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Biomedical subjects

C J Harris

Publications and source records attributed to C J Harris.

At least 37 records · Page 2Linked to original sources
PubMed1995

Long-term intrathecal baclofen therapy in patients with intractable spasticity.

BACKGROUND: Severe spasticity unresponsive to oral drugs may respond satisfactorily to baclofen delivered intrathecally. METHODS: Intrathecal baclofen (IB) therapy delivered by means of implanted infusion pumps was used for nine patients with severe spasticity. Six patients had multiple sclerosis, two cervical spinal cord injury, and one head injury. All were non-ambulatory. RESULTS: Patients showed improvement in many areas, including ability to transfer, seating, pain control, personal care, and liability to skin breakdown. Before IB therapy, only three of the nine patients were able to live at home in the community and six were institutionalized. At the end of our follow-up period, only one patient remained institutionalized, three lived in group homes and five lived at home in the community. In the year preceding pump implantation, the nine patients spent a total of 755 days in acute care hospitals. In the year following onset of IB therapy, they spent only 259 days in hospital. CONCLUSIONS: IB therapy can improve patient quality of life and can be cost-effective in carefully selected patients with severe spasticity and disability. The drug delivery catheter is that part of the therapeutic system most vulnerable to failure. Because of the varied expertise required to manage these patients effectively, and the potential for a variety of complications, it is essential that an IB program is supported by a well-organized multi-disciplinary medical team.

Adult↗
PubMed1995

Long term treatment of intractable reflex sympathetic dystrophy with intrathecal morphine.

BACKGROUND: Some patients with reflex sympathetic dystrophy (RD) develop intractable symptoms unresponsive to conventional therapy. Recently, intrathecal morphine therapy has been used with some success in such patients. METHODS: The clinical course of two patients with intractable reflex sympathetic dystrophy (RSD) is described. Both patients developed intractable leg pain, swelling and autonomic changes after a leg injury. Numerous medical treatments and surgical sympathectomies failed to provide long term relief. RESULTS: Relatively satisfactory symptom control was achieved only with the use of long term intrathecal morphine therapy delivered by subcutaneously implanted infusion pumps. Exacerbations of the RSD continued to occur, at times in association with further leg trauma, but these could be controlled by a temporary escalation of the intrathecal morphine dose. Complications of morphine therapy were relatively minor. A red rash appearing over the pump site was the first sign that a drug catheter break had occurred, necessitating surgical catheter revision. CONCLUSION: Long term intrathecal morphine therapy is a useful treatment option for patients with intractable severe RSD who have failed other therapies and remain markedly disabled.

Adolescent↗
PubMed1995

A perspective and critique of adaptive neurofuzzy systems used for modelling and control applications.

This paper outlines some of the theoretical and practical developments being made in neurofuzzy systems. As the name suggests, neurofuzzy networks were developed by fusing the ideas that originated in the fields of neural and fuzzy systems. A neurofuzzy network attempts to combine the transparent, linguistic, symbolic representation associated with fuzzy logic with the architecture and learning rules commonly used in neural networks. These hybrid structures have both a qualitative and a quantitative interpretation and can overcome some of the difficulties associated with solely neural algorithms which can usually be regarded as black box mappings, and with fuzzy systems where few modelling and learning theories existed. Both B-spline and Gaussian Radial Basis Function networks can be regarded as neurofuzzy systems and soft inductive learning algorithms can be used to extract unknown, qualitative information about the relationships contained in the training data. In a similar manner, qualitative rules or information about the network's structure can be used to initialise the system. These areas, coupled with the extensive work being carried out on theoretically analysing their modelling, convergence and stability properties means that this research topic is highly applicable in "intelligent" modelling and control problems. Apart from outlining this work, the paper also discusses a wide variety of open research questions and suggests areas where new efforts may be fruitfully applied.

Algorithms↗
PubMed1994

Synthesis and inhibitory activity on platelet aggregation of 13'-aza and other omega-chain modified BW245C analogues.

BW245C analogues which have 15'-keto, -oximino, -sulphinyl, -sulphonyl, -methyl, -1-adamantyl, 14'-hydroxy, 16'-hydroxy, 13'-14'-NH=CH, -NH-CH2, or -NH-CO groups have been synthesized and evaluated for their activity in inhibiting platelet aggregation and for their cardiovascular actions: the 13'-aza analogues 13 and 14 are more potent inhibitors of human platelet aggregation than BW245C (0.3, 0.6 and 0.2 x PGI2, respectively) and these inhibitory activities on platelet aggregation increase on incubation in vitro. The prostaglandin mimetic properties of 13 (BW68C) and 14 (BW361C) were studied in more detail and their platelet inhibitory and vasodilatory effects found to be of longer duration than those of BW245C. All other modifications to the omega-chain of BW245C led to less potent or inactive compounds.

Animals↗
PubMed1994

Psychomotor skills of surgical trainees compared with those of different medical specialists.

Forty-eight trainees in surgery, psychiatry, anaesthetics and medicine underwent objective testing of manual dexterity (Mandex test), hand-eye coordination (Gibson spiral maze test) and visuospatial ability (embedded figures task). Surgical trainees performed significantly more quickly on the spiral maze test than psychiatrists (P = 0.03) but made more errors (P = 0.02). Combining male and female subjects across all groups, women were significantly more accurate than men. When men only were compared no psychomotor differences between specialty groups could be demonstrated. There were no differences in visuospatial ability by either sex or specialty. Self-selection on the basis of such skill is therefore unlikely.

Adult↗
PubMed1994

Characterisation of the solution conformation of a cyclic RGD peptide analogue by NMR spectroscopy allied with a genetic algorithm approach and constrained molecular dynamics.

The solution conformation of a cyclic RGD peptide analogue, cyclo-(S,S)-2-mercaptobenzoate-arginine-glycine-aspartate-2-mer captoanilide, has been determined via two independent approaches for the searching of conformational space and identification of conformations consistent with NMR and CD spectroscopic data: (i) the use of a binary genetic algorithm and (ii) a molecular dynamics simulation. Inter-proton distances were obtained via analysis of cross-peak volumes from a two-dimensional ROESY NMR spectroscopy experiment at 600 MHz and were used as constraints for the computational calculations. The mercaptoanilide amide proton resonance chemical shift had a very small temperature coefficient, indicating that this proton was hydrogen-bonded. Circular dichroism data showed that, in solution, the torsion angle about the disulfide bond was negative, consistent with one of the distinct conformations around this bond in the 200 ps molecular dynamics simulation. The backbone conformations of the structures resulting from the two different approaches were very similar.

Amides↗
PubMed1993

Synthesis and platelet aggregation inhibiting activity of acid side-chain modified hydantoin prostaglandin analogues.

A series of hydantoin prostaglandin analogues, in which the hexamethylene moiety of the acid side chain was replaced by other spacing groups possessing either ether, sulphide and/or olefin functionality, were prepared and evaluated for platelet aggregation inhibiting activity. The 4-thia analogue 13*) proved to be the most potent inhibitor (ca. 22x PGE1) and the 3-thia- and 3-oxa-analogues, 6 and 10 respectively, are approximately equipotent with BW245C (ca. 14x PGE1). Z-olefinic analogues (e.g. 11) were usually more potent than their E-isomers (e.g. 12). Structure-activity relationships are discussed in detail.

Alprostadil↗
PubMed1993

Mobile Work Site Health Promotion Programs can reduce selected employee health risks.

This study examined the effect of participation in a mobile work site health promotion program (MWHPP) on selected health risks. Measures of blood pressure, cholesterol total and total/high-density lipoprotein ratio, percent body fat, and submaximal fitness were taken at baseline, 6-, 12-, and 18-month intervals from 113 employed adults. Significant reductions (P < or = .01) were observed in all variables measured. Further analysis of the number of employees who went from high risk to low risk demonstrated a significantly reduced risk of hypercholesterolemia, cholesterol total/high-density lipoprotein ration, and obesity (average significant chi 2 = 9.3, P < or = .05). It was concluded that participation in MWHPPs can significantly reduce several major cardiovascular risk factors. MWHPPs are relatively inexpensive compared with in-house health promotion programs and are one of the most cost-effective methods of reducing employee health risk.

Adult↗
PubMed1993

Identification of a novel operon in Lactococcus lactis encoding three enzymes for lactic acid synthesis: phosphofructokinase, pyruvate kinase, and lactate dehydrogenase.

The discovery of a novel multicistronic operon that encodes phosphofructokinase, pyruvate kinase, and lactate dehydrogenase in the lactic acid bacterium Lactococcus lactis is reported. The three genes in the operon, designated pfk, pyk, and ldh, contain 340, 502, and 325 codons, respectively. The intergenic distances are 87 bp between pfk and pyk and 117 bp between pyk and ldh. Plasmids containing pfk and pyk conferred phosphofructokinase and pyruvate kinase activity, respectively, on their host. The identity of ldh was established previously by the same approach (R. M. Llanos, A. J. Hillier, and B. E. Davidson, J. Bacteriol. 174:6956-6964, 1992). Each of the genes is preceded by a potential ribosome binding site. The operon is expressed in a 4.1-kb transcript. The 5' end of the transcript was determined to be a G nucleotide positioned 81 bp upstream from the pfk start codon. The pattern of codon usage within the operon is highly biased, with 11 unused amino acid codons. This degree of bias suggests that the operon is highly expressed. The three proteins encoded on the operon are key enzymes in the Embden-Meyerhoff pathway, the central pathway of energy production and lactic acid synthesis in L. lactis. For this reason, we have called the operon the las (lactic acid synthesis) operon.

Amino Acid Sequence↗
PubMed1991

Imidazolidin-2-one prostaglandin analogues.

The 5-desoxy analogue of BW245C, imidazolidin-2-one 3, has been synthesized by reduction of the N-benzyl hydantoin derivative 6. Compound 3 was found to be approximately equipotent with BW245C as an inhibitor of platelet aggregation and this result indicates that the 5-keto group of BW245C is not essential for platelet inhibitory activity.

Cyclohexanes↗
PubMed1989

Peroxisomal bifunctional enzyme deficiency.

Peroxisomal function was evaluated in a male infant with clinical features of neonatal adrenoleukodystrophy. Very long chain fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain fatty acids in cultured fibroblasts was significantly impaired. Although the level of the bile acid intermediate trihydroxycoprostanoic acid was slightly elevated in plasma, phytanic acid and L-pipecolic acid levels were normal, as was plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical neonatal adrenoleukodystrophy. In addition, electron microscopy and catalase subcellular distribution studies revealed that, in contrast to neonatal adrenoleukodystrophy, peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblasts peroxisomal fractions showed that they contained acyl-CoA oxidase and beta-ketothiolase, but bifunctional enzyme was not detected. Northern analysis, however, revealed that mRNA coding for the bifunctional enzyme was present in the patient's fibroblasts. These results indicate that the primary biochemical defect in this patient is a deficiency of peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone.

3-Hydroxyacyl CoA Dehydrogenases↗