into EcoRI-cleaved plasmids ColE1 and CR1 was expressed regardless of its orientation of insertion. Mitomycin C, a compound that induces colicin E1 production in ColE1-containing bacteria, stimulated tryptophan synthetase alpha production in cells containing ColE1-TRPA plasmids with the trpA fragment inserted in one orientation but not the other. We conclude that in the inducible plasmids trpA can be expressed from the colicin E1 promoter.
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