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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 253 records · Page 14Linked to original sources
PubMed1998

Primary care. LIZ (London Initiative Zone): a legacy for London.

More than half the LIZ funding has been spent on improving GP premises and practice staffing. But many premises are still below standard. The programme has had no effect on reducing the number of GPs over 65 working in London. In some areas of London the proportion has increased. Almost half (46 per cent) of practices in London still consist of a doctor working alone. Nationally, the figure is 30 per cent. London GPs' lists are significantly higher than in the rest of the country. Further improvements in London's primary care are vital.

Age Distribution↗
PubMed1998

The impact of reference pricing on clinical lipid control.

AIM: Reference pricing has recently been introduced into New Zealand in an attempt to curb rising pharmaceutical costs. Although budget savings may be significant, the resulting alteration of established drug prescriptions has the potential to cause harm. We undertook to assess the impact of these changes in patients switching from simvastatin to fluvastatin following the introduction of reference-based pricing in New Zealand. METHODS: The fasting lipid profiles of 262 patients in a defined geographic region were obtained after at least six weeks of fluvastatin therapy. These were compared to mean lipid levels obtained from laboratory databases for the patients while previously receiving simvastatin. RESULTS: There was a significant increase in total cholesterol, LDL cholesterol and triglyceride levels (p < 0.01). The elevation was less pronounced where higher incremental doses of fluvastatin were used, although still significant for LDL cholesterol and total cholesterol (p < 0.01). Those receiving maximal therapy with fluvastatin experienced similar elevations in lipid as did those on lower doses. CONCLUSION: The lipid elevations seen in this audit relate both to the lesser potency of fluvastatin and underdosing. In this high risk population, significant lipid elevations may conceivably produce an excess of vascular events. The responsibility to the taxpayer should be weighed carefully against the ethical responsibility to the individual patient and the potential to do harm. Subtherapeutic treatment may prove more costly than all the savings from reference pricing.

Drug Utilization↗
PubMed1998

Negative regulation of T cell antigen receptor signal transduction by hematopoietic tyrosine phosphatase (HePTP).

The hematopoietic tyrosine phosphatase (HePTP) is predominantly expressed in thymocytes and T lymphocytes and at lower levels in other hematopoietic cells. Expression of the gene is enhanced by the T cell growth factor interleukin-2, suggesting a role for HePTP in T cell proliferation or differentiation. We report that HePTP blocks T cell antigen receptor (TCR)-induced transcriptional activation of a reporter gene driven by a nuclear factor of activated T cells(NFAT)/AP-1 element taken from the interleukin-2 gene promoter. This effect was specific to HePTP and was abolished by a mutation (C270S) that impaired its phosphatase activity. Co-expression of HePTP also reduced TCR-induced activation of the mitogen-activated protein kinase Erk2 and the TCR-induced appearance of phosphorylated Erk. In contrast, HePTP did not affect the activation of the N-terminal c-Jun kinase, Jnk. Together these findings suggest that HePTP plays an active negative role in TCR signaling by dephosphorylating one or several signaling molecules between the receptor and the mitogen-activated protein kinase pathway.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Hospitals. Close call.

Health authorities and trusts need to listen hard to positive offers of help from the community to maintain services such as cottage hospitals. The determination of the local action group should be assessed early on, with a view to potential collaboration. The HA can take control by establishing a joint working group and funding an external consultant. The process can help restore community support for local health services.

Community Health Planning↗
PubMed1998

Reproductive factors and breast cancer in New Zealand.

A national population-based case-control study was used to assess the influence on breast cancer risk of reproductive factors and the possibility of an interaction with age at diagnosis. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. There was a declining risk of breast cancer with increasing age at menarche (p = 0.06), the strongest effect being seen in women aged less than 40. Parous women had a 27% lower risk of breast cancer than nulliparous women, a reduced risk being evident in all but the youngest age group. A falling risk of breast cancer with rising parity was clear only in women diagnosed when aged at least 45 years. Breast cancer risk tended to fall amongst parous women with increasing duration of breastfeeding (p = 0.14); the association was most apparent in the youngest women, while those over 40 years at diagnosis showed no clear negative trend. There was no association of breast cancer risk with age at first full-term pregnancy, time since last full-term pregnancy, abortion (spontaneous or induced), abortion before first full-term pregnancy, or ability to conceive, and there was no trend in risk with age at natural menopause. Women in the highest category of body mass index at age 20 had the lowest risk of breast cancer in the age group studied. When each reproductive factor was formally tested for effect modification by age at diagnosis, the interaction term in logistic models approached statistical significance only for parity (p = 0.07).

Adult↗
PubMed1998

Modification of phosphatidylinositol 3-kinase SH2 domain binding properties by Abl- or Lck-mediated tyrosine phosphorylation at Tyr-688.

In cells expressing the oncogenic Bcr-Abl tyrosine kinase, the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells, and by endogenous kinases in transfected Jurkat T cells upon triggering of their T cell antigen receptor. Using these systems, we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85. This provides an additional candidate to the list of SH2 domains regulated by tyrosine phosphorylation and may explain why association of phosphatidylinositol 3-kinase with some cellular ligands is transient or of lower stoichiometry than anticipated.

Fusion Proteins, bcr-abl↗
PubMed1998

School performance in adolescent Jamaican girls: associations with health, social and behavioural characteristics, and risk factors for dropout.

Health, nutrition and behavioural determinants of school achievement, attendance and dropout were examined in 452 girls aged 13-14 years, randomly selected from grade 8 in nine schools in inner-city Kingston, Jamaica. Girls who were anaemic, sexually active or aggressive had worse achievement levels. Better achievement levels were associated with possession of school materials and access to reading material outside of school. Poor attendance, early sexual activity, and not living with both parents predicted school dropout in the subsequent year. Strategies to reduce anaemia, to improve sex education and reduce the levels of aggression may benefit school performance.

Achievement↗
PubMed1998

Respiratory arrest following intrathecal injection of sufentanil and bupivacaine in a parturient.

PURPOSE: To present a case of respiratory arrest following the use of intrathecal sufentanil and bupivacaine for combined spinal-epidural anaesthesia in a healthy labouring parturient. CLINICAL FEATURES: A 20-yr-old term parturient received 10 micrograms sufentanil and 2.5 mg bupivacaine intrathecally as part of a combined spinal-epidural technique for labour analgesia. She had received no previous analgesics. Twenty-three minutes after the intrathecal injection she became unresponsive and suffered a respiratory arrest. Resuscitation included manual bag/mask ventilation with oxygen and intravenous naloxone. CONCLUSION: Respiratory arrest is a rare but potentially life-threatening complication associated with the use of intrathecal opioids for labour analgesia. Vigilance in post-procedure patient monitoring is imperative.

Adult↗
PubMed1998

Endothelial sodding of the Permaflow prosthetic coronary artery bypass conduit.

BACKGROUND: Experiments were designed to determine the feasibility of sodding an endothelial monolayer within the lumen of a prosthetic conduit applied to the canine coronary circulation. METHODS: Autologous endothelial cells were sodded onto the luminal surface of the Permaflow conduit and immediately implanted to bypass the left circumflex coronary artery in adult mongrel dogs (n = 9). Unsodded Permaflow conduits were implanted as controls (n = 8). At 3 weeks, grafts were explanted and examined by scanning electron microscopy and immunostained for canine von Willebrand factor. RESULTS: Sodded grafts contained a confluent endothelial cell layer devoid of adherent thrombus or platelets and stained positively for canine von Willebrand factor. Unsodded grafts contained no endothelium and retained adherent platelets, collagen, and fibrin. Effluent from sodded grafts stimulated with calcium ionophore A23187 caused a significantly greater relaxation of its bioassay ring than effluent from unsodded grafts (60%+/-21% versus 12%+/-5%; n = 8, p < 0.03). CONCLUSIONS: Sodding of endothelial cells onto a Permaflow coronary artery bypass graft results in a confluent, viable, nonthrombogenic, endothelial monolayer and releases vasodilator substances in response to calcium ionophore A23187. Endothelial sodding may optimize prosthetic grafts.

Animals↗
PubMed1998

Prefrontal involvement in "temporal bridging" and timing movement.

Brain activity exclusively related to a temporal delay has rarely been investigated using modern brain imaging. In this study we exploited the temporal resolution of functional magnetic resonance imaging (fMRI) to characterise, by sinusoidal regression analysis, differential neuroactivation patterns induced in healthy subjects by two sensorimotor synchronization tasks different in their premovement delay of either 0.6 s or 5 s. The short event rate condition required rhythmic tapping, while the long event rate condition required timing of intermittent movements. Left rostral prefrontal cortex, medial frontal cortex, SMA and supramarginal gyrus demonstrated increased MR signal intensity during low frequency synchronization, suggesting that these brain regions form a distributed neural network for cognitive time management processes, such as time estimation and motor output timing. Medial frontal cortex showed a biphasic pattern of response during both synchronization conditions, presumably reflecting frequency-independent motor output related attention. As predicted, sensorimotor and visual association areas demonstrated increased MR signal intensity during high frequency synchronization.

Adult↗