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Biomedical subjects

A Burgess

Publications and source records attributed to A Burgess.

At least 19 recordsLinked to original sources
PubMed2006

The perioperative specialist practitioner: developing and evaluating a new surgical role.

INTRODUCTION: This paper describes the design, implementation and evaluation of a new professional role in surgery. The role of the perioperative specialist practitioner (PSP), conceived as a response to the Working Time Directive, provides integrated preoperative and postoperative care to patients undergoing surgery in hospital. METHODS: A 1-year training programme was designed, dealing with a wide range of knowledge, skills and attitudes. Effective communication was a key component. Nine intensive 5-day modules at Imperial College London (London, UK) alternated with supervised experience of the surgical team at each participant's home trust. Detailed evaluation of the role and the training programme was provided by an independent research team, using an interview-based qualitative approach. Observational data were provided by the project team. Data were analysed using standard qualitative methods. RESULTS: 27 PSPs across 12 National Health Service trusts took part in two PSP training programmes. A total of 124 interviews (94 individual and 30 group) were carried out with PSPs and their colleagues. Overall, the role was seen as successful and positive, with great potential for dealing with reductions in junior medical cover. Each site encountered different opportunities and problems. Lack of mentorship was a key issue, and the role provoked considerable opposition in trusts. The training programme was viewed as highly successful. DISCUSSION: PSPs can provide high levels of expertise, but within clear limits. Our training programme has been effective and is perceived to be of high quality. However, introducing a new role requires time and sensitivity if opposition is to be minimised.

Adult↗
PubMed2005

Developing a standard short questionnaire for the assessment of patient satisfaction with out-of-hours primary care.

BACKGROUND: Governmental reviews of out-of-hours services in England and Scotland have recommended that a standard questionnaire should be used to assess patient satisfaction. This is important because of the rapid introduction of new forms of care. OBJECTIVE: To produce a brief, reliable and valid measure of patient satisfaction for use by a wide variety of providers of out-of-hours primary care. METHODS: The Short Questionnaire for Out-of-Hours care was designed and compared with a longer questionnaire which had been validated and used in earlier research. Questionnaires were sent to 1906 people contacting an out-of-hours GP co-operative. Three versions of the short questionnaire were used with different formats. Analysis compared the response rates, measurement properties, concurrent and construct validity of the short and long questionnaires, and of different versions of the short questionnaire. RESULTS AND CONCLUSIONS: There was no significant difference in the overall response rates obtained from the short or long questionnaires (45.7% versus 41.9%; P = 0.17). The effective response rate of questionnaires from which all satisfaction scales could be calculated was higher for the short questionnaire (43.0% versus 36.4%; P = 0.01). There were no significant differences in response rates or distribution of responses between different versions of the short questionnaire. There was moderate agreement between items on the short questionnaire and corresponding scales on the long questionnaire. Scores using the short questionnaire showed anticipated relationships with the age and sex of patients and with characteristics of how the service was delivered. The SQOC is valid and reliable for routine service use.

After-Hours Care↗
PubMed2003

Causes and outcomes of mild traumatic brain injury: an analysis of CIREN data.

Approximately one-half of vehicle occupants with traumatic brain injury (TBI) have a mild TBI (admission Glasgow Coma Scale (GCS) score of 13-15 with transient loss of consciousness). However, despite the label of "mild", many of these injuries result in long-term consequences; frequently these sequelae go unrecognized, as the patients are lost to medical follow-up. The Crash Injury Research Engineering Network (CIREN) project affords us the opportunity to examine the crash circumstances, injury sources and outcomes of mild TBI cases in greater detail.

Accidents, Traffic↗
PubMed2001

Platelet-derived growth factor requires epidermal growth factor receptor to activate p21-activated kinase family kinases.

The platelet-derived growth factor (PDGF) receptor (PDGFR) transactivates the epidermal growth factor (EGF) receptor (ErbB1) to stimulate the cell migration of fibroblasts through an unknown mechanism (Li, J., Kim, Y. N. & Bertics, P. (2000) J. Biol. Chem. 275, 2951-2958). In this paper we provide evidence that the transactivation of the EGF receptor (EGFR) by PDGFR is essential for PDGF to activate p21-activated kinase (PAK) family kinases. Fetal calf serum (10%) transiently stimulates the PAK activity in NIH 3T3 fibroblasts. The activation of PAK was completely inhibited by either PDGFR-specific inhibitor (AG1295) or EGFR-specific inhibitor (AG1478), suggesting that serum requires either the PDGF- or EGF-dependent pathway or the combination of both to activate PAK. PDGF-induced activation of PAK is completely inhibited by either AG1295 or AG1478, indicating that PDGF requires both PDGFR and EGFR for PAK activation. In support of this notion, a mouse embryo fibroblast cell line derived from the EGFR -/- mouse (from Dr. Erwin Wagner) doesn't activate PAK in response to PDGF. Expression of human EGFR in this cell line restores the ability of the PDGF to induce PAK activation. Our results indicate that PDGF activates PAK through transactivation of ErbB1.

3T3 Cells↗
PubMed2000

c-Raf-1 RBD associates with a subset of active v-H-Ras.

Mutational analysis of the cRaf-1 Ras binding domain (RBD) identified several point mutants with elevated Ras binding. Detailed examination of the binding kinetics of one mutant (A85K) suggests that it associates with a greater range of isomeric conformers of v-H-Ras than wt-RBD. At limiting v-H-Ras concentrations, saturation binding to A85K-RBD is higher than to wt-RBD. Notably, in assay systems where the RBD concentration is limiting, no difference exists between wt-RBD and A85K-RBD saturation levels in the presence of a sufficiently large molar excess of Ras. The inability of wt-RBD to saturate all bindable Ras/GTP (defined by its binding to A85K-RBD) suggests that Ras/GTP exists as several isoforms and that only a minority of these isoforms are capable of associating with wt-RBD. These findings provide the first experimental evidence in support of functionally distinct Ras/GTP isoforms. We also describe a novel analysis of such isoforms.

Binding Sites↗
PubMed2000

Point mutants of c-raf-1 RBD with elevated binding to v-Ha-Ras.

A mutational analysis of the Ras-binding domain (RBD) of c-Raf-1 identified three amino acid positions (Asn(64), Ala(85), and Val(88)) where amino acid substitution with basic residues increases the binding of RBD to recombinant v-Ha-Ras. The greatest increase in binding (6-9-fold) was observed with the A85K-RBD mutant. The elevated binding for the A85K-RBD and V88R-RBD mutants was also detected with Ras expressed in cultured mammalian cells, namely NIH-3T3 and BAF cells. None of the wild type residues in RBD positions Asn(64), Ala(85), and Val(88) have been previously implicated in the interaction with Ras (Block, C., Janknecht, R., Herrmann, C., Nassar, N., and Wittinghofer, A. (1996) Nat. Struct. Biol. 3, 244-251; Nassar, N., Horn, G., Herrmann, C., Scherer, A., McCormick, F., and Wittinghofer, A. (1995) Nature 375, 554-560). The discovery of elevated binding among the mutants in these positions implies that additional RBD residues can be used to generate the Ras. RBD complex. These findings are of particular significance in the design of Ras antagonists based on the RBD prototype. The A85K-RBD mutant can be used to develop an assay for measuring the level of activated Ras in cultured cells; Sepharose-linked A85K-RBD.GST fusion protein served as an activation-specific probe to precipitate Ras.GTP but not Ras.GDP from epidermal growth factor-stimulated cells. A85K-RBD precipitates up to 5-fold more Ras.GTP from mammalian cells than wild type RBD.

Amino Acid Sequence↗
PubMed2000

Characterization of a novel human immunodeficiency virus type 1 neutralizable epitope within the immunodominant region of gp41.

Previously, we generated human monoclonal antibodies using peripheral blood mononuclear cells from an asymptomatic human immunodeficiency virus type 1 (HIV-1)-seropositive donor. One of these monoclonal antibodies (designated clone 3, CL3) recognized 10 amino acids (GCSGKLICTT) within the immunodominant region (cluster I) of the transmembrane envelope glycoprotein gp41 and neutralized infection of target cells with different laboratory isolates. Because the epitope recognized by CL3 has two cysteine residues that could potentially produce a disulfide loop in gp41, we analyzed binding of our monoclonal antibody to the cyclic and linear motif of the peptide sequence IWGCSGKLICTTAVP (residues 600-614). The CL3 antibody did not bind to the synthetic cyclic peptide but did recognize the linear form. Two polyclonal rabbit sera against both the linear and cyclic peptides were then generated. Both antisera bound to viral glycoproteins gp41 and gp160, but neither sera neutralized HIV-1 laboratory isolates. Using a set of alanine-substituted IWGCSGKLICTTAV peptides, we analyzed binding of polyclonal antisera and CL3. The profile of binding of polyclonal antisera to these peptides was different from that of CL3 to the same peptides. This suggests that CL3 recognized a unique neutralizable core epitope, which was not immunogenic in either the cyclic or the linear IWGCSGKLICTTAVP peptides used as immunogens in the rabbits.

Amino Acid Sequence↗
PubMed2000

Fine-needle aspiration biopsy of metastatic chordoma: case report and review of the literature.

Chordoma is a distinct malignant neoplasm arising from the remnants of the notochord and occurring mostly in the fifth or sixth decade of life, and occupying most frequently the sacral area (Bibbo, Comprehensive Cytopathology 1997; p 534). Metastases of the neoplasm may occur in 10-40% of cases (Jenkins et al., Clin. Radiol. 1995;50:416-417). Because of its rarity, the diagnosis of chordoma may be difficult to render, especially on fine-needle aspiration biopsy (FNAB). However, a clear-cut distinction of chordoma from other neoplasms is of utmost importance, since the prognosis and treatment of the patient will depend on the final diagnosis. This distinction in the case of metastases can be made easily, where correlation of previous histology has been done and/or ancillary studies have been performed. Diagn. Cytopathol. 2000;22:104-106.

Biomarkers, Tumor↗
PubMed2000

Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells.

Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic integrity. An increasing number of tumor suppressors are being demonstrated to have roles in checkpoint mechanisms, implying that checkpoint dysfunction is likely to be a common feature of cancers. Here we report that histone deacetylase inhibitors, in particular azelaic bishydroxamic acid, triggers a G2 phase cell cycle checkpoint response in normal human cells, and this checkpoint is defective in a range of tumor cell lines. Loss of this G2 checkpoint results in the tumor cells undergoing an aberrant mitosis resulting in fractured multinuclei and micronuclei and eventually cell death. This histone deacetylase inhibitor-sensitive checkpoint appears to be distinct from G2/M checkpoints activated by genotoxins and microtubule poisons and may be the human homologue of a yeast G2 checkpoint, which responds to aberrant histone acetylation states. Azelaic bishydroxamic acid may represent a new class of anticancer drugs with selective toxicity based on its ability to target a dysfunctional checkpoint mechanism in tumor cells.

Cell Cycle↗
PubMed2000

Determinants of disability after lower extremity fracture.

BACKGROUND: Factors influencing the progression of physical impairment to patient-perceived disability are not well known. We sought to better understand this relationship in the setting of injury. METHODS: We followed a cohort of 302 patients with lower extremity fractures over a 1-year period. Physical impairment was assessed by range of motion, strength, and pain. Range of motion and strength were assessed together as a proportion of normal function of the extremity (impairment score). Pain was assessed using a Visual Analogue Scale (VAS) pain score. Disability was assessed using the Sickness Impact Profile (SIP), a widely used measure of patient-perceived limitations of everyday activities attributable to illness. The SIP was administered during hospitalization to assess preinjury baseline. Impairment assessment and readministration of the SIP were performed at 12 months after injury. RESULTS: Impairment in leg function (range of motion and strength) was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 23% of the variance in overall SIP scores. Likewise, VAS pain score was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 29% of the variance in overall SIP scores. In a multivariate linear regression analysis, variables that were independently associated with overall SIP score included impairment score, VAS pain score, preinjury SIP, poverty status, education status, social support, having hired a lawyer, and involvement with workers' compensation. These variables accounted for 52% of the variance in overall SIP scores at 12 months. CONCLUSION: The degree of physical impairment accounts for only a small amount of the variance in disability from lower extremity fracture. Identifiable patient characteristics including age, socioeconomic status, preinjury health, and social support together with impairment account for over half of the variance in long-term disability. Further research is needed to increase understanding of other factors that influence the progression of impairment to disability, especially those factors that may be amenable to intervention.

Adolescent↗
PubMed1999

A physical and transcriptional map of the preaxial polydactyly locus on chromosome 7q36.

Preaxial polydactyly is a congenital hand malformation that includes duplicated thumbs, various forms of triphalangeal thumbs, and duplications of the index finger. A locus for preaxial polydactyly has been mapped to a region of 1.9 cM on chromosome 7q36 between polymorphic markers D7S550 and D7S2423. We constructed a detailed physical map of the preaxial polydactyly candidate region. With a combination of methods we identified and positioned 11 transcripts within this map. By recombination analysis on families with preaxial polydactyly, using newly developed polymorphic markers, we were able to reduce the candidate region to approximately 450 kb. The homeobox gene HLXB9, a putative receptor C7orf2, and two transcripts of unknown function, C7orf3 and C7orf4, map in the refined candidate region and have been subjected to mutation analysis in individuals with preaxial polydactyly.

Base Sequence↗
PubMed1999

Genetic pathway to recurrent chromosome translocations in murine lymphoma involves V(D)J recombinase.

Chromosome translocations involving antigen receptor loci are a genetic hallmark of non-Hodgkin's lymphomas in humans. Most commonly, these translocations result in juxtaposition of the immunoglobulin heavy-chain (IgH) locus with one of several cellular proto-oncogenes, leading to deregulated oncogene expression. The V(D)J recombinase, which mediates physiologic rearrangements of antigen receptor genes, may play a mechanistic role in some lymphoma translocations, although evidence is indirect. A high incidence of B-lineage lymphomas has been observed in mice with severe combined immunodeficiency (SCID) and p53-null mutations. We show that these tumors are characteristic of the pro-B-cell stage of development and that they harbor recurrent translocations involving chromosomes 12 and 15. Fluorescence in situ hybridization (FISH) shows retention of IgH sequences on the derivative chromosome 12, implying that breakpoints involve the IgH locus. Pro-B-cell lymphomas were suppressed in SCID p53(-/-) mice by a Rag-2-null mutation, demonstrating that DNA breaks generated during V(D)J recombination are required for oncogenic transformation, and suggesting that t(12;15) arise during attempted IgH rearrangement in pro-B cells. These studies indicate that the oncogenic potential inherent in antigen receptor diversification is controlled in vivo by efficient rejoining of DNA ends generated during V(D)J recombination and an intact cellular response to DNA damage.

Animals↗
PubMed1998

Breastfeed till two.

I would like to comment on the article on breast feeding in emergency situations (AH Sept '97). The first sentence, "Breast feeding is widely recognized as the optimal feeding option for an infant up to the age of 6 months," might give the impression--albeit unintentionally--that breast feeding is only important during this period. It is generally recommended that breast feeding should continue, accompanied by suitable complementary foods, until around 2 years. I think it is now established that effective suckling by the baby is as crucial for successful breast feeding as the mother's let-down reflex. Proper positioning of the infant on the breast may be as important as helping the mother feel confident about breast feeding. WHO has not ignored this issue. It has produced a review version of the document "Guiding principles for feeding infants and young children during emergencies" (doc NIT.97.3), which promotes breast feeding for all children under 2 years.

Adolescent↗
PubMed1997

Neurophysiological changes associated with psychiatric symptoms in HIV-infected individuals without AIDS.

HIV-1 infection may be complicated by a number of psychopathological conditions. While organic mental disorders, such as HIV-related psychosis and dementia, are late manifestations, mood disorders may occur during both asymptomatic and symptomatic stages of infection. The possible impact of brain involvement due to neurotropism of HIV-1 has not been investigated systematically in these latter conditions. The psychiatric caseness of HIV-seropositive individuals without AIDS and seronegative controls was assessed using a standardized clinical interview (Present State Examination). A comparison was made between individuals with and without psychiatric caseness using clinical, neuropsychological, and neurophysiological assessments. An increased prevalence of current psychiatric illness was found in subjects with early symptomatic HIV infection compared to those with asymptomatic infection and controls. This could not be attributed to psychiatric history, as well as to clinical and immunological markers of HIV infection, however, psychiatric caseness in early symptomatic infection was associated with marked neurophysiological changes, detectable by quantitative electroencephalography. Altogether, this study provided preliminary evidence that psychiatric symptoms in symptomatic but not asymptomatic HIV infection may be associated with subtle brain involvement preceding the immunological and neurocognitive impairment characteristic for AIDS.

Adult↗
PubMed1997

Prospective evaluation of local excision for small rectal cancers.

OBJECTIVE: Most data on local excisions for rectal cancer are based on retrospective studies. We review the results of a prospective registry of patients eligible for local excision of rectal cancer using a transanal, transsphincteric, or transcoccygeal technique combined with multimodality therapy for lesions penetrating the muscularis propria (T2) or perirectal fat (T3). METHODS: Patients with lesions less than 4 cm in diameter and less than 10 cm from the dentate line, with no evidence of distant metastases or invasion into the perirectal fat, were eligible for local excision. Patients with invasion into the muscularis propria (T2) or greater (T3) received adjuvant chemoradiation therapy. RESULTS: Forty-eight patients have been followed prospectively. Average age is 63 years. Thirty-three patients underwent a transanal excision. Fifteen patients underwent either a transsphincteric or technique excision. There was no perioperative mortality. Pathology revealed 1 Tis, 21 T1, 21 T2, and 5 T3 cancers. Mean follow-up is 40.5 months. Cancer-related overall mortality was 4 percent. Overall local or distant recurrence rate was 8 percent (4/48). Recurrence appeared to be related to presence of a positive margin or aggressive histology (lymphatic invasion). Local recurrences were treated with salvage therapy. CONCLUSION: Local excision can be used selectively for small rectal cancers, with minimum morbidity. Recurrence rates are low (8 percent). Patients with either a positive margin or lymphatic invasion need to be considered for further therapy, including abdominoperineal resection, even with T1 lesions. Adjuvant chemoradiation appears to be a benefit for all T2 or T3 cancers.

Adenocarcinoma↗
PubMed1996

Cloning, expression and sequence analysis of the Bartonella henselae gene encoding the HtrA stress-response protein.

A cloned fragment of Bartonella (Rochalimaea) henselae (Bh) DNA was found to direct synthesis of an immunoreactive protein in Escherichia coli (Ec). Sequence analysis revealed an open reading frame of 1509 nucleotides encoding a protein of 503 amino acids that exhibited extensive identity (over the entire protein) with the HtrA stress-response proteins of Brucella abortus (59%), Ec (37%) and Salmonella typhimurium (36%). When the putative htrA gene was amplified by polymerase chain reaction and used as template for in vitro transcription and translation, a protein with an apparent molecular mass of 62 kDa was synthesized from the plasmid template. These results suggest that the immunoreactive Bh protein is homologous to the HtrA class of stress-response proteins.

Bartonella henselae↗
PubMed1996

Hypothesis: "Rogue cell"-type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncopenesis.

The hemagglutination inhibition antibody titers against the JC and BK polyoma viruses (JCV and BKV, respectively) are significantly elevated in individuals exhibiting "rogue" cells among their cultured lymphocytes. However, the elevation is so much greater with respect to JCV that the BKV elevation could readily be explained by cross reactivity to the capsid protein of these two closely related viruses. The JCV exhibits high sequence homology with the simian papovavirus, simian virus 40 (SV40), and inoculation of human fetal brain cells with JCV produces polyploidy and chromosomal damage very similar to that produced by SV40. We suggest, by analogy with the effects of SV40, that these changes are due to the action of the viral large tumor antigen, a pluripotent DNA binding protein that acts in both transcription and replication. The implications of these findings for oncogenesis are briefly discussed.

Adolescent↗