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Biomedical subjects

S Harrison

Publications and source records attributed to S Harrison.

At least 19 recordsLinked to original sources

Safety and complexity: inter-departmental relationships as a threat to patient safety in the operating department.

PURPOSE: Current thinking about "patient safety" emphasises the causal relationship between the work environment and the delivery of clinical care. This research draws on the theory of normal accidents to extend this analysis and better understand the "organisational factors" that threaten safety. DESIGN/METHODOLOGY/APPROACH: Ethnographic research methods were used, with observations of the operating department setting for 18 month and interviews with 80 members of hospital staff. The setting for the study was the Operating Department of a large teaching hospital in the North-West of England. FINDINGS: The work of the operating department is determined by inter-dependant, "tightly coupled" organisational relationships between hospital departments based upon the timely exchange of information, services and resources required for the delivery of care. Failures within these processes, manifest as "breakdowns" within inter-departmental relationships lead to situations of constraint, rapid change and uncertainty in the work of the operating department that require staff to break with established routines and work with increased time and emotional pressures. This means that staff focus on working quickly, as opposed to working safely. ORIGINALITY VALUE: Analysis of safety needs to move beyond a focus on the immediate work environment and individual practice, to consider the more complex and deeply structured organisational systems of hospital activity. For departmental managers the scope for service planning to control for safety may be limited as the structured "real world" situation of service delivery is shaped by inter-department and organisational factors that are perhaps beyond the scope of departmental management.

Central Supply, Hospital↗

Improving the management and referral of patients with transient ischaemic attacks: a change strategy for a health community.

PROBLEM: Rapid referral and management of patients with transient ischaemic attacks is a key component in the national strategy for stroke prevention. However, patients with transient ischaemic attacks are poorly identified and undertreated. DESIGN AND SETTING: Before and after evaluation of quality improvement programme with controlled comparison in three primary care trusts reflecting diverse populations and organisational structures in an urban district in the North of England. KEY MEASURES FOR IMPROVEMENT: The proportion of patients receiving antiplatelet drugs and safe driving advice on referral to a specialty clinic, and the numbers of referrals, adjusted for age, to the specialist clinic before and after the improvement programme. STRATEGIES FOR CHANGE: Interviews with patient and professionals to identify gaps and barriers to good practice; development of evidence based guidelines for the management of patients with transient ischaemic attacks; interactive multidisciplinary workshops for each primary care trust with feedback of individual audit results of referral practice; outreach visits to teams who were unable to attend the workshops; referral templates and desktop summaries to provide reminders of the guidelines to clinicians; incorporation of standards into professional contracts. EFFECTS OF CHANGE: A significant improvement occurred in identification and referral of patients with transient ischaemic attacks to specialist clinics, with a 41% increase in referrals from trained practices compared with control practices. There were also significant improvements in the early treatment and safety advice provided to patients before referral. LESSONS LEARNT: A strategic approach to effective quality improvement across a diverse health community is feasible and achievable. Careful planning with patient and professional involvement to develop a tailored and multifaceted quality improvement programme to implement evidence based practice can work in very different primary care settings. Key components of the effectiveness of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication, and use of established networks and opinion leaders.

Communication↗

Evacuation decisions in a chemical air pollution incident: cross sectional survey.

OBJECTIVE: To compare the health outcomes in sheltered and evacuated populations after a chemical incident in a plastics factory. DESIGN: Cross sectional survey. SETTING: Urban area in southwest England. PARTICIPANTS: 1750 residents from the area exposed to the chemical smoke, of which 472 were evacuated and the remaining 1278 were advised to shelter indoors. MAIN OUTCOME MEASURE: Number of adverse health symptoms. A case was defined by the presence of four or more symptoms. MAIN RESULTS: 1096 residents (63%; 299 evacuated, 797 sheltered) provided data for analyses. The mean symptom score and proportion of cases were higher in evacuated people than in the sheltered population (evacuated: symptom score 1.9, cases 19.7% (n = 59); sheltered: symptom score 1.0, cases 9.5% (n = 76); P < 0.001 for both). The difference between the two groups attenuated markedly at the end of two weeks from the start of the incident. The two main modifiable risk factors for the odds of becoming a case were evacuation (odds ratio 2.5, 95% confidence interval 1.7 to 3.8) and direct exposure to smoke for more than two hours on the first day of the incident (2.0, 1.7 to 2.3). The distance of residence from the factory or level of exposure before intervention (first six hours) had little effect on the odds of a person becoming a case. CONCLUSIONS: Sheltering may have been a better protective action than evacuation in this chemical incident, which is consistent with the prevailing expert view. Although this study has limitations, it is based on a real event. Evacuations carry their own risks and resource implications; increased awareness may help to reduce unnecessary evacuations in the future.

Air Pollutants↗

Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival.

Endothelial differentiation gene (Edg) proteins are G-protein-coupled receptors activated by lysophospholipid mediators: sphingosine-1-phosphate (S1P) or lysophosphatidic acid. We show that in the CNS, expression of Edg8/S1P5, a high-affinity S1P receptor, is restricted to oligodendrocytes and expressed throughout development from the immature stages to the mature myelin-forming cell. S1P activation of Edg8/S1P5 on O4-positive pre-oligodendrocytes induced process retraction via a Rho kinase/collapsin response-mediated protein signaling pathway, whereas no retraction was elicited by S1P on these cells derived from Edg8/S1P5-deficient mice. Edg8/S1P5-mediated process retraction was restricted to immature cells and was no longer observed at later developmental stages. In contrast, S1P activation promoted the survival of mature oligodendrocytes but not of pre-oligodendrocytes. The S1P-induced survival of mature oligodendrocytes was mediated through a pertussis toxin-sensitive, Akt-dependent pathway. Our data demonstrate that Edg8/S1P5 activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival and that these effects depend on the developmental stage of the cell.

Amino Acid Sequence↗

Rules and guidelines in clinical practice: a qualitative study in operating theatres of doctors' and nurses' views.

BACKGROUND: The current orthodoxy within patient safety research and policy is characterised by a faith in rules based systems which limit the capacity for individual discretion, and hence fallibility. However, guidelines have been seen as stifling innovation and eroding trust. Our objectives were to explore the attitudes towards guidelines of doctors and nurses working together in surgical teams and to examine the extent to which trusting relationships are maintained in a context governed by explicit rules. METHODS: Fourteen consultant grade surgeons of mixed specialty, 12 consultant anaesthetists, and 15 nurses were selected to reflect a range of roles. Participant observation was combined with semi-structured interviews. RESULTS: Doctors' views about the contribution of guidelines to safety and to clinical practice differed from those of nurses. Doctors rejected written rules, instead adhering to the unwritten rules of what constitutes acceptable behaviour for members of the medical profession. In contrast, nurses viewed guideline adherence as synonymous with professionalism and criticised doctors for failing to comply with guidelines. CONCLUSIONS: While the creation of a "safety culture" requires a shared set of beliefs, attitudes and norms in relation to what is seen as safe clinical practice, differences of opinion on these issues exist which cannot be easily reconciled since they reflect deeply ingrained beliefs about what constitutes professional conduct. While advocates of standardisation (such as nurses) view doctors as rule breakers, doctors may not necessarily regard guidelines as legitimate or identify with the rules written for them by members of other social groups. Future safety research and policy should attempt to understand the unwritten rules which govern clinical behaviour and examine the ways in which such rules are produced, maintained, and accepted as legitimate.

Attitude of Health Personnel↗

A cysteine-rich plant protein potentiates Potyvirus movement through an interaction with the virus genome-linked protein VPg.

We have identified a cellular factor that interacts with the virus genome-linked proteins (VPgs) of a diverse range of potyviruses. The factor, called Potyvirus VPg-interacting protein (PVIP), is a plant-specific protein with homologues in all the species examined, i.e., pea, Arabidopsis thaliana, and Nicotiana benthamiana. The sequence of PVIP does not identify a specific function, although the existence of a "PHD finger" domain may implicate the protein in transcriptional control through chromatin remodeling. Deletion analysis using the yeast two-hybrid system showed that the determinants of the interaction lay close to the N terminus of VPg; indeed, the N-terminal 16 amino acids were shown to be both necessary and sufficient for the interaction with at least one PVIP protein. From a sequence comparison of different potyvirus VPg proteins, a specific amino acid at position 12 was directly implicated in the interaction. This part of VPg is distinct from regions associated with other functional roles of VPg. Through mutation of Turnip mosaic virus (TuMV) at VPg position 12, we showed that the interaction with PVIP affected systemic symptoms in infected plants. This resulted from reduced cell-to-cell and systemic movement more than reduced virus replication, as visualized by comparing green fluorescent protein-tagged wild-type and mutant viruses. Furthermore, by using RNA interference of PVIP in Arabidopsis, we showed that reduced expression of PVIP genes reduced susceptibility to TuMV infection. We conclude that PVIP functions as an ancillary factor to support potyvirus movement in plants.

Amino Acid Motifs↗

Re-thinking accountability: trust versus confidence in medical practice.

In seeking to prevent a reoccurrence of scandals such as that involving cardiac surgery in Bristol, the UK government has adopted a model of regulation that uses rules and surveillance as a way of both improving the quality of care delivered and increasing confidence in healthcare institutions. However, this approach may actually act to reduce confidence and trust while also reducing the moral motivation of practitioners. Accountability in health care is discussed, and it is suggested that openness about the difficult dilemmas that arise when practitioners have a duty to be accountable to more than one audience may be an alternative means of restoring trust. A greater emphasis on the sharing of information between individual health professionals and their patients would increase trust and would allow patients to hold their doctors to account for the quality of care they receive. Concentrating more on developing trust by the sharing of information and less on the futile search for complete confidence in systems and rules may improve the quality of care delivered while also nurturing the moral motivation of professionals upon which the delivery of high quality health care depends.

Humans↗

Antitussive activity of iodo-resiniferatoxin in guinea pigs.

BACKGROUND: Iodo-resiniferatoxin (I-RTX) has recently been described as an ultra potent antagonist of the transient receptor potential vanilloid-1 (TRPV1). METHODS: The ability of I-RTX to inhibit cough induced by inhalation of two putative TRPV1 stimulants (capsaicin and citric acid) was tested in non-anaesthetised guinea pigs. RESULTS: Pretreatment with I-RTX either intraperitoneally (0.03-0.3 micromol/kg) or by aerosol (0.1-3 microM) reduced the number of coughs produced by inhalation of citric acid (0.25 M) and capsaicin (30 microM) in a dose dependent manner. Capsazepine (CPZ) also reduced citric acid and capsaicin induced cough, but the activity of I-RTX was 10-100 times more potent than CPZ in all the experimental conditions tested. CONCLUSIONS: I-RTX is a novel and potent antitussive drug which inhibits cough mediated by agents possibly acting via TRPV1 activation.

Animals↗

Outbreak of Escherichia coli O157 associated with a busy bathing beach.

Between 7 and 20 August 1999 a Public Health Department was notified of seven cases of Escherichia coli O157 infection. Phage typing demonstrated that four were related and three unrelated. The investigation centred around the three cases of E. coli O157 phage type 21/28 who visited the same beach during the last week of July. The fourth related infection was identified as a result of the investigation. Although the investigation failed to identify a source of infection, interviews with the families of the four related cases suggested that they had occupied the same part of the beach on the same day and so it is possible that a contaminated area of beach was the source. We believe this to be the first outbreak of E. coli O157 to be associated with a bathing beach.

Bathing Beaches↗

Immunoglobulin-binding domains: Protein L from Peptostreptococcus magnus.

Protein L is a multidomain cell-wall protein isolated from Peptostreptococcus magnus. It belongs to a group of proteins that contain repeated domains that are able to bind to Igs without stimulating an immune response, the most characterized of this group being Protein A ( Staphylococcus aureus ) and Protein G ( Streptococcus ). Both of these proteins bind predominantly to the interface of C(H)2-C(H)3 heavy chains, while Protein L binds exclusively to the V(L) domain of the kappa -chain. The function of these proteins in vivo is not clear but it is thought that they enable the bacteria to evade the host's immune system. Two binding sites for kappa -chain on a single Ig-binding domain from Protein L have recently been reported and we give evidence that one site has a 25-55-fold higher affinity for kappa -chain than the second site.

Amino Acid Sequence↗

Hair colouring, permanent styling and hair structure.

Hair is an important component of body image and has immense psychological importance for both men and women. Women, in particular, over the ages have modified their appearance through changing their hair colour or style. Hair can be straight, wavy or curly, blonde, black, brown or red. These natural variations are an important part of our identity that can be manipulated according to the dictates of fashion, culture or society. Different types of hair have varying affinity for the different colouring and waving methods. Damaged hair also has a different affinity for hair products than normal healthy hair. The hair shaft is remarkably strong and resistant to the extremes of nature. Hair cosmetics are widely available and manipulate the structural properties of hair. Whilst most procedures are safe, there is considerable potential for damage to the hair and hair problems of acute onset, including hair breakage, hair loss and loss of condition, are frequently blamed on the last product used on the hair. Hair problems are particularly prevalent among people who repeatedly alter the natural style of their hair.

Journal Article↗

Reduction of sulfide, ammonia compounds, and adhesion properties of Lactobacillus casei strain KE99 in vitro.

The ability of Lactobacillus casei strain KE99 to reduce sulfide, ammonia, and to adhere to bio-surfaces was characterized and compared with three lactobacillus reference strains. Sulfide reduction by strain KE99 in MRS broth increased exponentially after 10-h growth and reached a maximum (>300 ppm reduction) within 48 h. KE99 demonstrated a maximum reduction of sulfide under anaerobic (341 ppm) growth conditions at pH 6.0-8.0 range. Maximum anaerobic reduction of sulfide was demonstrated by L. casei 393 at pH 7.0 (272 ppm); L. rhamnosus at pH 8.0 (277 ppm); and L. reuteri at pH 7.0 (244 ppm). KE99 reduced sulfide more (p < 0.0001) in MRS broth spiked with Na2S (374 ppm) than (NH4)2S (340 ppm) salts. Ammonia reduction by strain KE99 and the three lactobacillus reference strains in MRS broth was low. Ammonia reduction reached a maximum within 36 h and remained unchanged over extended incubations of 48 h to 72 h or further. KE99 reduced ammonium sulfate (37 ppm) more readily than the nitrate (31 ppm), hypophosphate (29 ppm), or chloride (20 ppm) salts of ammonia. KE99 and the three reference strains of lactobacilli demonstrated avid binding to Bio-coat (Cn type-I, Cn type-IV, laminin, fibronectin), Matrigel, and Caco-2 cell monolayers in vitro. The number of lactobacilli binding to Caco-2 was estimated at 74/cell with strain KE99, which was significantly higher compared with 40/cell (p < 0.0001), 26/cell (0.0001), and 64/cell (p < 0.002) with L. casei 393, L. reuteri, and L. rhamnosus, respectively. The interaction of KE99 to immobilized Cn type-I was saturable and reached an equilibrium within 1 h at room temperature. KE99 binding to Cn type-I occurred at a wide pH range and was biphasic with maximum binding at pH 5.5 and 7.5. Inhibition and binding-displacement experiments with different salts and sugars suggested that the KE99 binding to immobilized Cn type-I may involve a combination of electrostatic and lectin-type interactions. KE99 effectively detached the Cn-adherent E. coli O157:H7 in the range of 55% (ATCC43895) to 76% (ATCC43894). The binding-displacement values for L. casei 393, L. reuteri and L. rhamnosus to detach Cn-adherent E. coli O157:H7 (ATCC43894) were 66 +/- 4%, 59 +/- 2%, and 64 +/- 2%, respectively. Also, a reconstituted solution of the freeze-dried KE99 preparation effectively detached the Cn-adherent E. coli O157:H7 in a dose-dependent manner that reached a binding-displacement equilibrium of 85% at a 1% wt/vol KE99 concentration.

Ammonia↗

Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1.

The vanilloid receptor-1 (VR1) is a heat-gated ion channel that is responsible for the burning sensation elicited by capsaicin. A similar sensation is reported by patients with esophagitis when they consume alcoholic beverages or are administered alcohol by injection as a medical treatment. We report here that ethanol activates primary sensory neurons, resulting in neuropeptide release or plasma extravasation in the esophagus, spinal cord or skin. Sensory neurons from trigeminal or dorsal root ganglia as well as VR1-expressing HEK293 cells responded to ethanol in a concentration-dependent and capsazepine-sensitive fashion. Ethanol potentiated the response of VR1 to capsaicin, protons and heat and lowered the threshold for heat activation of VR1 from approximately 42 degrees C to approximately 34 degrees C. This provides a likely mechanistic explanation for the ethanol-induced sensory responses that occur at body temperature and for the sensitivity of inflamed tissues to ethanol, such as might be found in esophagitis, neuralgia or wounds.

Animals↗

Telogen effluvium.

The term telogen effluvium, first coined by Kligman in 1961, refers to the loss of club (telogen) hair in disease states of the follicle. Kligman's hypothesis was that whatever the cause of hair loss, the follicle tends to behave in a similar way, namely the premature termination of anagen. "The follicle is precipitated into catagen and transforms into a resting stage that mimics telogen." Ipso facto the observation of telogen hair loss does not infer a cause. To establish the cause of the hair loss, one requires a history to identify known triggers, biochemical investigations to exclude endocrine, nutritional or autoimmune aetiologies and in many cases histology to identify the earliest stages of androgenetic alopecia. The duration of the hair loss at presentation helps predict those patients in whom further investigation will have the greatest yield. "It is unfortunate that baldness has been approached with an eye toward "regrowing" or "restoring hair", and thus with a tendency toward commercialism. Locked within the metamorphosing hair follicles in the balding scalp are all the secrets of growth and differentation. Searching for these secrets should transcend the eagerness to "regrow" hair on a bald scalp, an achievement which is of no great consequence. When we know these answers, we shall have the key, not to hair growth alone, but to all growth, which is, after all, the basis of all biological phenomena." William Montagna, 1959.

Acute Disease↗

A randomized clinical trial to compare the effectiveness of canine lacebacks with reference to canine tip.

AIM: To assess the effectiveness of canine lacebacks on the proclination of the upper incisors with reference to pre-treatment canine tip. STUDY DESIGN: Randomized clinical trial. SAMPLE: Patients receiving upper and lower fixed appliances attending the orthodontic departments of five orthodontic treatment providers. Sixteen patients received canine lacebacks as part of their treatment and 19 patients did not have canine lacebacks. METHOD: Patients were randomly allocated to receive canine lacebacks or not receive canine lacebacks. Upper study models were collected at the initial archwire placement and then when the working 0.019 x 0.025-inch stainless steel archwire was placed. The start canine angulation, change in upper incisor proclination/overjet, and any mesial movement of the upper first permanent molars during levelling and aligning was measured with a reflex metrograph. STATISTICS: The effect of the use of canine lacebacks on upper incisor proclination and mesial molar movement was assessed using Student t-tests. Regression analysis was used to evaluate any effect of the initial angulation of the canine. RESULTS: A mean incisor retroclination of 0.5 mm was observed in the canine lacebacks compared with a mean proclination of 0.36 mm when canine lacebacks were not used (P = 0.025). There was no statistically significant difference between groups for mesial movement of upper first molars (P = 0.99). If the canine was more distally inclined at the start of treatment, the incisors was more likely to procline, regardless of whether or not canine lacebacks were used (P = 0.027). CONCLUSIONS: The effect of canine lacebacks on preventing upper incisor proclination at the start of treatment is in the order of 1 mm and their effect on mesial molar movement is insignificant. Canines lacebacks have similar effects that are independent of pre-treatment canine angulation.

Adolescent↗

Randomised crossover study of the Flutter device and the active cycle of breathing technique in non-cystic fibrosis bronchiectasis.

BACKGROUND: Airway clearance techniques are an important part of the routine care of patients with bronchiectasis. The use of the Flutter, a hand held pipe-like device causing oscillating positive expiratory pressure within the airways, has been proposed as an alternative to more conventional airway clearance techniques. METHODS: A randomised crossover study was performed in 17 stable patients with non-cystic fibrosis bronchiectasis at home, in which 4 weeks of daily active cycle of breathing technique (ACBT) were compared with 4 weeks of daily physiotherapy with the Flutter device. RESULTS: No significant differences between the two techniques were found. Median weekly sputum weights were similar with a median treatment difference of 7.64 g (p=0.77) and there was no evidence of treatment order or order interaction effects (p=0.70). Health status (Chronic Respiratory Disease Questionnaire) and ventilatory function did not change significantly during either treatment period. There was no significant change in peak expiratory flow rate or in breathlessness (Borg score) after individual physiotherapy sessions with either technique. A questionnaire indicated subjectively that patients preferred the Flutter (11/17) to ACBT for routine use. CONCLUSIONS: Daily use of the Flutter device in the home is as effective as ACBT in patients with non-cystic fibrosis bronchiectasis, and has a high level of patient acceptability.

Bronchiectasis↗

Ferrets as a transmission model for influenza: sequence changes in HA1 of type A (H3N2) virus.

Ferrets were used as an animal model to study whether controlled transmission of type A influenza is similar to human transmission when sequence changes in HA1 are used as the outcome. Ferrets were infected initially with A/Sydney/5/97 (H3N2) or A/LA/1/87 (H3N2) intranasally, and transmission chains were established by housing infected ferrets with noninfected ferrets with no influenza antibody titer against the infecting virus. Ferrets infected with A/Sydney were seronegative for A/Sydney and A/LA; ferrets infected with A/LA were seronegative for A/LA but had hemagglutination inhibition titers against A/Sydney. Titers of naturally transmitted influenza were higher than those after direct intranasal infection, but lymphocyte counts from nasal washes diminished with transmission. Ferrets infected with A/LA had 2 amino acid differences in HA1 after transmission through 5 ferret cohorts, but those infected with A/Sydney had none. The results show the value of the ferret model. A/LA resembled the transmission of influenza in humans when under antibody pressure.

Adult↗