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Biomedical subjects

P Nicholson

Publications and source records attributed to P Nicholson.

12 recordsLinked to original sources

Evaluation of the optimal hand-scrub duration prior to total hip arthroplasty.

Orthopaedic surgeons in many major arthroplasty centres advocate the use of a prolonged surgical hand-scrub prior to total joint replacement. In this study we evaluated the antimicrobial efficacy of a 5 compared with a 10 min scrub before both long (> 90 min) and short (< 90 min) operations for total hip arthroplasty. Surgical hand disinfection was performed on one occasion for 5 min and on a second for 10 min by 41 surgeons and theatre nurses using 4% chlorhexidine gluconate as a detergent formulation ('Hibiscrub', ICI Pharmaceuticals). None of the subjects had previously scrubbed on the day of each test. Bacterial colony counts on the fingers were measured using the method described by Rotter (vide infra) before scrubbing, immediately after scrubbing, and at the end of each operation. Our results showed that for arthroplasty procedures lasting less than 90 min (35 operations) a 5 min hand-scrub was equally as effective as one of 10 min. However, following longer procedures (36 operations) colony counts were significantly higher on subjects who had scrubbed for 10 min than on those who only scrubbed for 5 (P < 0.05, Mann-Whitney U-Test). This study suggests that the practice of a prolonged scrub before total joint replacement does not have a scientific basis and that such a policy should be discontinued where it is still practised.

Aerosols

Localization of the herpes simplex virus type 1 major capsid protein VP5 to the cell nucleus requires the abundant scaffolding protein VP22a.

The intracellular distributions of three herpes simplex virus type 1 (HSV-1) capsid proteins, VP23, VP5 and VP22a, were examined using vaccinia virus and plasmid expression systems. During infection of cells with HSV-1 wild-type virus, all three proteins were predominantly located in the nucleus, which is the site of capsid assembly. However, when expressed in the absence of any other HSV-1 proteins, although VP22a was found exclusively in the nucleus as expected, VP5 and VP23 were distributed throughout the cell. Thus nuclear localization is not an intrinsic property of these proteins but must be mediated by one or more HSV-1-induced proteins. Co-expression experiments demonstrated that VP5 was efficiently transported to the nucleus in the presence of VP22a, but the distribution of VP23 was unaffected by the presence of either or both of the other two proteins.

Biological Transport

Assembly of herpes simplex virus type 1 capsids using a panel of recombinant baculoviruses.

Immature or B capsids of herpes simplex virus type 1 (HSV-1) are composed of seven proteins encoded by six viral genes. The proteins encoded by UL18 (VP23), UL19 (VP5), UL35 (VP26) and UL38 (VP19C) are components of the outer capsid shell whereas those specified by UL26 (VP21 and VP24) and UL26.5 (VP22a), are involved in scaffold formation. We have used a panel of recombinant baculoviruses, each expressing one of the capsid protein genes, to examine the requirements for capsid assembly. Coexpression of the six genes in insect cells resulted in the formation of capsids that were indistinguishable in appearance and protein composition from those made during HSV-1 infection of mammalian cells. This demonstrates that the proteins encoded by the known capsid genes contain all the structural information necessary for capsid assembly and that other virus-encoded proteins are not required for this process. Omission of single recombinant baculoviruses from this system allowed the role of individual HSV-1 proteins in capsid assembly to be determined. Thus, capsid assembly did not take place in the absence of VP23, VP5 or VP19C, whereas lack of VP26 had no discernible effect on capsid formation. Capsids assembled in the absence of the UL26 gene products had a large-cored phenotype resembling that previously described for the HSV-1 mutant ts1201 which has a lesion in this gene. Some apparently intact capsid shells were also made in the absence of the major scaffolding protein, VP22a, whereas the omission of both UL26 and UL26.5 resulted in the appearance of large numbers of partial and deformed capsid shells.

Animals

The action of nine chelators on iron-dependent radical damage.

Nine iron chelators were tested in five systems for their effects on radical-generation and conversion at chelator: iron molar ratios from 0.1 to 10. Stimulatory actions might distinguish toxic from safer chelators. Radical-generating reactions which represent different aspects of iron (ferrous and ferric) availability were studied: a) the reaction with hydrogen peroxide to hydroxylate benzoate; b) the oxidation of ascorbate; c) the reaction with hydrogen peroxide to fragment proteins; d) the reaction with hydrogen peroxide to permit amplified chemiluminescence; and e) the induction of peroxidation of mitochondrial membrane lipids. The compounds used were HBED, CP130, Desferal, EDTA, pyridine-hydrazone (CGP 43'902B), Ferrozine, CP94 (CGP 46'700), L1 (CGP 37,391) and rhodotorulic acid (CGP 45 274). Only the hexadentate compounds HBED, CP130 and Desferal were uniformly inhibitory ("protective"). The protective compounds were also apparently more stable during radical fluxes than the other chelators.

Animals

Prostaglandin deficiency.

Healthy cells from virtually all tissues synthesize a variety of prostaglandins, autacoids which can significantly alter cellular functions. An absolute or relative deficiency of prostaglandins has now been demonstrated in many diseases or clinical conditions. These include 'natural' disorders such as peptic ulcer disease and diabetes mellitus. These also include 'acquired' or iatrogenic conditions such as cyclosporine nephrotoxicity and the gastropathy induced by nonsteroidal anti-inflammatory drugs. We believe that the diversity of the disorders associated with prostaglandin deficiency may be wider and of greater pathogenetic importance than is currently recognized. We propose: 1) that prostaglandin deficiency will be demonstrated in many abnormalities which are now described as of uncertain etiology; and 2) that adverse effects from many commonly prescribed drugs may also be related to an unrecognized and unfavorable alteration in prostaglandin synthesis, disposal, or activity.

Humans

Stress-induced protein synthesis in Chlamydomonas reinhardtii.

Following exposure to UV light the synthesis of six polypeptides (112, 100, 89, 76, 71 and 65 kDa) was found to be enhanced or induced in the alga Chlamydomonas reinhardtii. Treatment with 4-nitroquinoline-N-oxide (NQO) resulted in the enhanced/induced synthesis of six polypeptides with molecular masses similar to those enhanced following exposure to UV light. Heat shock resulted in the enhanced synthesis of five polypeptides (89, 76, 71, 60 and 22 kDa), three of which (89, 76 and 71 kDa) had apparently identical mobilities to polypeptides whose synthesis was enhanced following UV treatment.

4-Nitroquinoline-1-oxide

Types of Salmonella paratyphi B and their phylogenetic significance.

The substrates inositol, rhamnose, d-tartrate and m-tartrate used in fermentation tests with 338 cultures of Salmonella paratyphi B differentiated strains in some phage types to give information that could be used in epidemiological investigations. Xylose in Bitter's medium, the fifth substrate by which 13 of a potential 32 biotypes were identified, differentiated few cultures with the negative character. The possession of a specific type of outer-membrane protein receptor for colicin M or bacteriophage ES18 and the particular type of ribosomal ribonucleic acid present, defined three groups among the phage-typed and biotyped cultures. The possibility that the serotype S. paratyphi B contains clones of different phylogenetic origin and the consequent implications for nomenclature are discussed.

Bacteriophage Typing

Studies on the subunit structure of textilotoxin, a potent neurotoxin from the venom of the Australian common brown snake (Pseudonaja textilis).

Textilotoxin is a presynaptic neurotoxin from the venom of the Australian common brown snake, Pseudonaja textilis. It has the highest lethality and is structurally the most complex of any known snake venom neurotoxin. It was resolved into its five non-covalently linked subunits in a single step by reverse-phase HPLC. Two of the subunits were identical. The N-terminal amino-acid sequence and amino-acid composition of each subunit were determined. Subunit A was the only one found to possess phospholipase A activity. Separation of textilotoxin into its subunits was reversible and reformed textilotoxin had the same Mr and lethality in mice as the native toxin. Experiments with various unnatural combinations of subunits have led to interesting variations in lethality and Mr of the resulting complexes.

Amino Acid Sequence

IgE FAST inhibition: a rapid technique for the standardization of pollen allergen extract potency.

An IgE FAST(TM) inhibition protocol has been developed as a rapid in vitro method for determining relative potencies of in vivo allergenic extracts. Results are obtained within one day and correlate well with those of the RAST inhibition protocol (r = .96), making the FAST assay a preferable procedure for inprocess potency determination during the manufacture of standardized allergenic extracts.

Allergens

Controlled randomized group comparison of nomifensine and imipramine in depressive illness.

1. Nomifensine, an isoquinoline dopaminergic agonist, was investigated in a randomized double-blind group comparison with imipramine, in 40 out-patients with depression. 2. Assessments were made at weekly intervals for 4 weeks using the Hamilton Depression Scale and the Beck Depression Inventory. Blood, kidney and liver function were also monitored weekly. 3. Nomifensine was shown to be at least as effective as imipramine in relieving depression and to relieve tha anxiety component of the disease significantly more rapidly. Neither drug produced serious unwanted effects.

Adult

One minute wisdom.

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Activities of Daily Living