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Biomedical subjects

J Cooke

Publications and source records attributed to J Cooke.

At least 109 records · Page 6Linked to original sources

Patients' knowledge concerning their medications on discharge from hospital.

Fifty patients were interviewed, on discharge from hospital, about their medications. Nine (18%) patients did not know, and a further four (8%) had inappropriate beliefs about why they were taking at least one of their discharge medications. Very few patients knew of significant side-effects which they might expect, or precautions which they should take, and over half did not know how long they were to continue taking their medicines. A small proportion was unable to read the bottle or open the container. Thus, even patients who, by virtue of an in-patient stay, have had a prolonged opportunity for education regarding their medicines have very little knowledge of their medicines upon discharge from hospital.

Drug Therapy↗

Reformatted computed tomography of the female pelvis: normal anatomy.

Axial computed tomography (CT) of the pelvis provides useful information in patients with gynaecological malignancies, both for initial staging, to follow disease progression and to assess response to treatment. Additional useful information may be available from reformatted coronal and sagittal images. Knowledge of normal anatomy is essential for correct interpretation of pathology. The anatomy and technique used to acquire the images are described in this paper.

Cervix Uteri↗

Potentiation by the lithium ion of morphogenetic responses to a Xenopus inducing factor.

We have cultured explants of Xenopus blastular animal cap tissue from embryos that had received an earlier treatment with LiCl and from their untreated siblings, in various concentrations of XTC-cell-derived mesoderm-inducing factor (XTC-MIF, Smith, 1987; Smith et al. 1988). The pretreatment with lithium that we used transforms later morphogenesis in the whole embryo to give radialized body forms with anterior/dorsal levels of structure grossly over-represented. In addition, animal caps from 'Li+' embryos were allowed to develop without exposure to in vitro MIF (Li+ controls) and compared with normal uninduced control explants, and explants were made from normal early blastulae but given various initial treatments with LiCl in culture. The results confirm that the lithium ion itself will not induce mesoderm in competent, animal cap tissue of Xenopus. It does, however, enhance the responsiveness of this tissue to XTC-MIF, in a way that parallels its recently reported effect in the case of another mesoderm inducer of different character, bFGF (Slack et al. 1988). The effects observed are sufficient to imply that the altered body pattern that follows lithium treatment, in whole embryos, could be caused by modulation of the responses to an unaltered pattern of in situ inductive stimuli. We also observe evidence that appreciable inductive signals reach animal pole tissue beyond the limits of mesoderm formation in normal development. Relatively low concentrations of MIF prevent the development of an epidermis-specific marker in dissociated blastular animal cap cells (Symes et al. 1988). When such experiments are repeated in relation to the lithium pretreatment of embryos, such treatment is seen to have sensitized the cell population, so that the MIF concentration range that assures complete suppression of the marker is reduced. The results are discussed in relation to induction considered as pattern formation.

Animals↗

Xenopus mesoderm induction: evidence for early size control and partial autonomy for pattern development by onset of gastrulation.

Experiments are described that examine the state of organisation of the presumptive mesoderm and ectoderm of the Xenopus embryo at stages up to the onset of gastrulation. It is shown that a process during blastula stages, establishing the normal proportions in which this cell population is partitioned to found the two outer 'germ layers', has a positive regulative property. An operation has been performed to excise the yolky endodermal core, at the beginning of gastrulation, leaving only the presumptive territories of mesoderm, neural tissue, epidermis and supra-blastoporal endoderm. This reveals that by this time a stable capacity exists within the induced tissue to express the craniocaudal sequence of the normal pattern, including the proper numbers of somite segments. The mediolateral organisation of such body patterns is however abnormal. The relevance of the observations to understanding mechanisms of axial pattern control is discussed.

Animals↗

Mesoderm-inducing factors and Spemann's organiser phenomenon in amphibian development.

Certain proteins from 'growth factor' families can initiate mesodermal development in animal cap cells of the amphibian blastula. Cells that are in early stages of their response to one such factor, XTC-MIF (Smith et al. 1988), initiate the formation of a new axial body plan when grafted to the ventral marginal zone of a similarly aged host embryo (Cooke et al. 1987). This replicates the natural control of this phase of development by the dorsal blastoporal lip when similarly grafted; the classical 'organiser' phenomenon. I have explored systematically the effect, upon the outcome of this pattern formation using defined inducing factors, of varying graft size, XTC-MIF concentration to which graft cells were exposed, length of exposure before grafting, and host age. The 'mesodermal organiser' status, evoked by the factor, appears to be stable, and the variables most influencing the degree of completeness and orderliness of second patterns are graft size and factor concentration. Inappropriately large grafts are not effective. A Xenopus basic fibroblast growth factor homologue, present in the embryo and known to be a strong inducer but of mesoderm with a different character from that induced by XTC-MIF, produced no episode of pattern formation at all when tested in the procedure described in this paper. Organiser status of grafts that have been exposed to mixtures of the two factors is set entirely by the supplied XTC-MIF concentration. Lineage labelling of these grafts, and of classical dorsal lip grafts, reveals closely similar though not identical patterns of contribution to the new structure within the host. Implications of the results for the normal mechanism of body pattern formation are discussed.

Animals↗

Inducing factors and the control of mesodermal pattern in Xenopus laevis.

The mesoderm of Xenopus laevis and other amphibia is formed through an inductive interaction during which cells of the vegetal hemisphere act on cells of the animal hemisphere. Two groups of factors mimic the effects of the vegetal hemisphere. One group consists of members of the fibroblast growth factor (FGF) family, while the other is related to transforming growth factor type beta (TGF-beta). In this paper we discuss the evidence that the FGF family represents 'ventral' mesoderm-inducing signals, and the TGF-beta family 'dorsal' signals. The evidence includes a discussion of the cell types formed in response to each type of factor, the fact that only XTC-MIF (a member of the TGF-beta family) and not bFGF can induce animal pole ectoderm to become Spemann's organizer, and an analysis of the timing of the gastrulation movements induced by the factors.

Animals↗

S-nitrosocaptopril. I. Molecular characterization and effects on the vasculature and on platelets.

We have synthesized an S-nitrosylated derivative of captopril, S-nitrosocaptopril, that manifests nitrosovasodilatory activity, inhibits angiotensin converting enzyme activity and inhibits platelet aggregation. The direct vasodilatory effects of S-nitrosocaptopril reflect the effects of the thionitrite bond, the presence of which does not in any way influence S-nitrosocaptopril's ability to inhibit angiotensin converting enzyme. Thionitrite stimulation of both vascular and platelet soluble guanylate cyclase activity leads to increases in intracellular cyclic GMP that are accompanied by vasodilatation and platelet inhibition, respectively. S-nitrosocaptopril is a novel hybrid molecule that has potential use in the treatment of hypertension regardless of renin status, angina pectoris and congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

Induction and the organization of the body plan in Xenopus development.

Various experiments are surveyed in this paper that may throw light on how the degree of spatial organization of the Xenopus embryo increases during development. The events of the 100 minutes or so that follow fertilization may do little more than orientate and give proportions, within the egg's yolky vegetal region, to the system that originates patterned inductive signals for organization of the mesodermal and ectodermal regions during blastula stages (10(2)-10(4) cells). By onset of gastrulation, an outline plan for mediolateral and anteroposterior body organization has developed within induced tissue around the equator of the embryo, which seems to control subsequent development in two ways. It sets the spatial and temporal pattern of mechanical activities whereby the mesoderm rudiment drives the crucial shape changes that lay it and the neural rudiment out correctly. It is also the probable starting point for positionally specific gene transcription that begins immediately after gastrulation. Experiments with known inducing factors that explore the possible bases for the early 'pre-organization' in mesoderm are informative, but leave us far from a complete understanding. Evidence that inhibitory or modulating, as well as activating, signals are involved is surveyed.

Animals↗

The anatomy and pathology of the brachial plexus as demonstrated by computed tomography.

Computed tomography (CT) scanning can demonstrate a wide range of abnormalities affecting both the brachial plexus and the surrounding structures. Narrow section (4 mm) CT was used with bolus intravenous enhancement to examine the root of the neck and axilla in 62 patients with cancer, many of whom had symptoms of brachial plexus neuropathy. The normal anatomy of the plexus and its relations are described and illustrated. Examples of pathological changes caused by tumour and irradiation are also presented. The narrow scanning width (4 mm) is needed as the details sought are small and will be missed on thicker slice widths, particularly the changes of fibrosis in the upper axilla. Injection of intravenous contrast medium is essential for identifying the vascular structures which are used to locate the brachial plexus, especially when disease processes and post-irradiation fibrosis have destroyed the tissue planes.

Axilla↗

The diagnosis by computed tomography of brachial plexus lesions following radiotherapy for carcinoma of the breast.

The region of the brachial plexus in the root of neck and axilla was examined by computed tomography (CT) in 62 patients attending the Royal Marsden Hospital. Forty-two of these patients had been treated by surgery and subsequent radiotherapy for carcinoma of the breast. Computed tomography was able to identify varying grades of abnormality that were ascribed to radiation fibrosis. Twenty-eight patients had neurological symptoms affecting the arm or hand on the treated side and CT changes were seen in 96%. The grading and significance of these CT abnormalities is discussed. The patients had been treated by two different radiotherapy techniques (three-field and four-field) which utilised either a large or small treatment fraction. The higher grades of abnormality on CT were seen in 57% of those treated with the large fraction size and 27% of those treated with the small fraction size. However, the changes on CT did not relate to the different radiotherapy techniques.

Brachial Plexus↗

The restrictive effect of early exposure to lithium upon body pattern in Xenopus development, studied by quantitative anatomy and immunofluorescence.

We have carried out an anatomical study of Xenopus larval and gastrula stages resulting from treatment of synchronous early blastulae for brief periods with Li+. We confirm the proposal that such treatment causes a particular transformation, and partial elimination, of the normal body pattern. Coordinated restriction of pattern, without appreciable loss of cell number, is seen in all three germ layers. The distortion has been investigated by quantitative study of mesoderms at a standard stage, in relation to the normal fate map for mesoderm, and with the help of immunofluorescence on sections for somitic muscle and for blood. In the extreme syndrome, mesoderm arises from all around the blastula as usual, but is symmetrical and corresponds to that arising near the dorsal/anterior meridian of the normally specified egg or embryo with a large posterior subset of the normal pattern values thus missing. The effect is independent of any inhibition of archenteron formation or mesoderm migration (i.e. the cell mechanics of gastrulation) incurred by the treatment. It is also quite separate from a syndrome caused by more prolonged exposure to Li+ during gastrulation. A small, but distinctive, anterior pattern region is also not expressed and, anomalously in relation to their general nature, these forms differentiate considerable blood tissue. We consider the implications of some details of the pattern restriction for our understanding of interaction in the normal development and propose that the Li+ embryo is likely to be useful as a specific 'differential screen', in relation to the normal, during the search for those gene products that mediate initial regionalization of the body.

Animals↗

Pre-operative assessment of soft tissue sarcomas by computed tomography.

The current trend towards limb-sparing surgery in patients with soft tissue sarcomas has increased the need for accurate pre-operative assessment of the primary tumour. Tumour site, extent and relationship to bone and neurovascular structures determine whether adequate radical surgery is feasible or whether more limited excision as a part of multimodality treatment is appropriate. Pre-operative computed tomography (CT) was compared with operative findings in 38 patients with soft tissue sarcomas. CT prediction of muscle group involvement by tumour was correct in 95 per cent and prediction of major artery or vein invasion was correct in 92 per cent and 97 per cent respectively. Assessment of tumour relationship to major peripheral nerve was accurate for thigh sarcomas but was not possible in upper limb tumours. While CT confirmed frank bony involvement in two patients, it failed to distinguish between tumours closely adjacent to periosteum and those with periosteal invasion. Detection of residual or recurrent tumour nodules is less reliable; CT is most accurate before any surgical intervention.

Adolescent↗

Low-dose phenobarbitone as an indicator of compliance with drug therapy.

1 To assess the potential value of low-dose phenobarbitone (PB) as a marker of compliance we studied the relationship between plasma level of PB and dose (2-16 mg daily) following 3 or 4 weeks treatment in healthy volunteers (n = 26) and in-patient volunteers (n = 7). 2 Also, to simulate poor compliance, PB levels were measured in some volunteers following alternate-day (n = 6) or short-term (n = 5) treatment with similar doses. These levels, expressed as the level: dose ratios (LDRs), did not overlap with those obtained following 3 or 4 weeks of daily PB intake. 3 To evaluate the efficacy of this marker in patients taking other drugs we gave a group of out-patients (n = 24) compound tablets containing B vitamins and a small dose (16 mg) of PB; their compliance over 2-5 weeks was assessed both by measuring plasma levels of PB and residual tablet counting. 4 In the latter study, as well as providing absolute evidence of good compliance by many patients, the plasma levels of PB proved particularly valuable when non-compliant individuals 'forgot' to bring their residual tablets. 5 We suggest that phenobarbitone, in doses low enough to be non-sedative and non-enzyme inducing, is potentially useful as a pharmacological indicator of compliance with drug therapy.

Adult↗

The organization of mesodermal pattern in Xenopus laevis: experiments using a Xenopus mesoderm-inducing factor.

In this paper, we study the mechanism by which a Xenopus cell line-derived mesoderm-inducing factor (MIF) might establish the spatial pattern of cellular differentiation in the mesoderm. The effects of the factor on competent animal pole tissue are consistent with it being identical to the natural mesoderm-inducing factor. The signal can only act on those membrane domains of the animal pole that face the blastocoel, but it can be stably recorded there, such that axial mesoderm is formed, after 15 min exposure or less. This exposure can end some hours, or several cell cycles, before the onset of RNA synthesis yet nevertheless be fully effective, although competence to respond also extends well after the onset of transcription. Exposure of the entire blastocoel lining of intact embryos to MIF causes a synchronous and sudden transformation of the behaviour and adhesive properties of all inner animal cap cells. This transformation mimics and is contemporaneous with the involution behaviour of normal mesoderm in the early gastrula marginal zone. Although high concentrations of MIF totally disorganize gastrulation, lower concentrations permit gastrulation to proceed. However, the pattern of mesoderm in these embryos is disrupted and ectopic mesoderm is formed around the blastocoel remnant. When MIF is injected directly into blastomeres, rather than into the blastocoel, it has no effect. This suggests that the molecule is secreted from source cells and affects target cells through an extracellular receptor. Finally, we show that small pieces of animal pole tissue recently exposed to MIF go on to produce morphogenetic signals perhaps distinct from MIF. We discuss the role of these signals in establishing and modifying the spatial pattern of cellular differentiation in the mesoderm of Xenopus.

Animals↗

The midblastula cell cycle transition and the character of mesoderm in u.v.-induced nonaxial Xenopus development.

Xenopus embryos (UV embryos) resulting from u.v. (254 nm) irradiation to the vegetal egg hemisphere and thus developing little or no axial pattern (UV5-Scharf & Gerhart, 1983), have been compared histologically with synchronous normal siblings at each of three stages. In addition, the relative amounts of blood-forming tissue produced in normal and in UV embryos have been studied by Western blotting total protein from larval stages and by immunofluorescence on sections. The observations on midblastulae (around 5000 cells) were aimed at detecting any systematic retardation, due to u.v., of the slowing of the cell cycle that normally commences at the 2-4000 cell stage and makes possible zygotic transcription and the preparation for gastrulation. No such retardation was apparent. Observations on postgastrular stages gave an assessment of the size and character of the population of mesoderm founder cells, in relation to the control, for embryos visibly undergoing entirely nonaxial development. Little deficit in total mesodermal cell number was found, though the entire mesoderm adopted the histological character proper to only some 40% of that in the normal pattern i.e. trunk lateral plate. Blood-forming capacity appears to be enhanced out of all proportion to the size of the mesoderm as a whole. The results are discussed in terms of the probable nature of the primary positional system for axial pattern and the later mechanisms of mesodermal patterning.

Animals↗

Dynamics of the control of body pattern in the development of Xenopus laevis. IV. Timing and pattern in the development of twinned bodies after reorientation of eggs in gravity.

The mesendodermal anatomy of twinned larval axes is described in relation to the normal single pattern, when twinning has been caused by experimental tilting of eggs before first cleavage. The formation of two origins for gastrulation movements (dorsal lips) and their relatively rapid spread and coalescence to give a circular blastopore, is a predictor of twin formation in individual embryos after treatment. The anatomy of twins where development has been disturbed from the outset in this way is appreciably different from that induced by the later operation of second dorsal lip implantation. It is also variable in a systematic way. The total sizes of cellular allocations to individual notochords and prechordal head patterns are enhanced above normal if they arise relatively close together in the tissue, but significantly reduced if they arise far apart. These and other features of twinned patterns due to precleavage disturbance are discussed in terms of what they might indicate about the physicochemical nature of the body positional system. The results confirm that by a variety of rather simple, nonsurgical manipulations the relative amounts of territory in the egg devoted to different parts of the body can be greatly influenced.

Animals↗

Doctors' unawareness of the drugs their patients are taking: a major cause of overprescribing?

We studied the accuracy of both hospital and general practitioners' records of current drug treatment in consecutive patients who attended a general medical review clinic. Either the hospital or the general practitioner's records (obtained in a questionnaire), or both, were inaccurate for over 70% of 59 patients interviewed with their medicine. Most of the errors were due to patients taking drugs in addition to those shown in their records. Some of these were inappropriate, and many seemed unnecessary. It appears that neither hospital doctors nor general practitioners are fully aware which drugs their patients are taking, and this may contribute to overprescribing. We believe that considerable financial savings might be made if patients brought all their medicines to every consultation.

Awareness↗