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Biomedical subjects

K Stanley

Publications and source records attributed to K Stanley.

At least 37 records · Page 2Linked to original sources
PubMed1998

Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulinaemic euglycaemic clamp technique.

OBJECTIVE: To perform measurements of insulin resistance serially in pregnancy and after childbirth in normal women. DESIGN: Longitudinal study. SETTING: Teaching hospital. METHODS: Ten normal women were studied using the hyperinsulinaemic euglycaemic clamp technique before pregnancy, at 16, 26 and 36 weeks gestation, and 8 weeks after delivery. All women breastfed their infants. Insulin resistance was measured by the glucose infusion rate required to maintain the plasma glucose at 4.5 mmol/l. RESULTS: There was a progressive increase in insulin resistance in all women as pregnancy progressed. The increase in resistance was most marked between 16 and 26 weeks of gestation, with only minimal progression thereafter. Lactation does not alter insulin resistance. CONCLUSION: The timing and extent of changes in insulin resistance are of physiological importance because they affect all classes of maternal and fetal substrates.

Adult↗
PubMed1995

Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group.

OBJECTIVE: To compare the safety and efficacy of continuing zidovudine therapy with that of zalcitabine alone or zalcitabine and zidovudine used together. DESIGN: A randomized, double-blind, controlled trial. SETTING: AIDS Clinical Trials units and National Hemophilia Foundation sites. PATIENTS: 1001 patients with symptomatic human immunodeficiency (HIV) disease and 300 or fewer CD4 cells/mm3 or asymptomatic HIV disease and 200 or fewer CD4 cells/mm3 who had tolerated zidovudine therapy for 6 months or more. INTERVENTION: Patients were randomly assigned to receive zidovudine, 600 mg/d; zalcitabine, 2.25 mg/d; or zidovudine, 600 mg/d, and zalcitabine, 2.25 mg/d. MEASUREMENTS: The primary end point was time to disease progression or death. RESULTS: The median follow-up time was 17.7 months. The estimated 12-month event-free rates were 70%, 67%, and 73%, respectively, for the zidovudine, zalcitabine, and combination groups (P = 0.26). A trend analysis showed significantly lower progression rates for combination therapy compared with zidovudine therapy as the pretreatment CD4 cell count increased (P = 0.027). For patients with 150 or more CD4 cells/mm3, those receiving combination therapy were less likely to have disease progression or to die than were those receiving zidovudine (relative risk, 0.51; 95% CI, 0.28 to 0.93; P = 0.029). We observed no difference between the zalcitabine and zidovudine groups (relative risk, 0.74; CI, 0.40 to 1.36; P = 0.33). For patients with 50 to 150 CD4 cells/mm3 or fewer than 50 CD4 cells/mm3, we found no differences among the treatment groups (P = 0.69 and P = 0.57, respectively). Severe toxic effects occurred less frequently among patients with 150 or more CD4 cells/mm3. CONCLUSIONS: We found no overall benefits of zalcitabine used alone or with zidovudine. However, a trend analysis suggested a better outcome for combination therapy compared with zidovudine as the pretreatment CD4 cell count increased.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Delayed gastric emptying as a factor in delayed postprandial glycaemic response in pregnancy.

OBJECTIVE: To determine whether an alteration in gastric emptying contributes to an altered postprandial glycaemic response in normal pregnancy. DESIGN: A longitudinal study in normal pregnancy and postpartum. SETTING: Teaching hospital in Sheffield. SUBJECTS: Primigravid women with uncomplicated pregnancies. INTERVENTIONS: Simultaneous meal tolerance and paracetamol absorption tests. MAIN OUTCOME MEASURES: 1. Gastric emptying: maximum concentration (Cmax) and time to maximum concentration (Tmax) of paracetamol; 2. glycaemic response: Cmax, Tmax, and area under the curve of plasma glucose; 3. insulinaemic response: Cmax, Tmax, area under the curve of plasma insulin. RESULTS: An increased, but not delayed, insulin response, and an increased initial glucose response to a test meal in the third trimester were not accompanied by any simultaneous delay in gastric emptying. CONCLUSION: Gastric emptying does not seem to be a factor in the glycaemic response of pregnancy.

Acetaminophen↗
PubMed1994

Isolation and sequence of a full length cDNA encoding a novel rat inositol 1,4,5-trisphosphate 3-kinase.

Immunoscreening a rat liver cDNA expression library has led to the isolation of a full-length cDNA clone encoding a novel isoform of rat inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase). Sequence comparison shows it (i) to be 93% identical to human hippocampus IP3 3-kinase B over 468 residues at the protein level, and (ii) to encode a protein 204 amino acids larger than the published sequence of its human homologue.

Amino Acid Sequence↗
PubMed1994

Prevalence and patterns of use of concomitant medications among participants in three multicenter human immunodeficiency virus type I clinical trials. AIDS Clinical Trials Group (ACTG).

Data on the prevalence and patterns of use of concomitant medications among participants in three large phase III clinical trials of zidovudine (ZDV) in human immunodeficiency virus type 1 (HIV-1) infection were analyzed. Overall, 2,801 patients reported 43,331 uses of concomitant medications. Over 85% of clinical trial participants used one or more concomitant medications at some point during the study. Patients with acquired immune deficiency syndrome (AIDS) used an average of 7.1 drugs per month. Patients with AIDS-related complex (ARC) or who were asymptomatic used relatively fewer drugs: 3.1 and 2.7 per month, respectively. Fourteen percent of patients with AIDS used more than 10 concomitant medications per month. The three most commonly utilized classes of drugs were antiinfectives (57%), analgesics or antipyretics (55%), and vitamins (47%). A total of 17% of patients overall and 30% of AIDS patients used acyclovir while on trial. Consumption of prescription drugs was greater, and "over-the-counter" drugs less, among AIDS patients. Reported use of agents not approved by the Food and Drug Administration or approved drugs used for off-label indications was infrequent. Overall use of concomitant medications did not differ across demographic subgroups when corrected for disease stage at the time of enrollment. White, non-Hispanic, homosexual and bisexual men consumed significantly more antivirals and vitamins than other trial participants. Women in all three protocols took more analgesics or antipyretics than did men.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗
PubMed1993

The inter-relationship between insulin and chromium in hyperinsulinaemic euglycaemic clamps in healthy volunteers.

Evidence in the literature suggests that the trace element chromium may have a role in glucose homeostasis through the regulation of insulin action. We have previously reported a significant reduction in plasma chromium levels in healthy individuals, following a 75 g oral glucose load, and after meals and glucose-dependent uptake of chromium in insulin-dependent tissues in vitro. However, in vivo it is unclear whether the changes in plasma chromium relate to changes in plasma glucose or insulin. The present study describes a series of euglycaemic hyperinsulinaemic clamps designed to attempt to define the initiator of changes in plasma chromium levels in ten healthy individuals. The data showed a significant (P < 0.01) reduction in fasting plasma chromium levels following glucose infusion and an initial bolus of insulin. Significant (P < 0.02) increases in post-clamp urinary chromium excretion were insufficient to explain the decrease in plasma levels. During the recovery phase of an extended two-phase clamp protocol we found plasma insulin levels decreased by 70% within 10 min, associated with an increase in plasma chromium levels of 30% and no significant change in plasma glucose level. These data indicate that alterations in plasma glucose are unlikely to be directly related to changes in plasma chromium, whilst supporting the hypothesis that plasma insulin may influence plasma levels of this trace element. In contrast, plasma zinc was unaffected throughout these clamp studies.

Adult↗
PubMed1993

Clinical research units for the treatment of patients with HIV disease: operational issues and components needed to conduct clinical trials.

Clinical trials are of paramount importance for the development and evaluation of new therapies for patients with human immunodeficiency virus (HIV) disease. The objective of an HIV clinical research unit is to conduct high quality clinical research with patients who have HIV disease. The conduct of these research studies requires accurate and complete data collection. Coordination of the patients' primary care must be complemented by a working knowledge of the relevant ethical issues. In addition, technical, managerial, and clinical expertise is needed for conducting the trials and collecting data. To accurately plan the research, personnel and resource allocation should be periodically assessed. Clinicians, particularly those who have not previously conducted clinical trials or who are considering the incorporation of a research program into a primary care setting, must be familiar with these issues in order to create and supervise this type of clinical research unit. A smoothly running clinic observing a defined cohort of patients is attractive to government agencies and pharmaceutical sponsors for funding of clinical trials and research projects.

Clinical Protocols↗
PubMed1992

Signal transduction by the epidermal growth factor receptor is attenuated by a COOH-terminal domain serine phosphorylation site.

It has been proposed that the acute desensitization of epidermal growth factor receptor (EGF-R) function can be accounted for, in part, by the effect of EGF to increase phosphorylation of the receptor at Ser1046/7 (Countaway, J.L., Nairn, A.C., and Davis, R.J. (1992) J. Biol. Chem. 267, 1129-1140). Here, we show that the mutational removal of this phosphorylation site causes an activation of EGF-R function and a potentiation of signal transduction. The mechanism of potentiation results from 1) defective down-regulation of the EGF-R when cells are incubated with high concentrations of EGF; and 2) increased EGF-stimulated tyrosine phosphorylation. The increased EGF-stimulated phosphorylation is associated with an alteration of the apparent specificity of tyrosine phosphorylation and is independent of the down-regulation defect. Together, these data strongly support the hypothesis that Ser1046/7 is a biologically significant site of regulatory phosphorylation of the EGF-R.

Amino Acid Sequence↗
PubMed1992

Effect of hysterectomy on anorectal and urethrovesical physiology.

To investigate whether vaginal or total abdominal hysterectomy is associated with changes in anorectal and urethrovesical physiology, 26 women were studied before operation and six weeks and six months afterwards. The results showed a postoperative increase in both rectal and vesical sensitivity (p less than 0.01). Similar results were observed irrespective of the type of hysterectomy. No significant changes in rectal or bladder compliance were noted, and anal pressure and urethral pressure and length were unchanged after surgery. Whole gut transit was not affected by hysterectomy. Urinary symptoms occurred de novo in 6/26 women and gastrointestinal symptoms in 2/26 women. These results show that significant changes in rectal and vesical sensitivity occur after hysterectomy for benign disease. These persist for at least six months postoperatively but are not always associated with development of urinary or gastrointestinal symptoms.

Adult↗
PubMed1992

Mutational removal of the major site of serine phosphorylation of the epidermal growth factor receptor causes potentiation of signal transduction: role of receptor down-regulation.

The major site of epidermal growth factor receptor (EGF-R) serine phosphorylation is located within the COOH-terminal domain of the receptor at Ser1046/7. We have previously demonstrated that this phosphorylation site accounts for the acute desensitization of the EGF-R observed in EGF-treated cells. Here we show that the mutational removal of this negative regulatory phosphorylation site causes potentiation of signal transduction by the EGF-R. This potentiation can be accounted for in part by a block in the EGF-stimulated down-regulation of the EGF-R. These data indicate that the SER1046/7 phosphorylation site may have a regulatory role during long term incubation of cells with mitogenic concentrations of EGF.

Allosteric Regulation↗
PubMed1991

Constitutive phosphorylation of the epidermal growth factor receptor blocks mitogenic signal transduction.

The epidermal growth factor (EGF) receptor is phosphorylated by protein kinase C at Thr654. It has been proposed that the phosphorylation of this site is an important regulatory mechanism for the control of EGF receptor function. However, the physiological significance of the phosphorylation of EGF receptor Thr654 in intact cells is not understood. To address this question, the design of an experimental strategy is required that can be used to distinguish between the pleiotropic effects of kinase C activation and the specific effects of kinase C that are mediated by the phosphorylation of the EGF receptor at Thr654. The approach that we used was to examine the function of EGF receptors that are constitutively phosphorylated at residue 654. It was observed that the constitutive phosphorylation of the EGF receptor blocked mitogenic signal transduction by the receptor. These data are consistent with the hypothesis that the phosphorylation of the EGF receptor at residue 654 in intact cells inhibits EGF-stimulated cellular proliferation.

Animals↗
PubMed1991

Role changes at the pharmacy-nursing interface: Kimball Medical Center.

The original goals and objectives of the CST program have been realized. Medication safety, control, accountability, and utilization efforts of decentralized satellite pharmacists have been brought to fruition. A career ladder has been created for the pharmacy technician. This has enabled the Department of Pharmaceutical Services to recruit, retain, and develop an exceptionally competent and proficient technical staff. The pharmacy has earned a new found respect from the nursing division. A greater awareness of its staff's positions as drug experts and information resources has evolved. Credibility has been established for additional pharmacy programs and proposed clinical activities. Pharmacists and technicians have gained an in-depth understanding of the procedures, problems, and challenges of the nursing services, which has enabled a bridge of understanding and a common bond of team effort to be built between the two departments.

Hospital Bed Capacity, 300 to 499↗
PubMed1990

The 68 kDa protein of signal recognition particle contains a glycine-rich region also found in certain RNA-binding proteins.

Signal recognition particle (SRP) interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the endoplasmic reticulum. Membrane targeting is mediated by the 68 and the 72 kDa proteins of SRP. We have cloned and sequenced cDNA encoding the 68 kDa protein of canine signal recognition particle (SRP68). SRP68 is a basic protein comprised of 622 amino acid residues. Close to the amino terminus there is a glycine-rich region which SRP68 has in common with some RNA-binding proteins. SRP68 shares no detectable similarity to any of the proteins in data libraries.

Amino Acid Sequence↗
PubMed1990

The control of breast cancer. A World Health Organization perspective.

The greatest decrease in breast cancer mortality is likely to derive from applying globally existing therapies at an earlier stage. A high priority of the World Health Organization (WHO) cancer control program is the outreach approach that promotes worldwide access to cancer therapies of proven values. Therefore, the first priority in national health programs for breast cancer is to encourage patients to present for diagnosis and treatment at an earlier stage of the disease. In the development of guidelines for the early detection of breast cancer, the WHO emphasizes the importance of appropriate widespread coverage of high-risk groups as opposed to repetitive screening of low-risk groups, so that early detection will be effective. A WHO/USSR controlled trial of breast self-examination and community-based adjuvant therapy is helping to develop the WHO global recommendations for the control of breast cancer. Depending on the extent of the breast cancer problem, the local resources, and the cultural situation, national health strategies should include all three main elements--public education, early detection, locally available treatment, or a combination of these to a national comprehensive program for the control of breast cancer.

Adult↗
PubMed1989

The gene for the human putative apoE receptor is on chromosome 12 in the segment q13-14.

We have previously described the cDNA coding for a new lipoprotein receptor that contains domains closely related to the ligand-binding domain of the LDL receptor. We have now investigated the localization of the gene for this new receptor by hybridization of the cDNA to panels of rodent cells containing subsets of human chromosomes and by in situ hybridization of the cDNA to chromosomes. The gene maps to 12q13-14, a known hot spot for chromosomal rearrangements in human neoplasia. Of particular interest is the frequent involvement of the 12q13-14 segment in clonal abnormalities in lipomas and myxoid liposarcomas, and it is possible that LRP may play a role in the pathogenesis of such tumors.

Animals↗
PubMed1989

The gene for human complement C9 is on chromosome 5.

By hybridizing a cloned cDNA coding for human complement factor C9 to hybrid cells containing subsets of human chromosomes on a rodent background, we have determined that the human gene for C9 is localized on chromosome 5.

Autoradiography↗