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Biomedical subjects

D W Oliver

Publications and source records attributed to D W Oliver.

At least 19 recordsLinked to original sources
PubMed2006

The pharmacological effects of ozone on isolated guinea pig tracheal preparations.

Ozone is a potent oxidizing agent with a variety of potential uses, including its antimicrobial and deodorising properties. The recent increased use of ozone led to questions regarding its safety in humans. This study specifically focussed on the in vitro effect of ozone on isolated guinea pig tracheal tissue as well as its effect on the isolated trachea in the presence of various drugs with well-known effects, including methacholine and isoproterenol. The results found in this study identified two direct effects on the isolated trachea due to ozone exposure: (1) a definite contraction of the isolated trachea immediately after exposure to ozone, and (2) a clearly visible and significant hyper responsiveness of the isolated trachea to irritants, e.g. methacholine. Although ozone has a negative effect on the trachea, it was concluded that ozone has no adverse effect on muscarinic receptors. We found that ozone has a significant desensitizing effect on the pharmacological response of beta sympathomimetics (isoproterenol), while isoproterenol itself has a relaxing effect on the ozone-induced contraction of the isolated trachea. Observations in this in vitro study further emphasised that ozone does have a negative effect on respiratory health. It is underlined that the inhalation of ozone should be avoided by workers who are often in contact with the gas, and especially by those with existing airway diseases. An apparent EC(50) value of ozone on the trachea was established by two different methods as 5.71 and 9.78 x 10(-3 )M, respectively.

Animals↗
PubMed2004

In vivo measurements of the cerebral perfusion and cardiovascular effects of the novel guanidine ME10092 in the non-human primate, Papio ursinus.

The novel guanidines N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine (ME 10092) and N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N1-hydroxyguanidine (PR5) were recently reported to exhibit promising cardioprotective activities in myocardial ischaemia and reperfusion in rats. The current study investigated for the first time pharmacological effects of ME10092 in the primate, viz. the Cape baboon Papio ursinus. The effects of ME10092 (1 and 2 mg/kg doses) on the cerebral blood flow, heart rates and the systolic and diastolic blood pressure were investigated after intravenous injection to the baboon under anaesthesia. The cerebral perfusion effects of ME10092 were assessed using Single Photon Emission Computed Tomography according to the split-dose approach and 99mTc-hexamethyl-propylene amine oxime as brain perfusion tracer. The observation that the recovery times from the anaesthesia were unacceptably prolonged excluded doses beyond 2 mg/kg. The data indicate that no cerebral perfusion changes were induced at both the 1 and 2 mg/kg doses of ME10092. Both these doses of ME10092 showed blood pressure and heart rate effects, with the latter being more significant. Decreases in heart rate were seen directly after ME10092 administration reaching levels of about 20% for the 2 mg/kg dose and about 15% for the 1 mg/kg dose at around 6 min post drug administration. A transient decrease in both systolic and diastolic blood pressure was observed for the higher dose. The blood pressure data further suggest an attenuation of the anaesthesia induced increase in pressure usually present in non-intervention studies. ME10092 clearly exhibits mycocardial effects in the non-human primate, similar to the effects previously observed in the ischaemia-reperfusion rat model, where ME10092 showed strong protection.

Anesthesia↗
PubMed2004

Hirudo Medicinalis and the plastic surgeon.

Medicinal leech therapy is an ancient craft that dates back to ancient Egypt and the beginnings of civilisation. The popularity of Hirudo Medicinalis has varied throughout history, reaching such a peak in Europe in the early 19th century that supplies were exhausted. During the latter half of the 19th century, their use fell out of favour, as they did not fit in with the emerging concepts of modern medicine. Leeches have enjoyed a renaissance in the world of reconstructive microsurgery during recent years, and their first reported use in alleviating venous engorgement following flap surgery was reported in this journal [M Derganc, F Zdravic, Venous congestion of flaps treated by application of leeches, Br J Plast Surg 13 (1960) 187]. Contemporary plastic and reconstructive surgeons in units throughout the United Kingdom and Ireland continue to use leeches to aid salvage of failing flaps. We carried out a survey of all 62 plastic surgery units in the United Kingdom and the Republic of Ireland to assess the current extent of use, and to investigate current practice. We have shown that the majority of plastic surgery units in the UK and Ireland use leeches post-operatively and that the average number of patients requiring leech therapy was 10 cases per unit per year. Almost all units use antibiotic prophylaxis, but the type of antibiotic and combination used is variable. We outline current practice and suggest a protocol for the use of leeches. Whilst the use of leeches is widespread, the plastic surgery community has progressed little in defining indications for their use or in achieving an accepted protocol for their application in units throughout the UK and Ireland.

Health Care Surveys↗
PubMed2004

Recent advances in drug action and therapeutics: relevance of novel concepts in G-protein-coupled receptor and signal transduction pharmacology.

PROBLEM STATEMENT: During especially the past two decades many discoveries in biological sciences, and in particular at the molecular and genetic level, have greatly impacted on our knowledge and understanding of drug action and have helped to develop new drugs and therapeutic strategies. Furthermore, many exciting new drugs acting via novel pharmacological mechanisms are expected to be in clinical use in the not too distant future. SCOPE AND CONTENTS OF REVIEW: In this educational review, these concepts are explained and their relevance illustrated by examples of drugs used commonly in the clinical setting, with special reference to the pharmacology of G-protein-coupled receptors. The review also addresses the basic theoretical concepts of full and partial agonism, neutral antagonism, inverse agonism and protean and ligand-selective agonism, and the relevance of these concepts in current rational drug therapy. Moreover, the mechanisms whereby receptor signalling (and eventually response to drugs) is fine-tuned, such as receptor promiscuity, agonist-directed trafficking of receptor signalling, receptor trafficking, receptor 'cross-talk' and regulators of G-protein signalling (RGSs) are discussed, from theory to proposed therapeutic implications. CONCLUSIONS: It is concluded that the understanding of molecular receptor and signal transduction pharmacology enables clinicians to improve their effective implementation of current and future pharmacotherapy, ultimately enhancing the quality of life of their patients.

Cell Communication↗
PubMed2003

Publication rates for abstracts presented at the British Association of Plastic Surgeons meetings: how do we compare with other specialties?

We present a retrospective study of the publication rates of articles presented to five meetings of the British Association of Plastic Surgeons between 1995 and 1999. The PubMed database (http://www.ncbi.nlm.nih.gov/PubMed/) was searched using the presenter's name and key words from the abstract. Publication rates varied from 23% for the Winter Meeting of 1999 to 54% for the Winter Meeting of 1997. The mean time lag from presentation to publication varied between 13 and 25 months (range: 1-46 months). These results are comparable to those found in some other medical specialties.

Bibliometrics↗
PubMed2003

Effective management of the airway in the Pierre Robin syndrome using a modified nasopharyngeal tube and pulse oximetry.

Pierre Robin syndrome is a rare condition, first described by the French stomatologist, Pierre Robin in 1923. The severity of the syndrome varies widely, and associated upper airway obstruction is the most difficult problem to overcome. We present a case in which the airway was successfully managed with a modified naso-pharyngeal tube in addition to pulse oximetry. We also present a literature review discussing management of the airway in the Pierre Robin syndrome. The simple technique presented allows earlier patient discharge with home monitoring equipment.

Airway Obstruction↗
PubMed2001

Measurement of cerebral perfusion after zolpidem administration in the baboon model.

A recent report showed that zolpidem (CAS 82626-48-0) can lead to the arousal of a semi-comatosed patient. Zolpidem is clinically used for the treatment of insomnia. It belongs to the imidazopyridine chemical class and is a non benzodiazepine drug. It illicits its pharmacological action via the GABA receptor system through stimulation of particularly the omega 1 receptors. In this study, the effect of zolpidem on brain perfusion was examined by 99mTc hexamethyl-propylene amine oxime (HMPAO) split dose brain SPECT on four normal baboons and in one baboon with abnormal neurological behaviour. The global and regional brain perfusion was not significantly affected in the normal brains. In some regions of the abnormal baboon brain, however, there was a disproportionate increase in perfusion after zolpidem.

Algorithms↗
PubMed2001

A prospective, randomized, double-blind trial of the use of fibrin sealant for face lifts.

Fibrin sealant imitates the final phase of the blood coagulation process. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin, which is then cross-linked by factor XIIIa, creating a mechanically stable fibrin network. This fibrin network is thought to reduce the amount of postoperative bleeding by sealing capillary vessels and allowing raw operative surfaces to adhere. The authors conducted a prospective, double-blind, randomized, controlled trial on the use of fibrin sealant in 20 consecutive patients undergoing bilateral face lifts by the same surgeon. Each patient was randomized for the use of fibrin sealant on either the right or the left side with the contralateral side acting as the control. Total drainage was recorded on each side for 24 hours before drains were removed. The age range of the patients in the trial (all of whom were women) was 44 to 70 years (mean, 55). The side treated with fibrin glue had a median drainage of 10 ml and the control side 30 ml. The Wilcoxon signed rank test shows a significant difference in drainage between sides (p = 0.002). The reduction in postoperative drainage could also reduce pain and bruising, increasing patient satisfaction with this procedure. The need for drains may also be obviated.

Adult↗
PubMed2001

Discrimination between the functional and biochemical effects of two herbal oxytocics on the rat myometrium.

This study on the rat myometrium is the first report where the effects of herbal extracts used as oxytocics in traditional medicine have been systematically analysed in the same preparation at the level of functional (contractile) and biochemical (second messenger generation) responses. Extracts of Agapanthus africanus and Clivia miniata (used in South African traditional medicine) were compared with other uterotonic agents with regard to their ability to stimulate phosphoinositide metabolism in the rat myometrium and cause accumulation of [3H]inositol phosphates. The maximal contractile response of the isolated rat myometrium in response to stimulation by the herbal extracts and agonists was compared with the maximal contractile response to cumulative addition of acetylcholine. The rank order of intensity of stimulation of [3H]inositol phosphate generation was: oxytocin > Agapanthus > prostaglandin F2alpha(PGF2alpha) > serotonin > acetylcholine > Clivia > ergometrine. This differed from the rank order of maximum contractile response: oxytocin > acetylcholine > PGF2alpha > serotonin approximately Clivia > Agapanthus > ergometrine. Activity was also identified in chemical fractions of the plants and components common to both plants have been identified in the isolated active fractions. These results have identified that the uterotonic activity of Agapanthus is linked to increased turnover of phosphoinositides as a signal transduction mechanism, whereas this appears to play a less significant role in the uterotonic activity of Clivia. This study illustrates the benefits of using the measurement of stimulation of phosphoinositide metabolism as a bioassay in phytomedical research.

Animals↗
PubMed2001

Tutorial on risk-adjusted P-charts.

Several books are available that describe how to construct control charts. Unfortunately none of these books show how to adjust control charts for the severity of the patients' illness. Without such adjustments control charts not only loose face validity but could lead to wrong conclusions. In this article we provide a step-by-step guide regarding how to control for changes in patients' severity of illness across time periods. We illustrate the use of the approach in examining falls in nursing homes. A control chart was constructed to compare observed falls to the residents' risk of fall measured on admission. Analysis led to conclusions radically different from an unadjusted chart.

Accidental Falls↗
PubMed2000

The effects of herbal oxytocics on the isolated "stripped" myometrium model.

Decoctions of Agapanthus africanus and Clivia miniata are used as oxytocic agents in South African traditional herbal medicine. Aqueous extracts of A. africanus and C. miniata leaves have been shown to possess similar uterotonic activities in the isolated whole uterus preparation. The uterus however, comprises a myometrial and an endometrial layer and the activity of both oxytocin and the prostaglandins differs in these layers. The aim of this study was to determine the uterotonic activity of the herbal remedies in an endometrium-free preparation (i.e. "stripped" myometrium) and, if active, whether this effect could be related to prostaglandin synthesis or to interaction with specific receptors. The effects of the herbal extracts were tested on the isolated "stripped" rat myometrium preparation. Both herbal extracts caused a direct contractile response by the isolated tissue. Pretreatment of the myometrium with either plant extract augmented the initial response to acetylcholine. Preincubation with atropine inhibited the response to cumulative dosage of Agapanthus extract but had no effect on the response to Clivia. Indomethacin administration did not affect the response of the myometrium to cumulative dosage of acetylcholine, oxytocin or Clivia extract but inhibited the response to Agapanthus extract. These results clearly indicate that the Agapanthus and Clivia herbal extracts exhibited uterotonic activity in this model. The study illustrates that the "stripped" myometrium model has successfully differentiated between the mechanisms of action of two herbal oxytocics compared to the whole uterus preparation where their uterotonic activity was thought to be similar.

Animals↗
PubMed2000

Meningococcal septicaemia and plastic surgery--a strategy for management.

Meningococcal septicaemia is a severe life threatening illness that is part of the spectrum of meningococcal disease. It is of particular concern to the plastic and reconstructive surgeon because as the medical and intensive care of these patients improves, more are surviving the acute phase of the septicaemia and suffering from the associated complications such as skin necrosis and extremity loss. Recently there have been several reports in the literature concerning the management of skin infarction with both skin grafting and free flap surgery. This paper will provide an update on the proposed pathophysiological mechanisms involved, summarise the present data on plastic surgical care and suggest a stratagem for future management of these difficult cases.

Adolescent↗
PubMed2000

Dispersal of radioisotope labelled solution following deep dermal injection in Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is the commonest inherited disorder of connective tissue, affecting around 10 000 patients in the UK. Patients with EDS have reported that local anaesthetic is often ineffective. Patients with less severe skin laxity often have the most problems. We have postulated that this resistance to local anaesthetics is not due to the lax connective tissues as is often assumed. This study used radioactively labelled solution ((99m)Tc-pertechnetate) administered as a deep dermal injection in the forearm. The rate of dispersal of isotope was measured over 60 min and found to be identical between six patients with EDS and three controls. The effects of local anaesthetics are complex and depend on the individual chemical properties of the agent and a number of tissue factors. This study would suggest that the lack of effectiveness of local anaesthetic solutions is not due to rapid dispersal of solution. It is unlikely therefore that its lack of effect can be compensated for by simply increasing the amount used. The diagnosis of EDS should be considered in any patient who complains unexpectedly of pain during their procedure, particularly when the surgeon knows that an adequate volume of local anaesthetic has been used.

Administration, Cutaneous↗
PubMed2000

Anti-silicone antibodies and silicone containing breast implants.

The detection of anti-silicone antibodies in patients with silicone breast implants (SBI) has been undertaken principally in the USA. We undertook a study of 20 women with SBI from different manufacturers from 6 weeks to 20 years after surgery, including those with ruptured implants. They were compared with three control groups: 20 women without implants, 20 women with auto-immune disease and 20 anonymous blood donors. Potential anti-silicone antibodies (IgG) were tested against a variety of silicone polymer antigens using an enzyme linked immunosorbent assay (ELISA) technique which had previously detected positive results in an uncontrolled series. Silicone-free collecting tubes were used. No differences were found between the patients with SBI and controls. However, samples that had been stored for the longest time, or frozen and thawed several times, had the highest levels. These false positives appear to be due to an unknown but human specific IgG binding phenomenon. We conclude that there is no demonstrable anti-silicone antibody formation in these patients with SBI and we would caution that the effect of storage may have been an important factor in previously published assay methods. This study supports the safety of silicone containing breast implants.

Adolescent↗
PubMed2000

Effect of cyclodextrin complexation on the in vivo disposition of the brain imaging radiopharmaceutical 99mTechnetium ethyl cysteinate dimer (99mTc-ECD).

The brain imaging radiopharmaceutical, 99mTechnetium ethyl cysteinate dimer (99mTc-ECD, 99mTc-bicisate) is the most recent addition to the available set of radiopharmaceuticals for measuring cerebral blood flow. Ideally radiotracers should be trapped in the brain long enough so that their distribution can be quantitated and should demonstrate good spatial resolution. Furthermore, the stability (chemical and metabolic) and bioavailability of radiopharmaceuticals have in general proved to be a challenge during development and clinical administration. In view of these challenges and background, this study with 99mTc-ECD is presented. The aims of this research program were to develop novel approaches to improve the chemical and metabolic stability and the bioavailability of 99mTc-ECD across the blood brain barrier for cerebral blood flow determinations, using the well known non-human primate in vivo baboon model. These aims were addressed by investigating the influence of cyclodextrin--99mTc-ECD complexation on normal cerebral blood flow patterns, using two different cyclodextrins, i.e., gamma-cyclodextrin (CAS 17465-86-0) and beta-trimethylcyclodextrin (CAS 55216-11-0). The effect of incubation of 99mTc-ECD (with or without cyclodextrin complexation) in plasma, on metabolic esterase action, was also investigated. Possible protection against plasma esterase by acetylcholine (CAS 51-84-3) of 99mTc-ECD was further determined. The current study has shown that cyclodextrin complexation of 99mTc-ECD indeed offers a useful approach to improve the stability of the radiopharmaceutical against peripheral metabolism. The acetylcholine shows also potential to protect 99mTc-ECD. However, it is clear from the current data that the choice of cyclodextrin is of utmost importance, as has been observed from significantly reduced the bioavailability of 99mTc-ECD when complexed with beta-trimethylcyclodextrin. The plasma incubation procedures showed that gamma-cyclodextrin offers protection with only slightly reduced bioavailability. This study has indicated that novel approaches, such as cyclodextrin technologies, indeed show potential to modify the performance in its currently available 99mTc-ECD form.

Anesthetics, Dissociative↗