PubMed Health⌕ Search

Biomedical subjects

M Hamilton

Publications and source records attributed to M Hamilton.

At least 19 recordsLinked to original sources
PubMed2006

Implementation of the NICE guideline - recommendations from the British Fertility Society for national criteria for NHS funding of assisted conception.

Assisted conception providers in England were surveyed to establish the uptake of NICE guideline for infertility particularly in respect of assisted conception and the criteria used to accept patients for NHS funded treatment. Detailed information on selection criteria was obtained from a group of commissioning consortia at an advanced stage in their arrangements. While there was an overall increase in the number of NHS IVF cycles purchased in England, implementation is stalled at one fresh cycle in the vast majority of Primary Care Trusts (PCTs). There is little consensus about the criteria used for acceptance into an NHS programme. This is particularly so in respect of social criteria which are often arbitrary and used as a rationing tool. This information complements that provided by the survey of Primary Care Trusts performed in March 2005 by the All Party Parliamentary Group on Infertility (APPGI) in partnership with the National Infertility Awareness Campaign (NIAC) which together provide a basis for recommendations for NHS funding. The recommendations presented should be applied across England and Wales to ensure consistency, fairness and equity of access.

Adult↗
PubMed2006

Liver haemorrhage in haemophilia--a case report and review of the literature.

We present two patients with severe haemophilia A, who presented with haemorrhagic shock, secondary to a liver haematoma in the neonatal period. Both required emergency treatment and diagnosis of the hereditary coagulation defect. Major organ bleeding in severe haemophilia A in the newborn period is rare, and this unusual complication is not well recognized. Failure to recognize that the bleeding is due to a bleeding disorder, particularly in the absence of a family history, may lead to delay in appropriate management.

Adult↗
PubMed2006

A prospective double-blind randomised controlled trial of intraoperative pelvic instillation with bupivacaine for management of pain following laparoscopy and dye.

The aim of this randomised, double-blind, placebo-controlled trial was to evaluate the effectiveness of intraperitoneal instillation of bupivacaine following laparoscopy and dye test. Women received either 15 ml of 0.9% saline (n= 42) or 15 ml of 0.5% bupivacaine (n= 43), which was instilled intraperitoneally. Pain and nausea scores were recorded on a visual analogue scale (VAS). Pain perception was no different in the bupivacaine group compared with the control group with median values of VAS at 2 hours (18, 19; P= 0.8), 6 hours (21, 22; P= 0.5), 12 hours (19, 25; P= 0.8), 24 hours (27, 27; P= 0.9) and 48 hours (21, 13; P= 0.26). Women in the bupivacaine group were less nauseated than controls in the immediate postoperative period (with median VAS scores of 0, 8; P value = 0.03 at 2 hours and 0, 7; P= 0.01 at 6 hours).

Anesthetics, Local↗
PubMed2006

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations.

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Anti-Bacterial Agents↗
PubMed2005

Fatty acid metabolism in human preimplantation embryos.

BACKGROUND: Little is known of fatty acid metabolism in human embryos. This information would be useful in developing metabolic tests of embryo quality and improving embryo culture media. METHODS: The fatty acid composition of human embryos and their ability to accumulate 13C labelled fatty acids was assessed in relation to the stage of development using gas-chromatography and combustion-isotope-ratio-mass spectrometry. RESULTS: Compared with embryos which did not develop beyond the 4-cell stage, those that did had significantly higher concentrations of the unsaturates, linoleic (12% versus 3%; P=0.02) and oleic (14% versus 7%; P=0.02), and a lower concentration of total saturates (62% versus 77%; P=0.04). There was uptake of both 13C linoleic and palmitic, but the developmental pattern was different for each fatty acid. The net accumulation in pmol/embryo/24h for palmitic was 1 at the 2-cell to <8-cell stage, 4 at the 8-cell-morula stage and negligible at the blastocyst stage. For linoleic, there was little net accumulation at the 2-cell to <8-cell stage, 8 (8-cell-morula stage) and 17 pmol/embryo/24 h (blastocyst stage). CONCLUSION: Preimplantation human embryos actively take up individual fatty acids at different rates at different stages of development. The high unsaturated concentration at the later stages of development may be explained by preferential uptake of linoleic acid.

Biological Transport↗
PubMed2004

A phase 1 study of OSI-211 given as an intravenous infusion days 1, 2, and 3 every three weeks in patients with solid cancers.

PURPOSE: To define the maximum tolerated dose (MTD), recommended phase II dose (RD) and dose limiting toxicity (DLT) of liposomal lurtotecan, OSI-211 (formerly known as NX211), given as a short intravenous infusion on days 1, 2, and 3 every three weeks. EXPERIMENTAL DESIGN: Thirty-seven patients were enrolled and treated in a dose escalation study from a starting dose of 0.15 mg/m(2) daily x 3 to 2.1 mg/m(2) daily x 3. Detailed pharmacokinetic analyses of blood were done on both days 1 and 3 of the first cycle and toxicity was monitored. RESULTS: Two MTDs were defined; one for patients defined as minimally pretreated and one for those heavily pretreated. Dose limiting toxicity was myelosuppression: primarily thrombocytopenia although neutropenia was also noted. The MTD was 2.1 mg/m(2)/d (total dose of 6.3 mg/m(2)) in minimally pretreated patients and 1.8 mg/m(2)/d (5.4 mg/m(2) total dose) in heavily pretreated patients. Pharmacokinetics revealed that AUC and C (max) increased with dose and were significantly higher than that of free lurtotecan (AUC approx. 100 fold higher). The half life and duration of the active lactone form were also significantly longer than historical data on free drug. Two partial responses were seen, one each in a patient with breast and ovarian cancer. CONCLUSIONS: Two Phase II recommended doses were established for OSI-211 given as a daily x 3 schedule every three weeks. The recommended phase II dose is 1.8 mg/m(2) daily x 3 for minimally pretreated patients and 1.5 mg/m(2) for those heavily pretreated. Phase II studies should be initiated in sensitive tumours.

Adult↗
PubMed2004

Evaluating commercial weight loss programmes: an evolution in outcomes research.

The increasing prevalence of obesity has been mirrored by a parallel increase in the number of commercial weight loss programmes. Research evaluating these programmes is meagre, however, compared to the numbers treated. Reluctance of commercial weight loss programmes to meaningfully evaluate their weight loss efficacy may arise from fear that competitors will use the results against them. Evaluation of commercial weight loss programmes usually progresses from testimonials, often by famous people who were successful, to uncontrolled studies of past participants evaluated either by the programme itself or by an outside entity. The gold standard, however, is a scientifically rigorous, controlled study of the programme conducted by an independent entity. Such a study, published in a peer-reviewed journal, can gain credibility for a programme, as it did with Slim Fast, if the results are positive, or herald the end of the programme, as it was with Simeons human chorionic gonadotropin injection clinics. This review of the evolution of the evaluation process of commercial weight loss programmes leads us to conclude that consumers are likely to demand greater scientific rigour in the future, a change that will favour informed choice and discourage the practice of unrealistic advertising that raises false hopes.

Diet Fads↗
PubMed2001

Phosphorylation site specificity of the Pak-mediated regulation of Raf-1 and cooperativity with Src.

The p21-activated kinase, Pak, has recently been shown to phosphorylate Raf-1 on serine 338 (S338), a critical regulatory residue. The specificity requirements for Pak-mediated phosphorylation of S338 were examined by substitution analysis of Raf-1 peptides and conserved region 3 (CR3) proteins. Phosphorylation was found to be very sensitive to alterations in amino acid side chains proximal to S338. Loss of N-terminal arginines resulted in decreased peptide phosphorylation while loss of these residues, as well as C-terminal glutamates and bulky C-terminal hydrophobic residues, decreased phosphorylation of the CR3 protein. Phosphorylation of Raf-1 on tyrosine 341 is significant in epidermal growth factor- and Src-mediated signaling, suggesting that cooperativity may exist between Pak and Src phosphorylation of Raf-1. Purified Pak and Src were found not to be cooperative in phosphorylating peptides or purified CR3 protein. However, the phosphorylation of Raf-1 S338 by Pak was increased in the presence of Src. The complexity of this signaling module could thus account for the different levels of Raf-1 activation required for fulfillment of different biological roles within the cell.

Amino Acid Substitution↗
PubMed2001

Constitutive association of c-N-Ras with c-Raf-1 and protein kinase C epsilon in latent signaling modules.

Phorbol ester stimulation of the MAPK cascade is believed to be mediated through the protein kinase C (PKC)-dependent activation of Raf-1. Although several studies suggest that phorbol ester stimulation of MAPK is insensitive to dominant-negative Ras, a requirement for Ras in Raf-1 activation by PKC has been suggested recently. We now demonstrate that in normal, quiescent mouse fibroblasts, endogenous c-N-Ras is constitutively associated with both c-Raf-1 and PKC epsilon in a biochemically silent, but latent, signaling module. Chemical inhibition of novel PKCs blocks phorbol 12-myristate 13-acetate (PMA)-mediated activation of MAPKs. Down-regulation of PKC epsilon protein levels by antisense oligodeoxyribonucleotides blocks MAPK activation in response to PMA stimulation, demonstrating that PKC epsilon activity is required for MAPK activation by PMA. c-Raf-1 activity in immunoprecipitated c-N-Ras.c-Raf-1.PKC epsilon complexes is stimulated by PMA and is inhibited by GF109203X, thereby linking c-Raf-1 activation in this complex to PKC activation. These observations suggest that in quiescent cells Ras is organized into ordered, inactive signaling modules. Furthermore, the regulation of the MAPK cascade by both Ras and PKC is intimately linked, converging at the plasma membrane through their association with c-Raf-1.

Animals↗
PubMed2001

Regulation of p53 expression by the RAS-MAP kinase pathway.

Activation of MAP kinase leads to the activation of p53-dependent pathways, and vice-versa. Although the amount of p53 protein increases in response to MAP kinase-dependent signaling, the basis of this increase is not yet fully understood. We have isolated the mutant cell line AP14, defective in p53 expression, from human HT1080 fibrosarcoma cells, which have an activated ras allele. The expression of p53 mRNA and protein is approximately 10-fold lower in AP14 cells than in the parental cells. The high constitutive phosphorylation and activities of the MAP kinases ERK1 and ERK2 in HT1080 cells are greatly reduced in AP14 cells, although the levels of these proteins are unchanged, suggesting that the defect in the mutant cells affects the steady-state phosphorylation of ERK1 and ERK2. Overexpression of ERK2 in AP14 cells restored both MAP kinase activity and p53 expression, and incubation of the mutant cells with the phosphatase inhibitor orthovanadate resulted in strong coordinate elevation of MAP kinase activity and p53 expression. The levels of expression of the p53-regulated gene p21 parallel those of p53 throughout, showing that basal p21 expression depends on p53. The levels of p53 mRNA increased by 5-8-fold when activated ras was introduced into wild-type cells, and the levels of the p53 and p21 proteins decreased substantially in wild-type cells treated with the MEK inhibitor U0216. We conclude that MAP kinase-dependent pathways help to regulate p53 levels by regulating the expression of p53 mRNA.

3T3 Cells↗
PubMed2001

Clinical trial designs for the early clinical development of therapeutic cancer vaccines.

There are major differences between therapeutic tumor vaccines and chemotherapeutic agents that have important implications for the design of early clinical trials. Many vaccines are inherently safe and do not require phase I dose finding trials. Patients with advanced cancers and compromised immune systems are not good candidates for assessing either the toxicity or efficacy of therapeutic cancer vaccines. The rapid pace of development of new vaccine candidates and the variety of possible adjuvants and modifications in method of administration makes it important to use efficient designs for clinical screening and evaluation of vaccine regimens. We review the potential advantages of a wide range of clinical trial designs for the development of tumor vaccines. We address the role of immunological endpoints in early clinical trials of tumor vaccines, investigate the design implications of attempting to use disease stabilization as an end point and discuss the difficulties of reliably utilizing historical control data. Several conclusions for expediting the clinical development of effective cancer vaccines are proposed.

Adjuvants, Immunologic↗
PubMed2001

How to optimize the drop plate method for enumerating bacteria.

The drop plate (DP) method can be used to determine the number of viable suspended bacteria in a known beaker volume. The drop plate method has some advantages over the spread plate (SP) method. Less time and effort are required to dispense the drops onto an agar plate than to spread an equivalent total sample volume into the agar. By distributing the sample in drops, colony counting can be done faster and perhaps more accurately. Even though it has been present in the laboratory for many years, the drop plate method has not been standardized. Some technicians use 10-fold dilutions, others use twofold. Some technicians plate a total volume of 0.1 ml, others plate 0.2 ml. The optimal combination of such factors would be useful to know when performing the drop plate method. This investigation was conducted to determine (i) the standard deviation of the bacterial density estimate, (ii) the cost of performing the drop plate procedure, (iii) the optimal drop plate design, and (iv) the advantages of the drop plate method in comparison to the standard spread plate method. The optimal design is the combination of factor settings that achieves the smallest standard deviation for a fixed cost. Computer simulation techniques and regression analysis were used to express the standard deviation as a function of the beaker volume, dilution factor, and volume plated. The standard deviation expression is also applicable to the spread plate method.

Bacteriological Techniques↗