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Biomedical subjects

R W Clarke

Publications and source records attributed to R W Clarke.

At least 19 recordsLinked to original sources
PubMed2006

Recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a benign, often multi-focal neoplasm. A potentially fatal manifestation of human papilloma virus infection, the condition is characterised by multiple warty excrescences on the mucosal surface of the respiratory tract. RRP is rare--incidence is estimated at 3.5 per million person-years, with a prevalence of 4 in 100,000 children. Affected children usually require multiple interventions; the impact on patients, their families, and the healthcare system is considerable. Treatment of RRP accounts for an estimated dollar 109 million annual expenditure in the USA.

Antiviral Agents↗
PubMed2005

Paediatric otolaryngology services in the UK: a postal questionnaire survey of ENT consultants.

Approximately half a million children in England and Wales receive in-patient or day-case surgical treatment annually. Otolaryngology is the surgical specialty that provides the greatest number of episodes of such care. As 30-50 per cent of our total volume of work is paediatric, we feel it is important to assess current attitudes to paediatric otolaryngological practice. In its year 2000 document Children's Surgery: a First Class Service, The Royal College of Surgeons (RCS) of England sets out recommendations on how children's surgical services should be delivered in the UK. A postal questionnaire was sent to all UK-based ENT consultant members of the British Association of Otorhinolaryngologists-Head and Neck Surgeons (BAO-HNS). The questionnaire was designed to assess the current practice of paediatric otolaryngology in the UK with an emphasis on the RCS recommendations. Wide variations were found, and they are discussed with reference to the recommendations.

Anesthesiology↗
PubMed2005

Passive smoking, allergic rhinitis and nasal obstruction in children.

Allergic rhinitis is a common cause of nasal obstruction in childhood. This prospective study looked at the effect of passive smoking on nasal obstruction in children with and without allergic rhinitis. Eighty-one children took part. Each child was asked to score his or her degree of nasal obstruction on a visual analogue scale. Exposure to passive smoking was determined subjectively using a parental questionnaire, and objectively by measuring the urinary cotinine/creatinine ratio. Results were tabulated using Microsoft Excel and analysed with SPSS statistical software. Nasal obstruction was significantly worse in children with a positive history of allergic rhinitis (p < 0.05). There was also a trend towards a higher nasal obstruction score in children without allergic rhinitis exposed to passive smoking compared to those who were not so exposed. As would be expected, nasal obstruction is worse in children with allergic rhinitis than in those without. Passive smoking tends to increase the symptom of nasal obstruction in children without allergic rhinitis.

Adolescent↗
PubMed2005

Aryepiglottoplasty for laryngomalacia: the Alder Hey experience.

Laryngomalacia is the most common cause of stridor in infants. Severely affected children are at risk of feeding difficulties, apnoeic episodes and cor pulmonale secondary to upper airway obstruction. The aim of this study was to assess the outcome of aryepiglottoplasty. This is a simple surgical procedure that relieves the obstruction by dividing the aryepiglottic folds. Thirty children had an aryepiglottoplasty at the Royal Liverpool Children's Hospital between January 1995 and June 2001. The case notes of all 30 children were reviewed for age, sex, age at operation, indications, operative technique, complications and long-term outcomes. Complete resolution of stridor was obtained in 83 per cent of patients, with an improvement in a further 7 per cent. Post-operative complications included lower respiratory tract infections (13 per cent) and vomiting (7 per cent). In conclusion, simple endoscopic aryepiglottoplasty remains an effective way of treating upper airway obstruction in children. Its high resolution and low complication rate make it a safe, first choice procedure for treatment of moderate to severe laryngomalacia.

Arytenoid Cartilage↗
PubMed2005

Otitis media in children.

Otitis media is the term used for a group of conditions characterized by inflammation of the middle-ear cleft. These conditions are particularly common in children where they present important diagnostic and therapeutic dilemmas.

Acute Disease↗
PubMed2004

Endoscopy: a must in neonatal respiratory distress.

Respiratory distress in a newborn presents both diagnostic and therapeutic dilemmas. Definitive treatment must be preceded by an accurate diagnosis other than in extremes. Complete tracheal rings are a very rare congenital cause of airway obstruction. Unlike other causes of upper airway obstruction, this cannot be relieved by tracheostomy, which may be counterproductive. We report the case of an 8-day-old female baby who presented with respiratory distress and was found to have complete tracheal rings and right pulmonary agenesis. The value of tracheo-bronchoscopy in this case cannot be overstressed.

Airway Obstruction↗
PubMed2004

Complete tracheal rings: lower airway symptoms can delay diagnosis.

Bronchial asthma is a very common condition seen in children diagnosed by clinical examination. While treating these children, all the other possible causes of breathlessness including complete tracheal rings should be considered. Further investigations in the form of endoscopy may need to be carried out in doubtful cases.

Airway Obstruction↗
PubMed2004

A sinonasal primary Ewing's sarcoma.

Nasal fractures are a common complaint familiar to all otolaryngologists. Sinonasal primary Ewing's sarcomas are extremely rare. The case of a 9-year-old boy is presented whose nasal fracture and subsequent lateral nasal wall hematoma revealed an underlying Ewing's sarcoma. There are several unusual features in the history and clinical course of this patient. Following biopsies, immunohistochemistry proved essential in distinguishing a Ewing's sarcoma from other small cell tumours. It is important that a seemingly common condition can be the first presentation of a less common, more sinister pathology.

Biopsy, Fine-Needle↗
PubMed2004

Advances in genetic manipulations in the treatment of hearing disorders.

Gene transfer into the inner ear is an attractive technology for clinical applications. It offers the hope of preventing, arresting, reversing or curing vestibular or hearing disorders caused by hereditary diseases or environmental insults. There are currently very few treatment options for vestibular disorders and sensorineural hearing loss, and therefore, it is important to investigate and develop new technologies for inner ear disease. In utero gene transfer may indeed be an option, but this technology will have many technical and ethical issues that remain to be overcome.

Gene Transfer Techniques↗
PubMed2004

Glutamate and tachykinin receptors in central sensitization of withdrawal reflexes in the decerebrated rabbit.

This study assessed the involvement of NMDA and group I metabotropic glutamate receptors, and tachykinin NK1 and NK3 receptors, in central sensitization of withdrawal reflexes in the decerebrated rabbit. Reflexes evoked in the ankle flexor tibialis anterior and the knee flexor semitendinosus by electrical stimulation at the base of the toes were enhanced for 29-63 min after application of 20% mustard oil to the tips of the toes. Selective antagonists of mGlu1, mGlu5, NMDA and NR2B-subunit-containing NMDA glutamate receptors, as well as NK1, and NK3 receptors, and a non-selective blocker of all tachykinin receptors, were assessed for their effects on the magnitude and duration of the increase in reflexes induced by mustard oil. Dizocilpine, an antagonist of all NMDA receptors (1 mg intrathecal) abolished facilitation of tibialis anterior reflexes and significantly reduced the magnitude and duration of increase of the semitendinosus response. The NR2B-subtype selective antagonist CP-101,606 decreased the magnitude of facilitation of both reflexes but had no effect on duration of enhancement. Selective antagonists for the mGlu1 (CPCCOEt, 1-3 mg intrathecal), mGlu5 (MPEP, 0.2-1 mg intrathecal), NK1 (L-733,060, 0.3 mg intrathecal) or NK3 (SR 142,801, 1 mg kg(-1) i.v.) receptors had no effect on the amplitude or duration of sensitization. However, the non-selective tachykinin receptor blocker ZD-6021 (0.3 mg intrathecal) reduced the amplitude but not the duration of sensitization in the flexor reflexes. Combination of ZD-6021 with CP-101,606 (doses as above) decreased both aspects of the sensitization response. Dizocilpine reduced reflexes evoked from the heel per se, and dizocilpine, CP-101,606 and ZD-6021 reduced arterial blood pressure. Otherwise the drugs used had no effects on baseline variables. The present data confirm the importance of NMDA receptors as a critical part of the process of central sensitization, provide no evidence for a role of metabotropic glutamate receptors, and show that simultaneous blockade of all tachykinin receptors is required to reveal their role in hyperalgesia. The data further indicate that a combined pharmacological approach offers a potential way forward for the development of new antihyperalgesic agents.

Animals↗
PubMed2003

Direct lung delivery of para-aminosalicylic acid by aerosol particles.

Para-aminosalicylic acid (PAS), a tuberculostatic agent, was formulated into large porous particles for direct delivery into the lungs via inhalation. These particles possess optimized physical properties for deposition throughout the respiratory tract, a drug loading of 95% by weight and physical stability over 4 weeks at elevated temperatures. Upon insufflation in rats, PAS concentrations were measured in plasma, lung lining fluid and homogenized whole lung tissue. Systemic drug concentrations peaked at 15 min, with a maximum plasma concentration of 11+/-1 microg/ml. The concentration in the lung lining fluid was 148+/-62 microg/ml at 15 min. Tissue concentrations were 65+/-20 microg/ml at 15 min and 3.2+/-0.2 microg/ml at 3h. PAS was cleared within 3 h from the lung lining fluid and plasma but was still present at therapeutic concentrations in the lung tissue. These results suggest that inhalation delivery of PAS can potentially allow for a reduction in total dose delivered while providing for higher local and similar peak systemic drug concentrations as compared to those obtained upon oral PAS dosing. Similar particles could potentially be used for the delivery of additional anti-tuberculosis agents such as rifampicin, aminoglucosides or fluoroquinolones.

Administration, Inhalation↗
PubMed2003

Tetrodotoxin block of A-fibre conduction and its effect on reflex responses evoked by electrical stimulation of the sural nerve in the decerebrated rabbit.

In the present study, we have investigated the viability of using tetrodotoxin (TTX) to induce selective blockade of myelinated fibre conduction in rabbit sural nerve, and explored some aspects of reflexes evoked by non-myelinated sural nerve afferents before and after application of TTX. In rabbits decerebrated under halothane-nitrous oxide anaesthesia, application of 30 nM TTX to the desheathed sural nerve completely blocked Abeta and Adelta waves of the compound action potential evoked by electrical stimulation of the nerve at 95 times threshold. The amplitude of C-fibre volleys evoked by these stimuli was reduced to a mean of 60 % of pre-treatment values. Reflexes evoked in medial gastrocnemius motoneurones by sural nerve stimulation showed corresponding changes after TTX treatment, with activation latency increasing from 5-7 ms in the control state to > 100 ms after TTX application. Temporal summation (wind up) in long latency reflexes (> 100 ms) was significantly enhanced after application of TTX. These data show that low concentrations of TTX can selectively block conduction in rabbit sural nerve A-fibres, providing a method for studying the central actions of non-myelinated C-fibres in isolation.

Animals↗
PubMed2002

Interactions between cutaneous afferent inputs to a withdrawal reflex in the decerebrated rabbit and their control by descending and segmental systems.

Previous studies have suggested that activation of nociceptive afferents from the heel recruits a supraspinal mechanism, which is modulated by adrenergic descending inhibition, that augments withdrawal reflexes in medial gastrocnemius (MG) motoneurones. To test this idea, we have studied the temporal evolution of reflexes evoked in MG by electrical stimulation of sural nerve A(beta)-, A(delta)- and C-fibre axons at 1 Hz, in decerebrated rabbits. Reflexes were analysed in three time bands, estimated to accord to afferent drive from A(beta)- (phase 1), A(delta)- (phase 2) and C-fibre (phase 3) inputs. Stimulation of A(delta)- and C-fibres gave significant temporal summation of all reflexes. The alpha(2)-adrenoceptor antagonist RX 821002 ((2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)-4,5-dihydro-1-H-imidazole)-HCl) (100 microg intrathecal (i.t.)) potentiated, and the alpha(2)-agonist dexmedetomidine (1-30 microg i.t.) depressed all reflexes per se, but the effects of these drugs on temporal summation were secondary to changes in baseline excitability. When C-fibres were stimulated, the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (1 mg i.t.) reduced temporal summation of phase 2 and 3 but not phase 1 reflexes. Spinalisation at L1 in the absence of drugs increased phase 2 and 3 reflexes but had no effect on phase 1, whereas spinalisation after RX 821002 resulted in decreased phase 1 responses with no significant change in later phases. Spinalisation in the presence of dizocilpine resulted in small reductions in phase 3 reflexes only. In all cases spinalisation virtually abolished temporal summation. In spinalised animals, dizocilpine selectively reduced late reflexes, and the opioid antagonist naloxone (100 microg i.t.) augmented all reflexes but gave rise to temporal subtraction of reflexes when C-fibres were stimulated.The present experiments have revealed a number of novel and important features of the sural-MG reflex pathway: (i) activity in fine afferent axons augments the reflexogenic potential of all subsequent afferent input, thereby allowing all afferent drive from the sural field to contribute to withdrawal of the heel; (ii) endogenous adrenergic control of this reflex pathway is completely non-selective; (iii) there is a non-adrenergic element of descending inhibition that is selective for the late components of MG reflex responses, and this element is directed particularly against transmission through NMDA receptors; (iv) temporal summation in this reflex is dependent on NMDA receptor-dependent and -independent mechanisms; and (v) this temporal summation is in some way dependent on the integrity of descending pathways.

Adrenergic alpha-Agonists↗
PubMed2002

RX 821002 as a tool for physiological investigation of alpha(2)-adrenoceptors.

RX 821002 is the 2-methoxy congener of idazoxan. In binding and tissue studies it behaves as a selective antagonist of alpha(2)-adrenoceptors, with at least 5 times greater affinity for these receptors than any other binding site. It does not select between the different types of alpha(2)-receptor. Although this drug probably has no future as a therapeutic agent, it remains a good probe for physiological activity at alpha(2)-adrenoceptors in animal experiments. A particularly useful feature of this compound is its lack of binding at I(1) and I(2) imidazoline receptors. However, it has relatively high affinity for 5-HT(1A) receptors (at which it acts as an antagonist) and a tendency to behave as an inverse agonist at alpha(2A)-adrenoceptors in some cell culture systems. These potential drawbacks may be overcome by careful design of experiments, and the greater selectivity of RX 821002 renders it much superior to yohimbine or idazoxan as a tool for probing physiological actions at alpha(2)-receptors. It can be compared favorably with other selective antagonists such as atipamezole. In physiological studies, RX 821002 augments norepinephrine release in the frontal cortex and increases drinking behavior in rat. In rabbit, intrathecal administration of this drug enhances somatic and autonomic motor outflows, showing that tonic adrenergic descending inhibition of withdrawal reflexes and sympathetic pre-ganglionic neurons is strong in this species. The potentiation of reflexes may be considered a pro-nociceptive action. In the same model, RX 821002 antagonizes the inhibitory effects of the mu opioid fentanyl, indicating that exogenous opioids synergize with endogenously released norepinephrine in the spinal cord. Thus, the careful use of RX 821002 has revealed several aspects of the physiological activity of alpha(2)-adrenoceptors in rabbit spinal cord and rat brain. We recommend that RX 821002 and/or compounds with similar selectivity for alpha(2)-adrenoceptors (atipamezole, MK-912, RS-79948) should be used in preference to yohimbine or idazoxan in all future studies of this type.

Adrenergic alpha-Agonists↗