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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 19 recordsLinked to original sources
PubMed2006

Heterotopic gastric mucosa in the cervical oesophagus (inlet patch) and globus pharyngeus--an under-recognised association.

Globus pharyngeus is a symptom commonly encountered in ENT practice. The usual complaint is that of the sensation of a ball or lump in the throat generally unaccompanied by dysphagia. This sensation is often more pronounced when taking an 'empty swallow'. The precise mechanism of this remains enigmatic in many cases. Irritant factors such as gastroesophageal reflux, postnasal drip and excessive throat clearing may be contributory factors as may be stress and psychological influences. Although gastric type mucosa occupying the cervical oesophagus has been long recognised, mainly in the specialised gastrointestinal literature, there appears to be more limited awareness of the condition in ENT practice and the clinical significance of such heterotopia is not well established. We present five recent cases of globus pharyngeus encountered in our ENT practice in which rigid pharyngoesophagoscopy and biopsy revealed heterotopic gastric mucosa within the postcricoid and cervical oesophagus constituting a so-called gastric 'inlet patch'. One case re-presented with invasive adenocarcinoma within a short time. Herein we compare and contrast inlet patch with columnar lined oesophagus, discuss the potential clinical significance of inlet patch and comment upon further management of the condition.

Adult↗
PubMed2006

High case-fatality rates of meningococcal disease in Western Norway caused by serogroup C strains belonging to both sequence type (ST)-32 and ST-11 complexes, 1985-2002.

A total of 293 meningococcal disease (McD) patients from Western Norway hospitalized during 1985-2002 were examined for risk factors related to death. The case-fatality rate (CFR) increased from 4% during 1985-1993 to 17% during 1994-2002. We analysed the phenotypic and genotypic characteristics of the meningococcal patient isolates, with the aim of identifying whether highly virulent meningococcal strains contributed to the increased CFR. The Norwegian epidemic strain B:15:P1.7,16/ST-32 complex was overall the most common phenotype/genotype (n=75) and caused most deaths (n=9; CFR 12.0%). However, fatality was significantly associated with disease caused by serogroup C meningococcal strains; C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains, which had the highest CFRs of 21.1% and 18.2% respectively. Serogroup B strains of the ST-32 complex differing by serotype and/or serosubtype from the epidemic strain had a CFR of 5.1%, while the CFR of disease caused by other strains (all phenotypes and genotypes pooled) was 2.2%. The distribution of phenotypes/clonal complexes varied significantly between 1985-1993 and 1994-2002 (P<0.001); B:15/ST-32 complex strains decreased whereas both C:15:P1.7,16/ST-32 complex strains and strains with other phenotypes/clonal complexes increased. Our results indicate that C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains were highly virulent strains and contributed to the high CFR of McD in patients from Western Norway. To reduce fatality, rapid identification of such virulent strains is necessary. In addition, early and specific measures should include public information, vaccination of populations at risk of disease and carriage eradication, when clustering of patients occurs.

Genotype↗
PubMed2006

Drug therapy for obstructive sleep apnoea in adults.

BACKGROUND: The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during sleep. However this is not tolerated by all patients and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea and could be of value in patients intolerant of CPAP. A number of mechanisms have been proposed by which drugs could reduce the severity of OSA. These include an increase in tone in the upper airway dilator muscles, an increase in ventilatory drive, a reduction in the proportion of REM sleep, an increase in cholinergic tone during sleep, a reduction in airway resistance and a reduction in surface tension in the upper airway. OBJECTIVES: To determine the efficacy of drug therapies in the treatment of sleep apnoea. SEARCH STRATEGY: We carried out searches on the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2005. SELECTION CRITERIA: Randomised, placebo controlled trials involving adult patients with confirmed OSA . We excluded trials if continuous positive airways pressure, mandibular devices or oxygen therapy were used. No restriction was placed upon publication language or trial duration. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion, undertook data extraction according to pre-specified entry criteria, and quality assessment of studies. No response for further information was forthcoming from study authors. Results were expressed as mean differences and 95% Confidence Intervals (CI). MAIN RESULTS: Twenty-six trials of 21 drugs, involving 394 participants contributed data to the review. Most of the studies were small and many trials had methodological limitations. Each of the studies states that the subjects had OSA but diagnostic criteria were not always explicit and it is possible that some patients with central apnoeas may have been recruited. Six drugs had some impact on OSA severity and two altered daytime symptoms. One study reported that apnoea hypopnea index (AHI) was lower following treatment with intranasal fluticasone compared with placebo (23.3 versus 30.3) in 24 participants with sleep apnoea and rhinitis. Subjective alertness in the daytime also improved. Physostigmine gave an AHI of 41 compared to 54 on placebo (10 participants) and in a similar study Mirtazipine 15 mg produced an AHI of 13 compared to 23.7 for placebo (10 participants). Topical nasal lubricant given twice overnight resulted in an AHI of 14 compared to 24 with placebo (10 participants). These three latter studies were of single night crossover design and so there are no data on the acceptability of these treatments or their effect on symptoms. Paroxetine was shown to reduce AHI to 23.3 compared to 30.3 for placebo, most of the 20 participants tolerated the treatment but there was no improvement in daytime symptoms. Acetazolamide also reduced the AHI (one crossover trial of nine patients, mean difference 24 (95% CI 4 to 44). However there was no symptomatic benefit from the drug and it was poorly tolerated in the long term. Protriptyline led to a symptomatic improvement (improved versus not improved) in two out of three crossover trials (13 participants, Peto Odds Ratio 29.2 (95% CI 2.8 to 301.1) but there was no change in the apnoea frequency. In one trial naltrexone did reduce AHI, but total sleep time favoured placebo. No significant beneficial effects were found for medroxy progesterone, clonidine, mibefradil, cilazapril, buspirone, aminophylline, theophylline doxapram, ondansetron or sabeluzole. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short-term outcome. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24 and 45%. For fluticasone, mirtazipine, physostigmine and nasal lubricant, studies of longer duration are required to establish whether this has an impact on daytime symptoms. Individual patients had more complete responses to particular drugs. It is likely that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study.

Humans↗
PubMed2006

Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AI) are increasingly used in early breast cancer and there is a growing interest in associated long-term side-effects of profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis are often managed with vaginal estrogen preparations. These are generally perceived to result in minimal systemic absorption of estrogen. We followed serum estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in seven postmenopausal women using vaginal estrogen preparations whilst on AIs for breast cancer. PATIENTS AND METHODS: Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal estradiol. Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women. RESULTS: Serum estradiol levels rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks. By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women. CONCLUSIONS: The vaginal estradiol tablet Vagifem significantly raises systemic estradiol levels, at least in the short term. This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated.

Aromatase Inhibitors↗
PubMed2006

Variations in case fatality and fatality risk factors of meningococcal disease in Western Norway, 1985-2002.

In a retrospective epidemiological study, 293 meningococcal disease patients hospitalized during 1985-2002, were examined for fatality and risk factors related to death. The overall case fatality rate (CFR) was 8.2%, but increased from 4% during 1985-1993 to 17% during 1994-2002. The latter 9-year period was characterized by more serogroup C infections and more patients with thrombocytopenia on admission to hospital. All patients categorized as meningitis on admission survived. Of the 24 patients who died, 21 had meningococcal skin rash on admission, 23 had an onset to admission time of < or =24 h, and 16 had severe septicaemia with hypotension and/or ecchymoses without meningitis on admission. By multivariate analyses, a short onset to admission time, >50 petechiae, thrombocytopenia and severe septicaemia on admission were associated with fatality. More lives could be saved through earlier admission to hospital. This can be achieved through more information to the public about the early signs of meningococcal septicaemia, with the recommendation to look for skin rash in patients with acute fever during the first day and night.

Adolescent↗
PubMed2006

Rising to the challenges of achieving day surgery targets.

Day surgery provides high quality and efficient care for a wide variety of surgical procedures. Patients appreciate the rapid recovery and effective analgesia, while the health service benefits from a streamlined service with lower costs. Despite the numerous advantages, day surgery practices vary enormously and many patients are still denied this excellent form of care. Fundamental to improving this situation is a change in emphasis, with day surgery becoming the default option for many surgical procedures--rather than being applied selectively--with inpatient care being used only where specifically indicated. Appropriate patient preparation is facilitated by consultant-led, nurse-run pre-assessment using modern selection criteria; only conditions which will still cause problems a few hours beyond the end of the operation should be barriers to day surgery. Pre-assessment also provides an excellent opportunity to begin patient education and ensures that pre-existing pathology is optimally treated. Efficient day surgery is best delivered by a specialised, dedicated, multi-disciplinary team, but consultant anaesthetists have a major role to play in co-ordinating policies and providing leadership. Individual anaesthetists should develop techniques that allow their patients to undergo day surgery with minimum stress, maximum comfort and the optimal chance of early discharge. Improving day surgery rates is a win-win situation, with both clinical and financial benefits.

Ambulatory Surgical Procedures↗
PubMed2005

How we do it: the Bradford grommet trainer: a model for training in myringotomy and grommet insertion.

Myringotomy and grommet insertion is the most common operative procedure in otological practice. We describe a simple, cheap and effective model for the junior trainee to develop the skills required for myringotomy and grommet insertion without compromising patient safety. As the materials required for our model are more readily available, it is more likely to gain widespread acceptance in ENT training.

Clinical Competence↗
PubMed2005

Growth factor signalling and response to endocrine therapy: the Royal Marsden Experience.

De novo resistance to endocrine therapy is a near-universal feature of oestrogen receptor (ER)- negative breast cancer. Although many ER-positive breast cancers also show no response to tamoxifen or aromatase inhibitors on objective clinical grounds the large majority show reduced proliferation indicating that some oestrogen dependence is present in almost all ER-positive breast cancer. In neoadjuvant studies HER2 positivity is associated with poor response rates to tamoxifen but not aromatase inhibitors, consistent with preclinical models. Acquired resistance to tamoxifen is associated with decreases in ER positivity but most recurrent lesions remain ER-positive. A small proportion of these show increased HER2 expression and in these patients increased phospho-p38 may contribute to the tamoxifen-resistant phenotype. There is an unfortunate paucity of clinical and biological data on acquired resistance to aromatase inhibitors.

Antineoplastic Agents, Hormonal↗
PubMed2005

Convulsions and Coma Associated with Iatrogenically Elevated CSF Calcium Levels Post Spinal Surgery: A Case Report.

Following elective revision of lumbar decompression and non-instrumented fusion, a 69 year old woman developed confusion, convulsions and coma associated with greatly elevated cerebrospinal fluid (CSF) calcium levels. It is presumed that the elevated calcium was secondary to the use of OsteoSet, a calcium sulfate pellet preparation used to augment autologous bone graft growth.

Journal Article↗
PubMed2004

Interventions to improve compliance with continuous positive airway pressure for obstructive sleep apnoea.

BACKGROUND: Continuous Positive Airways Pressure (CPAP) is currently considered to be the cornerstone of therapy for sleep apnoea (OSA). However compliance with this treatment is frequently poor, which may lead to ongoing symptoms of sleep disruption, daytime sleepiness and poor waking cognitive function. Mechanical and psychological/educational interventions have been proposed to try to increase the hours of use of CPAP therapy. OBJECTIVES: To determine the efficacy of interventions designed to increase compliance with CPAP. SEARCH STRATEGY: We searched the Cochrane Airways Group Sleep Apnoea Specialised Register (January 2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing interventions to improve compliance with CPAP usage were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two reviewers assessed articles for inclusion in the review and extracted data. Attempts were made to obtain additional unpublished data from the trialists. MAIN RESULTS: 24 studies met the inclusion criteria with 1007 participants. Each of the mechanical interventions was compared with fixed CPAP alone. Auto-CPAP (13 studies): A small, significant difference was observed in compliance but this effect disappeared when we took account of the variation between the studies. There may be a subgroup of patients who respond better than others. Most participants preferred auto-CPAP to fixed CPAP where this was measured. Bi-level PAP (3 studies): No significant differences were observed in compliance. One small study found no difference in preference. Patient titrated CPAP (1 study): No significant difference was observed in compliance. Humidification(1 study): This small study found no significant difference in compliance. Educational/psychological interventions (6 studies): One small study demonstrated superior compliance in patients treated with cognitive behavioural therapy + CPAP versus CPAP alone but only after 12 weeks. In one, larger study intensive support including home visits increased hours of use. No other study demonstrated significant effects in favour of active treatment. REVIEWERS' CONCLUSIONS: The effect of Auto-CPAP in increasing hours of use in unselected patients starting this treatment remains unclear. Different pooled analyses gave conflicting results and it may be that carefully selected participants may respond more favourably than others. The evidence in support of Bi-PAP, self-titration and humidification is lacking and studies are required in these areas. There is some evidence that psychological/educational interventions improve CPAP usage. This requires confirmation in larger studies of longer duration, with rigorous follow-up. The cost-benefit ratio of such interventions requires assessment. Future studies need to consider the effects of treatment in participants who are poorly compliant. The studies assembled were characterised by high machine usage in the control groups, and low withdrawal rates making it less likely that any benefit could be demonstrated.

Adult↗
PubMed2004

Global Partnership to Stop TB: a model of an effective public health partnership.

SETTING: The Global Partnership to Stop TB. OBJECTIVE: To describe the need for a partnership, its development, its aims and how it goes about its business. RESULT: The international health community finds itself working under new constraints and in the presence of new actors and opportunities, including globalisation, economic and cultural changes, lack of resources, and the need for intersectoral collaboration. The World Health Organization (WHO) declared tuberculosis a global emergency in 1993. However, political commitment to controlling the growing pandemic was lacking, and TB continued to exact its remorseless toll. The Global Partnership to Stop TB can be seen as the result of the development over the last century of progressively more powerful forms of international organisations against tuberculosis. An outline is given of the current Global Partnership to Stop TB, including its goals, its progress from values to achievements and how it functions through various bodies. CONCLUSION: The Partnership is potentially an effective model for other public health issues. As such, it can contribute to and catalyse a new era of international cooperation.

Communicable Disease Control↗
PubMed2004

The Global TB Drug Facility: innovative global procurement.

The Global TB Drug Facility (GDF) is a new initiative to increase access to high quality tuberculosis drugs. The GDF, a project of the Global Partnership to Stop TB, is managed by its secretariat, in the World Health Organization (WHO), Geneva. It aims to provide tuberculosis drugs to treat up to 11.6 million patients over the next 5 years and to assist countries to reach the WHO global TB control targets by 2005. The GDF was launched on 24 March 2001. Six rounds of applications have been completed, with 46 countries and non-governmental organisations (NGOs) approved for support. The GDF is not a traditional procurement mechanism. It has adopted an innovative approach to the supply of drugs, by linking demand for drugs to supply and monitoring, using partners to provide services, using product packaging to simplify drug management and linking grants to TB programme performance. This paper describes the GDF operational procedures and experience gained so far. Key achievements to date are also outlined, including the creation of a flexible supply system to meet differing programme needs, rapid establishment of procedures, reduction in TB drug prices--a catalyst for DOTS expansion in countries, standardisation of products, and collaboration with partners. The GDF is flexible enough to meet the needs of countries with a TB burden. The GDF experience could be used as an example for global procurement of drugs and commodities for other diseases, such as HIV/AIDS and malaria. In the future it is likely that the GDF will expand to include second-line drugs and diagnostic materials for TB and could assist other partnerships to develop similar mechanisms and facilities to meet country needs.

Antitubercular Agents↗
PubMed2003

FcgammaRIIa and FcgammaRIIIb polymorphisms were not associated with meningococcal disease in Western Norway.

Fcgamma-receptor (FcyR) polymorphisms have been associated with acquisition and severity of invasive meningococcal disease. We studied FcgammaR polymorphisms in a population with a high incidence of meningococcal disease. Fifty meningococcal disease patients aged 14-60 years, with bacteriologically confirmed disease and without detected complement deficiency, together with 100 healthy adult controls were included in the study. Clinical and bacteriological data were collected prior to FcgammaRIIa and FcgammaRIIb genotyping, which was performed by polymerase chain reaction. The distribution of the FcgammaRIIa and FcgammaRIIIb allotypes and their allele frequencies were not significantly different amongst the patients and the controls. The combination FcgammaRIIa-R/R and FcgammaRIIb-Na2/Na2 was less common among patients than controls (OR = 0.11, Fisher's exact P = 0.05). No significant association was found between the two FcgammaRs and severity of disease, meningococcal serogroup, age groups or gender. In contrast to previous findings, our study indicates that in Norwegian teenagers and adults, the FcgammaRIIa and FcgammaRIIIb allotypes are not decisive for the acquisition or for the severity of meningococcal disease.

Adolescent↗
PubMed2003

Sevoflurane: an ideal agent for adult day-case anesthesia?

Sevoflurane has several properties which make it potentially useful as a day case anaesthetic. Following induction of anaesthesia with propofol, awakening from sevoflurane is faster compared to isoflurane, faster or similar compared to propofol and comparable (in the majority of studies) to desflurane. Subsequent recovery and discharge is generally similar following all agents. Sevoflurane may also be used to induce anaesthesia, which is generally well-received and causes less hypotension and apnoea compared to propofol. When used as a maintenance anaesthetic, the incidence of postoperative nausea and vomiting after sevoflurane is comparable to other inhaled anaesthetics, but this complication appears more common after inhaled inductions. The tolerability and low solubility of sevoflurane facilitate titration of anaesthesia and may reduce the need for opioid analgesia, which in turn may limit the occurrence of nausea and vomiting.

Adult↗
PubMed2002

Drug treatments for obstructive sleep apnoea.

BACKGROUND: The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airway pressure (CPAP) via a mask during sleep. However this is not tolerated by all patients and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea. The mechanisms by which drugs might reduce OSA include; a reduction in the proportion of rapid eye movement (REM) sleep (during which apnoeas tend to be more frequent), an increase in ventilatory drive or an increase in upper airway muscle tone during sleep. OBJECTIVES: To determine the efficacy of drug therapies in the treatment of sleep apnoea. SEARCH STRATEGY: Searches were carried out on the Cochrane Airways Group RCT Register. Additional hand searching was performed as relevant. SELECTION CRITERIA: Double blind, randomised placebo controlled trials were included, involving patients with confirmed obstructive sleep apnoea. Trials were excluded if continuous positive airways pressure, mandibular devices or oxygen therapy were used. No restriction was placed upon publication language or trial duration. DATA COLLECTION AND ANALYSIS: A total of 51 references were identified by electronic searches. 42 studies were retrieved for selection and 9 trials were included in the review. The results for 91 patients were available. No response for further information was forthcoming from the study authors. Results were expressed as (WMD) and 95% Confidence Intervals (95% CI) MAIN RESULTS: Only acetazolamide reduced the Hypopnoea Index (1 crossover trial of 9 patients, Weighted Mean Difference -24; 95%Confidence Intervals (95% CI): -4, -44). However there was no symptomatic response and the drug was poorly tolerated. Protriptyline led to a symptomatic improvement (improved vs not improved) in two out of three crossover trials (13 patients, Peto Odds Ratio 29.2; 95%CI 2.8, 301.1) but there was no change in the apnoea frequency. No beneficial effects were found for medroxy progesterone, clonidine, buspirone, aminophylline, theophylline or sabeluzole. REVIEWER'S CONCLUSIONS: The data available do not support the use of drugs as a therapy for OSA. Although the studies examined had limitations there was little to justify further trials of these particular drugs.

Humans↗
PubMed2002

Analysis of venom constituents from the parasitoid wasp Pimpla hypochondriaca and cloning of a cDNA encoding a venom protein.

Venom from Pimpla hypochondriaca, an endoparasitoid of pupae, was size-fractionated using gel filtration chromatography and analysed by SDS-PAGE in the presence and absence of reducing agent. A complex mixture of more than 20 venom constituents was identified which ranged in M(r) between approximately 5 and 100 kDa. Venom from a wide range of size fractions inhibited the motility of larval haemocytes and prevented the formation of cell aggregates when analysed in vitro, indicating that anti-haemocytic activity is mediated by multiple venom components. Sephadex A25 beads injected into the haemocoel of pupae were encapsulated within 24h. This reaction was abolished when the pupae were injected with 30 microg of venom protein, equivalent to one-fifth of a venom sac, 1h prior to implantation of the beads, confirming that venom suppresses encapsulation in pupae. Using random 5' end sequencing of a P. hypochondriaca venom gland cDNA library, we have isolated a cDNA encoding a 25.3 kDa protein containing a signal peptide and having sequence similarity to serine proteases. The N-terminal sequence of six residues from two venom proteins of 28 and 30 kDa was the same and identical to amino acids encoded by the cDNA, confirming that two mass forms of the protein are secreted into the venom sac. The N-terminal sequence of both venom proteins began nine residues towards the C terminus following the predicted signal sequence cleavage site, suggesting that the proteins are proteolytically processed before or during storage in the venom sac. The general applicability of using random 5' sequencing to identify cDNAs encoding secretory products is discussed.

Amino Acid Sequence↗