This thesis explores the role of technology as a resource in the structure of medical domination of birth and death, stressing technology's pivotal position at the intersection of control and uncertainty. Based in Intensive Care and Obstetrics (between which the health status of patients diverges sharply), it notes the convergence of technology used and examines the contest for control within the labour process. This includes using technology to facilitate a 'standardized' birth or death; a more retrospectively defensible event. In general, the 'burden of proof' is concluded to lie with those wishing not to intervene rather than the reverse. Given the (cognitively male) biomedical model, mind-body dualism is an assumption embedded in medical technology: this is especially significant in childbirth, where it fractures the woman's ontological experience of giving birth. Its positivistic and pathological emphasis is associated with a reification of processes and a commodification of their 'solution': which becomes located in technology. It is argued that commodification in health provision will increase with the further application of market principles to the NHS. It is concluded that 'uncertainty', endemic to medicine and a possible challenge to control, is proactively manipulated and pressed into the service of medical domination. Technology is used to mask uncertainty and aid the medical profession's control of patients/relatives, and subordinate work groups. A technological fix may be viewed as the opposite to re-discovering societal dreams and myths, however, more paradoxically, it is concluded that dreams and myths have become attached to technology. Thus, the symbolic role of technology is: to provide hope of continued survival (or cure), the veiling of existential uncertainty and the offer of 'absolution' - should all efforts fail (a freedom from guilt in the assurance that "everything possible was tried"). Its 'heroic' project is viewed as an existentially 'masculine' health provision and 'feminized' health care is posited as an alternative.

The overall aim of the project was to investigate the role of the cell membrane as a barrier and/or target for drug action and relate this to the development of strategies for overcoming multiple drug resistance (MDR). The effects of doxorubicin on various bacterial strains expressing different levels of anionic phospholipid were compared. Giowth of wild-type Echerichia coli (E. coli) strain MRE600 was severely affected up to 9 hours following doxorubicin treatment (15uM), but resistance occurred after 9 hours. E. coli strain FIDL1 1 was resistant to doxorubicin (1 O0piM) over 9 hours, however, increasing the anionic lipid content showed little difference in sensitivity. The mouse mammary tumour cell line (EMT6-S) and MDR sub-line (EMT6-R) were characterised with regard to growth kinetics, susceptibility to doxorubicin and membrane lipid composition. The log phase doubling times (h) were found to be 21.8 (EMT6-S)and 25.0 (EMT6-R) and the IC 50 values for doxorubicin to be 2.2 x 10-8 M and 1.8 x 10-6 M for EMT6-S and EMT6-R cells, respectively. No difference was observed between the phospholipid profiles of the two cell lines and total fatty acid composition was similar, however, the level of linoleic acid appeared to be higher in the resistant cells. The photocytotoxicity of the cationic dyes methylene blue (MB), toluidine blue (TBO) and Victoria blue BO (VBBO) against the EMT6 cell lines was compared to the cyotoxic effect of doxorubicin and cis-platinurn. The cytotoxic effect of VBBO was enhanced 10-fold by illumination (7.2 J cm2) in both EMT6-S and EMT6-R cells. In order to overcome resistance, however, the EMT6-R cells required a 10-fold greater level of the dye than the parental cells to reach an IC50 value. By contrast, doxorubicin required almost a 100-fold increase in concentration to overcome this resistance. Pre-treatment of EMT6-S and EMT6-R cells with low concentrations of VBBO resulted in a 2-fold increase in doxorubicin toxicity in both cell lines. Pre-treatment with MB and TBO resulted in a 1.4-fold and 2-fold increase in doxorubicin toxicity, respectively, in the sensitive cells, increasing to 2-fold and 3-fold, respectively in the resistant cells. Glutathione (GSH) depletion of EMT6-S and EMT6-R cells did not enhance the photocytotoxicity of VBBO, suggesting that the primary site of action of VBBO is at an intracellular site not protected by GSH or that the mechanism of action is not via the in situ generation of singlet oxygen. Addition of the chemosensitizer, verapamil (7gM), increased the efficacy of doxorubicin by 2-fold in EMT6-S cells and by 18-fold in EMT6-R cells. By contrast, the presence of verapamil did not increase the cytotoxicity of YBBO in either cell line. A series of compounds, PVB, MVB and MOVB, based on the skeleton of VBBO was examined. VBBO was found to be the most effective photosensitizer. The rate of uptake for VBBO, MVB and PVB appeared to be very similar, whereas that of MOVB was slower. The uptake/dose trend was also similar four all four drugs tested and conelated to the levels of lipophilicity of the agents. Confocal microscopy studies showed all the photosensitizers to be distributed widely throughout the cytoplasm, with considerable accumulation of VBBO and PVB in the perinuclear region. Time course studies showed the intracellular distribution of VBBO in both cell lines to be similar, although uptake of the drug appeared slower in the resistant cell line. VBBO was clearly localised throughout the cytoplasm, in a punctate pattern, which may be consistent with the widespread distribution of mitochondria. No interaction with the plasma membrane was evident. By contrast, doxorubicin was found to localise mainly in the nucleus of the sensitive cell line, whereas no nuclear involvement was seen in the resistant cells. The drug was also effluxed more rapidly from EMT6-R cells than EMT6-S cells. Time course studies with EMT6-S cells showed that the drug clearly interacts with both the plasma membrane and the nucleus. These results indicate that the main modes of action for the two drugs differ markedly, suggesting interaction with both the membrane and the nucleus in the case of doxorubicin, but possibly mitochondrial involvement for VBBO.

We do not known the optimum amount of physiotherapy for individual patients and recent trials have been inconclusive. We conducted an individual-patient-data meta-analysis of trials testing increased levels of physiotherapy input. Results: We incorporated 9 trials (951 subjects). We found no statistically significant differences between patients receiving intensive or standard amounts of physiotherapy, in terms of overall disability or overall impairment scores, length of hospital stay or survival. Secondary analyses showed improvements on Motricity Index scores for the upper limbs (5.2 units, 95% CI 1.5 to 8.8, P=0.0058) and lower limbs (6.8 units, 95% CI 2.2-11.4, P=0.0042), Improvements were also seen in Action Research Arm Test scores (1.8 units, 95% CI – 1.2 to 4.8, P=0.25) in younger patients (under 70 years) and those with higher baseline Barthel scores, and in recovery of walking speed (increase of 0.0.56 m/s, 95% CI -0.018 to 0.130, P=0.14) (when the target of treatment was lower limb or gait focused). There was no significant difference in change in ADL (measured by BI (7 trials)) between the groups (0.15 units of change in BI, 95% CI -0.38 to 0.67, P=0.58). There were increased odds of a “good recovery” i.e. (improvement of 6 points or up to the maximum of 20 / 20 on BI), (odds ratio 1.33; 0.96 – 1.85; P=0.09) and of “excellent recovery” (> 8 points or up to the maximum on BI), (odds ratio 1.47; 1.03 – 2.05; P=0.04) in the augmented group. The higher contrast trials in our study (typically 15 – 44 hrs additional physiotherapy, with earlier onset at 7-10 days after admission, higher daily contrast and longer duration) are more likely to show treatment effects than lower contrast trials, with respect to impairment measured by the Motricity index and disability measured by the BI.

Sensitive and selective methods were applied to the analysis of two batches of bottled wines. The relationship between the antioxidant activity, based on the reduction in Fremy's radical, vasodilation activity (batch 1 only), and phenolic content was investigated. Wines were selected to provide a range of origins, grape varieties and vinification methods. Batch 1 wines were sourced mainly from the Old World, while those in batch II were predominantly from the New World. The total phenolic content was determined by the Folin-Ciocalteu colorimetric assay and by the cumulative measurements obtained by HPLC. Total anthocyanins were determined using a spectral assay. While the wines exhibited a wide range in values in all parameters, with both batches the total phenol content, determined by both the Folin-Ciocalteu assay and HPLC, was very closely correlated with the ESR-derived antioxidant activity. Likewise a strong correlation was noted between the phenolic content and the vasodilation activity of Batch I wines. The antioxidant activity of Batch I wines was significantly correlated with the gallic acid, total stilbene and total flavin-3-ol content. Similarly with Batch II wines, gallic acid and total flavan-3-ols, along with polymeric pigments were significantly correlated with the ESR-derived antioxidant activity. Batch I and II had significantly different phenolic profiles though in both cases the flavin-3-ols and anthocyanins were quantitatively the major skin-derived phenolics present. However, in thirteen of the sixteen Batch I wines the major phenolics present were the flavin-3-ols compared with only five of the twenty-two Batch II wines. This discrepancy may be attributed to the viticultural practices of the Southern Hemisphere where many of these wines originated.

I have studied the GNB3 gene as a candidate gene for hypertension and left ventricular mass in a systematic and comprehensive manner. I have carried out association studies in three independent populations - A case-control study with well characterised hypertensive and their matched controls; a twin study looking at echocardiographic LV mass; and a large family based study analysing blood pressure and ECG LV mass. In addition I have also looked at three additional candidate genes including ACE, aldosterone synthase and beta-1 adrenoceptor. Though these studies concluded that there was no association between the C825T polymorphism and blood pressure or LV mass, I have demonstrated a significant heritability of various electrocardiographic measures of LV mass and an interaction between GNB3, ACE and SF1 explaining the variability of continuous measures of LV mass in this population. I studied the functional aspects of the GNB3 polymorphism by measuring platelet aggregation in normal human volunteers, using it as a marker of G-protein related signal transduction. However, there was also no association between epinephrine or platelet activating factor induced platelet aggregation and the GNB3 genotype. Finally, I performed molecular studies using cells transfected with b3 (wild-type) and b3-s (splice-variant) of GNB3 along with a fusion construct of a2AGi, and measuring of GTPase activity and calcium signalling. There was no significant difference between b3 or b3-s transfected cells, in terms of epinephrine stimulated GTPase activity, onset-delay of calcium release and time-to-peak of calcium signal. However, cells expressing b3-s showed a significantly lower rate of calcium release compared to cells expressing b3. These results indicate that the G protein b3-s subunit has no functional difference or possible slightly reduced effect compared to the wild type.

Diss.--Marburg. / Bibliography: p. 165-174.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 196-220).

Zugl.: Freiburg (Breisgau), Univ., Lizentiatsarb.

Stuttgart, Univ., Fakultät Informatik, Diplomarb., 1998.

Thesis (Ph. D.--Music--University of California, San Diego, 1997. / Vita. "The complete script of And wolf shall inherit the moon and a comprehensive collection of chants written by Wolf Project members are included as appendices."--P. xiv. Includes ninth draft of And wolf shall inherit the moon (leaves 403-446). Includes bibliographical references (leaves 498-501). Includes selected bibliography and works list for R. Murray Schafer (leaves 502-512).