Biomedical subjects

C E Chapman

Publications and source records attributed to C E Chapman.

At least 19 recordsLinked to original sources

PubMed2006

Changing indications for red cell transfusion from 2000 to 2004 in the North of England.

Falling donor numbers and the threat of transfusion-transmitted variant Creutzfeldt-Jakob disease may lead to shortages in the national blood supply. Knowledge of current patterns of transfusion and trends in usage will help predict future change in blood use. Our previous survey identified medical indications as the major reason for transfusion, but detailed information within this category was limited. We performed prospective surveys of indications for red cell transfusion for two 14-day periods in 2004 in the North of England, concentrating on medical reasons for transfusion. Data were obtained for transfusion indications of 9003 units, which accounted for over 99% of red cell issues from the regional blood centre during the study. In 2004, medical patients received 62% (5558 units) of all transfused units, surgical patients 33% (3001 units) and Obstetric & Gynaecology patients 5% (444 units). These figures compare with 52, 41 and 6% for Medicine, Surgery, and Obstetrics & Gynaecology in 1999/2000. The three largest uses of blood within the medical category were for patients with primary haematological disorders (18.2% of all transfused blood), for management of gastrointestinal haemorrhage (13.8%) and for patients with nonhaematological malignancies (8.8%). There has been a significant reduction in use of blood for surgical indications over the last 5 years, but an absolute increase in use of blood for medical indications. Lower transfusion triggers, education, use of cell salvage, the increasing price of a unit of red cells and changing population demographics may all have contributed to the reduction in surgical blood use. Promotion of good transfusion practice and alternatives to allogeneic transfusion should now focus on medical and surgical use of blood transfusion.

Age Factors↗

PubMed2005

Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation.

Chronic allograft rejection is the major problem encountered in solid organ transplantation and is the end point of several complex processes. A number of recent studies show both alloimmune and autoimmune responses may have roles to play. The importance of HLA antibodies in transplantation is well documented, but despite the introduction of very sensitive HLA screening assays, antibody-mediated allograft rejection still occurs without detectable HLA antibodies. The target for antibody-mediated allograft rejection in these circumstances remains elusive, perhaps due to the variety of potential targets presented on endothelial cells. Recent studies identifying C4d and immunoglobulin deposits in patients undergoing late allograft loss provide evidence that chronic rejection involves humoral as well as cellular components. Several endothelial cell antigens that might be important in chronic rejection have been suggested, including MHC class I chain-related genes; Lewis; and the intermediate filament protein, vimentin. Vimentin is an ideal candidate antigen for antibody-mediated rejection as it is found in endothelial cells and is exposed to the immune system following surgery or by chronic allograft rejection due to endothelial cell breakdown, where the development of antibodies may cause further damage. We have developed a flow cytometric assay for the detection of antibodies to vimentin and have investigated whether HLA or vimentin antibodies are present in renal transplant recipients undergoing chronic rejection.

Graft Rejection↗

PubMed2005

Single centre experience of umbilical cord stem cell transplantation for primary immunodeficiency.

Primary immunodeficiencies (PID) are an important cause of childhood mortality. Haematopoietic stem cell transplantation (HSCT) is the best treatment for many PID. Umbilical cord stem cells are an alternative source of HSC. There is little data regarding outcome of umbilical cord stem cell transplantation (UCSCT) for PID. Our single centre experience is reported. A retrospective study of 14 of 148 patients transplanted for PID, who have received 15 UCSCT was performed, with specific regard to graft-versus-host disease (GvHD) and immune reconstitution. Eight patients with severe combined immunodeficiency (SCID), and six with other combined immunodeficiencies were treated. Of the patients, 12 received unrelated cords, and two had sibling transplants. Median age at transplant was 3.5 months, median nucleated cell dose was 0.8 x 10(8)/kg. All engrafted. Median time to neutrophil engraftment was 22 days, median time to platelet engraftment was 51 days. One developed significant grade III GvHD post transplantation. In total, 11 patients had full donor T and six full donor B-cell chimerism, six of nine patients >1 year post-BMT had normal IgG levels and specific antibody responses to tetanus and Hib vaccines; two are being assessed. Two patients died of multi-organ failure related to pre-existing infection and inflammatory complications respectively. UCSCT should be considered for patients requiring stem cell therapy for PID.

Antibody Formation↗

PubMed2004

Transfusion-related acute lung injury caused by two donors with anti-human leucocyte antigen class II antibodies: a look-back investigation.

Transfusion-related acute lung injury (TRALI) is considered as one of the most important complications of blood transfusion. Previous look-back investigations have revealed unrecognized cases. We report two cases of TRALI in brief and the outcomes of transfusion in the recipients of previous components from the implicated donors. This look-back investigation was a retrospective case-note study assessing whether there were any untoward events associated with the previous transfusions. 18 patients were identified as having received a blood component transfusion from one of the two donors with anti-human leucocyte antigen (HLA) antibodies to antigens occurring frequently in the local population. One of the five patients receiving a unit of fresh frozen plasma had an evidence of TRALI, which was not diagnosed at the time. A second patient, who had been HLA typed and who carried a full match of antigens for the antibody specificities of the plasma received, had no evidence of a reaction. There were no documented reactions in 13 recipients of red cells in optimal additive (OA) solution. Cases of TRALI may go unrecognized. Not all patients with antibody/antigen concordance will develop clinical signs. Red cells in OA solution from donors with anti-HLA antibodies appear to have a low risk of causing clinically evident lung damage.

Adult↗

PubMed2003

Successful umbilical cord blood stem cell transplantation for chronic granulomatous disease.

Chronic granulomatous disease (CGD) causes growth failure, inflammatory lung damage and often early death. Prophylactic cotrimoxazole improves medium-term survival, but cannot prevent inflammatory sequelae. We report the first patient with CGD who underwent successful HLA identical sibling umbilical cord stem cell transplantation (UCSCT) after myeloablative conditioning. The patient presented with colitis, confirmed as CGD at 2 years of age. Following BU16/CY200 conditioning, he had UCSCT from his unaffected HLA identical sister. A year post-transplant, his colitis had resolved clinically and on radioisotope scan growth has improved. Neutrophil oxidative burst was 92% normal with full donor lymphocyte reconstitution.

Child, Preschool↗

PubMed2002

Where does blood go? Prospective observational study of red cell transfusion in north England.

OBJECTIVE: To collect population based information on transfusion of red blood cells. DESIGN: Prospective observational study over 28 days. SETTING: Hospital blood banks in the north of England (population 2.9 million). MAIN OUTCOME MEASURES: Indications for transfusion, number of units given, and the age and sex of transfusion recipients. PARTICIPANTS: All patients who received a red cell transfusion during the study period. Data completed by hospital blood bank staff. RESULTS: The destination of 9848 units was recorded (97% of expected blood use). In total 9774 units were transfused: 5047 (51.6%) units were given to medical patients, 3982 (40.7%) to surgical patients, and 612 (6.3%) to obstetric and gynaecology patients. Nearly half (49.3%) of all blood is given to female recipients, and the mean age of recipients of individual units was 62.7 years. The most common surgical indications for transfusion were total hip replacement (4.6% of all blood transfused) and coronary artery bypass grafting (4.1%). Haematological disorders accounted for 15.5% of use. Overall use was 4274 units per 100 000 population per year. CONCLUSION: In the north east of England more than half of red cell units are transfused for medical indications. Demand for red cell transfusion increases with age. With anticipated changes in the age structure of the population the demand for blood will increase by 4.9% by 2008.

Adolescent↗

PubMed2002

Effect of WBC reduction of transfused RBCs on postoperative infection rates in cardiac surgery.

BACKGROUND: WBC-replete blood transfusion has been suggested as an independent cause of increased postoperative infection. STUDY DESIGN AND METHODS: A total of 597 patients undergoing elective coronary artery or heart valve surgery were randomly assigned to receive plasma-reduced (PR), buffy coat-depleted (BCD), or WBC-filtered (WCF) RBCs in the event of requiring blood transfusion. Details of postoperative course were recorded. Further information was collected from the patient's general practitioner 3 months after discharge. RESULTS: No significant difference in inpatient infection rates was observed among patients randomly assigned to receive PR, BCD, or WCF RBCs. When only those receiving transfusion were analyzed (n = 509), use of PR RBCs was associated with more events coded as infections (p < or = 0.05) compared with BCD or WCF RBCs. However, when events coded as urinary tract infections were excluded, there was no significant difference among the three groups. Follow-up performed after discharge showed no difference in readmission rates, but a higher reported rate of infection in those randomly assigned to receive WCF RBCs (p < 0.02). CONCLUSION: No evidence has been found, analyzed by intention to treat, that use of WBC-reduced, BCD, or WCF RBCs reduces postoperative inpatient infection in patients undergoing cardiac bypass surgery.

Aged↗

PubMed2001

Identification and quantification of anti-D, -C and -G in alloimmunized pregnant women.

Our objectives were to investigate possible overestimation of maternal anti-D due to co-existing anti-C and/or anti-G, and to confirm the presence of anti-D in plasma presumed to contain anti-D+C. We investigated 96 samples (from 22 antenatal patients and 74 blood donors) initially identified as containing anti-D+C using routine investigation procedures. Anti-D quantification was performed using an Astoria Pacific International 300 (API 300) continuous flow analyser with R1R1 and R2R2 reagent red cells. Where possible, samples were tested manually using a rare D+, C-, G- cell, to confirm the presence of anti-D. Fifty-two of 96 samples (11/22 antenatal patients and 41/74 blood donors) gave >50% higher anti-D quantification results with R1R1 cells than with R2R2 cells. Anti-D was not detected using manual techniques in 16 of 73 samples tested (10/22 antenatal patients and 6/51 blood donors). Anti-D quantification using R1R1 reagent red cells may cause inaccurate estimation of anti-D levels, when anti-C and/or anti-G are present. Indeed, a significant number of cases, where apparent anti-D+C is identified, may contain only anti-C+G and lack an anti-D component. This may in turn lead to a failure to administer prophylactic anti-D immunoglobulin to RhD negative patients in cases where anti-D is not present, putting these patients at risk from immunization with possible consequences to future pregnancies.

Blood Grouping and Crossmatching↗

PubMed2000

Relative effects of the spatial and temporal characteristics of scanned surfaces on human perception of tactile roughness using passive touch.

The present experiments were designed to determine the ability of humans to estimate the roughness of raised dot surfaces using passive touch (subject immobile, surfaces scanned proximo-distally under the tip of the middle digit). In two initial experiments, the spatial period in the direction of the scan (longitudinal SP) was varied from 1.5 to 5 mm, while the transverse SP was kept constant at 2 mm. These surfaces were identical to those used in single unit recording experiments in primates which have shown that neurones in primary somatosensory cortex (SI) show graded changes in discharge over the same range of SPs. In the third and fourth experiments, roughness perception was studied over an extended range of longitudinal SPs (1.5-8.5 mm); transverse SP was either 1 or 2 mm. We also examined the effects on roughness perception of presenting the surfaces at two different scanning speeds (approximately 50 and approximately 95 mm/s), similar to those employed in the unit recordings. Magnitude estimates of perceived roughness increased in a nearly linear fashion as longitudinal SP was increased up to either 5 mm (experiments 1 and 2) or 8.5 mm (experiments 3 and 4). A modest increase in the transverse SP elicited a small increase in roughness estimates, with preservation of the linear relation between roughness and longitudinal SP. The roughness sensation evoked by each surface was not affected by the change of the temporal pattern of scanning (Low and High speeds). These results showed that there is perceptual constancy for roughness across a twofold change in passive scanning speed, and that roughness is a function of the spatial characteristics of these raised dot surfaces. While a spatial code may underlie this observation, it is suggested that a simpler intensive code may be sufficient to explain the psychophysical observations. Based on the results of neurophysiological recordings in SI cortex, it is suggested that an invariant central representation of surface roughness could be extracted from the ambiguous peripheral signals that covary with roughness and the stimulating conditions (e.g. speed) by means of a simple subtraction process.

Adult↗

PubMed2000

Time course and magnitude of movement-related gating of tactile detection in humans. II. Effects of stimulus intensity.

This study examined the effect of systematically varying stimulus intensity on the time course and magnitude of movement-related gating of tactile detection and scaling in 17 human subjects trained to perform a rapid abduction of the right index finger (D2) in response to a visual cue. Electrical stimulation was delivered to D2 at five different intensities. At the lowest intensity, approximately 90% of stimuli were detected at rest (1 x P(90)); four multiples of this intensity were also tested (1.25, 1.5, 1.75, and 2. 0 x P(90)). At all intensities of stimulation, detection of stimuli applied to the moving digit was diminished significantly and in a time-dependent manner, with peak decreases occurring within +/-12 ms of the onset of electromyographic activity in the first dorsal interosseous (25-45 ms before movement onset). Reductions in the proportion of stimuli detected were greatest at the lowest stimulus intensity and progressively smaller at higher intensities. No shift in the timing of the decreases in performance was seen with increasing intensity. Once the weakest intensity at which most stimuli were perceived during movement had been established (2 x P(90)), magnitude estimation experiments were performed using two stimulus intensities, 2 x P(90) (5 subjects) and 3 x P(90) (3 subjects). Significant movement-related decreases in estimated stimulus magnitude were observed at both intensities, the time course of which was similar to the time course of reductions in detection performance. As stimulus intensity increased, the magnitude of the movement-related decrease in scaling diminished. A model of detection performance that accurately described the effect of stimulus intensity and timing on movement-related reductions in detection was created. This model was then combined with a previous model that described the effects of stimulus localization and timing to predict detection performance at a given stimulation site, intensity, and time during movement. Movement-related gating of tactile perception represents the end result of movement-related effects on the transmission and subsequent processing of the stimulus. The combined model clearly defines many of the requirements that proposed physiological mechanisms of movement-related gating will have to fulfill.

Adolescent↗

PubMed1998

MRC trial of alpha2b-interferon maintenance therapy in first plateau phase of multiple myeloma. MRC Working Party on Leukaemia in Adults.

Plateau phase has been achieved in 64% of all newly diagnosed patients with multiple myeloma treated with the ABCM (adriamycin, BiCNU, cyclophosphamide and melphalan) regimen in the Medical Research Council (MRC) trials; this stable clinical stage of the disease is associated with no more than minimal symptoms. Several studies have found that alpha-interferon (alpha-IFN) maintenance therapy increases the duration of plateau phase, but it is less clear if this translates into prolonged survival. We report the effect of alpha-IFN on the duration of plateau phase and overall survival in a trial with 284 patients who were randomized to receive alpha2b-IFN (Intron-A) or no maintenance therapy during first plateau phase. The minimum follow-up after randomization was 21 months. There was no significant difference in the overall survival between the two treatment groups (X2=0.32, P=0.57). There was a trend towards longer relapse-free survival in the patients allocated alpha-IFN, but this trend to longer plateau phase was not statistically significant (X2 = 1.62, P = 0.2). Disease progression at relapse on alpha-IFN appears to be more severe with greater elevations from plateau levels of serum paraprotein (P = 0.06) and beta2-microglobulin (P= 0.03) levels. Physicians tended to start chemotherapy sooner after diagnosis of relapse when patients had received alpha-IFN (P = 0.16). Although, in common with most other studies, there is a trend for patients treated with alpha-IFN to have a longer plateau phase, this is counteracted by morbidity attributable to the treatment and a somewhat shortened survival post relapse. Meta-analysis of interferon trials is required to assess whether the minor trend for longer survival in patients maintained on alpha-IFN found in some studies is significant and, if so, the extent of this advantage.

Adult↗

PubMed1998

Time course and magnitude of movement-related gating of tactile detection in humans. I. Importance of stimulus location.

The time course and spatial extent of movement-related suppression of the detection of weak electrical stimuli (intensity, 90% detected at rest) was determined in 118 experiments carried out in 47 human subjects. Subjects were trained to perform a rapid abduction of the right index finger (D2) in response to a visual cue. Stimulus timing was calculated relative to the onset of movement and the onset of electromyographic (EMG) activity. Electrical stimulation was delivered to 10 different sites on the body, including sites on the limb performing the movement (D2, D5, hand, forearm and arm) as well as several distant sites (contralateral arm, ipsilateral leg). Detection of stimuli applied to the moving digit diminished significantly and in a time-dependent manner, with the first significant decrease occurring 120 ms before movement onset and 70 ms before the onset of EMG activity. Movement-related and time-dependent effects were obtained at all stimulation sites on the homolateral arm as well as the adjacent trunk. A pronounced spatiotemporal gradient was observed: the magnitude of the movement-related decrease in detectability was greatest and earliest at sites closest to the moving finger and progressively weaker and later at more proximal sites. When stimuli were applied to the distant sites, only a small (approximately 10%), non-time-dependent decrease was observed during movement trials. A simple model of perceptual performance adequately described the results, providing insight into the distribution of movement-related inhibitory controls within the CNS.

Adolescent↗

PubMed1998

Inhibitory influence of soleus massage onto the medial gastrocnemius H-reflex.

It has previously been reported that the soleus Hoffmann (H-)reflex is diminished in amplitude during a massage of the ipsilateral triceps surae. A question arises as to the origin of this decrease. The purpose of this study was to determine whether massage does indeed diminish motoneuronal excitability or whether the decrease is an artefact associated with the experimental procedures, i.e. saturation of the transmission capacity of the afferent pathway. H-reflexes and the corresponding muscle (m-)responses were recorded from the medial gastrocnemius (MG) muscle during a 3-minute massage of the ipsilateral soleus muscle in 12 neurologically healthy adults during 4 control conditions (C1, C2, C4, C5) and 1 experimental (C3-massage) condition. Peak-to-peak mean amplitudes of the MG H-reflex obtained during massage were significantly reduced in comparison to all control values recorded while the subjects were at rest. These results suggest that massage does indeed diminish motoneuronal excitability, since these effects were not restricted to the homonymous motoneurone pool, but could also be demonstrated for a close synergistic muscle, uninvolved in the massage.

Adult↗

PubMed1997

HPA genotyping by PCR sequence-specific priming (PCR-SSP): a streamlined method for rapid routine investigations.

We describe a streamlined method for the simultaneous identification of alleles of the human platelet antigens (HPA) 1-5. The method employs the polymerase chain reaction with sequence specific primers (PCR-SSP). Although PCR-SSP has been applied to HPA genotyping, all methods previously described have required different reaction mixes and PCR conditions. We have designed a set of sequence-specific primers for HPA 1-5 which react optimally under identical reaction and PCR conditions. Comparative testing with reference samples gave 100% concordance. The advantages of this method include speed; accuracy; smaller sample requirements and no reliance on human typing sera or platelet integrity. The method also has the potential to be applied to amniotic fluid. Simplified DNA techniques will lead to more extensive and proficient platelet antigen typing. This will facilitate accurate laboratory diagnosis of alloimmune thrombocytopenia and the provision of HPA-matched blood products.

Alleles↗

PubMed1997

Outcome of post-transfusion hepatitis C: disease severity in blood-component recipients and their implicated donors.

The UK 'Look-back Program' identifies recipients of blood products from hepatitis C antibody (anti-HCV) positive donors. Of 60 such recipients tested by the Newcastle Transfusion Service, 28(46.7%) were anti-HCV-negative, 25(41.7%) were anti-HCV-positive, and seven (11.6%) had equivocal serology. We studied 29 anti-HCV-positive/indeterminate recipients and eight of their implicated donors, using serial liver function tests (LFTs), liver histology when clinically indicated, HCV RNA and serotyping. Presumed resolved hepatitis C, with persistently normal LFTs and negative HCV RNA, was found in 28%, of whom 63% had indeterminate anti-HCV by RIBA (1 band of 4 detected on third-generation recombinant immunoblot assay). Resolved hepatitis C was significantly more common in women (p < 0.05) and tended to be associated with younger age at transfusion. There was complete concordance in serotype between donor-recipient pairs. There was no correlation in disease severity between recipients and their implicated donors, nor between recipients from the same donor. A history of alcohol consumption above recommended 'safe' limits (median 30 units) was associated with more severe histological disease (p < 0.01). Host factors, including gender and alcohol consumption, may be important in determining the wide variability in outcome of post-transfusion hepatitis C.

Adolescent↗

PubMed1997

Neuronal encoding of texture changes in the primary and the secondary somatosensory cortical areas of monkeys during passive texture discrimination.

Two rhesus monkeys were trained to discriminate, with the use of passive touch, a standard surface [rectangular arrays of raised dots with a spatial period (SP) of 2 mm across the rows and columns] from three modified surfaces in which the SP between rows was increased to 3, 4, or 5 mm over the second half of the surface. After the surface presentation (to digit tips 3 and 4 of one hand) the monkeys indicated the presence or absence of a change in texture by pulling or pushing a lever, respectively, with the opposite hand. Of 193 neurons recorded from primary somatosensory cortex (SI, 3 hemispheres) and 94 neurons from secondary somatosensory cortex (SII, 1 hemisphere), all contralateral to the stimulated hand, the discharge of 51 SI and 19 SII neurons was classified as texture related. Two types of texture-related responses were obtained. Graded neurons showed a linear relationship between mean discharge frequency and SP; nongraded neurons showed a significant change in discharge over the modified half of the surfaces but the discharge did not distinguish between the three modified surfaces. The distribution of these texture responses was significantly different in SI and SII: whereas most of the texture-related neurons in SI (44 of 51, 86%) were graded, the majority of those in SII (12 of 19, 63%) were nongraded. The results were interpreted as suggesting that the nongraded responses reflect feature extraction in SII, signaling the presence of a change in texture but not its magnitude, and so support the notion that texture signals are processed sequentially, first in SI and then in SII.

Animals↗

PubMed1996

The incidence of anti-Wra and Wra antigen in blood donors and hospital patients.

A retrospective study of positive 37 degrees C indirect antiglobulin test (IAT) for compatibility following negative antibody screens in a hospital laboratory revealed an unexpectedly high incidence of Wra-incompatible units. Over the course of 1 month 1112 routine patients' samples containing no other atypical antibodies were tested for the presence of anti-Wra. Anti-Wra was found in 88 patients, an incidence of 7.9%. Testing of 5098 healthy blood donor samples found 54 donors positive for anti-Wra, an incidence of 1.06%. A survey of 5253 healthy blood donor samples for Wra antigen found only two Wra-positive samples, suggesting an incidence between 1 in 1000 and < 1 in 10,000. The significance of this finding is discussed in relation to the continuing use of an IAT compatibility test.

Antibodies↗

PubMed1996

Hepatitis C virus: epidemiology and genotypes in the north east of England.

The epidemiology of hepatitis C virus (HCV) infection was studied in an English teaching hospital over an 18 month period. A total of 104 HCV antibody positive patients were referred for further investigation. They were divided into those diagnosed through screening (blood donors and intravenous drug abusers) and those diagnosed for other reasons, and their mean ages, known risk factors for HCV transmission, genotypes, and liver biopsy histology were analysed. Screened patients were significantly younger than the others. No significant difference in age was found between genotypes. Most patients genotyped (69%) were genotype 1. Intravenous drug abusers had a higher proportion of subtype 1a, and patients who acquired HCV through blood transfusion had a higher proportion of subtype 1b. Liver biopsy specimens were scored using a histological activity index for liver inflammation and fibrosis. Patients with subtype 1b had significantly more severe liver disease than other genotypes when the histological activity index scores for fibrosis were analysed (p < 0.05). Liver disease worsened significantly with age according to all three histological activity index scores (portal activity: p < 0.01, acinar activity: p < 0.001, fibrosis: p < 0.0001). Liver disease worsened with increased duration of infection (p < 0.002), and patients who also abused alcohol presented at a significantly younger age (cirrhosis, p < 0.05, hepatocellular carcinoma, p < 0.02).

Adult↗