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Biomedical subjects

R Cunningham

Publications and source records attributed to R Cunningham.

At least 19 recordsLinked to original sources

The dependence of amino acid pair correlations on structural environment.

A statistical analysis was performed to determine to what extent an amino acid determines the identity of its neighbors and to what extent this is determined by the structural environment. Log-linear analysis was used to discriminate chance occurrence from statistically meaningful correlations. The classification of structures was arbitrary, but was also tested for significance. A list of statistically significant interaction types was selected and then ranked according to apparent importance for applications such as protein design. This showed that, in general, nonlocal, through-space interactions were more important than those between residues near in the protein sequence. The highest ranked nonlocal interactions involved residues in beta-sheet structures. Of the local interactions, those between residues i and i + 2 were the most important in both alpha-helices and beta-strands. Some surprisingly strong correlations were discovered within beta-sheets between residues and sites sequentially near to their bridging partners. The results have a clear bearing on protein engineering studies, but also have implications for the construction of knowledge-based force fields.

Amino Acids

Isolation of Campylobacter jejuni from groundwater.

A pollution event which occurred at a spring in the Arnside area of Cumbria provided an opportunity to investigate whether Campylobacter jejuni could be detected in groundwater. Hydrological evidence suggested that the source of contamination was a dairy farm situated within the hydrological catchment of the polluted spring. The microbiological quality of the polluted spring was monitored during intervals over the following 12 months and compared with others in the area. Campylobacter jejuni was isolated by filter enrichment of 500 ml and 100 ml filtered volumes of groundwater. It was not isolated in the absence of faecal indicator species. Some strains of Camp. jejuni from water had identical biotypes to strains isolated from the dairy herd. This paper reports the first isolation of Camp. jejuni from groundwater using cultural methods and supports the theory that groundwater may be a vehicle for Campylobacter transmission.

Animals

Routine antenatal screening for hepatitis B using pooled sera: validation and review of 10 years experience.

AIMS: To validate the sensitivity of universal antenatal screening for hepatitis B surface antigen (HBsAg) by testing pools of 10 sera, and to review 10 years' experience using this method. METHODS: 66,945 antenatal patients were tested between 1986 and 1996 using the pooled method. All sera from 1996 (n = 6050) were retrieved and retrospectively tested individually. An in vitro determination of the effect of pooling on sensitivity was performed by checkerboard neutralisation assay. RESULTS: 26 HBsAg positive women were detected by universal screening over 10 years; 12 had non-European surnames and five had known risk factors for hepatitis B infection. High titre anti-HBs sera in the pool reduced the sensitivity of the HBsAg assay, though the effect was only significant at low levels of HBsAg carriage. CONCLUSIONS: The prevalence of hepatitis B is extremely low in the antenatal population served by Plymouth PHL. Pooling is unlikely to reduce sensitivity enough to lead to significant preventable vertical transmission, and is a cost-effective and valid strategy in areas of low seroprevalence.

Blood Specimen Collection

Counselling someone with severe aphasia: and explorative case study.

PURPOSE: To explore a counselling approach for a client, H.N., with a severe aphasia. METHOD: The principles of Personal Construct Therapy were used. Therapy (six sessions) was started and finished by H.N. producing a repertory grid. Sessions were patient-led but the information from the repertory grids was used to help facilitate the process. Each session was video taped. RESULTS: Analysis of therapy sessions revealed H.N. was following a pattern, if erratic. He used good conversational strategies to control the less structured sessions. The therapist was dominant when the repertory grids were produced. Statistical analysis of the repertory grids was mainly nonsignificant but there was a shift for the final grid to a greater variety of and more positive responses. General improvement in comprehension was also noted. CONCLUSION: A 'counselling' approach with someone with severe aphasia is possible. Using a repertory grid was a useful tool for understanding H.N. better. It seemed to initiate H.N. to discuss things of importance. The changes seen in him could have been due to an improvement in confidence as a communicator. This study has implications for how we can enable people with limited language to adapt to their situations.

Adaptation, Psychological

Prospective case-control study of role of infection in patients who reconsult after initial antibiotic treatment for lower respiratory tract infection in primary care.

OBJECTIVE: To assess direct and indirect evidence of active infection which may benefit from further antibiotics in adults who reconsult within 4 weeks of initial antibiotic management of acute lower respiratory tract infection in primary care. DESIGN: Observational study with a nested case-control group. SETTING: Two suburban general practices in Arnold, Nottingham, over 7 winter months. SUBJECTS: 367 adults aged 16 years and over fulfilling a definition of lower respiratory tract infection and treated with antibiotics. 74 (20%) patients who reconsulted within 4 weeks for the same symptoms and 82 "control" patients who did not were investigated in detail at fallow up. MAIN OUTCOME MEASURES: Direct and indirect evidence of active infection at the time of the reconsultation or the follow up visit with the research nurse for the controls. Investigations performed included sputum culture, pneumococcal antigen detection, serial serology for viral and atypical pathogens and C reactive protein, throat swabs for detecting viral and atypical pathogens by culture and polymerase chain reaction, and chest radiographs. RESULTS: Demographic and clinical features of the groups were similar. Two thirds of the 74 patients who reconsulted received another antibiotic because the general practitioner suspected continuing infection. Any evidence of infection warranting antibiotic treatment was uncommon at reconsultation. The findings for the two groups were similar for the occurrence of identified pathogens; chest x ray changes of infection (present in 13%); and C reactive protein concentrations, which had nearly all fallen towards normal. Only three patients in the reconsultation group had concentrations > or = 40 mg/l. Pathogens identified at follow up in the 156 patients in both groups included ampicillin sensitive bacteria in six. Atypical infections diagnosed in 27 (Chlamydia pneumoniae in 22) and viral infections in 54 had probably been present at the initial presentation. CONCLUSION: Our study suggests that active infection, which may benefit from further antibiotics, is uncommon in patients who reconsult after a lower respiratory tract infection, and a repeat antibiotic prescription should be the exception rather than the rule. Other factors, such as patients' perception of their illness, may be more important than disease and infection in their decision to reconsult.

Adolescent

Once-daily gentamicin: translating theory into practice.

Gentamicin continues to have an important role in the treatment of serious bacterial infections. There is increasing interest in once-daily administration, which is more convenient than multiple-dose regimens. Animals studies and clinical trials suggest that once-daily administration is as efficacious and no more toxic for a variety of infections, but there is still some reluctance to use once-daily regimens routinely in neutropenic patients, because of the potential risk of breakthrough bacteraemia. A number of aspects of the serum concentration monitoring of once-daily gentamicin remain unresolved. The most commonly used assay systems are not sensitive enough, without some modification in technique, to detect the very small pre-dose concentrations seen with once-daily dosing, and it is not clear what constitutes an acceptable pre-dose concentration. Until the results from further studies become available, it is prudent to maintain a pre-dose concentration below 1 mg.1(-1), and local arrangements are necessary to address the frequency and timing of assays. It seems likely that once-daily administration will become the norm, because of its many advantages.

Animals

Post-transplant renal artery stenosis: impact of therapy on long-term kidney function and blood pressure control.

PURPOSE: We assessed the long-term outcome of different treatment methods for transplant renal artery stenosis. MATERIALS AND METHODS: Outcome data for 23 patients with transplant renal artery stenosis treated during a 16-year period were reviewed and analyzed. RESULTS: There was a higher incidence of renal artery stenosis in cadaveric donor kidneys compared to living donor kidneys (2% versus 0.3%, p < 0.02), and in cadaveric kidneys from pediatric donors less than 5 years old compared to those from adults (13.2% versus 1.3%, p < 0.01). Six patients underwent primary medical treatment for renal artery stenosis, with a successful outcome in 4 (mean followup plus or minus standard error 57 +/- 22 months) and failure in 2. Of the patients 16 were treated with percutaneous transluminal angioplasty, including 12 who were cured or improved with respect to hypertension (followup 44.7 +/- 7.6 months). Five patients underwent surgical revascularization for renal artery stenosis with postoperative improvement of hypertension (followup 18.8 +/- 11.6 months). Overall, 21 of 23 patients (91%) were treated successfully for transplant renal artery stenosis with cure or improvement of associated hypertension. Posttreatment renal function was stable or improved in 18 patients, while renal function deteriorated due to parenchymal disease in 3. CONCLUSIONS: Most patients with transplant renal artery stenosis can be treated successfully. Percutaneous transluminal angioplasty is the initial interventive treatment of choice for high grade renal artery stenosis. Surgical revascularization is indicated if percutaneous transluminal angioplasty cannot be done or is unsuccessful.

Adult

Air ambulance trauma transport: a quality review.

OBJECTIVE: Provincial air ambulance transports of injured patients were quality reviewed prospectively to determine utilization and appropriateness of care. METHODS: All trauma air ambulance transports over a 2-month span were reviewed prospectively. Revised Trauma Score, Injury Severity Score, probability of survival, prehospital time, distance of transport, procedures performed, and outcome were determined. Quality control questions were asked of the sending and receiving physicians. RESULTS: The majority of air ambulance transports reviewed (N = 97) were indicated for mechanism and severity of injury. Economics and requirement for advanced medical care were indications in only 15%. Physicians tended to perform more advanced procedures, likely related to higher patient Injury Severity Score (23 vs. 15, p = NS). Four problems with air ambulance access were identified. The overtriage rate was 5%. Inappropriate patient care was documented in six (6%) cases; a physician was present for only one of these. CONCLUSIONS: A low overtriage rate was documented, raising concerns that the undertriage rate may be too high. Injured patients air transported without physician accompaniment more often received inappropriate care, suggesting that physician accompaniment is beneficial.

Adult

Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections.

Staphylococcus aureus is an important cause of bone and joint infections. In recent years, significant changes in the incidence of septic arthritis and osteomyelitis have occurred. Haematogenous osteomyelitis is now less common during childhood, but secondary spread of infection to bone or joint from a contiguous site in adults is increasing in incidence. Infection introduced at the time of surgery or arising by the haematogenous route is a significant complication of prosthetic joint implantation, and the effect of bone cement on local immune function may be important in this setting. ALthough S. epidermis is a more common cause of prosthetic joint infection, S. aureus is more difficult to treat. S. aureus produces a number of extracellular and cell-associated factors, but it is unclear what role these have as virulence factors in vivo. Furthermore, it is difficult in animal models to simulate transient bacteraemia followed by non-fulminating septic arthritis or osteomyelitis, as occurs in the patient. Surface factors which may be important in pathogenesis include the cell wall (activates complement and stimulates cytokine release), capsular polysaccharide (promotes adhesion to host cell surfaces), collagen receptors and fibronectin-binding protein. Staphylococcal toxic shock syndrome toxin (TSST-1) and the enterotoxins are superantigens and have the potential to suppress plasma cell differentiation and antibody responsiveness. TSST-1-positive isolates have been shown to cause more severe joint infection in one animal model, but most other studies to date have focused on in-vitro rather than in-vivo effects. There is little evidence supporting a role for coagulase, lipase and the haemolysins in staphylococcal bone and joint infections. Despite the clinical importance of these infections, surprisingly little is known about pathogenesis at the cellular level. Future research should focus on the role of the host immune system in limiting spread of infection, and the expression of virulence factors in animal or other models incorporating isogenic mutant strains.

Arthritis, Infectious

An unusual cause of stress fracture of the first rib.

An unusual case of stress fracture of the first rib that occurred in a young male as a result of the constant loading due to carrying a heavy schoolbag is reported. This case demonstrates the difficulty in diagnosis and highlights the need for awareness of this condition, thus avoiding invasive investigation.

Adolescent

Amphotericin B responsive Scedosporium apiospermum infection in a patient with acute myeloid leukaemia.

A 71 year old man with newly diagnosed acute myelomonocytic leukaemia developed a soft tissue infection of his foot during his first course of chemotherapy. Scedosporium apiospermum was isolated from the lesion, which resolved rapidly on treatment with intravenous amphotericin B despite being resistant in vitro to this agent. This observation suggests that sensitivity testing of S apiospermum should be interpreted with caution and that clinical response may be a better indicator of outcome.

Aged

Recurrent Streptococcus pneumoniae endocarditis.

A case of recurrent endocarditis due to Streptococcus pneumoniae, a rare cause of endocarditis, is reported. The first episode of infection resulted in valvular damage, necessitating replacement of the aortic and mitral valves, and the second episode was treated successfully with antibiotics alone. Recurrence occurred even though the organism was fully susceptible to the antibiotics used and the patient showed no evidence of immune deficiency.

Atrial Fibrillation

Detection of cytomegalovirus using PCR in serum from renal transplant recipients.

AIMS: To develop a polymerase chain reaction (PCR) assay for the detection of cytomegalovirus (CMV) DNA in serum and leucocytes of renal transplant recipients and compare this assay with CMV culture and serodiagnosis. METHODS: Monthly specimens were obtained from 12 patients starting immediately before transplant. CMV infection was monitored by IgM enzyme linked immunosorbent assay, virus culture and PCR on serum and leucocytes. RESULTS: Two of four IgG positive patients had reactivation of CMV disease confirmed by culture, three of eight seronegative patients had a primary infection, one confirmed by serology and two by culture. PCR was positive earlier than conventional methods in three cases and concurrently in two. No positive PCR reactions occurred in the seven patients who remained negative by culture and serology. CONCLUSIONS: CMV DNA is detectable in serum; serum may be positive before virus is detectable by buffy coat culture; and PCR may be useful as an early indication of potential CMV disease in renal transplant recipients.

Adult

Reliability of the Assessment of Communicative Effectiveness in Severe Aphasia.

The Assessment of Communicative Effectiveness in Severe Aphasia (ACESA) was developed to measure the communicative effectiveness of people with severe aphasia following a stroke. The reliability was evaluated. Ten patients with severe communication difficulties (particularly limited expression) were assessed and videoed. The videos were rated by three trained raters. Reliability was calculated to demonstrate intrarater and interrater reliability, and test-re-test reliability. Reliability was good but needed to be improved across raters. It was concluded that the ACESA has the potential to be a useful clinical and research tool.

Adult