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Biomedical subjects

S J Palmer

Publications and source records attributed to S J Palmer.

At least 19 recordsLinked to original sources
PubMed2006

Cortical muscle coupling in Parkinson's disease (PD) bradykinesia.

OBJECTIVES: To determine if novel methods establishing patterns in EEG-EMG coupling can infer subcortical influences on the motor cortex, and the relationship between these subcortical rhythms and bradykinesia. BACKGROUND: Previous work has suggested that bradykinesia may be a result of inappropriate oscillatory drive to the muscles. Typically, the signal processing method of coherence is used to infer coupling between a single channel of EEG and a single channel of rectified EMG, which demonstrates 2 peaks during sustained contraction: one, approximately 10 Hz, which is pathologically increased in PD, and a approximately 30 Hz peak which is decreased in PD, and influenced by pharmacological manipulation of GABAA receptors in normal subjects. MATERIALS AND METHODS: We employed a novel multiperiodic squeezing paradigm which also required simultaneous movements. Seven PD subjects (on and off L-Dopa) and five normal subjects were recruited. Extent of bradykinesia was inferred by reduced relative performance of the higher frequencies of the squeezing paradigm and UPDRS scores. We employed Independent Component Analysis (ICA) and Empirical Mode Decomposition (EMD) to determine EEG/EMG coupling. RESULTS: Corticomuscular coupling was detected during the continually changing force levels. Different components included those over the primary motor cortex (ipsilaterally and contralaterally) and over the midline. Subjects with greater bradykinesia had a tendency towards increased approximately 10 Hz coupling and reduced approximately 30 Hz coupling that was erratically reversed with L-dopa. CONCLUSIONS: These results suggest that lower approximately 10 Hz peak may represent pathological oscillations within the basal ganglia which may be a contributing factor to bradykinesia in PD.

Antiparkinson Agents↗
PubMed2003

The cost-effectiveness of a new statin (rosuvastatin) in the UK NHS.

Statins are central to the government's National Service Framework (NSF) for coronary heart disease (CHD). NHS spending on statins is currently about pounds sterling 500 million per annum and rising at an annual rate of 30%. Although generally considered to be a cost-effective treatment for hyperlipidaemia and cardiovascular disease, given the high and rising expenditure on statins in the UK, there is a pressing need to ensure that the choice between available statins reflects cost-effectiveness considerations. A decision model was developed to establish the cost-effectiveness of treating new hypercholesterolaemic patients to UK and European target levels of blood total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), using rosuvastatin, atorvastatin, simvastatin, pravastatin or fluvastatin. The model was used to estimate the proportion of patients reaching target and the associated costs over a one-year period from the perspective of the NHS. The effectiveness of the alternative statins were modelled using data from the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial. Monte Carlo simulation was used to reflect uncertainty in the parameter estimates applied in the model. Rosuvastatin is demonstrated to dominate (i.e. lower costs and a higher number of patients treated to target) atorvastatin, simvastatin and pravastatin. Compared with fluvastatin, the incremental cost per additional patient to target (PTT) for rosuvastatin was pounds sterling 24 using LDL-C and pounds sterling 83 using TC. The probability that rosuvastatin is cost-effective exceeds 95%, provided the NHS is prepared to pay at least pounds sterling 35 per PTT to achieve target LDL-C cholesterol levels (pounds sterling 160 for TC). The analysis demonstrates rosuvastatin is more cost-effective than the other statins in achieving UK and European cholesterol targets.

Coronary Disease↗
PubMed2001

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

BACKGROUND: The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). METHODS: A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. RESULTS: The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. CONCLUSION: rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.

Cost-Benefit Analysis↗
PubMed2000

The cost and implications of reoperation after surgery for fracture of the hip.

Revision operations after fracture of the hip are costly, in both monetary and personal terms. We have assessed whether these costs applied equally to all complications after the primary procedure. We studied 3,154 consecutive patients with fracture of the hip and analysed the complications and financial implications related to reoperation within one year of injury. The results showed that revision surgery is not always associated with a significant increase in morbidity, financial cost or mortality, but is directly related to the underlying complication.

Aged↗
PubMed1998

Sticky egyptians: a technique for assembling genes encoding constrained peptides of variable length.

Naturally occurring peptides, such as those produced by the poisonous marine snails of the genus Conus , have the ability to form tight, highly specific molecular interactions. The rigidity of the peptide framework which promotes these interactions is usually maintained by disulphide bonds, and it seems that the overall main chain conformation (or fold) of the peptide is determined by its length and the sequence distribution of the pairs of cysteine residues participating in these bonds. The fold of the peptide in turn is largely responsible for its shape. Since highly effective molecular interactions occur between species complementary in shape, we reasoned that peptides with the greatest potential in therapy or diagnosis would be found in a library of shapes, those peptides with a shape complementary to a given target being identified, for example, by selection. As a first step towards constructing such a peptide shape library, we have developed a method for assembling DNA fragments which encode an even number of cysteine residues and which are of variable length. We describe this method here.

Cysteine↗
PubMed1998

Phosphorylcholine-coated metallic stents in rabbit iliac and porcine coronary arteries.

The arterial wall reaction to phosphorylcholine-coated metal stents was examined in rabbits and pigs. Compared to non-coated stents, no significant difference was found by angiography and histology. We conclude that although phosphorylcholine-coating does not provoke arterial neointima formation or decrease luminal diameter compared to stainless steel stents, the coating does not seem to reduce restenosis.

Angiography↗
PubMed1998

The Y* rearrangement in mice: new insights into a perplexing PAR.

In essence, the Y* rearrangement in the mouse is a Y chromosome that has been hijacked by a non-Y centromere attached distal to the pseudoautosomal region (PAR). All the Y-unique material is thought to be unaltered, but the recombinatory behaviour of the Y* with the X during male meioisis led to the conclusion that part of the PAR is inverted. In the course of a cross set up to introduce the X-linked mutation Patchy fur (Paf) into XY* males, the Y* chromosome was found to carry the wild type allele of Paf. Paf maps close to the X PAR boundary, so we hypothesised that the inverted region of the Y* PAR originated from an X chromosome that provided not only an inverted copy of proximal PAR, but also an X PAR boundary together with some adjacent X-unique material that included the Paf locus. This hypothesis was validated by Southern analysis using an X PAR boundary probe to show that Y* has an X PAR boundary. Thus the Y* PAR has resulted from an end to end fusion of an X and a Y PAR. Furthermore, it was shown that in conjunction with this PAR-PAR fusion, there has been deletion of both copies of the distally located pseudoautosomal gene Steroid sulfatase (Sts).

Animals↗
PubMed1997

Endoluminal local delivery of PCNA/cdc2 antisense oligonucleotides by porous balloon catheter does not affect neointima formation or vessel size in the pig coronary artery model of postangioplasty restenosis.

Localized delivery of antisense oligonucleotides directed against cell cycle regulatory proteins has been proposed as a means to prevent restenosis after angioplasty. To test whether single endoluminal delivery of a combination of proliferating cell nuclear antigen (PCNA) and cell-division cycle 2 kinase (cdc2) antisense might affect restenosis, we delivered 2 ml of lipid-complexed PCNA/cdc2 antisense oligomers (1.35 mg) to the coronary arteries of pigs after balloon overstretch angioplasty (AS group) and performed planimetric histomorphometry on arterial sections of the tissue, harvested at 4 wk. Compared with controls receiving 3'-5' reversed sequence oligomers (REV group), there were no differences in absolute intimal area (AS 1.36 +/- 0.08 mm2, REV 1.23 +/- 0.10 mm2, P = NS), intimal area normalized to extent of injury (AS 0.67 +/- 0.03, REV 0.77 +/- 0.10, P = NS), or vessel perimeter (AS 7.72 +/- 0.19 mm, REV 7.36 +/- 0.22 mm, P = NS). We conclude that single endoluminal delivery of antisense against key cell cycle regulatory proteins does not affect neointima formation or vessel size in this model of restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1997

Pharmacokinetics and tissue localization of antisense oligonucleotides in balloon-injured pig coronary arteries after local delivery with an iontophoretic balloon catheter.

When delivered locally to the arterial wall by passive fluid transfer systems such as perforated balloons, water-soluble compounds in aqueous solution are not readily taken up by tissue, show low levels of cellular localization, and are quickly lost by wash-out. One approach to improve delivery is addition of an "active" component to the catheter system to change the nature of the drug-to-tissue interaction. Using an iontophoretic balloon catheter to deliver antisense oligonucleotide (ODN) to pig coronary arteries after balloon angioplasty, we determined the quantity and localization of ODN in the tissue. By radiolabeling, 7.3 +/- 2.4 micrograms ODN was present at 30 min, 1.5 +/- 0.6 at 2 h, 0.52 +/- 0.35 at 24 h, and 0.26 +/- 0.11 at 7 d. By fluorescent labeling, circumferential medial uptake and adventitial delivery at the site of medial injury was observed, with primarily cellular localization. The iontophoretic catheter thus appears to be a useful device for ODN delivery to arterial tissue.

Angioplasty, Balloon, Coronary↗
PubMed1996

Hepatitis A vaccine responses in HIV-positive persons with haemophilia.

The safety and immunogenicity of subcutaneously (s.c.) administered hepatitis A (HA) vaccine was evaluated in HIV positive and negative patients with haemophilia and healthy male controls. The vaccine was well tolerated. Seroconversion occurred among all controls after one dose of vaccine but was delayed among patients, particularly if HIV-positive-4 of 17 (24%) failed to respond to three doses of vaccine. Following the third dose of vaccine, geometric mean titres were significantly higher among controls (1354) than among HIV infected patients (204) (P < 0.05). Non-responders failed to develop an immune response following boosting with high titre vaccine. Patients with haemophilia may be vaccinated against HA s.c. but consideration should be given to ensuring that HIV-positive individuals with haemophilia and other immunosuppressed individuals should have their immune responses checked since additional booster doses or passive prophylaxis may be necessary in such individuals.

Adolescent↗
PubMed1995

Intracoronary radiation before stent implantation inhibits neointima formation in stented porcine coronary arteries.

BACKGROUND: Stent implantation has been shown to reduce restenosis by establishing a larger lumen but not by reducing neointima formation. We have previously shown that ionizing radiation reduced neointima formation after balloon injury in a swine model of restenosis. The purpose of this study was to determine whether endovascular irradiation of the coronary artery before stent implantation would affect neointima formation. METHODS AND RESULTS: Nine normolipemic pigs underwent coronary angiography, and segments of the left anterior descending and left circumflex arteries were chosen as targets for stenting. A high-activity 192Ir source was used to deliver 14 Gy by random assignment to one of the vessels. After this, 3.5-mm tantalum stents were implanted in both arteries. Three additional pigs were treated with a 90Sr/Y source (a pure beta-emitter) delivering 14 Gy to five segments of coronary vessels that were stented immediately after irradiation. Stent-to-artery ratio was similar in the radiated and the control arteries. Animals received aspirin 325 mg daily and were killed at 28 days. The intimal area was significantly reduced in the irradiated stented arteries compared with control arteries treated with stent only (1.98 mm2 with 192Ir and 2.53 mm2 with 90Sr/Y versus 3.82 mm2 in the control stented arteries, P < .005). CONCLUSIONS: Endovascular radiation before coronary stenting reduces neointima formation and may further reduce the restenosis rate after stent implantation.

Animals↗
PubMed1994

Successful treatment of veno-occlusive disease with recombinant tissue plasminogen activator in a patient requiring peritoneal dialysis.

There have been encouraging reports of the use of recombinant tissue plasminogen activator (tPA) in established veno-occlusive disease (VOD). Haemodialysis has been considered a contraindication to this therapy in view of the potential haemostatic complications. We report a case of a woman who developed moderately severe VOD complicated by anuria following an allogeneic bone marrow transplant for relapsed acute myeloid leukaemia. Following initiation of peritoneal dialysis she received tPA at a dose of 10 mg/day for 5 days. There was rapid improvement in her urine output and liver function with no bleeding complications. This case suggests that the requirement of dialysis may not preclude the use of tPA in established VOD and therefore warrants further study.

Adult↗
PubMed1994

Graft-versus-host disease following interferon therapy for relapsed chronic myeloid leukaemia post-allogeneic bone marrow transplantation.

The combination of donor leucocytes, with or without interferon, has produced encouraging responses in patients with haematological relapse following allogeneic BMT for chronic myeloid leukaemia (CML). A 25-year-old male received low-dose interferon-alpha alone for haematological relapse occurring 10 months following an allogeneic BMT for Ph-positive CML. Interferon therapy was complicated by severe GVHD requiring immunosuppressive therapy. The patient was subsequently found to be in complete haematological and cytogenetic remission, raising the possibility of an immune-mediated antileukaemic action.

Adult↗
PubMed1993

Care of sick children by parents: a meaningful role.

Parental involvement in their child's care in hospital has undergone great change over the last century. Studies have shown how 'maternal deprivation' and 'separation anxiety' expressed by children are detrimental to a child's recovery in hospital. Striving efforts have been made to develop family-centred care, promote normality of the family unit and continue with the normal routine of the child's life within the limitations of a hospital environment and the child's illness. Expectations of the parental role in hospital need to be identified and expressed from both the parents and staff to establish an understanding that will ultimately be best for the child. Many studies have highlighted benefits to both parent and child from parental participation in hospital. However, disadvantages have been identified from resident parents who feel captive to their new situation and role. Efforts for family-centred care are highly advocated now. Care-by-Parent units have been set up in some areas to promote this idea and, although many advantages have been identified, they are not without their problems. The success of parental involvement is dependent on both parents' and staff's attitudes, enthusiasm and willingness to work together.

Child↗