Medicine's need for kaizen.
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Biomedical subjects
Publications and source records attributed to R Smith.
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OBJECTIVE: To determine age specific prevalence of HIV antibody, incidence of pregnancy, and likelihood of detection and correct assignment to risk category by antenatal screening of women known to be positive for HIV antibody, from 1984 to 1989. DESIGN: Retrospective analysis of reproductive history and risk behaviour of women positive for HIV antibody and prediction of detection by screening on the basis of blood group samples, Guthrie tests, and rubella tests. SETTING: City of Dundee, where the prevalence of HIV is high, since the appearance of HIV in 1984, predominantly among heterosexual intravenous drug users. PATIENTS: All (61) women known to be positive for HIV antibody who had had clinically indicated tests, for whom case notes were available for 60. MAIN OUTCOME MEASURES: Risk assessment according to case notes and reported to the laboratory, incidence of infection, geographical location, age, date of positive test result, and reproductive history. RESULTS: With 61 infected women the overall minimum prevalence among women within the city of Dundee was 0.67/1000 and 2.9/1000 among women in their third decade. Of the 60 women whose reproductive history was available, 35 had 57 pregnancies, 36 of which occurred after seroconversion was known to have taken place, representing 8.7% of the total number of affected pregnancies reported for the United Kingdom. If antenatal screening for HIV had been performed between 1984 and 1989 it could not have detected positivity for HIV antibody in 25 (42%) women who had no pregnancies during this time. Among the remaining 35 women, screening samples taken for blood grouping could have identified a maximum of 34 (57%), samples taken to check rubella susceptibility a maximum of 22 (37%), and blood spots on Guthrie cards a maximum of 19 (32%). Retesting would have occurred in 14 women 33 times with samples taken for blood grouping, but three and four women would have been tested twice using samples taken for rubella testing and Guthrie cards respectively. Anonymous screening would have been unable to determine risk category as a history of intravenous drug use was known in 47 (79%) women before testing but this was increased by a further 5 (8%) who admitted to it after the test result was known. CONCLUSION: Interpreting the results of antenatal screening programmes will be complex and will underestimate overall prevalence of HIV antibody among women; this will be exaggerated by strategies based on anonymous testing with Guthrie cards or on samples taken for rubella testing, which do not include women who have had an earlier loss of pregnancy. Only open testing with consent will permit satisfactory attribution to
Consideration is given to the interactions of ligand with self-associating acceptor systems for which preferential ligand binding is an ambiguous term, in that the acceptor species with greater affinity for ligand possesses relatively fewer binding sites. A paradoxical situation wherein ligand-mediated self-association is seemingly detrimental to ligand binding is shown to be the predicted outcome for a transient range of ligand concentrations. This outcome reflects the existence of a critical point in the dependence of the extent of acceptor self-association upon ligand concentration that coincides with a cross-over point of ligand-binding curves for different, fixed total concentrations of acceptor. By classical differentiation methods the conditions for the existence of these critical points are established not only for two-state acceptor systems but also for three-state acceptor systems in which the ligand-binding form of monomer also undergoes reversible isomerization to an inactive state. Similar procedures are used to comment upon the forms of binding curves for the three-state acceptor systems, the Scatchard representations of which may exhibit as many as three critical points (two maxima and a minimum). This delineation of quantitative expressions for critical points and other distinctive features associated with the conflicting interplay of ligand-binding and self-association behaviour should provide a more definitive means of characterizing systems with one acceptor state the preferred binding form on affinity grounds but with the other the preferred state from the viewpoint of binding-site numbers.
End-to-end helical dimers of gramicidin A form transmembrane pores in lipid bilayers, through which monovalent ions may pass. The groups within the peptide that interact with these ions have been studied by application of solid-state spectroscopic methods to a series of gramicidin A analogues synthesized with 13C in selected peptide carbonyl groups. The resonances of D-Leu10, D-Leu12 and D-Leu14 analogues were perturbed in the presence of 0.16 M sodium ions, whereas the resonances of the carbonyls of Gly2, Ala3, D-Leu4 and Val7, which are closer to the formylated N-terminal end of the peptide, were unaffected. The observed changes in chemical shift anisotropy are indicative of a change in orientation of the abovementioned leucine carbonyls.
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It is not certain which protein kinase (A, C or both) is involved in the acute phase of beta-endorphin (beta-EP) release stimulated in the corticotrope by vasopressin (VP) and corticotropin-releasing factor (CRF). We have employed an isolated ovine anterior pituitary cell superfusion system to determine the dynamic effects of forskolin, a protein kinase A (PKA) stimulator, and phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator. Both secretagogues stimulated beta-EP release within 5 min and therefore both PKA and PKC are potential mediators of the acute phase of hormonal stimulation of the corticotrope. Pretreatment with PMA specifically desensitized the pituitary cell columns to subsequent PMA exposure while not significantly altering sensitivity to forskolin or 50 mM KCl.
Percutaneous transseptal mitral valvotomy was performed on 14 occasions in 13 patients; in one patient, the procedure was unsuccessful at the first attempt, but was repeated successfully. All other attempts were successful, giving a procedure success rate of 93% and a patient success rate of 100%. The only complication was transient diplopia in one patient, presumably due to a small cerebral embolus. This early experience confirms that this procedure is easily learnt, and can be performed with good results and low risk in selected patients with mitral stenosis.
The binding of myelin basic protein to lysolauroylphosphatidylcholine (lysoLPC) and lysolauroylphosphatidylethanolamine was investigated at neutral pH using gel partition chromatography and equilibrium dialysis at 20 and 37 degrees C. The results show that the protein-lysolipid interactions are highly cooperative and that the free lysolipid concentration at which the binding commences is markedly influenced by both the chemical structure of the lysolipids and the temperature. The binding begins just below the critical micelle concentration for both lysolipids, which suggests that the forces governing micellization and the binding are similar. Circular dichroism (CD) spectroscopy was used to follow changes in the conformation of the protein caused by lysomyristoylphosphatidylcholine and lysoLPC. The CD results indicate that lysolipid association with the protein commences below the critical micelle concentration and continues above this concentration. Mechanisms for the lysolipid-protein interaction, which are consistent with the binding and CD data, are discussed.
Amitriptyline hydrochloride was compared with placebo in 46 veterans with chronic posttraumatic stress disorder. Treatment continued up to 8 weeks, and efficacy was measured by five observer and two self-rated scales. Percent recovery rates were higher for amitriptyline than placebo on two measures. In patients who completed 4 weeks (n = 40), better outcome with amitriptyline was noted on the Hamilton depression scale only. In the group completing 8 weeks of treatment (n = 33), the drug was superior to placebo on Hamilton depression, Hamilton anxiety, Clinical Global Impression severity, and Impact of Event scales. There was no evidence for drug effects on the structured interview for posttraumatic stress disorder. Drug-placebo differences were greater in the presence of comorbidity in general, although recovery rates were uniformly low in the presence of major depression, panic disorder, and alcoholism. At the end of treatment, 64% of the amitriptyline and 72% of the placebo samples still met diagnostic criteria for posttraumatic stress disorder.
The effects of epidermal growth factor (EGF) on androgen stimulation of accessory sex gland growth and biochemistry were determined for prepubertal male Swiss-Webster mice. For the seminal vesicle and anterior prostate, 5 alpha dihydrotestosterone (5 alpha DHT) treatment significantly increased the quantitative levels of organ wet weight, DNA content, polyamine content, and stereologically determined epithelium and lumen volumes above the control group. EGF treatment alone slightly enhanced the levels of most measured parameters from control values. However, when a combined EGF&5 alpha DHT treatment was compared with 5 alpha DHT treatment alone, the 5 alpha DHT treatment effects on epithelial and lumen volumes and polyamine content were antagonized by the action of EGF.
A new semi-automatic method for quantifying regional cerebral uptake of 99m technetium-hexamethylpropylene amine oxime (99mTc-HMPAO) was used to assess single photon emission tomograms from 5 normal subjects, 14 patients with Alzheimer's disease, 14 patients with dementia of frontal lobe type and 4 patients with dementia with motor neurone disease. Uptake in both posterior cortical regions, although not in other regions, was significantly lower (P less than 0.05) in Alzheimer's disease than in normal controls. Conversely in both dementia of frontal lobe type and dementia with motor neurone disease, uptake was significantly reduced (P less than 0.05) compared with controls in all anterior cortical regions but not in posterior regions. Numerical findings in each disease mirrored the pattern of reduced tracer uptake previously reported by visual assessment. Nine patients were re-examined after an interval of at least 1 year. Comparison of follow-up scans with original images showed significant decreases in mid-anterior, left anterior and left posterior cortical uptake (P less than 0.01) in patients with Alzheimer's disease and in left middle, left posterior and right posterior cortical uptake (P less than 0.01) in patients with dementia of frontal lobe type. The method of quantification may be a useful adjunct to the visual assessment of single photon emission tomograms.
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The relationships between mood change, obstetric experience and alterations in plasma cortisol, beta-endorphin (beta-EP) and corticotrophin-releasing hormone (CRH) were examined in a prospective study of 97 primiparous Australian women. Psychological measures were administered between the 28th week of pregnancy and the 3rd postnatal month, including the Profile of Mood States (POMS) and the Montgomery Asberg Depressive Rating Scale (MADRS). Blood samples were collected for cortisol, beta-EP and CRH assay on most of these occasions and during labour. Factor analysis was used to identify key subsets of psychological variables for use in the subsequent analyses. 'Mood disturbance' and 'tiredness' factors peaked at 38 weeks' gestation, while 'difficulty falling asleep' was greatest around the time of birth. Cortisol, beta-EP and CRH concentrations rose significantly as pregnancy advanced and peaked at birth; plasma CRH correlated with plasma cortisol (r = 0.54) and beta-EP (r = 0.32). Women with the highest 'mood disturbance' and MADRS depression scores at 28 weeks' gestation received significantly more pain relief during labour. Those women whose mood deteriorated from 38 weeks' gestation to postnatal day 2 had larger falls in plasma beta-EP after delivery (p less than 0.01) than those women whose mood improved or remained constant. Women in this mood-deteriorated subgroup also had significantly higher MADRS depression scores at 3 months (p less than 0.01). Mild antenatal depression (MADRS greater than 13) occurred in 5.2% of women and mild postnatal depression in 4.7%. Overall, these data suggest a role for circulating CRH in the regulation of maternal cortisol secretion and significant relationships between maternal postnatal mood states and beta-EP and between antenatal mood states and obstetric events.
Benign cystic teratoma of the omentum is a rare abdominal tumor. Review of the literature describes seven reported cases of omental teratomas in association with ovarian teratomas. Our patient is a 68-year-old woman who presented with an asymptomatic abdominal mass and uterine prolapse. Ultrasound revealed a right-sided, cystic and solid pelvic mass. CT scan revealed a second mass with calcifications situated along the right iliac crest. This is the first description of an omental teratoma in association with a benign ovarian cystic teratoma coexistent with a malignant neoplasm. Possible etiologies of the present case are discussed and additional literature investigated.
Five groups of heifers were immunized with various subcellular fractions of Brucella abortus and tested for their responsiveness in lymphocyte proliferative responses in vitro. The five subcellular fractions used as immunogens were: (1) a mixture of recombinant outer membrane proteins fused to Escherichia coli beta-galactosidase, (2) a mixture of outer membrane proteins BaomI, BaomIIB1, and BaomIII1, (3) a mixture of outer membrane proteins 7.5 kDa and 8.8 kDa, (4) a complex of smooth lipopolysaccharide and proteins, and (5) a complex of outer membranes and peptidoglycan (OM-PG complex) from a rough strain. All immunogens were emulsified in adjuvant and administered twice at a 61-day interval. Two other groups of cows were included; one immunized with strain 19 and the other with adjuvant only. Strain 19 and the rough OM-PG complex induced responsiveness in lymphocyte proliferation assays in a high percentage of immunized cows. The smooth lipopolysaccharide-protein complex induced responsiveness in fewer cows. The lowest frequencies of responding cows were found in groups that received either recombinant proteins or purified protein mixtures. Based on these results, we concluded: (1) cellular immunity, as measured by in vitro lymphocyte proliferative responses, can be induced with subcellular fractions of B. abortus and (2) the more complex the immunogen, the greater the frequency of responding cows.
The outer membrane-peptidoglycan complex (OM-PG) from rough strains of Brucella abortus was tested for its ability to induce lymphocyte responsiveness in cattle. Six groups of heifers were immunized with varying doses and administration schedules of rough OM-PG and assayed for responsiveness of their lymphocytes in proliferation assays in vitro. All OM-PG preparations were emulsified in a commercial adjuvant for administration. Two other groups of heifers were immunized with strain 19 vaccine or adjuvant alone. Three groups of heifers received two inoculations of OM-PG antigens from a naturally-occurring rough strain at a 57-day interval. The doses of OM-PG given in these three groups were 400 micrograms, 1200 micrograms, and 4000 micrograms at each inoculation. The frequency of cows that responded in lymphocyte proliferation assays increased with the dose of OM-PG given. Two groups received single inoculations of OM-PG, either 2400 micrograms or 8000 micrograms. Although there were responsive cows in these immunization groups, their frequency was lower than in the groups receiving the same total dose in two inoculations. A sixth group of cows was inoculated with OM-PG from a rough transposon mutant of B. abortus, and the frequency of responsive cows in this immunization group was comparable to that of responsive cows immunized with the same dose of OM-PG from the spontaneous rough mutant. In comparisons of cows inoculated with strain 19 to those inoculated with OM-PG preparations, differences were observed in the relative responsiveness of their lymphocytes to whole cells and OM-PG in the in vitro lymphocyte proliferation assays. These differences suggested that lymphocytes stimulated by strain 19 vaccination have different specificities than those stimulated by immunization with OM-PG of rough mutant strains of B. abortus.