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Biomedical subjects

C Chadwick

Publications and source records attributed to C Chadwick.

At least 19 recordsLinked to original sources

Guidelines for the control of glycopeptide-resistant enterococci in hospitals.

The increase since the mid 1980s in glycopeptide resistant enterococci (GRE) raised concerns about the limited options for antimicrobial therapy, the implications for ever-increasing numbers of immunocompromised hospitalised patients, and fuelled fears, now realised, for the transfer of glycopeptide resistance to more pathogenic bacteria, such as Staphylococcus aureus. These issues underlined the need for guidelines for the emergence and control of GRE in the hospital setting. This Hospital Infection Society (HIS) and Infection Control Nurses Association (ICNA) working party report reviews the literature relating to GRE prevention and control. It provides guidance on microbiological investigation, treatment and management, including antimicrobial prescribing and infection control measures. Evidence identified to support recommendations has been categorized. A risk assessment approach is recommended and areas for research and development identified.

Anti-Bacterial Agents↗

Autologous blood pleurodesis for pneumothorax complicating graft-versus-host disease-related bronchiolitis obliterans.

Bronchiolitis obliterans (BO) is a manifestation of chronic graft-versus-host disease (GVHD) after allogeneic haemopoietic stem cell transplantation. Complications associated with this include persistent air-leak syndromes such as pneumothorax. Many methods have been described for treating this condition, both surgical and nonsurgical. We describe an 8-year-old boy with acute lymphoblastic leukaemia complicated by chronic GVHD-related BO, and subsequent pneumothorax with persistent air leak, who was treated successfully with autologous blood pleurodesis.

Blood↗

Management of acute cholecystitis in UK hospitals: time for a change.

Early cholecystectomy for patients with acute cholecystitis is safe, cost effective, and leads to less time off work compared with delayed surgery. This study was designed to assess current practice in the management of acute cholecystitis in the UK. A postal questionnaire was sent to 440 consultant general surgeons to ascertain their current management of patients with acute cholecystitis. Replies were received from 308 consultants who were involved in treating patients with acute cholecystitis of whom 18 transferred these patients on to another team for further management the day after admission. Thirty two consultants (11%) routinely treated patients by early cholecystectomy, with limiting factors stated to be the availability of surgical staff, theatre space, and radiological investigations. The remaining consultants (n = 258) routinely manage their patients conservatively with intravenous antibiotics and allow the inflammation to resolve before undertaking cholecystectomy at a later date. Indications for undertaking early cholecystectomy during the first admission by this latter group included the presence of spreading peritonitis due to bile leak, empyema, and unexpected space on theatre list. The commonest method for both elective and early cholecystectomy is laparoscopic, but the percentage of consultants using an open method rises from 8% in the elective situation to 47% for urgent early cholecystectomy. Despite evidence which strongly advocates early cholecystectomy, this practice is routinely carried out by only 11% of consultants in the UK at present.

Acute Disease↗

Acute cholecystitis--room for improvement?

AIMS: A recent survey of UK general surgeons showed that almost 90% prefer to manage patients with acute cholecystitis by initial conservative management and delayed cholecystectomy (DC). The aim of this study was to assess the effectiveness of this management policy in a large university hospital. PATIENTS AND METHODS: All patients admitted with acute cholecystitis between January 1997 and June 1999 who went on to have a cholecystectomy were identified. Patients were required to have right upper quadrant pain for > 12 h, a raised white cell count and findings consistent with acute cholecystitis on ultrasound to be included in the study. RESULTS: 109 patients were admitted with acute cholecystitis (76 female, 33 male) with a median age of 62 years (range, 22-88 years). Conservative management failed in 16 patients (14.7%) who underwent emergency cholecystectomy due to continuing symptoms (9), empyema (4) and peritonitis (3). Symptoms settled in 93 patients and delayed cholecystectomy was performed without further problems in 66 (60.6%). 27 patients were re-admitted with further symptoms before their elective surgery and, of these, 3 were admitted for a third time before surgical intervention. Ten of the 30 re-admission episodes (33%) occurred within 3 weeks of discharge but 15 (56%) occurred more than 2 months after discharge. Elective surgery was undertaken at a median of 10 weeks post-discharge with 67% of operations occurring within 3 months. Mean total hospital stay (days) +/- SEM, for the three groups were: emergency surgery group, 10.21 +/- 0.85; uncomplicated DC group, 12.48 +/- 0.37; re-admitted group, 14.75 +/- 0.71. CONCLUSIONS: The policy of conservative management and DC was successful in 60.6% of cases but 14.7% of patients required emergency surgery and 24.8% were re-admitted prior to elective surgery with a resultant increase in total hospital stay. Performing elective surgery within 2 months of discharge in all cases would have reduced the re-admission rate by 56% and this along with the increased use of early cholecystectomy during the first admission are areas where the treatment of acute cholecystitis could be significantly improved.

Acute Disease↗

Tanning salon exposure and molecular alterations.

BACKGROUND: Human studies of the short-term cellular effects of tanning salon exposures are lacking. Findings of such studies may prove extremely helpful in educating consumers considering or currently attending tanning salons. OBJECTIVE: Our purpose was to determine whether tanning salon exposure causes DNA alterations and p53 protein expression in epidermal keratinocytes and/or circulating peripheral lymphocytes. METHODS: Eleven subjects received 10 full-body tanning salon exposures over a 2-week period. UV-induced DNA cyclobutane pyrimidine dimers and p53 protein expression were examined, comparing pretreatment peripheral blood lymphocytes and epidermal biopsy specimens with analogous specimens obtained after the 10 tanning salon exposures. RESULTS: Cyclobutane pyrimidine dimers in DNA and p53 protein expression were detected in epidermal keratinocytes, but were absent in lymphocytes. CONCLUSION: Similar to outdoor sun exposure, short-term recreational tanning salon exposure causes molecular alterations believed essential in the development of skin cancer.

Adolescent↗

Current practice in the management of acute cholecystitis

AIMS: Several recent papers have advocated emergency cholecystectomy for patients with acute cholecystitis, stating that it is safe, cost effective and leads to less time off work. This study was designed to assess current practice in the management of acute cholecystitis in the UK. METHODS: A postal questionnaire was sent to 357 consultant surgeons who were thought to be involved in a general surgical on-call rota, to ascertain their current management of patients with acute cholecystitis. Replies were received from 250 consultants (70 per cent) of whom 242 (68 per cent) were involved in a general surgical take. Sixteen of these consultants, however, handed their patients with acute cholecystitis on to a different team the following day for further management. RESULTS: Twenty-seven consultants (12 per cent) routinely treat their patients by emergency cholecystectomy whenever possible, with 24 stating that they would do this within 72 h. Limiting factors to this practice were stated to be availability of surgical staff (15), theatre space (nine) and radiological investigations (four). The remaining consultants (n = 199) routinely manage their patients conservatively initially and providing they settle, either (1) book directly for cholecystectomy (n = 94, 47 per cent), (2) reassess as an outpatient (n = 65, 33 per cent), (3) either of above (n = 21; 11 per cent) or (4) refer on to a colleague (n = 19, 10 per cent). The commonest indications for acute cholecystectomy stated by consultants whose initial treatment policy is conservative are spreading peritonitis due to bile leak (93 per cent), empyema (89 per cent), unexpected space on a theatre list (28 per cent) and failure of an acute episode to settle (21 per cent). The laparoscopic method is the commonest for both elective and emergency cholecystectomy, but the percentage of consultants using an open method rises dramatically from 9 per cent in the elective situation to 48 per cent for emergency cholecystectomy. CONCLUSIONS: Despite evidence to support the increased use of emergency cholecystectomy, this practice is routinely carried out by only 12 per cent of consultants. However, of the consultants who treat their patients conservatively, 28 per cent are prepared to undertake emergency cholecystectomy if an unexpected space appears on the theatre list.

Journal Article↗

Mesalazine preparations.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗

Vancomycin-resistant enterococci: implications for infection control.

The incidence of vancomycin-resistant enterococci (VRE) infection is increasing. Immunosuppressed individuals are particularly vulnerable to infection with VRE. Strict attention to infection control measures is important in preventing the spread of multiresistant organisms.

Anti-Bacterial Agents↗

Enzyme therapy of xeroderma pigmentosum: safety and efficacy testing of T4N5 liposome lotion containing a prokaryotic DNA repair enzyme.

Xeroderma pigmentosum (XP) is a rare genetic disease in which patients are defective in DNA repair and are extremely sensitive to solar UV radiation exposure. A new treatment approach was tested in these patients, in which a prokaryotic DNA repair enzyme specific for UV-induced DNA damage was delivered into the skin by means of topically applied liposomes to supplement the deficient activity. Acute and chronic safety testing in both mice and humans showed neither adverse reactions nor significant changes in serum chemistry or in skin histology. The skin of XP patients treated with the DNA repair liposomes had fewer cyclobutylpyrimidine dimers in DNA and showed less erythema than did control sites. The results encourage further clinical testing of this new enzyme therapy approach.

Adolescent↗

A comparison of proliferation markers (BrdUrd, Ki-67, PCNA) determined at each cell position in the crypts of normal human colonic mucosa.

Samples of microscopically normal human sigmoid colon fixed in 70% ethanol from 15 patients who had received bromodeoxyuridine (BrdUrd) prior to surgery have been reanalyzed using a combination of proliferation markers. The specimens have been immunostained for proliferating cell nuclear antigen (PCNA) and after microwave treatment, they have been stained for BrdUrd and Ki-67. The 15 patients selected comprised 5 patients whose mucosa previously gave high BrdUrd labelling indices in the crypt, 5 that gave median values for BrdUrd labelling and 5 that gave low values for bromodeoxyuridine labelling on a previous analysis using tissue fixed in 70% ethanol and formal saline and using a different antibody (Potten et al., 1992). The relative levels of labelling at each cell position in the crypts has been compared using the 3 proliferation markers with the data being compared with the BrdUrd labelling as a standard labelling for S phase cells. One objective was to see whether all three proliferation markers discriminated equally well between the three groups of patient samples. The data show that the distinction between high, medium and low values seen with BrdUrd labelling was retained when Ki-67 immunostaining was analysed. PCNA immunostaining resulted in high levels of labelling and the different levels of labelling seen with BrdUrd and Ki-67 were largely lost.

Aged↗

Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma.

Apoptosis is an important mechanism of cell death in tumours and it is seen both prior to and following radiotherapy. In this study patients with proven carcinoma of the cervix had measurement made of the percentage of apoptotic cells (apoptotic index or AI) in pre-therapy biopsies. Measurements of intrinsic radiosensitivity (SF2), already shown to be a predictor of outcome, had previously been made on the same pre-therapy biopsies. Mitotic index (MI) and Ki-67 antigen staining were also recorded as markers for proliferation. Patients were divided into those with an AI above or below the median and in general increasing apoptosis was associated with poor prognosis. The 5-year survival rate for tumours with an AI below the median was 79% and was significantly greater than the rate of 47% for those with an AI above the median (p = 0.003). There was also a significantly increased 5-year local recurrence-free rate for patients with an AI below the median compared with those with an AI above the median (79 versus 61%, p = 0.012). In addition, AI and SF2 acted as independent prognostic indicators. Patients with both an SF2 and AI value above the median did badly (25% 5-year survival, 46% local control) compared with those with an SF2 and AI below the median (80% 5-year survival, 100% local control). Apoptosis showed correlation with MI (n = 66, r = 0.34, p = 0.002) and cell staining for the Ki-67 antigen (n = 57, r = 0.25, p = 0.03), but neither MI nor Ki-67 were related to patient outcome. This suggests that while apoptosis may be a reflection of tumour proliferation this cannot in itself explain the ability of apoptosis to predict clinical outcome for this series of patients. The study raises the possibility of AI and SF2 being used together as predictors of tumour response to radiotherapy.

Adult↗

Cryo-EM of the native structure of the calcium release channel/ryanodine receptor from sarcoplasmic reticulum.

The native structure of the calcium release channel (ryanodine receptor) from rabbit skeletal muscle has been analyzed in two dimensions from electron micrographs of frozen hydrated specimens. Within a resolution of 3.0 nm there is excellent agreement between the structure as seen in vitreous water and in negative stained specimens. Features seen in the three-dimensional reconstruction of the negatively stained channel can be identified in the projection of the unstained receptor.

Animals↗

The MRC Multicentre Study of Cognitive Function and Ageing: a EURODEM incidence study in progress.

The purpose of this paper is to describe the design and methodology of this multicentre study of cognitive function and ageing, which is currently funded by the Medical Research Council (MRC) and the Department of Health for a period of 5 years. The study is designed to estimate and compare the prevalence and incidence of dementia in five centres in the United Kingdom, to examine the natural history of cognitive decline and dementia in the population and to evaluate the degree of disability associated with any decline. This will be achieved by the examination, twice, of the cognitive function of individuals aged 65 and over, with an interval of 2 years between the examinations. A 20% subsample, taken across the full range of cognitive function will be reviewed annually in more detail to chart the level of cognitive function and to ascertain a diagnosis of dementia. This represents the first systematic examination of different populations using a common methodology in the United Kingdom.

Aged↗

Molecular cloning and characterization of the ryanodine receptor/junctional channel complex cDNA from skeletal muscle sarcoplasmic reticulum.

Major progress has been made in elucidating the calcium release mechanism involved in excitation-contraction coupling. The ryanodine receptor of sarcoplasmic reticulum has been isolated and found to be morphologically identical to the foot structure, which is involved in the junctional association of terminal cisternae with the transverse tubule. The foot structure also contains the calcium release channel itself. For this reason, we refer to the foot structure as the junctional channel complex (JCC). The JCC consists of an oligomer of a single high molecular weight protein. Although progress has been made in characterizing important aspects of the structure and function of the JCC, further understanding of the JCC protein subunit awaits the molecular cloning of the JCC. We report on the isolation of cDNA clones encoding portions of the JCC from rabbit fast-twitch skeletal muscle and its tissue distribution and expression. The large size and lack of solubility of the JCC protein posed particular challenges to cloning this molecule. Among these was the necessity to develop techniques for partially digesting the JCC protein subunit with endoproteases in the presence of detergent. With this approach we obtained partial amino acid sequences from regions of the JCC and designed oligonucleotide primers and probes to synthesize and screen cDNA libraries. The rabbit skeletal muscle JCC mRNA encodes an approximately 16-kilobase mRNA present in skeletal, heart, and aortic smooth muscle, as determined by RNA blot analysis with a 700-base-pair cDNA probe. Whereas the JCC mRNA appears to be relatively abundant in adult rabbit fast-twitch skeletal muscle, it is much less abundant in heart and smooth muscle. The JCC mRNA in BC3H1 (a myoblast cell line) is reversibly regulated by growth factors in a manner similar to muscle-specific contractile protein genes.

Amino Acid Sequence↗

Availability of treatment and diagnostic labelling.

A sample of pre-1967 case records with a hospital diagnosis of schizoaffective disorder were presented for rediagnosis to members of the present staff of the Institute of Psychiatry/Maudsley Hospital. The raters were asked to make a diagnostic choice of either schizophrenia or schizoaffective disorder or affective disorder and indicate how useful they would consider certain treatments for the present episode and for the long term. There was a significant trend in diagnosis to affective disorder but this trend was not correlated with the usefulness of certain treatments, e.g. lithium, a drug which had not been in use before 1967.

Affective Disorders, Psychotic↗