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Biomedical subjects

K Wilkinson

Publications and source records attributed to K Wilkinson.

At least 19 recordsLinked to original sources
PubMed2006

How long does a fetal scalp blood sample take?

The study aim was to identify the time from a decision to perform a fetal blood sample to the result of the test being available. A total of 100 consecutive fetal scalp blood samples taken on women in labour were identified from the blood gas analysers on the delivery suite. Eighty-nine percent of attempts yielded a result. The median time taken was 18 minutes (interquartile range 12-25 minutes). In 9% of women, the result took longer than 30 minutes. This is important clinically when repeated testing is required or in the second stage when operative vaginal delivery is achievable. Furthermore, when retrospectively analysing cases with a poor outcome, the time to obtain a result needs to be taken into account when determining the time at which a baby could have been delivered.

Acidosis↗
PubMed2004

Macaque dendritic cells infected with SIV-recombinant canarypox ex vivo induce SIV-specific immune responses in vivo.

Dendritic cells (DCs) infected with recombinant avipox vectors express the introduced genes and activate antigen-specific T cells. DCs exhibit distinct differentiation-dependent immune functions. Moreover, immature DCs are readily infected by canarypox vectors, but undergo tumor necrosis factor (TNF)-alpha-dependent death, while fewer mature DCs get infected and resist dying. A pilot study was performed using the rhesus macaque system to explore whether immature and mature DCs infected with SIV-recombinant canarypox (vCP180) ex vivo could induce primary virus-specific immune responses in vivo. After subcutaneous (sc) reinjection, functional monocyte-derived DCs migrated to lymph nodes (LNs) within 1-2 days and primed T cells in vivo. This was observed by monitoring dye-labeled DCs in the draining LNs and tetanus toxoid (TT)-specific T cell responses after injection of TT-loaded DCs. DCs from simian immunodeficiency virus (SIV)-naïve rhesus macaques were infected with vCP180 (SIVmac142 gag, pol, and env genes), and sc reinjected into donor animals. Low-level SIV-specific T cell proliferation, but little if any interferon (IFN)-gamma production was detected. DCs pulsed with vCP180 in combination with TT and keyhole limpet hemocyanin (KLH) (to activate additional T cells and provide "helper" cytokines) induced SIV-, TT-, and KLH-specific T cell responses, including IFN-gamma responses not seen when vCP180-carrying DCs were used alone. Interleukin (IL)-10 and low-level antibody responses were also observed. This pilot study provides the proof of principle that sc injected ex vivo SIV-recombinant canarypox-infected DCs safely induce low-level SIV-specific immune responses in vivo.

Animals↗
PubMed2004

Leg weakness is a complication of ilio-inguinal nerve block in children.

BACKGROUND: Ilio-inguinal nerve block is commonly used in children to provide analgesia after surgery in the groin. Several case reports and clinical studies have described leg weakness after this technique and suggest that it may caused by inadvertent femoral nerve block. No prospective studies describing the incidence of this complication have been published. METHODS: We carried out a prospective, observational study to find out how many children had leg weakness after ilio-inguinal nerve block. We studied 200 children having day-case surgery in the groin under a general anaesthetic with an ilio-inguinal nerve block. All children performed a simple leg-raising test with each leg before induction of general anaesthesia with a standardized ilio-inguinal nerve block on the side of surgery. When the child was awake and comfortable after surgery, they repeated the leg-raising test. RESULTS: Sixteen of 182 children (8.8%) had leg weakness after surgery on the side of the nerve block only, as detected by a leg-raising test. CONCLUSIONS: Leg weakness consistent with a femoral nerve block occurs after ilio-inguinal nerve block in approximately one in nine children.

Ambulatory Surgical Procedures↗
PubMed2003

The clinical course of fistulating Crohn's disease.

AIM: To determine the clinical characteristics, management and outcome of Crohn's fistulas from the time of first presentation. METHODS: Patients treated for fistulas 6 years previously were assessed for disease demographics, fistula characteristics and treatment from first presentation to final follow-up. RESULTS: Eighty-seven patients with active Crohn's fistulas were evaluated. The median age was 35 years and the median duration of Crohn's disease was 8 years at study entry. Disease was ileo-colonic or colonic in 85%, and 65% had rectal involvement. A single fistula was present in one-third and multiple fistulas in two-thirds; 65% of fistulas were perianal; 80% of fistulas were complex. After a median follow-up from the last treatment of 5.9 years, 68% of patients showed healing of all fistulas, 18% showed healing of some fistulas and 14% showed no healing of fistulas. The fistula site did not influence healing. Perianal and recto-vaginal fistulas took a median of 2.6 years to heal. Half of the complex fistulas required a stoma, resection or proctectomy. CONCLUSIONS: Healing is usually achieved. However, morbidity is great and healing is slow. Proctectomy is required in one-fifth of patients, and perineal healing is often slow. Defining the perianal fistula anatomy as complex or simple determines the likelihood of healing and the type of surgical approach required.

Adult↗
PubMed2001

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Adolescent↗
PubMed2001

Interval between decision and delivery by caesarean section-are current standards achievable? Observational case series.

OBJECTIVES: To audit interval from decision to delivery in urgent caesarean section to determine whether the current standard of 30 minutes is achievable routinely; to determine whether delay leads to an excess of admissions to special care. DESIGN: Three audit cycles over four years followed by a continuous audit over 32 months. SETTING: Large district general hospital delivering 5500 women each year. PARTICIPANTS: All women delivered by urgent caesarean section for abnormal fetal heart rate patterns, cord prolapse, failed instrumental delivery, or suspected placental abruption. MAIN OUTCOME MEASURES: Proportion of women delivered within 30 and 40 minutes of decision. Admission rates to special care by length of interval between decision and delivery. RESULTS: In the continuous audit 478 of 721 (66.3%) women were delivered in 30 minutes and 637 (88.3%) within 40 minutes; 29 (4.0%) were undelivered at 50 minutes. If the woman was taken to theatre in 10 minutes, 409 of 500 (81.8%) were delivered in 30 minutes and 495 (97%) in 40 minutes. There was no significant difference in the proportion of babies born at 36 weeks or later who were admitted to special care, when analysed by interval from decision to delivery. 36/449 (8%) babies with an interval from decision to delivery of less than 30 minutes were admitted to special care and 3/23 (13%) with an interval of more than 50 minutes were admitted. CONCLUSIONS: The current recommendations for the interval between decision and delivery are not being achieved in routine practice. Failure to meet the recommendations does not seem to increase neonatal morbidity.

Cesarean Section↗
PubMed2001

Identification of chest pain patients appropriate for an emergency department observation unit.

There are no perfect tests or algorithms to exclude ACI. Because acute coronary occlusion often occurs in patients with low-grade coronary stenosis, the diagnostic goal of a chest pain diagnostic protocol is not to identify patients with CAD, but rather to identify patients who may be safely discharged home without the development of complications such as MI, unstable angina, death, shock, or CHF over the next 1 to 6 months. There is an advantage to evaluating patients at the time of their symptoms. Patients who have a small plaque that is ruptured, leading to intracoronary thrombosis and ischemia, will manifest ischemia on diagnostic testing that could missed in routine outpatient testing when their plaque were stable. The diagnosis and risk stratification of acute coronary ischemia in the ED depends on a careful history and interpretation of the ECG. Multiple regression models using readily available data (e.g., history, physical examination, and ECG) provide the best tools for risk stratification. If one is deciding how to select patients for an EDOU chest pain evaluation, diagnostic tools that have previously been tested and validated in this setting are preferable. These include the Multicenter Chest Pain Study derived tools (i.e., Goldman, Lee), the ACI and ACI-TIPI tools, and sestamibi risk stratification tools. This is not to say that other tools may not play a role at individual institutions. It is probably better to select a consistent approach and evaluate its performance, rather than to allow random variation to dictate practice. The future direction probably will involve standardization of the ED chest pain population. This allows outcome and cost-effectiveness comparative research of various strategies for patients with normal or nondiagnostic ECGs and normal biomarkers. Although this approach allows more precise stratification, the risk will never be zero, meaning that there will never be a substitute for good clinical judgment and close follow-up care.

Chest Pain↗
PubMed2000

Functional outcome after restorative panproctocolectomy for ulcerative colitis decreases an otherwise enhanced quality of life.

BACKGROUND: Restorative panproctocolectomy is a favoured operation for ulcerative colitis, but altered bowel habit may adversely affect overall quality of life. METHODS: Specific and generic quality of life questionnaires and an instrument to award money for continuing disability based on government guidelines were sent to 103 patients who had curative surgery for ulcerative colitis between 1995 and 1997. Seventy-one patients returned completed questionnaires: 30 with an ileostomy (representing incontinence and abnormal body image), 11 with a Koch pouch (representing continence and abnormal body image) and 30 with a pelvic pouch (representing continence and normal body image). RESULTS: Patients valued the disability of having an ileostomy similar to that for a Koch pouch or a pelvic pouch: pound 40 000, pound 30 000 and pound 40 000 respectively (P = 0. 97). There was no sex difference. Body image measured with a visual analogue scale (least = 1, worst = 10) was worst with the ileostomy and Koch pouch (8 each) and best with a pelvic pouch (5) (P = 0.06). However, pelvic pouches scored significantly worse than an ileostomy with regard to altered bowel emptying (pelvic pouch, 8; Koch pouch, 7; ileostomy, 5) (P = 0.01). CONCLUSION: Poor function after pelvic pouch surgery offsets any advantage in body image over an ileostomy. Thus, overall quality of life and perceived monetary damage were the same for the two operations. Improved pelvic pouch function is likely to be reflected in better quality of life after restorative panproctocolectomy.

Adult↗
PubMed2000

Validation of a structured interview for the assessment of diabetes self-management.

OBJECTIVE: The authors developed and validated a semi-structured interview; the Diabetes Self-Management Profile (DSMP), to measure self-management of type 1 diabetes. The DSMP includes the following regimen components: exercise, management of hypoglycemia, diet, blood glucose testing, and insulin administration and dose adjustment. RESEARCH DESIGN AND METHODS: Families of youths with type 1 diabetes (n = 105) who were entering a controlled trial of intensive therapy (IT) versus usual care (UC) were administered the DSMP Analyses assessed the reliability and validity of the DSMP, including its associations with HbA1c and quality of life. RESULTS: The DSMP total score has adequate internal consistency (Cronbach's alpha 0.76), 3-month test-retest reliability (Pearson correlation, r = 0.67), inter-interviewer agreement (r = 0.94), and parent-adolescent agreement (r = 0.61). DSMP total scores (r = -0.28) and 3 subscales correlated significantly with HbA1c (diet [r = -0.27], blood glucose testing [r = -0.37], and insulin administration and dose adjustment [r = -0.25 ]). Adolescents' reports of self-management did not differ from parental reports. Higher DSMP scores were associated with more favorable quality of life for mothers and youths. CONCLUSIONS: The DSMP is a convenient measure that yields a reliable and valid assessment of diabetes self-management. Compared with extant similar measures, the DSMP is more strongly correlated with HbA1c.

Adolescent↗
PubMed1999

Induction of cellular immunity to a mycobacterial antigen adsorbed on lamellar particles of lactide polymers.

Microspheres prepared from synthetic, biodegradable poly (L-lactide) [PLA] and copolymers of lactide and glycolide such as poly (DL lactide co-glycolide) [PLG] have been widely investigated for controlled delivery of encapsulated vaccine antigens. In this study we describe novel lamellar microparticles produced from PLA to which protein antigens can be adsorbed. These particles when administered to mice, induced strong Th1-type T cell responses to the adsorbed 38 kDa protein antigen from M. tuberculosis characterised by high levels of Interferon-gamma. In addition to proteins, we were also able to adsorb synthetic peptides resulting in specific T cell proliferation. Induction of strong cellular immunity together with the versatility of antigen adsorption to these particles should make such lamellae a useful tool to deliver protective antigens from intracellular pathogens.

Adsorption↗
PubMed1999

Urinary monitoring of saccharin and acesulfame-K as biomarkers of exposure to these additives.

A method was developed to determine the levels of two intense sweeteners, saccharin and acesulfame-K, in human urine. Measurement of these two analytes in urine allowed an assessment to be made of dietary exposure to the sweeteners using intake/excretion curves. This paper describes an intake/excretion study in which 22 volunteers consumed known amounts of saccharin and acesulfame-K at five different levels ranging between 1.4 and 70 mg of saccharin (0.7-30% of the ADI for a 60 kg person) and 2.2-102 mg of acesulfame-K (0.4-19% of the ADI for a 60 kg person). Urine collections were then carried out by the volunteers for 24 h after each dose. The data obtained from this study were used to construct intake/excretion curves for both sweeteners. To test the methodology developed, 188 volunteers aged between 3 and 74 years were asked to carry out a 24-h urine collection whilst keeping a 48-h food diary. Comparison of the intake data obtained using the biomarker approach with the questionnaire-based results was generally good, although discrepancies due to the format and assessment of the questionnaire data were noticed.

Adolescent↗
PubMed1999

Interaction of Mycobacterium tuberculosis-induced transforming growth factor beta1 and interleukin-10.

Mycobacterium tuberculosis is associated with the activation of cytokine circuits both at sites of active tuberculosis in vivo and in cultures of mononuclear cells stimulated by M. tuberculosis or its components in vitro. Interactive stimulatory and/or inhibitory pathways are established between cytokines, which may result in potentiation or attenuation of the effects of each molecule on T-cell responses. Here we examined the interaction of transforming growth factor beta1 (TGF-beta1) and interleukin-10 (IL-10) in purified protein derivative (PPD)-stimulated human mononuclear cell cultures in vitro. TGF-beta1 induced monocyte IL-10 (but not tumor necrosis factor alpha) production (by 70-fold, P < 0.02) and mRNA expression in the absence but not in the presence of PPD. Both exogenous recombinant (r) IL-10 and rTGF-beta1 independently suppressed the production of PPD-induced gamma interferon (IFN-gamma) in mononuclear cells from PPD skin test-positive individuals. Synergistic suppression of IFN-gamma in cultures containing both rTGF-beta1 and rIL-10 was only seen when the responder cell population were peripheral blood mononuclear cells (PBMC) and not monocyte-depleted mononuclear cells and when PBMC were pretreated with rTGF-beta1 but not with rIL-10. Suppression of PPD-induced IFN-gamma in PBMC containing both rTGF-beta1 (1 ng/ml) and rIL-10 (100 pg/ml) was 1.5-fold higher (P < 0.05) than cultures containing TGF-beta1 alone and 5.7-fold higher (P < 0.004) than cultures containing IL-10 alone. Also, neutralization of endogenous TGF-beta1 and IL-10 together enhanced PPD-induced IFN-gamma in PBMC in a synergistic manner. Thus, TGF-beta1 and IL-10 together potentiate the downmodulatory effect on M. tuberculosis-induced T-cell production of IFN-gamma, and TGF-beta1 alone enhances IL-10 production. At sites of active M. tuberculosis infection, these interactions may be conducive to the suppression of mononuclear cell functions.

Animals↗