Board confronts community opposition to hospital merger. Interview by Karen Gardner.
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Biomedical subjects
Publications and source records attributed to D Carroll.
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This article discusses issues that are of interest and concern to all parents of adolescents, but that may be particularly difficult for single parents to manage. It also provides a framework for examining the areas of similarity as well as difference between the adolescent and the single parent. Attention is paid to the potential advantages of single-parent status.
A human alpha-amylase-encoding cDNA has been cloned in a transcription vector. When messenger RNA (mRNA) made in vitro from this construct was injected into Xenopus oocytes, amylase (AMY) activity was detected both in oocyte homogenates and in the incubation medium, indicating that the oocyte machinery correctly translated and processed the protein. Because AMY activity is easy to detect with a blue-starch assay, this expression system was used to determine the parameters of antisense oligodeoxyribonucleotide (oligo) inhibition of translation in the oocytes. Unique oligos complementary to the AMY mRNA sequence were effective in arresting translation, at approximately stoichiometric levels. Mixed oligos also inhibited translation, at levels that suggest that some mismatches may be tolerated in the formation of DNA-RNA hybrids. The AMY system provides a convenient probe of oocyte protein synthesis and processing machinery and can serve as a control substrate in investigations of other mRNAs.
To determine whether fitness alters psychological and physiological indices of well-being, male police officers were assigned to either an aerobic or anaerobic training condition or to a no treatment control group. The training groups met three times per week in 45 min sessions aimed at improving either cardiovascular endurance or muscle strength. Aerobic fitness level, heart rate, blood pressure and self-report of stress and well-being were measured prior to and following 10 weeks of training. Post-training fitness measures confirmed the effectiveness of training and between group differences for physiological and self-report measures were found. Subjects undergoing aerobic training evinced larger changes on the self-report measures of well-being and stress than the anaerobic trainers and both groups showed significant improvement when compared to controls. This experiment provides support for the hypothesis that exercise, and in particular aerobic exercise, has positive effects of well-being. It is suggested that future research might usefully explore the particular contribution of different aspects of the training situation to these effects.
In a double-blind multiple-dose cross-over study benzydamine 3% cream was compared with placebo for the treatment of post-herpetic neuralgia. Pain relief, pain intensity, sleep, escape analgesic consumption and side effects were assessed by diary methods for the 2 week treatment periods, with 1 week run-in and 1 week wash-out. There were no significant differences between the 2 treatments. The implications of the results for other antiprostaglandin remedies recommended for treatment of post-herpetic neuralgia are discussed. An important observation with methodological significance for similar studies of chronic conditions was that short treatment periods may produce false positive results. Patients' expectations are high, and if the first study treatment is ineffective, initial significant benefit may be noted when crossing over to the next treatment; this may not last longer than 1 week. Cross-over studies in which neither treatment is effective may, therefore, produce erroneous results if treatment periods are shorter than 2 weeks.
In a double-blind, placebo-controlled, single-dose, parallel-group study, oral doses (5, 10 and 25 mg) of the prostaglandin synthetase inhibitor bromfenac were compared with acetaminophen (1000 mg) and placebo for postoperative orthopedic pain. Analgesic measurements were made by nurse observers by use of standard verbal rating and visual analog scales. For most pain intensity and pain relief measurements, 1000 mg acetaminophen was statistically superior to placebo, demonstrating assay sensitivity, and 10 and 25 mg doses of bromfenac were statistically better than both placebo and 5 mg bromfenac for ordinal and analog ratings of pain intensity and pain relief; 25 mg bromfenac produced significantly longer time to remedication than acetaminophen. The 5 mg dose of bromfenac was statistically superior to placebo for some measures, including remedication time. There were no untoward adverse effects or alterations in vital signs. Overall, 10 mg bromfenac produced analgesia equivalent to that of 1000 mg acetaminophen in this pain context.
One hundred fifty-one patients with chronic cancer pain were studied during chronic treatment with oral morphine. Plasma concentrations of morphine and metabolites (M3G and M6G) were measured. The ratio of plasma morphine to metabolites was not affected by dose. Generalized linear interactive modeling analysis using morphine dose, age, sex, renal and hepatic dysfunction, and concomitant medication as explanatory variables accounted for 70% of the variance in plasma concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Increasing morphine dose was a significant factor for increased plasma concentrations of morphine, M3G, and M6G. Other significant factors were: age greater than 70 years (increased M3G and M6G plasma concentrations), plasma creatinine greater than 150 mumol/L (increased M3G and M6G plasma concentrations), male sex (decreased morphine and M6G plasma concentrations), raised creatinine plus coadministration of tricyclic antidepressants (increased M3G plasma concentrations), ranitidine (increased morphine plasma concentrations), and raised creatinine plus coadministration of ranitidine (increased M6G plasma concentrations).
Heart rate, systolic and diastolic blood pressure, and respiratory and metabolic activity were recorded prior to and during mental arithmetic and a video game task in 20 young men with mildly elevated casual systolic blood pressures. Twenty-five unambiguously normotensive young men were tested under the same protocol. For pretask baseline physiological activity, group differences emerged for all cardiovascular and metabolic variables; thus the elevated blood pressure group displayed not only higher resting cardiovascular levels than normotensive subjects, but higher levels of metabolic activity too. With regard to change in physiological activity from rest to task, the group with mildly elevated blood pressure showed reliably larger increases in heart rate to the mental arithmetic task than the normotensive subjects. These effects, however, were not paralleled by group differences in metabolic activity increase. Physiological measures were also taken prior to and during graded dynamic exercise. The subsequent calculation of individual heart rate-oxygen consumption exercise regression lines allowed the comparison of actual and predicted heart rates during psychological challenge. The subjects with mildly elevated blood pressure displayed significantly greater discrepancies between actual and predicted heart rate values than normotensives during the psychological tasks in general and mental arithmetic in particular. Group differences in physiological activity during exercise largely reflected the pattern seen at rest. A possible exception here was systolic blood pressure. Not only were systolic blood pressure levels higher throughout the exercise phase for mildly elevated blood pressure subjects, but this group evidenced more of an increase from rest to exercise than the normotensives.
This paper reviews evidence for the effectiveness of stress management techniques in reducing three risk factors for coronary heart disease: Type A behaviour, raised serum cholesterol, and hypertension. Preliminary evidence suggests that such interventions not only reduce individual risk factors, they can also reduce mortality and morbidity to CHD. Consideration now has to be given to the most effective system of delivery of such interventions.
Plasmid DNA substrates were X-irradiated and injected into the nuclei of Xenopus laevis oocytes. After incubation for 20 h, DNA was recovered from the oocytes and analyzed simultaneously for repair and for intermolecular homologous recombination by electrophoresis and bacterial transformation. Oocyte-mediated repair of DNA strand breaks was observed with both methods. Using a repair-deficient mutant Escherichia coli strain and its repair-proficient parent as hosts for the transformation assay, we also demonstrated that oocytes repaired oxidative-type DNA base damage induced by X-rays. X-irradiation of a circular DNA stimulated its potential to recombine with a homologous linear partner. Recombination products were detected directly by Southern blot hybridization and as bacterial transformant clones expressing two antibiotic resistance markers originally carried separately on the two substrates. The increase in recombination was dependent on X-ray dose. There is some suggestion that lesions other than double-strand breaks contribute to the stimulation of oocyte-mediated homologous recombination. In summary, oocytes have considerable capacity to repair X-ray-induced damage, and some X-ray lesions stimulate homologous recombination in these cells.
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We have tested the effects of serum-stimulated growth of quiescent WI38 human lung fibroblasts on cellular casein kinase II (CK-II) activity. Using the casein kinase II synthetic substrate RRREEETEEE we find a transient 6-fold elevation in CK-II activity in cell homogenates within 30 min following serum stimulation. Additional cycles of CK-II activation and inactivation are seen at 12 and 24 h after stimulation. The oscillations in CK-II activity are largely independent of de novo protein synthesis, and, thus, are likely to reflect cycles of post-translational activation and inhibition of the cellular kinase pool. In contrast to the activity profile of CK-II, we find that cyclic AMP-dependent protein kinase is rapidly inhibited upon serum-stimulation of WI38 cells. These results demonstrate that CK-II activity is subject to unique cellular regulation during proliferation and are consistent with the postulate that CK-II plays an important role in cell growth.
A combination of 20 mg codeine base and ibuprofen 400 mg was compared with ibuprofen 400 mg in a randomised double-blind cross-over study of multiple doses in 25 patients after 2-stage bilateral third molar removal. The combination produced significantly greater pain relief and doubled the hours of minimum pain intensity and maximal relief on the day of surgery. The patients rated the combination significantly better than ibuprofen alone, and the combination was preferred by 16 of the 22 patients expressing a preference. There was no significant increase in side-effect incidence with the combination. The 30% increase in analgesic effect may be of clinical benefit, and this trial design, cross-over with multiple dosing in out-patients, may be a sensitive test for analgesics, potentially more predictive of side-effect problems than single-dose studies.
Eighteen volunteer female subjects received preliminary instruction in a simple gymnastics bench sequence. They were then given a pre-intervention test on a bench at ground level. Self-reported distress, an independent observer's ratings of distress and heart rates were monitored immediately prior to performance of the sequence. Performances were also videotaped and formally scored by a qualified gymnastics judge. Subjects were then randomly assigned to a stress inoculation training group or a 'no stress management' training control group. Stress inoculation group subjects then received seven sessions of training in relaxation, imagery and making self-statements in order to develop a set of coping skills. Control group subjects also received seven training sessions during which they practised a series of coordination exercises, but no psychological stress management training was given to this group. All subjects were then re-tested on the bench sequence but this time at a height of 1.52 m. Self-reported stress, observer's ratings of distress and heart rate were recorded as before. Performance was again videotaped for scoring. The stress inoculation group reported significantly less stress prior to the test on the elevated beam than the control group. However, the groups did not differ in terms of heart rate. Further, the stress inoculation group performed reliably better than the control group on the elevated bench.
Linear DNA injected into Xenopus laevis oocyte nuclei recombines with high efficiency if homologous sequences are present at overlapping molecular ends. We found that injected linear DNA was degraded by a 5'----3' strand-specific exonuclease activity during incubation in the oocyte nucleus to leave a heterogeneous population of 3'-tailed molecules. Decreasing the concentration of DNA injected increased the heterogeneity and the average rate of degradation. The 3' tails created were relatively stable; among molecules persisting after overnight incubation, many had 3' tails intact to within 10 bases of the original ends. DNA molecules that were efficient substrates for homologous recombination in oocytes were also partially degraded, leaving 3' tails. We found no evidence for other potent nuclease activities. If molecules with recessed 3'-OH ends were injected, endogenous polymerase efficiently resynthesized complementary strands before degradation of the 5' tails occurred. 3'-tailed molecules are plausible intermediates in the initiation of homologous recombination events in Xenopus oocyte nuclei.
Members of two related families of transposable elements, Tx1 and Tx2, were isolated from the genome of Xenopus laevis and characterized. In both families, two versions of the elements were found. The smaller version in each family (Tx1d and Tx2d) consisted largely of two types of 400-base-pair tandem internal repeats. These elements had discrete ends and short inverted terminal repeats characteristic of mobile DNAs that are presumed to move via DNA intermediates, e.g., Drosophila P and maize Ac elements. The longer versions (Tx1c and Tx2c) differed from Tx1d and Tx2d by the presence of a 6.9-kilobase-pair internal segment that included two long open reading frames (ORFs). ORF1 had one cysteine-plus-histidine-rich sequence of the type found in retroviral gag proteins. ORF2 showed more substantial homology to retroviral pol genes and particularly to the analogs of pol found in a subclass of mobile DNAs that are supposed retrotransposons, such as mammalian long interspersed repetitive sequences, Drosophila I factors, silkworm R1 elements, and trypanosome Ingi elements. Thus, the Tx1 elements present a paradox by exhibiting features of two classes of mobile DNAs that are thought to have very different modes of transposition. Two possible resolutions are considered: (i) the composite versions are actually made up of two independent elements, one of the retrotransposon class, which has a high degree of specificity for insertion into a target within the other, P-like element; and (ii) the composite elements are intact, autonomous mobile DNAs, in which the pol-like gene product collaborates with the terminal inverted repeats to cause transposition of the entire unit.
Eighty subjects were assigned to two conditions in which readings of blood pressure were taken simultaneously by an observer using a Hawkesley Random Zero Sphygmomanometer and by a Pollenex BP-850 Automatic Sphygmomanometer either in its standard form or silenced to stop it bleeping whilst recording blood pressure. Forty subjects were assigned to a comparison group, where simultaneous readings by two observers were taken from one Hawkesley. Analyses performed included correlations, t-tests, and Bland and Altman's (Lancet, 1986, i: 307-310) differences against the mean method. Cues from observer behaviours or the bleeping Pollenex resulted in higher concordance between measures in the standard condition and the Hawkesley comparison condition. However, even in the silent condition the Pollenex proved to be as reliable a monitor of blood pressure as the Hawkesley.
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