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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 19 recordsLinked to original sources
PubMed1992

Management of elderly patients with sustained hypertension.

OBJECTIVE: To assess the clinical benefits of treating hypertension in elderly patients and to derive practical guidelines regarding indications, goals, and forms of treatment. DESIGN: Review of six published randomised trials. RESULTS: Active treatment of hypertension in elderly patients was associated with significant improvements in several indices of cardiovascular morbidity and mortality, particularly the incidence of fatal and non-fatal strokes. On the basis of the trial data, combined systolic and diastolic hypertension was defined as a sustained systolic pressure greater than 160 mmHg and diastolic pressure greater than 90 mmHg. There is convincing evidence that efforts should be made to reduce both systolic and diastolic pressures to below these levels in patients up to the age of 80 years. Isolated systolic hypertension was defined as a systolic pressure greater than 160 mmHg in the presence of a diastolic pressure less than 90 mmHg. Two trials reported benefit from the treatment of isolated systolic hypertension in patients up to the age of 80, and further trials are underway to support or refute this recommendation. Diuretics have an established role in the management of hypertension in elderly patients; beta adrenoceptor antagonists have given variable results, and the benefits are less impressive than with diuretic based regimens. Newer agents show promise in the treatment of elderly patients, particularly in the presence of coexisting disease, but their effects on morbidity and mortality have not been evaluated in large randomised trials. CONCLUSIONS: Diuretics rather than beta blockers are the treatment of choice for patients with uncomplicated hypertension, but combinations of drugs may be required in as many as 50% of patients.

Adrenergic beta-Antagonists↗
PubMed1992

MHC-binding peptides for immunotherapy of experimental autoimmune disease.

It is now well accepted that T helper cells play a central role in the induction and maintenance of autoimmune disease. Many experimental models have emphasized this fact and have illustrated the efficacy of therapeutic strategies aimed at disrupting T cell recognition of autoantigens. Antibodies directed at either class II proteins of the major histocompatibility complex (MHC) or CD4 accessory molecules have been universally successful. However, the potential use of antibodies for therapy in humans is complicated by host anti-globulin and anti-idiotype responses. An alternative approach to anti-MHC blockade with antibodies is peptide blockade of MHC molecules. In addition, peptides may be used as agonists of autoantigens in order to modulate the autoimmune response. The use of synthetic peptides for therapy is an innovative yet relatively unexplored approach and will be the subject for discussion in this article.

Amino Acid Sequence↗
PubMed1992

The differential staining pattern of the X chromosome in the embryonic and extraembryonic tissues of postimplantation homozygous tetraploid mouse embryos.

(C57BL x CBA)F1 hybrid female mice were mated with hemizygous Rb(X.2)2Ad males to distinguish the paternal X chromosome. Homozygous tetraploids were produced by blastomere fusion at the 2-cell stage, and 161 of these were transferred to recipients and analysed on the 10th day of gestation. 59 implants contained resorptions and 76 contained either an embryo and/or extraembryonic membranes. 38 (20, XXXX and 18, XXYY) were analysed to investigate their X-inactivation pattern. Embryonic and yolk sac endodermally- and mesodermally-derived samples were analysed by G-banding and by Kanda analysis. In the XX and XY controls, the predicted pattern of X-inactivation was observed, though 12.2% of metaphases in the XX series displayed no X-inactivation. In the XY series the Y chromosome was seen in a high proportion of metaphases. In the XXXX tetraploids, 8 cell lineages were recognized with regard to their X-inactivation pattern, though most belonged to the following 3 categories: (XmXm)XpXp, Xm(XmXp)Xp and XmXm(XpXp). The other categories were only rarely encountered. In the embryonic and mesodermally-derived tissue the ratio of these groups was close to 1:2:1, whereas in the endodermally-derived tissue it was 1:4.11:4.88, due to preferential paternal X-inactivation. A significant but small proportion of all 3 tissues analysed displayed no evidence of X-inactivation. Indirect evidence suggests that this represents a genuine group because of the high efficiency of the Kanda staining. The presence of the Xm(XmXp)Xp category is consistent with the expectation that X-inactivation occurs randomly in 2 of the 4 X chromosomes present. The presence of small numbers of preparations with no evidence of X-inactivation and other unexpected categories suggests that these are probably selected against during development.

Animals↗
PubMed1992

Electrofusion of mouse embryos results in uniform tetraploidy and not tetraploid/diploid mosaicism.

Some previous attempts to produce tetraploids experimentally have resulted in a proportion of treated embryos becoming 2n/4n mosaics at a frequency which may be as high as 20%, when using cytochalasin B as a fusigenic stimulus and cytogenetic techniques to identify putative tetraploid embryos. To investigate the possible occurrence of 4n/2n mosaicism, tetraploid embryos were produced by electrofusion, a process which allows adjacent blastomeres at the 2-cell stage to fuse following exposure to electric field pulses. Embryos used for electrofusion were hemizygous for a transgene consisting of approximately 1000 copies of the mouse beta-globin gene. After in situ hybridization, one hybridization signal is expected per diploid genome. Tetraploid cells in 7.5-, 8.5-, 9.5- and 10.5-day-old conceptuses were distinguished from diploid cells by performing in situ hybridization on histological sections. The frequency of nuclei with two hybridization signals in the 'hemizygous' tetraploid embryos was compared to diploid embryos which were either hemizygous or homozygous for the beta-globin transgene. Comparison of the frequency of nuclei with two hybridization signals between tissues of 'hemizygous' tetraploid conceptuses and homozygous diploid conceptuses showed no significant difference, which implies that the tissues in the tetraploid conceptuses were uniformly tetraploid. No evidence was found to suggest that electrofusion results in 2n/4n mosaicism.

Animals↗
PubMed1992

Monte Carlo modelling of the performance of a rotating slit-collimator for improved planar gamma-camera imaging.

Planar imaging with a gamma camera is currently limited by the performance of the collimator. Spatial resolution and sensitivity trade off against each other; it is not possible with conventional parallel-hole collimation to have high geometric sensitivity and at the same time excellent spatial resolution unless field-of-view is sacrificed by using fan- or cone-beam collimators. We propose a rotating slit-collimator which collects one-dimensional projections from which the planar image may be reconstructed by the theory of computed tomography. The performance of such a collimator is modelled by Monte Carlo methods and images are reconstructed by a convolution and backprojection technique. The performance is compared with that of a conventional parallel-hole collimator and it is shown that higher spatial resolution with increased sensitivity is possible with the slit-collimator. For a point source a spatial resolution of some 6 mm at a distance of 100 mm from the collimator with a x7 sensitivity compared with a parallel-hole collimator was achieved. Applications to bone scintigraphy are modelled and an improved performance in hot-spot imaging is demonstrated. The expected performance in cold-spot imaging is analytically investigated. The slit-collimator is not expected to improve cold-spot imaging. Practical design considerations are discussed.

Equipment Design↗
PubMed1992

Optimization by simulated annealing of three-dimensional, conformal treatment planning for radiation fields defined by a multileaf collimator: II. Inclusion of two-dimensional modulation of the x-ray intensity.

Interest is rapidly growing in using multiple x-radiation fields defined by a multileaf collimator to achieve conformal radiotherapy. Three-dimensional treatment planning in such situations is in its infancy and most 3D planning systems provide no tools for optimizing therapy. A previous paper addressed how to calculate optimum beamweights when both the target volume and all or some parts of organs at risk were in the fields-of-view. This work allowed a maximum of two weights per field. The present paper extends this technique to allow each radiation port to be spatially modulated across the geometrically shaped field. An optimization method based on simulated annealing is presented. It is shown that including spatial modulation leads to a wider separation between the dose-volume histograms of the target volume and organs at risk. The improvement is quantified in terms of the tumour control probability at constant normal tissue complication probability. Possible limitations of the a posteriori applied biological model are discussed in detail.

Humans↗
PubMed1992

A survey of infertility, surgical sterility and associated reproductive disability in Perth, Western Australia.

Infertility, surgical sterility and associated reproductive disability were studied in a stratified cluster sample of 1,511 couples with women aged 16 to 44 years resident in metropolitan Perth in 1988. Sixteen couples were omitted from analysis because of missing data. The proportion of couples affected by current infertility was 3.5 per cent (53 of 1,495), and 67.9 per cent of these (36 of 53) had a reproductive disability, meaning that they were unable to achieve their desired level of reproductive function. Those affected by surgical sterility accounted for 37.1 per cent (555 of 1,495), and of these couples 2.0 per cent (11 of 555) had a reproductive disability. Empirically, the prevalence of both infertility and reproductive disability peaked at ages 30 to 34 years in the female partner. Of the factors studied, infertility was associated with surgery for a ruptured appendix, a history of pelvic inflammatory disease and number of sexual partners. In 10 of the 47 couples with reproductive disability, contraceptive sterilisation had been a cause of later regret. Most other cases were due to infertility. Almost one half of couples with reproductive disability had sought treatment. The affected couples had at least one child from the current union in 23 of the 47 cases of reproductive disability. The results support the need for development of a strategy to prevent infertility and other causes of reproductive disability.

Adolescent↗
PubMed1992

A survey of contraceptive use and unplanned pregnancy in Perth, Western Australia.

Contraceptive use and unplanned pregnancy were studied in a stratified cluster sample of 1,511 couples with women aged 16 to 44 years resident in metropolitan Perth in 1988. Twenty-one couples were excluded from analysis owing to missing data. The proportion of couples using contraception was 76.8 per cent (1,144 of 1,490), and all but three of the remaining couples gave a reason for nonuse. Among users, surgical sterilisation made up 42.3 per cent (484 of 1,144) of all methods, with a slight predominance of tubal ligation over vasectomy. Oral contraceptives accounted for just over half of nonsurgical methods. Comparisons with a Victorian survey performed in 1978 suggested that surgical methods and condom use may have increased, whereas use of oral contraceptives and intrauterine devices may have fallen. Unplanned pregnancies conceived during the 12 months before the interview affected 3.4 per cent (51 of 1,490) of respondents. The incidence of unplanned pregnancy was four times higher in couples with inconsistent usage patterns of contraception.

Adolescent↗
PubMed1992

Increased lung endothelin-1 production in rats with idiopathic pulmonary hypertension.

The role of endogenous circulating or locally produced endothelin-1 (ET-1) in pulmonary hypertensive states is unknown. To investigate this we measured ET-1 levels and preproendothelin-1 (prepro-ET-1) mRNA expression at various ages in control Sprague-Dawley (SDR) rats and in fawn-hooded rats (FHR), a strain which develops idiopathic pulmonary hypertension. Although serum ET-1 levels were similar in SDR and FHR, we found twofold increases in FHR whole lung homogenate ET-1 levels by radioimmunoassay. Coexisting threefold increases in preproET-1 mRNA expression were found in FHR lungs by densitometric analysis of Northern blots and by filter hybridization, suggesting the increase in lung ET-1 was due to enhanced intrapulmonary production of the peptide. To test whether the increase in lung preproET-1 mRNA was primary or secondary to established pulmonary hypertension, we compared preproET-1 mRNA expression prior to development of pulmonary hypertension in fetal (19 day gestation) and neonatal (5 day old) FHR and SDR. Despite similar right ventricular size in SDR and FHR, preproET-1 mRNA was already elevated in neonatal FHR lungs. Furthermore, we found no increase in lung preproET-1 mRNA or ET-1 levels in adult SDR with an equivalent degree of pulmonary hypertension due to chronic hypoxia, implying that the increases in ET-1 production in FHR were not a common consequence of all pulmonary hypertensive states. The functional significance of these observations remains unclear but raises the possibility of a role for ET-1 in the pathophysiology of pulmonary hypertension in the FHR.

Animals↗
PubMed1992

Factors influencing the idiopathic development of pulmonary hypertension in the fawn hooded rat.

Fawn hooded rats (FHR), a strain of rat with a hereditary bleeding tendency due to a genetic defect in platelet aggregation, have recently been found to develop pulmonary hypertension. However, whether the pulmonary hypertension in FHR has a genetic basis or simply reflects the influence of extrinsic factors known to increase pulmonary artery pressure in other rat strains has not been fully evaluated. To further examine the structural and hemodynamic changes of pulmonary hypertension in FHR, and to investigate the extent to which alveolar hypoxia may have promoted these abnormalities, hemodynamic and morphometric measurements were made in FHR (4 to 24 wk) and compared with age-matched Sprague-Dawley (SDR) control rats. Increases in mean pulmonary artery pressure, total pulmonary resistance, and right ventricular enlargement were present in both male and female FHR and were evident at an early age (4 wk). Morphometric analysis of barium gelatin-infused lungs revealed marked pulmonary vascular remodelling in FHR characterized as extension of muscle into more peripheral pulmonary vessels, medial hypertrophy of proximal vessels, and reduced number of barium-filled arteries. The increases in pulmonary artery pressure in FHR were not due to the influence of more severe hypoxia, hypoventilation, or polycythemia, as blood gas tension and hematocrit were similar in FHR and SDR. Moreover, we found that pulmonary hypertension could be transmitted to backcross and second filial generation offspring arising from selective matings between FHR and control Wistar Kyoto rats, confirming the heritable basis for pulmonary hypertension in the FHR.

Animals↗
PubMed1992

Case reviews in the family physician's office.

The majority of patients with emotional or psychiatric disorders are treated in the primary care setting without psychiatric input. Psychiatrists need to find ways of helping family physicians manage these patients without necessarily taking over their care. One way of achieving this is for a psychiatric consultant to visit the family physician's office on a regular basis to discuss the physician's problem cases. This paper describes such a pilot project, outlines the kinds of problems family physicians discussed and recommendations that were made, and discusses the benefits of this collaborative approach.

Community Mental Health Centers↗
PubMed1992

Historical experiments predating commercially available computed tomography.

Computed tomography (CT) was a revolution in radiology. Commercially available CT scanners appeared in 1972, a joint effort between the EMI Company, Atkinson Morley's Hospital, London and the Department of Health and Social Security (DHSS). The name of Sir Godfrey Hounsfield will always be associated with these developments. Like most developments in science the breakthrough came by standing on the shoulders of giants and many experiments can, with the curious wisdom of hindsight, be considered precursors to CT. Gabriel Frank's patent in 1940 showed apparatus for back-projection CT and Takahashi developed equipment in the 1940s for reconstructing from a sinogram; in both cases using an optical "computer". A medical CT scanner was reportedly constructed in 1957 in Kiev. Transmission CT was performed by Kuhl in 1965. Cormack built an experimental scanner in 1963. Oldendorf identified what was needed for successful CT as early as 1960. Throughout the 1960s a host of independent workers were busy on the mathematical problems of reconstructing from projections with both medical scanning and non-medical applications in mind. Experiments in early emission tomography influenced the development of CT. With imagination one can even see how close "classical" tomography, as started even before 1920, came to the realization of CT. The pioneering British radiographer Watson stands out from a galaxy of inventors. The lecture at Radiology and Oncology '91 in Brighton was a thumbnail sketch of the origins of radiological CT. A fuller story is told elsewhere (Webb, 1990).

History, 20th Century↗
PubMed1992

Testing for creatine kinase and creatine kinase-2 in Ontario: reference ranges and assay types.

In 1991, 246 and 136 Ontario laboratories performed total creatine kinase (CK; EC 2.7.3.2) and creatine kinase-2 (CK-2) assays, respectively. A questionnaire mailed to these laboratories requested information about the types of assay used, the origin of their reference ranges, and the source of their instruments and reagents. All laboratories used current test formulations for CK, although seven laboratories did not assay at 37 degrees C. For CK, 69% of all laboratories reported different upper reference limits for men and women (5th-95th percentiles: 160-250 and 115-215 U/L, respectively); 31% reported similar ranges for both sexes. Fifty-six percent derived their own ranges; the remainder used either kit inserts or literature references, and nearly 60% of this latter group claimed to have validated these suggested ranges before use. For 6% of all laboratories, their pediatric ranges were similar to their adult ranges. For CK-2, only 32% used their own reference range; the remainder used kit inserts or literature references, but only 49% of this group validated these ranges before use. Reference limits (5th-95th percentiles) for CK-2 were as follows: activity 6-24 U/L; fraction of CK, 0.022-0.06; and, for mass assays, 5-10 micrograms/L and relative index 0.015-0.04.

Creatine Kinase↗